ACS Surgery 7

FOR IMMEDIATE RELEASE
New Editor, New Vision for ACS Surgery

BC Decker Inc, publisher of the acclaimed general surgical
reference, ACS Surgery, is honored to announce the
appointment of Stanley W. Ashley, MD, FACS as the new
Editor-in-Chief.
Dr. Ashley is the Frank Sawyer Professor and Vice Chairman

of the Department of Surgery, and Program Director of the
General Surgery Residency Program at Brigham and Women’s
Hospital/Harvard Medical School, Boston. He is also Chief of
General Surgery for Harvard Vanguard Medical Associates.
As the new Editor-in-Chief, Dr. Ashley brings his estimable

experience in, and unique vision of, surgery to bear on ACS
Surgery, an official publication of the American College of
Surgeons. “The opportunity to adapt ACS Surgery to the
evolving needs of surgical residents and practicing surgeons is
extremely exciting to me,” remarked Dr. Ashley.
"Stan Ashley will be a wonderful new editor of ACS Surgery, who will build on the outstanding
work Dr. Souba did in transitioning the original loose-leaf work into the modern era. Dr. Ashley
will continue that trend by taking this excellent educational product to the next level," said ACS
Executive Director Thomas R. Russell, MD, FACS.
In addition to many exciting changes, Dr. Ashley envisions adding operative videos to the online
home of ACS Surgery, www.acssurgery.com. He believes that these videos, teaching slide sets,
and pod casts will enhance the educational experience for residents and practicing surgeons
before entering the OR. He also would like the text to begin to integrate with the new general
surgery residency curriculum being developed by the Surgical Committee on Resident Education
(SCORE). He also hopes to expand the scope of the work by including chapters by a variety of
experts with differing perspectives on general surgery and the subspecialties. Together with
Decker, Dr Ashley will promulgate the effort to make ACS Surgery an internationally adopted
surgical reference.
Optimism for the new Editor-in-Chief is described succinctly by Brian Decker, President and
Publisher: “We are persuaded that Dr. Ashley’s stewardship will enhance the already remarkable
success of ACS Surgery. The work draws its strength from its rich history, but its vitality stems
from the fresh vision that Dr. Ashley brings to the enterprise. Since its first incarnation as
Scientific American Surgery, this work has been the benchmark for innovation in surgical
education. We expect the track record to be extended during the Ashley regime.”
About Stanley W. Ashley, MD, FACS

Stanley W. Ashley is a graduate of Oberlin College and Cornell University Medical College. He
completed a residency in general surgery at Washington University in St. Louis and subsequently
joined the faculty. He spent seven years at UCLA before assuming his current position at
Brigham and Women’s Hospital/ Harvard Medical School in 1997. Dr. Ashley is a
gastrointestinal surgeon whose primary interests are diseases of the pancreas and inflammatory
bowel disease. His research, which has been funded by the VA the NIH, has examined the
pathophysiology of small bowel and pancreas. An author of more than 200 journal articles, he
serves on numerous editorial boards, including the Journal of Gastrointestinal Surgery, the
Journal of the American College of Surgeons, and Current Problems in Surgery. He is a director
of the American Board of Surgery and member of the Board of Trustees of the Society for
Surgery of the Alimentary Tract.
About BC Decker Inc

BC Decker Inc has published some of the most important works in medicine and surgery,
including Cameron’s Current Surgical Therapy, Cameron-Sandone’s Atlas of Gastrointestinal
Surgery, and Grillo’s Surgery of the Trachea. Decker is respected for the quality of its titles and
renowned for its authors. The company realizes half of its sales outside the United States
through its relationships with the best international houses. Decker also publishes ACP
Medicine, née Scientific American Medicine, and 20 specialty journals in medicine and dentistry.
Every Decker publication is available in print and digital formats. The company’s publishing
partners include American College of Surgeons, American Board of Surgery, American Board of
Otolaryngology, American Academy of Otolaryngology, and the American College of
Physicians.
About the American College of Surgeons

The American College of Surgeons is a scientific and educational organization of surgeons that
was founded in 1913 to raise the standards of surgical practice and to improve the care of the
surgical patient. The College is dedicated to the ethical and competent practice of surgery. Its
achievements have significantly influenced the course of scientific surgery in America and have
established it as an important advocate for all surgical patients. The College has more than
76,000 members and is the largest organization of surgeons in the world.
For more information, please contact:

Jeff Decker
BC Decker Inc
800-568-7281, ext.2251
###
competency-based surgical care
1 PROFESSIONALISM IN SURGERY
Jo Shapiro, MD, FACS, Steven M. Steinberg, MD, FACS, and Wiley W. Souba, MD, ScD, MBA, FACS
Over the past decade, the American health care system has were previously required or even valued. Many surgeons
had to cope with and manage an unprecedented amount have flourished in this new environment: leading a cohesive
of change. As a consequence, the medical profession has team dedicated to excellent outcomes is highly rewarding.
been challenged along the entire range of its cultural values Unfortunately, however, as a profession, we have not explic-
and its traditional roles and responsibilities. It would be dif- itly taught these teamwork and leadership skills, nor have
ficult, if not impossible, to find another social issue directly we always helped our colleagues remediate deficiencies in
affecting all Americans that has undergone as rapid and such skills.
remarkable a transformation—and oddly, a transformation
in which the most important protagonists (i.e., the patients
The Meaning of Professionalism
and the doctors) remain dissatisfied.1
Nowhere is this metamorphosis more evident than in Professionalism is the basis of our contract with society. A
the field of surgery. Marked reductions in reimbursement, profession is a collegial discipline that regulates itself by
explosions in surgical device biotechnology, a national means of mandatory, systematic training. It has a base in
medical malpractice crisis, and the disturbing emphasis on a body of technical and specialized knowledge that it
commercialized medicine have forever changed the surgical both teaches and advances; it sets and enforces its own stan-
landscape, or so it seems. The very foundation of patient dards; and it has a service orientation, rather than a profit
care—the doctor-patient relationship—is in jeopardy. Surgeons orientation, enshrined in a code of ethics.3–5 To put it more
find it increasingly difficult to meet their responsibilities succinctly, a profession has cognitive, collegial, and moral
to patients and to society as a whole. In these circumstances, attributes. These qualities are well expressed in the familiar
it is critical for us to reaffirm our commitment to the sentence from the Hippocratic oath: “I will practice my art
fundamental and universal principles and values of medical with purity and holiness and for the benefit of the sick.”
professionalism. Historically, the legitimacy of medical authority is based
The concept of medicine as a profession grounded in com- on three distinct claims2,6: first, that the knowledge and
passion and sympathy for the sick has come under serious competence of the professional have been validated by a
challenge.2 One eroding force has been the growth and community of peers; second, that this knowledge has a
sovereignty of biomedical research. Given the high position scientific basis; and third, that the professional’s judgment
of science and technology in our societal hierarchy, we may and advice are oriented toward a set of values. These aspects
be headed for a form of medicine that includes little caring of legitimacy correspond to the collegial, cognitive, and
but becomes exclusively focused on the mechanics of treat- moral attributes that define a profession.
ment, so that we deal with sick patients much as we would The American College of Surgeons (ACS) Task Force
a flat tire or a leaky faucet. In such a form of medicine, on Professionalism has developed a Code of Professional
healing becomes little more than a technical exercise, and Conduct,7 which emphasizes the following four aspects of
any talk of morality that is unsubstantiated by hard facts is professionalism:
considered mere opinion and therefore carries little weight.
1. A competent surgeon is more than a competent technician.
The rise of entrepreneurialism and the growing corporati-
2. Whereas ethical practice and professionalism are closely
zation of medicine also challenge the traditions of virtue-
related, professionalism also incorporates surgeons’ rela-
based medical care. When these processes are allowed to
tionships with patients and society.
dominate medicine, health care becomes a commodity. As
3. Unprofessional behavior must have consequences.
Pellegrino and Thomasma remark, “When economics and 4. Professional organizations are responsible for fostering
entrepreneurism drive the professions, they admit only professionalism in their membership.
self-interest and the working of the marketplace as the
motives for professional activity. In a free-market economy, Specifically, the ACS Code of Professional Conduct
effacement of self-interest, or any conduct shaped primarily includes tenets of professionalism that relate to both
by the idea of altruism or virtue, is simply inconsistent with our care of individual patients and our role in society [see
survival.”2 Table 1].
Another profound change in the practice of medicine is The Accreditation Council on Graduate Medical Educa-
the shift from a largely autonomous focus, with the surgeon tion (ACGME) has identified six competencies that must be
both shouldering tremendous personal responsibility and demonstrated by the surgeon: (1) patient care; (2) medical
wielding considerable control and independence, to a complex, knowledge; (3) practice-based learning and improvement;
team-based focus. Within this new paradigm, leadership of (4) interpersonal and communication skills; (5) professional-
a surgical team requires vastly different competencies than ism; and (6) systems-based practice. These competencies
are now being integrated into the training programs of all
accredited surgical residencies.
Financial disclosure information is located at the end of this chapter Being a professional demands unwavering personal integrity
before the references. and a commitment to lifelong learning and improvement. It
ACS Surgery: Principles and Practice

© 2012 Decker Intellectual Properties DOI 10.2310/7800.2005
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comp-based surg care 1 professionalism in surgery — 2
Table 1 American College of Surgeons’ Code of Professional Conduct27

During the continuum of pre-, intra-, and postoperative care, we accept responsibilities to
• Serve as effective advocates for our patients’ needs;
• Disclose therapeutic options, including their risks and benefits;
• Disclose and resolve any conflict of interest that might influence the decisions of care;
• Be sensitive and respectful of patients, understanding their vulnerability during the perioperative period;
• Fully disclose adverse events and medical errors;
• Acknowledge patients’ psychological, social, cultural, and spiritual needs;
• Encompass within our surgical care the special needs of terminally ill patients;
• Acknowledge and support the needs of patients’ families; and
• Respect the knowledge, dignity, and perspective of other healthcare professionals.
Our profession is also accountable to our communities and to society. In return for their trust, as Fellows of the American College of
Surgeons, we accept responsibilities to
• Provide the highest quality of surgical care;
• Abide by the values of honesty, confidentiality, and altruism;
• Participate in lifelong learning;
• Maintain competence throughout our surgical careers;
• Participate in self-regulation by setting, maintaining, and enforcing practice standards;
• Improve care by evaluating its processes and outcomes;
• Inform the public on subjects within our expertise;
• Advocate strategies to improve individual and public health by communicating with government, healthcare organizations, and
industry;
• Work with society to establish a just, effective, and efficient distribution of healthcare resources;
• Provide necessary surgical care without regard to gender, race, disability, religion, social status, or ability to pay; and
• Participate in educational programs addressing professionalism.
places the responsibility to serve (care for) others above conflict with one another, creating tension sometimes inter-
self-interest and reward [see Sidebar Elizabeth Blackwell: A nally and at other times between various groups. For
Model of Professionalism8]. example, the patient may want a specific treatment that
Regrettably, examples of unprofessional behavior exist. is not yet supported by evidence but may be of benefit.
An excerpt from a note from a third-year medical student Meeting the patient’s expectations and needs may directly
to the core clerkship director reads as follows: “I have seen conflict with the expectation that we are advocates for
attendings make sexist, racist jokes or remarks during sur- “efficient distribution of health care resources.” Another
gery. I have met residents who joke about deaf patients direct challenge to several professionalism obligations is
and female patients with facial hair. [I have encountered] trying to balance the important adherence to the duty hours
teams joking and counting down the days until patients die” mandate with the equally important value of continuity of
(personal communication, 2004). This kind of exposure to care.10
unprofessional conduct and language can influence young The underpinning of medicine as a compassionate, caring
people negatively, and it must change.
profession is the doctor-patient relationship, a relationship
Most of us went to medical school because we wanted
that has become jeopardized and sometimes fractured over
to help and care for people who are ill. This genuine desire
the past decade. Our individual perceptions of what this
to care is unambiguously apparent in the vast majority of
relationship is and how it should work will inevitably have
personal statements that medical students prepare as part of
their application process. To quote William Osler, “You are a great impact on how we approach the care of our patients.2
in this profession as a calling, not as a business; as a calling The view of the physician-patient relationship as a cove-
which extracts from you at every turn self-sacrifice, devo- nant does not demand devotion to medicine to the exclusion
tion, love and tenderness to your fellow man. We must work of other responsibilities and is not inconsistent with the
in the missionary spirit with a breath of charity that raises fact that medicine is also a science, an art, and a business.2
you far above the petty jealousies of life.”9 To keep medicine Nevertheless, in our struggle to remain viable in a health
a calling, we must explicitly incorporate into the meaning care environment that has become a commercial enterprise,
of professionalism those nontechnical practices, habits, and efforts to preserve market share cannot take precedence over
attributes that the compassionate, caring, and competent the provision of care that is grounded in charity and com-
physician exemplifies. We must remind ourselves that a true passion. It is exactly for this reason that medicine always
professional places service to the patient above self-interest will be, and should be, a relationship between people. To
and above reward. fracture that relationship by exchanging a covenant based
One of the core tenets of professionalism is being con- on charity and compassion for a contract based solely on
sistently respectful not only toward our patients and their the delivery of goods and services is something none of
families but also toward our colleagues and other health us would want for ourselves. The nature of the healing rela-
care team members. Although no one would argue with this tionship is itself the foundation of the special obligations of
in principle, there are many factors that challenge our ability physicians as physicians.2
to hold true to this precept, including poor interpersonal
communication skills, lack of training in conflict resolution,
resource constraints, and cultural tradition. Translation of Theory into Practice
Given that professionalism is so multifaceted, it is not It is encouraging to note that many instances of unprofes-
surprising that various important professional values may sional conduct that once were routinely overlooked—such
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Elizabeth Blackwell: A Model of Professionalism8 and write an article in a medical journal about billing errors.
The university spent many millions in legal fees and eventu-
Elizabeth Blackwell was born in England in 1821, the daughter of
a sugar refiner. When she was 10 years old, her family emigrated
ally settled the billing issues with the federal government for
to New York City. Discovering in herself a strong desire to prac- one of the highest Physicians at Teaching Hospitals (PATH)
tice medicine and care for the underserved, she took up residence settlements ever.
in a physician’s household, using her time there to study using Fortunately, such extreme cases of unprofessionalism are
books in the family’s medical library. quite uncommon. Nevertheless, there are numerous reports
As a young woman, Blackwell applied to several prominent in the literature of other types of unprofessional behavior,
medical schools but was snubbed by all of them. After 29 rejec-
tions, she sent her second round of applications to smaller col- such as disruptive behavior,7 that can lead to patient safety
leges, including Geneva College in New York. She was accepted risks.12–14 To this end, The Joint Commission has mandated
at Geneva—according to an anecdote, because the faculty put the that all of our hospitals have zero tolerance for disruptive
matter to a student vote, and the students thought her application behavior. Regardless of the practice setting, it remains our
a hoax. She braved the prejudice of some of the professors and responsibility as professionals to prevent such behaviors
students to complete her training, eventually ranking first in her
from developing and from being reinforced. A study pub-
class. On January 23, 1849, at the age of 27, Elizabeth Blackwell
became the first woman to earn a medical degree in the United lished in 2004 demonstrated an association between displays
States. Her goal was to become a surgeon. of unprofessional behavior in medical school and subsequent
After several months in Pennsylvania, during which time she disciplinary action by a state medical board.15 The authors
became a naturalized citizen of the United States, Blackwell concluded that professionalism is an essential competency
traveled to Paris, where she hoped to study with one of the lead- that students must demonstrate to graduate from medical
ing French surgeons. Denied access to Parisian hospitals because
of her gender, she enrolled instead at La Maternité, a highly school. Who could disagree? Yet we know that throughout
regarded midwifery school, in the summer of 1849. While attend- our careers, there will be challenges, both personal and
ing to a child some 4 months after enrolling, Blackwell inadver- external, to our consistently behaving professionally.
tently spattered some pus from the child’s eyes into her own In addition to the reports recounting acts of unprofes-
left eye. The child was infected with gonorrhea, and Blackwell sional behavior, various publications describing methods
contracted a severe case of ophthalmia neonatorum, which later
of teaching and assessing professionalism have begun to
necessitated the removal of the infected eye. Although the loss of
an eye made it impossible for her to become a surgeon, it did not appear in the past few years.16,17 As an example, Kumar and
dampen her passion for becoming a practicing physician. colleagues found that using ACS case-based multimedia
By mid-1851, when Blackwell returned to the United States, materials enhanced the ability of residents to recognize and
she was well prepared for private practice. However, no male discuss matters related to professional behavior.18 Surgical
doctor would even consider the idea of a female associate, no residents who viewed these materials scored higher on
matter how well trained. Barred from practice in most hospitals,
Blackwell founded her own infirmary, the New York Infirmary
an assessment tool than did residents with the same level
for Indigent Women and Children, in 1857. When the American of experience who did not use the materials. An additional
Civil War began, Blackwell trained nurses, and in 1868 she encouraging finding was that residents of all years were able
founded a women’s medical college at the Infirmary so that wom- to define the components of professionalism. In another
en could be formally trained as physicians. In 1869, she returned publication, Gauger and colleagues described an evaluation
to England and, with Florence Nightingale, opened the Women’s instrument used to evaluate residents with respect to the
Medical College. Blackwell taught at the newly created London
School of Medicine for Women and became the first female physi- aspects of professionalism.19 They divided the concept of
cian in the United Kingdom Medical Register. She set up a private professionalism into 15 domains and modified a standard
practice in her own home, where she saw women and children, resident evaluation form to assess the faculty’s perception of
many of whom were of lesser means and were unable to pay. In resident performance in each domain. This evaluation tool
addition, Blackwell mentored other women who subsequently proved to be internally consistent, but in the absence of
pursued careers in medicine. She retired at the age of 86.
In short, Elizabeth Blackwell embodied professionalism in
any other gold standard tools with which to compare it, its
her work. In 1889 she wrote, “There is no career nobler than that validity could not be determined.
of the physician. The progress and welfare of society is more Hickson developed a system to monitor patient complaint
intimately bound up with the prevailing tone and influence of the data and use this to improve the behavior of individual
medical profession than with the status of any other class.” physicians.20 Others have developed 360° assessment tools
to give feedback to physicians regarding how their pro-
fessionalism skills are perceived by their team members.21
as mistreating medical students, speaking disrespectfully to Assessment tools and formal courses alone are not enough
coworkers, and fraudulent behavior—are now being dealt to support the significant adaptive challenge22 that is involved
with. Still, from time to time, an incident is made public in maintaining a culture of professionalism.10 Several authors
that makes us all feel shame. In March 2003, the Seattle Times have argued for a nuanced approach to supporting profes-
carried a story about the chief of neurosurgery at the Uni- sional behaviors—one that acknowledges that professional-
versity of Washington, who pleaded guilty to a felony charge ism is not a fixed trait but rather a set of developmental
of obstructing the government’s investigation and admitted skills that need to be continuously taught, role-modeled, and
that he asked others to lie for him and created an atmosphere reflected on throughout one’s career.23 Understanding that pro-
of fear in the neurosurgery department.11 According to the fessional behavior is contextual and situation dependent is
US Attorney in Seattle, University of Washington employees crucial to developing programs to support professionalism.
destroyed reports revealing that university doctors sub-
mitted inflated billings to Medicare and Medicaid. The
department chair lost his job, was barred from participation The Future of Surgical Professionalism
in Medicare, and, as part of his plea bargain, had to pay a It is often subtly implied—or even candidly stated—that
$500,000 fine, perform 1,000 hours of community service, no matter how well we adjust to the changing health care
05/12
environment, the practice of surgery will never again be science-education.nih.gov/snapshots.nsf/story?openform

quite as rewarding as it once was. This need not be the case. &pds~Elizabeth_Blackwell_Doctor (accessed March 21, 2012).
The ongoing advances in surgical technology, the increasing 9. Hinohara S, Niki H, editors. Osler’s “Way of Life” and other
opportunities for community-based surgeons to enrol their addresses, with commentary and annotations. Durham
patients into clinical trials, the growing emphasis on lifelong (NC): Duke University Press; 2001.
learning, and the increased focus on teamwork and shared 10. Lucey C, Souba W. The problem with the problem of
responsibility are factors that not only help satisfy social and professionalism. Acad Med 2010;85:1018–24.
organizational demands for quality care but also are in the 11. Ostrom CM. A neaurosurgeon ‘crisis’: Insurer drops
best interest of our patients. doctors’ group. The Seattle Times 2003 June 7.
In the near future, maintenance of certification for sur- 12. Rosenstein AH, O’ Daniel M. A survey of the impact of
geons will involve much more than taking an examination disruptive behaviors and communication defects on patient
every decade. The ACS is taking the lead in helping to safety. Jt Comm J Qual Patient Saf 2008;34:464–71.
develop new measures of competence. Whatever specific 13. Rosenstein AH, O’Daniel M. Disruptive behavior and clini-
form such measures may take, displaying professionalism cal outcomes. Am J Nurs 2005;105:54–64.
and living up to a set of uncompromisable core values24 14. The Joint Commission. Behaviors that undermine a culture
will always be central indicators of the performance of the of safety. Sentinel Event Alert 2008;40:1–3.
individual surgeon and the integrity of the discipline of 15. Papadakis M, Hodgson C, Teherani A, Kohatsu ND. Unpro-
surgery as a whole. fessional behavior in medical school is associated with
Although surgeons vary enormously with respect to per- subsequent disciplinary action by a state medical board.
sonality, practice preferences, areas of specialization, and Acad Med 2004;79:244.
style of relating to others, they all have one role in common: 16. Papadakis MA, Osborn EH, Cooke M, Healy K. A strategy
that of healer. Indeed, it is the highest of privileges to be for the detection and evaluation of unprofessional behavior
able to care for the sick. As the playwright Howard Sackler in medical students. University of California, San Francisco
once wrote, “To intervene, even briefly, between our fellow School of Medicine Clinical Clerkships Operation Commit-
creatures and their suffering or death, is our most authentic tee. Acad Med 1999;74:980–90.
answer to the question of our humanity.”25 Inseparable from 17. Yao D, Wright S. National survey of internal medicine
this privilege is a set of responsibilities that are not to be residency program directors regarding problem residents.
taken lightly: a pledge to offer our patients the best care JAMA 2000;284:1099–104.
possible and a commitment to teach and advance the science 18. Kumar A, Shibru D, Bullard K, et al. Case-based multime-
and practice of medicine. Commitment to the practice of dia program enhances the maturation of surgical residents
patient-centered, high-quality, cost-effective care is what regarding the concepts of professionalism. J Surg Educ
gives our work meaning and provides us with a sense of 2007;64:194.
purpose.26 As surgeons, we must participate actively in the 19. Gauger P, Gruppen L, Minter R, et al. Initial use of a novel
current evolution of integrated health care. By doing so, we instrument to measure professionalism in surgical residents.
help build our own future. Am J Surg 2005;189:479.
20. Hickson G, Pichert JW, Webb LE, Gabbe SG. A complemen-
Jo Shapiro, MD, FACS, or their significant other, has disclosed a tary approach to promoting professionalism: identifying,
potential conflict of interest as follows: grants and/or salary by measuring and addressing unprofessionalism behaviors.
Health Dialog Acad Med 2007;82:1040–8.
21. Harmon L, Gregory P, Hiller N, Batista L. PULSE (Physi-
cians Universal Leadership Skills Education Survey) techni-
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Rev 1953;23:33. mean? J Surg Res 2003;115:171.
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8. Speigel R. Elizabeth Blackwell: the first woman doctor. duct. Available at: www.facs.org/memberservices/codeof-
Snapshots in science and medicine. Available at: http:// conduct.html (accessed March 21, 2012).
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elements of contemporary practice
2 PERFORMANCE MEASUREMENT IN
SURGERY
Justin B. Dimick MD, MPH, and John D. Birkmeyer MD
With growing recognition that the quality of surgical care Although the NQF is the central organization for evaluating
varies widely, good measures of performance are in high quality measures, many organizations develop candidate
demand. Patients and their families are looking to make measures and submit them for endorsement. The Agency
informed decisions about where and from whom to get for Healthcare Research and Quality (AHRQ) has focused
their surgical care.1 Employers and payers need measures primarily on quality measures that take advantage of read-
on which to base their contracting decisions and pay-for- ily available administrative data, such as the hospital dis-
performance initiatives.2 Finally, clinical leaders need mea- charge data sets comprising the Healthcare Cost and Utiliza-
sures that can help them identify “best practices” and guide tion Project (HCUP) [see Table 2]. Because little information
on process of care is available in these data sets, these mea-
their quality improvement efforts. An ever-broadening array
sures are mainly structural (e.g., hospital procedure volume)
of performance measures is being developed to meet these
or outcome based (e.g., risk-adjusted mortality).
different needs.
The Leapfrog Group (http://www.leapfroggroup.org), a
However, considerable uncertainty remains about which coalition of large employers and purchasers, has developed
measures are most useful for measuring surgical quality. perhaps the most visible set of surgical quality indicators for
Current measures are remarkably heterogeneous, encom- its value-based purchasing initiative. The organization’s
passing different elements of health care structure, process original standards focused exclusively on procedure volume
of care, and patient outcomes. Although each of these three but later expanded its standards to include selected process
types of performance measures has unique strengths, each variables (e.g., the use of beta blockers in patients undergo-
is also associated with conceptual, methodological, and/or ing abdominal aortic aneurysm repair) and outcome mea-
practical problems. The baseline risk and frequency of the sures, such as mortality. Most recently (2010), the Leapfrog
procedure are obviously important considerations in weigh- Group began using a composite of operative mortality and
ing the strengths and weaknesses of different measures.3 So hospital volume, the so-called “Survival Predictor,” as the
too is the underlying purpose of performance measurement. primary measure for its evidence-based hospital referral
Measures that work well when the primary intent is to steer initiative. Such composite measures are discussed further
patients to the best hospitals or surgeons (selective referral) below.
may not be optimal for quality improvement purposes and Several surgical professional organizations have played a
vice versa. large part in developing many of the quality measures en-
dorsed by the NQF. The Society of Thoracic Surgeons (STS)
Expanding on other recent reviews of performance
has been a leader in the development of quality measures
measurement,3–5 this chapter provides an overview of mea-
for cardiac and thoracic procedures [see Table 3 and Table 4].
sures commonly used to assess surgical quality, considers These measures include the structure, process, and outcomes
their main strengths and limitations, and closes with recom- of cardiac surgical care. In addition, the STS recently devel-
mendations for selecting the optimal quality measure oped a composite measure that combines all of these
[see Table 1]. domains of quality into a single hospital rating. The Nation-
al Surgical Quality Improvement Program (NSQIP) has
Overview of Current Measures also developed measures for colectomy, lower extremity
bypass, and elderly surgical patients [see Table 3 and Table 4].
The number of performance measures that have been Finally, the Society for Vascular Surgery (SVS) has acted
developed for the assessment of surgical quality is already as the steward for measures of process of care for carotid
large and continues to grow. Many surgical quality indica- endarterectomy [see Table 4].
tors are already used in hospital accreditation, pay-for-
performance, or public reporting efforts. Over the past few
Structural Measures of Quality
years, the National Quality Forum (NQF) has emerged as
the leading organization endorsing quality measures. Many Health care structure reflects the setting or system in
influential organizations, including the Joint Commission on which care is delivered. Many structural measures describe
Accreditation of Healthcare Organizations (JCAHO) and the hospital-level attributes, such as the physical plant and
Centers for Medicare and Medicaid Services (CMS), rely on resources or staff coordination and organization (e.g., nurse-
to-bed ratios, designation as a Level I trauma center).
the endorsement of the NQF before applying a measure to
Other structural measures reflect attributes associated with
practice. The number of measures relevant to surgery that
the relative expertise of individual physicians (e.g., board
have been endorsed by the NQF has grown rapidly.
certification, subspecialty training, or procedure volume).
strengths
Financial disclosure information is located at the end of this chapter From a measurement perspective, structural measures of
before the references. quality have several attractive features. First, many of these

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elem cont prac 2 performance measurement in surgery — 2
Table 1 Primary Strengths and Limitations of Structure, Process, and Outcome Measures
Structure Process Outcomes
Examples Procedure volume, intensivist- Appropriate use of prophylactic Risk-adjusted mortality rates for CABG
managed ICUs antibiotics from state or national registries
Strengths Expedient, inexpensive Reflect care that patients actually Face validity
Efficient—one measure may relate to receive—buy-in from providers Measurement alone may improve
several outcomes Directly actionable for quality outcomes (i.e., Hawthorne effect)
For some procedures, better predictor improvement activities
of subsequent performance than Do not need risk adjustment for many
other measures measures
Limitations Limited number of measures Many measures hard to ascertain with Sample size constraints
Generally not actionable existing databases Expense of clinical data collection
Do not reflect individual performance, Variable extent to which process Concerns about risk adjustment with
considered unfair by providers measures link to important patient administrative data
outcomes
Lack of high leverage,
procedure-specific processes
CABG = coronary artery bypass grafting; ICU = intensive care unit.
Table 2 Surgical Performance Measures that Apply to Multiple Surgical Procedures Endorsed by the
National Quality Forum
Diagnosis or Procedure Performance Measure Steward
All surgical procedures Appropriate antibiotic prophylaxis (selection, timing, and duration) AMA
Hair clipping prior to surgery CMS
Appropriate venous thromboembolism prophylaxis AMA/CMS
Perioperative temperature management CMS
Preoperative beta blockers continued after surgery CMS
Urinary catheter removed postoperative day 2 CMS
Risk-adjusted surgical mortality or major complications in elderly patients ACS/NSQIP
Accidental puncture or laceration AHRQ
Iatrogenic pneumothorax AHRQ
Wound dehiscence AHRQ
Postoperative respiratory failure AHRQ
Failure to rescue AHRQ
Postoperative venous thromboembolism AHRQ
Foreign body left after procedure AHRQ
Superficial surgical site infection CDC
Cardiac and thoracic surgery Participation in a systematic quality improvement database STS
Pediatric surgery Risk-adjusted mortality in neonates undergoing noncardiac surgery CHOP
ACS = American College of Surgeons; AHRQ = Agency for Healthcare Research and Quality; AMA = American Medical Association; CDC = Centers for Disease Control
and Prevention; CHOP = Children’s Hospital of Pennsylvania; CMS = Centers for Medicare and Medicaid Services; JCAHO = Joint Commission on Accreditation of
Healthcare Organizations; NSQIP = National Surgical Quality Improvement Program; STS = Society of Thoracic Surgeons.
measures are strongly related to patient outcomes. For surgeon procedure volume is associated not only with lower
example, with esophagectomy and pancreatic resection, operative mortality but also with lower perioperative mor-
operative mortality rates at very high-volume hospitals bidity and higher late survival rates.9–11 Intensivist model
are as much as 10% lower, in absolute terms, than at lower- intensive care units are linked to shorter length of stay and
volume centers.6,7 In some instances, structural measures reduced resource use, as well as lower mortality.12,13
such as procedure volume are more predictive of subse- The third and perhaps most important advantage of struc-
quent hospital performance than any known processes of tural variables is expediency. Many can be assessed easily
care or direct mortality measures8 [see Figure 1]. with readily available administrative data. Although some
A second advantage is efficiency. A single structural structural measures require surveying hospitals or provid-
measure may be associated with numerous outcomes. ers, such data are much less expensive to collect than
For example, with some types of cancer surgery, hospital or measures requiring patient-level information.
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Table 3 Surgical Performance Measures Endorsed by the National Quality Forum that Apply to Spe-
cific Cardiac and Vascular Procedures
Diagnosis or Procedure Performance Measure Steward
Coronary artery bypass grafting Hospital volume STS
Risk-adjusted mortality rate STS
Postoperative renal failure STS
Internal mammary artery use STS
Preoperative beta blockade STS
Postoperative glucose controlled by 6 am the day after surgery JCAHO
STS composite measure STS
Reoperation for tamponade, bleeding, or other cardiac reason STS
Antiplatelet therapy at discharge STS
Beta-blocker therapy at discharge STS
Antilipid therapy at discharge STS
Deep sternal wound infection rate STS
Prolonged intubation STS
Stroke STS
Aortic valve replacement Risk-adjusted mortality rate STS
Hospital volume STS
Mitral valve replacement/repair Risk-adjusted mortality rate STS
Hospital volume STS
Pediatric heart surgery Hospital volume AHRQ
Risk-adjusted mortality rates AHRQ
Abdominal aneurysm repair Hospital volume AHRQ
Lower extremity bypass Risk-adjusted mortality or major complications CMS
Carotid endarterectomy Perioperative antiplatelet therapy SVS
Patch closure of arteriotomy SVS
AHRQ = Agency for Healthcare Research and Quality; CMS = Center for Medicare and Medicaid Services; JCAHO = Joint Commission on Accreditation of Healthcare
Organizations; STS = Society of Thoracic Surgeons.
disadvantages of structural variables Process of Care Measures

Among the downsides, there are relatively few structural Processes of care are the clinical interventions and ser-
measures that may be potentially useful as quality indica- vices provided to patients. Process measures have long been
tors. Second, in contrast to process measures, most struc- the predominant quality indicators for both inpatient and
tural measures are not readily actionable. For example, a outpatient medical care, and their popularity as quality
small hospital can increase the number of surgical patients measures for surgical care is growing rapidly. Perhaps the
receiving antibiotic prophylaxis but cannot readily make best example of the trend toward using process measures is
itself a high-volume center. Thus, although selected structur- the CMS Surgical Care Improvement Program (SCIP). The
al measures may be useful for selective referral initiatives, SCIP mandates all hospitals to collect and publicly report
they have limited value for quality improvement purposes. process measures related to prevention of surgical site
Finally, structural measures generally describe groups of infections (SSIs), postoperative cardiac events, venous
hospitals or providers with better performance but do not thromboembolism (VTE), and respiratory complications.
adequately discriminate performance among individuals.
For example, in aggregate, high-volume hospitals have strengths
much lower mortality rates than lower-volume centers Given that processes of care reflect the care that physi-
for pancreatic resection. However, some individual high- cians deliver, they have face validity and enjoy greater
volume hospitals may have high mortality rates. Although buy-in from providers. They are usually directly actionable
difficult to confirm empirically (for sample size reasons), and thus good substrate for quality improvement activities.
some low-volume centers may have excellent performance.14 Although risk adjustment may be important for
For this reason, structural measures are viewed as “unfair” outcomes, it is not required for many process measures.
by many providers. For example, when measuring appropriate prophylaxis
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Table 4 Surgical Performance Measures Endorsed by the National Quality Forum that Apply to Spe-
cific General Surgical Procedures
Diagnosis or Performance Measure Steward
Procedure
Esophageal resection Hospital volume AHRQ
Risk-adjusted mortality STS/AHRQ
Preoperative assessment of performance status STS
Pancreatic resection Hospital volume AHRQ
Colon resection Risk-adjusted mortality or major complications ACS/NSQIP
For cancer, adjuvant chemotherapy within 4 months for lymph node–positive ACS
disease
For cancer, at least 12 lymph nodes are harvested ACS
For cancer, complete pathology reporting ACS
Melanoma Coordination of care AMA
Breast cancer Post–breast conservation radiation ACS
Appropriate axillary staging Intermountain Healthcare
Adjuvant hormonal therapy in receptor-positive patients ACS
Adjuvant chemotherapy in appropriate patients ACS
Needle biopsy to establish diagnosis of cancer precedes surgical excision/resection ACS
Appendicitis Proportion with perforation AHRQ
Incidental appendectomy in the elderly AHRQ
ACS = American College of Surgeons; AHRQ = Agency for Healthcare Research and Quality; AMA = American Medical Association; NSQIP = National Surgical Quality
Improvement Program; STS = Society of Thoracic Surgeons.
against postoperative VTE, one of the SCIP measures, it mortality. A growing body of empirical data supports this
is not necessary to account for patient differences in risk. statement. Most of the data come from the literature on
Given that virtually all patients undergoing open abdominal medical diagnoses (e.g., acute myocardial infarction), where
surgery should be offered some form of prophylaxis, there the link between process and outcome is much stronger than
is little need to collect detailed clinical data about illness it is in surgery.16–18 For example, the JCAHO/CMS process
severity for the purpose of risk adjustment. measures for acute myocardial infarction explained only 6%
Finally, process measures are generally less constrained of the observed variation in risk-adjusted mortality for this
by sample size problems than direct outcome measures. condition.17
Whereas important outcomes (e.g., perioperative death) are There is reason to believe that existing process measures
relatively rare, most targeted process measures are relevant explain very little of the variation in important outcomes
to a larger proportion of patients. Moreover, because they in surgery. First, most process measures currently used in
generally target aspects of general perioperative care, pro- surgery relate to secondary rather than primary outcomes.
cess measures can often be assessed on patients undergoing For example, although the value of antibiotic prophylaxis
numerous different procedures, increasing sample sizes and in reducing the risk of superficial SSI should not be under-
measurement precision. estimated, this process is not among the most important
adverse events of major surgery (including death). Second,
limitations
process measures in surgery often relate to complications
At the current time, a major limitation of process mea- that are very rare. For example, there is a consensus that
sures is the lack of a reliable data infrastructure for ascer- prophylaxis for VTE is necessary and important. Accord-
taining them. Administrative data sets lack the requisite ingly, the SCIP measures, endorsed by the NQF, include the
clinical detail and specificity for this purpose. Measurement use of appropriate prophylaxis. However, pulmonary embo-
systems based on clinical data, including that of the lism is very uncommon; therefore, improving adherence to
NSQIP,15 focus on patient characteristics and outcomes these measures will not avert many deaths.
and do not collect information on process of care. Presently, Several recent empirical studies on the relation between
pay-for-performance programs rely on self-reported infor- SCIP processes and patient outcomes support this assertion.
mation from hospitals, but the reliability of such data is For example, Nicholas and colleagues examined the relation
uncertain (particularly when reimbursement is at stake). between hospital SCIP process compliance and risk-adjusted
Even if this limitation were overcome, a second limitation rates of mortality, thromboembolism, and surgical infec-
remains to be considered—namely, that process variables tion.19 Despite wide variation in process compliance, there
are limited in their ability to explain observed variations in was no association between adherence to SCIP measures
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a
14
12
Risk-Adjusted Mortality (2007–2008) 10.3
10
8.3
8
6.5
5.4 5.5
6
4.3
0
Best Middle Worst High Medium Low
Risk-Adjusted Mortality Hospital Volume
Hospital Rankings (2005–2006)
b 20
18
16 14.3
Risk-Adjusted Mortality (2007–2008)
13.5
14
12 10.6
9.9
8.9
10
8 6.7
0
Best Middle Worst High Medium Low
Risk-Adjusted Mortality Hospital Volume
Hospital Rankings (2005–2006)
Figure 1 Relative ability of historical (2005–2006) measures of hospital volume and risk-adjusted mortality to predict subsequent (2007–2008)
risk-adjusted mortality in US Medicare patients. (a) Pancreatic resection. (b) Esophageal resection.
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and any of these risk-adjusted outcomes. Until a better hospitals had adequate caseloads to rule out a mortality
understanding is achieved regarding which details account rate twice the national average. Although identifying
for variations in the most important complications, espe- poor quality outliers is an important function of outcomes
cially those adverse events leading to death, process mea- measurement, focusing on this goal alone significantly
sures will continue to be of limited usefulness in surgical underestimates problems with small sample sizes. Discrimi-
quality improvement. nating among individual hospitals with intermediate levels
of performance is even more difficult.
Other limitations of direct outcomes assessment depend
Direct Outcome Measures
on whether outcomes are being assessed from administra-
Direct outcome measures reflect the end result of care, tive data or clinical information abstracted from medical
from a clinical perspective or as judged by the patient. records. For outcomes measurement based on clinical data,
Although mortality is by far the most commonly used mea- the major problem is expense. For example, it costs over
sure in surgery, other outcomes that could be used as qual- $100,000 annually for a private sector hospital to participate
ity indicators include complications, hospital readmission, in the NSQIP.
and a variety of patient-centered measures of satisfaction or With administrative data, the adequacy of risk adjustment
health status. remains a major concern. High-quality risk adjustment may
There are several ongoing, large-scale initiatives involving be essential for outcome measures to have face validity with
direct outcomes assessment in surgery. Proprietary health providers. It may also be useful for discouraging gaming,
care rating firms (e.g., Healthgrades) and state agencies for example, hospitals or providers avoiding high-risk
are assessing risk-adjusted mortality rates using Medicare or patients to optimize their performance measures. However,
state-level administrative data sets. However, most of the it is not clear how much the scientific validity of outcome
current interest in outcomes measurement involves large measures is threatened by imperfect risk adjustment with
clinical registries. Cardiac surgery registries in New York, administrative data. Although administrative data lack
Pennsylvania, and a growing number of other states are clinical detail on many variables related to baseline risk,21–24
perhaps the visible examples. At the national level, the it is not clear to what extent case mix varies systematically
STS and the American College of Cardiology (ACC) have across hospitals or surgeons. Among patients undergoing
implemented systems for tracking morbidity and mortality the same surgical procedure, there is often surprisingly little
with cardiac surgery and percutaneous coronary interven- variation. For example, we examined risk-adjusted mortality
tions, respectively. Although most outcomes measurement rates for hospitals performing coronary artery bypass
efforts have been procedure specific (and largely limited to grafting in New York State, as derived from their clinical
cardiac procedures), the NSQIP of the American College registries.25 Unadjusted and adjusted hospital mortality rates
of Surgeons (ACS) assesses hospital-specific morbidity and were nearly identical in most years (correlations exceeding
mortality rates aggregated across surgical specialties and 0.90). Moreover, hospital rankings based on unadjusted
procedures.16 and adjusted mortality were equally useful in predicting
subsequent hospital performance.
strengths
Direct outcome measures have at least two major advan-
tages. First, direct outcome measures have obvious face Matching the Measure to the Purpose
validity and thus are likely to get the greatest “buy-in” from Performance measures will never be perfect. Over time,
hospitals and surgeons. Second, outcomes measurement analytical methods will be refined. Access to higher-quality
alone may improve performance—the so-called Hawthorne data may improve with the addition of clinical elements to
effect. For example, surgical morbidity and mortality rates administrative data sets or broader adoption of electronic
in Veterans Affairs’ hospitals have fallen dramatically since medical records. However, some problems with perfor-
implementation of NSQIP in 1991.15 No doubt many surgical mance measurement, including sample size limitations, are
leaders at individual hospitals made specific organizational inherent and not fully correctable. Thus, clinical leaders,
or process improvements after they began receiving feedback patient advocates, payers, and policy makers will not escape
on their hospitals’ performance. However, it is very unlikely having to make decisions about when imperfect measures
that even a full inventory of these specific changes would are good enough to act upon.
explain such broad-based and substantial improvements in A measure should be implemented only with the expecta-
morbidity and mortality rates. tion that acting will result in a net improvement in health
quality. Thus, the direct benefits of implementing a particu-
disadvantages of direct outcome measures lar measure cannot be outweighed by the indirect harms.
Hospital- or surgeon-specific outcome measures are Unfortunately, these benefits and harm are often difficult to
severely constrained by small sample sizes. For the large measure and heavily influenced by the specific context and
majority of surgical procedures, very few hospitals (or who—patients, payers, or providers—is doing the account-
surgeons) have sufficient adverse events (numerators) and ing. For this reason, there is no simple answer for where to
cases (denominators) for meaningful, procedure-specific “set the bar.”
measures of morbidity or mortality. For example, Dimick It is important to ensure a good match between the per-
and colleagues used data from the Nationwide Inpatient formance measure and the primary goal of measurement.
Sample to study seven procedures for which mortality rates The right measure depends on whether the underlying goal
have been advocated as quality indicators by the AHRQ.20 is (1) quality improvement or (2) selective referral—directing
For six of these procedures, a very small proportion of US patients to higher-quality hospitals and/or providers.
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Although many pay-for-performance initiatives have both outcomes on average. Many measures meet this latter
goals, one often predominates For example, the ultimate interest while failing on the former.
objective of CMS’s pay-for-performance initiative with pro- For example, Krumholz and colleagues used clinical
phylactic antibiotics is improving quality at all hospitals— data from the Cooperative Cardiovascular Project to assess
not directing patients to those centers with high compliance the usefulness of Healthgrades’ hospital ratings for acute
rates. Conversely, although it may indirectly incentivize myocardial infarction (based primarily on risk-adjusted
quality improvement, the Leapfrog Group’s efforts in sur- mortality rates from Medicare data).27 Relative to one-star
gery are primarily aimed at getting patients to hospitals (worst) hospitals, five-star (best) hospitals had significantly
likely to have the best outcomes (selective referral). lower mortality (16% versus 22%, p < .001) after risk adjust-
For quality improvement purposes, a good performance ment with clinical data. They also discharged significantly
measure—most often a process of care variable—must be more (appropriate) patients on aspirin, beta blockers,
actionable. Measurable improvements in the given process and angiotensin-converting enzyme (ACE) inhibitors, all
should translate to clinically meaningful improvements in recognized quality indicators. However, the Healthgrades’
patient outcomes. Although quality improvement activities ratings poorly discriminated among any two individual
are rarely “harmful,” their major downsides relate to their hospitals. In only 3% of head-to-head comparisons did five-
opportunity cost. Initiatives hinged on bad measures siphon star hospitals have statistically lower mortality rates than
away resources (e.g., time and focus of physicians and other one-star hospitals.
staff) from more productive activities. Thus, some performances measures that clearly identify
With selective referral, a good measure will steer patients groups of hospitals or providers with superior performance
to better hospitals or physicians (or away from worse ones). may be limited in their ability to discriminate individual
As one basic litmus test, a measure based on prior perfor- hospitals from one another. There may be no simple solution
mance should reliably identify providers likely to have to resolving the basic tension implied by performance
superior performance now and in the future. At the same measures that are unfair to providers yet informative for
time, an ideal measure would not incentivize perverse be- patients. However, it underscores the importance of being
haviors (e.g., surgeons doing unnecessary procedures to clear about both the primary purpose (quality improvement
meet a specific volume standard) or negatively affect other or selective referral) and whose interests are receiving top
domains of quality (e.g., patient autonomy, access, and priority (provider or patient).
satisfaction).
Measures that work well for quality improvement may
Future of Performance Measurement
not be particularly useful for selective referral, and vice versa.
For example, appropriate use of perioperative antibiotics in Although great progress has been made, the science of
surgical patients is a good measure for quality improve- surgical quality measurement is still in its infancy. Several
ment. This process of care is clinically meaningful, linked barriers must be overcome before performance measures
to lower risks of SSIs, and directly actionable. Conversely, can be optimally used to improve patient care. Perhaps the
antibiotic use would not be particularly useful for selective biggest barrier is the lack of an accurate and affordable mea-
referral purposes. It is unlikely that patients would use this surement infrastructure. One practical solution that may
information to decide where to have surgery. More impor- reduce the expense of detailed data collection with clinical
tantly, surgeons with high rates of appropriate antibiotic registries is to create hybrid systems that join data elements
use may not necessarily do better with more important from administrative and clinical data sets. Although admin-
outcomes (e.g., mortality). Physician performance with istrative data are criticized for their lack of accuracy in iden-
one quality indicator is often poorly correlated with other tifying coexisting diseases, they can reliably identify the
indicators for the same or other clinical conditions.26 type of procedure performed, certain demographic variables
As a counter example, the two main quality indicators (e.g., age, gender, and race), and some outcome variables
for pancreatic cancer—hospital volume and operative (e.g., vital status, discharge to a skilled nursing facility, and
mortality—are very informative in the context of selective length of stay). This set of variables could then be linked to
referral. Patients would markedly improve their odds of a limited set of clinical risk factors that would allow robust
surviving surgery by selecting hospitals highly ranked by risk adjustment. This solution will be even more attractive
either measure [see Figure 1]. However, neither measure as administrative data come to contain more accurate
would be particularly useful for quality improvement information (e.g., present-on-admission codes to distinguish
purposes. Volume is not readily actionable; mortality complications from coexisting problems).28
rates are too unstable at the level of individual hospitals In addition to improving the efficiency of data collection,
(because of small sample size problems) to identify top it would be worthwhile to rethink how existing registries
performers, identify best practices, or evaluate the effects of are designed so as to make them less expensive and more
improvement activities. useful. For example, although the ACS-NSQIP is in a key
Many believe that a good performance measure must position to become the leading measurement platform for
discriminate performance at the individual level. From the surgical quality improvement, several changes could be
provider perspective in particular, a “fair” measure must made to ensure its success.29 First, the burden of data collec-
reliably reflect the performance of individual hospitals or tion could be reduced; this would substantially decrease the
physicians. Unfortunately, as described earlier, small casel- costs of participating. The number of data elements could be
oads (and sometimes case-mix variation) conspire against reduced by creating more parsimonious risk adjustment
this objective for most procedures. Patients, however, should models.30 Second, the sampling strategy could be changed to
value information that improves their odds of good sample 100% of the most important operations; this change
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would allow assessment of procedure-specific outcomes. surgery, as described with other changes in a recent “blue-
Ultimately, participating hospitals would need procedure- print” for a new NSQIP, discussed above. As the advantages
specific outcome data to target specific operations for of this technique become more widely known, there is
improvement. Third, clinical processes of care could be no doubt that it will become the standard technique for
added to the data collection process; this would allow hos- reporting risk-adjusted outcomes.
pitals to respond to national pay-for-performance mandates Another barrier to improving surgical performance is
and to provide more actionable quality measures. This last the lack of good global measures of performance. With the
change would require the ACS-NSQIP to manifest a level of proliferation of pay-for-performance pilot programs, vari-
ous stakeholders have been confronted with the problem
flexibility that it has not exhibited to date. With the flexibility
of how to make sense of multiple competing measures
to change data measurement periodically, the ACS-NSQIP
of quality. Most have responded by combining multiple
would not only be able to add other measures that are used
domains to create a composite measure of performance. The
in national mandates (e.g., SCIP) but also to evaluate their Premier/CMS Hospital Quality Incentive Demonstration
importance. uses a composite of process and outcome as a quality mea-
One of the biggest limitations of surgical quality measure- sure for coronary artery bypass surgery. The STS’s Task
ment is the statistical noise from the small sample sizes at Force on Quality Measurement advocates a composite score
most hospitals. An emerging technique, reliability adjust- based on a set of outcome and process measures endorsed
ment, directly addresses the problem of statistical noise. by the NQF.32 In these composite approaches, the different
This technique, based on hierarchical modeling, quantifies measures are essentially weighted equally, with no empiri-
and subtracts statistical noise from the measurement pro- cal determination of which ones are the most important.
cess.31 Essentially, it “shrinks” a provider’s performance There are, however, emerging techniques that use empiri-
back toward average, unless they deviate to such an extreme cally derived weighting to create a composite score that
that it is safe to assume that they are truly different. In optimally predicts future mortality for high-risk surgery.33
this way, it gives providers the benefit of the doubt. For As such methods become more fully developed, composite
example, Figure 2 shows the risk-adjusted mortality measures will no doubt continue to gain popularity.
and morbidity rates for colon resection in 20 ACS-NSQIP Given that most existing quality improvement efforts
hospitals before and after reliability adjustment. Prior to focus on optimizing measurement of technical quality, it is
reliability adjustment, rates of mortality and morbidity vary important not to lose sight of the fact that many quality con-
cerns arise upstream from the operation itself—that is, with
greatly across these hospitals. After reliability adjustment,
the decision to operate in the first place. Wide variations in
however, the “noise” has been removed and rates of mor-
the use of surgery have long been recognized. Some of these
bidity and mortality vary much less, yielding a range of
variations are attributable to differences in disease preva-
performance that is clinically more realistic. These reliabili- lence and physician practice style. Some, however, arise
ty-adjusted mortality rates are much more accurate at from overuse, underuse, or misuse of surgical management.
capturing true performance, as assessed by their ability to For a full accounting of surgical quality, it will be necessary
predict future performance. to develop reliable means of measuring the appropriateness
Despite increasing use in other fields, such as ambulatory of surgical treatment and the extent to which patient prefer-
care, reliability adjustment is only beginning to find applica- ences are incorporated into clinical decisions, in addition to
tions in surgery. Perhaps the most prominent example is the measures assessing how well patients do after surgery.
Massachusetts cardiac surgery report card, which publishes
reliability-adjusted mortality rates for each hospital. This Financial Disclosures: Dr. Dimick and Dr. Birkmeyer are both
approach will also likely be applied to general and vascular equity owners and paid consultants for ArborMetrix, Inc.
a b
15 50
Risk-Adjusted Mortality (%)
Risk-Adjusted Mortality (%)
40
10
30
5 20
10
0
0
Not Adjusted Adjusted for
Not Adjusted Adjusted for
for Reliability Reliability
for Reliability Reliability
Figure 2 Risk-adjusted (a) mortality and (b) morbidity rates for colon resection at individual hospitals before and after adjustment for
reliability. Data are from the 2007 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP).
02/12
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16. Fink A, Campbell DJ, Mentzer RJ, et al. The National 32. O’Brien SM, Shahian DM, DeLong ER, et al. Quality
Surgical Quality Improvement Program in non-Veterans measurement in adult cardiac surgery: part 2—statistical
Administration hospitals: initial demonstration of feasibility. considerations in composite measure scoring and provider
Ann Surg 2002;236:344–53. rating. Ann Thorac Surg 2007;83(4 Suppl):S13–26.
17. Fonarow GC, Abraham WT, Albert NM, et al. Association 33. Dimick JB, Staiger DO, Baser O, Birkmeyer JD. Composite
between performance measures and clinical outcomes for measures for predicting surgical mortality in the hospital.
patients hospitalized with heart failure. JAMA 2007;297:61. Health Aff (Millwood) 2009;28:1189–98.
02/12
3 STRATEGIES FOR IMPROVING SURGICAL

QUALITY
Nancy J.O. Birkmeyer, PhD
Surgical morbidity and mortality are major public health COE to their enrollees without restricting choice. Examples
concerns. At least 1 million surgical patients die, and many of selective referral programs include the Leapfrog Group’s
times more experience a serious complication each year Evidence-Based Hospital Referral program, Blue Cross
worldwide.1 The outcomes of surgery have been shown and Blue Shield Association Blue Distinction Centers for
to differ among providers2–7 and according to provider Specialty Care, and bariatric surgery COE programs of the
attributes such as procedure volume8–10 and subspecialty American College of Surgeons and the American Society for
training.11–13 This variability in the outcomes of surgical Metabolic and Bariatric Surgery.
procedures has long suggested opportunities to improve The extent to which selective referral programs result in
the quality of surgical care. For this reason, many large-scale improvements in surgical quality has been assessed in a
quality improvement efforts target patients undergoing number of recent studies. One group of studies has exam-
surgery. ined whether COE programs successfully identify hospitals
Payers, health care policy makers, and surgeons’ profes- with better outcomes. For example, one study investigated
sional organizations have implemented a range of strategies whether Medicare patients undergoing major cancer resec-
to improve surgical quality. With selective referral, payers tions (1994 to 1999) at National Cancer Institute (NCI) cancer
use various methods to try to steer patients to providers centers have lower mortality rates than patients at control
that they have deemed to be of higher quality. Pay-for- hospitals matched for procedure volume.14 NCI cancer cen-
performance programs, such as the Surgical Care Improve- ters had significantly lower adjusted surgical mortality rates
ment Project (SCIP), provide incentives for providers’ than control hospitals for four of the six procedures assessed,
compliance with specific evidence-based processes of peri- including colectomy, pulmonary resection, gastrectomy,
operative care. Many professional organizations, including and esophagectomy. Trends toward lower adjusted opera-
the American College of Surgeons National Surgical Quality tive mortality rates at NCI cancer centers were also observed
Improvement Program (NSQIP), have instituted outcomes for cystectomy and pancreatic resection. However, there
measurement and feedback programs to stimulate quality were no important differences in subsequent 5-year mortal-
improvement at the local level. Regional collaborative quality rates between NCI cancer centers and control hospitals
ity improvement programs go beyond outcomes measure- for any of the procedures. A subsequent study including
ment and feedback to broad-scale implementation of quality Survival, Epidemiology, and End Results (SEER)-Medicare
improvement interventions. patients from 1999 to 2003 did find improved survival rates
These strategies, which we refer to as selective referral, for patients undergoing surgery for colorectal cancer at
process compliance, outcomes measurement and feedback, NCI cancer centers compared with other hospitals, reflecting
perhaps the difference in time periods between the two
and regional collaborative quality improvement, are the cur-
studies and/or the ability to control for tumor stage with
rent, dominant approaches to surgical quality improvement
the data source used in the later study.15 In bariatric surgery,
in the United States. This chapter reviews these strategies
two studies found that bariatric COE hospitals do not
and some of the major ongoing initiatives in each [see
have lower rates of surgical complications than other
Table 1]. In addition, the evidence to date for the effective-
hospitals.16,17
ness of each of these strategies in improving surgical quality
Two recent studies considered whether selective
is summarized.
referral programs have altered referral patterns for high-risk
surgery and whether these trends have resulted in improve-
Selective Referral ments in operative mortality with those procedures.
One study found that increased market concentration was
Selective referral includes strategies that aim to identify
strongly associated with declining mortality with some
and steer patients toward providers with the best results for
high-risk cancer operations [see Figure 1], including pancre-
certain procedures. Payers’ selective referral programs may
atectomy, esophagectomy, and cystectomy.18 A smaller pro-
involve the use of tiered health plans and benefits packages
portion of mortality improvements could be attributed to
that give patients’ financial incentives (e.g., lower copay-
market concentration for lung resection, abdominal aortic
ments or monthly premiums) for selecting providers that
aneurysm repair, and aortic valve replacement, but trends
they have deemed to be of higher quality. Some payers
in market concentration had no role in declining mortality
restrict their enrollees’ choice of providers to selected
with coronary artery bypass grafting (CABG) and carotid
Centers of Excellence (COE) for certain high-risk procedures,
endarterectomy. A study based on data from Washington
whereas others simply provide information about approved
State found that the proportion of patients undergoing
surgery in hospitals meeting the Leapfrog Groups’ volume
Financial disclosure information is located at the end of this chapter standard had significantly increased for pancreatectomy
before the references. and esophagectomy, but not aortic aneurysm repair, since

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elem cont prac 3 strategies for improving surgical quality — 2
Table 1 Characteristics of Different Strategies for Improving Surgical Quality

Selective Referral Process Compliance Outcomes Measurement and Regional Collaborative
Feedback Quality Improvement
Mechanism Steer patients to best Increase compliance with Spur internal quality Identify and broadly
hospitals or surgeons evidence-based improvement with implement best practices
processes of care feedback on benchmarked
outcomes
Examples Leapfrog Group’s Surgical Care Improve- National Surgical Quality Northern New England
Evidence-Based ment Project (SKIP) Improvement Program Cardiovascular Disease
Hospital Referral Surgical Checklist projects (NSQIP) Study Group
Program Society of Thoracic Surgeons Blue Cross and Blue
Payers’ Center of (STS) National Cardiac Shield of Michigan/Blue
Excellence (COE) Surgery Database Care Network Value
programs Partnership program
Evidence: pro Effective for relatively Programs that involve Effective for motivating Improved outcomes in the
rare procedures with active participation of internal quality areas where it has been
strong evidence linking surgeons and other improvement efforts tried: cardiovascular
provider characteristics clinicians (e.g., check- among low-performing procedures, other general
(e.g., procedure lists) may be effective providers and vascular surgery, and
volume) and outcomes regardless of actual bariatric surgery
content of intervention
Evidence: con COE programs based on Disappointing results Do not provide guidance for Strategy has not been
self-reported, unreliable for other process how to improve either to widely adopted perhaps
data not effective in compliance interventions low-performing providers because expense and
identifying higher- or others complexity and lack of a
quality providers natural sponsor
implementation of the Leapfrog Groups’ Evidence-Based referral is probably best reserved for high-risk procedures
Hospital Referral Program.19 Although mortality rates tend- where a strong relation between provider structural charac-
ed to be lower for hospitals meeting the volume thresholds, teristics (such as procedure volume or subspecialty training)
statewide mortality rates did not improve over the time and outcomes has been demonstrated. Selective referral pro-
period.19 grams should not rely on self-reported and/or unverifiable
Selective referral is arguably the most controversial of the information to determine which providers have the highest
quality improvement strategies discussed in this chapter. quality.16,17,21
Although selective referral strategies are effective in improv-
ing outcomes in a number of procedures, they are less useful
Process Compliance
for many others. This strategy is also highly divisive, with
many arguing that providers should be judged by their own Another strategy for improving surgical quality is for
clinical outcomes rather than having their outcomes judged hospitals to increase their use of evidence-based processes
by imperfect proxy measures, such as volume.20 Selective of care. Public and private payers’ ongoing pay-for-
performance programs, which provide financial incentives
for high rates of compliance, best exemplify this strategy.
The largest pay-for-performance program targeting surgery
Decrease in operative mortality (%)
40
is the SCIP, which links Medicare hospital reimbursement
Increased market concentration Other to satisfactory adherence to processes for reducing rates of
surgical site infection, postoperative cardiac events, venous
30 thromboembolism, and ventilator-associated pneumonia.
surgical care improvement project (scip)

20 The relation between SCIP measure compliance and out-
comes has been assessed in a number of studies [see Table 2].
Nicholas and colleagues used national Medicare data to
examine whether rates of compliance with the SCIP mea-
10
sures were associated with rates of surgical site infection,
venous thromboembolism, or surgical mortality for patients
undergoing high-risk cancer or cardiovascular procedures.22
0 Although process compliance ranged from 53.7% for
Esophagectomy Pancreatectomy Cystectomy Lung resection
hospitals in the bottom tercile to 91.4% for hospitals in the
Figure 1 Percent of mortality decline for esophagectomy, pancre- top tertile, there was no relation between rates of process
atectomy, cystectomy, and lung resection attributable to increases in compliance and rates of surgical site infection, venous
market concentration, based on 2001 to 2008 national Medicare data.18 thromboembolism, or surgical mortality overall or for any of
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Table 2 Evidence Regarding the Relation between Compliance with Surgical Care Improvement Project
(SCIP) Measures and Clinical Outcomes
Study, Year Data Sources (Year) Patient Population (n) SCIP Measure* Infection VTE Mortality
Nicholas et al, 2000 US hospitals/ 6 high-risk procedures SCIP INF/VTE- No No No

201022 Medicare/Hospital (325,052) Composite
Compare (2005–2006)
Ingraham et al, 200 ACS-NSQIP hospitals/ General and vascular SCIP INF-1 No No
201023 Hospital Compare (2008) surgery (81,524) SCIP INF-2 Yes No
SCIP INF-3 No No
SCIP INF-6 No No
Stulberg et al, 398 Premier Inc. hospitals/ Inpatient surgery SCIP INF-1 No
201025 Hospital Compare (405,720) SCIP INF-2 No
(2006–2008) SCIP INF-3 No
SCIP INF-4 No
SCIP INF-6 No
SCIP INF-7 No
SCIP INF-Composite Yes
Lehtinen, 201041 1 ACS-NSQIP hospital Gastrointestinal surgery SCIP INF-10 No

(2006–2009) (469)
Pastor, 201042 1 US hospital (2006–2008) Colorectal surgery (491) SCIP INF-Composite No
Hawn et al, 200826 95 Veterans Affairs hospitals Elective orthopedic, SCIP INF-1 No
(2005–2006) colon, and vascular
surgery (9,195)
Forbes et al, 200827 1 Canadian hospital Major hepatobiliary or SCIP INF-Composite Yes—NS
(2004–2007) colorectal surgery
(208)
Berenguer, 201029 1 ACS-NSQIP hospital Colorectal surgery (197) SCIP INF-Composite

(2006–2008)
Hedrick et al, 1 hospital (2000–2005) Colorectal surgery (307) SCIP INF-Composite Yes
200728
ACS-NSQIP = American College of Surgeons-National Surgical Quality Improvement Program; NS = not statistically significant; VTE = venous thromboembolism.
*SCIP measures: SCIP INF-1: prophylactic antibiotic received within 1 hour prior to surgical incision; SCIP INF-2: prophylactic antibiotic selection for surgical patients; SCIP
INF-3: prophylactic antibiotics discontinued within 24 hours after surgery end; SCIP INF-4: cardiac surgery patients with controlled 6 am postoperative blood glucose; SCIP
INF-6: surgery patients with appropriate hair removal; SCIP INF-7: colorectal surgery patients with immediate postoperative normothermia; SCIP INF-10: surgery patients
with perioperative temperature management; SCIP VTE-1: surgery patients with recommended venous thromboembolism prophylaxis ordered; SCIP VTE-2: surgery patients
who received appropriate venous thromboembolism prophylaxis within 24 hours prior to surgery to 24 hours after surgery.
the six procedures individually. Numerous studies have simply are not representative of their use in general practice.
examined the relation between the subset of SCIP measures This is sometimes referred to as the difference between the
related to the prevention of surgical site infection (SCIP INF) effectiveness and the efficacy of an intervention. Another
and clinical outcomes. Of these, one found that just one plausible explanation is that high rates of compliance or
of the measures (SCIP 2: appropriate antibiotic given) was improvements in rates of compliance are really indicative
associated with rates of surgical site infection.23 Another of better documentation rather than actual compliance
study found that only SCIP 1 (antibiotic given within 1 hour or clinical care processes. The three single-site studies27–29
of surgery) was associated with rates of surgical site infec- showing the effectiveness of these process changes in the
tion among colorectal surgery patients.24 Another study prevention of surgical site infections for colorectal surgery
found that none of the individual SCIP INF measures were patients at their sites following changes in clinical care
associated with rates of surgical site infection but that a would support this explanation.
global composite measure was.25 The other studies found
no relation between SCIP INF measures and clinical
Checklists
outcomes.26
Taken as a whole, these studies provide scant evidence Although not yet a target of pay-for-performance or other
for the effectiveness of process compliance in improving incentive programs, surgical checklists can be considered
outcomes in surgery. Given that the SCIP measures were another process compliance strategy. Checklists, which have
chosen on the basis of randomized trials supporting their long been used in aviation, came to be used in health care
effectiveness, these findings are somewhat counterintuitive. following the publication of a study documenting their
One explanation may be that in the randomized trials, these effectiveness for the prevention of catheter-related blood-
interventions were assessed under tightly controlled condi- stream infections in intensive care units.30 Surgical checklists
tions (e.g., patient populations, hospital environments) that range from simple preoperative “timeouts” to prevent rare
01/12
but dreadful errors, such as operating on the wrong site for certain high-risk procedures, most frequently coronary
or patient, to broad lists of practices known to reduce bypass surgery.
complications and/or improve teamwork. There is strong evidence that outcomes measurement
Checklists have been the subject of two recent process and feedback are an effective strategy for reducing rates of
compliance studies in surgery. A study supported by the surgical morbidity and mortality. For example, surgical
World Health Organization (WHO) tested the effects of a complication rates decreased by more than 40% in VA
19-item intraoperative checklist among nearly 4,000 patients hospitals following the implementation of the NSQIP.33
undergoing noncardiac surgery at eight large hospitals Surgical complication rates also dropped among private
around the world using a pre/post study design.31 The sec- sector hospitals after the implementation of NSQIP, although
ond study evaluated the effects of a comprehensive checklist much less dramatically than in the VA hospitals.34 Mortality
(11-part instrument with more than 100 items, encompass- among Medicare patients undergoing coronary bypass
ing all phases of care) in six regional and tertiary care surgery in the state of New York declined by 41% between
centers and five control hospitals in the Netherlands.32 1989 and 1992 with the implementation of the New York
Despite differences in the extensiveness of checklists and in State Department of Health Cardiac Reporting Systems.35
the scientific rigor of the study designs, both studies found During this same time period, mortality among Medicare
that the use of a surgical checklist resulted in dramatic patients undergoing coronary bypass nationally declined by
reductions in surgical morbidity and mortality. In the WHO only 13%.36 Another study assessed rates of mortality with
study, mortality was reduced by almost 50% and complica- coronary artery bypass with (Ohio, New Jersey, New York,
tions dropped from 11% to 7%. In the de Vries and col- and Pennsylvania) and without public outcomes reporting
leagues study, mortality was also cut in half and rates of systems between 1994 and 1999.37 Coronary bypass mortal-
complications were reduced from 15% to 11%.32 ity rates in states with public reporting systems decreased
In each of the two surgical checklist studies, all types of between 20 and 33% more than those in states without these
complications were reduced rather than just those that systems.
would be expected based on the content of the checklists. Outcomes measurement and feedback can be an effective
This suggests that checklists may have indirect effects that way to improve surgical care. However, certain conditions
are necessary for the success of this approach, including
may be as, if not more important, than their specific content.
mandatory reporting of all hospitals, audits of data quality,
For example, checklists could reduce the rates of surgical
a neutral third party to analyze and report data, and some
complications by improving hospitals’ safety culture, lead to
kind of pressure (e.g., public reporting) for poor performers
more effective communication and/or handoffs between
to improve.38 It also probably works best for procedures
different types of providers, or reduce distractions in the
where the primary outcomes occur within the perioperative
operating room. The durability of improvements in out-
period and can be measured and verified at a relatively low
comes attained with checklists is yet to be determined as
cost. Finally, the way that this approach works is by stimu-
neither of the two studies had a very long duration of
lating improvements among low-performing providers.
postintervention study time (3 to 6 months). It is also to be
However, it does not provide those institutions in need of
determined what specific items are essential for an effective
improvement with information they will need to accomplish
surgical checklist. Nonetheless, checklists should be con- that goal. Outcomes measurement and feedback programs
sidered among the more promising interventions for also do not provide the motivation or the information
improving rates of morbidity and mortality with surgery. required to improve care overall.
Outcomes Measurement and Feedback Regional Collaborative Quality Improvement

Many of the professional organizations in surgery have Regional collaborative quality improvement goes beyond
focused their quality improvement efforts on the develop- the measurement and feedback of outcomes data with re-
ment and dissemination of clinical registries for tracking gion-wide implementation of explicit quality improvement
surgical outcomes. The goal of these efforts is to provide interventions. Similar to outcomes measurement and feed-
benchmarking data with which hospitals and surgeons can back programs, regional collaborative quality improvement
compare their outcomes with those of their peers. The ratio- programs are based on clinical registry data, which are used
nale for benchmarking performance is to allow hospitals to to provide regular feedback on performance. Where region-
identify opportunities for quality improvement and there- al collaborative quality improvement programs differ from
fore to be motivated to engage in internal quality improve- straight outcomes measurement and feedback programs is
ment activities. The Society of Thoracic Surgeons (STS) is that they convene regularly to review and interpret registry
considered a pioneer in this area, and virtually all US hospi- data with a specific focus on areas of variation in practice
tals involved in cardiac surgery now participate in its regis- or outcomes. Once the processes that are associated with
try. The NSQIP is the largest outcomes measurement plat- the best outcomes (best practices) are identified, they are
form in noncardiac surgery. The NSQIP was developed broadly implemented throughout the region. The Northern
for use in Veterans Affairs (VA) hospitals, but since being New England Cardiovascular Disease Study Group, which
adapted for use in the private sector by the American started in 1987, is the original regional collaborative quality
College of Surgeons, several hundred private sector hospi- improvement collaborative. In Michigan, Blue Cross and
tals now participate. Finally, a number of states have been Blue Shield of Michigan/Blue Care Network (BCBSM/BCN)
measuring and publicly reporting risk-adjusted outcomes has funded similar programs in many clinical areas,
01/12
including surgery (cardiac, bariatric, and other types of defined by the Adult Cardiac Surgery Registry of the
general and vascular surgery). STS), indicating that its aggregate performance exceeded
For many years, the only evidence for the effectiveness of national norms and falls within the top 10th of hospitals
regional collaborative quality improvement has been from nationwide.
the Northern New England Cardiovascular Disease Study Despite growing evidence of the effectiveness of regional,
Group. During the first 5 years of the collaborative (1987 to collaborative quality improvement, this approach has not
1992), the group received regular feedback on outcomes and been widely adopted because it is expensive, is complicated
training in continuous quality improvement techniques, and to coordinate, and lacks a natural sponsor. The programs in
teams from each of the hospitals engaged in round robin site Michigan exist because the state’s largest private insurer
visits to observe perioperative care for CABG patients at has not only funded the costs of running them but has also
other sites.39 The CABG mortality rate decreased by 24% offered additional financial incentives for hospitals to par-
over the study time period. A subsequent study based on ticipate. Convincing others, including other private payers,
Medicare data showed that northern New England and New public payers, purchasers, and provider systems, to invest
York State had a combination of the lowest CABG mortality in regional, collaborative quality improvement will require
rates in 1992 and the greatest improvement in mortality a convincing demonstration of return on investment.
rates over this time period in the country.36 Although there are substantial obstacles to more widespread
With the funding of numerous regional collaborative adoption, this is the only approach that works by reducing
quality improvement programs in the state of Michigan, variation in practice and improving quality overall. In con-
there are now many more data on which to gauge the effects trast, the other strategies aim to improve performance among
of this approach.40 For example, risk-adjusted morbidity poor performers or, in the case of selective referral, to steer
rates among patients undergoing general or vascular sur- patients away from them.
gery in hospitals participating in ACS-NSQIP in Michigan
fell from 13.1% in 2005 to 10.5% in 2009 (p < .001). In con- Summary
trast, morbidity rates in non-Michigan hospitals participat-
Each of the approaches to surgical quality improvement
ing in ACS-NSQIP remained essentially flat between 2005
addressed in this chapter has advantages and disadvantages.
and 2008 at approximately 12.5%, before dipping slightly to
Selective referral strategies are probably best reserved for
11.5% in 2009. Risk-adjusted 30-day mortality with bariatric
relatively rare procedures for which outcomes have been
surgery in Michigan fell from 0.21% in 2007 to 0.02% in 2009
shown to vary dramatically according to provider factors
(p = .004) [see Figure 2]. During this time period, bariatric
such as procedure volume. COE programs that rely on self-
surgery mortality at non-Michigan hospitals participating
reported and unaudited information have not been effective
in ACS-NSQIP did not improve significantly (0.18% to
in identifying high-quality providers. As they are currently
0.11%). In cardiac surgery, during its initial reporting peri-
configured, process compliance programs have mainly
ods (2006 to 2007 and 2007 to 2008), composite quality scores focused on improving adherence to a small number of
for Michigan hospitals as a whole were statistically indistin- evidence-based practices in perioperative care. That many
guishable from national benchmarks. Michigan hospitals of the results for process compliance programs have been
have now achieved a three-star rating from the STS (on an disappointing may reflect that what these programs have
11-item composite quality measure, which includes risk- improved is the documentation of clinical care practices
adjusted mortality, complications, internal mammary graft rather than the actual clinical care processes. Process compli-
use, and several other important processes of care, as ance efforts involving surgical checklists and the active par-
ticipation of surgeons and other members of operative teams
are having more promising results. Outcomes measurement
0.25 and feedback programs, especially where they are publicly
reported, can motivate local quality improvement efforts
0.20 among hospitals with poor performance. Finally, regional
Non-Michigan hospitals collaborative quality improvement programs may accelerate
Mortality (%)
participating in ACS-NSQIP improvement by having the ability to rapidly identify and

0.15
broadly implement best practices. However, this strategy
has not been widely adopted, perhaps because of the
0.10 expense and complexity of these programs as well as their
Michigan hospitals lack of a natural sponsor.
0.05
Financial Disclosures: None Reported
0.00
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39. O’Connor G, Plume S, Olmstead E, et al. A regional pro- prevent surgical site infections after gastrointestinal sur-
spective study of in-hospital mortality associated with coro- gery: Holy grail or false idol? Ann Surg 2010;252:696–704.
nary artery bypass grafting: the Northern New England 42. Pastor C, Artinyan A, Varma MG, Kim E, et al. An increase
Cardiovascular Disease Study Group. JAMA 1991;266:803–9. in compliance with the Surgical Care Improvement
40. Share DA, Campbell DA, Birkmeyer N. et al. How a regional Project measures does not prevent surgical site infection in
collaborative of hospitals and physicians in Michigan colorectal surgery. Dis Colon Rectum 2010;53:24–30.
01/12
© 2009 BC Decker Inc ACS Surgery: Principles and Practice
ELEMENTS OF CONTEMPORARY PRACTICE 4 EVIDENCE-BASED SURGERY — 1
4 EVIDENCE-BASED SURGERY
Samuel R.G. Finlayson, MD, MPH
Evidence-based surgery describes the consistent and judicious analytic tools that a modern, evidence-based surgeon needs
use of the best available scientific evidence in making deci- to navigate the surgical literature and implement practices
sions about the care of surgical patients. Evidence-based sur- that are based on sound science.
gery is part of a broader movement—evidence-based
medicine—to apply the scientific method to medical practice.
This movement has its historical roots in the pioneering work Guidelines and Secondary Sources of Scientific
of the Scottish epidemiologist Archibald Cochrane (1909– Evidence
1988), for whom the preeminent international organization To meet the growing demand for evidence-based practice
for research in evidence-based medicine, the Cochrane Col- information, a market has developed around the work of
laboration, is named. The term “evidence-based medicine” pooling and interpreting “best scientific evidence.” Scientific
itself was popularized through a landmark article advocating reviews serve as secondary sources for evidence-based prac-
a new approach to medical education that appeared in the tice and are increasingly found in journals, in books, and on
Journal of the American Medical Association in 1992.1 This the Internet. Prominent examples include Clinical Evidence
article urged the de-emphasis of “intuition, unsystematic (published semiannually by the British Journal of Medicine and
clinical experience, and pathophysiologic rationale as suffi- continually updated online4), the Cochrane Database of Sys-
cient grounds for clinical decision making.” In essence, advo- tematic Reviews,5 and the Institute for Healthcare Improve-
cates of evidence-based medicine seek to demote “expert ment.6 For surgical practices specifically, the Surgical Care
opinion” to the least valid basis for clinical decision making. Improvement Project serves as a clearinghouse for evidence-
The practice of surgery, once driven more by the eminence based guidelines.
of tradition than the evidence of science, now increasingly Efforts to summarize and disseminate information about
requires its students to adopt evidence-based scientific stan- evidence-based surgery provide a convenient “user interface”
dards of practice. for the surgical literature that can be very helpful to practicing
The imperative that surgical care be delivered in accor- surgeons. However, because such aids are far from complete
dance with the best available scientific evidence is only one and new evidence emerges continually, surgeons cannot rely
facet of evidence-based surgery. In addition, evidence-based on these sources entirely. The modern “evidence-based sur-
surgery refers to systematic efforts to establish standards of geon” must learn to assess the quality of individual scientific
care supported by science, as well as the movement to popu- studies and interpret their implications for his or her practice.
larize evidence-based practice. Systematic reviews of the lit-
erature are often generated by independent researchers or
collaborative study groups (e.g., Cochrane collaborations) Levels of Evidence
and published as review articles in journals or disseminated Evidence for surgical practice comes in many forms with
as practice guidelines. The movement to propagate evidence- variable reliability. At one end of the spectrum is an empirical
based surgical practice is a relatively recent phenomenon impression that a practice makes physiologic sense and seems
exemplified by the collaborative efforts to develop the Surgi- to work well. Much of what surgeons do in practice falls into
cal Care Improvement Project Core Measure Set2 and by the this category and has not been formally tested. At the other
US federal government’s efforts to reward best practices with end of the spectrum is evidence accumulated from multiple
“pay for performance” policies.3 Although researchers are carefully conducted scientific experiments with consistent
charged with generating and disseminating scientific evidence, and reproducible results. The task of the evidence-based sur-
the greatest responsibility for the success of evidence-based geon is to judge the reliability of scientific evidence and select
surgery is ultimately with individual surgeons, who must not practices that conform to the best evidence available.
only practice evidence-based surgery but also understand and To help clinicians judge the strength of scientific evidence,
appropriately interpret an immense surgical literature. researchers have attempted to create hierarchies of evidence,
This chapter provides a framework for evaluating the which range from those sources that are most reliable to those
strength of evidence for surgical practices, the validity of sci- that are least sure. With the understanding that not all practices
entific studies in surgery, and the role of evidence-based sur- have been subjected to the highest levels of scientific scrutiny,
gery in assessing and improving the quality of surgical care. clinicians are advised to base practices on evidence gleaned
The intent is to provide the reader with conceptual and from studies as high on the evidence hierarchy as possible.
DOI 10.2310/7800.SECC04
02/09
A commonly cited example of such a hierarchy is the “levels However, even studies with this design can lead to erroneous
of evidence” system popularized by the U.S. Preventive Med- conclusions if they are not performed properly. Evaluating
icine Task Force (USPMTF) [see Table 1].7 Since its incep- the quality of clinical evidence requires a close look at how
tion, the hierarchy of scientific evidence created by the the study that produced it was conceived, implemented, ana-
USPMTF has become common parlance among clinicians. lyzed, and interpreted.
Hence, frequently heard references to “level 1 evidence” refer Scientific evidence from studies of clinical practice relies on
to well-conducted randomized controlled trials. However, two important inferences. The first inference is that the
almost as soon as the USPMTF released its evidence grading observed outcome is the result of the practice and cannot be
system, debate about its adequacy began.8 The predominant attributed to some alternative explanation. When this infer-
criticism has been that the system is too simple and inflexible ence is deemed true, the study is considered to have internal
to accurately describe the strength of evidence for clinical validity. The second inference is that what was observed in the
practices. Although the system identifies the design of the clinical study is relevant to scenarios outside the study where
study from which the evidence is drawn, it does not describe the surgeon seeks to implement the practice. The extent to
important factors that influence the quality of the study. For which this is true is called external validity or generalizability.
example, in the USPMTF system, the same grade is awarded Whereas internal validity relies on how well the study is con-
to a randomized, double-blind, placebo-controlled trial with ducted and the results analyzed, external validity relies on
50,000 subjects as to an unblinded randomized trial with 30 how well the study plan reflects the real-world clinical ques-
subjects. The latter trial would, in turn, be graded higher tion that inspired it and how well the study’s conclusions
than a well-designed and conducted, multi-institution, pro- apply to real-world scenarios outside the study [see Figure 1].
spective cohort study with 10,000 subjects. Poor external validity can also refer to the difference between
In response to these deficiencies, numerous alternative an intervention’s efficacy (how well it works when applied
grading systems have been developed that take into account perfectly) and its effectiveness (whether it has the same effect
factors other than study design, such as quality, consistency, when applied generally in an uncontrolled environment).
and completeness. However, it is widely recognized that no
single grading system is perfect,9 and surgeons are often
required to judge the quality and applicability of scientific Evaluating the Quality of a Study: Internal Validity
evidence for themselves. Assessment of the internal validity of a study requires
an understanding of the potential influence of chance, bias,
and confounding [see Table 2]. Chance refers to unpredictable
Appraising Scientific Evidence
randomness of events that might mislead researchers. Bias
Specific study designs are associated with different levels of refers to systematic errors in how study subjects were selected
confidence about cause and effect. The clinical study design or assessed. Confounding refers to differences in the com-
that is considered to have the greatest potential for determin- parison groups (other than the intended exposure) that lead
ing causation is the randomized, controlled clinical trial. to differences in outcomes.
Table 1 Levels of Evidence, as Stratified by the chance

U.S. Preventive Services Task Force
In clinical studies that compare outcomes between two or
Level of Evidence Source of Evidence more groups, the assumption that there is no difference in
I At least one properly randomized controlled outcomes is called the null hypothesis. Erroneous conclusions
trial with regard to the null hypothesis can sometimes occur by
II – 1 Well-designed controlled trials without chance alone. There are two types of chance-related errors:
randomization type I and type II. Type I error (also called error) occurs
II – 2 Well-designed cohort or case-control ana- when researchers erroneously reject the null hypothesis, that
lytic study, preferably from more than is, infer that there is a difference in outcomes when there is
one center or research group really no difference. Type II error (also called error) occurs
II – 3 Multiple time-series with or without inter- when researchers erroneously confirm the null hypothesis,
vention or possibly dramatic results that is, infer that there is no difference in outcomes when, in
from uncontrolled trials (e.g., penicillin reality, a difference exists.
treatment in the 1940s)
III Opinions from respected authorities based Type I Errors
on clinical experience, descriptive stud-
ies and case reports, or committees of
Statistical testing is used to quantify the likelihood of a type
experts I error. A “p value” indicates the probability that observed
differences between groups might be due to chance alone. The
Category of Basis of Recommendation
Recommendation threshold for “statistical significance” is conventionally set at
a p value of .05, signifying that the likelihood of the observed
Level A Good and consistent scientific evidence
differences being due to chance alone is 5 out of 100. Although
Level B Limited or inconsistent scientific evidence a likelihood of 5% falls short of absolute certainty, this level of
Level C Consensus and/or expert opinion confidence is generally accepted as scientific proof.
An alternative expression of statistical likelihood is con-
This simple categorization scheme is generally considered inadequate but is still
frequently referenced. fidence intervals. Confidence intervals show the range of
02/09
“THE REAL WORLD”
Ask the question &

design the study
Apply evidence
to practice
Processes related
to external validity
Processes related
to internal validity
Conduct Measure the results Analyze & interpret

the study the results
THE STUDY
Figure 1 Processes that affect the internal and external validity of a clinical study.
the observed difference that would be expected if the same

Table 2 Methods Observed in Published Clinical Studies study were repeated an infinite number of times. For
that Demonstrate Efforts to Minimize the Effects of example, a 95% confidence interval would include the
Chance, Bias, and Confounding observed difference 95% of the times that the study was
Chance repeated.
Many statistical tests can be used to calculate p values and
Power calculations during design of the study
confidence intervals. The appropriate statistical test must be
Appropriate statistical test to avoid type I error selected according to several factors, including the number of
Large enough sample size to avoid type II error observations in the comparison groups, the number of groups
being compared, whether two or more groups are being com-
Bias
pared with each other or one group is being compared with
Prospective study designs itself after some interval of time, what kind of numerical data
Careful subject selection are being analyzed (e.g. continuous, categorical), or whether
Good sampling strategy risk adjustment is required. Although most surgeons are
unlikely to fully comprehend all of the nuances of more com-
Appropriate inclusion and exclusion criteria
plex statistical analyses, most clinical surgical studies are
Blinding designed simply enough to employ statistical tests that are
Clear and careful protocols for data collection within reach of the nonstatistician. Fortunately, several useful
and concise texts are available that can help surgeons become
Confounding
conversant in basic statistical methods.10–12
Study design
Randomization Type II Errors
Restriction Type II errors (erroneously accepting the null hypothesis)
Matching often occur when sample size is simply insufficient to detect
small but clinically important differences in outcomes. When
Instrumental variables
a study’s sample size is too small to detect differences in out-
Data analysis comes between comparison groups, it is said to lack sufficient
Risk adjustment statistical power. Once a study is complete, no amount of
Stratification
analysis can correct for insufficient statistical power. Before
starting a study, researchers should perform a “power calcu-
Propensity scores lation,” which involves determining the minimum size of a
02/09
meaningful difference in outcomes and then calculating the illness confounds the observed association between mortality
number of observations required to show that difference sta- and surgical approach.
tistically. Surgeons should be particularly cautious when In evaluating the strength of evidence in a published study,
evaluating studies with null findings, particularly when no readers must assess how well the researchers accounted for
power calculation is explicitly reported. An evidence-based the potential effect of confounding. Confounding can be
surgeon is wise to remember the adage, “No evidence for minimized in several ways, both in the design of the study
effect is not necessarily evidence of no effect.” and in the analysis of the study’s results. In the design of a
study, confounding is most effectively addressed with ran-
bia s domization. When subjects are randomized, potentially con-
Bias refers to a systematic problem with a clinical study founding variables (both recognized and unrecognized) are
that results in an inaccurate estimate of the differences in likely to be evenly distributed across comparison groups.
outcomes between comparison groups. There are two general Thus, whereas the baseline rate of outcomes in the entire
types of bias: selection bias and measurement bias. The former cohort might be influenced by these factors, the differences
results from errors in the choice of study subjects. The latter across comparison groups are less likely to be affected.
results from errors in the way information about exposures or Where randomization is not practical, restriction or matching
outcomes (or other pertinent data) is obtained. can be used to prevent confounding. Restriction refers to the
Selection bias refers to any imperfection in the selection pro- tight control of study entry criteria (e.g., enter only elective
cess that results in either the wrong types of subjects (people colectomy cases in the study described above). However,
who are not typical of the target population) or a sample of restrictive entry criteria can sometimes limit generalizability.
subjects that is for some reason (unrelated to the intervention) Matching refers to using a comparison group of unexposed
more likely to have the outcome of interest. For example, paid (control) subjects who are identical to the exposed (case)
volunteer subjects may be more motivated to comply with subjects across a set of characteristics (e.g., age, sex, resi-
treatment regimens and report favorable results, resulting in an dence) that have the potential to result in confounding.
overestimate of the effect of an intervention. This would affect A more complicated technique used to limit the effect of
both internal validity (inference about size of the effect) and confounding is instrumental variable analysis. This approach
external validity (generalizability to other populations) As involves studying the effect of a given exposure on outcomes
another example, selecting subjects from among diners at a by comparing groups with different levels of a third factor
Szechuan Chinese restaurant for a trial of medical versus surgi- (the instrumental variable) that is highly correlated with the
cal treatment of gastroesophageal reflux might lead to results exposure but does not independently affect the outcome.13
favoring medical treatment (people with reflux who consume For example, an observational study of the effect of catheter-
Szechuan Chinese food are more likely to have symptoms that ization and revascularization on mortality following acute
are already well-controlled medically). When assessing the myocardial infarction is prone to confounding related to dif-
validity of scientific evidence, surgeons must carefully consider ferences in baseline health characteristics of the populations
the characteristics of the subjects selected for study. receiving or not receiving these treatments. To limit this
Measurement bias refers to problems caused by the way potential source of confounding, a group of researchers stud-
information about outcomes or other pertinent data is ied the effect of these treatments (the exposure) on mortality
obtained. For example, in a study of sexual function after after myocardial infarction (the outcome) by comparing
surgery for rectal cancer, subjects may report symptoms dif- groups of patients living at different distances from hospitals
ferently in an in-person interview than they would in an providing these services (the instrumental variable).14 The
anonymous mailed survey. As another example, using sur- researchers assumed that potentially confounding health
geons to assess hernia repair outcomes in their own patients characteristics would be distributed randomly geographically
might result in erroneous reported rates of chronic pain. Ret- and that geographic distance would affect mortality only indi-
rospective studies are particularly prone to a variety of types rectly through its correlation with access to treatment. In a
of measurement bias. For example “recall bias” may occur way, they used distance to “randomize” their study popula-
because of subjects’ selective memory of past events, and tion to different levels of treatment for acute myocardial
“ascertainment bias” may occur if the outcome is likely to infarction.
influence how hard observers look for information about In addition to minimizing confounding through good study
exposures. Sources of measurement bias may be more subtle design, confounding can also be addressed during the ana-
than selection bias and require careful attention to reported lytic phase of a study. The most common approach is the use
study methods. Efforts to control measurement bias include of statistical risk adjustment techniques, typically with multi-
blinding (not telling the subject or assessor what intervention variate regression analysis. This approach involves taking into
was performed) and prospective study design. account differences in the prevalence of recognized confound-
ers across comparison groups. However, statistical risk adjust-
Confounding ment has two important limitations. First, only recognized
Confounding refers to differences in outcomes that occur confounders can be addressed. Second, every potential con-
because of differences in the baseline risks of the comparison founding variable added to a statistical model decreases the
groups. Confounding is often the result of selection bias. For model’s statistical power and thereby increases the chance of
example, a comparison of mortality after open versus laparo- resulting in a type II error.
scopic colectomy might be skewed because of the greater like- Other analytic techniques used to address confounding
lihood of open colectomy being performed as an emergency include stratification (subanalyses in which subjects with sim-
in a critically ill patient. In this example, the severity of the ilar risk profiles are compared) and propensity score risk
02/09
adjustment.15 The latter technique addresses the problem cre- surgeons who had done more than 250 cases and surgeons
ated by unequal chances of receiving treatment caused by who had less experience. Surgeons deciding whether evidence
differences in health characteristics. In an observational study supports the use of laparoscopic repair would need to exam-
of the outcomes of a given treatment, a propensity score is a ine their own experience before determining the generaliz-
scalar summary of all observed confounders that predict the ability of this study to their practices. Furthermore, some
probability of receiving the treatment. Propensity scores are have argued that one of the laparoscopic techniques com-
typically calculated using multivariate regression models and monly used in the VA trial (transabdominal preperitoneal
are used as the basis for stratified analysis or for matching repair) is outmoded and more hazardous.19 Surgeons who
cases and controls in observational studies. avoid using this approach might reasonably question the gen-
eralizability of this study to their practices.
The type of outcome measured can also affect the generaliz-
Interpreting and Applying Evidence to Practice: ability of clinical studies. Outcomes chosen for clinical studies
External Validity may be those that are most convenient or most easily quanti-
Once one is convinced that a clinical study is internally fied and may not be the outcomes of greatest interest to
valid (i.e., that the observed outcome is the result of the expo- patients. In the VA hernia trial, several outcomes were studied,
sure or intervention and cannot be attributed to some alterna- including operative complications, hernia recurrence, pain,
tive explanation), then the challenge to the surgeon is judging and length of convalescence. Some of the outcome differences
the study’s external validity (i.e., determining whether the favored open repair, whereas some favored laparoscopic repair.
findings are applicable to the clinical scenario he or she faces). The interpretation of the trial evidence for one type of repair
An assessment of external validity requires attention to sev- versus the other involves implicit value judgments regarding
eral components of a clinical study, including the patient which outcomes are most important to patients. Surgeons
population, the intervention, and the outcome measure. In applying the VA hernia trial evidence to decisions about hernia
the discussion that follows, a large prospective randomized repair must examine the specific outcomes measured before
clinical trial of laparoscopic versus open inguinal hernia repair knowing whether a study is generalizable to an individual
performed in the Veterans Administration (VA) will be used patient with specific values and interests.
as an illustrative example.16 This trial concluded that out-
comes of open repair are superior to those of laparoscopic
repair. The trial was well designed and well conducted but Evidence-Based Surgery and Quality of Care
generated substantial discussion about the generalizability of In clinical studies, the efficacy of a surgical practice is mea-
the results. sured in terms of the resulting patient outcomes. Similarly,
As noted above, subject selection bias can adversely affect efforts to assess the quality of surgical care have until recently
the external validity (or generalizability) of a study’s results. focused almost exclusively on clinical outcomes. In recent
If the population studied is in some important measure differ- years, however, the movement to promote evidence-based
ent from the population for which a surgeon is making clinical surgery has offered an alternative measure of surgical quality:
decisions, he or she may not achieve similar results. In the VA adherence to processes of care (e.g., routine use of periop-
hernia trial, subjects were military veterans, who tend to be, erative antibiotics) supported by the best available scientific
on average, older than the nonveteran general population. If evidence.
older subjects are more prone to the risks of laparoscopic The question of whether efforts to assess quality should
hernia repair (e.g., general anesthesia), one might expect that focus on evidence-based processes of care or clinical out-
the difference in morbidity outcomes would be exaggerated in comes is as much practical as philosophical. The practical
the VA trial. In this respect, a surgeon might consider the argument against outcomes is largely driven by a growing rec-
evidence provided by the trial applicable to his or her older ognition that individual hospitals and surgeons generally have
patients but reserve judgment on the use of laparoscopy to too few adverse outcomes to provide enough statistical power
repair hernias in younger, healthier patients. to show meaningful differences between providers.20 The
A striking example of the potential effect of selection bias practical argument against evidence-based processes of care
on generalizability comes from the Asymptomatic Carotid is driven by the paucity of high-leverage, procedure-specific
Artery Stenosis (ACAS) trial.17 In this large prospective ran- processes for which sound evidence is available, as well as the
domized study, volunteers for the trial were substantially logistical challenge of measuring such processes. A more
younger and healthier than the average patient who under- complete discussion of this topic is provided elsewhere
goes carotid endarterectomy. As a result, the observed peri- [see EC:2 Performance Measures in Surgical Practice].
operative mortality rate in the trial was considerably lower Given its current momentum, the evidence-based surgery
than that observed in the general population or even in the movement will likely play a progressively larger role in efforts
very hospitals where the trial was conducted.18 Although the to assess and improve quality of surgical care. Furthermore,
results of the ACAS trial significantly changed practice, one as payers increasingly turn to “pay for performance” strate-
could argue that the evidence provided by the ACAS trial gies to improve quality and control costs, the demand for
may have been generalizable only to younger populations. evidence-based practice guidelines will continue to grow.
The external validity of a clinical study can also be affected More importantly, efforts to identify and implement
by who provides the intervention and by what type of inter- evidence-based surgical practices will ultimately provide
vention is provided. In the VA hernia trial, surgeons had vari- patients with safer, better care.
able experience with the laparoscopic approach, and the trial
reported twofold differences in hernia recurrences between Financial Disclosures: None Reported
02/09
References
1. Evidence-Based Medicine Working Group. Services Task Force: a review of the process. Analysis using instrumental variables. JAMA
Evidence-based medicine: a new approach Am J Prev Med 2001;20 Suppl 3:21–35. 1994;272:859–66.
to teaching the practice of medicine. JAMA 8. Woloshin S. Arguing about grades. Eff Clin 15. Braitman LE, Rosenbaum PR. Rare out-
1992;268:2420–5. Pract 2000;3:94–5. comes, common treatments: analytic
2. Surgical Care Improvement Project Core 9. Atkins D, Eccles M, Flottorp S, et al. Sys- strategies using propensity scores. Ann
Measures. Available at http://www.jointcom tems for grading the quality of evidence and Intern Med 2002;137:693–5.
mission.org/PerformanceMeasurement/ the strength of recommendations I: Critical 16. Neumayer L, Giobbe-Hurder O, Johansson O,
PerformanceMeasurement/SCIP+Core+ appraisal of existing approaches—the et al. Open mesh versus laparoscopic mesh
Measure+Set.htm (accessed January 29, GRADE Working Group. BMC Health Serv repair of inguinal hernia. N Engl J Med
2009). Res 2004;4:38. 2004;350:1819–27.
3. Payment and Performance Improvement 10. Glanz S. Primer of biostatistics. 6th ed. 17. Executive Committee for the Asymptomatic
Programs Committee on Redesigning Health New York: McGraw-Hill Medical; 2005. Carotid Atherosclerosis Study. Endarterec-
Insurance Performance Measures. Reward- 11. Motulsky H. Intuitive biostatistics. tomy for asymptomatic carotid artery stenosis.
ing provider performance: aligning incen- New York: Oxford University Press; 1995. JAMA 1995;273:1421–8.
tives in medicare. Washington (DC): 12. Dawson B, Trapp R. Basic & clinical biosta- 18. Wennberg DE, Lucas FL, Birkmeyer JD,
National Academies Press; 2007. tistics. 4th ed. New York: McGraw-Hill et al. Variation in carotid endartectomy mor-
4. Clinical Evidence. Available at http://www. Medical; 2004. tality in the Medicare population: trial hospi-
clinicalevidence.bmj.com (accessed January 13. Stukel TA, Fisher ES, Wennberg DE, et al. tals, volume, and patient characteristics.
29, 2009). Analysis of observational studies in the pres- JAMA 1998;279:1278–81.
5. The Cochrane Collaboration. Available at ence of treatment selection bias: effects of 19. Grunwaldt LJ, Schwaitzberg SD, Rattner
http://www.cochrane.org/ (accessed January invasive cardiac management on AMI sur- DW, Jones DB. Is laparoscopic inguinal her-
29, 2009). vival using propensity score and instrumen- nia repair an operation of the past? J Am Coll
6. Institute for Healthcare Improvement. Avail- tal variable methods. JAMA 2007;297: Surg 2005;200:616–20.
able at http://www.ihi.org (accessed January 278–85. 20. Dimick JB, Welch HG, Birkmeyer JD. Sur-
29, 2009). 14. McClellan M, McNeil B, Newhouse J. Does gical mortality as an indicator of hospital
7. Harris RP, Helfand M, Woolf SH, et al. more intensive treatment of acute myocar- quality: the problem with small sample size.
Current methods of the US Preventive dial infarction in the elderly reduce mortality? JAMA 2004;292:847–51.
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© 2011 Decker Intellectual Properties ACS Surgery: Principles and Practice
ELEMENTS OF CONTEMPORARY PRACTICE 5 PATIENT SAFETY IN SURGICAL CARE: A SYSTEMS
APPROACH — 1
5 PATIENT SAFETY IN SURGICAL

CARE: A SYSTEMS APPROACH
Robert S. Rhodes, MD, FACS, and Caprice C. Greenberg, MD, MPH, FACS
High-profile catastrophes such as the explosion of the nuclear These factors also challenged the notion that medical injury
power plant at Chernobyl, the near meltdown of the nuclear is primarily the result of “bad apples” and that safety can be
power plant at Three Mile Island, the explosion of a chemical improved largely by ridding the system of these persons.
plant in Bhopal, numerous aviation disasters, and the loss of Undoubtedly, bad apples exist, but it is increasingly clear that
the space shuttles Challenger and Columbia share important health care–related injuries represent system failures and are
characteristics. First, the casualties are notable for their rarely solely the result of negligence on the part of a single
number, their celebrity, or both. Second (and more germane provider. Furthermore, there is a growing recognition that
to this chapter), each occurred as a result of multiple failures modern health care systems are as complex as—if not more
within complex systems. Human errors played a role in all of complex than—the systems associated with nuclear power,
these failures, but the errors were not single acts of negligence aviation, and space flight.1 The cognitive and technical
as much as they were magnifications of multiple seemingly complexity of the tasks performed in the operating room, the
small interactions, the significance of which was initially intensive care unit, and the emergency department certainly
unrecognized or underestimated. rivals that of these other endeavors. Furthermore, optimal
Until about a decade ago, medical errors, unlike the above patient care increasingly requires coordination among an
events, rarely received much publicity. This was in part expanding number of participants. For instance, in the early
because they affected only one patient at a time, and, as a 20th century, it is estimated that health care involved the
result, their aggregate number was neither recognized nor interaction of three persons, on average; a century later that
well publicized. Another factor has been the tendency to number had risen to 16.
regard error in medicine as a special case of medicine rather This chapter seeks to address the characteristics of systems
than as a special case of error.1 The unfortunate result of this in general and the system of surgical care in particular. It
view has been the isolation of medical errors from much of describes the growing knowledge of factors that affect human
the body of theory, analysis, and application that has been performance and how these factors contribute to adverse
developed to deal with error in other high-risk work domains surgical outcomes. The chapter also outlines current obsta-
cles to improving safety, identifies systems approaches to
such as aviation and nuclear power.
making improvements, and discusses ways in which surgeons
Yet at least two factors now appear to be changing this
can take the lead in overcoming these obstacles. An overall
view. One, the 1999 report of the Institute of Medicine
goal is that acceptance of error and a willingness to investi-
(IOM), To Err Is Human: Building a Safer Health System,
gate its underlying causes will allow health care professionals
made national headlines with its estimates of the frequency
to make use of the lessons learned from study of nonmedical
and severity of adverse events in health care, including that
systems. Although issues of patient safety are often inter-
as many as 98,000 medical error–related deaths occur each
twined with those of the overall cost-effectiveness and quality
year in the United States.2 This estimate far exceeds the
of surgical care,4 the latter are discussed in greater detail
number of casualties from more publicized nonmedical disas-
elsewhere.
ters, and if it is accurate, then medical errors would be one
of the leading causes of death in the United States. Moreover,
surgical adverse events represent over half of all adverse Nature and Magnitude of Adverse Events in Surgical
events experienced by hospitalized patients, and 75% of Care
those have their origin in the operating room.3 This highlights For most of the important concepts bearing on patient
the critical importance of patient safety in surgical care, safety in the surgical setting, generally accepted definitions
particularly in the operating room. exist [see Sidebar Definitions of Terms Related to Patient
A second factor affecting this view was advances in cogni- Safety]; the ensuing discussion is based on these definitions.5
tive psychology that greatly increased the understanding of A solid understanding of the key concepts—such as the
the influences that lead to error and affect human perfor- distinctions between an adverse event (or adverse outcome),
mance. The observation that the basic principles of human an error, and negligence—is critical for managing errors as
error are highly applicable to clinical practice has markedly system failures rather than as isolated incidents.6 In particu-
advanced our understanding and willingness to address lar, such an understanding can help in navigating the often
error in this setting. Medical errors are not a special case turbulent emotional milieu that can surround adverse patient
of medicine, and their underlying causes are not unique to events. Given their motivation to help patients, physicians
medical practice. tend to be highly sensitive to issues of causation, and this
DOI 10.2310/7800.2009
01/11
APPROACH — 2
Definitions of Terms Related to Patient Safety5 patientsafety). In 2001, these programs received reports of
105,603 errors, 2,539 (2.4%) of which resulted in patient
• An adverse event is an injury that was caused by medical
management and that results in measurable disability. injury. Of these, 353 necessitated hospitalization or
• An error is the failure of a planned action to be completed as prolonged its duration, 70 necessitated interventions to
intended or the use of a wrong plan to achieve an aim. Errors sustain life, and 14 resulted in a patient’s death. The main
can include problems in practice, products, procedures, and contributing factors were distractions (47%), workload
systems.
• A preventable adverse event is an adverse event that is increases (24%), and staffing issues (36%). Miscalculating
attributable to error. patient weight conversions (e.g., from pounds to kilo-
• An unpreventable adverse event is an adverse event resulting grams) and subsequent improper dosing are all too
from a complication that cannot be prevented given the common among pediatric patients. Errors in the adminis-
current state of knowledge.
• A near miss is an event or situation that could have resulted in tration of radiopharmaceuticals are also frequent and may
accident, injury, or illness but did not, either by chance or involve the wrong isotope (68.9%), the wrong patient
through timely intervention. (24%), the wrong dose (6.5%), or the wrong route
• A medical error is an adverse event or near miss that is
(0.6%).12 One study estimated that the US rates would
preventable with the current state of medical knowledge.
• A latent error is a condition of the system that is removed from have to be reduced by one third to match the benchmark
the adverse event, such as poorly designed equipment, rates in Germany and the United Kingdom with regard
management decisions, or physical plan of the operating room. to medical mistakes, medication errors, or laboratory
Latent errors set up the conditions in which an adverse event
can occur, but their impact is not directly recognized.
test errors.13
• An active error is an action that directly leads to the adverse • Blood transfusions continue to be plagued by patient mis-
event.
• A system is a regularly interacting or interdependent group of identification.
items forming a unified whole. • Device-related deaths and serious injuries also occur at an
• A systems error is an error that is not the result of an individu- alarming rate, even after premarket safety testing.14 The
al’s actions but the predictable outcome of a series of actions
Food and Drug Administration (FDA) maintains a regis-
and factors that make up a diagnostic or treatment process.
try of the thousands of such injuries that occur each year.
• A survey noted that 35% of physicians and 42% of the
public said that they had experienced a medical mistake in
sensitivity can then interfere with the recognition and their own care or in the care of a family member.15
management of safety issues. As might be expected, the IOM report prompted a great
The two most widely cited estimates of adverse medical deal of debate. Some medical professionals questioned the
events derive from the Harvard Medical Practice Study accuracy of the estimates, whereas others disagreed with the
(HMPS)7 and from a study in Colorado and Utah.3 The definitions of medical error and adverse event, with the extent
HMPS, a population-based study of patients hospitalized in to which either or both were considered preventable. Still
New York State during 1984, found that nearly 4% of patients others argued that adverse events that are caused by concep-
experienced an adverse event and that about half of such tual errors (e.g., a contraindicated, unsound, or inappropriate
events occurred in surgical patients. The Colorado/Utah
approach) should be differentiated from the side effects of an
study, which randomly sampled 15,000 nonpsychiatric
intended action that is correct in the circumstances (e.g.,
discharges during 1992, found that the annual incidence of
an indicated diagnostic or therapeutic procedure).16 The
adverse surgical events was 3.0% and that 54% of these
aim of this argument was to sharpen the distinction between
events were preventable. Nearly half of all adverse surgical
accidents (i.e., unplanned, unexpected, and undesired
events were accounted for by technique-related complica-
events) and true side effects (which result from correct
tions, wound infections, and postoperative bleeding. This
management and which are often accepted as reasonable
study also identified common operations that were associated
therapeutic tradeoffs).
with a significantly higher risk of an adverse event and a
The HMPS attempted to address these issues by character-
significantly higher risk of a preventable event.
izing adverse events as either preventable or unpreventable in
Other studies yielded comparable or higher estimates,8 and
the light of the prevailing state of knowledge. Preventable
still others evaluated the rates at which specific events
errors were further subclassified as either diagnostic errors or
occurred, as follows:
treatment errors; treatment errors included preventive errors
• Retained sponges or surgical instruments were estimated such as failure of prophylaxis and failure to monitor and
to occur at a rate between one in 8,801 and one in 18,760 follow treatment.7,17 The HMPS found that preventability
inpatient procedures at nonspecialty acute care hospitals.9 varied according to the type of event: 74% of early surgical
• Wrong-site surgery is more than just an isolated event,10 adverse events were judged preventable, compared with 65%
and the apparent increased frequency at which such events of nonsurgical adverse events, and more than 90% of late
are currently being reported probably reflects previous surgical failures, diagnostic mishaps, and nonprocedural
underreporting. therapeutic mishaps were judged preventable.
• Medication errors (e.g., wrong drug, wrong dose, wrong The above estimates of patient injury rates have also raised
patient, wrong time, or wrong administration route) are speculations about trends in the frequency of these events.
alarmingly frequent.11,12 The US Pharmacopeia monitors To some, the observation that the rate of such events was
these events through its reporting programs (www.usp.org/ lower in the Colorado/Utah study than in the HMPS suggests
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APPROACH — 3
that patient safety was improving even before the IOM report. decisions or plans that are removed from the point of care.
Although there may be some improvements in care, wide They do not produce an immediate result but rather set up
gaps in quality persist (www.healthgrades.com/business/ the conditions in which a given result can arise. The impor-
study/quality.aspx). tance of a system’s latent failures as contributing factors in
Regardless of any actual trend, there is agreement that adverse outcomes may be illustrated by considering a general
progress since the IOM report has been slow, that the results schema of an injury [see Figure 1].21 Whereas overt system
have been modest at best, and that the gap between the best problems are relatively easy to identify and correct, latent
possible care and the care actually being delivered remains failures are insidious and often do not become evident until
large.18–20 Although the lack of more evident improvement has a seemingly improbable series of events produces errors in
been somewhat disappointing, clear progress has nevertheless otherwise routine processes. Latent failures tend to be intro-
been made with respect to (1) understanding the complexities duced by persons who work at the “blunt end” of the system
of medical care systems, (2) identifying the challenges to (e.g., management or housekeeping) but do not actively
improving these systems, and (3) developing new perspec- participate in the main processes of care. A typical injury
tives on the assessment of errors. Thus, an increase in pathway is one in which organizational processes introduce
estimates of the incidence of adverse events may simply latent failures, which in turn produce system defects, which
reflect improved reporting rather than actual increases in in turn interact with external events so that persons who work
their occurrence. at the “sharp end” of the system (e.g., anesthesiologists,
nurses, or surgeons) commit unsafe acts. These unsafe acts
Nature and Characteristics of Systems precipitate an active failure that then penetrates the final
safety barrier or barriers.22 Indeed, the greatest risk of an
A system may be broadly defined as a regularly interacting adverse event in a complex system may come not from a
or interdependent group of items that form a unified whole. breakdown of one or more major subsystems or from isolated
System functions or tasks usually involve sequential steps that operator errors but from the presence or accumulation of
have human, technological, and logistical components. The latent failures.21,23,24
overall probability of a system failure (i.e., an adverse out-
come), then, is a function of the probability of error within
each step, the total number of steps, and the degree to which Surgical Care as a System
the steps are coupled. The degree of coupling is the extent to The characteristics of systems already discussed (see above)
which an error at one step can propagate through subsequent have many attributes directly applicable to medicine in
steps and adversely affect the final outcome. Loosely coupled general and to surgery and anesthesiology in particular. In
systems tend to have built-in redundancy that acts as a safety addition to the parallels between the habitats associated with
barrier to prevent errors from propagating to subsequent surgery (e.g., the operating room, the intensive care unit, and
steps. As a result, satisfactory outcomes in such systems are the emergency department) and those associated with many
far less dependent on successful completion of each step. high-tech, high-risk nonmedical endeavors, strong parallels
Errors in loosely coupled systems are more readily “trapped” exist between observed behavior in the operating room and
by these safety barriers. behavioral issues in an airplane cockpit.25,26
In contrast to loosely coupled systems, tightly coupled The nature of the operating room as a system and the com-
systems have relatively little redundancy and relatively few plexity of the interactions that occur there have been studied
fail-safe mechanisms. Consequently, successful outcomes in extensively. The performance of the operating room system
tightly coupled systems are highly dependent on the success depends on the individual performance of practitioners, the
of each step in essentially a factorial fashion. Thus, the interactions of those individuals or teamwork, and the envi-
probability of success in a tightly coupled linear 20-step pro- ronment in which the practitioners work. It is important to
cess with a 1% likelihood of error at each step is equivalent note the interdependence of each of these components of the
to 0.99 factored 20 times, or 0.818. Thus, even though the system. To understand the role that each plays, we examine
probability of error for each step is .01, the overall likelihood each and their impact on surgical safety in turn: individual
of an unintended outcome is 0.182. performance, teamwork, and environmental or structural
Given that safety barriers are generally more numerous in factors.
loosely coupled than in tightly coupled systems, it is relatively
unusual for an isolated error to produce an injury or system
failure in the former. Thus, failures in loosely coupled Factors that Affect Performance
systems typically involve malfunctions at multiple steps. A
tradeoff with the level of redundancy in loosely coupled cognitive psychology of individual performance
systems is that it makes the system more complex, and the Because human factors play a major role in system failure,
added complexity can introduce its own errors. any attempt to improve patient safety must be based on an
James Reason was the first to distinguish between active understanding of the factors that affect human performance
and latent system errors and their individual importance in and their relation to human error.27 Major advances in the
understanding the overall role in system failures.21 Active field of cognitive psychology over the past several decades
errors are what might be traditionally associated with the have greatly enhanced the understanding of human perfor-
term “error”: a discrete action that produces an immediate mance. A widely accepted schema classifies such performance
effect. Latent errors, on the other hand, are structural into the following three types,28 in descending order of
characteristics of the system, features of the environment, or familiarity with the specific task:
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APPROACH — 4
Fallible Defenses
Decisions
No Actual Injury
Unsafe Acts Prevented by
Defenses
Line
Management
Window
Deficiencies
of Injury
Opportunity
Precursors of Latent Unsafe Active

Unsafe Acts Failures Acts Failures
Figure 1 Schematic depiction of the process by which system failures (latent and active) may lead to injury. Defenses may be
inadequate if they allow the formation of a window of injury opportunity.
1. Skill-based performance. This type of performance is gov- Table 1 Common Modes of Failure Associated with
erned by stored patterns of preprogrammed instructions. Specific Types of Performance21
It occurs without conscious control and uses long-term Failures of Skill-Based Performance
memory. Inattention
2. Rule-based performance. This type involves solving prob- Double-capture slips
lems by means of stored rules of the if-then variety. Like Omissions following interruptions
skill-based performance, it uses long-term memory; Reduced intentionality
Perceptual confusions
however, unlike skill-based performance, it is associated Interference errors
with a consciousness that a problem exists.23 The rules Overattention
are usually based on experience garnered from previous Omissions
similar situations and are structured hierarchically, with Repetitions
Reversals
the main rules on top; their strength appears to be a func-
tion of how recently and how frequently they are used.27 Failures of Rule-Based Performance
Rule-based performance varies according to expertise: Misapplication of good rules
First exceptions
novices tend to rely on a few main rules, whereas experts Countersigns and nonsigns
have many side rules and exceptions. Informational overload
3. Knowledge-based performance. This type involves conscious Rule strength
analytic processes and stored knowledge. It relies on General rules
Redundancy
working memory, which is comparatively slow and of
Rigidity
relatively limited capacity. Typically, people resort to Application of bad rules
knowledge-based performance when their existing skills Encoding deficiencies
are not applicable or their repertoire of rules has been Action deficiencies
exhausted. Wrong rules
Inelegant rules
Successful performance or problem solving has three main Inadvisable rules
phases: planning, storage, and execution. Errors resulting Failures of Knowledge-Based Performance
from failures in performance may be classified as slips, lapses, Selectivity
or mistakes,21 depending on which phase of the problem- Workspace limitations
Out of sight, out of mind
solving sequence is involved. Slips are failures of the execu- Confirmation bias
tion phase, the storage phase, or both, and they may occur Overconfidence
regardless of whether the plan from which they arose was Biased reviewing
adequate. Lapses are failures of the storage phase. Generally, Illusory correlation
slips are overt, whereas lapses are covert. Mistakes are Halo effects
Problems with causality
failures of planning, reflecting basic deficiencies or failures in Problems with complexity
selecting an objective or specifying the means to achieve it,
regardless of how well the plan was executed.
A key concept is that specific types of error tend to be failures of knowledge-based performance (i.e., attributable to
associated with specific modes of failure [see Table 1].21 Slips lack of expertise) or failures of rule-based performance (i.e.,
and lapses are failures of skill-based performance and gener- attributable to failure of expertise). They typically arise during
ally precede recognition of a problem. Mistakes may be either attempts to solve a problem. Mistakes tend to be more subtle,
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APPROACH — 5
more complex, and less well understood than slips or lapses surgeon-reported errors37 and a review of closed malpractice
and thus more dangerous. It has been suggested that experi- claims.38 In the former, cognitive factors (primarily involving
enced surgeons are more prone to slips and lapses and that errors in judgment or vigilance) were involved in 86% of the
junior surgeons and trainees are more prone to mistakes.29 incidents, whereas inexperience or lack of competence con-
Underspecification of the problem is common in clinical tributed to 53% of errors. The latter study reported similar
practice and clearly affects performance. A problem may findings: errors in judgment, failure of vigilance or memory,
seem underspecified when limited attention is paid, when the and lack of technical competence or knowledge were factors
wrong cues are picked up, when the problem is truly ill- in 66%, 63%, and 41% of the cases, respectively.
defined, or when the problem falls outside the known rules. Further analysis revealed that 65% of the technical errors
Underspecification is more likely to occur in situations where were linked to manual error, 9% to errors in judgment
cues change dynamically or are ambiguous and is associated or knowledge, and 26% to both manual and judgment or
with two types of error forms: similarity matching and fre- knowledge error.39 Seventy-three percent of technical errors
quency bias (or frequency gambling). In similarity matching, occurred with experienced surgeons operating within their
a present situation is thought to resemble a previous one field of expertise, and over 80% were performing routine
and consequently is addressed in the same way (which is not operations but often under extenuating circumstances, such
necessarily appropriate). In frequency gambling, a course of as complicated patient factors (61%) or systems failures
action is chosen that has worked before, and the more often (21%). Current approaches to decreasing technical perfor-
that course of action has been successfully used, the more mance include such interventions as volume-based referral or
likely it is to be chosen. These behavior patterns have been regionalization, increased specialization, and more stringent
confirmed among anesthesiologists, who, like many dynamic credentialing for high-risk procedures. The results of this
decision makers, use approximation strategies (or heuristics) study, however, suggest that these approaches are unlikely
to handle ambiguous situations.1 to lead to significant improvement. Rather, attention should
Confirmation bias is another characteristic problem of be paid to improving technical performance (including
performance. It may be defined as the propensity to stick with both manual and judgment) in general but particularly when
a chosen diagnosis or course of action and either to interpret operating under complicated conditions.
new information so as to favor the original choice or to In one sense, a surgeon’s performance is a system factor,
disregard such information entirely. It is also referred to as but in another sense, their cognitive and technical abilities
cognitive fixation, cognitive lockup, or fixation error and make up a large part of the system’s safety barriers. There is
is often associated with knowledge-based performance.30 much that can be learned about human performance by
Confirmation bias is particularly likely when the situation is studying how providers compensate when things start to go
unusual or evolving and when there is concomitant pressure wrong and return the system to a safe state. Legal concerns
to maintain coherence31—again, situations frequently encoun- aside, it is vital that surgeons not overemphasize the first
tered in surgical practice. A well-known adage is relevant sense and interpret it as an excuse for avoiding responsibility
here: good surgeons believe what they see; bad ones see what for complications.40 Nevertheless, placing too much emphasis
they believe.32 The issue of how cognitive psychology affects on surgeons’ individual role retards rather than advances
diagnostic and clinical reasoning has been addressed in detail understanding of system failure and tends to evoke defensive-
elsewhere.33–35 ness rather than constructive action.22,23,41 Regardless of
Confirmation bias may be considered an error of percep- whether these adverse events are performance failures or
tion; other errors may be classified as errors of cognition or errors, eliminating them entirely is an impossible goal; a more
execution. Thus, classification schemes may be modified to realistic goal is to gain a better understanding of the contrib-
meet specific needs.36 For instance, some experts categorize uting and compensatory factors and then to minimize—or
errors according to whether they can be addressed by engi- possibly even eliminate—their consequences. The overall
neering, design, societal, or procedural changes; others prefer implication here is that to achieve meaningful improvements
to emphasize psychological intervention and modification; in safety, it is necessary to shift the focus from fallible indi-
and still others classify errors by their mode of appearance— viduals to the situational and organizational circumstances
for example, as errors of omission, errors of insertion, errors through which human performance leads to medical
of repetition, or errors of substitution (e.g., misadministration errors.26
of lidocaine, heparin, or potassium chloride as a result of poor Another important consideration in performance is an
package labeling). individual’s physical and psychological well-being. The effects
of sleep deprivation and fatigue on performance and learning
relation of individual performance to surgical have been particularly studied.42–46 Fatigue, by impairing
error
vigilance, can accentuate confirmation bias. In addition,
To many, the concepts of performance and error, as they errors increase as time on task increases; no other hazardous
relate to patient care, seem straightforward—obvious, even. industry permits—let alone requires—employees to work the
To others, however, it is crucial to make a distinction between regular long hours common in hospitals.30 Stress may increase
human error and human performance, both because the the likelihood of error, but it is clearly neither necessary nor
assignment of error is often retrospective and thus subject to sufficient for cognitive failure.21 Unfortunately, physicians
hindsight bias and because the term “error” is inherently tend to have unrealistic beliefs about their ability to deal with
prejudicial. stress and fatigue and so may not seek help even when they
Important advances in our understanding of the role of clearly need it.47 Recent studies have highlighted the striking
surgeon performance in error come from an analysis of prevalence of burnout among surgeons and the high degree
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APPROACH — 6
of correlation between burnout and medical errors.48 Sur- junior team members would not question the decisions of
geons also appear to have only a limited ability to assess their more senior staff led to significant policy changes and safety
own learning needs, with those who are least skilled and those enhancements.55 Given the traditional surgical hierarchy,
who are most confident being the worst at this task.49 As a similar attitudes may exist in the operating room. Such
corollary, surgical skill is positively related to the ability to varying perceptions can not only compromise patient safety
detect errors.29 but also hinder teaching and learning. Unfortunately, there
The mental overload that can occur in situations involving is no broad consensus on how to achieve optimal team
a plethora of tasks may compromise the ability to respond to coordination in this setting.
secondary tasks. Errors related to loss of vigilance include not The critical role of communication in surgical errors has
observing a data stream at all, not observing a data stream been described in a number of studies. Two or more
sufficiently frequently, and not observing the particular data clinicians substantially contributed to error in 70% of
stream that is optimal for the existing situation. In watching surgeon-reported errors, and three or more were involved
for rare occurrences (a not uncommon situation in medicine), in 18% of the incidents.37 Communication breakdowns
it is difficult to remain fully alert for longer than 10 to contributed to approximately one quarter of surgical errors
20 minutes. Knowing when and how to verify data is an that led to patient injury as detected on malpractice claims
important metacognitive skill. An analysis of intraoperative analysis.56 These tended to be verbal communications between
safety identified high workloads, poor workload leveling, and two or more people and were equally as likely to be cross-
multiple competing tasks as a major threat to performance disciplinary as intradisciplinary. They occurred with equal
and safety.50 frequency in the pre-, intra-, and postoperative period, and
In addressing these types of errors, a great deal of emphasis the surgical attending physician was most often involved
has been placed on reducing work hours, but there seems to either as the transmitter or the receiver. Intraoperative field
have been relatively little consideration of the impact of work- observations suggest that communication breakdowns and
load and workflow on medical errors.37 Yet data on resident failures are pervasive in the operating room, occurring in up
work activities indicate that residents experience extremely to one third of communication events.50,57
fragmented workflows that result in frequent interruptions
and changes in focus.51 Moreover, the current limit on resi- Environmental and Organizational Factors
dent work hours does not appear to have improved patient The importance of the structural characteristics of the
safety52 or reduced the incidence of technical complications.53 system in which care is provided is underscored by the
Thus, demands for greater productivity within a health care relation between variations in the frequency of risk-adjusted
system that is increasingly constrained by cost considerations outcomes among institutions and differences in the systems
may also contribute to an increase in medical errors.
of care in place within those institutions.58 The substantial
Psychological framing effects also play a role in judgment.
similarities between medical and nonmedical systems
Examples of such effects are the irrational preference for
notwithstanding, the complex content and organizational
established treatments when outcomes are framed in terms of
structure of health care make it distinctive. Many system
gain (e.g., survival) and the similarly irrational preference
concepts that derive primarily from analyses of human-
for risky treatments when outcomes are framed in terms of
engineered, highly technical, nonbiologic systems may not be
loss (e.g., mortality). The impetus to “do the right thing” can
fully applicable to the more complex issues of patient safety.59
adversely affect medical judgment.54
Linearly engineered systems are likely to be far more predict-
relation of system factors to surgical error able than biologic systems, in which appropriate processes do
not always result in good outcomes. Patients frequently differ
Teamwork and Communication greatly from each other in terms of their ability to communi-
Teamwork and communication among team members also cate relevant issues, their severity of illness, their comorbidi-
play essential roles in determining performance, particularly ties, and their responses to diagnosis and treatment. When a
when there is a lack of cohesion and mutual support among system is not expected to work perfectly at all times—as
team members.1,30 On the one hand, a team structure that is health care is not—it becomes more difficult to distinguish
too informal tends to undermine patterns of authority and problems related to individual error from problems related to
responsibility and to hinder effective decision making. On flaws in the system. This distinction between nonmedical
the other hand, a hierarchy that is too strong may make it mechanical systems and medical systems may be akin to the
excessively difficult for juniors to question decisions made by distinction between complicated and complex endeavors.60
those at higher levels of authority. Rigid behavior may impair Differences in organizational structure between medical
the ability to cope with unforeseen events and discourage and nonmedical systems may be particularly relevant. A non-
initiative. medical system is typically a single structure that is managed
Teamwork can be an especially complex matter in the vertically through hierarchical control. Patient care, in con-
operating room. The crews from nursing, surgery, and anes- trast, tends to consist of numerous diverse subsystems that
thesia often have fundamentally different perceptions of their may be only loosely aggregated.61 These subsystems tend to
respective roles, and these perceptual differences can adversely function in isolation, and intrasystem changes tend to be
affect situational awareness. For example, anesthesiologists managed laterally across individual subsystems. The resulting
and nurse anesthetists are much more likely to feel that a loose structure often leads to the creation of ineffective or
preoperative briefing is important for team effectiveness than even contradictory policies, all of which increase the chances
are surgeons and surgical nurses. In aviation, concern that of error.
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APPROACH — 7
The potential role of a systems approach in improving Table 2 Handoff Coordination and Communication
safety is further suggested by data that correlate improved Objectives and Relevant Strategies65
outcomes with higher hospital or surgeon volume.62,63 Whether Improve handoff update effectiveness
these findings are explained by “practice makes perfect” or by 1. Face-to-face verbal update with interactive questioning
“perfect makes practice” is yet to be resolved, but in either 2. Additional update from practitioners other than one being
case, it seems likely that the improved outcomes reflect better replaced
3. Limit interruptions during update
care systems. That some high-volume hospitals and surgeons 4. Topics initiated by incoming and outgoing team members
have below-average outcomes and many low-volume hospi- 5. Limit initiation of operator actions during update
tals and surgeons have excellent ones is consistent with the 6. Include outgoing team’s stance toward changes to plans
role of systems.64 and contingency plans
7. Readback to ensure that information was correctly
The physical characteristics of the system in which care is
received
provided can influence the safety of the system. Issues such
as ergonomics, lighting, equipment malfunctions, noise levels, Improve handoff update efficiency and effectiveness
8. Outgoing writes summary before handoff
and interruptions can increase the vulnerability to error and 9. Incoming assesses current status
adverse outcomes. 10. Update information in the same order every time
A system’s results may be summed up as follows: “Whether 11. Incoming scans historical data before update
your output is good or bad, it is, nonetheless, the only output 12. Incoming reviews automatically captured changes to
sensor-derived data before update
of which your systems, processes, and methods are currently 13. Intermittent monitoring of system status while “on call”
capable.”59 Otherwise stated, every system is perfectly 14. Outgoing has knowledge of previous shift activities
designed for the results it gets. Increase access to data
15. Incoming receives primary access to the most up-to-date
information
Lessons from Other High-Risk Domains 16. Incoming receives paperwork that includes handwritten
A systems approach to safety improvement has led to major annotations
advances in a number of other high-risk work environments, Improve coordination with others
such as aviation and other transportation domains. As we 17. Unambiguous transfer of responsibility
18. Make it clear to others at a glance which personnel are
start to understand health care as a system and the role of
responsible for which duties at a particular time
human factors in system performance, we can learn from the
advances made in these other fields. Patterson and colleagues Enable error detection and recovery
19. Overhear others’ updates
identified handoff strategies that were identified in other 20. Outgoing oversees incoming’s work following update
settings with high consequences for failure (space shuttle
Delay transfer of responsibility during critical activities
mission control, nuclear power, railroad and ambulance 21. Delay the transfer of responsibility when concerned about
dispatchings) that could be applied to improve the safety of status/stability
handoffs in health care [see Table 2].65
Significant advances have been made in adopting the
technique of crew resource management (CRM) from Approaches to Improving Patient Safety
aviation to health care and surgery. CRM was first used by
the aviation industry to improve airline crew coordination, Given the similarities between medical and nonmedical
and the IOM report To Err Is Human: Building a Safer Health systems, it should not be surprising that many safety improve-
System identified it as a strategy to reduce medical errors and ment techniques derived from nonmedical settings have been
successfully applied in medical contexts [see Table 3].68,69
improve patient safety.2 Since this call for its implementation,
Other useful strategies include prioritization of tasks, distri-
the use of CRM has been evaluated in various health care
bution of the workload over time or resources, changing
fields, including operating room teams. In one study, teams
the nature of the task, monitoring and checking all available
underwent an 8-hour training course that covered six key
data, effective leadership, open communication, mobilization
areas of CRM: managing fatigue; creating and managing a
and use of all available resources, and team building.1 The
team; recognizing adverse situations; cross-checking and
communication techniques; developing and applying shared
mental models for decision making; and giving and receiving
performance feedback.66 Although 95% of respondents agreed Table 3 Nonmedical System Techniques Also Applicable
to Medical Systems
that the training would reduce errors in their workplace,
cultural barriers still exist within surgery. Whereas only 26% Simplify or reduce handoffs
Reduce reliance on memory
of pilots denied that fatigue has a detrimental effect on
Standardize procedures
performance, 70% of surgeons and 47% of anesthesiologists Improve information access
felt that they can perform effectively even when fatigued.67 In Use constraining or forcing functions
the same study, only about half of attending surgeons favored Design for errors
Adjust work schedules
a flat hierarchy in which junior members of a team could
Adjust the environment
question decisions made by senior team members, whereas Improve communication and teamwork
94% of pilots advocated for this approach. Perhaps more Decrease reliance on vigilance
broad adoption of CRM will help bridge this cultural Provide adequate safety training
divide. Choose the right staff for the job
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APPROACH — 8
general idea behind many of these approaches is to redesign A further approach to improving patient safety has been the
the problem space to reduce the cognitive workload.28,70 development of specific tools and indicators for identifying
A vital early step in improving patient safety is to establish common safety problems. Examples of these are the Patient
a safety culture throughout the workplace. An important Safety Indicators from the Agency for Healthcare Research
development in this area is the ability to make valid measure- and Quality (AHRQ) (www.ncbi.nlm.nih..gov/bookshelf/
ments of an organization’s safety climate.71 An appropriate br.fcgi?book=techrev5) [see Table 4] and the serious report-
organizational culture views errors as signals for needed able event list from the National Quality Forum (NQF)
changes and focuses on learning rather than on accountabil- (www.qualityforum.org/Projects/s-z/SRE_Maintenance_2006/
ity. If the team or organization is designed to learn from Fact_Sheet_-_Serious_Reportable_Events_in_Healthcare_
and benefit from experience, its collective wisdom should be 2005-2006_Update.aspx) [see Table 5]. The lists are similar
greater than the sum of the wisdom of its individual mem- in some respects but not identical: the NQF further sub-
bers. Needed changes often involve difficult choices among categorizes events into surgical events, product or device
strategic factors and sometimes introduce new latent flaws.37,72 events, patient protection events, care management events,
Accordingly, once a change in procedure or policy has been environmental events, and criminal events. Both lists specify
implemented, its impact must be monitored closely.73 New clearly identifiable and readily measurable events, both
latent failures may result from either oversimplification31 or include a variety of causes in addition to medical errors that
redundancy. As noted (see above), the latter enhances lead to such adverse events, and both were developed
reliability, but its benefits are often offset by greater complex- by panels of experts. Yet a recent study indicated that,
ity and a consequent increase in the risk of human failure.30 relative to risk managers, physicians were less aware of
In addition, the more complex the system, the greater the error-reporting systems in their hospitals or the adequacy of
chance that a change will have more than local effects. How such mechanisms.77
to control some errors without relaxing control over others is
a general problem in error management.30,74 Techniques for Identifying System Flaws
Good teamwork requires that team members share a clear
Intensive examination of system flaws is most often trig-
understanding of what is happening and what should happen
gered by a catastrophic failure or, less often, by a near miss.
(i.e., situational awareness).30 Unfortunately, there is a
The appropriate investigation of such events is known as
common tendency to believe that the prevailing level of situ-
root cause analysis (RCA). The Joint Commission (formerly
ational awareness is greater than it actually is. For example,
the JCAHO) (www.jointcommissioninternational.org/Books-
the aviation industry further improved its safety record when
and-E-books/Root-Cause-Analysis-in-Health-Care-Tools-
it identified and removed barriers that impeded junior officers
and-Techniques-Fourth-Edition/1502) has a matrix for RCA,
from communicating with the captain. This achievement is
and experience with RCA in health care institutions has been
noteworthy because these improvements took place after
reported.78,79
good communication was already thought to exist.75
In the case of an actual failure, the next steps are to identify
Even though physicians have increasing access to all the relevant subsystems and to assemble a team whose
information technology in practice (www.hschange.org/CON- members represent all of the components. Determining all of
TENT/891), physician acceptance of computerization has the components within a complex system can be challenging,
been neither easy nor universal, and medicine is far behind and it may prove necessary to add members to the team as
other industries in terms of the extent to which it has adopted more subsystems are identified. In this regard, it is better
such technology. Studies from the past few years suggest that to err on the side of inclusiveness rather than exclusivity to
only about one third of physicians receive any data (process minimize the chances of missing latent flaws and maximize
data, outcome data, or patient surveys) about the quality of the number of possible solutions. Studies that relate nurse
care they provide.76 This finding may be partly explained by staffing to quality of care illustrate the important roles that
the cost of introducing information technology (which can
become outmoded relatively quickly).
Another possible factor here is concern that caregivers
might become too dependent on computerized advice-giving Table 4 Agency for Healthcare Quality and Research
systems and thus might start making a habit of perfunctorily Patient Safety Indicators
acceding to the computer’s advice rather than trusting their
Complications of anesthesia
own judgment. Issues of legal liability then arise: how much Death in low-mortality diagnosis-related group
computer advice is too much, and is relying on such advice Decubitus ulcer
tantamount to abandoning responsibility for critical indepen- Failure to rescue
Foreign body left during procedure
dent thought? A related concern is that many patient care
Iatrogenic pneumothorax
tasks may be too complex for computerization and thus may Selected infections
be better suited to human performance. The tradeoff for Postoperative hip fracture
retaining the human ability to deal with such complexity is Postoperative hemorrhage or hematoma
the human susceptibility to error: systems that rely on error- Postoperative pulmonary embolism or deep vein thrombosis
Postoperative sepsis
free human performance are destined to experience failures. Postoperative wound dehiscence
Because the kinds of transitory mental states that cause errors Accidental puncture or laceration
are both unintended and largely unpredictable, they are the Transfusion reaction
last and least manageable links in the error chain. Obstetric trauma
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Table 5 National Quality Forum List of Health Care Facility–Related Serious Reportable Events
Category Event
Surgical A. Surgery performed on the wrong body part
B. Surgery performed on the wrong patient
C. Wrong surgical procedure on a patient
D. Unintended retention of a foreign object in a patient after surgery or other procedure
E. Intraoperative or postoperative death in an ASA class I patient
Product or device A. Patient death or serious disability associated with use of contaminated drugs, devices, or biologics
B. Patient death or serious disability associated with use or function of a device in patient care, in which the device
is used or functions otherwise than intended
C. Patient death or serious disability associated with intravascular air embolism
Patient protection A. Infant discharged to the wrong person
B. Patient death or serious disability associated with patient elopement (disappearance)
C. Patient suicide or attempted suicide resulting in serious disability
Care management A. Patient death or serious disability associated with a medication error
B. Patient death or serious disability associated with a transfusion reaction
C. Maternal death or serious disability associated with labor and delivery in a low-risk pregnancy
D. Patient death or serious disability associated with hypoglycemia
E. Death or serious disability associated with failure to identify or treat neonatal hyperbilirubinemia
F. Stage 3 or 4 pressure ulcer acquired after admission
G. Patient death or serious disability associated with spinal manipulative therapy
H. Artificial insemination with wrong donor sperm or wrong egg
Environmental A. Patient death or serious disability associated with electrical shock
B. Any incident in which a line designated for oxygen or other gas to be delivered to a patient contains the wrong
gas or is contaminated by toxic substances
C. Patient death or serious disability associated with a burn incurred from any source
D. Patient death or serious disability associated with a fall
E. Patient death or serious disability associated with the use of restraints or bedrails
Criminal A. Any care ordered by someone impersonating a physician or other licensed health care provider
B. Abduction of a patient of any age
C. Sexual assault of a patient
D. Death or significant injury of a patient or staff member from a physical assault
ASA = American Society of Anesthesiologists.
other members of the health care team play in ensuring and possess a number of other advantages.84,85 RCA can be
patient safety.80–82 In some situations, it may be difficult to automated,86 but the potential advantages of doing so may be
generate interest in RCA because the circumstances are so offset by a dependence on the developer’s interpretation of
unusual that they are unlikely ever to combine in the same the risk reduction process or by the factors identified as the
way again. principal event.
Systems analyses in the presence of a near miss, or in the Regardless of the data source, the process is likely to be
absence of any specific event, require a more global approach evolutionary: rarely is a perfect set of measures available from
to help avoid future errors. Areas where such analyses might the start. Although the findings from such an analysis might
be fruitful include those identified by AHRQ [see Table 4], seem to offer little benefit to the institution in which they
the NQF [see Table 5], and the Joint Commission. Another occurred, such incidents may occur frequently enough at a
source for specific topics is AHRQ WebM&M (www.webmm. regional or national level to make the analysis worthwhile.
ahrq.gov), an AHRQ-developed Web site that provides expert Other analyses associated with successful quality improve-
analysis of medical errors in five specialty areas (including ment efforts include patient notification systems,87 patient
surgery), as well as interactive learning modules. AHRQ has safety systems,88 analyses of system failures in laparoscopic
also created extensive lists of other quality measures (www. surgery,89 and analyses of medical microsystems.72 Critical
qualitymeasures.ahrq.gov) and tools for improving patient analyses of evidence-based practices also identified 11 surgi-
safety. The next steps in this situation are to decide on cally relevant quality improvement practices for which the
measures for analysis and to identify appropriate data sources. data were strong enough to support more widespread imple-
Medical record audits yield far greater detail than claims data mentation [see Table 6].90,91 A note of caution that should be
but are expensive, labor intensive, and time-consuming. sounded here is that exclusive emphasis on evidence-based
Moreover, information on the environment or behavior in data could skew safety priorities and might actually prevent
medical records may be irrelevant or even contradictory. relatively few adverse events.92 Another potential area for
This problem can sometimes be mitigated by employing review involves changes in policy or equipment that might
appropriate screening criteria.83 Some of the shortcomings of introduce unanticipated problems or unexplained variations
medical record audits can be avoided by using administrative in a relevant outcome measure. Every change in a system
data, but such data often lack sufficient accuracy or depth. necessitates a new learning cycle, and the new environment
Electronic health records can potentially simplify this process may be conducive to failures from new latent errors.93
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APPROACH — 10
Table 6 Surgically Relevant Quality Improvement Practices Appropriate for Widespread Implementation90
Appropriate use of prophylaxis to prevent venous thromboembolism in patients at risk
Use of perioperative beta blockers in appropriate patients to prevent perioperative morbidity and mortality
Use of maximum sterile barriers while placing central venous catheters to prevent infection
Appropriate use of antibiotic prophylaxis to prevent postoperative infections
Requesting that patients recall and state what they have been told during the informed consent process
Continuous aspiration of subglottic secretions to prevent ventilator-associated pneumonia
Use of pressure-relieving bedding materials to prevent pressure ulcers
Use of real-time ultrasound guidance during central line placement to prevent complications
Patient self-management for warfarin to achieve appropriate outpatient anticoagulation and prevent complications
Appropriate provision of nutrition, with particular emphasis on early enteral nutrition in critically ill and surgical patients
Use of antibiotic-impregnated central venous catheters to prevent catheter-related infections
Successes and Obstacles to Success in situational awareness and a shared mental model; however,
In view of the complexities of health care, taking a systems whatever the mechanism, the use of checklists, adopted from
approach to safety improvement may seem a daunting aviation, changes the system in which care is delivered and
endeavor. Nevertheless, there are a number of cases in which the behavior and interactions of the team and individual
practitioners.
this task has been successfully accomplished. For the pur-
Another emerging success is the use of technological
poses of illustration, it is worthwhile to review these examples
adjuncts in the tracking of surgical sponges. The traditional
briefly.
approach to preventing retained objects following surgery
Anesthesiologists were among the first physicians to take a
depends on several members of the surgical team manually
systems approach to patient safety, and their success is irre-
counting every item that is introduced onto the sterile field
futable: anesthesia-related mortality fell from approximately
and again at the end of the operation. These protocols
two in 10,000 to the current one in 200,000 to one in
have been shown to be labor intensive as well as unreliable.103
300,00094–96—a degree of safety approaching that advocated
Seventy to 88% of cases of retained surgical equipment are
for nonmedical industries (i.e., < 3.4 defects or errors/106
associated with a correct count.9 The recognition that manual
products or events).97 This improvement primarily resulted
counts will not be sufficient to completely ameliorate retained
from a broad effort involving teamwork, practice guidelines,
objects after surgery, making it a true “never event,” has led
automation, simplification of procedures, and standardization
to the development of several technological solutions. Radio-
of equipment and many functions. For instance, before the
frequency identification tags and bar codes are two examples
anesthesiologists’ safety initiatives, design standards for anes- of such solutions. A randomized, controlled trial suggests that
thesia machines did not exist. As a result, it was not unusual bar-coding sponges can improve the ability to track sponges
to have one machine in which turning a valve in a given direc- during an operation.104
tion would increase gas flow and other machines in which These examples of success are encouraging, but consider-
turning it in the same direction would decrease flow; in fact, able obstacles to improving patient safety still exist. Specific
both types might be present in the same hospital. Equipment obstacles include (1) a residual lack of awareness that a
manufacturers subsequently worked together to standardize problem exists; (2) a traditional medical culture based on
anesthesia equipment, and these kinds of arbitrary design individual responsibility and blame (and shame); (3) a
variations are no longer seen. perceived vulnerability to legal discovery and liability; (4)
The experience with safety efforts in anesthesiology primitive medical information systems; (5) the time and
underscores the importance of understanding the human- expense involved in defining and implementing evidence-
technology interface and the ergonomics of equipment based practice; (6) inadequate resources for quality improve-
design.98 To improve patient safety, it is necessary to under- ment and error prevention; (7) the local nature of health care;
stand the devices and techniques employed, the ways in and (8) the perception of a poor return on investment (i.e.,
which individual persons use the technology, and the means the lack of a business case).105 Although the need to redefine
by which these users interact with other aspects of the health care on the basis of value seems obvious, the current
system.98,99 Similar considerations should be applied to environment still appears to focus primarily on cost; value
innovative practices.100 (i.e., quality per unit cost) is not part of the equation.106
Another example is the recent high-profile application of One hindrance to improving patient safety is the idea that
procedural checklists. These checklists serve as the corner- traditional improvement methods are adequate to address the
stone of system-based interventions aimed at improving problem. The persistence of patient safety problems in the
safety. A Michigan-wide collaborative targeting best practices face of the ongoing use of these methods should be a suffi-
around central line placement markedly reduced the morbid- cient argument for the inadequacy of existing approaches.
ity and mortality associated with central lines in an intensive For instance, morbidity and mortality (M & M) conferences
care setting.101 A surgical safety checklist implemented in are perhaps the most traditional venue for discussion of
eight international hospitals similarly was associated with adverse events, but they often do not consider all complica-
a decrease in death and complications from nonpediatric tions, are not consistently well attended, do not categorize
surgical procedures.102 A number of different mechanisms complications systematically, and often do not involve exten-
may underlie the association between the checklists and sive debriefing.37,107–109 One study that compared NSQIP with
improved outcomes, including better communication, less traditional M & M conferences noted that the latter failed
reliance on individual knowledge and memory, and increases to consider about 50% of the deaths and about 75% of the
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complications.110 Furthermore, M & M conferences tend to This tendency was illustrated by a study of anesthetic care
be intradepartmental and thus provide little opportunity for in which differences in outcome significantly influenced the
discussion of system problems that involve other departments perception of negligence, even when the care provided was
(e.g., anesthesiology or nursing). M & M conferences also equivalent.117 Hindsight bias focuses too narrowly on adverse
typically do not consider near misses (i.e., close calls), even outcomes and pays insufficient attention to the processes
though such events can identify important actual and poten- of care. Yet another defect of the liability process is that it
tial system flaws. Finally, M & M conferences have a tradition can be emotionally devastating for physicians (and their
of focusing on the actions of individuals rather than on the families),118–120 often adversely affecting their problem-solving
circumstances within which the individuals acted. This tradi- abilities. To the extent that experience with or fear of a
tion serves to perpetuate a defensive attitude among trainees liability action deters efforts at quality improvement, it is
that is counterproductive. It is possible, however, that a more counterproductive. Defensive medicine, with its attendant
systematized review process could improve the value of the costs, adds very little value to health care.121
M & M conference.111,112 Many believe that major reform of the professional
Joint Commission accreditation of hospitals is based on liability system is a prerequisite for achieving any significant
analyses of safety and quality information (www.jointcom- improvements in quality. Undoubtedly, tort reform is highly
missionreport.org). However, it has been observed that the desirable; however, the real prerequisite for improving iden-
Joint Commission’s accreditation program lacks the ability to tification and correction of system failures is the provision of
identify many patient safety problems.113 increased protection for privileged discussion of such failures.
Peer review organizations were originally intended as a The federal Patient Safety and Quality Improvement Act
mechanism for professional self-evaluation but subsequently of 2005 (Public Law 109-41) was enacted for the purpose
became subject to anticompetitive abuse and other undesired of improving patient safety by encouraging voluntary and
consequences.114 The potential for inequity was a particular confidential reporting of events that adversely affect patients.
concern in that physicians who relinquished privileges on This act creates patient safety organizations whose goal is to
their own initiative might be treated more leniently than those collect, aggregate, and analyze confidential information
against whom action was initiated by a peer review commit- reported by health care providers. It also calls for establishing
tee. Moreover, the data reviewed by peer review organizations a network of patient safety databases as an interactive,
were often legally discoverable, and this lack of anonymity evidence-based management resource. The act limits the
and confidentiality tended to deter voluntary participation. use of this information in criminal, civil, and administrative
Even when peer review organizations identified problems, proceedings and includes provisions imposing monetary
they were often unable to implement solutions. Peer review penalties for violations of confidentiality or privilege protec-
organizations have now been largely supplanted by quality tions. The notion that a reduction in liability concerns may
improvement organizations, although it is not yet clear facilitate disclosure and discussion of mistakes is suggested by
whether the latter are substantially more effective.115,116 international comparisons of health care systems. In one
Hospital incident reports have much the same shortcom- study, patients in New Zealand, which has no-fault medical
ings as the peer review process. They place limited emphasis malpractice, were the most likely to report error discussions
on close calls and tend to lack systematic follow-up. Indi- with their physicians.13
viduals also may be reluctant to file reports out of fear that It is to be hoped that the tort reform movement and the
their employment might be jeopardized or that the reported patient safety movement can seek and find common ground.122
party might seek retribution. The improvements in patient safety achieved by anesthesiolo-
The present professional liability system is particularly gists speak for the benefits of such an approach. Instead of
controversial with respect to whether it facilitates or hinders pushing for laws to protect them against patients’ lawsuits,
improvements in patient safety. This system has its basis in anesthesiologists focused on improving patient safety. As
the traditional paradigm of surgical care (see below), which a result, they pay less for malpractice insurance today, in
holds the individual surgeon accountable as the “captain of constant dollars, than they did more than 20 years ago.123
the ship.” This paradigm has enabled many great achieve- Even before the enactment of the Patient Safety Act, the
ments in surgical care, but it has also probably fostered a view that open discussion of medical errors was appropriate
dangerous sense of infallibility. As a consequence, errors tend appeared to be gaining adherents.21 Today, there is even
to be equated with negligence, and questions of professional more evidence that such open communication may reduce
liability tend to involve blaming individuals. Indeed, the very the likelihood of legal action and enhance public confidence
willingness of professionals to accept responsibility for their in health care providers.124,125 Unfortunately, some hospitals
actions makes it convenient to focus more on individual persist in separating risk management from quality assurance
errors than on collective ones22; an individual surgeon is a issues, to the detriment of both.126
more satisfactory target for the anger and grief of a patient or The obvious need for liability reform notwithstanding,
family than a faceless organization would be. This is certainly there are issues involved in enhancing safety and quality that
not to say that surgeons should avoid responsibility; rather, are too complex to be addressed solely by changes in the
the point is that focusing on the errors of individual surgeons liability system. Major safety and quality problems exist in
without addressing flaws in the underlying system does little nations where professional liability is not an issue; however,
to improve health care. the higher rates of adverse events in these countries should
Another notable flaw in the liability process is that not be taken as evidence of the benefits of the current US
judgments of causality or fault are vulnerable to hindsight liability system. Physicians tend to act defensively even in a
bias, which can skew experts’ assessments of quality of care. no-fault liability system. To minimize such defensiveness,
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APPROACH — 12
greater emphasis must be placed on measurement for believe that a health care reporting system can succeed only
improvement than on measurement for judgment.127 if legal immunity is available.133 The fear of being sued is
widespread among physicians; however, the perceived risk of
being sued is three times greater than the actual risk, and
Changing the Traditional Surgical Paradigm
there is no good correlation between hospitals’ claims ratings
Contemporary surgical practice requires that surgeons and their injury rates.72
rethink the traditional paradigm of surgical practice (see A mandatory, anonymous, confidential, and nondiscover-
above). The burgeoning growth of knowledge, the accompa- able reporting system has been instituted in the state of
nying increase in specialization, the expanding role of Pennsylvania. Founded in 2003, the Pennsylvania Patient
technology, and the rising complexity of practice are making Safety Reporting System, a statewide database maintained by
surgeons more and more dependent on persons or factors the Pennsylvania Patient Safety Authority, collects over
beyond their immediate control. As a result, surgeons are 200,000 annual reports of near miss and adverse events.
finding it more and more difficult even to appreciate, let (http://patientsafetyauthority.org). The events are evaluated,
alone manage, the larger context within which they provide summarized, and analyzed to identify patterns that can be
care. The traditional surgical paradigm, despite its past used to develop patient safety solutions and interventions.
successes, is no longer entirely adequate to the task now at Whether such reporting should be voluntary or mandatory
hand [see Table 7].128 Paradoxically, surgeons seeking to is still a matter of debate. On the one hand, voluntary report-
improve patient safety must acquire a deeper understanding ing has a high inaccuracy rate even when mandated by state
of patient care systems at the very time when those systems or federal regulations. On the other hand, many surgeons
are becoming increasingly difficult to understand. believe that mandatory reporting may increase the pressure
To achieve the requisite understanding, it is necessary to to conceal errors rather than analyze them; that it is unwork-
have a reporting system that collects, tabulates, and analyzes able in the current legal system; and that it may result not in
data on the frequency and nature of both adverse events and constructive error-reducing solutions but merely in more
near misses.129 The primary function of a patient safety punishment or censure.134
reporting system should be to identify both real and potential Some argue that patient safety efforts should focus (at least
adverse consequences of latent flaws and make them visible initially) on medical injury rather than on medical errors.135,136
to others. Once these real and potential adverse events are A focus on medical injury recognizes the difficulties of
identified and made visible, the system can be redesigned so identifying medical errors and is based on a public health
as to eliminate or minimize them. improvement model that has been useful in addressing other
A successful reporting system such as the highly successful types of injuries; it also recognizes that most medical injuries
Aviation Safety Reporting System (ASRS) is typically are not caused by negligence. Such an approach may be more
nonpunitive, confidential (and preferably anonymous), compatible with the current liability system and may help
independent, timely, systems oriented, and responsive.22,88,130 restore physicians’ stature as patient advocates. Moreover,
In addition, it includes expert analysis, meaning that reports placing the initial focus on medical errors rather than injuries
are evaluated by persons who understand the relevant might divert attention from other system flaws, with the result
circumstances and are trained to recognize underlying system- that such flaws go uncorrected. Although, ultimately, a
based causes. A successful reporting system usually also tabu- successful reporting system must focus both on errors and on
lates seemingly rare incidents (including near misses) even if injuries, an initial focus on injury may achieve greater initial
there seems to be little direct or immediate benefit to doing buy-in from surgeons and may therefore be a more pragmatic
so; in addition to their potential value in larger contexts, such first step. The issues associated with reporting errors or inju-
analyses may help institutions predict and thereby avoid ries must also be distinguished from those associated with
errors and system failures. The absence of a punitive focus reporting outcomes to the public. The latter type of report is
reduces health care workers’ concerns that reports might be currently being seen with increasing frequency, but it may
used against them and thus minimizes underreporting.36,131,132 have unintended consequences.137
The concerns about the possible adverse consequences of a The complexities involved in understanding and improving
reporting system are quite strong—so much so that many health care systems make it likely that patients’ expectations
of improved safety may grow faster than they can be met.138,139
This potential disparity between expectations and perfor-
Table 7 Contrasting Characteristics of Medical Practice mance may be further exacerbated by the likelihood that
in the 20th and 21st Centuries129 errors have been substantially underreported.140 A reporting
20th century characteristics system that is punitive or not anonymous may discourage
Autonomy appropriate reporting of medical errors. Underreporting of
Solo practice adverse events is also more likely if side effects are delayed or
Continuous learning
Infallibility
unpredictable, if there is a longer survival or latency interval,
Knowledge or if a patient has been transferred from one facility to another.
In addition, inadequate doses of drugs or anesthetics may not
21st century characteristics
Teamwork/systems be reported if they cause no immediately evident injury.
Group practice Another challenge facing surgeons is how to incorporate
Continuous improvement current concepts of performance and error into undergradu-
Multidisciplinary problem solving ate and residency education.141 The optimal basis for such
Change
education might be an objective-based curriculum that
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APPROACH — 13
provides defined skills, rules, and knowledge.142,143 The blame- substantial increase in the percentage of patients who would
and-shame approach must be eliminated from both the choose a highly rated surgeon whom they had not seen before
educational setting and the practice atmosphere. If, instead, over a less highly rated surgeon whom they had seen before
educators focus on making residents aware of their tendencies (www.ahrq.gov/qual/kffhigh00.htm). Improving patient safety
in the presence of uncertainty, residents (like pilots) may be thus becomes a matter of self-interest for the provider. It also
able to develop better responses to underspecified situations. may have a direct bearing on the maintenance of physicians’
In addition, it is vital to monitor the residents to ensure that social contract with their patients.
they learn to assess and address knowledge deficits, as well The systems approach to improving patient safety is based
as acquire healthy and effective techniques for dealing with on three principles: (1) human error, as an inherent aspect of
errors. Such monitoring will make the learning curve less human work, is unavoidable; (2) faulty systems allow human
painful for all concerned.144 error to injure patients; and (3) systems can be designed that
There is some question as to whether safety improvements prevent or detect human error before such injuries occur.149,150
are more likely to result from compliance with standards Support for a systems approach to patient safety will come
(i.e., individual performance) or from improvements in the from patients, purchasers from both the public and the
system. Better training of individual physicians will certainly private sector, professional societies, and specialty boards.151
improve performance, but only so far. For substantial It is crucial for all of these parties to acknowledge that most
improvements in safety, it is probably necessary to make use medical errors are attributable to system flaws rather than
of both approaches.145 If every system is perfectly designed to incompetence or neglect. It is also essential to recognize that
achieve the results it gets, the obvious conclusion is that to the current systems of surgical care are shaped by the larger
obtain the desired results, it is necessary to change the system. system within which all of these parties interact. This means
Determining what form the new system should take is a
that any worthwhile effort to improve such systems is likely
critical step.106,146
to require substantial collaboration among the parties
involved,152 as well as significant change in the larger
Conclusions system.
Medical errors have a substantial impact on 90-day costs
Reducing adverse events during the course of medical care
is a dauntingly complex topic, and the progress made in and outcomes of surgical patients.153 Moreover, there appears
reducing such errors has, in many cases, been disappointingly to be a business case for investing in patient safety.154 Physi-
slow. Roughly a century ago, surgeons were called on to cians, with their history of patient advocacy and scientific
report their results, but over the intervening years, this call innovation, are in the best position to provide the leadership
largely went unheeded.147 It must be said, however, that at necessary for such changes.87,155 To restore the public’s trust
the beginning of the 20th century, the basic principles of in the health care system, safety and quality must be made
human performance and error were not as well understood high priorities,156 and transparency must be ensured.157 If
as they currently are, and the tools necessary for systems physicians do not take the opportunity to lead the movement
analysis did not exist. A further difference between then and to improve the safety and quality of care, they may anticipate
now is the increase in public awareness of safety issues, as further erosion of public trust and further loss of professional
well as the potential consequences of this awareness.13,148 For autonomy.
instance, the growing concern about safety is changing the
way in which patients select providers: there has been a Financial Disclosures: None Reported
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APPROACH — 16
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244:642–8. building the business case for investing Figure 1 Seward Hung
01/11
6 PREOPERATIVE TESTING, PLANNING,

AND RISK STRATIFICATION
Randi Smith, MD, Valerie Ng, MD, PhD, Patrick Twomey, MD, and Alden H. Harken, MD*
In most circumstances in medicine, diagnosis precedes In addition to functional capacity and comorbid condi-
treatment. Consensus statements and regulatory guidelines tions, age is a robust determinant of operative risk, as is
endorse the long-hallowed practice of identifying patients at the type of operation. Vascular procedures and prolonged,
increased risk for complications. This is called “prognostic complicated thoracic, abdominal, or head and neck proce-
testing.” The implication is that the benefit of special risk dures carry higher levels of risk. None of this is surprising.
reduction strategies should be confined to these patients. The purposes of this chapter are as follows:
Most of the cardiovascular (and pulmonary) “screening”
1. To explore the tools available to the surgeon for assessing
tests considered below are of the prognostic type only.
patient vulnerability to operative stress
Much more useful than prognostic testing is predictive
2. To examine the practical specifics of preoperative func-
or directive testing, which means identifying patients
tional status testing
who will benefit from a specified, available intervention.
3. To analyze methods of quantifying surgical stress
By definition, this discriminates a subset of “bad prognosis”
4. To develop patient status and operative insult-specific
patients who can be helped and thus requires the existence
indications for some “routine” preoperative tests
of a therapeutic intervention of demonstrated benefit. This
5. To suggest some strategies to reduce risk in specified
often includes identifying those patients who are not too ill
groups of patients
but not too well to benefit from the associated therapy.
Proof that a testing strategy is predictive, not merely
prognostic, is best demonstrated by randomized trials Preoperative Laboratory Testing
comparing outcomes in groups receiving best conventional There are at least 33 reasons why surgeons order pre-
care with or without the proposed test. This is a high stan- operative laboratory tests; some are unique to teaching
dard but has been met in situations such as screening mam- environments, and most are not clinically useful or relevant
mography for breast cancer in women ages 50 to 70 and in the “otherwise healthy patient in the absence of a specific
computed tomographic (CT) scans in closed-head injury. indicator.”3 There is poor correlation between the number of
In medicine and surgery, we like to think of ourselves as tests ordered and quality of care or physician competence,
scientists who make decisions and perform procedures and the wide variation in test ordering suggests that some,
based on the results of studies and clinical trials that support or perhaps many, tests are ordered unnecessarily.4
our management strategies. Traditionally, we always obtain As a corollary, surgeons order preoperative laboratory
a clinical history and perform a physical examination. tests for fear of malpractice, for detection of an unsuspected
This interaction with our patients helps us focus and refine disease, or because they “have always done it that way.”
our therapies but, equally importantly, promotes the health Note that detecting an unsuspected disease in the preopera-
literacy of our patients.1 There is good evidence that patients tive period is no different from screening for disease in a
who understand their disease and who participate actively population, albeit a selected (preoperative) population.
in their therapy will fare better.1 Comprehensive literature reviews and government publi-
However, once we have finished talking with our patients, cations guiding reimbursement for preoperative testing (or
the data-driven support for the traditional model of pre- lack thereof)2,5,6 lament the lack of Level I evidence to guide
operative testing begins to break down. We define a “routine policy making, but most admit that the preponderance
test” as a test that we obtain on an asymptomatic, appar- of nonrandomized clinical trial data demonstrates that
ently healthy patient in the absence of any specific clinical preoperative testing is not clinically useful. Amazingly,
indication.2 Then we examine the frequency of abnormal this question has been studied formally for at least 50 years
routine test results, but it gets cloudier when we try to (yes, half a century), with the following strikingly similar
determine how often an abnormal test result changes our conclusions. Preoperative laboratory testing
management. There is almost no information relating a
test-driven alteration in management to any benefit in 1. Has no clinical value for asymptomatic healthy individuals,
outcome. Intuitively, we do know that the more fragile in the absence of a specific clinical indication, such as a
the patient and the bigger the surgical procedure, the more diuretic
likely it is that we should anticipate trouble. 2. Has only marginal value for those with known disease
3. Will yield abnormal results for 1 to 2% of all test results
4. Yields results that would have been predicted from the
* The authors and editors gratefully acknowledge the contribu- underlying patient diseases
tions of the previous authors, Cyrus J. Parsa, MD, Andrew E. 5. Does not change treatment when abnormal results are
Luckey, MD, Nicolas V. Christou, MD, to the development obtained
and writing of this chapter. 6. Yields abnormal results that are often ignored by the
ordering physician
Financial disclosure information is located at the end of this chapter 7. Allows considerable unrealized cost savings derived from
before the references. not performing these preoperative tests

Red highlighting indicates that the text is tied to a SCORE learning objective. Please 03/12
see the HTML version online at www.acssurgery.com.
elem cont prac 6 preoperative testing, planning, and risk stratification — 2
So let us chronologically recapitulate selected studies for their Veterans Affairs Medical Center alone. They con-
chosen to demonstrate the evolution of this issue through cluded that preoperative testing limited exclusively to those
the lenses of multiple medical specialties. In 1965, patholo- patients with clinical indications would have no effect on the
gists Bold and Corrin published their study titled “Use quality or safety of care.
and Abuse of Clinical Chemistry in Surgery.”7 This study In a similar study of 520 patients undergoing elective
was performed in the early days of clinical pathology, before general, vascular, thoracic, and head and neck surgery, pre-
automated analyzers were commercially available. One operative tests included electrolytes, blood urea nitrogen
hundred fifty of 344 (44%) tests were preoperative tests (BUN), creatinine, glucose, hemoglobin/hematocrit, total
of “urea and electrolytes and metabolic abnormalities in protein, albumin, total lymphocyte count, PT, PTT, platelet
patients with renal calculi.” Almost all of the preoperative count, urinalysis, electrocardiography (ECG), and chest
test results were within accepted reference ranges and radiography.9 Age, gender, and specific concomitant illnesses
were euphemistically termed “useful negative” results. This were associated with predictably abnormal laboratory tests.
study pioneered the acquisition of nonuseful preoperative Routine preoperative laboratory testing was identified as
laboratory data. “neither useful nor cost-effective.” Perhaps in response to
Automated clinical laboratory testing became widely this wave of data, preoperative testing practice at four
available in the late 1960s, exponentially increasing the institutions over 8 years and for only four surgical proce-
opportunity for unnecessary laboratory testing. In the early dures was examined. Although wide variations from
1980s, several groups assessed preoperative laboratory test- “operation to operation, test to test and institution to institu-
ing (they termed it “screening”) for 2,000 patients. Many tion,” were unexpectedly identified, an approximately 20%
tests were ordered “by protocol,” including complete blood decrease in both unnecessary and medically indicated testing
count (CBC), white blood cell (WBC) differential, prothrom- was achieved. For the unnecessary tests alone, the authors
bin time (PT), partial thromboplastin time (PTT), platelet extrapolated to the entire United States and estimated an
count, “six-factor automated multiple analysis” (sodium, approximately $320 million annual savings.
potassium, chloride, total carbon dioxide content, serum The obvious question is what happens to patients who
urea nitrogen, creatinine), and glucose. Of 2,785 routine do not enjoy the safety of preoperative laboratory testing?
preoperative admission tests, the authors concluded that Narr and colleagues reviewed the outcomes of 1,044 ran-
approximately 60% were “unindicated” (i.e., the patient domly selected patients from 5,120 patients who had no
lacked a recognizable clinical indication for testing). Four laboratory tests performed within 90 days before a surgical
results (0.22%) were substantially significant so as to affect procedures.9 Ninety-seven percent of the patients were
anesthetic or surgical management, yet there was no docu- “relatively healthy.” Zero deaths or major perioperative
mentation that care management was altered based on these complications resulted. Furthermore, this group observed
abnormal laboratory results. Furthermore, there was no that no laboratory test performed intra- or postoperatively
documentation by physicians of further exploration of these changed surgical or medical management “substantially.”
abnormal results, presumably raising (rather than limiting) They concluded that patients who, following a history and
issues of legal liability for the ordering physician. The physical examination, are “determined to have no preopera-
authors concluded that preoperative testing should be tive indication for laboratory tests can safely undergo anes-
performed only for patients with an identified disease or thesia and operation with tests obtained only as indicated
for whom the surgical procedure would be altered based on intra- and postoperatively.”
the result. They extrapolated that approximately 9,000 tests In 1995, laboratory medicine, surgery, and anesthesia
annually could have been avoided, resulting in approxi- practitioners collaborated to develop laboratory testing
mately $147,000 decreased charges and a cost savings of guidelines before admission for elective surgery.10 Testing
$95,800 (1985 dollar value). guidelines were developed and categorized into four major
Physicians and surgeons are perhaps guilty of a certain groups, as well as by age and gender. The surgeons then
amount of intellectual inertia as similar studies paradoxi- agreed to delegate test ordering to nurses and anesthesiolo-
cally concluded that preoperative testing was “useful” even gists who evaluated the patients before surgery. Volume
when the authors acknowledged that test abnormalities and appropriateness of ordered tests were compared before
provoked no clinical consequences. A consistent finding was and after guideline adoption. They observed a 67% reduc-
a 1 to 2% incidence of abnormal results, a lack of clinical tion in the overall number of tests ordered per patient for
consequences, and an absence of physician response to the the first 2 years after guideline implementation, with an
abnormal laboratory tests. improvement in the appropriateness of test ordering (65%
Anesthesiologists have been the first discipline to substan- were considered “appropriate” prior to guideline imple-
tively engage in the debate. When managed care capitation mentation and 81 to 86% postimplementation). They noted
was introduced and cost containment became critical to marked fiscal savings related to this performance improve-
the survival and success of health care organizations, anes- ment initiative, quantified as $66,981 in year 1 and $75,995
thesiologists were the first group to responsibly respond. in year 2.
Allison and Bromley assessed the clinical usefulness of pre- In the late 1990s, anesthesiologists Vogt and Henson con-
operative testing in 60 randomly selected veterans prior ducted a prospective, cross-sectional study in a university
to ambulatory surgery.8 They concluded that two thirds of hospital, studying 312 consecutive patients scheduled for
testing was inappropriate and estimated the unnecessary elective surgery and evaluated by an anesthesiologist in a
costs at $47 for a veteran and $80 for a community hospital preoperative clinic.11 The goal of the study was to determine
patient (1996 dollar value), with potential savings of $11,757 if there was a difference in the ordering of “unindicated
03/12
elem cont prac 7 mechanical ventilation — 3
preoperative laboratory tests” for healthy (American Society • “Physicians should not be criticized for selective test
of Anesthesiologists [ASA] physical status I and II) versus ordering before surgery.”
sicker (ASA physical status III) patients. The anesthesiolo- • “Physicians and institutions recommending routine pre-
gists evaluated the test ordering by surgeons relative to operative testing for all patients provide no clinical value
ASA status and concluded that 72.5% of tests ordered by to their patients at considerable cost.”
surgeons were considered not indicated by the anesthesiolo-
gists. Although there were fewer “unindicated” tests with A subset of studies have noted specific abnormal labora-
worsening ASA status, the overall conclusion was that a tory results related to age, gender, and concomitant underly-
large proportion of surgeon-ordered preoperative tests ing illnesses. The latter, selective testing for concomitant
were unnecessary. By eliminating unnecessary testing, they underlying illnesses, is accepted practice for routine medical
estimated an annual cost savings of $80,000 (1997 dollars). care regardless of anticipated surgery. The common theme
In 2002, the ASA Task Force on Preanesthesia published appears to be that if the physician would request a test in
its review and practice advisory.5 Regarding laboratory the absence of anticipated surgery, the test is also warranted
tests, a clear distinction was made between “routine” and prior to surgery. Extremes of age and gender do keep
“selective” preoperative tests. Routine tests were defined reappearing as potential independent predictors of trouble.
as those intended to discover a disease or disorder in an
age
asymptomatic individual. The task force bluntly stated that
routine tests “do not make an important contribution to the Dzankic and colleagues assessed the importance of pre-
process of perioperative assessment and management of the operative laboratory testing in 544 patients 70 years and
patient by the anesthesiologist.” In contrast, the task force older undergoing noncardiac surgery.14 They observed that
recommended performing selective tests, that is, those 0.5 to 5% had electrolyte and platelet count abnormalities,
tests medically indicated because of the history and physical 12% had elevated serum creatinine (> 1.5 mg/dL), 10% had
findings, medical record review, and type of invasiveness of hemoglobin less than 10 g/dL, and 7% had serum glucose
the planned procedure and anesthetic, because their results greater than 200 mg/dL. None of these abnormalities
“may assist the anesthesiologist in making decisions about were predictive of postoperative adverse outcomes. The
the process of perioperative assessment and management.”5 ASA classification and surgical risk were stronger univariate
Clinical studies are very hard to do, and it is easy to criticize predictors for adverse outcome than abnormal serum elec-
them. Perhaps these studies were performed in settings trolyte or creatinine values, and only the ASA classification
where timely treatment of chronic diseases was available, and surgical risk by multivariate logistic regression were
allowing maximal optimization of patients prior to elective predictive of postoperative adverse outcomes. The authors
surgery. The recommendations of a conscientious task force concluded that age alone was not sufficient justification
are difficult to ignore, however. So what happens to surgical for routine preoperative laboratory testing and recommend-
patients in developing countries where no chronic disease ed using the history and physical examination to guide
management is available? preoperative testing.
Pal and colleagues retrospectively studied the benefit of Ophthalmologists Schein and colleagues conducted a
preoperative testing in 216 asymptomatic healthy surgical landmark study of 9,408 patients aged 80 years and older
patients in Pakistan.12 Their findings were strikingly similar who underwent 9,626 cataract surgeries without preopera-
to those of previous studies; the most common preoperative tive testing, compared with 9,411 patients undergoing
laboratory abnormality was a low hemoglobin in 42 of 216 9,624 operations who had routine preoperative laboratory
(19%) patients, almost all females. Chest x-ray abnormalities testing.15 They found no difference between groups relative
were the next most common abnormality, present in 11 of to intraoperative or postoperative events. Routine preopera-
103 (10.6%) patients, followed by mild hypokalemia in 6 tive testing offered no benefit over that attained from
of 123 (4.8%) patients and an elevated glucose in 1 of ASA classification and medical history. They concluded that
113 (0.88%) patients. Aside from a single preoperative routine preoperative testing before cataract surgery did not
intervention for a patient with a preoperative hemoglobin measurably increase the safety of surgery.
of 4.8 g/dL, treatment plans or outcomes were not affected. Schein and colleagues noted that cataract surgery was the
The authors concluded that the history and physical exami-
most commonly performed operation in elderly people in
nation were the most reliable and cost-effective preoperative
developed countries, with 1.5 million cataract operations
screening tools available. They endorsed the existing ASA
in 1996.15 From their study, it was estimated that the cost
guidelines for class I (asymptomatic healthy) patients, that
of routine preoperative testing prior to cataract surgery
is, no preoperative testing is recommended.
exceeded $150 million annually and, given the lack of
In 2003, the general medicine and primary care practitio-
benefit from testing, suggested that these costs could be
ners entered the debate. Smetana and Macpherson reviewed
saved without a negative effect on patient outcome.
the published literature on preoperative testing and con-
The screening value of preoperative laboratory findings in
cluded that “almost all “routine” laboratory tests before
children is the same as that for adults: not clinically useful
surgery have limited clinical value.”13 Based on their review,
for healthy children presenting for minor elective surgery.
they recommended the following:
Burk and colleagues encouraged preoperative coagulation
• “Clinicians should order tests only if the outcome of an testing to identify rare, undiagnosed congenital or heredi-
abnormal test will influence management.” tary bleeding disorders in children prior to tonsillectomy.16
• “When an abnormal test results from such testing, it is This value, however, was clearly offset by the rarity of the
critical that physicians document their thinking about the disorders coupled with the high frequency of false positive
result.” bleeding histories and laboratory tests.
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gender
Table 3 American Society of Anesthesiologists’
A relatively common finding in many preoperative Physical Status Classification5
testing studies was anemia in women of childbearing age.
Classification Description Examples
This is the only gender-specific “abnormality” reported and
would support preoperative inquiry if the clinical presenta- Class I Healthy patient with
tion would prompt the clinician to respond to an abnormal no systemic
disorder
result.
Several decades ago, a group at the Mayo Clinic began Class II Mild to moderate Chronic obstructive
systemic disorder pulmonary disease
to realize that subjecting patients to large numbers of
that need not be Diet-controlled diabetes
preoperative tests did not change surgical results.17,18 They associated with the Extremes of age
further observed that when preoperative testing returned surgical problem Medication-controlled
an abnormal result, they rarely did anything differently hypertension
anyway17 [see Table 1 and Table 2]. Moderate obesity
In summary, the overwhelming majority of studies Class III Severe systemic Insulin-dependent
have concluded that there is little to no value of screening disease that limits diabetes
activity but is not Lifestyle-limiting
preoperative laboratory tests in asymptomatic patients in
incapacitating pulmonary insuffi-
the absence of a specific clinical indication [see Table 3]. Lab- ciency
oratory tests within 6 months of surgery to gauge surgical Morbid obesity
and anesthesia risk are acceptable if the patient’s condition Stress-induced angina
has not changed clinically in the intervening period. Con- Class IV Incapacitating, Active cardiac ischemia
versely, if the patient’s condition has changed, laboratory life-threatening Advanced hepatic,
systemic disease pulmonary, or renal
disease
Refractory arrhythmia
Table 1 Effect of Abnormal Screening Results Signs of congestive heart
on Physician Behavior18 failure
Unstable angina
Screening Test % Abnormal Test % Resulting in
Results Management Change Class V Moribund patient, not Major cerebral trauma
expected to survive with increasing
Bleeding time 3.8 Abnormal result rarely
24 hours without intracranial pressure
led to change
an operation Major trauma with
Chest x-ray 2.5–3.7 2.1 shock
Massive pulmonary
Coagulation time 4.8 Abnormal result rarely embolus
led to change Ruptured aortic
Electrocardiogram 4.6–31.7 0–2.2 aneurysm with
profound shock
Hemoglobin 5 (for < 10 g/dL; Abnormal result rarely
< 9 g/dL was led to change
rare)
testing is medically indicated as specifically dictated by the
Partial thrombo- 15.6 Abnormal result rarely
plastin time led to change change in clinical condition.2,5,6,13
A color-coded “at a glance” guide modeled on traffic
Total leukocyte <1 Abnormal result rarely
count led to change
signals (green = consensus to do a test; red = consensus not
to do a test; amber = absence of consensus, “consider testing”)
Urinalysis 1–34.1 0.1–2.8 has been prepared to guide busy practitioners regarding
when to order what preoperative test [see Figure 1]6; other
similar guides abound [see Figure 219 and Table 4]. Audits20
Table 2 Minimum Preoperative Test of current preoperative laboratory testing practices will
Requirements at the Mayo Clinic (in 1993)17 remain scrutinized by conscientious investigators, but profes-
Age (yr) Tests Required sional guidelines consistently reveal persistent unnecessary
preoperative testing.21
< 40 None
40–59 Electrocardiography, measurement of creatinine,
measurement of glucose Changing Paradigms of Surgical Success
g 60 Chest x-ray, complete blood cell count, It is now clear that postoperative survival by itself is no
electrocardiography, measurement of creatinine, longer an adequate assay of surgical success. Risk must be
measurement of glucose
stratified before operation, and the degree of risk must be
In addition, the following guidelines apply: (1) a complete blood cell count is evaluated in light of both the quantity and the quality of
indicated in all patients who undergo blood typing and are crossmatched; (2) mea- postoperative life. Cost must then be judiciously assessed
surement of potassium is indicated in patients taking diuretics or undergoing
bowel preparation; (3) a chest x-ray is indicated in patients with a history of car- relative to a risk-stratified, quality-adjusted postoperative
diac or pulmonary disease or with recent respiratory symptoms; and (4) spirometry year of life. In 2008, Cohen and colleagues published an
(forced vital capacity) is indicated in patients 40 years of age or older who have a
history of cigarette smoking and are scheduled for an upper abdominal or thoracic
assessment of health economics.22 These authors calculated
procedure. the cost-effectiveness ratio by dividing the incremental costs
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ASA/Surgery CXR ECG CBC Lytes BUN/Cr Glucose LFTs PT/PTT UA

ASA = 1 < 1 y/o
1–60 y/o
60–80 y/o
> 80 y/o
ASA = 2 < 1 y/o
1–60 y/o
60–80 y/o
> 80 y/o
ASA = 3 < 1 y/o
1–60 y/o
60–80 y/o
> 80 y/o
ASA = 4 < 1 y/o
1–60 y/o
60–80 y/o
> 80 y/o
Neurosurgery < 1 y/o
1–60 y/o
60–80 y/o
> 80 y/o
Cardiovascular < 1 y/o
1–60 y/o
60–80 y/o
> 80 y/o
Figure 1 Appropriate preoperative tests related to the patient’s American Society of Anesthesiology (ASA) classification and age. Red indicates
that the preponderance of evidence suggests that the test will not be useful (or positively influence patient care); yellow indicates that the test is
controversial; green indicates that the test is useful. BUN = blood urea nitrogen; CBC = complete blood count; Cr = creatinine; CXR = chest x-ray;
ECG = electrocardiogram; LFT = liver function test; PT = prothrombin time; PTT = partial thromboplastin time; UA = urinalysis; y/o = years
old.
of surgical therapy by incremental benefits as quality- professionals who must perform this kind of balancing act,
adjusted year of life (QALY), compared with standard we are the ones who do it most conspicuously.
medical care. They reported that cochlear implants for Continuing refinement of the methods employed to strat-
profoundly deaf children reduced lifetime aggregate costs ify preoperative risks permits surgeons to “handicap” both
and improved health; liver transplantation for primary patients and surgical procedures with greater precision.
sclerosing cholangitis cost $41,000/QALY; implantation of Outcome assessment must clearly incorporate the “sickness
cardioverter-defibrillators in patients with left ventricular quotient,” which is typically expressed in terms of the ratio
dysfunction cost $52,000/QALY, and surgery in 70-year-old of observed to expected outcome (O/E), into the assessment
men with a new diagnosis of prostate cancer increased costs of therapeutic value. If a surgeon were to operate only on
and compromised health compared with watchful waiting.22 Olympic athletes with single-organ diseases (or no disease
Thus, the purposes of this section are to add “dollar cost”
at all), his or her patients would likely do very well.
and postoperative quality of life to the preoperative risk
Those of us who must operate on a more diverse patient
assessment equations. We also propose to describe the
population will have less gratifying results.
potential preoperative cardiac, pulmonary, and laboratory
The most widely used risk classification system was
tests; analyze the significance of abnormal results; and
ultimately develop a strategy for relating patient character- developed by the ASA and is based on the patient’s func-
istics and the magnitude of the procedure to the menu of tional status and comorbid conditions (e.g., diabetes melli-
preoperative studies. tus, peripheral vascular disease, renal dysfunction, and/or
Although no one ever truly wants to undergo a surgical chronic pulmonary disease) [see Table 3].24 The ASA index
procedure, the results of surgery can be formidably gratify- generally associates poorer overall health with increased
ing to both patient and surgeon when the right operation is postoperative complications, longer hospital stays, and
performed accurately, expeditiously, and for the right rea- higher mortality.
sons, on the right patient at the right time. In attempting to In addition to functional capacity and comorbid condi-
bring about this state of affairs, surgeons must consciously tions, age is a robust determinant of operative risk, as is the
and honestly balance the physiologic, psychological, social, type of operation. Vascular procedures and prolonged, com-
and financial burdens of surgery against the anticipated plicated thoracic, abdominal, or head and neck procedures
benefits.23 Although surgeons are not the only medical carry higher levels of risk. None of this is surprising.
03/12
TESTS Rx
Frailty Medical Cardiology Resting 2–3 ETT MUGA PFTs Beta

"Eyeball" Consult Consult ECG Flights Blockers Statins
ASA/Surgery Test Stairs
ASA = 1 < 1 y/o
1–60 y/o
60–80 y/o
> 80 y/o
ASA = 2 < 1 y/o
1–60 y/o
60–80 y/o
> 80 y/o
ASA = 3 < 1 y/o
1–60 y/o
60–80 y/o
> 80 y/o
ASA = 4 < 1 y/o
1–60 y/o
60–80 y/o
> 80 y/o
Neurosurgery < 1 y/o
1–60 y/o
60–80 y/o
> 80 y/o
Cardiovascular < 1 y/o
1–60 y/o
60–80 y/o
> 80 y/o
Figure 2 Preoperative assessment strategies and recommended risk-reducing therapy relative to American Society of Anesthesiologists (ASA)
classification performed by the surgeon and age. Red indicates that the preponderance of evidence suggests that the strategy or therapy will not
be useful (or positively influence patient care); yellow indicates that it will be controversial; green indicates that it will be useful. Each discipline
has its own quasisubjective test for perceived patient fortitude. The anesthesiologists term it the ASA classification; surgeons use the frailty index
or the “eyeball” test. Nutritionists refer to the subjective global assessment, whereas oncologists rely on Karnofsky scoring. In each instance,
the subjective “eyeball” impression of a seasoned clinician has traditionally proven to be gratifyingly valuable. ECG = electrocardiogram;
ETT = exercise tolerance testing; MUGA = multigated acquisition; PFT = pulmonary function test; y/o = years old.
what to look for in the patient’s history congestive heart failure (11 points), any nonsinus cardiac
We all deteriorate as we age. In fact, the Mayo Clinic uses rhythm (7 points), and advanced age (5 points). These
age alone as the initial filter in its selection of preoperative cardiac risk factors were assigned high numbers of points,
tests for “healthy” patients. The anesthesiologists refine although, perhaps surprisingly, no other warning signs
this ASA policy by defining the “health” of the patient received more than three—not even carbon dioxide tension
[see Table 3], which requires a search for comorbid disease. (Pco2) greater than 50 mm Hg, BUN greater than 50 mg/dL,
The diseases and other indicators that seem to count most bicarbonate less than 20 mM/L, or potassium less than
are those that reflect cardiovascular compromise: angina, a 3.0 mM/L. Liver function tests were so insensitive that they
past myocardial infarction, and surrogates for coronary were deemed insignificant. In 1995, Mangano and Goldman
artery disease, such as diabetes, hypertension, obesity, and repeated this study and reported the same conclusions.26
advanced age. Nothing else seems to have much effect. Many risk stratification systems refer to “otherwise
Goldman and colleagues first reported this observation healthy patients.” The term “healthy patient” should be
in 1977.25 They followed 1,001 patients through a major translated as “asymptomatic patient.” When you are taking
surgical procedure and related their preoperative history, the patient’s history, you should focus on probing for the
physical findings, and routine laboratory work to major indicators of cardiac disease.
complications: perioperative myocardial infarction, cardio-
indicators of cardiac risk
genic pulmonary edema, ventricular tachycardia/fibrilla-
tion, and death. They then applied univariate analysis In a successful attempt to simplify Goldman and colleagues’
to ascribe varying numbers of points to each preoperative equation, Boersma and colleagues refined the Lee and
factor that predicted postoperative problems. All of the colleagues Revised Cardiac Risk Index (RCRI), which is
ominous preoperative signals were those that reflected currently the most widely applied cardiac risk stratification
cardiovascular disease: recent myocardial infarction (10 points), system.27,28 The RCRI identifies six predictors of major
03/12
Table 4 Preoperative Assessment Strategies Related to Purposes and Potential Information Derived
Assessment Strategy Information Derived Purpose(s) Indication/Comments
Medical consultation Assessment of chronic disease To stabilize chronic disease ASA classes III and IV (not typically
useful in ASA I, II, or V)
Cardiac clearance Assessment of chronic cardiac To stabilize chronic ASA classes III and IV (not typically
disease cardiopulmonary disease useful in ASA I, II, or V)
Frailty (“eyeball”) test Global assessment of surgical risk/ Practical guide to surgical Useful in assessing necessity/benefits of
benefit risk/benefit surgical intervention
Resting ECG (1) Cardiac rhythm; (2) may reflect To determine resting cardiac Disappointing indicator of cardiac status
prior muscle damage (Q waves) rhythm
Climbing 2–3 flights of Practical indicator of strength and Subjective indicator of Useful indicator of cardiopulmonary
stairs cardiopulmonary status cardiopulmonary status status in sorting out ASA class III
patients
Exercise tolerance test Quantitative indicator of Objective indicator of Useful if results might lead to cardiac
cardiopulmonary status cardiopulmonary status intervention in the absence of
proposed elective general surgery
Multigated acquisition Ejection fraction To assess ventricular function Low yield in ASA class I, II, and III
(MUGA) scan patients
Pulmonary function Pulmonary status To assess medical reversibility Valuable in discriminating patients with
tests (PFTs) of lung dysfunction equivocal 2–3 flights of stairs climbing
test
ASA = American Society of Anesthesiologists; ECG = electrocardiogram.
cardiac complications (high risk surgical procedures, combined task forces to clarify current recommendations
ischemic heart disease, history of congestive heart failure, for national quality initiatives in perioperative stratification
history of cerebrovascular disease, insulin use and a creati- and risk modification.30 Their strategy bases diagnostic and
nine greater than 2.0 mg/dL). Scores range from 0 to 5, therapeutic approaches on clinical screening for disease state
and the likelihood of major perioperative complications and functional capacity. Specialized testing is conservatively
increases with rising scores [see Table 5].25,26 This index has employed only when additional information provided by
weaknesses. It was derived from calculations that excluded the proposed test is likely to impact the outcome. The ACC/
emergency surgical patients and neurosurgical patients, AHA consensus guidelines recommend aggressive medical
whereas thoracic, vascular, and orthopedic patients were management to provide myocardial protection in the peri-
overrepresented. In addition, it classified surgical proce- operative period to mitigate cardiac risk. This strategy has
dures simplistically into two categories: high risk and proven to be both efficient and cost-effective in vascular
non–high risk. Despite these weaknesses, the predictive surgery patients. The most recent update of these guidelines
accuracy of the RCRI has been validated in large cohorts.27 was published in late 2007.30
Whereas the RCRI documents cardiac risk factors, the The ACC/AHA guidelines employ a five-step algorithm
American College of Cardiology (ACC)/American Heart designed to guide patient risk stratification and subsequently
Association (AHA) Task Force guidelines (see below) were
determine appropriate cardiac evaluation. This algorithm is
developed to serve as a national quality initiative for use of
available on the ACC website (http://www.acc.org/clinical/
the RCRI and optimization of perioperative risk by medical
guidelines/perio/update/fig1.htm).
or, rarely, surgical means. The goal of a preoperative cardiac
Step 1 involves assessing the urgency of the operation.
consultation is to determine the most appropriate testing
Step 2 is the process of looking for active cardiac conditions,
and treatment strategies for optimizing patient care while
avoiding unnecessary testing. This represents a definite including unstable coronary syndromes, decompensated
paradigm shift from the stratification and revascularization heart failure, significant dysrhythmias, and severe valvular
strategies commonly employed only a decade ago. disease. If any of these conditions are present and the
Interestingly, these guidelines are not always followed in operation is elective, the patient should be evaluated further
clinical practice. One survey found that despite the avail- and treated according to ACC/AHA guidelines. Step 3 is
ability of the guidelines, 40% of cardiology consultations activated when no active cardiac condition is present
resulted in the simple recommendation to proceed with and the proposed operation is low risk. In this instance, the
surgery, without modification of perioperative plans or surgeon may proceed without further intervention. Step 4
optimization of risk factors.29 Patients selected for noninva- includes operations that are deemed to be of intermediate to
sive testing do appear to receive more medical therapy (e.g., high risk. The patient’s functional status must be determined
beta blockers, statins, and platelet inhibitors) than patients [see Table 6]. If the patient is asymptomatic and functional
who are not referred for further cardiac evaluation. status is good, the planned operation may proceed without
further intervention. If the patient is symptomatic or functional
acc/aha task force guidelines status is undetermined or poor (defined as the inability to
Routine preoperative cardiac evaluation and testing suffer perform activities involving energy expenditure greater than
significant inherent limitations. The ACC and the AHA have 4 metabolic equivalents [METs]), further investigation is
03/12
but only if the results might change management. Patients

Table 5 Revised Cardiac Risk Index26
with three or more clinical risk factors who are undergoing
No. of Risk Factors Risk of Major Cardiac a vascular procedure should receive further evaluation, but,
Complications (%)
again, only if the results might change management.
0 0.4
1 0.9
Identification of Factors Affecting Cardiac Risk
2 7.0
Heart failure is the most common discharge diagnosis in
3+ 11.0 hospitals across the United States. The prevalence of heart
There are six clinical risk factors: (1) high-risk surgery; (2) ischemic heart disease failure increases with age, and as our surgical population
(myocardial infarction, positive treadmill test, use of nitroglycerin, current chest ages, we treat more and more elderly patients with relevant
pain, pathologic Q waves on electrocardiogram); (3) congestive heart failure (docu-
mented history, pulmonary edema, paroxysmal nocturnal dyspnea, S3 or chest x-
degrees of heart failure.
ray with pulmonary vascular redistribution); (4) cerebrovascular disease (transient Numerous cardiac risk indices have been created over
ischemic attack or cerebrovascular accident); (5) insulin-dependent diabetes mellitus; the past three decades. During that period, risk stratification
and (6) renal failure (progressive serum creatinine > 2.0 mg/dL).
has evolved from the early Goldman and colleagues criteria,
the first substantial effort at risk assessment, to the RCRI
necessary. In step 5, the final step, the surgeon searches for developed by Lee and colleagues27 [see Table 5]. A review of
major clinical predictors of specific cardiac risk. As defined the initial and updated multivariate analysis of risk predic-
by the ACC/AHA Task Force, clinical cardiac risk factors tors prior to noncardiac surgery attributes the lion’s share of
include a history of ischemic heart disease, compensated or risk to the cardiovascular system.25,26 If your patient suffers
previous heart failure, cerebrovascular disease, diabetes a major perioperative complication (myocardial infarction,
mellitus, and/or renal insufficiency.30 Patients with no his- cardiogenic pulmonary edema, sustained ventricular tachy-
tory of clinical risk factors may proceed to surgery. Patients cardia/fibrillation, or death), the only organ system that
with one or two clinical risk factors who are undergoing a appears to matter much is the heart.
vascular procedure or patients with one or more clinical risk To reiterate, Mangano and Goldman ascribe 11 points
factors who are undergoing an intermediate-risk operation to any preoperative evidence of congestive heart failure,
have the option of either proceeding with surgery after 10 points to a myocardial infarction within the last 6 months,
appropriate beta blockade or receiving additional evaluation, 7 points to any ECG rhythm other than sinus rhythm, and
Table 6 Approximate Metabolic Equivalents and Peak Oxygen Intake Related to Common Daily
Activities and Stages of the Bruce Protocol (Modified Duke Activity Status Index)
Activities: “Are you able to...” Metabolic Peak Oxygen Bruce Protocol Correlates
Equivalents (METs) Intake* (mL/kg/min)
Stage % Grade mph
Lie in bed with minimal movement (bedridden)? ≈ 1.00 < 10 NA† NA† NA†
Sit up in bed independently? 1.25
Walk around the house? 1.75 10–15 1 10 1.7
Take care of yourself (toilet, feed, bathe, and clothe yourself?) 2.75
Do light housework, such as washing dishes? 2.75
Walk two blocks at ground level? 3.00 15–20
Do moderate housework, such as vacuuming/sweeping floors? 3.50
Do yard work, such as raking leaves? 4.50 20–25 2 12 2.5
Have sexual relations? 5.25
Walk up a hill or climb two or three flights of stairs? 6.00
Participate in moderate recreational activities such as 6.00
swimming, golf, or slow dancing?
Do heavy housework such as lifting or moving heavy furniture? 8.00 > 25 3 14 3.4
Run a short distance? 10.00
Participate in strenuous sports such as volleyball or basketball, 12.00 4 16 4.2
run on a treadmill, or use an elliptical machine?
Run a long distance? 12.00+
NA = not applicable.
*Estimates of peak oxygen uptake are based on comparison data obtained from various levels of an exercise cardiac stress test (i.e., the Bruce protocol). These numbers vary
by age and gender and hence represent estimates for women and men of differing ages.
†
Bedridden patients are unable to participate in exercise stress testing. Hence, no data are available for this group in regard to Bruce protocol staging.
A physician may assess functional status as part of a preoperative checklist, but the patient usually provides only a snapshot of his or her most recent activities. Activity
levels are not static but, rather, dynamic. Indeed, exercise tolerance can be gained over time with work (“training”). If patients are able to climb the ladder of activity status
and tolerate more vigorous exercise, this is the ultimate cardiac stress test. Hence, increasing exercise in patients (“training”) is a constructive preoperative formula.
03/12
5 points to age greater than 70 years of age (a surrogate ventricular diastolic compromise, valvular heart disease, and
for coronary disease).25,26 No other indices (including a Pco2 myocardial ischemic disease resulting in electrophysiologic
greater than 50 mm Hg or a creatinine level greater than instability.
3.0 mg/dL) warrant more than 3 points. So a seemingly
innocuous sigmoid resection (abdominal surgery = 3 points) functional capacity
in a 70-year-old gentleman (5 points) in atrial fibrillation Patients who are able to exercise regularly without
(7 points, and 20% of septuagenarians exhibit atrial fibrilla- limitation generally have sufficient cardiovascular reserve to
tion) who suffered just a “little” heart attack 3 months ago withstand stressful operations. Those with limited exercise
(10 points) climbs into the highest risk category with 26 total capacity are prone to exhibit this poor cardiovascular
points. In the Goldman and colleagues and Mangano and reserve either during or after noncardiac surgery. Even out-
Goldman studies, class IV risk (patients scoring more than side the surgical arena, patients with poor functional status
25 points) suffered a 26% chance of major complications enjoy a shorter life span.32
such as ventricular tachycardia or ventricular fibrillation or Functional capacity is readily expressed in terms of
death.25,26 METs. One MET is equivalent to the energy expended
Now—15 to 30 years later—we may be doing a little (or the oxygen used) in sitting and reading this chapter
better, but the cardiovascular system remains the culprit. (3.5 mL O2/kg/min). For a 70 kg person, one MET amounts
The purposes of this section are to review the various tests to 70 kg x 3.5 mL O2/kg/min, or 245 mL O2/kg/min.
of cardiovascular function and to develop a practical and Multiples of the baseline MET value can then be used to
safe algorithm for preoperative cardiac evaluation. There are quantify the aerobic demands posed by specific activities.
no surprises here. The bigger the operation, the higher the A modification of the Duke Activity Status Index33 developed
cardiac risk; the older the patient, the riskier the outcome is 20 years ago is still a practical guide [see Table 6].
likely to be. Conversely, even two decades ago, Warner and Functional status correlates with exercise treadmill
colleagues reviewed the 30-day mortality of over 45,000 testing. Multiple studies have indicated that perioperative
patients undergoing outpatient anesthesia and surgery31 cardiac and long-term risks are increased in patients who
[see Figure 3]. Adjusting for age and gender, these authors are unable to meet the 4-MET demand associated with
concluded that the low-risk surgical procedure provoked no most normal daily activities. This higher-risk status can be
more deaths than would have occurred during a month signaled by poor performance on a treadmill test protocol
without surgery. On the other hand, when a surgeon is [see Table 7]. However, just by talking with your patient, you
confronted with a high-risk patient needing a high-risk pro- can assess the patient’s exercise capacity. This assessment
cedure, a strategic alternative is not a retreat; it is responsible is a practical, inexpensive, and accurate predictor of your
medicine. All too often, however, an elderly patient presents patient’s ability to tolerate a surgical stress.
with a clear mesenteric vascular accident, and surgical
intervention is the only option. This situation obligates a resting electrocardiogram
compassionate explanation to the patient, a sensitive discus- To determine whether a patient or an organ can tolerate a
sion with the family, and a bold acceptance of reality by stress, we must stress that organ or patient. Intuitively, it
the surgeon. Most often, however, both the patient and the does not make much sense to obtain a resting ECG in an
procedure are solidly positioned in an intermediate gray asymptomatic young or middle-aged patient. With older
zone. patients, the resting ECG can exhibit abnormal rhythms
Conceptually, cardiac dysfunction may be comfortably and an old scar (big Q waves). In a retrospective analysis of
discriminated into four broad categories. Each may be 23,036 patients undergoing cardiac surgery, the preopera-
defined using standard cardiac function tests. These cardiac tive ECG improved the predictive value of perioperative
dysfunction categories are ventricular systolic compromise, cardiac events in comparison with clinical risk stratification
alone.34 This predictive benefit was not apparent in low-risk
patients undergoing low-risk procedures.34 We conclude
High that a routine resting ECG prior to even major surgery in a
Big Operation young or middle-aged asymptomatic patient (ASA I/II)
with no historical red flags is very low yield. Vascular dis-
ease, however, is systemic disease. Prior to vascular surgery,
patients deserve a resting ECG.
Procedure
Age
Risk
and
Comorbidities Table 7 Bruce Protocol Stress Test
Stage % Grade mph METs
Small Operation 1 10 1.7 4.7
Low 2 12 2.5 7.0
Low Patient Risk High 3 14 3.4 10.1
Figure 3 A low-risk operation (such as a cataract) renders negligible 4 16 4.2 12.9
additional morbidity and mortality to a patient (irrespective of
5 18 5.0 15.0
American Society of Anesthesiologists [ASA] status) with or without
the surgical procedure. MET = metabolic equivalent.
03/12
Current guidelines discourage routine preoperative non- slope are increased [see Table 7]. Four outcome variables are
invasive cardiac testing for most intermediate-risk preopera- continuously monitored: angina, ST-T wave changes, ectopy
tive patients. In a 2006 study, 1,476 patients were stratified as a reflection of ischemia, and, most importantly, blood
according to their RCRI scores.35 Of these, 770 patients on pressure. When a healthy person exercises, the blood
beta-blocker therapy with tight heart rate control met the pressure should rise. No change, or a decrease in blood
criteria for intermediate risk. This intermediate-risk group pressure, is ominous both for perioperative cardiovascular
was split and randomly assigned to receive either cardiac complications and as a prognostic indicator of nonoperative
stress testing or continued beta-blocker therapy. Some life expectancy.32
degree of ischemia was noted in 25.8% of the patients in In 2009, the ACC collaborated with the AHA Task Force
the testing group, but analysis of the 30-day outcomes after on Practice Guidelines and produced a comprehensive
operation found no difference between the two groups with analysis of exercise stress testing for myocardial ischemia
respect to the incidence of major cardiac adverse events. and functional capacity.36 These authors provided a table
The major difference was that patients in the untested group cataloguing 10 published studies in which high-risk patients
underwent their procedures 3 weeks sooner than patients prior to peripheral vascular or abdominal aortic aneurysm
in the tested group. Noninvasive cardiac testing even in (high-risk) surgery were subjected to exercise stress testing
intermediate-risk patients just takes additional time without preoperatively.
discernible benefit. When exercise tolerance testing (ETT) is used to identify
In general, indications for specialized testing are the same obstructive coronary disease, the results are disappointing.
prior to surgery as in the nonoperative setting. If your As many as half of the patients with a single 70% coronary
patient exhibits the kind of cardiac indicators that might artery stenosis will sail through ETT with a “normal” result.
warrant coronary revascularization in the absence of an For patients with involvement of all three major coronary
impending surgical procedure, proceed with noninvasive arteries or even left main disease, the sensitivity is better at
testing; otherwise, do not proceed. 86%, the specificity remains only 53%.37
The timing of cardiac testing depends on the urgency The mechanics of an ETT are relatively straightforward.
of the noncardiac procedure, the risk factors present, A 12-lead ECG is continuously monitored as the patient
and specific considerations associated with the procedure. walks on a treadmill. The Bruce protocol is most commonly
Coronary revascularization before noncardiac surgery has used [see Table 7]. The patient is required to walk at 1.7 mph
sometimes been advocated as a way of enabling a patient to (not very fast) on a 10% incline. Every 3 minutes, the incline
tolerate a noncardiac procedure, but it is appropriate only is increased by 2%, and the treadmill speed is increased, as
for a very small subset of very high-risk patients. indicated below.
The ACC/AHA guidelines provide the following summary The patient is questioned continuously concerning chest
recommendations. In each instance, evidence is persuasive, pain and fatigue, while the blood pressure is determined at
or only Level B: the end of each stage. Although the early stages of the Bruce
protocol do not seem like a lot of exercise, this may need to
1. Pre- and postoperative resting 12-lead ECG is not be modified to a lower workload for sedentary and elderly
indicated in asymptomatic patients undergoing low-risk patients. Thus, the first two stages of a “modified Bruce
surgical procedures. protocol” are conducted at 1.7 mph at a zero grade (stage I)
2. Vascular disease is a systemic disease, so resting 12- and then a 5% grade (stage II).
lead ECG is indicated in patients undergoing vascular The inconvenience and expense of formal exercise testing
surgery. have prompted many investigations to develop more acces-
3. Preoperative resting 12-lead ECG is recommended sible and practical historical questioning and functional
in patients with the following clinical risk factors: cerebro- testing strategies. Therefore, the ACC and the AHA equate
vascular disease, diabetes mellitus, renal insufficiency, a the ability to walk around the block on level ground as stage
history of ischemic heart disease, or a history of congestive I (Bruce protocol) or less than 4 METs; walking up two flight
heart failure. of stairs is around 6 METs or stage II (Bruce protocol).37
This leaves a relatively wide gray zone, in which there is Nikolić and colleagues refined stair climbing by monitoring
only Level C, or “pretty good,” evidence: pulse oximetry in 101 patients prior to thoracic surgery
as they climbed stairs.38 Eighty-seven of the 101 patients
1. Preoperative resting 12-lead ECG is not helpful in asymp- suffered at least one postoperative complication. Disap-
tomatic patients undergoing intermediate-risk surgical pointingly, age, gender, and oximetry-monitored stair climb-
procedures. ing were not predictive. This is an example of high-risk
2. Resting 12-lead ECG is recommended in patients with patients undergoing high-risk surgery, so the experienced
known coronary artery disease prior to intermediate-risk surgeon should have been prepared for trouble irrespective
operations. of any preoperative tests.
Conversely, multiple groups have linked the graded
cardiac exercise stress testing results of an ETT to a patient’s annual mortality.32 These
A monitored exercise stress test would logically appear to investigators identified 12% of a medically treated group of
be a safe way of reproducing the hemodynamic components patients with coronary artery disease who could manage
of surgical stress. Exercise testing on a treadmill has the only stage I of a Bruce protocol. These patients suffered over
advantage that the results can be quantified in METs 5% annual mortality. In this study, 34% of patients carrying
achieved, and the test (unlike an operation) can be rapidly the diagnosis of coronary artery disease who could accom-
aborted. The patient walks on a treadmill as the speed and plish stage III of a Bruce protocol suffered less than 1%
03/12
annual mortality. It would appear to be a minor conceptual and inexpensive test of performance capacity. Brunelli and
leap to assume that the risk characteristics predicting a colleagues studied 640 patients scheduled for pulmonary
short life are similar to the patient limitations that cause resective surgery with a preoperative, symptom-limited
perioperative morbidity and mortality. For example, Myers stair climbing test.39 Patients who climbed less than 12 m
and colleagues retrospectively studied the ETT results of (less than two flights of stairs) experienced a twofold
6,000 veterans (with and without a diagnosis of coronary increase in complications (p < .0001) and a 13-fold increase
artery disease) and compared the maximum METs achieved in mortality (p <.0001) and incurred costs 2.5 times higher
with annual medically treated mortality data.32 Again, than patients who could manage a climb of 22 m (more
patients who could achieve 8 METs or more suffered less than two flights). These investigators then refined the stair
than half of the mortality of patients who could not com- climbing test by concurrently measuring finger oximetry.
plete Bruce protocol stage I. The predictive value of METs While studying 536 patients breathing room air during
in this study also overwhelmed smoking, hypertension, stair climbing, they sought to determine whether oxygen
body mass index of 30 or greater, chronic obstructive saturation less than 90% or desaturation greater than 4%
pulmonary disease (COPD), and diabetes.32 drop from resting level better discriminated the likelihood
So functional capacity, measured in METs, is a compre- of postoperative complications. The stair climbing was
hensive assessment of cardiopulmonary status and muscle uniquely suited to elicit oxygen desaturation, and patients
strength and would appear to be superior to tests specific exhibiting oxygen desaturation greater than 4% were twice
for myocardial ischemia in calibrating a patient’s risk for as likely to suffer postoperative problems. Exercise-induced
perioperative morbidity and mortality. desaturation (> 4%) appeared superior to resting finger
oximetry as a predictor of postoperative problems.
ventricular function testing
Radionuclide angiography, cardiac ventriculography,
gated blood pool imaging, and multigated acquisition Pulmonary Function Tests
(MUGA) scans are different names for the same procedure. Conceptually, pulmonary dysfunction may comfortably
An intravenous injection of technetium-99m (pertechnetate) be divided into four broad categories: obstructive airway
labels the patient’s red blood cells (RBCs) in vivo. The disease, hyperinflation, restriction, and diffusion (compro-
patient’s heart is then scanned with a gamma camera. mise). Each of these categories may be defined through the
Low-level gamma radiation is emitted by RBCs tagged with use of standard pulmonary function tests (PFTs).
technetium, and the radiation detected at end-systole is then
related to the radiation at end-diastole and thus permits obstructive airway disease
calculation of an ejection fraction. The radiation emitted When surgeons receive multiple-page PFT results, we
during a single cardiac cycle is not sufficient signal to almost always focus first on a single parameter: forced
reliably calculate the ventricular volumes, so multiple cycles expiratory volume in 1 second (FEV1). This measurement
are acquired “gated” to the ECG (thus, “multigated acquisi- requires patients to inhale to maximum lung volume (total
tion”). A healthy ventricle ejects about 60% of its end- lung capacity) and then exhale as forcefully and quickly as
diastolic volume with each heartbeat. they are able to [see Figure 4]. These tests may require a “race
Exercise MUGA scanning can also be performed, typically correction” for ethnicity of as much as 6 to 12%. Healthy
with the patient on a stationary bicycle. With exercise, both young adults can exhale almost all of their total lung capac-
the patient’s blood pressure and ejection fraction should ity within a second or two, so a healthy FEV1 approaches
rise. 4 to 5 L! After 2 seconds, healthy lungs have emptied down
With advancing age and congestive failure, the increasing to residual volume. A patient with asthma or COPD cannot
stiffness of the ventricles can be measured in terms of the move air through airways that have been constricted by
time to peak filling rate. The shorter this interval, the more bronchospasm [see Figure 4]. So if your patient, following
compliant the ventricle. Diastolic dysfunction is now bronchodilators, can only exhale in 1 second (FEV1) less than
increasingly recognized as an etiology of heart failure; the 70% of all they can inhale (forced vital capacity [FVC]), they
ventricle becomes too stiff to fill during diastole. A healthy have met the Global Initiative for Obstructive Lung Disease
heart should be capable of filling completely within 130 to (GOLD) criterion for COPD (FEV1/FVC < 70%).
200 milliseconds. In a patient with significantly compromised airway
In patients with a normal, healthy exercise capacity, resistance, pulmonary function should also be assessed
preoperative measurement of ventricular function will following inhaled aerosolized bronchodilators. These drugs
be very low yield, and the possibility of modifying any come in three varieties: short-acting beta2 agonists, such as
perioperative strategy by virtue of this test is unlikely. albuterol; long-acting beta2 agonists, such as salmeterol; and
In addition to the obvious patients who present with methylxanthines, such as caffeine and theophylline.
congestive failure and/or limited functional capacity, the Many receptor agonist/antagonist drugs are somewhat,
surgeon should be mindful of patients on chemotherapeutic but not absolutely, receptor specific. So in this chapter,
drugs. Two common culprits are doxorubicin (Adriamycin) when we recommend a beta2 agonist for perioperative bron-
and immunotherapy (trastuzumab [Herceptin]), which are chodilation and simultaneously encourage a cardiospecific
both frequently cardiotoxic. beta1 inhibitor (such as metoprolol or atenolol) for cardio-
protection, you may appropriately envision a patient enter-
stair climbing: putting it all together ing the operating room with one foot capably placed on the
Arguably, climbing stairs incorporates cardiopulmonary accelerator while the other foot is simultaneously placed on
status, muscle strength, and “vitality” into a single practical the brakes.
03/12
6
5
5 VC TLC
4
Healthy
4
Liters
3
3 Closing Volume
2 PEEP
Liters /s
2 FRC
1
COPD RV
Exhale
1
Time
0 Figure 5 Spirometric lung volumes. The therapeutic purpose of
1 2 3 4 5 6 7 8
positive end-expiratory pressure (PEEP) is to raise the functional
Time (s)
1 residual capacity (FRC), or the lung volume following tidal exhalation,
above closing volume so that terminal airways never close during
Inhale tidal exhalation. RV = residual volume; TLC = total lung capacity; VC
2 = vital capacity or the volume of the air exhaled from the TLC to RV.
Figure 4 A flow-volume loop relates volume of exhaled/inhaled gas to 7.35%. The sigh must have uncovered an additional
to time (seconds). Note that the volume of air that a young, healthy volume of distribution or volume of previously trapped gas.
person can forcibly exhale in 1 second (FEV1) can be as high as 4 to The new total volume of helium distribution is now 13.61 L
8 L. Chronic obstructive pulmonary disease (COPD) dramatically minus 10 L (spirometer) minus 3.33 L (FRC), and the volume
reduces air flow.
of trapped gas is 280 mL. This volume of trapped gas cannot
be due to atelectasis, because collapsed alveoli could not
further dilute the helium concentration in the system.
hyperinflation Therefore, this additional decrease in helium concentration
Lung volumes are measured using a relatively simple must be due to previously trapped alveolar gas, producing
dilutional principle. For example, 1 L of 100% nondiffusible perfused but not ventilated lung (shunt). Histologically,
helium is added to a spirometer and mixed. When the heli- terminal airways have no cartilaginous rings to hold them
um concentration gauge reads 10% helium, the volume of open. With age, increasing interstitial lung water (which
the spirometer can be calculated to be 10 L. The respiratory is characteristic of congestive heart failure), and obesity,
technician then places a tube into the patient’s mouth and these terminal airways collapse at lower lung volumes. The
connects the tube to the spirometer with a handheld valve. lung volume at which terminal airways collapse is termed
The patient is instructed either to achieve total lung capacity “closing volume.” Thus, a big barrel chest with a flat
(TLC) and exhale down to residual volume (RV) or just to diaphragm, an increased anteroposterior diameter, and
breathe comfortably, initiating each breath from functional radiolucent lungs on a chest x-ray is a natural attempt by the
residual capacity (FRC) [see Figure 5]. When the technician patient to set the FRC above the closing volume. When the
observes the patient to be at the desired lung volume, closing volume is above the FRC, terminal airways close
the technician flips the valve connecting the patient to the during each tidal breath, creating a transient shunt.
spirometer. The increased volume of dilution equals the Therapeutically, when we ventilate a patient, we can
patient’s lung volume at the time the valve was opened. So elevate FRC above closing volume by adding positive end-
if the valve is opened at the end of a comfortable tidal breath expiratory pressure (PEEP) [see Figure 5]. A decade ago, the
(FRC) and the helium gauge concentration falls to 8%, then Acute Respiratory Distress Syndrome Network (ARDSnet)
the total volume of dilution must be 12.5 L (spirometer plus reported that lower tidal volume ventilation (6 mL/kg) in
FRC volume), or 12.5 L minus 10 L (for the spirometer) patients with acute respiratory distress syndrome reduced
equals a 2.5-liter FRC. mortality and increased ventilator-free days compared
If the patient continues to breathe while connected to the with traditional tidal volume ventilation (10 to 15 mL/kg).40
spirometer, the helium concentration should stabilize at Controversy lingers as to whether these lower tidal volumes
8%. promote further airway collapse.
We all sigh frequently. Try not to sigh for several minutes,
and you will become surprisingly uncomfortable. When a restrictive lung disease
young patient sighs, the helium concentration will remain The ability to expand the lung can be constrained by chest
at 8% (no increased volume of distribution). But when an wall scarring (secondary to a large burn), pleural fibrosis
elderly patient sighs, the helium concentration, which had (secondary to tuberculosis), or a decrease in lung parenchy-
previously leveled off at 7.5%, revealing a higher “hyperin- mal compliance secondary to pulmonary interstitial fibrosis
flated” FRC of 3.33 L, typically falls a little further, perhaps (multiple inflammatory etiologies).
03/12
Pulmonary function studies exhibit reduced lung bad prognostic sign [see Table 6]. In cancer patients, func-
volumes. The patient’s vital capacity is reduced, but there tional status is typically more important than nodal status,
is no obstruction to the airway flow, so the exhaled gas cytologic differentiation, or surgical margins in predicting
(the limited volume that there is) can be exhaled quickly. morbidity and mortality. But assessing functional status
Therefore, the FEV1/FVC ratio is normal or may actually be provides no direct information on selection of therapy.
increased. Much more therapeutically useful than prognostic testing
is predictive (or directive) testing, which means identifying
diffusion compromise
patients who will benefit from a specified, available
Once oxygen arrives in an alveolus, it is uncommon intervention. By definition, predictive testing identifies
for transfer across the alveolar-capillary membrane to be that subset of “bad prognosis” patients who can be helped.
limited. One can imagine, however, circumstances in which This requires the existence of a therapeutic intervention of
this could occur. At extremely high pulmonary blood flow, demonstrated benefit. It also requires the identification of
blood might not linger in the pulmonary capillaries long those patients not too ill but not too well to benefit from the
enough to saturate hemoglobin. Conversely, with anemia, associated therapy.
all available hemoglobin might be saturated very early as Proof that a testing strategy is predictive or directive,
RBCs traverse the pulmonary capillaries. With hemorrhage not merely prognostic, is best demonstrated by randomized
into the lung parenchyma, oxygen can be diverted away trials comparing outcome in groups receiving best conven-
from pulmonary capillaries. In late-stage emphysema, the tional care with or without the proposed test. This is a high
alveolar septae are destroyed and the effective alveolar- standard but has been met in some situations.
capillary surface area is reduced, but this is not a diffusion The therapy-prediction conundrum exists in nutritional
problem. The classic pulmonary diffusion disease is an idio- support where possibly effective therapies have been
pathic interstitial pneumonitis (Hamman-Rich syndrome). applied in patients not able to benefit due to absence of an
Patients present with nonspecific shortness of breath. A lung accurate predictive test to select the best target population.
biopsy reveals noncellular debris thickening the diffusion
For example, identification of the role of vitamin B12 in
distance from alveolus to pulmonary capillary. The measured
treating anemia awaited the ability to identify macrocytosis
diffusion of carbon monoxide test (DLCO) should reveal
and, later, vitamin B12 serum levels. Previously, most popu-
compromised gas diffusion. Fortunately, true limitation of
lations of anemic patients were dominated by those with
oxygen diffusion across the alveolar-capillary membrane is
iron deficiency, and no predictive test was available to find
not common.
the subset benefiting from vitamin B12 supplementation, so
For a DLCO test, the patient inhales a tiny concentration
the benefit of vitamin B12 remained unknown.
of a maximally diffusible gas (carbon monoxide 0.3%) and
A vivid illustration of the difference between prognostic
a small volume of a maximally nondiffusible gas, such as
versus predictive/directive testing has recently arisen in
helium, along with a large amount of room air. The patient
breast cancer. The presence in breast tumor cells of human
holds his or her breath for 10 seconds and exhales. Concen-
trations of carbon monoxide and helium are then measured epidermal growth factor receptor type 2 (HER-2) has long
in the exhaled gas. Both gases will have been diluted by been recognized as an indicator of poor prognosis, indepen-
the inhaled breath, so the concentrations of both gases will dent of stage, differentiation, or estrogen receptor status.
decrease. Most of the diffusible carbon monoxide should Initially, nothing could be done in response to this informa-
have been transferred to the pulmonary capillary blood. The tion until the development of a blocker for HER-2, trastuzumab
lower the exhaled carbon monoxide, the better the diffusion (Herceptin). Suddenly, HER-2 receptor testing permitted
capability of the lung. Unfortunately, there are many ways identification of a target patient capable of response. Patients
to introduce error into this test. If the patient inhales rapidly, with positive receptors given the blocker improved, whereas
he or she can translocate additional blood into the pulmo- those with negative receptors did not. Not only was the
nary capillaries and falsely enhance the apparent diffusing HER-2 receptor test predictive, its prognostic implication
capacity. Conversely, severe anemia permits rapid satura- also reversed itself. The receptor-positive patients now do
tion of the limited hemoglobin with carbon monoxide, better than average.
resulting in a false depression in the DLCO. A heavy smok- In nutrition for surgical patients, a variety of composite
er may live with carboxyhemoglobin as high as 10% and scores and indices have been proposed to predict prognosis.
actually excrete carbon monoxide, thus confounding the One clearly labeled prognostic measure, the Prognostic
test. Even most pulmonologists acknowledge that the DLCO Nutritional Index (PNI), was proposed in 1980 to quantify
is not a very good test. surgical risk. This measure was used (in modified form)
in the design of a large prospective, randomized trial of
preoperative total parenteral nutrition (TPN) in veterans
Testing for Nutritional Abnormalities undergoing major general, vascular, or thoracic surgery.41
For nutritional support, consensus statements and regula- Patients judged too well nourished or too malnourished by
tory guidelines endorse the long-hallowed practice of this screen were omitted from the study, and the remainder,
identifying patients at increased risk for complications judged “moderately malnourished,” were randomized into
due to protein or calorie deficits. Again, this is called prog- TPN or no TPN preoperatively. The modified PNI score
nostic testing. The implication is that the benefit of special was composed of albumin and weight loss scores only,
support will be confined to these patients. Poor functional which had previously been shown to be prognostic and easy
status (“bedridden, requires assistance to ambulate”) is a to apply.
03/12
Unfortunately, after randomizing and treating 395 patients,

60
the investigators found no outcome difference between the
treatment groups, and in this sense, the trial’s main result
was negative.42 Retrospective subsetting by degree of sever-
ity within “moderate malnutrition” using a Subjective Glob- 40
Risk Reduction (%)

al Assessment (SGA) tool43 was then performed. This was
interpreted to show that patients not severely enough
malnourished to benefit from the extra protein and calories
suffered increased septic complications and overall did 20
worse with TPN. In contrast, the more malnourished
patients did exhibit a net benefit.
For the studies reviewed in the following section, we use
0
a scoring system that grades the conclusions as follows:
Level A, supported by prospective, randomized, controlled
trials (PRCTs) or meta-analyses of PRCTs; Level B, support-
ed by nonrandomized, prospective, retrospective, or case- -20
controlled studies; and Level C, supported by uncontrolled
published experiences, case reports, or “expert opinion.” N = 40 21 105 395 101 125 113 34 19 124 66 100 15 1,258
Fan-1
Thompson
Muller1-lipid
VA Co-op
von Meyenfeldt
Muller1-gluc
Muller2-gluc
Smith
Heatley
Fan-2
Meguid
Bellantone-2
Moghissi
Pooled
preoperative total parenteral nutrition
We have defined preoperative TPN to be intravenous pro-
vision of calories and nitrogen sufficient to meet metabolic
needs for 5 or more days before elective surgery. Fourteen
randomized, controlled trials of this approach, involving Authors
over 1,100 patients, have been examined,42,44–49 chiefly involv-
ing gastrointestinal cancer patients with at least moderate Figure 6 Effect of preoperative total parenteral nutrition on
malnutrition and typically providing at least 7 to 10 days of postoperative complications.101
preoperative TPN. Ten of these 14 studies found a benefit
from TPN, which in five reached conventional statistical In the majority of trials summarized here, the quantity
significance for reduced postoperative morbidity. The and type of substrates given were not what is now thought
pooled results indicate an overall reduction in the risk of to be optimal. For example, calories were often given in
postoperative morbidity of about 10% in the TPN groups, amounts substantially greater than metabolic needs. It is
that is, a reduction in the rate of complications of approxi-
mately 30%. Only one center found a statistically significant
reduction in mortality [see Figure 6]. 80
Based on these studies, we conclude that for malnourished
gastrointestinal cancer patients, 7 to 10 days of preoperative 60
TPN reduces postoperative morbidity (Level A).
Risk Reduction (%)
40
postoperative total parenteral nutrition
Routine administration of TPN to general surgical patients 20
in the immediate postoperative period has been studied
in nine randomized, controlled trials involving over 700 0
patients.46,50–54 No consistent benefit has been demonstrated,
and the possibility of harm has been raised. These data are -20
summarized in Figure 7.
Based on these studies, we conclude that, outside of a -40
study situation in defined patient groups, routine use of
postoperative TPN is not recommended (Level A). -60
It is also clear that nutritional support of patients unable N = 44 117 47 300 122 56 20 20 726
to eat for long periods after surgery is needed to prevent
Abel
Brennan
Preshaw
Sandstrom
Woolfson
Holter
Jensen
Collins
Pooled
starvation. The duration of starvation that can be tolerated

without increased morbidity is unknown and depends
in part on the previous nutritional status and current
metabolic stresses the patient faces. Most feel that, after 5
to 10 days without adequate intake, special support is Authors
appropriate (Level C). For stressed or already malnourished Figure 7 Effect of early postoperative total parenteral nutrition
patients, this interval will be shorter. Although the enteral (TPN) on postoperative complications. These results are disappoint-
route of administration is preferable, if the gut is not ing, but the quantity and type of substrates infused in these trials were
working adequately, TPN is needed (Level B). not what is now thought to be optimal.101
03/12
probable that outcomes in many of these trials would mixtures of arginine, fish oil, RNA fragments, and some-
improve if the trials were repeated using present-day under- times glutamine, in various proportions, for which no ratio-
standing of caloric needs and other metabolic requirements nale is given. The more recent of these trials have been much
in specific patient groups (Level C). less encouraging than the earlier reports, with actual harm
being reported in several trials of products containing high
special enteral feeding arginine levels. The recent publication from Holland of a
Provision of special enteral nutrition via tubes placed in randomized blinded trial of nearly 600 patients testing this
the gastrointestinal tract perioperatively has been studied in strategy is unequivocally negative and may serve to foster a
10 randomized trials.55–57 Five of these compared the enter- more cautious scientific approach toward evaluating such
ally supported to patients receiving TPN, and the other five strategies.62
used a comparison group of routine oral feeding. In the Immunonutrition and “designer” feeds are not supported
enteral nutrition versus TPN trials for postoperative trauma by a satisfactory evidence base (Level C).
patients, septic morbidity and mortality were minimized
with enteral feeding, which is deemed superior to TPN. preoperative oral carbohydrate loading
One study reported a decrease in mortality in burned The traditional dictum of nihil per os (NPO) after mid-
children provided with high-protein enteral supplementa- night for procedures to be performed under general anes-
tion compared with standard feeding.56 A trial of nocturnal thesia has been challenged in some centers in Scandinavia
tube feeding in malnourished female hip fracture patients and eastern Europe since the 1990s. In these facilities,
demonstrated speedier rehabilitation and shorter hospital anesthesiologists provide several hundred milliliters of
stays.57 carbohydrate-enriched electrolyte solutions swallowed 2 hours
On the basis of the available information, we conclude prior to surgery. The rationale is that stress-induced insulin
that special enteral nutrition is helpful in burn and malnour- resistance is normalized and patient well-being improved
ished hip fracture patients (Level A). In trauma patients by ingestion of these “potions.”63 Interestingly, similar bio-
requiring special support, the enteral route is associated chemical changes are also produced by glucose-containing
with decreased septic morbidity compared with the intravenous lines in fasting preoperative patients.64
parenteral route (Level A). Ingestion of 200 mL clear liquids does not increase the
risk of aspiration pneumonia as long as there is a delay of
tight glucose control 1.5 to 2 hours before anesthesia. A Cochrane Review first
Extending work from the world of chronic diabetes published in 2003 concludes that no strong evidence of harm
management, in which ever-tighter glucose regulation is from this practice can be adduced.65 The generally small
associated with improved outcomes, Van den Berghe and sample size in these reports contributes to this conservatism;
colleagues presented two large randomized trials on inten- most reports include fewer than 50 patients per group and
sive care (ICU) patients receiving supplemental calories are thus not powered to detect rare but catastrophic events.
early in their courses.58,59 The first of these, on surgical Gastric fluid secretion is traditionally quantified at approxi-
patients (chiefly postoperative cardiac patients), revealed a mately 100 mL/hr, so the gastric volumes are not likely to
clear benefit in morbidity—and a raw reduction in mortality be influenced measurably by this preoperative cocktail.
of 11%—when glucose levels were maintained below Those concerned about insulin resistance might more
110 mg/dL. Hypoglycemia in this ICU setting was not a easily and conventionally start the usual intravenous line
serious problem.58 A follow-up study from the same authors an hour or two earlier and administer glucose by that route.
showed little or no benefit using the same approach in But wetting the patient’s thirsty tongue with 200 mL of clear
medical ICU patients.59 Finally, a large (over 6,000 patients) fluid 2 hours prior to surgery is very likely to enhance
multinational study coordinated from Australia and New patient comfort at negligible risk of aspiration (Level B).
Zealand found a worsening of mortality with tight glucose
control in similar patients.60
How Can We Make Surgery Safer?
The issue of tight control is of obvious importance in
TPN patients, and it may be that disappointing results in the The problem with searching the available, conscientiously
perioperative trials summarized above might be improved conducted clinical trials for answers is that the patients
with better glucose regulation. Tighter glucose control recruited for those trials never really fit the patient you are
carries risks of hypoglycemia and hypokalemia.36 currently considering for surgical therapy. As indicated
Target glucose levels in recent randomized trials appear above [see Figure 3], patients undergoing “low-risk” opera-
to be converging toward about 140 to 150 mg/dL. Until tions will do pretty well even if they present with significant
more definitive data are available, this target seems safe for comorbidities—or as well as they would do without sur-
patients treated outside an ICU (Level C). gery.31 The risk stratification strategies25,26 [see Table 3 and
Table 527] each target the patient’s cardiovascular system
immunonutrition and “designer feeds” as the overwhelmingly dominant culprit promoting
The provision of special nutrients with the intent of perioperative trouble.
stimulating the immune system, or providing targeted Over the past decades, the scope of perioperative efforts
support for a failing liver or kidneys, and thereby reducing to reduce cardiac risk with cardioprotective therapy has
septic complications has been studied in a large number of changed. At present, the emphasis is on plaque stabilization,
trials that were reviewed by Dhaliwal and Heyland,61 with reduction of myocardial oxygen demand (reduction of
variable results. A fundamental problem is the use of ad hoc oxygen delivery to oxygen consumption mismatch), and
03/12
myocardial protection, with revascularization reserved for to detect. However, in high-risk vascular procedures,
a discrete subset of patients who would be candidates the data are overwhelmingly persuasive. Poldermans and
for cardiac revascularization regardless of any elective pre- colleagues screened 1,351 vascular patients (high risk) and
operative evaluation. It is hypothesized that the likelihood identified 846 patients with one or more cardiac risk factors
of coronary artery plaque rupture may be increased by peri- (very high risk).72 Of this group, 173 patients exhibited
operative stressors such as amplified sympathetic activation, positive dobutamine stress echocardiography (very, very
vasospasm, disruption of coagulation homeostasis, and high risk). Fifty-nine patients were randomly assigned to
oxygen supply-demand mismatch.66 perioperative beta blockade and were compared with 53
Physicians, and perhaps more clearly surgeons, are suffi- patients who received “standard” perioperative care. The
ciently intellectually arrogant that we are more comfortable primary end point of death or nonfatal myocardial infarc-
accepting a conclusion if we can understand the “mecha- tion occurred in two (3.4%) of the beta-blocker group and
nism” of the recommendation. Thus, if the heart is the organ in 18 (34%) of the standard care group (3.4% versus 34%;
that most endangers our patients, and we can reduce cardiac p < .001). It is clearly not permissible to extrapolate from
work/stress with a beta blocker, why not give this peri- this “very, very high risk” procedure-specific group to a
operative, antiadrenergic protection to all of our patients— “routine” general surgical patient.
or at least to all surgical patients with cardiovascular dis- Unfortunately, the studies on the opposite end of the risk
ease? Interestingly, and perhaps predictably, perioperative spectrum are more confusing. Lindenauer and colleagues
beta blockade produced a significant reduction in mortality divided 782,969 patients (a huge number) into high, inter-
in patients undergoing abdominal aortic aneurysmectomy mediate, and low risk for major, noncardiac surgery.73 Again,
(most likely patients with concurrent coronary artery perioperative beta blockade was associated with reduced
disease).67 No such benefit was appreciated in patients who risk for in-hospital death in high-risk patients. Perhaps
were less likely to suffer comorbid coronary artery disease surprisingly, beta blockade appeared to provoke increased
undergoing esophagectomy, hepatectomy, pancreatectomy, trouble in the low-risk group. Subsequent review of this
study design suggested that the low-risk patients did not
colectomy, gastrectomy, or pulmonary lobectomy.67 These
receive beta blockers preoperatively and did not enter the
investigators concluded that evidence-based process mea-
beta-blocker arm of the study until after their operation, at a
sures are “procedure specific” and do not necessarily reflect
time when they were treated for a postoperative cardiac
overall hospital quality.
event.
If some patients do not appear to benefit from periopera-
The POISE Study Group attempted to resolve any recom-
tive beta blockade, is overuse of this particular therapy
mendation to liberalize the use of beta blockers in noncar-
likely to hurt them? Some controversy remains regarding
diac surgery by prospectively randomizing 8,351 patients at
appropriate management of patients identified preopera-
190 hospitals in 23 countries.74 The frighteningly formidable
tively as having significant but stable coronary artery dis-
logistics of this study obligated a simplified investigative
ease. Current data support the use of presumptive medical strategy. A large dose (two to eight times the standard dose)
therapy, and this has led to reductions in the extent of of extended-release metoprolol was given 2 to 4 hours
preoperative cardiac assessment, thereby decreasing the before surgery to 4,174 patients unless their heart rate was
time from surgical diagnosis to surgical therapy. Perhaps below 60 beats/min. Fewer patients in the metoprolol group
surprisingly, documented coronary stenoses account for (5.8%) than in the placebo group (6.9%) reached the primary
only 50% of perioperative myocardial infarctions; the end point (p < .0399), but more patients in the beta-blocker
remaining 50% occur in vascular distributions unrelated to group suffered a stroke (1.0% versus 0.5%) and/or died
documented coronary disease.68,69 The presence of severe (3.1% versus 2.3%). In commentary on the POISE study, the
stenosis is more a “marker” of disease, and thus the subset 2009 ACC/AHA consensus document endorsed the use
of patients at risk, rather than a finite predictor of endan- of beta blockers in high-risk patients but cautioned that:
gered myocardial territory. In part, preoperative cardiac “routine administration of higher dose long-acting metopro-
testing identifies this “at-risk” subset, even though the lol in beta-blocker naïve patients on the day of surgery and
stenotic lesion may not be the cause of the postoperative in the absence of dose titration is associated with an increase
ischemic event. The inability to assess the propensity for in mortality.”75 Clinical investigation is hard to do. To
coronary plaque rupture proves to be the main challenge in enhance patient recruitment and standardize the POISE
both risk stratification and risk factor modification. experimental protocol, patients with a heart rate over
60 beats/min were given a large dose of an extended-release
the beta-blocker controversy
beta blocker. In high-risk patients, even this regimen pro-
The purported advantages of beta-blocker therapy include vided protection. However, neither we, nor they, should be
prolongation of diastole (and, thus, augmentation of dia- surprised that a large dose of beta blocker to a patient with
stolic filling with concurrent accompanying improvement a heart rate of 60 beats/min might provoke bradycardia and
in coronary artery perfusion), reduction of ischemic ven- hypotension with a resultant increase in cerebrovascular
tricular dysrhythmias, and reduction of sympathetic tone.70,71 accident and even death.
Despite the plethora of available data, the argument for pre- Multiple smaller studies examining noncardiac surgical
operative use of beta blockers to modify cardiac risk remains patients with surrogates for coronary artery disease such
controversial. Except in high-risk vascular procedures, peri- as diabetes,76 mild hypertension,77 and advanced age78
operative cardiac events are so rare among patients enrolled have typically reported fewer instances of perioperative
in randomized, controlled trials of perioperative beta block- myocardial ischemia in the beta-blocker group but were not
ade that any absolute reduction in cardiac risk is difficult sufficiently powered to detect more ominous outcomes.
03/12
To date, the issues of how, when, how long, titration lim- bypass surgery.83,84 Biccard examined the implications of
its and by whom beta blockers should be used in noncardiac comorbid disease associated with perioperative cardiovas-
surgical patients remain controversial. A conservative series cular risk for patients on statin therapy, the indications for
of recommendations might include the following: perioperative statin protection, and the efficacy of acute
perioperative beta blockade in addition to statin therapy
1. When preoperative beta-blocker therapy is used, it is and the effect of perioperative statin withdrawal.85 Although
optimally initiated 1 to 2 weeks prior to surgery, targeting many of the recent recommendations regarding retrospec-
a resting heart rate of 60 to 80 beats/min and monitored tive reporting of statin trials may minimize some inherent
to avoid hypotension (Level A). investigator bias, the benefit of perioperative statins appears
2. Although it is not permissible to extrapolate from patients secure. Statins seem to benefit surgical patients with both
following a myocardial infarction to patients during cardiovascular and neoplastic disease; age overwhelms
noncardiac surgery, Cucherat assembled 17 trials of beta both of these indications. Patients who benefit from periop-
blockers in post–myocardial infarction patients and esti- erative beta blockers are the same group that will likely
mated that each reduction in heart rate of 10 beats/min (in derive advantage from statins. The data here are fuzzier, but
the absence of hypotension) accrued a relative reduction in high-risk patients, both beta blockers and statins are use-
in cardiac death of 30% (Level A).79 ful. The dose and duration of preoperative prophylaxis are
3. When a patient presents already on beta blockers, do not not clear, but 2 weeks is better than 2 hours. When a patient
stop them (Level A). is already taking a statin, do not stop it.85
4. The higher the perceived risk of the (especially vascular
surgical) patient, the more likely it is that beta blockers will
help (Level A). Smoking Cessation Programs
5. Untitrated large doses of extended-release beta blockers It is hard to stop smoking; it is an addiction. Although
in drug-naïve, low-risk patients are contraindicated there is a paucity of data indicating that smoking cessation
(Level A). just prior to surgery changes outcome, there are a lot of data
6. This leaves a large middle “gray zone” group of patients linking smoking to perioperative trouble. So, intuitively, it
in whom surgeons are on their own to use their best makes sense to ask your patients to stop. A planned surgical
judgment. procedure, especially if the purpose is to resect cancer, can
provide persuasive incentive. Cooley and colleagues recom-
statins
mended smoking cessation to patients undergoing surgery
The statin (HMG-CoA [3-hydroxy-3-methylglutaryl coen- for lung cancer.86 Eighty-four patients (89%) were “ever-
zyme A] reductase inhibitor) story is complex but becoming smokers,” and 35 (37%) reported smoking at diagnosis.
clearer. HMG-CoA reductase is the rate-limiting step in Forty-six percent of the ever-smokers remained abstinent,
cholesterol synthesis. Statins both inhibit cholesterol synthe- 16% continued smoking, and 38% relapsed. In a separate
sis and increase expression of low-density lipoprotein analysis of lung cancer patients, these investigators cata-
(LDL) receptors, which results in an increased clearance of logued the factors associated with failure to stop as young
circulating LDL cholesterol. Cholesterol is, however, criti- age, depression, and a household member who smokes.87 A
cally important to cell membrane stabilization. Cholesterol similar study identified the red flags of smoking cessation
is the glue that holds the functionally important cell mem- failure as mentholated cigarettes and a habit of enjoying
brane phospholipids together. Only 20% of our cholesterol the first cigarette within 30 minutes of awakening in the
is ingested, whereas over 75% is synthesized by the liver. morning.88
So, intuitively, it should be dangerous to manipulate this Several groups have tested smoking cessation programs
structurally pivotal molecule. Over 40 years ago, the Fram- in a prospective, randomized fashion.89,90 Prior to elective
ingham study first associated hypercholesterolemia with surgery, 210 smokers were randomly allocated to a nicotine
atherosclerotic cardiovascular disease. So it made sense replacement group or a “usual care” group. A whopping
to try judiciously to lower cholesterol a little. A storm of 73% of dependent smokers (> 10 cigarettes/day) reported
inquiry followed. Law and colleagues recently reviewed (no confirmatory tests) abstinence prior to surgery compared
several hundred trials and concluded that a reduction with 56% abstinence in the “usual care” group. The bad
of LDL cholesterol by only 1.8 mmol/L conveyed a 60% news, however, is that 3 months following surgery, 82% and
decrease in ischemic heart disease and a 17% decrease in 95% of patients, respectively, were smoking again.89
stroke.80 Statins not only prevent heart disease; Poynter and A single puff on a cigarette produces profound vasocon-
colleagues reported a 47% reduction in the relative risk of striction. Some surgical groups believe that it is justified to
colorectal cancer after adjusting for other recognized risk refuse breast reconstructive surgery to smokers.91 Although
factors.81 If both atherosclerosis and malignant neoplastic it is clear that smokers suffer more postoperative complica-
degeneration are exacerbated by systemic inflammation, tions, it is not evident that these problems will vanish if they
then statins might be effective in pacifying inflamed patients stop.
(as evidenced by an elevated C-reactive protein) even inde- The news is not all bad, however. Varenicline is a partial
pendent of absolute LDL levels. And, Albert and colleagues agonist/antagonist selective for alpha4/beta2 nicotinic ace-
report that they are.82 tylcholine receptors that is touted as a first-line treatment
Surgery provokes inflammation. Logically, statins should smoking cessation option. Garrison and Dugan reviewed
help. Pan and colleagues and Ouattara and colleagues both eight clinical trials and reported continuous abstinence rates
reported a significant dose-dependent reduction in adverse ranging from 21.9 to 34.6% at a year.92 In a very slow race,
cardiovascular outcomes with statins in coronary artery even the lame can win.
03/12
Frailty Index: The “Eyeball” Test evaluation: a report by the American Society of Anesthesi-
ologists Task Force on Preanesthesia Evaluation. Anesthe-
Age is not the distance from the beginning but, more
siology 2002;96:485–96.
accurately, the proximity to the end. Although “frailty” has
6. National Institute for Clinical Excellence. Preoperative
not yet achieved a standardized definition, we all recognize
tests. The use of routine preoperative tests for elective
the status when we see it. Age and frailty are frequent,
surgery. Evidence, methods and guidance. Available at:
but not obligatory, partners. Frailty confers an increased risk
http://www.nice.org.uk/nicemedia/live/10920/29094/
of disability, falls, cognitive decline, hospitalization, and
29094.pdf (accessed February 7, 2011).
perioperative morbidity/mortality. Interestingly, the pheno-
7. Bold AM, Corrin B. Use and abuse of clinical chemistry in
type of frailty is not concordant with either disability or
surgery. Br Med J 1965;2:1051–2.
comorbidity, but the pathogenesis of frailty includes comor-
8. Allison JG, Bromley HR. Unnecessary preoperative inves-
bidities, and disability is more the outcome than the cause.
tigations: evaluation and cost analysis. Am Surg 1996;62:
Frailty can now be diagnosed as a medical syndrome.93
686–9.
Fried and colleagues identified this entity with three or more
9. Narr BJ, Warner ME, Schroeder DR, Warner MA.
of the following: (1) unintentional weight loss of more than Outcomes of patients with no laboratory assessment
10 pounds over a year; (2) self-reported exhaustion; (3) weak before anesthesia and a surgical procedure. Mayo Clin
grip strength; and (4) slow walking speed or low physical Proc 1997;72:505–9.
activity [see Figure 4].94 In this study, frailty was indepen- 10. Nardella A, Pechet L, Snyder LM. Continuous improve-
dently (stratifying for comorbidities) predictive (over 3 ment, quality control, and cost containment in clinical
years) of falls, declining mobility, hospitalization (and intui- laboratory testing. Effects of establishing and implement-
tively perioperative morbidity/mortality), and death, with ing guidelines for preoperative tests. Arch Pathol Lab Med
hazard ratios ranging from 1.82 to 4.46. Socioeconomic 1995;119:518–22.
status resurfaces again, with frailty associated with lower 11. Vogt AW, Henson LC. Unindicated preoperative testing:
education and income. As more statistics are successfully ASA physical status and financial implications. J Clin
dissociating frailty from age,95,96 frailty has now been Anesth 1997;9:437–41.
proposed as the missing element in predicting operative 12. Pal KM, Khan IA, Safdar B. Preoperative work up: are the
mortality.97 requirements different in a developing country? J Pak Med
Makary and colleagues prospectively measured frailty in Assoc 1998;48:339–41.
594 patients older than 65 years.98 They used a 5-point scale, 13. Smetana GW, Macpherson DS. The case against routine
including weight loss, weakness, exhaustion, low physical preoperative laboratory testing. Med Clin North Am 2003;
activity, and walking speed. Frailty independently predicted 87:7–40.
postoperative complications, length of hospital stay, 14. Dzankic S, Pastor D, Gonzalez C, Leung JM. The preva-
and nursing home discharge. Frailty even enhanced the lence and predictive value of abnormal preoperative
predictive power of the ASA risk index (p < .01). laboratory tests in elderly surgical patients. Anesth Analg
Although both the ASA and frailty indices aspire to quan- 2001;93:301–8.
titative status, the predictive (albeit subjective) value of the 15. Schein OD, Katz J, Bass EB, et al. The value of routine
“eyeball” test performed by an experienced surgeon remains preoperative medical testing before cataract surgery. Study
invaluable (although not formally tested). We continue to of Medical Testing for Cataract Surgery. N Engl J Med
endorse this test. 2000;342:168–75.
An exercise prescription as an antidote to frailty99,100 would 16. Burk CD, Miller L, Handler SD, Cohen AR. Preoperative
make intuitive sense in the preoperative period. Castillo- history and coagulation screening in children undergoing
Garzón and colleagues provided compelling evidence tonsillectomy. Pediatrics 1992;89:691–5.
that patient-specific exercise programs can attenuate the 17. Narr BJ, Hansen TR, Warner MA. Preoperative laboratory
negative consequences of frailty.100 screening in healthy Mayo patients: cost-effective elimina-
tion of tests and unchanged outcomes. Mayo Clin Proc
Financial Disclosures: None Reported 1991;66:155–9.
18. Macpherson DS. Preoperative laboratory testing: should
any tests be “routine” before surgery? Med Clin North Am
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findings. Am J Cardiol 2001;88:1413–4, A6. statin therapy is associated with a significant and dose-
69. Dawood MM, Gutpa DK, Southern J, et al. Pathology of dependent reduction of adverse cardiovascular outcomes
fatal perioperative myocardial infarction: implications after coronary artery bypass surgery. J Cardiothorac Vasc
regarding pathophysiology and prevention. Int J Cardiol Anesth 2009;23:633–8.
1996;57:37–44. 85. Biccard BM. A peri-operative statin update for non-cardiac
70. Cruickshank JM. Beta-blockers continue to surprise us. surgery Part II: Statin therapy for vascular surgery and
Eur Heart J 2000;21:354–64. peri-operative statin trial design. Anaesthesia 2008;63:
71. Poldermans D, Boersma E. Beta-blocker therapy in noncar- 162–71.
diac surgery. N Engl J Med 2005;353:412–4. 86. Cooley ME, Sarna L, Kotlerman J, et al. Smoking cessation
72. Poldermans D, Boersma E, Bax JJ, et al. The effect of is challenging even for patients recovering from lung
bisoprolol on perioperative mortality and myocardial cancer surgery with curative intent. Lung Cancer 2009;
infarction in high-risk patients undergoing vascular sur- 66:218–25.
gery. Dutch Echocardiographic Cardiac Risk Evaluation 87. Cooley ME, Sarna L, Brown JK, et al. Tobacco use in
Applying Stress Echocardiography Study Group. N Engl J women with lung cancer. Ann Behav Med 2007;33:
Med 1999;341:1789–94. 242–50.
73. Lindenauer PK, Pekow P, Wang K, et al. Pathology of 88. Robles GI, Singh-Franco D, Ghin HL. A review of the
fatal perioperative myocardial infarction: implications efficacy of smoking-cessation pharmacotherapies in
regarding pathophysiology and prevention. N Engl J Med nonwhite populations. Clin Ther 2008;30:800–12.
2005;353:349–61. 89. Wolfenden L, Wiggers J, Knight J, et al. A programme
74. POISE Study Group, Devereaux PJ, Yang H, Yusuf S, et al. for reducing smoking in pre-operative surgical patients:
Effects of extended-release metoprolol succinate in patients randomised controlled trial. Anaesthesia 2005;60:172–9.
undergoing non-cardiac surgery (POISE trial): a randomised 90. Sadr Azodi O, Lindström D, Adami J, et al. The efficacy of
controlled trial. Lancet 2008;371:1839–47. a smoking cessation programme in patients undergoing
75. Fleisher LA, Beckman JA, Brown KA, et al. 2009 ACCF/ elective surgery: a randomised clinical trial. Anaesthesia
AHA focused update on perioperative beta blockade 2009;64:259–65.
incorporated into the ACC/AHA 2007 guidelines on 91. Bikhchandani J, Varma SK, Henderson NP. Is it justified
perioperative cardiovascular evaluation and care for to refuse breast reduction to smokers? J Plast Reconstr
noncardiac surgery: a report of the American College of Aesthet Surg 2007;60:1050–4.
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92. Garrison GD, Dugan SE. Varenicline: a first-line treatment 98. Makary MA, Segev DL, Pronovost PJ, et al. Frailty as a
option for smoking cessation. Clin Ther 2009;31:463–91. predictor of surgical outcomes in older patients. J Am Coll
93. Xue QL. The frailty syndrome: definition and natural Surg 2010;210:901–8.
history. Clin Geriatr Med 2011;27:1–15. 99. Liu CK, Fielding RA. Exercise as an intervention for frailty.
94. Fried LP, Tangen CM, Walston J, et al. Frailty in older Clin Geriatr Med 2011;27:101–10.
adults: evidence for a phenotype. J Gerontol A Biol Sci 100. Castillo-Garzón MJ, Ruiz JR, Ortega FB, et al. Anti-aging
Med Sci 2001;56:M146–56. therapy through fitness enhancement. Clin Interv Aging
95. Gilleard C, Higgs P. Frailty, disability and old age: a 2006;1:213–20.
re-appraisal. Health 2010. [Epub ahead of print] 101. Klein S, Kinney J, Jeejeebhoy K. Nutrition support in
96. Mack MJ. Risk scores for predicting outcomes in valvular clinical practice: review of published data and recommen-
heart disease: how useful? Curr Cardiol Rep 2011;13: dations for future research directions. Summary of a con-
107–12. ference sponsored by the National Institutes of Health,
97. Chikwe J, Adams DH. Frailty: the missing element in American Society for Parenteral and Enteral Nutrition,
predicting operative mortality. Semin Thorac Cardiovasc and American Society for Clinical Nutrition. Am J Clin
Surg 2010;22:109–10. Nutr 1997;66:683–706.
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ELEMENTS OF CONTEMPORARY PRACTICE 7 ELEMENTS OF COST-EFFECTIVE NONEMERGENT
SURGICAL CARE — 1
7 ELEMENTS OF COST-EFFECTIVE
NONEMERGENT SURGICAL CARE
Robert S. Rhodes, MD, FACS, Charles L. Rice, MD, FACS, and Julie Ann Sosa, MA, MD, FACS
Citizens of industrialized nations generally enjoy a high level health care as a percentage of its GDP [see Figure 1] and per
of health, and the positive correlation between life expectancy capita [see Figure 2] than other industrialized nations, its citi-
and per capita income is among the best known relationships zens seem less healthy than those of many nations with respect
in international development.1 Yet there are differences to indices of population health, such as life expectancy and
among the health care systems of these nations with regard to infant mortality [see Figure 3 and Figure 4]. Thus, per capita
quality, cost, and access to care.2,3 There also appears to be health care expenditures have only a modest correlation with
a dynamic tension among these three characteristics, and the life expectancy. Although some of this disparity in the appar-
goal of providing broad access to high-quality health care at ent value of health care might be explained by specific char-
a reasonable cost is an increasing challenge. One particular acteristics of the US population, much of it cannot. Although
challenge is that health care costs tend to rise at a faster pace the United States has slight advantages over some countries
than the costs of other goods and services. In the United in 5-year survival rates for both breast and colorectal cancer,
States, for example, health care costs have consistently risen
the cost of such benefits seems disproportionately large.
faster than overall inflation for the past 65 years. Interest-
Overall, the United States lags behind other nations in
ingly, despite differences in the percentage of gross domestic
measures of illness and some chronic conditions amenable
product (GDP) that nations spend on health care, the
to health care.4 All of this suggests that the US health care
slopes of these curves often appear to increase in parallel [see
Figure 1]. system exhibits a relative lack of cost-effectiveness, the
The hyperinflation in health care costs, particularly in the causes of which include higher prices for health care goods
context of the recent economic downturn, often forces choices and services5 and waste related to overuse or misuse of
among social goals (e.g., health care versus education). Such resources.
choices may be more readily rationalized when the costs of As health care increasingly competes with other social goals
the chosen goal produce demonstrable value (i.e., if greater for the same funds, individuals, employers, and governments
health care spending generates measurably better health, it is all feel the strain. The impact on US citizens is reflected in
regarded as worthwhile; if it does not, it is regarded as waste- the fact that in 2007, over 62% of personal bankruptcies were
ful). Unfortunately, the latter appears to be the case in the related to health care issues, up from 46% 6 years earlier.6
United States. Although the United States spends more on Also, the percentage of nonelderly Americans who lived in
Health care spending as a % of GDP, 1960-2007
18.0
Canada
16.0
14.0 France
12.0 Germany
% GDP
10.0
Japan
8.0
6.0 UK
4.0 US
2.0
OECD Median
0.0
1960 1970 1980 1990 2000 2004 2007
Year
Figure 1 Health care spending as a percentage of gross domestic product (GDP) among selected countries within the Organisa-
tion for Economic Co-operation and Development (OECD). US health care spending has been increasing at a disproportionately
faster rate. Note that the x-axis scale does not have constant intervals. (www.oecd.org/health/hcqi. accessed July 5, 2010).
DOI 10.2310/7800.2011
03/11
SURGICAL CARE — 2
Per capita total health care spending in US dollars,

1960-2007
8,000
7,000 Canada
6,000
France
Dollars
5,000
4,000 Germany
3,000 Japan
2,000
1,000 UK
0 US
1960 1970 1980 1990 2000 2003 2007 OECD Median
Year
Figure 2 Health care spending per capita among selected countries within the Organisation for Economic Co-operation and
Development (OECD) in US dollars. Again, US health care spending is increasing at a disproportionately faster rate. Note that
the x-axis scale does not have constant intervals. (www.oecd.org/health/hcqi. accessed July 5, 2010).
Life expectancy in years, 1960-2007
85.0
Canada
Life expectancy
France
80.0
Germany
75.0 Japan
UK
70.0 US
OECD Median
65.0
1960 1970 1980 1990 2000 2003 2007
Year
Figure 3 Life expectancy among selected countries within the Organisation for Economic Co-operation and Development
(OECD). The increase in US life expectancy is falling behind the increases seen in other countries. Note that the x-axis scale
does not have constant intervals. (www.oecd.org/health/hcqi. accessed July 5, 2010).
families spending more than 10% of their income on health Many factors contribute to the costs of health care, but
care rose from 14.4% in 2001 to 19.1% in 2006.7 physicians’ decisions are the largest single factor; they are
The phrase “bending the cost curve” refers to efforts to estimated to account for 75% of these costs. This pronounced
minimize or eliminate differences in inflation in general and impact of physicians on health care costs explains, in turn,
inflation in the cost of health care. Accordingly, there is a why those who pay the bills increasingly seek to identify the
long history of attempts to control health care costs that most cost-effective physicians. Surgeons in particular are
includes price controls (the Nixon era), prospective payment likely to be a target of efforts to contain costs because surgical
(the Reagan era), and managed care (the Clinton era). Unfor- illnesses often are of relatively short duration, surgical out-
tunately, these initiatives had little long-term impact.8 More comes are readily quantified, and surgeon reimbursement
recently, concerns about increases in health care costs were often involves global fees.
sufficient to engender federal legislation aimed at controlling Given the impetus to improve the cost-effectiveness of
costs; whether this effort will be more successful has yet to be surgical care, the goals of this chapter are to (1) explore the
determined. fundamental principles of cost-effectiveness, particularly as
03/11
SURGICAL CARE — 3
Infant mortality per 1,000 live births, 1960-2007
40.0
Canada
35.0
Infant mortality
France
30.0
25.0 Germany
20.0 Japan
15.0 UK
10.0 US
5.0
OECD Median
0.0
1960 1970 1980 1990 2000 2003 2007
Year
Figure 4 Infant mortality per 1,000 live births among selected countries in the Organisation for Economic Co-operation and
Development (OECD). The decline in US infant mortality is not keeping pace with the declines seen in other countries. Note that
the x-axis scale does not have constant intervals. (www.oecd.org/health/hcqi. accessed July 5, 2010).
applied to surgical care; (2) review the attributes and com- Comparative effectiveness is another frequently used term
plexities of both cost and quality; (3) review current data on that compares the effectiveness of two or more treatments.
the relationship of cost and quality; and (4) identify specific Given that cost-effectiveness considers both cost and
skills and attributes to help surgeons deliver more cost- quality, changes in cost-effectiveness also represent changes
effective care. in the value of care. The interaction of cost and quality also
means that improvements in cost-effectiveness can result
from changes in the numerator, the denominator, or both.
Fundamental Principles of Cost-effectiveness Moreover, beneficial effects in one component of a strategy
Cost-effectiveness expresses the cost of a given strategy can be outweighed by adverse changes in the other, and vice
(in dollars) relative to a given measure of quality. Developed versa. These interactions are represented in Figure 5. Here,
strategies that increase quality and lower cost are highly
in the military and in the evaluation of how to spend govern-
desirable, and maximal cost-effectiveness is the optimal out-
ment monies on different public works projects (e.g., roads,
come that can be achieved with the least use of resources.
dams, bridges), cost-effectiveness analysis (CEA) was first Conversely, changes that lower quality and increase cost are
applied to health care in the mid-1960s. It was introduced clearly undesirable. In contrast, judgments of strategies
with enthusiasm to clinicians in 1977 by Weinstein and where costs and quality move in the same direction tend to
Stason9 but was received with skepticism or reluctance. Cost- be controversial.
effectiveness can be an absolute term, but a more frequent The controversial nature of such changes was evident
application in health care is to compare the value of two or during the debate on health care reform. Greater support for
more clinical strategies. Expressed mathematically, it is the cost-effectiveness research was included in the American
difference in the cost of a new strategy and the cost of current Reinvestment and Recovery Act (ARRA) of 2009, raising
practice divided by the difference in the effectiveness of concerns that health care decisions going forward might be
the new strategy and the effectiveness of current practice. made by outside agencies. This fueled at least some of the
Specific strategies might include assessing one intervention opposition to health care reform.11 Moreover, a recent survey
against another, assessing an intervention against no interven- indicated that a majority of consumers believed that more
tion, or assessing early treatment against delayed treatment. care meant higher-quality, better care.12 Many of these con-
sumer beliefs, values, and knowledge are at odds with what
An example of the last is a study of appendicitis that con-
policy makers described as evidence-based health care. These
cluded that each 10% increase in diagnostic accuracy was
beliefs likely account for the recent pushback on the changes
associated with a 14% increase in the perforation rate;
in recommendations proposed by the U.S. Preventive Ser-
the greater costs associated with higher morbidity from vices Task Force regarding the appropriateness of routine
perforation might offset the cost savings associated with mammography screening for women ages 40 to 49.13
reducing negative appendectomies through greater diagnostic
accuracy.10
Cost-effectiveness differs from cost-benefit, which mea- Attributes of Health Care Costs
sures return on investment (where the numerator and denom- Assessing cost-effectiveness may seem simple, but mea-
inator are expressed in dollars), and from efficiency, which is sures of costs have multiple dimensions that are reflected in
an expression of productivity (with outputs divided by inputs). the phrase “cost is a noun that never stands alone.” Thus,
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SURGICAL CARE — 4
Table 1 lists ways to categorize health care costs. Cost

+
traceability and its behavior in relation to output or activity
are particularly important concepts for surgeons and hospi-
tals.15 Examples of direct costs are salaries, supplies, rents,
REJECT CEA
and utilities, whereas indirect costs might be depreciation
and/or administrative costs associated with regulatory com-
pliance. Yet these definitions are not cast in stone, and some
COST
indirect costs might be considered direct costs depending on

the cost objective.
Cost behavior relative to an output or activity costs can
be variable, fixed, semivariable, or semifixed. Variable costs
CEA ADOPT (e.g., supplies) change in a constant, proportional manner
with changes in output, whereas fixed costs (e.g., equipment)
do not change in response to changes in volume. Semivari-
able costs (e.g., utilities) include elements of both fixed and
- EFFECTIVENESS + variable costs: there is a fixed basic cost per unit of time and
a direct, proportional relation between volume and cost.
Semifixed costs (also known as step costs) also change with
changes in output, but the changes occur in discrete steps
+
REJECT? rather than linearly. An example of a semifixed cost is the
number of full-time equivalents (FTEs) needed to run one
REJECT CEA operating room; labor costs will be constant whether that
room is used all the time or part-time. Conversely, when
operating room use is reduced, there may not be any cost
savings until a room is completely taken out of service. Unless
COST
ADOPT?
the step threshold is attained, costs do not change.
REJECT? Physicians affect hospital costs primarily via their impact
on fully variable and semifixed costs. Such costs typically
constitute 15 to 35% of total hospital costs, and this range
CEA ADOPT
often reflects substantial variations in the use of resources
among surgeons for similar types of patients or procedures.
ADOPT?
- EFFECTIVENESS + Table 1 Categories and Types of Hospital Costs
Category Type Example or Definition
Figure 5 Cost analysis methods. Adapted from the National
Information Center on Health Services Research and Health Traceability to Direct Salaries, supplies, rents,
Care technology of the US National Library of Medicine, the object and utilities
National Institutes of Health. Available at: http://www.nlm. being costed Indirect Depreciation and
nih.gov/nichsr/hta101/ta10106.html. accessed January 10, 2011. employee benefits
CEA = cost-effectiveness analysis. Behavior of cost Variable Supply
in relation to Fixed Depreciation
output or Semivariable Utilities
assessing the relative cost-effectiveness of a specific strategy activity Semifixed Number of full-time
requires a precise definition of the costs being considered.14 equivalents per step in
An important first step is to appreciate the distinction output
between costs and charges. Charges are the price at which Management — Often limited to direct,
a “seller” provides a given product or service, but this price responsibility variable costs
may not reflect the actual cost of that product or service (e.g., for control
a loss leader). Although aggregate hospital costs can be a Future versus Avoidable costs Costs affected by a
relatively constant fraction of hospital charges, there are often historical decision under
substantial variations among institutions in the cost-to-charge consideration
Sunk costs Costs not affected by a
ratio for specific goods and services. These differences can be decision under
attributed to differences in cost attribution among different consideration
accounting systems but are also evident within the relatively Incremental Changes in total costs
standardized accounting standards required by the Centers costs resulting from
for Medicare and Medicaid Services (CMS). Whether such alternative courses of
action
variations result from differences in efficiency or differences Opportunity Value forgone by using a
in accounting practices is often not clear. costs resource in a particular
Third-party reimbursements to hospitals and surgeons way instead of in its
reflect contractual agreements and, like charges, also do not next best alternative
way
reflect costs.
03/11
SURGICAL CARE — 5
This variability, in turn, can affect the “profitability” of a services), process (content of care), and outcomes.25 These
given disease-related group (DRG). Hospital administrators three components can be measured more objectively than
often are aware of this variability but seem reluctant to bring appropriateness and allow application of the quality control
it to a surgeon’s attention. Physicians also affect fixed costs techniques pioneered in industry by W. Edwards Deming.
as they influence investments in technology. This is discussed These techniques minimize variation in quality by examining
in greater detail in a later section. production systems. The analogy to health care is that the
Perspectives on costs also vary among payers (e.g., insur- production systems are the systems of care; the health care
ers), providers, and patients.16 Payers’ perspectives primarily systems’ structure and processes are independent variables,
focus on the impact of price and use, a perspective exempli- and patient outcome is a dependent variable.
fied by the introduction of laparoscopic cholecystectomy.17 Although outcomes are unquestionably a more definitive
Lower per procedure hospital costs were offset by an increase measure of quality than process, the nature of health care is
in procedure volume and an increase in aggregate costs to such that measuring processes of care (i.e., what is done to a
payers. This effect often accounts for differing opinions patient) may be more immediately relevant to improving the
among patients, providers, and insurers regarding the value quality of care than measuring outcome per se (i.e., what
of new technology. In this context, regional variation in happens to a patient). One reason for placing greater empha-
per capita Medicare spending appears to be more related to sis on process in health care is that all the factors that affect
differences in use than in price.18 outcomes in biologic systems may not be known or control-
The interval between an intervention and the point of mea- lable. This differs from mechanical systems such as aircraft,
surement may also affect estimates of value.19,20 Patients are where a given perturbation has a fairly predictable result.
likely to view outcomes over the long term, whereas providers Conversely, the adaptability inherent in biologic systems
and purchasers tend to have a shorter horizon (e.g., the term means that a poor outcome may not occur every time there
of a health care contract). To improve the comparability of is an incorrect decision or an error in process.26 Another
cost-effectiveness, the Panel on Cost-Effectiveness in Health reason to identify critical processes of care is that it avoids the
and Medicine (a nonfederal panel with expertise in CEA, methodological problems of risk-adjusting outcomes and/or
the statistical limitations of comparing outcomes for low-
clinical medicine, ethics, and health outcomes measurement
frequency procedures and/or events.
convened by the US Public Health Service) recommended
Ultimately, efforts to improve quality will need to account
that calculations of cost-effectiveness be based on a broad
for outcomes, but attempts to improve outcomes without
societal perspective rather than on that of patients, providers,
consideration for the relevant processes are likely to prove
or insurers. Such a perspective would more likely include
frustrating. Therefore, it is critically important to identify
costs incurred by patients or others (e.g., outpatient
processes that have the greatest impact on outcomes27; the
medication or home care after hospital discharge).
time and effort spent measuring processes not directly linked
to outcomes are likely to be wasteful. The ARRA seeks to
Defining Quality in Health Care promote the burgeoning field of cost-effectiveness research,
which informs health care decisions by providing evidence on
Assessing cost-effectiveness also requires suitable measures
the effectiveness, benefits, and harm of different treatment
of quality. Unfortunately, defining quality can be even more
options, whether they are drugs, medical devices, surgical
complex than assessing cost.21,22 Measures such as operative
procedures, or ways to deliver health care. Evidence can
mortality are straightforward but have become increasingly
come from existing data or by generating new evidence.
rare; therefore, mortality alone is not useful in the vast
majority of cases.
A long-held standard of health care quality was the appro- Connecting the Dots: Linking Quality to Systems of
priateness of care, and an individual physician’s knowledge Care
was the authority with regard to judging quality. In recent Given the importance of processes of care, a surgeon’s
decades, several factors have seriously undermined appropri- (or hospital’s) systems of care reflect the consistency with
ateness (and perhaps even physician authority) as a primary which the same processes of care are applied to a given situ-
indicator of quality. These factors included findings that ation. Indirect evidence for this link comes from data on the
some procedures had a high incidence of inappropriate indi- relationship between volume and outcomes for complex pro-
cations; judgments as to appropriate care relative to groups cedures; surgeons and/or hospitals that do a given operation
differed from such judgments relative to individuals23; retro- more frequently (i.e., high volumes) often have better out-
spective assessments often judged appropriateness on the comes.28–33 Moreover, the relative impact of hospital volume
basis of outcome without considering processes of care24; and and surgeon volume on outcomes can vary by procedure.
a realization that variations in procedure frequency often Thus, complex, team-dependent procedures such as cardiac
related to provider capacity (e.g., the number of hospital beds surgery, pancreatectomy, and esophagectomy have a stronger
per 1,000 persons). Unexplained variations in the use of relation with hospital volume even if performed by low-
health care services across small geographic areas, in particu- volume surgeons; by comparison, carotid endarterectomy
lar, have undermined physician authority on quality and are and thyroidectomy have a strong relation with surgeon
discussed in more detail in a later section. volume. A positive relation with outcomes also has been
The overall consequence is that appropriateness is not noted for surgical subspecialty training.28,32,34
sufficiently granular to be a useful measure of quality. These These volume-outcome relations data are intriguing,
shortcomings were addressed by Donabedian, who character- although they only represent associations and probabilities,
ized quality in terms of structure (faculties, equipment, and not cause-and-effect relationships.35 This raises the question
03/11
SURGICAL CARE — 6
of whether practice makes perfect or perfect makes practice. Linking Processes to Performance
The answer is not known but has produced two schools The desire to link processes to performance has become
of thought. The practice makes perfect school of thought manifest in pay-for-performance (P4P) programs that provide
advocates that quality improvements on a widespread basis incentives to adopt evidence-based process measures.42,43 The
will derive from the adoption of better systems or processes most conspicuous of these is Medicare’s Physician Quality
of care. These proponents note that low volume is not always Reporting Initiative (PQRI) (www.cms.hhs.gov/pqri). The
associated with worse outcomes, and high volume is not list of applicable measures has expanded considerably in the
always associated with improved outcomes. Thus, the find- last several years, and some specific measures related to surgi-
ings apply to surgeons in general but not to specific surgeons. cal care are listed in Table 2. A recent notable finding is that
This means that good outcomes can be achieved even with the infection control measures of the Surgical Care Improve-
low volumes if carried out using good systems. Conversely, ment Project (SCIP), which are closely aligned with similar
high volumes may result in worse outcomes in the presence PQRI measures, appear to be most effective when used in the
of poor systems. As a further caveat, the relative applicability aggregate rather than as individual measures.44
of the role of systems to complex care is suggested by findings Although the rationale for these programs seems straight-
from the Department of Veterans Affairs’ (VA) National forward, there are concerns about their long-term potential
Surgical Quality Improvement Project (NSQIP). One study effectiveness. One such concern is that only a small number
of eight common surgical procedures noted no correlation of surgical process measures have been identified so far. In
between hospital operative volume and postoperative addition, these measures tend to be related to general aspects
mortality.36 of care, with many processes of care more specific to the
In comparison, the perfect makes practice school advocates outcome of a given procedure or disease process yet to be
regionalizing care to those centers with better outcomes. identified.
Perhaps the best known of these advocates is the Leapfrog There are also concerns that the magnitude of the cost
Group (www.leapfroggroup.org), a large consortium of major reductions relative to the incentives is presently not known.
employers. They used empirical observations of cost and out- This is particularly relevant if health care finance is a zero-
comes to identify the minimum volumes for procedures such sum game. If incentive payments exceed the savings, there
as coronary artery bypass grafting, esophagectomy, carotid will be increased pressure to reduce other payments to main-
endarterectomy, and aortic aneurysm repair that were associ- tain budget neutrality. If the savings exceed the incentives,
ated with optimal outcomes. The empirical basis of these there may be increased pressure to increase the incentives.
determinations is subject to methodological problems.37 A further concern relates to assigning the benefits from
Moreover, changes in technology, such as the advent of endo- P4P. Surgeon-related quality improvements that appear to
vascular aortic aneurysm repair, have substantially under- confer disproportionate financial benefits on the insurer
mined the experience levels that were the basis of the original rather than on the surgeon may reduce the incentive for sur-
recommendations. geons to implement improvements. This concern also relates
Other proponents of regionalization are the Institute of to P4P measures where implementation requires coordina-
Medicine’s National Cancer Policy Board and the National tion of systems among providers rather than an isolated action
Research Council. They concluded that complicated cancer on the part of an individual or an institution. For example,
operations had better initial outcomes with high-volume pro- compliance with the measures for prophylactic antibiotics
viders.38 Higher volumes also were associated with improved may reward or penalize a surgeon even though she or he may
long-term survival. have little control over whether antibiotics are given in a
Although regionalization has proven effective in trauma timely fashion; the hospital systems needed for compliance
care, the basis of the improved quality in this setting may be may be a more important determinant of compliance with
better systems of care, not higher volume per se.39 Moreover, this measure. Indeed, one study found that a major barrier to
the perception of preventability of trauma deaths increased in compliance was that no single participant in the perioperative
parallel with the appreciation of the importance of the system. routine had acknowledged responsibility to administer pro-
Thus, regionalization of care without a solid understanding phylactic antibiotics.45 The need for coordination among
of the basis of the volume-outcome relation has the potential individuals in such situations has been recognized among
to create unintended or adverse consequences for overall commercial health maintenance organizations’ (HMOs) P4P
care. Consequently, many believe that it is too soon to use programs: only 13.3% of the physician-oriented programs
volume-outcome data as a surrogate for quality or as criteria focus solely on the individual physician as the unit of pay-
for establishing policy.40 The higher quality of care at level I ment.42,43 The need for such coordination has raised concern
trauma centers comes with a price; these centers’ better that the dispersion of patient care among multiple physicians
outcomes are also more expensive.41 This reflects both the could limit the effectiveness of initiatives that rely on a single
relative and absolute aspects of cost-effectiveness. Regional- retrospective method for assigning responsibility.46
ization of trauma care appears to be cost-effective relative to Another concern is that P4P may not be so much pay
lack of regionalization, with an associated incremental cost of for performance as it is pay for compliance. It is argued that
less than $50,000/life-year saved (LYS); LYS is a measure of the real goal should be to encourage innovation to optimize
the number of life-years saved as a result of a health inter- cost-effectiveness. Moreover, not all P4P programs focus on
vention. The $50,000 figure is a threshold conventionally evidence-based measures. For example, one study found
used to ascertain cost-effectiveness. A corollary is that cost- that 24% of physicians faced incentives derived from patient
effectiveness does not always equate to cost saving. satisfaction surveys and 14% faced incentives derived from
03/11
SURGICAL CARE — 7
Table 2 Current Physician Quality Reporting Initiative Measures by Surgical Specialty
General and Perioperative Measures, All Specialties

20. Perioperative Care: Timing of Antibiotic Prophylaxis — Ordering Physician
Percentage of surgical patients aged 18 years and older undergoing procedures with the indications for prophylactic parenteral
antibiotics, who have an order for prophylactic parenteral antibiotic to be given within 1 hour (if fluoroquinolone or vancomycin,
2 hours) prior to the surgical incision (or start of procedure when no incision is required)
21. Perioperative Care: Selection of Prophylactic Antibiotic — First- OR Second-Generation Cephalosporin
Percentage of surgical patients aged 18 years and older undergoing procedures with the indications for a first- OR second-generation
cephalosporin prophylactic antibiotic, who had an order for cefazolin OR cefuroxime for antimicrobial prophylaxis
22. Perioperative Care: Discontinuation of Prophylactic Antibiotics (Noncardiac Procedures)
Percentage of noncardiac surgical patients aged 18 years and older undergoing procedures with the indications for prophylactic
parenteral antibiotics who received a prophylactic parenteral antibiotic and have an order for discontinuation of prophylactic
parenteral antibiotics within 24 hours of surgical end time
23. Perioperative Care: Venous Thromboembolism (VTE) Prophylaxis (When Indicated in ALL Patients)
Percentage of patients aged 18 years and older undergoing procedures for which VTE prophylaxis is indicated in all patients, who
had an order for low-molecular-weight heparin, low-dose unfractionated heparin, adjusted-dose warfarin, fondaparinux, or
mechanical prophylaxis to be given within 24 hours prior to incision time or within 24 hours after surgery end time
30. Perioperative Care: Timely Administration of Prophylactic Parenteral Antibiotics
Percentage of surgical patients aged 18 years and older who receive an anesthetic when undergoing procedures with the indications
for prophylactic parenteral antibiotics for whom administration of the prophylactic parenteral antibiotic ordered has been initiated
within 1 hour (if fluoroquinolone or vancomycin, 2 hours) prior to the surgical incision (or start of procedure when no incision is
required)
46. Medication Reconciliation: Reconciliation after Discharge from an Inpatient Facility
Percentage of patients aged 65 years and older discharged from any inpatient facility (e.g., hospital, skilled nursing facility, or
rehabilitation facility) and seen within 60 days following discharge in the office by the physician providing ongoing care who had a
reconciliation of the discharge medications with the current medication list in the medical record documented
76. Prevention of Catheter-Related Bloodstream Infections: Central Venous Catheter (CVC) Insertion Protocol
Percentage of patients, regardless of age, who undergo CVC insertion for whom CVC was inserted with all elements of maximal
sterile barrier technique (cap AND mask AND sterile gown AND sterile gloves AND a large sterile sheet AND hand hygiene AND
2% chlorhexidine for cutaneous antisepsis [or acceptable alternative antiseptics per current guideline]) followed
114. Preventive Care and Screening: Inquiry Regarding Tobacco Use
Percentage of patients aged 18 years or older who were queried about tobacco use one or more times within 24 months
115. Preventive Care and Screening: Advising Smokers and Tobacco Users to Quit
Percentage of patients aged 18 years and older who are smokers or tobacco users and who received advice to quit smoking
124. Health Information Technology: Adoption/Use of Electronic Health Records (EHRs)
Documents whether provider has adopted and is using health information technology. To qualify, the provider must have adopted
and be using a certified/qualified EHR.
193. Perioperative Temperature Management
Percentage of patients, regardless of age, undergoing surgical or therapeutic procedures under general or neuraxial anesthesia of
60 minutes’ duration or longer, except patients undergoing cardiopulmonary bypass, for whom either active warming was used
intraoperatively for the purpose of maintaining normothermia or at least one body temperature g36°C (or 96.8°F) was recorded
within the 30 minutes immediately before or the 15 minutes immediately after anesthesia end time
Cardiac Surgery
43. Coronary Artery Bypass Graft (CABG): Use of Internal Mammary Artery (IMA) in Patients with Isolated CABG
Surgery
Percentage of patients aged 18 years and older undergoing isolated CABG surgery using an IMA graft
44. Coronary Artery Bypass Graft (CABG): Preoperative Beta Blocker in Patients with Isolated CABG Surgery
Percentage of patients aged 18 years and older undergoing isolated CABG surgery who received a beta blocker within 24 hours prior
to surgical incision
45. Perioperative Care: Discontinuation of Prophylactic Antibiotics (Cardiac Procedures)
Percentage of cardiac surgical patients aged 18 years and older undergoing procedures with the indications for prophylactic
antibiotics who received a prophylactic antibiotic and who have an order for discontinuation of prophylactic antibiotics within
48 hours of surgical end time
164. Coronary Artery Bypass Graft (CABG): Prolonged Intubation (Ventilation)
Percentage of patients aged 18 years and older undergoing isolated CABG surgery who require intubation > 24 hours
165. Coronary Artery Bypass Graft (CABG): Deep Sternal Wound Infection Rate
Percentage of patients aged 18 years and older undergoing isolated CABG surgery who developed deep sternal wound infection
(involving muscle, bone, and/or mediastinum requiring operative intervention) within 30 days postoperatively
166. Coronary Artery Bypass Graft (CABG): Stroke/Cerebrovascular Accident (CVA)
Percentage of patients aged 18 years and older undergoing isolated CABG surgery who had a stroke/CVA within 24 hours
postoperatively
167. Coronary Artery Bypass Graft (CABG): Postoperative Renal Insufficiency
Percentage of patients aged 18 years and older undergoing isolated CABG surgery who develop postoperative renal insufficiency or
require dialysis
168. Coronary Artery Bypass Graft (CABG): Surgical Reexploration
Percentage of patients aged 18 years and older undergoing isolated CABG surgery who require a return to the operating room for
mediastinal bleeding/tamponade, graft occlusion (attributable to acute closure, thrombosis, or technical or embolic origin), or other
cardiac reason
169. Coronary Artery Bypass Graft (CABG): Antiplatelet Medications at Discharge
Percentage of patients aged 18 years and older undergoing isolated CABG surgery who have antiplatelet medication at discharge
170. Coronary Artery Bypass Graft (CABG): Beta Blockers Administered at Discharge
Percentage of patients aged 18 years and older undergoing isolated CABG surgery who were discharged on beta blockers
171. Coronary Artery Bypass Graft (CABG): Lipid Management and Counseling
Percentage of patients aged 18 years and older undergoing isolated CABG surgery who have antilipid treatment at discharge
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SURGICAL CARE — 8
Table 2 Continued
197. Coronary Artery Disease (CAD): Drug Therapy for Lowering Low-Density Lipoprotein Cholesterol
Percentage of patients aged 18 years and older with a diagnosis of CAD who were prescribed a lipid-lowering therapy (based on
current American College of Cardiology/American Heart Association guidelines)
General Surgery/Colorectal Surgery
185. Endoscopy and Polyp Surveillance: Colonoscopy Interval for Patients with a History of Adenomatous Polyps —
Avoidance of Inappropriate Use
Percentage of patients aged 18 years and older receiving a surveillance colonoscopy and with a history of colonic polyp(s) in a
previous colonoscopy who had a follow-up interval of 3 or more years since their last colonoscopy documented in the colonoscopy
report
Ophthalmology
12. Primary Open-Angle Glaucoma (POAG): Optic Nerve Evaluation
Percentage of patients aged 18 years and older with a diagnosis of POAG who have an optic nerve head evaluation during one or
more office visits within 12 months
14. Age-Related Macular Degeneration (AMD): Dilated Macular Examination
Percentage of patients aged 50 years and older with a diagnosis of AMD who had a dilated macular examination performed that
included documentation of the presence or absence of macular thickening or hemorrhage AND the level of macular degeneration
severity during one or more office visits within 12 months
139. Cataracts: Comprehensive Preoperative Assessment for Cataract Surgery with Intraocular Lens (IOL) Placement
Percentage of patients aged 18 years and older with a procedure of cataract surgery with IOL placement who received a
comprehensive preoperative assessment of (1) dilated fundus examination; (2) axial length, corneal keratometry measurement, and
method of IOL power calculation reviewed; and (3) functional or medical indication(s) for surgery prior to the cataract surgery with
IOL placement within 12 months prior to cataract surgery
141. Primary Open-Angle Glaucoma (POAG): Reduction of Intraocular Pressure (IOP) by 15% OR Documentation of a
Plan of Care
Percentage of patients aged 18 years and older with a diagnosis of POAG whose glaucoma treatment has not failed (the most recent
IOP was reduced by at least 15% from the preintervention level), OR if the most recent IOP was not reduced by at least 15% from
the preintervention level, a plan of care was documented within 12 months
191. Cataracts: 20/40 or Better Visual Acuity within 90 Days following Cataract Surgery
Percentage of patients aged 18 years and older with a diagnosis of uncomplicated cataract who had cataract surgery and no
significant ocular conditions impacting the visual outcome of surgery and had best-corrected visual acuity of 20/40 or better
(distance or near) achieved within 90 days following the cataract surgery
192. Cataracts: Complications within 30 Days following Cataract Surgery Requiring Additional Surgical Procedures
Percentage of patients aged 18 years and older with a diagnosis of uncomplicated cataract who had cataract surgery and any of a
specified list of surgical procedures in the 30 days following cataract surgery that would indicate the occurrence of any of the
following major complications: retained nuclear fragments, endophthalmitis, dislocated or wrong power IOL, retinal detachment,
or wound dehiscence
Orthopedics
24. Osteoporosis: Communication with the Physician Managing Ongoing Care Postfracture of Hip, Spine, or Distal Radius
for Men and Women Aged 50 Years and Older
Percentage of patients aged 50 years and older treated for a hip, spine, or distal radial fracture with documentation of
communication with the physician managing the patient’s ongoing care that a fracture occurred and that the patient was or should
be tested or treated for osteoporosis
40. Osteoporosis: Management following Fracture of Hip, Spine, or Distal Radius for Men and Women Aged 50 Years and
Older
Percentage of patients aged 50 years and older with fracture of the hip, spine, or distal radius who had a central dual-energy x-ray
absorptiometry measurement ordered or performed or pharmacologic therapy prescribed
Otolaryngology
91. Acute Otitis Externa (AOE): Topical Therapy
Percentage of patients aged 2 years and older with a diagnosis of AOE who were prescribed topical preparations
92. Acute Otitis Externa (AOE): Pain Assessment
Percentage of patient visits for those patients aged 2 years and older with a diagnosis of AOE with assessment for auricular or
periauricular pain
93. Acute Otitis Externa (AOE): Systemic Antimicrobial Therapy — Avoidance of Inappropriate Use
Percentage of patients aged 2 years and older with a diagnosis of AOE who were not prescribed systemic antimicrobial therapy
94. Otitis Media with Effusion (OME): Diagnostic Evaluation — Assessment of Tympanic Membrane Mobility
Percentage of patient visits for those patients aged 2 months through 12 years with a diagnosis of OME with assessment of tympanic
membrane mobility with pneumatic otoscopy or tympanometry
Surgical Oncology
71. Breast Cancer: Hormonal Therapy for Stage IC–IIIC Estrogen Receptor/Progesterone Receptor (ER/PR)-Positive
Breast Cancer
Percentage of female patients aged 18 years and older with stage IC through IIIC, ER- or PR-positive breast cancer who were
prescribed tamoxifen or aromatase inhibitor during the 12-month reporting period
72. Colon Cancer: Chemotherapy for Stage III Colon Cancer Patients
Percentage of patients aged 18 years and older with stage IIIA through IIIC colon cancer who are referred for adjuvant chemothera-
py, are prescribed adjuvant chemotherapy, or have previously received adjuvant chemotherapy within the 12-month reporting period
99. Breast Cancer Resection Pathology Reporting: pT Category (Primary Tumor) and pN Category (Regional Lymph
Nodes) with Histologic Grade
Percentage of breast cancer resection pathology reports that include the pT category (primary tumor), the pN category (regional
lymph nodes), and the histologic grade
100. Colorectal Cancer Resection Pathology Reporting: pT Category (Primary Tumor) and pN Category (Regional Lymph
Nodes) with Histologic Grade
Percentage of colon and rectum cancer resection pathology reports that include the pT category (primary tumor), the pN category
(regional lymph nodes), and the histologic grade
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SURGICAL CARE — 9
Table 2 Continued
112. Preventive Care and Screening: Screening Mammography
Percentage of women aged 40 through 69 years who had a mammogram to screen for breast cancer within 24 months
113. Preventive Care and Screening: Colorectal Cancer Screening
Percentage of patients aged 50 through 75 years who received the appropriate colorectal cancer screening
136. Melanoma: Follow-up Aspects of Care
Percentage of patients, regardless of age, with a new diagnosis of melanoma or a history of melanoma who received all of the
following aspects of care within 12 months: (1) patient was asked specifically if he/she had any new or changing moles; AND (2) a
complete physical skin examination was performed and the morphology, size, and location of new or changing pigmented lesions
were noted; AND (3) patient was counseled to perform a monthly self skin examination
137. Melanoma: Continuity of Care — Recall System
Percentage of patients, regardless of age, with a current diagnosis of melanoma or a history of melanoma whose information was
entered, at least once within a 12-month period, into a recall system that includes a target date for the next complete physical skin
examination AND a process to follow-up with patients who either did not make an appointment within the specified time frame or
who missed a scheduled appointment
138. Melanoma: Coordination of Care
Percentage of patients, regardless of age, with a new occurrence of melanoma who have a treatment plan documented in the chart
that was communicated to the physician(s) providing continuing care within 1 month of diagnosis
157. Thoracic Surgery: Recording of Clinical Stage for Lung Cancer and Esophageal Cancer Resection
Percentage of surgical patients aged 18 years and older undergoing resection for lung or esophageal cancer who had clinical TNM
staging provided prior to surgery
194. Oncology: Cancer Stage Documented
Percentage of patients, regardless of age, with a diagnosis of breast, colon, or rectal cancer who are seen in the ambulatory setting
who have a baseline AJCC cancer stage or documentation that the cancer is metastatic in the medical record at least once within
12 months
Urology
102. Prostate Cancer: Avoidance of Overuse of Bone Scan for Staging Low-Risk Prostate Cancer Patients
Percentage of patients, regardless of age, with a diagnosis of prostate cancer at low risk of recurrence receiving interstitial prostate
brachytherapy, OR external-beam radiotherapy to the prostate, OR radical prostatectomy, OR cryotherapy who did not have a bone
scan performed at any time since diagnosis of prostate cancer
104. Prostate Cancer: Adjuvant Hormonal Therapy for High-Risk Prostate Cancer Patients
Percentage of patients, regardless of age, with a diagnosis of prostate cancer at high risk for recurrence receiving external-beam
radiotherapy to the prostate who were prescribed adjuvant hormonal therapy (GnRH agonist or antagonist)
105. Prostate Cancer: Three-Dimensional Radiotherapy
Percentage of patients, regardless of age, with a diagnosis of clinically localized prostate cancer receiving external-beam radiotherapy
as a primary therapy to the prostate with or without nodal irradiation (no metastases; no salvage therapy) who receive three-
dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiation therapy
Vascular Surgery
126. Diabetes Mellitus: Diabetic Foot and Ankle Care, Peripheral Neuropathy — Neurologic Evaluation
Percentage of patients aged 18 years and older with a diagnosis of diabetes mellitus who had a neurologic examination of their lower
extremities within 12 months
127. Diabetes Mellitus: Diabetic Foot and Ankle Care, Ulcer Prevention — Evaluation of Footwear
Percentage of patients aged 18 years and older with a diagnosis of diabetes mellitus who were evaluated for proper footwear and
sizing
158. Carotid Endarterectomy: Use of Patch During Conventional Carotid Endarterectomy
Percentage of patients aged 18 years and older undergoing conventional (noneversion) carotid endarterectomy who undergo patch
closure of the arteriotomy
163. Diabetes Mellitus: Foot Examination
Percentage of patients aged 18 through 75 years with diabetes who had a foot examination
172. Hemodialysis Vascular Access Decision Making by Surgeon to Maximize Placement of Autogenous Arteriovenous (AV)
Fistula
Percentage of patients aged 18 years and older with a diagnosis of advanced chronic kidney disease (stage 4 or 5) or end-stage renal
disease requiring hemodialysis vascular access documented by surgeon to have received autogenous AV fistula
186. Wound Care: Use of Compression System in Patients with Venous Ulcers
Percentage of patients aged 18 years and older with a diagnosis of venous ulcer who were prescribed compression therapy within the
12-month reporting period
195. Stenosis Measurement in Carotid Imaging Studies
Percentage of final reports for all patients, regardless of age, for carotid imaging studies (neck magnetic resonance angiography, neck
computed tomographic angiography, neck duplex ultrasonography, carotid angiography) performed that include direct or indirect
reference to measurements of distal internal carotid diameter as the denominator for stenosis measurement
201. Ischemic Vascular Disease (IVD): Blood Pressure Management Control
Percentage of patients aged 18 years and older with IVD who had most recent blood pressure in control (less than 140/90 mm Hg)
202. Ischemic Vascular Disease (IVD): Complete Lipid Profile
Percentage of patients aged 18 years and older with IVD who received at least one lipid profile within 12 months
203. Ischemic Vascular Disease (IVD): Low-Density Lipoprotein (LDL) Cholesterol Control
Percentage of patients aged 18 years and older with IVD who had most recent LDL cholesterol level in control (less than
100 mg/dL)
204. Ischemic Vascular Disease (IVD): Use of Aspirin or Another Antithrombotic
Percentage of patients aged 18 years and older with IVD with documented use of aspirin or other antithrombotic
The number of each measure is that assigned by the Centers for Medicare and Medicaid Services. Available at: https://www.cms.gov/PQRI/Downloads/2010_
PQRI_MeasuresList_111309.pdf. accessed January 10, 2011.
AJCC = American Joint Committee on Cancer; GnRH = gonadotropin-releasing hormone.
03/11
SURGICAL CARE — 10
profiling based on use of medical resources, whereas 19% important conclusions to be drawn from these efforts are as
faced incentives derived from quality of care measures. Patient follows: physician-initiated interventions can be as effective as
satisfaction is undoubtedly important, but it is not clear external review (and possibly more effective) in improving
that improved patient satisfaction alone suffices to address quality; a systems approach to quality improvement is better
problems of cost-effectiveness. than a bad apple approach; and it is possible to conduct
Lastly, there is the issue of how providers might react when quality improvement programs involving practice groups that
there are differences in P4P programs among the various might otherwise be viewed as competitors.
health plans in which they participate. Many providers would The VA’s NSQIP is another example of a successful qual-
prefer health plans to use a single standardized set of ity initiative, achieving a 27% reduction in 30-day mortality
measures, but local market environments can make such after major procedures and a 45% decrease in morbidity.53
standardization unlikely.47 As a result, providers may ignore NSQIP found the two most important risk factors for pro-
measures that seem to be contradictory, are perceived as too longed hospital stay after major elective surgery to be the
complex, or derive from health plans from which they get intraoperative processes of care and postoperative adverse
relatively few patients. A related concern is that some P4P events.54 Notably, the savings from improved surgical care
programs could have unintended negative consequences if far exceeded investment in the project.55 NSQIP has now
physicians are convinced that the program does not incorpo- expanded into the broader community under the auspices of
rate adequate risk adjustment mechanisms. Providers then the American College of Surgeons (ACS). NSQIP data also
might simply opt out of seeing challenging patients.48,49 To have been used to validate the AHRQ Patient Safety Indica-
avoid some of these problems, the Agency for Healthcare tors (www.academyhealth.org/2005/ppt/tsilimingras.ppt).
Research and Quality (AHRQ) has a specific section of their Other successful surgically related quality improvement
website (www.ahrq.gov/qual/p4pguide.htm) devoted to P4P efforts include Intermountain Health Systems in Utah; the
programs, including a decision guide for purchasers. Maine Medical Assessment Foundation56; the Washington
P4P and “value-based purchasing” are incentive payment State Surgical Clinical Outcomes Assessment Program
or shared savings programs that are related to “gainsharing.” (SCOAP)57; Quality Surgical Solutions in Kentucky58; the
The Office of the Inspector General (OIG) has defined Michigan Surgical Quality collaborative59; the Society for
gainsharing as an “arrangement in which a hospital will share Thoracic Surgery national database, which is now widely
with each physician group a percentage of the hospital’s cost accepted as a benchmark for quality in cardiac surgery60;
savings arising from the physician groups’ implementation of the New England Colorectal Cancer Quality Project61; the
cost reduction methods.”50 Although intended to encourage Vascular Study Group of Northern New England62; and the
physicians to deliver quality care, such gainsharing arrange- National Surgical Infection Collaborative.45
ments can technically look like a model of a kickback; more- The Maine and Michigan efforts are notable in that they
over, they are barred by the civil monetary penalty law, which have been carried out in conjunction with insurers.63–65 More-
prohibits hospitals from rewarding physicians for reducing over, none of these efforts increased liability exposure; indeed,
services to patients. The Deficit Reduction Act of 2005 they often reduced it. Because the practice profiles were
directed the CMS to conduct demonstration projects, and physician initiated, there was little risk that the findings would
these are now under way. be used to make decisions about credentialing, reimburse-
These programs notwithstanding, substantial direct evi- ment, or contracting.56 It is also noteworthy that the parties
dence of the link between systems and quality comes from the that funded these efforts (including insurers) usually agreed
quality improvement efforts of organizations that analyze and to confidentiality in return for the benefit associated with
standardize systems of care. Perhaps the most notable of voluntary physician involvement.
these efforts is the multi-institutional Northern New England
Cardiovascular Disease Study Group (NNECVDSG).51 This
Measuring Health Outcomes
group began in 1990 and consisted of cardiac surgical teams
(e.g., surgeons, nurses, anesthesiologists, pump technicians) As noted above, the primary goal of investigating the struc-
that received feedback on outcomes, were trained in ture and process components of care is, ultimately, to improve
Deming’s quality improvement techniques, and site-visited outcomes. Using outcomes to assess quality can be con-
other participating centers. They also periodically met to founded by a number of factors, however. One such factor is
share data and discuss processes of care. The result has been the reduced usefulness of traditional metrics. For instance,
to substantially reduce morbidity and mortality from cardiac mortality is infrequent with most surgical procedures, and
surgery and to minimize the year-to-year mortality variations morbidity such as wound infection rates can be difficult to
among the institutions. They also had a low incidence of assess in an era of early discharges. Other short-term outcome
procedures that did not adhere to recommended indications metrics, such as length of stay, readmission, or return to
for surgery.52 work, are often influenced by deeply rooted social and
The group’s success can be attributed to several character- economic factors. A further issue is that many measures of
istics: there is no ambiguity of purpose, the data are not quality lack standard definitions.66
owned by any member or subgroup of members, members Another factor confounding the measurement of health
have an established safe place to work, a forum is set up for care outcomes has been the growth of knowledge and tech-
discussion, and there is regular feedback. This was achieved nology that has increased surgical care related to chronic and/
without personal criticism or an attempt to identify any or degenerative diseases. Recent data show that 133 million
proverbial “bad apples.” Despite concerns that the findings people, or almost half of all Americans, live with a chronic
would lead to unfavorable publicity, this did not occur. Three condition.67 That number is projected to increase by more
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than 1% per year by 2030, resulting in an estimated chroni- As with other aspects of cost-effectiveness, estimates of
cally ill population of 171 million. Moreover, almost half of QALYs are confounded by different perspectives among
all people with chronic illnesses have multiple conditions. patients, providers, and payers with regard to the experiential,
Integrated health care delivery via the chronic care model physiologic, and resource-related dimensions that should
is intended to address the many deficiencies in the current apply. Thus, the weight given to clinical probabilities, patient
management of diseases such as diabetes, heart disease, utilities and preferences, and cost will affect the calculations.
depression, and asthma. Traditional measures of quality Assessment of quality is further complicated when there is no
(e.g., 30-day mortality) that are applied to acute conditions consensus across perspectives with regard to the preferred
such as perforated ulcer are not as applicable here. Given that strategy or outcome. Finally, quality of life studies can be
the number and complexity of treatment options for many compromised by other methodological flaws, such as a rela-
surgical conditions have increased, it has become necessary tive paucity of validated instruments for measuring health-
to identify quality metrics for each treatment strategy. There related quality of life, especially in certain specialty areas.75 In
also is increasing emphasis on patient-centered care; given this context, a 2008 review could not identify a fully validated
the multicultural nature of US society, the result is substan- instrument for assessing postoperative recovery.76
tial heterogeneity in patient perspectives on quality. Overall,
there has been little research (i.e., clinical trials) on the interpreting and⁄or initiating cost-effectiveness
quality perspectives of vulnerable populations. analyses
Health care quality in this context is typically assessed in A primer to initiate and/or interpret CEA is available
terms of quality-adjusted life years (QALYs),68,69 a measure at www.acponline.org/shell-cgi/printhappy.pl/journals/ecp/
that reflects the length of time during which a patient experi- sepoct00/primer.htm.
ences a given health status. The lexicon of research in this Several important principles that must be considered when
area is extensive. Cost-utility analysis is the form of CEA of performing and/or interpreting a CEA are the comparison,
alternative interventions where costs are measured in mone- perspective, direct and indirect costs, time horizon, discount-
tary units and outcomes in terms of patient utility, usually to ing, and sensitivity analyses.77–79 The specific comparison
the patient, in QALYs. A patient utility is the relative desir- between one health care intervention and another should be
ability or preference from the patient’s perspective for a given precisely defined at the outset of the analysis. Alternative
health outcome. QALYs are units of health outcomes that perspectives are of society overall (favored by many), a third-
adjust gains or losses of years of life subsequent to a health party payer, a physician, a hospital, or a patient. CEA should
care intervention by the quality of life during those years. incorporate two types of cost; direct costs represent the value
Other (although less frequently employed) measures for of all goods, services, and other resources consumed in pro-
patient utilities include disability-adjusted life-years (DALYs) viding health care or dealing with the side effects of the care,
and health-year equivalents (HYEs). DALYs are units of whereas indirect costs (or productivity losses) include the
health status adjusting age-specific life expectancy by loss of costs of lost work attributable to absenteeism or early retire-
health and years of life attributable to disability from disease ment, impaired productivity at work, or premature mortality.
or injury, whereas HYEs are the number of years of perfect Intangible costs (i.e., pain, suffering, and grief) are often
health considered to be equal to the remaining years of life in omitted, which is an important limitation of most CEA. The
their respective health states. time horizon of a CEA is the time frame of the study and
QALYs are applicable to assessing surgical outcomes. They should be long enough to capture streams of health and eco-
can be calculated by several different methods; some include nomic outcomes; depending on the research question, the
objective measures (e.g., functional status), whereas others time horizon might encompass a disease episode, patient life,
only consider subjective estimates of well-being. Even the or even multiple generations. Discounting allows the model
objective measures consider patient-desired outcomes to to account for the effect of the passage of time on the values
capture the meaningfulness of a given functional status. For of costs and outcomes, such that costs and outcomes are
instance, a patient may not be able to walk as far as another, discounted relative to their present value (e.g., at a rate of 3
but whether the former has a worse quality of life depends on to 5% per year). Inflation should be a separate consideration.
each patient’s lifestyle.70 The result is that QALYs data tend Finally, sensitivity analyses should be performed to determine
not to follow a normal distribution, and comparative analyses
if plausible variations in the estimates of certain variables
often require use of nonparametric techniques.71
thought to be subject to significant uncertainty affect the
Estimates of QALYs can be affected by other factors.26,72
results of the cost analysis.
For instance, estimates of the future value of an outcome
Lower values of cost-effectiveness are understood to be
measure may vary with the prevailing circumstances at the
“more cost-effective” or have “increased cost-effectiveness.”
time of assessment (e.g., acute pain) or with the patient’s age
In contrast “less cost-effective” and “decreased cost-
(e.g., elderly patients often place great value on the ability
effectiveness” refer to higher costs per LYS. Cost-
to live independently). Calculation of QALYs may also be
effectiveness that has a negative value implies that money
affected by gender, ethnicity, socioeconomic status, religious
would be saved.
beliefs, time away from work, and other factors that affect
Particular points that warrant consideration are as
attitudes about health care. One study noted that surgeons
follows:
tended to underestimate the importance of patients’ social
and spiritual themes.73 Adjusting outcome measures to • CEA is highly sensitive to the choice of compared strate-
account for health status and severity of illness before gies: it often involves marginal benefits, and excluding a
treatment also can be difficult.74 simple strategy in which the only comparison is between
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treatment and no treatment can make a particular strategy applicability to highly specific groups of patients (e.g., elderly
appear far more cost-effective than it otherwise might and/or pregnant patients are often excluded); they can be
seem. CEA does not answer the question of which strategy expensive; and the numbers of patients needed for statistical
is economically preferred; rather, it identifies which purposes can be impractical. In addition, study findings that
strategy is more effective in terms of LYS for a given might seem to apply to a particular patient may be difficult
expenditure.80 to reproduce in settings that differ from the controlled condi-
• The quality of supporting evidence is another important tions of the original trial. Also, the pressure to enroll patients
consideration. Data garnered in real practice or from a in such trials has, on occasion, led to questionable ethical
registry are more likely to be generalizable than data that behavior by the investigators.
are modeled or collected from a clinical trial. Three particularly valuable sources for identifying studies
• Determinations made under optimal circumstances relevant to cost-effectiveness and judging the quality of those
(efficacy) tend to overestimate cost-effectiveness compared studies are MEDLINE (www.ncbi.nlm.nih.gov/PubMed/
with determinations made under real-world conditions medline.html), the Cochrane Collaboration (www.cochrane.
(true effectiveness). This distinction between efficacy and org), and the CEBM (www.cebm.net). Each site has relative
effectiveness is reflected in how differences in postopera- advantages and disadvantages. The Cochrane Collaboration
tive stroke rates influence the cost-effectiveness of carotid is an international network of epidemiologists and clinicians
endarterectomy. Randomized, controlled trials (RCTs) who systematically review the best available medical evidence;
it includes sources not always accessible through MEDLINE
show this procedure to be efficacious when performed by
but, in contrast to MEDLINE, requires a subscription.
surgeons, with low rates of perioperative stroke and death.
Recent Cochrane Collaboration reviews are abstracted
As the incidence of stroke and other complications increases
monthly in the Journal of the American College of Surgeons
with more general use, the procedure becomes less effec-
(JACS).
tive or even ineffective.81–83 If effectiveness can vary over
The ACS also makes several literature resources available.
a relatively narrow range of outcomes, there is a strong
These include Selected Readings in General Surgery (SRGS),
ethical motivation for surgeons to be familiar with their
a trusted point of reference that is also available in a Web-
own clinical outcomes and seek their patients’ informed
based version; and Evidence Based Reviews in Surgery (EBRS),
consent based on their personal results.84 In this context, a Web-based program developed jointly with the Canadian
differences in quality or cost measures may be more a Association of General Surgeons. Each month during the
function of patient mix than the abilities of the wider academic year, EBRS presents a clinical and methodological
surgeon population. article that teaches critical appraisal skills. More information
• There needs to be awareness of recent concerns that there about these programs is available at www.facs.org. A series of
may be a bias related to the funding of the study. publications by the Evidence-Based Medicine Working Group
These and other considerations require surgeons to possess also provides further insight into critical literature analysis
fundamental skills related to critical analysis of the medical (http://jamaevidence.com/resource/520).
literature, technology assessment, use of diagnostic testing, The complexities of literature analysis are reflected in a
and clinical decision analysis. Specifics on these skills are prospective study of the value of computed tomography (CT)
further detailed below. in diagnosing appendicitis. This study compared the clinical
likelihood of appendicitis (as estimated by the referring
critical analysis of the medical literature surgeon) to the estimated probability of appendicitis (as
determined by CT) and the pathologic condition (or absence
The medical literature is so expansive that one can keep
thereof), which was then confirmed by operation or recov-
current only with a small fraction of it. Moreover, the poten-
ery.86 The clinical likelihood of appendicitis was assigned to
tial value of a given study is assigned a level of evidence based
one of four categories: (1) definitely appendicitis (80 to 100%
on the study’s methodology. Yet even here there are a number
likelihood), (2) probably appendicitis (60 to 79%), (3) equiv-
of accepted techniques for grading level of evidence that
ocally appendicitis (40 to 59%), and (4) possibly appendicitis
include that from the Centre for Evidence Based Medicine
(20 to 39%). The real-life observed incidence of appendicitis
(CEBM; www.cebm.net/index.aspx?o=1025), the U.S. Pre- in these four categories was 78%, 56%, 33%, and 44%,
ventive Health Task Force, or the Grading of Recommenda- respectively. Thus, CT interpretations had a sensitivity of
tions, Assessment, Development and Evaluation (GRADE) 98%, a specificity of 98%, a positive predictive value of 98%,
system.85 The GRADE Working Group is an international a negative predictive value of 98%, and an accuracy of 98%
collaboration of guideline developers, methodologists, and for either diagnosing or ruling out appendicitis.
clinicians whose recommendations on clinical practice guide- Although these results may seem relatively clear-cut, it is
lines have been increasingly validated in a number of practice possible that the study could have yielded different results
settings. Many guideline organizations and medical societies and reached other conclusions if it had been performed
have endorsed the system and adopted it for their guideline at another institution. For example, the clinical diagnosis of
processes. Further discussion of guidelines is in the section appendicitis is more accurate among men than among women,
on Clinical Guidelines below. and, as a result, the relative value of CT scanning will vary
RCTs are at the high end of all these scales, and meta- according to the gender distribution of the study group. Also,
analyses of RCTs have even higher validity. Still, even RCTs variability in the estimates of the clinical likelihood of appen-
have shortcomings: the reporting methods are not fully stan- dicitis among surgeons in that institution, the availability of
dardized; their stringent inclusion criteria tend to limit their less expensive alternatives to in-hospital observation, and
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use of the emergency department for triage all might lead to fully known. Other providers, fearful of being left behind,
substantially different results. The impact of variability in then follow suit. If the new technology is beneficial, capacity
clinical estimates of appendicitis is reflected by the fact that may grow to the point that it exceeds community’s needs;
in this report, 53% of the patients had appendicitis; in con- if not beneficial, injudicious adoption severely reduces cost-
trast, other studies have shown that only 30% of patients with effectiveness. Although some advocate competition among
an admitting diagnosis of appendicitis eventually underwent providers as a way of restraining health care costs, competi-
appendectomy.87 The impact of the accuracy of CT or tion driven by the technological imperative can contribute
ultrasonography on negative appendectomies also has been to inflationary increases in these same costs. A further con-
reported.88 sideration is the opportunity costs related to differences in
Literature analysis also requires a distinction between efficiency among competing surgical devices.96
relative and absolute risk reduction. The degree of relative Innovations that involve new applications of existing
improvement is a function of the baseline results such that technology are a particular challenge.97 Laparoscopic chole-
a treatment that reduces the incidence of an undesired out- cystectomy is a striking example of an existing technology
come from 5% to 4% and a treatment that reduces it from that was rapidly and widely adopted into a new surgical pro-
50% to 40% both achieve a 20% relative reduction in risk. cedure before its nuances were fully appreciated or mastered.
However, the second treatment achieves a 10-fold greater Although now a relatively safe procedure, the learning curve
absolute risk reduction. In addition, the cost-effectiveness of of laparoscopic cholecystectomy was associated with a number
these two treatments is likely to be very different. This dis- of bile duct injuries; it is conceivable that at least some of
tinction between absolute and relative improvement is an these adverse events could have been avoided had the proce-
important aspect of patient-centeredness in decision making. dure been introduced in a more systematic fashion. Impor-
It is particularly relevant to patients’ willingness to participate tant lessons here come from a study that analyzed the time
in trials of adjuvant cancer therapy. Their decisions for or needed to learn minimally invasive cardiac surgery.98 Fast-
against such therapy may be affected more by the potential learning teams were characterized by members who worked
for absolute benefit than by relative benefit. well together in the past, had gone through the early learning
Interpretation of the literature also needs to consider dis- phase together before adding new members, scheduled
ease staging. Earlier diagnosis may appear to improve long- several of the new procedures close together, discussed each
term survival but actually only identifies the condition for a case in detail beforehand and afterward, and carefully tracked
longer time. This is known as lead-time bias, and it can lead results. Notably, surgeons on the fast-learning teams were
to overestimation of disease prevalence.89 less experienced than those on the slow-learning teams but
Literature assessment skills are also needed to keep pace were more willing to accept input from others on the team.
with patients’ growing access to medical information. There Given this background, there are a number of questions
are tens of thousands of health-related Web sites, and tens of that should be asked whenever a new technology or an
millions of adults find health information online. Patients innovation in surgical care is being considered:
also get information from poorly monitored sources, such as • Has the new technology or innovation been adequately
disease-specific bulletin boards. At least some of this informa- tested for safety and efficacy?
tion will be inaccurate, misleading, out-of-date, incomplete, • Is the new technology or innovation at least as safe and
or unconventional.90 For example a recent study of thyroid effective as existing, proven techniques?
cancer information on the Internet determined that the data • Is the individual proposing to perform the new procedure
pertaining to surgical treatment, in particular, were wanting, fully qualified to do so? This raises issues pertaining to
and only 38% of Web sites were updated in the previous surgeon education, skill acquisition, team identification,
2 years. No predictors of quality were identified.91 Indeed, credentialing, and systems preparation failure.
a study of the methodological quality of economic analyses • Is the new technology effective for the intended purpose?
of surgical procedures concluded that studies of cost- Does the new technology or innovation improve cost-
effectiveness in surgery in the medical literature often do not effectiveness?
meet established criteria.92 • Has allowance been made for appropriate patient selection
and informed consent?
technology assessment
• What is the appropriate role of industry in new technology
The “technological imperative” reflects a prevailing soci- education efforts?
etal attitude that equates the latest with the best and creates • What role do media and public expectations and desires
considerable pressure to acquire the newest equipment and play in driving the application of new technology?
techniques, even before its value is evident. The explosive
growth of technology in recent years has been a particularly use of diagnostic testing
important contributor to the rapid growth of health care Laboratory and imaging studies account for a large share
costs.93,94 Although many technological advances have unde- of health care costs, and there are substantial variations in the
niably improved surgical care, some new technologies do not use of such studies. Improving cost-effectiveness goes beyond
prove to be useful. Accordingly, surgeons need to know how just being aware of a test’s sensitivity (i.e., the ability to iden-
to make decisions about technology acquisition95 and how tify patients with a disease) and specificity (i.e., the ability to
they may contribute to excess capacity and increase health identify patients without a disease). It also depends on the
care costs. The problem begins with providers who succumb prevalence of the disease in the population in question.99 As
to the technological imperative before a technology’s value is an example, if a given test has a 98% sensitivity and a 98%
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specificity and is applied to a group of patients with a disease general practice (where the disease prevalence is low) but
prevalence of 10% (i.e., 10% of them has the disease), the may have high value as a diagnostic tool in a specialty practice
results of 49 of 500 patients will be true positives (500 × 0.98 (where referrals increase the relative prevalence of the dis-
× 0.1) and 9 (500 × 0.02 × 0.9) will be false positives. If this ease). The above calculations illustrate how CEAs can be
same test is applied to a population with a disease prevalence performed on diagnostic tests and screening techniques as
of 1% (a more likely prevalence in the real world), the results well as more traditional comparisons of treatment.
of fewer than five of every 500 patients tested (500 × 0.98 × A specific example of how test utility might affect clinical
0.01) will be true positives and just under 10 (500 × 0.02 × decision making is that of the functional assessment of inci-
0.99) will be false positives. Thus, for any given sensitivity, dental adrenal masses.102 Biochemical testing of patients with
the ratio of false true positives to true positives increases these masses in the absence of concrete signs and symptoms
inversely with disease prevalence. may be of relatively little value. Analyses of many other
If this example was applied to a screening test, which if “routine” preoperative tests also suggest that they may add
positive might then indicate the need for a riskier downstream little value.103,104 Whether a recent increase in testing noted
test, the likelihood is that an increasing number of false posi- among cancer patients has added value is unknown.105
tives would be exposed to the cost and safety risks of the
follow-up test without potential benefit. This illustrates the clinical decision analysis
shortcomings of appropriateness as a measure of quality Clinical decision analysis involves identifying and quantify-
where the relation between health care cost and quality was ing the effect or impact of each option involved in a diagnos-
seen exclusively as positive. Given that complications of tic or therapeutic decision. On the basis of the best estimates
downstream tests are just as likely to occur among patients available, the outcome of each decision acquires a probabil-
with false positives as among patients with true positives, the ity, and each component of the decision tree carries an
net effect of such testing is to decrease the slope of the cost- explicit assumption that allows an appreciation of how spe-
benefit curve and increase the slope of the cost-harm curve. cific factors affect the outcome. Management of penetrating
The differential effects of such testing on these curves alter colon trauma106 and treatment of asymptomatic carotid artery
the relation of quality to cost and produce a negative slope stenosis107 are two examples subject to such analyses. It is
[see Figure 6].100 This is more than just a theoretical relation important to emphasize that physicians should not feel unduly
as there are now data to show that hospitals’ performance on constrained by these clinical decision analyses; depending on
quality of care is not associated with the intensity of their individual patient circumstances, it may be reasonable to give
spending.101 Another key point is that the slope between greater consideration to some options and discount others.
two points represents the incremental changes in cost- Thus, decision trees are not intended as absolute mandates
effectiveness.80 Thus, changes in cost-effectiveness may vary, but rather as tools for reducing uncertainty and thereby
depending on which portion of the curve is considered. increasing cost-effectiveness.108–110
This effect of disease prevalence on the incidence of false Some find the mathematics and lexicon of clinical decision
positives establishes a test’s value or utility and explains why analyses intimidating; others may perceive such analyses as
a test may have relatively little value as a screening test in exemplifying a “cookbook” approach to health care. Markov
modeling involves a set of mutually exclusive states for which
there are transition probabilities of moving from one state to
another. States have a uniform time period, and transition
probabilities remain constant over time, which is often not
a realistic circumstance. Nonetheless, it is clear that formal
clinical decision analysis yields estimates of the importance of
Quality of Care
specific facets of health care that might be difficult to obtain

otherwise.111
practice guidelines⁄critical pathways

Practice guidelines, also known as critical pathways, intend
to indicate the best known processes of care for improving
safety and quality. They seek to standardize medical pro-
cesses, especially in high-volume, high-risk, or complex
1 2 3 4
procedures.112 Such standardization is intended to minimize
the variations in practice that imply consequent variations in
the cost and quality of care. These pathways are increasingly
Cost of Care developed by specialty societies and consensus conferences;
they are also available commercially and through focused
Figure 6 The new concept of quality and cost.99 A positive
publications. Online guidelines are available through the
association between quality and cost still exists in zones 1 and
National Guideline Clearinghouse (NGC) of the AHRQ
2, but the slope of the curve flattens in zone 3 and actually
becomes negative in zone 4. Here, further cost increases are at www.guideline.gov or through evidence-based practice
associated with decreasing quality because increased use of centers. Critical pathways seek to improve cost-effectiveness
sophisticated (albeit riskier) technology in earlier (or even by displaying optimal goals for both patients and providers.
just suspected) stages of disease may result in a flat slope The potential benefit of these pathways can be quantified
(zone 3) or even a negative one (zone 4). using deviation-based cost modeling.113
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These guidelines have been criticized on several accounts: decision support.126 Studies of computerized clinical decision
the evidence and knowledge needed for such guidelines are support systems indicate that practitioners perform better
often lacking114; there may be a lack of consensus regarding with systems that provide automatic prompts than systems
what constitutes “best practice”; guidelines from different that first require system activation. Such studies also find that
sources may be at odds with each other; they may not adhere there is a greater likelihood of better performance in systems
to established methodological standards115,116; they may developed by the authors than in those who were not.127
become quickly outdated117; they have been criticized as Computerized physician order entry has been shown to
embodying an overly simplistic approach to health care; the reduce medication errors128 and facilitate ventilator wean-
focus on quality and efficiency of care is often adopted after ing129 but is not foolproof and can introduce other types of
a decision has been made to admit a patient or perform a errors.130
procedure; and they often do not apply to particular patients
and can be difficult to use in patients with other, more urgent
Strategies for Improving Cost-effectiveness
medical problems. Finally, there are emerging data calling
into question whether published practice guidelines are incor- It is human nature that every surgeon believes that she or
porated adequately into all aspects of day-to-day practice, he is among the best. Yet data often show considerable varia-
particularly with regard to vulnerable populations, such as the tions in resource use, cost, and outcomes among surgeons.
elderly.118,119 Moreover, these variations cannot readily be accounted for by
In summary, use of these guidelines may not automatically differences in disease prevalence or severity. Furthermore,
improve quality. Thus, they should best be understood not as areas with higher frequencies of procedures do not have
rigid rules but rather as ways to codify experiences so that demonstrably better procedure-related health.131,132 As a
others can avoid mistakes. Accordingly, critical pathways result, these variations are thought to be related more to com-
should be considered flexible and should be modified on the munity signatures or physician uncertainty. Curiously, data
basis of experience. on individual surgeon performance are often available to
hospital administrators and insurance companies but not the
coordination of care surgeons themselves. The result has been that strategies for
The growing complexity of health care makes teamwork cost containment and/or quality improvements often origi-
and communication increasingly essential. Lack of coordina- nate at the “blunt” end of a system rather than focusing
tion can increase costs through the duplication of tests and on direct surgeon involvement. Examples of some of these
unnecessary delays; it can also decrease patient satisfaction. strategies are outlined in the following sections.
One study categorized delays as being attributable to test
benchmarking claims data
scheduling (31%), availability of other facilities postdischarge
(18%), physician decision making (13%), discharge planning Insurers use claims data to create hospital and physician
(12%), and surgical scheduling (12%).120 Moreover, poor performance profiles of costs and outcomes. The most favor-
coordination of care is a notable factor in professional liability able data are then used to establish benchmarks. Unfortu-
claims against surgeons.121 nately, such benchmarks have limitations. For example, they
tend to reflect an ideal or exceptional patient population and
electronic medical records may not fully account for severity factors that affect out-
Electronic medical records have been advocated as a means come.133 Adjustments for disease severity are particularly dif-
of expediting the transfer of important information and ficult to make on the basis of claims data because in many
improving the coordination of care. Indeed, a key portion of cases, the requisite data either are not collected or are mis-
the ARRA was the Health Information Technology for Eco- coded.134 Medical record review is effective at accounting for
nomic and Clinical Health Act (HITECH), which includes severity but is more time-consuming and costly. Even with
substantial funding for implementation of “meaningful use” medical record review, the effects of comorbid conditions on
of information technology. The goal is to bring US health cost and outcome can be difficult to sort out. As a result, it
care fully into the Information Age. To date, the effect of is still difficult to account for much of the cost variation.135
introducing information technology (IT) into hospitals and Another limitation of benchmarks is that some differences
practices has been a mixed bag. The VA has estimated in cost and length of stay are related to factors that are not
substantial benefits from its investment,122 but the benefit of under surgeons’ direct control, such as patient age, gender,
electronic medical records at private sector hospitals and in and various cultural, ethnic, or socioeconomic factors extrin-
private practices appears to be marginal. Electronic medical sic to the medical care system.136–138 Selection bias can affect
records are not a panacea, and their benefit in reducing outcome reporting.139 High rates of functional health illiteracy
failure to inform patients of clinically significant outpatient also can adversely affect compliance and thereby outcomes.140
tests was greatest in practices that already had good processes In the end, some efforts to meet benchmark performance
for recording progress notes and test results.123 levels actually have the unintended effect of increasing the
IT is invaluable in improving safety124,125 as it facilitates use risk of adverse outcomes in patients with complicated health
of strategies to reduce medical errors. Such strategies include problems who need more complex care.
tools to improve communication, make information more
readily accessible, acquire key pieces of information for sub- public report cards
sequent process steps, assist with calculations, perform checks Another approach to improving cost-effectiveness has been
in real time, assist with monitoring information, and provide to distribute provider outcomes directly to the public in the
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form of report cards.141 The rationale is that patients armed consistently emphasize that effective change strategies include
with this information will choose providers with better out- reminders, patient-mediated interventions, outreach visits,
comes. Such an effort by the CMS (then the Health Care input from opinion leaders, and multifaceted activities.
Financing Administration, or HCFA) in the 1980s calculated Specific factors associated with an increased probability of
mortality data for individual hospitals using a risk adjustment practice change are peer interaction, commitment to change,
model based on DRGs. Subsequently, however, the CMS and assessment of the results of change.151–153 Successful
acknowledged the flaws in the associated mortality model and activities place substantial emphasis on performance change
stopped releasing these data. Subsequently, the CMS (using rather than simply on learning.154,155 Additional evidence sug-
Medicare data) and some states publicly disclosed provider- gests that improvement in care is more likely to occur with
specific data on the outcomes of cardiac surgery. Although CME activity that is directly linked to processes of care.156
these efforts used more criteria than were available through An underlying tenet from the outset should be that improv-
DRGs alone,142,143 the profiles remained controversial because ing cost-effectiveness is an ongoing process akin to peeling an
they still did not adequately account for all the differences onion: initial steps inevitably lead to deeper analyses. A start-
in case mix and disease severity. Good surgeons operating ing place may be as simple as choosing a particularly bad
on high-risk patients could be adversely affected and less outcome and taking steps to avoid its occurrence or recur-
qualified surgeons operating on low-risk patients (or rence. Simple data charts may reveal changes or patterns in
perhaps even without indications for surgery) inappropriately outcomes or resource consumption that might not otherwise
rewarded. be obvious. On occasion, merely standardizing a process
Although release of these data did lower patient mortality, is sufficient to substantially improve outcomes. With time,
it also might have had the unintended consequence of creat- strategies for optimal practice are likely to emerge. However,
ing incentives to reduce mortality by avoiding high-risk the majority of these efforts are unlikely to eliminate all vari-
patients.144,145 These report cards also appeared to have lim- ations in provider outcomes. For instance, when advances in
ited credibility among cardiovascular specialists.145 Moreover, the care of cystic fibrosis were adopted nationwide, outcomes
the data seemed to be of limited value to the target audience improved for most centers, but some centers still had better
(i.e., patients undergoing cardiac surgery) in that there risk-adjusted outcomes than others.157 Identifying the
were few changes in market share among the involved factors responsible for these remaining differences is a diffi-
institutions. cult but critical undertaking to achieve the next level of
improvement.
The success of provider report cards in prompting quality
improvement depends on several factors.146,147 These include
the strength of the research design and the ease with which Improving Cost-effectiveness in the Operating Room
the public can understand the text and/or the data display.
The operating room is a frequent target for efforts to
Despite their shortcomings, use of report cards has now
improve efficiency. Delays in room turnover are a common
expanded to other specialties. One Web site (www. complaint, the responsibility for which is variously ascribed
healthgrades.com) contains hospital outcomes for cardiac, to nurses, anesthesiologists, and surgeons themselves. Main-
orthopedic, neurologic, pulmonary, and vascular surgery. taining large inventories to satisfy individual surgeon pre-
Transplantation outcomes are also available from the United ferences also contributes to higher costs, and the growth of
Network for Organ Sharing (UNOS) at www.unos.org. minimally invasive surgery has added new dimensions to this
To date, evidence supporting a positive effect from these challenge.158 Key issues in this setting include reusable versus
various strategies remains mixed. A 2002 literature review disposable equipment, variations in the costs of different
concluded that, based on limited evidence, explicit incentives types of equipment used to accomplish the same task, and
placing physicians at financial risk appeared to be effective just-in-time inventory. Major pieces of equipment often are
in reducing resource use.148 However, the empirical evidence duplicated to allow similar cases to be performed simultane-
regarding the effectiveness of bonus payments on physician ously in different rooms, but this duplication often means
resource use was mixed. A more recent review of the value of that the equipment may then be idle for relatively long peri-
publicly reported performance data on effectiveness, safety, ods. More efficient use of such equipment reduces costs, but
and patient-centeredness failed to identify conclusive evi- this requires levels of cooperation and coordination among
dence that such reporting was effective.149 Moreover, only a surgical staff members that heretofore have been hard to
minority of providers appear to be participating in the PQRI achieve.
program. This makes it difficult to assess the effect of the To improve efficiency, surgeons, who have heretofore often
program on overall quality. It is still not clear whether the been steeped in the view that they are the “captain of the
refusal to pay for some “never events” (i.e., shocking medical ship,” must embrace the view that all members of the surgical
errors that should never occur) by Medicare150 and by some team have interdependent goals for quality, safety, and effi-
private insurers will beneficially impact quality and safety. cient use of the operating room. Indeed, the team concept
Given the limitations of these externally initiated efforts requires abandoning the idea that the operating room is
and the remarkable success of physician-initiated efforts staffed by separate surgical, nursing, and anesthesia crews.
noted above, the most difficult step in enhancing cost- Models for achieving greater efficiency have been proposed,
effectiveness may be developing a local willingness to initiate largely based on the airline industry and aerospace travel
the process. Studies of factors associated with practice coordination.159 Successful team efforts have led to cost
change in relation to continuing medical education (CME) reductions in trauma care160,161 and to the development of
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protocols to guide ventilator weaning.162,163 More human idea that many operative decisions are based on opinion
factors research is needed to identify and overcome insidious rather than on evidence.176 This idea is further supported by
barriers to human communication.164–168 data indicating that variations in procedure frequency are
Ambulatory surgical units often are heralded as cost- often procedure specific and inversely related to the degree of
effective. However, potential savings are likely to depend on consensus regarding indications.177 Procedures with highly
existing operating room capacity and on specific payer specific indications (e.g., repair of a fractured hip or appen-
issues.169 By taking less complex cases away from the hospital, dectomy) often show minimal frequency variation, whereas
there may be fewer cases on which the hospital can amortize procedures with seemingly less definitive indications (e.g.,
fixed costs. Another reason ambulatory surgical units may carotid endarterectomy, hysterectomy, and coronary angio-
cost less is that they do not have to maintain standby capabil- graphy) often show a great deal of variation.178 Variations in
ity to deal with emergencies. As more surgical procedures are frequency also can have downstream effects179; one example
performed on an outpatient basis, there is a growing tension of this is the relatively close relation between the intensity of
between hospitals and surgeons over the facilities used for local diagnostic testing and the subsequent performance of
such procedures. Independent facilities may be able to elimi- invasive cardiac procedures.180
nate some costs, but they also contribute to excess capacity One issue of debate in interpreting these geographic fre-
and probably will not reduce health costs in the long run. quency variations is whether high rates of use are too high or
This means that sooner or later, surgeons and hospitals low rates are too low. The association between variation and
will have to address their common interests.170 Eliminating the ratio of hospital beds to population has raised concerns
some of the barriers to gainsharing is likely to facilitate such that low frequency of use may reflect restricted access to
efforts. care.181 In one study where patients in the aggregate received
about half the recommended level of care,182 a lack of access
Ethical and Legal Concerns to health services did not appear to be the underlying
problem. To date, efforts to find evidence supporting other
Efforts to improve cost-effectiveness are often seen as forc-
possible explanations for these variations (e.g., differences in
ing health professionals to face conflicts among the needs of
disease incidence and in the appropriateness of use) have not
individual patients, the interests of society as a whole, and
been successful.183
third parties. Physicians are no strangers to such potential
Although some might attribute variations in frequency to
conflicts. Indeed, the vast majority of physicians successfully
the potential conflict of interest inherent in a fee-for-service
avoid the temptations inherent in fee-for-service care. The
system, similar variations in procedure frequency are known
managed care era raised some concerns about conflicts
to occur among VA medical care facilities,184 as well as in
between corporate and patient interests, but these concerns
countries that do not have fee-for-service reimbursement.
proved to have relatively little foundation and have since
The current belief is that the high use rates are too high
abated. Some have suggested that evidence-based data
derived from large populations may not readily apply to indi- and is supported by findings that patients from areas with
vidual patients, but the rationale for this view is not clear.23 widely disparate use rates have comparable health status.
Thus, physicians should be able to represent both an These findings have led to the conclusion that “marked vari-
individual patient’s viewpoint and a societal perspective. ability in surgical practices and presumably in surgical judg-
The high costs of the terminally ill frequently generate con- ment and philosophy must be considered to reflect absent or
troversy, particularly among patients who require intensive inadequate data by which to evaluate surgical treatment.”185
care. To mitigate the dilemmas that may face physicians in This was supported by a study in the 1970s that estimated
making life-ending decisions, increasing emphasis is being that only about 15% of common medical practices had docu-
placed on patient self-determination. Even the best efforts of mented foundations in medical research.186 Although this
physicians and institutions to comply with patient or family does not necessarily mean that only 15% of care is effective,
choices in the setting of terminal illness may not substantially it does raise concerns about the lack of hard evidence for
reduce costs or improve outcomes.171 Actual savings may be most care. A more recent estimate is that one third of current
small.172 health care spending may be wasteful.187
A related issue is whether these variations should be used
to formulate public policy.188,189 Some discount these varia-
Quality in the Aggregate: Small Geographic Area tions by arguing that they are not risk adjusted for differences
Variation among patients and cannot predict which will be better at
Earlier in this chapter, it was noted that physician decisions saving lives. Others acknowledge that the Dartmouth analy-
powerfully impact a large proportion of health care costs. The ses are not perfect but are better than other existing methods.
traditional approach has been to honor physicians’ deference Both views agree that these variations should not be used as
in such decisions. An increasing challenge to physicians’ the sole method to set hospital payment rates and that end-
authority as an arbiter of quality is the long recognized, poorly of-life data used for these analyses provide only limited insight
explained variation in the frequency of surgical procedures into the overall quality of care.
among small geographic areas.173–175 These variations have The point is that in addition to misuse, overuse and under-
been intensively studied and found to remain relatively con- use also can reflect quality. Although there has been some
stant over time. The result is that some communities acquire improvement in the adoption of processes of proven value
distinct “surgical signatures”—a finding that supports the (e.g., the optimal timing and duration of perioperative
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antibiotics), overall progress has been disappointingly increasing burden of proof as to the quality of care. More-
slow.190 over, health care payers are likely to address substantial
variations in frequency and cost of care by using apparent
similarities in quality to contract for less expensive care. How
Reassessing the Relationship between Cost and Quality
this tension will be resolved remains to be determined. One
in Health Care
view is that the pressure on physicians will be based on an
This chapter sought to emphasize that health care costs do assumption by payers that physicians will not knowingly or
not necessarily have to have a direct relation to quality (i.e., willingly sacrifice quality. Indeed, some believe that value-
better care does not need to be more expensive). Indeed, based competition may spark physicians to provide care that
higher-quality health care can cost less. Unfortunately, US exceeds patients’ expectations.203,204
physicians are more likely than physicians in other countries In response, physicians need to remain cognizant of a pre-
to report that interventions in patient care geared to cost con- dominant theme of this chapter: physician-led organizations
trol were threatening the quality of care they could provide appear to be more successful in improving the cost-
their patients.191 Thus, recognizing that quality does not have effectiveness of care than external policies. Practicing sur-
to be sacrificed with reductions in cost is essential to over- geons, who are at the “sharp” end of the system, will need to
coming fears that health care reform will adversely affect access data on their performance and participate in the devel-
quality. In this context, it is likely to take time for evidence opment of better outcome measures. These metrics then can
supporting higher-quality/lower-cost care to evolve. Hopes be used to improve performance by redesigning processes of
that such evidence might come quickly have been dashed care.205 Physicians need to acknowledge variations in inter-
by reports showing that hospital P4P measures were not vention rates and outcomes and to increasingly make medical
strongly associated with better outcomes192,193 or produced decisions that are evidence based. They are the best equipped
only modest reductions in mortality.194 On the positive side, participants in the health care system to identify cost-effective
there are studies that show an inverse relation between care because they have the necessary knowledge and skill set.
volume and cost.195,196 Thus, high volume might improve If physicians can respond constructively to these challenges,
cost-effectiveness by affecting both the numerator and the rather than simply ignore or dismiss them, they stand a
denominator of the equation. good chance of recapturing much of their lost stature and
Although it is clear that more data are needed with regard autonomy.
to the relation between cost and quality in health care, an In this context, the fee-for-service payment system may be
activity likely to bear fruit is reducing costs by reducing the increasingly criticized because it lacks incentives that reim-
complications of surgical care. A useful approach here may burse physicians based on quality. It seems likely, therefore,
be to consider the added costs of a complication in a given that new payment systems will emerge that are more closely
patient with respect to the frequency of that complication in linked to quality than the current P4P programs. In one such
the entire population undergoing a given treatment.197 The approach, the Geisinger Health System established incentives
goal is to establish priorities for quality improvement efforts through a warranty program for elective cardiac surgery in
to prevent complications based on both the incidence of the which there is no added reimbursement for managing com-
complication and its contribution to resource use.198 plications occurring within the first 90 days after surgery.
Reassessing the relation between cost and quality may also Geisinger was able to adopt this approach because many of
suffer if there is a relative lack of emphasis on the latter by its patients were also insured through the Geisinger system.
hospital boards.199 Similarly, a national survey found that This eliminated many of the conflicts that might otherwise be
39% of managed care organizations were moderately or present with third-party payers. In creating this program,
largely influenced in their initial physician selection by previ- Geisinger embedded best practices within their processes of
ous patterns of costs or use, and nearly 70% profiled their care, and the program’s initial success is largely attributed to
member physicians.200 On the other hand, at least one HMO high compliance rates.206 Interestingly, Geisinger patients
recognized that practices with high scores on service and insured by other payers also benefit from this system.207
quality indicators attracted significantly more new enrollees Although such changes may seem daunting, surgeons
than practices with lower scores. A challenge in considering should recognize that the growing interest in assessing perfor-
both cost and quality is that potential benefits may not occur mance is not new. In the early 1900s, Ernest Codman, a
concurrently. Thus, cost savings may appear before quality Boston surgeon, crusaded for hospitals and surgeons to pub-
improvement, or quality might improve before long-term cost licize their results, yet his efforts often met with disinterest,
savings are evident. defensiveness, or outright opposition.208 The current call to
assess surgeon performance is clearly here to stay. If physi-
cians respond dismissively or defensively (e.g., explaining
The Future variations in outcomes by invoking care for sicker patients),
All indications are that the efforts to reduce the cost and/or they may miss an important opportunity to reestablish their
improve the quality of the US health care system will remain authority on quality. Surgeons who preemptively familiarize
strong for the foreseeable future. As an example, large employ- themselves with their own outcomes will be better positioned
ers increasingly provide incentives to use “high-performance” to participate in efforts to improve the cost-effectiveness of
health provider networks.201 Physicians may dispute the valid- surgical care.
ity of cost profiling202 and other challenges to their authority
as arbiters of quality; regardless, they will have to bear an Financial Disclosures: None Reported
03/11
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8 HEALTH CARE ECONOMICS: THE

BROADER CONTEXT
Linda G. Lesky, MD, MA, Robert S. Rhodes, MD, FACS, and Charles L. Rice, MD, FACS*
In a companion chapter [search ACS Surgery for information 1. In spending more on health care, society spends less on
on cost-effective nonemergency surgical care], we review the other goods and services—a process referred to as dis-
principles of cost-effective surgical care and discuss the placement. Thus, health care consumes resources that
implications of such principles for health care spending. might otherwise have been allocated to services such as
Our primary focus there is on the interaction between education or public safety.
an individual surgeon and an individual patient. In this 2. The health care sector of the economy is so large—not
chapter, we explore some of the issues surrounding health only in terms of the amounts of money involved but
care spending on a larger (i.e., national) scale. It is important also in terms of the number of people employed—that
for surgeons to have a broad understanding of these short-term changes in its growth rate (in either direction)
issues, in particular because such concerns are increasingly necessarily exert substantial and painful economic effects.
becoming the subject of political debate. Moreover, the potential magnitude of these effects
thwarts political consideration of potential changes to the
system.
US Health Care Expenditures and Health Outcomes 3. As costs increase, voluntary participation by employers
In 2009, US national health expenditures amounted to in the provision of health insurance to employees and
$2.5 trillion (approximately 17.6% of the gross domestic retirees comes under increasing pressure, with the result
product [GDP]).1 According to data from the World Health that employers either shift more and more of the costs
Organization, if the current level of US health care spending of insurance to employees or decide to stop providing
were viewed as a separate economy, it would be the seventh health insurance altogether. Between 2001 and 2006, the
largest economy in the world, nearly equal to the GDPs of contribution of households to health care expenditures
France and the United Kingdom.2 This level of spending increased by more than 35%.3
translates into a per capita expenditure of $8,086, which is 4. A specific concern also relates to the extent to which
more than double the average of other Organisation for spending on Medicare threatens the long-term solvency
Economic Co-operation and Development (OECD) countries of the US government. In 2009, Medicare spending grew
and which surpasses the per capita expenditure of the next 7.9% to $502.3 billion. Absent policy change, the CBO
highest-spending country, Switzerland, by more than 30%. estimates that Medicare spending will grow at an aver-
Between 1950 and 2001, US per capita spending on health age of 7% each year from 2010 to 2018, rising to $879
care in constant dollars increased more than 11-fold. billion annually and 4% of GDP. The rate of growth
Since the end of World War II, the growth rate of health of Medicare spending over the long term is predicted to
care spending has exceeded the overall growth of the econ- exceed the rate of growth of federal revenues and the
omy. Although the rate of growth of per capita health care overall economy,5 which most believe is unsustainable.
spending has slowed over the past 4 years, there is reason As a result, discussions of health care reform have
to believe that this slowing trend will be short-lived.3 Over focused not only on reducing the number of uninsured
the past 30 years, total national spending on health care but also on “bending the health care cost curve” to
has more than doubled as a share of GDP. According to reduce the rate of growth of health care spending (see
Congressional Budget Office (CBO) projections, total health below).
care spending will reach $4 trillion by 2015, and in the Others dismiss these concerns and argue that the health
absence of a significant change in the long-term trends, the care share of GDP has no natural limit as long as health care
share of GDP will double again by 2035, to 31% of GDP. is more highly valued than the goods and services that it
Only a small percentage of this spending growth can be displaces.6 Proponents of this viewpoint distinguish between
attributed to general inflation, growth in the size of the spending that is affordable (i.e., sustainable) and spending
population, and changes in the age distribution of the popu- that the country is unwilling to sustain.
lation.4 The majority is projected to be attributable to rising The proponents of these two perspectives agree that
costs of care and increasing amounts of care. increases in spending should reflect the increased value
Economists differ on the extent to which such spending placed on health care services relative to non–health care
represents a risk to the overall economic well-being of the goods and services that are forgone. There is substantial
United States. Those who are concerned about both the
amount that is spent on health care and the rate at which
this amount is growing cite a number of concerns:
* The views expressed are those of the authors and do not
reflect the official policy or position of the Uniformed Services
University of the Health Sciences, the Department of Defense,
Financial disclosure information is located at the end of this chapter the United States Government, or the American Board of
before the references. Surgery.

02/12
elem cont prac 8 health care economics: the broader context — 2
evidence, however, that increased health care expenditures

are not invariably associated with demonstrable improve- Supply: Qs= fs(P)
ments in health outcomes. Although the United States
spends more on health care than any other OECD country,
its health status rankings do not compare well with those of
Price
other industrialized countries. OECD data indicate that of
the 30 OECD countries, the United States has the highest
rate of obesity and ranks 15th in infant mortality, 13th Pe
in cancer mortality, 21st in mortality from ischemic heart
disease, and 15th in life expectancy at 65 years.7 An analysis
of mortality from causes that were potentially avoidable Demand: Qd= fd(P)
with timely and effective health care in 19 industrialized
countries found that the United States ranked last in the Qe
level of decline in these deaths between 1997 and 2002.8 Quantity
Within the United States, several major studies have
shown that patients treated in higher-spending regions do Market Equilibrium
not have either better health outcomes or greater satisfaction Qe=Qd=Qs
with their care than patients treated in lower-spending
regions.9 One such study reported that the differences in Figure 1 The model of supply and demand determines the quantity
spending were largely attributable to the higher frequency produced at a given price. Illustrated here is the application of this
of physician visits, the tendency to consult specialists more model to health care. Persons who fall below the equilibrium point on
readily, the ordering of more tests, the performance of more the demand curve cannot afford health care at the market price and
must either do without care or seek it in the safety-net health care
minor procedures, and the more extensive use of hospital
system. P = price; Q = quantity; Qd (quantity demanded) = fd(P) (the
and intensive care services in the higher-spending regions. demand equation, which includes price); Qs (quantity supplied) = fs(P)
The authors could find no evidence that these types of (the supply equation, which includes price).
increased use resulted in improved survival, better func-
tional status, or enhanced satisfaction with care. These
findings have profound implications for efforts aimed at
containing the further growth of health care spending. amount of a good or service that the market is willing
and able to purchase at a given price. Similarly, the supply
curve represents the total quantity of a good or service that
Discrepancy between Costs and Outcomes suppliers are willing to produce at a given price. The point
Many factors influence the cost of health care and the where the two curves intersect represents the equilibrium
health outcomes of a population. The increase in the size price and quantity of the good or service.
of the uninsured population is often cited as contributing This equilibrium between supply and demand gives
to poorer health outcomes of US residents and the slow markets their most valued attributes. A competitive market
decline in the US amenable mortality.8 Wider availability of price forces producers to satisfy consumers’ demands for a
advanced technology, an increasingly older population, quality product with the least-cost methods of production.
newer and more expensive prescription drugs, inefficiencies Markets also ensure the most efficient and least wasteful
in health care delivery, and the rising costs of medical allocation of resources in that only the quantity demanded
malpractice insurance are all contributors to rising health at a specific price is produced. Markets assume, however,
care costs. However, the single factor that distinguishes that consumers who cannot afford to pay the market price
health care in the United States from that in other developed either will find a less expensive substitute product or will
countries is the market-based delivery system that charac- do without. They also assume that consumers can be
terizes US health care. With the exception of the aging of knowledgeable enough about a product to assess its quality
the population, the health care market influences all of the and appropriateness for their needs. Finally, markets exist
factors that contribute to the cost of health care and health to maximize both the utility of consumers through the
care outcomes in the United States. A simple review of how purchase of goods and services and the profits of suppliers.
the health care market functions reveals why a market-based Research and the development of innovative products are
health care delivery system contributes to rising costs and driven by the opportunity to be the first to enter a market
poor health outcomes. with a new or improved product and thus reap maximum
profits.
model of supply and demand A key question is whether the features that are normally
The model of supply and demand is a useful tool for associated with well-functioning markets in other areas
understanding the behavior of buyers and sellers in a are also applicable to health care. Further analysis of the
market [see Figure 1]. With price on the vertical axis and supply-and-demand model as it relates to the health care
quantity of a particular good or service on the horizontal market may shed some light on this question.
axis, the demand curve represents the total demand by all
consumers for that good or service. The downward slope of affordability of health care
this curve reveals that as price decreases, consumers are Despite the massive growth of employer-sponsored
willing to purchase more. The demand curve also shows the health insurance, the universal coverage of the Medicare
02/12
population over the age of 65, the addition of more than 1 setting, not only do physicians function as suppliers of
million disabled persons under Medicare, and widespread health care services, but they also play a major role in deter-
coverage of the poor under Medicaid, more than 45 million mining the level of demand for these services. For example,
US citizens (almost one of every six) have no health physicians advise patients about the frequency of office
insurance coverage. visits, the types of diagnostic tests to undergo, and the
Health insurance, in and of itself, leads to distortions in treatment or treatments that may be needed. Asymmetry
the market because consumers of health care do not see the of knowledge between patients and their physicians forces
actual price being paid for health care goods and services. patients to rely on this advice for health care decisions.
This creates a situation referred to as moral hazard. This Substantial evidence exists to support the notion that
term originated with the purchase of fire insurance in the physicians do increase the demand for health care. Supply-
19th century, when it was recognized that the owner of a and-demand theory dictates that the entry of more sellers
property that was insured might have an incentive to incur into a market should result in increased competition, lower
a loss either by deliberately setting a fire (a moral hazard)
prices, and lower total costs for goods and services. Yet
or by not taking steps to reduce the likelihood of a fire.
in health care, it has been demonstrated repeatedly that
The implication of the moral hazard effect for health care
an increased supply of health care services results in an
spending is that those who are insured (or more generously
increased demand for services and an increase in costs.
insured) will tend to use more health services without
Initial concerns about this unusual market behavior stemmed
regard to cost. Insurers seek to reduce the extent of the
moral hazard problem by increasing the coinsurance and from the observation that in geographic areas that were
making the consumer pay a larger share of the full cost. similar with respect to demographics, socioeconomic char-
A more significant economic and ethical concern centers acteristics, and burden of disease, hospital use rates were
on those persons with no health insurance coverage, who higher in areas with a greater supply of hospital beds.14 In
fall below the equilibrium point on the demand curve [see a study of the supply of surgeons and the demand for
Figure 1]. In a well-functioning market, it is expected that surgery, it was estimated that a 10% increase in the supply
those who cannot afford to pay the market price for a good of surgeons, as measured by the surgeon-to-population
or service will do without, but our society seems unwilling ratio, led to a 3% increase in the per capita surgery rate.15
to allow this when it comes to health care. The result is a A number of other studies have addressed the effect of
patchwork of substitute care that serves the uninsured and physician ownership on health care use rates. In a study
underinsured. The so-called safety-net health care system examining the issue of physician ownership of ancillary
comprises hospitals, community health centers, “free” clin- services, 50% more visits were ordered at physician-owned
ics, and emergency departments. The Institute of Medicine physical therapy clinics in Florida than were ordered at clin-
estimated that in 2001, the safety-net health care system cost ics that received no referrals from owners.16 The authors of
$99 billion in direct services and $65 to $130 billion in lost the study could find no discernible difference in the quality
productivity.10 Under current arrangements, the costs of this of care across ownership structures. An analysis of more
care are built into the prices charged to those who do have than 65,000 insurance claims found that doctors who owned
the ability to pay. A 1992 analysis of the distribution of the imaging machines ordered more than four times more imag-
health care financing burden associated with the US health ing studies than those who referred to independent radiolo-
care system showed that the greatest financial burden fell gists.17 Finally, in a study addressing the impact of the 1990
on those in the middle class: the fourth to seventh income Medicare physician reimbursement changes on thoracic
deciles devoted approximately 12% of their cash income surgeons who were predicted to lose substantial income
to finance health care, whereas the highest income decile if surgical volumes remained unchanged, the Medicare
devoted about 8%.11
fee cuts led to volume increases in both Medicare and
Despite this degree of public spending, the safety-net
private-pay patients, to the point where 70% of the fee
health care system does not ensure continuity of care or
loss from Medicare was recaptured through higher patient
access to all needed care, and as a consequence, the unin-
volume.18
sured have poorer health outcomes than those with con-
These findings make supplier-induced demand (SID) one
tinuous health insurance coverage.12 Not only does this
safety-net system cost a great deal and result in suboptimal of the most controversial issues in health economics. If SID
health outcomes for the population it serves, but there is also exists to a substantial extent, economic analysis would then
increasing evidence that in the United States, all patients suggest that competitive markets are useless as a means
seeking emergency care for critical conditions wait longer of managing health care delivery and reducing costs [see
for needed attention as a consequence of overcrowding and Figure 2]. Although numerous other hypotheses have been
the use of emergency departments by uninsured patients offered to explain the empirical findings of the increases
who lack a regular source of health care.13 The structure of in demand associated with increased supply, none disprove
any market assumes that there are those who cannot or will SID.
not pay for the good or service at the market price. As long Physicians find the SID hypothesis disturbing because it
as a market structure for health care delivery is maintained, suggests that they manipulate the demand for health care to
there will be those who will not have access to appropriate advance their own economic interests. Most physicians are
health care. aware of the relation between service volume and income,
but various other factors (e.g., rapidly evolving technolo-
asymmetrical knowledge gies, medical uncertainties at all levels of care, and defensive
Consumers rely heavily on the advice of their physicians practices to avoid the risk of litigation) make it impossible
for guidance regarding diagnosis and treatment. In this to determine the exact impact of SID. The concept of target
02/12
Supply = Marginal Cost

S1 S2
Pm
2 1
Price
Price
Pc
P3
P1 D2 Demand
P2 Marginal Revenue
D1
Qm Qc
Quantity
Q1 Q2 Q3
Physician Services Figure 3 Monopolies set prices to maximize profits by equating the
marginal cost of production and the marginal revenue. This process
Figure 2 Given an initial supply and demand for physician ser- results in higher prices and lower levels of production than would be
vices at S1 and D1, assume that the number of physicians increases found in a competitive market. Pc = competitive price; Pm = monopoly
(arrow 1), thereby shifting the supply curve to the right. In normal price; Qc = competitive quantity; Qm = monopoly quantity.
economic conditions, the quantity of physician services would
increase (to Q2), and the price would fall (to P2). Empirical evidence,
however, suggests that the demand for services also increases, shift-
ing the demand curve to D2 (arrow 2) and resulting in an increase in spending).19 Similarly, expenditures on prescription drugs
both price (P3) and quantity (Q3). D = demand; P = price; Q = quantity; doubled between 1990 and 2000 and are expected to account
S = supply; subscripts 1, 2, and 3 reflect the order in which quantity for one seventh of total health care costs by 2012 [see
and price change in response to a change in supply (arrow 1) followed Table 1].20 Moreover, whereas consumers pay less than 3% of
by a change in demand (arrow 2). hospital service costs out of their own pockets, they pay
about 32% of pharmaceutical costs.
One of the factors contributing to these increased costs
incomes is certainly known to be a factor in other arenas of is the presence of legal restrictions, in the form of patents
the economy. Regardless of the true extent of SID’s impact afforded to pharmaceuticals and medical devices that pre-
on the cost of health care, it is the market-based structure of vent other firms from entering the market with a similar
health care that creates incentives for physicians to influence product. Patents give pharmaceutical companies and device
the demand for health care. manufacturers legal monopolies for a period of 20 years.
The purpose of this law, as expressed in Article 1, Section 8
markets, monopolies, new drugs, and technology of the US Constitution, is “to promote the progress of
The market is uniquely effective in fostering innovation science and the useful arts by securing for limited times to
and technological advances. Firms compete to introduce inventors the exclusive right to their respective discoveries.”
new products, and in doing so, they gain monopoly power In addition, at the end of the patent period, pharmaceutical
and enhance profits through increased market share and companies can switch their products from prescription
monopoly pricing. Unlike competitive markets, where supply to over-the-counter status and gain 3 additional years of
and demand determine the price of a good or service, market exclusivity if they can demonstrate that any misuse
monopolies set their own price. The profit-maximizing price of a drug will not endanger a consumer’s health. During
is achieved by equating the marginal cost of producing one these protected periods, companies work to establish brand
additional unit to the marginal revenue from selling one loyalty among physicians and consumers.
additional unit [see Figure 3]. This results in a higher price Pharmaceutical companies and device manufacturers
and a lower level of production than would be achieved argue that the costs of research, development, and testing
in a competitive market. Monopoly profits are typically would be impossible to recoup without these legal
short-lived because as more suppliers enter the market,
the marginal revenue curve shifts so that it eventually
equals the demand curve, thereby reducing the price and
increasing the quantity supplied. Table 1 Major Components of Health Spending,
In virtually every other sector of the economy, the 1999–2009
introduction of new technology tends to reduce the cost of a 1990 1993 1997 2000 2003 2006 2009
particular good or service. Health care is one of the few
Hospital care 9.6 8.0 3.6 5.6 7.5 7.0 5.1
exceptions to this general rule. A 2003 analysis of the rela-
tion between the availability of advanced technologies and Physician and 12.8 8.5 4.6 7.0 8.5 5.9 4.0
clinical services
health care spending found that for certain technologies
(e.g., diagnostic imaging, cardiac catheterization facilities, Prescription 12.8 8.2 11.1 15.3 10.5 8.5 5.3
drugs
and intensive care facilities), increased availability was
often accompanied by increased use (and hence increased Adapted from Martin A et al.38
02/12
protections. Others, however, are concerned that companies it has on other markets, and improvements in price trans-
are using their monopoly power to raise prices, restrict parency may be less effective. So far, preliminary data from
output, and earn excessive profits. Since 1980, the rate of New Hamphire26 and California22 suggest that this is the
growth in drug prices has exceeded consumer price inflation case. Neither state demonstrated any effect of hospital price
rates. In addition, the profitability of drug firms has been transparency 2 years after initiation.
consistently higher than that of the manufacturing industry
adminstrative costs
average.21
Again, pharmaceutical companies argue that the high In general economic terms, markets function best and
rate of profit observed in the industry is justified by the society benefits most when multiple suppliers compete
significant risk and cost of innovations. However, not all to produce the highest-quality product at the lowest cost.
innovations are costly to the company, risky to investors, With health care, however, this process has resulted in a
or beneficial to society. One of the most notable examples bewildering array of insurers and contracts. Virtually every
of profiteering by a pharmaceutical company was the intro- physician in the United States has had to expend consider-
duction of the “new little purple pill.” The original purple able time and effort dealing with complicated, arcane, and
pill, Prilosec (a trade name for omeprazole), was introduced apparently deliberately confusing rules and requirements.
in 1989 by AstraZeneca. In 2000, it was the best-selling drug The repeal in 1986 of laws that sought to regulate the
in the world, with over $6 billion in sales per year. When the growth of the health care industry resulted in an abandon-
patent was due to expire in 2001, the company applied for a ment of all efforts to constrain market-based entrepreneur-
patent for the “new little purple pill,” Nexium (esomepra- ship in health care. Not-for-profit hospitals and health
zole magnesium), which was simply a chemical isomer of maintenance organizations converted to for-profit status.
Prilosec. Despite the Food and Drug Administration’s deter- Consolidation of the insurance industry reduced the
mination that Nexium offered no significant clinical advance number of plans available in a market area, thus affording
insurers monopoly power and leading to higher prices. The
over Prilosec, a patent was awarded. The company launched
cost of administering private health insurance in the United
a very successful marketing campaign, and in 2006, sales
States reached $143 billion in 2005.27 For-profit insurance
of Nexium exceeded $5 billion. The price of Prilosec for
companies have reaped impressive profits and gains in stock
consumers is $30 per month, whereas that of Nexium is $200
value, as well as significant political power.
per month. The current market-based model of new product
As a reaction to this state of affairs, some critics of the
development accompanied by long periods of monopoly
US system have asserted that the adoption of a simplified,
protection can be predicted to increase the costs of health
Canadian-style, single-payer health insurance system would
care substantially.
yield large savings in administrative costs, which could
price transparency then be used to expand coverage to those who are currently
uninsured. A 2003 study compared administrative health
For most goods and services, price transparency leads
care costs in the United States with those in Canada.28 In
to lower and more uniform prices, a view consistent with
1999, per capita health administration costs amounted to
standard economic theory. Currently, there is considerable $1,059 in the United States (for a total cost of $294 billion),
variation in prices for similar procedures. For example, a in contrast to $307 in Canada [see Table 2]. The authors
comprehensive metabolic panel costs $97 at San Francisco arrived at these figures by analyzing data from govern-
General Hospital and $1,733 at Doctors Hospital in Modesto, ments, hospitals, insurance companies, and physicians. They
California. A single Percocet tablet costs $6.68 at San Fran- argued that much of the difference between the two coun-
cisco General, $15.00 at UC Davis in Sacramento, and $35.50 tries was accounted for by the multiple sources of health
at Doctors Hospital in Modesto.22 If evidence from other coverage in the United States, as opposed to the single
markets could be applied to health care, then reforms that source in the Canadian system. This analysis has not been
increase transparency should result in lower and more uni- replicated by others, and an accompanying editorial ques-
form prices.23,24 However, there are reasons to be concerned tioned the methodology used.29 Nevertheless, the author of
that greater price transparency would not have the desired the editorial did agree that the current system is “an admin-
effect. Health care differs from other consumer goods in istrative monstrosity, a truly bizarre mélange of thousands
ways that make it difficult to apply empirical evidence from of payers with payment systems that differ for no socially
other markets. For one, patients with insurance pay little of beneficial reason.”
the cost of their medical care and are therefore less price
sensitive. In addition, there is evidence to suggest that price the patient protection and affordable care act
acts as a proxy for quality in health care, with many believ- and other legislative initiatives
ing that higher-cost care is better care.25 Second, physicians The most significant impact of the Patient Protection and
typically make choices for patients, such as what tests to Affordable Care Act (ACA) is that an estimated 32 million
order, whether and where to hospitalize, and which special- Americans will gain insurance coverage by 2019. The health
ists to recommend. Patients are unlikely to challenge this reform law mandates that currently uninsured Americans
advice to save a few dollars. Finally, transparency could obtain health insurance. Medicaid eligibility is expanded
create an incentive to raise prices. Hospitals that charge and substantial subsidies are provided to make insurance
different payer types different prices would be inclined to more affordable for those ineligible for public insurance
publish the higher price. For these reasons, pricing may programs. Currently, the uninsured rely heavily on the
have a more muted effect on the health care market than safety-net health care system, which is associated with
02/12
Table 2 Administrative Costs of Health Care: United States versus Canada

Administrative Cost United States Canada
Category
Total Cost ($ billion) Per Capita Cost ($) Total Cost ($ billion) Per Capita Cost ($)
Insurance overhead 72 259 1.43 47
Employer costs 15.9 57 0.257 8
Hospital administration 87.6 315 3.1 103
Practitioners 89.9 324 3.3 107
Total 294.3 1,059 9 307
higher costs and poorer health outcomes. If previous trends appointment to see an internist in Massachusetts was
hold, the newly insured will enjoy better health outcomes, 31 days in 2008, up from 17 days in 2005.34 Patients without
but the cost implications of health care reform are less access to primary care will be forced to continue to seek
clear. care at high-cost, poor-continuity sites, such as emergency
Both the Centers for Medicaid & Medicare Services (CMS) departments. General surgery also faces shortages that are
and the CBO have projected that health care reform will result likely to be exacerbated by health care reform. The overall
in an expansion of national health care expenditures.30,31 The number of general surgeons has declined by 26% over the
ACA includes a number of mechanisms to offset the new past 25 years.35 Rural areas are most acutely affected. The
spending, including a reduction in the update factor for income gap between generalist and subspecialist careers
Medicare hospital reimbursement, a reduction in the over- and rising medical student debt account for most of the
payment to Medicare Advantage insurers, an assessment decline in medical student interest in both of these generalist
on employers whose employees use subsidies rather than careers.
employer-sponsored insurance, and an increase in the The ACA and the American Recovery and Reinvestment
Medicare tax for high-income families. The CBO estimates Act of 2009 include several provisions aimed at highlighting
that the revenue increases will exceed the increased costs the importance of primary care and general surgery. The
and ultimately reduce the federal deficit by more than economic stimulus package provided about $500 million
$100 billion in the first decade and more than $1 trillion in for training programs in health professions, including
the second decade.22 However, critics argue that although $300 million for expanding the National Health Service
these measures may pay for health care reform, they do Corps, a program that offers scholarships and loan repay-
nothing to rein in the growth of health care costs. Health ment for health professionals who agree to serve in shortage
care spending in the United States already accounts for 17% areas for 2 to 5 years. The ACA includes additional funding
of GDP. At the current rate of growth, it will reach 38% to support training of primary care providers, redistributes
of GDP by 2075. The ACA includes a variety of provisions approximately 900 unfilled residency positions into primary
intended to lower the rate of cost growth (bend the health care and general surgery, provides a 10% bonus under
care cost curve), including physician payment reform, incen- the Medicare fee schedule for primary care providers, and
tives to coordinate care for patients with chronic conditions, requires that states increase Medicaid payment to Medicare
increased access to electronic health records, and funding rates for primary care services. Notably missing in the provi-
for comparative effectiveness research, but there is currently sions is a lifting of the cap on the total number of residency
little evidence that any of these measures actually work. positions, which were frozen by the Balanced Budget
A second implication of increased access to health insur- Amendment of 1997. In the absence of an expansion of total
ance is the need for a larger primary care workforce. Numer- residency training positions, it is not clear that the provi-
ous studies have demonstrated that access to primary care sions will make a significant dent in the projected primary
is associated with improved outcomes at reduced cost. care and general surgery shortages.
Although primary care physicians provide 57% of all patient
visits, they represent only 35% of the US physician work-
Implications for Surgeons
force.32 Even without the new demands created by health
care reform, the aging of the population and the increasing Market-based health care has not only increased the costs
proportion of the population with a chronic medical condi- of care but has also changed the professional behavior of
tion have strained the capacity of the primary care work- physicians. Organized medicine’s priorities place the finan-
force. The 2008 Medicare Payment Advisory Commission cial interests of physicians above access to and quality of
(MedPAC) beneficiary survey found that 28% of beneficia- care. Hospitals invest in programs that promise a high
ries without a primary care physician reported a problem return on investment with less regard for evidence of benefit
finding one.33 This represented a 17% increase from 2006. or greater societal need. The fragmentation of the profession
The number of beneficiaries reporting a problem finding a into over 130 specialties and subspecialties has resulted
new specialist declined. The Massachusetts experience with in competition among disciplines, further promoting self-
expanded health insurance coverage illustrates the discon- interest over best practices. In this environment and despite
nection between access to health insurance and access to advances in evidence-based medicine, individual physicians
care. The average wait time for a new patient to obtain an are equally tempted to place their own interests above those
02/12
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02/12
ELEMENTS OF CONTEMPORARY PRACTICE 9 MINIMIZING VULNERABILITY TO MALPRACTICE
CLAIMS — 1
9 MINIMIZING VULNERABILITY
TO MALPRACTICE CLAIMS
William R. Berry, MD, MPH, FACS*
No surgeon wants to be sued. The threat of a medical mal- to the standard of care, both sides use “expert” witnesses
practice suit is, however, a reality for everyone who practices to provide opinions about the care.
surgery. Lawsuits can extract a tremendous price from those 3. The surgeon’s negligence must have been the cause of the
who are sued. The surgeon who has been sued bears the injuries that the patient sustained.
burden of the lawsuit for a period of years while it slowly 4. The injuries that the patient has suffered must have
works its way through a system that is not designed for speed caused measurable damage. This reflects the civil nature
or efficiency. Life decisions are often postponed. Sometimes of malpractice, whereby injuries are compensated with a
careers are forever changed. Confidence is shaken, and sleep payment.
is lost. For some, there is no relief until it is over; for others,
The judge and/or the jury are responsible for determining
it repeatedly intrudes on life. It is better to never be sued.
whether each of these conditions has been met and uses a
The situation, however, is not totally out of the surgeon’s
standard of “more likely than not.” Unlike criminal law, the
control—nor is it hopeless. Armed with knowledge of the
evidence does not have to reach the level of “beyond a rea-
legal system and an understanding of why patients seek the
sonable doubt”—only that there is a greater than 50% chance
courts, the surgeon can decrease the likelihood of ever being
that the conditions were met. In our judicial system, the
named. This chapter provides strategies for avoiding lawsuits
judge and the jury interpret and decide whether the “standard
and advice for dealing with a suit if one is ever filed against
of care” was met.
you.
Malpractice lawsuits often begin with the filing of suit
papers that are delivered or “served” to those being sued. A
What Is Medical Malpractice? written demand for compensation for an injury from the
Medical malpractice law is a subset of the law of torts patient or an attorney is usually called a claim and can pre-
or law that concerns itself with civil injuries as a result of cede the filing of a suit. Suits and claims can end in different
negligent behavior or a failure to practice due diligence. ways, and not all involve a jury trial. They can be dropped by
For a medical malpractice suit to be successful, a number of the patient at any time; denied by the insurance carrier and
elements must be satisfied. A plaintiff (the patient or the not pursued by the patient; settled with a payment before,
patient’s estate) must prove, by a preponderance of the during, or after a trial; dismissed by the court; or ended with
evidence, that the defendant (the surgeon) was negligent or a jury verdict.
failed to exercise due care in the circumstances. A plaintiff
must also show that the defendant’s negligence caused his Personal Issues for the Defendant Physician
injuries and that he has suffered injuries or quantifiable
How physicians cope personally with being a defendant in
damages as a result.
a medical malpractice suit varies, but a number of factors
Four conditions must be met:
come to bear on the amount of stress that litigation inflicts.
1. There must be a “relationship” of some kind between the These factors include the physician’s previous exposure to
patient and the surgeon. The relationship can be a direct litigation claims, degree of familiarity with the legal system
one, in which the surgeon operated on the patient, or a and the litigation process, and previous experience testifying
more indirect one, in which the surgeon only consulted. in the courtroom or in depositions; the size of the claim as
2. The surgeon must be “negligent,” which means that he measured by the seriousness of the alleged injury; and the
or she did not perform to the “standard of care.” The presence or absence of a claim for punitive damages—which,
definition of the standard of care varies from state to state of course, are not insured by professional liability policies.
but usually means that the surgeon failed to perform in a Some physicians experience a sense of profound isolation
manner consistent with the care that would be given by the when they are first named in a suit, particularly when service
average physician practicing in the same specialty. To help of suit papers is accompanied by the standard instruction
the judge and the jury understand the evidence in relation from their risk management office or legal counsel not to
discuss the case with anyone.
Allegations of negligence or substandard care, in and of
* The author and editors gratefully acknowledge the contribu- themselves, are bitter pills to swallow, but they are all the
tions of the previous authors, Grant H. Fleming Esq and Wiley more painful when they are accompanied with a claim for
W. Souba, MD, ScD, FACS, to the development and writing punitive damages. Such claims, announced in the formal
of this chapter. complaint, are then typically followed promptly with a grim
DOI 10.2310/7800.2013
06/11
CLAIMS — 2
letter to the defendant physician from the insurers involved, It has become increasingly clear that surgeons can reduce
reminding the physician that there is no coverage for punitive the likelihood of litigation by adopting a few key habits
damages awarded. The allegations in the plaintiff’s complaint and practices with their patients and their patients’ families.
necessary to support a claim for punitive damages are hurtful These include building trust through open communication,
and sometimes outrageous; the physician is accused of willful, making effective use of the informed consent process, keeping
reckless, and wanton behavior bordering on intent to injure accurate and complete medical records, and educating office
the plaintiff. The awards sought in such cases reach far staff.
beyond fair compensation for the injured plaintiff. Rather,
communication and interpersonal skills in the
punitive damages are calculated to punish the defendant
physician-patient relationship
physician—the perceived wrongdoer—and to serve as public
sanctions. The physician against whom punitive damages are Although advancing medical technology has elevated
sought then undergoes pretrial discovery, sometimes shortly patients’ level of expectation regarding treatment outcome,
after suit is filed. This process involves requests (interrogato- easy public access to medical information on the Internet has
ries) for detailed accounting of personal assets that might be encouraged patients to become partners with their physicians
available to be attached in the event of a judgment in the in their own care. Experience with juries over the past few
plaintiff’s favor. decades continues to support the belief that, in general,
Whether or not punitive damages are sought, it is difficult laypersons have a high regard for physicians and a deep
for most physicians to regard being harpooned by a medical respect for their superior level of knowledge and training.
malpractice claim as merely a cost of doing business, and for At the same time, patients expect and deserve to receive
many, the arduous and seemingly never-ending nature of the thorough understandable explanations from their physicians
regarding their diagnosis, their treatment plan, and the
claim is distracting and potentially debilitating.
risks and benefits of their treatment. Even when the disease
process is beyond the physician’s control, the physician can
Who Brings Medical Malpractice Claims? create an environment for effective communication with
Brennan and colleagues have shown that there is no rela- the patient. Years of listening to patients and their family
tion between the occurrence of adverse events and the asser- members relate their experiences at depositions and trials
have confirmed that the quality of communication and the
tion of claims, nor is there any association between adverse
presence of trust between physician and patient are the most
events and negligent or substandard care.1 These authors did,
important factors in the patient’s decision to file a medical
however, find a relation between the degree of disability and
malpractice suit.
the payment of claims. They found that patients who were
Several researchers have analyzed physician-patient com-
injured through negligent care usually did not file suit and
munication and its relation to claims for damages for alleged
that the patients who did file suit often did not suffer from
professional negligence. Beckman and colleagues studied
negligent care. Further, they also found that patients do turn
45 deposition transcripts of plaintiffs in settled malpractice
to the courts when they are disabled in the course of medical
suits, focusing on the question of why these plaintiffs decided
care. The need to pay for long term care for themselves or a
to bring malpractice actions.5 They concluded that the pro-
dependent often contributes to the filing of the suit.
cess of care, rather than the adverse outcome, determined
Only a small fraction of patients who are injured through
the decision to bring the claim. They found that 71% of the
substandard care or treatment actually bring claims or suits.2 depositions revealed problems with physician-patient com-
Localio and colleagues concluded that although 1% of hospi- munication in four major categories: (1) perceived unavail-
talized patients sustain a significant injury as a result of ability (“You never knew where the doctor was,” “You asked
negligent care, fewer than 2% of these patients initiate a for a doctor and no one came,” “No one returned our calls”);
malpractice claim.3 Other authors have found that only 2 to (2) devaluing of the patient’s or the family’s views (e.g., per-
4% of patients injured through negligence file claims, yet five ceived insensitivity to cultural or socioeconomic differences);
to six times as many patients who sustained injuries that do (3) poor delivery of medical information (e.g., lack of informed
not meet the threshold for malpractice also file malpractice consent, failure to keep patients informed during care, or
claims.4 failure to explain why a complication occurred); and (4)
failure to understand the patient’s perspective.
Strategies for Preventing Malpractice Suits Vincent and colleagues examined the reasons patients and
their relatives take legal action in a survey of 227 patients and
Clearly, not every malpractice suit can be prevented. relatives.6 Over 70% of respondents were seriously affected
When catastrophic injuries follow surgery or treatment, the by incidents that gave rise to litigation. However, the decision
emotional impact of the tragedy, coupled with overwhelming to take legal action was determined not only by the original
economic pressures, can create an environment in which a injury but also by insensitive handling and poor communica-
claim is likely. On the other hand, not all adverse outcomes tion after the original incident. Patients taking legal action
from treatment result in claims. Why is it that some patients wanted greater honesty, an appreciation of the severity of the
and families sue for adverse outcomes and some do not? trauma they had suffered, and assurances that lessons had
Why do some patients sue for adverse outcomes that are been learned from their experiences.
expected and that occur in the context of high-quality care? Levinson and colleagues studied specific communication
The answers to those questions typically have to do with behaviors associated with malpractice history.7 Although they
physician-patient relationships rather than professional skill. did not discover a relation between those two factors in the
06/11
CLAIMS — 3
surgeons they studied, they found that primary care physi- 2. Ensuring patient understanding. Ask patients whether they
cians who had no claims filed against them used more state- understand what they have been told; check the under-
ments of orientation (i.e., they educated patients about what standing by listening to the patient after providing an
to expect), used humor more with their patients, and employed explanation. Demonstrate respect for any cultural or socio-
communication techniques designed to solicit their patients’ economic differences that may be impeding the patient’s
level of understanding and opinions (i.e., they encouraged understanding.
patients to provide verbal feedback). 3. Emotionally engaging the patient. Demonstrate concern and
Hickson and colleagues studied specific factors that led understanding of the patient’s complaints. Express empa-
patients to file malpractice claims after perinatal injuries thy; use humor where appropriate. Demonstrate aware-
by surveying patients whose claims had been closed after ness of the patient’s occupation, social circumstances,
litigation.8 Dissatisfaction with physician-patient communica- hobbies, or interests.
tion was a significant factor: 13% of the sample believed 4. Following up with the patient. Return telephone calls.
that their physicians would not listen, 32% felt that their Explain the protocol for substitute or resident coverage
physicians did not talk openly, 48% believed that their physi- and introduce patients to other personnel who may be
cians had deliberately misled them, and 70% indicated following their care. During longer hospitalizations,
that their physicians had not warned them about long-term keep the patient and the family informed of the patient’s
developmental problems. progress or treatment plan. Keep the referring physician
The American College of Surgeons’ Patient Safety and promptly informed by providing treatment or discharge
Professional Liability Committee performed a closed claims summaries. In the event of a patient’s death, meet with the
study of 460 liability claims between April 2004 and Febru- family several weeks later to review and explain autopsy
ary 2006.9 Ninety of the claims (19.8%) were filed because findings and answer questions that they might have about
what happened to their loved one.
of failures in communication that predominantly involved
patients or their families. Among some of the claims, the Further guidelines apply when an adverse outcome occurs.
standard of care was clearly met. However, defendants In the hospital setting, prompt disclosure of an untoward
suffered litigation solely because they failed to spend the time or unexpected event that causes injury or harm is mandated
required to provide the insight and satisfaction necessary to by the Joint Commission on the Accreditation of Healthcare
defuse anger and mistrust. Organizations (JCAHO). JCAHO standards require disclo-
Many defense attorneys recount stories of surgeons who sure of unanticipated outcomes “whenever those outcomes
had developed a positive rapport with their patients and were differ significantly from the anticipated outcome.”10 The
not named in a suit, whereas other physicians involved in the responsibility to communicate lies with both the attending
patient’s care were named. Patients apparently made these physician and, in the case of a complication incident to
decisions without regard to the extent of each defendant’s surgery, the person accountable for securing consent for the
factual involvement in the case but instead sued physicians procedure.
with whom they had poor or weak relationships. A component When possible, it may be advisable to invite other respon-
of the motivation to sue may be simply an unsatisfactory or sible caregivers to take part in the discussion of the adverse
incomplete explanation of how and why an adverse outcome event with the patient and the family. Consideration should
occurred. Patients who remain uninformed often assume the also be given to inviting other persons who may be sources of
worst: that their physician is uncomfortable talking about the support for the patient and could benefit from the disclosure.
complication because he or she made a mistake, was careless, During the discussion, express regret for the occurrence,
or is hiding something. Malpractice plaintiffs have sometimes without ascribing blame, fault, or neglect to oneself or any
claimed that when they sat through the process of jury educa- other caregiver. Describe the decisions that led to the adverse
tion during the trial, it was the first time they received any event, including those in which the patient participated.
explanation of the complication for which they had brought Explain and outline the course of events, using factual,
suit. Physicians should make a point of explaining to patients nontechnical language, without admitting fault or liability
and their families how and why adverse conditions arose, or ascribing blame to anyone else. Do not speculate or
independent of any possible deficiencies in the quality of care hypothesize. State the nature of the mistake or error, if one
received at home or in patient compliance. Patients and their was made, and highlight the expected consequences and
families are keenly sensitive to unintended inferences that prognosis, if known. Outline the plan of corrective action
blame for the bad outcome rests with them. with respect to the patient. In the event that certain informa-
The principles of good communication are the same, tion is unknown at the time of the discussion (e.g., the
whether or not an adverse event has occurred. They include etiology of the condition, suspected equipment malfunction
the following: in the absence of controlled testing, or pending laboratory
test results), tell the patient and family that such information
1. Educating and informing the patient. Convey medical infor- is currently unknown and offer to share the information with
mation in descriptive terms that patients can understand, them when it becomes available.
using illustrations, sketches, and diagrams. Ask about the A special case exists when children suffer injuries. Parents
response to the therapeutic regimen. Provide counseling may seek subconsciously to avoid blaming themselves and so
and instruction if no improvement is observed. Inform may attempt to transfer the responsibility to the health care
the patient about specific steps in the examination or providers. After a complication or adverse event arises in a
treatment plan. pediatric case, the physician should speak openly with the
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parents. The discussion should cover possible or known discussion presents an important opportunity for the surgeon
causes or mechanisms of the injury or death that are indepen- to develop a rapport and a positive relationship with the
dent of any care rendered by the parents, including prenatal patient. Such a rapport can be invaluable in the event of a
care or home care of a chronically ill child. later complication or adverse outcome. An effective informed
consent discussion may reduce the likelihood of a claim for a
the informed consent process particular adverse outcome if the patient remembers that the
Effective informed consent can reduce the risk of litigation. risk of its occurrence was disclosed and discussed.
The informed consent process is an extension of good Informed consent is not the consent form; it is the process
communication practices, albeit one that is mandated by law. of informing the patient. The form is merely a piece of
The tort of informed consent is derived from the concept of evidence documenting that informed consent occurred; the
battery—for example, unauthorized touching. Patients are critical factor is the content of the discussion. For the form
deemed not to have consented to a procedure unless they to be effective, it must cogently summarize the discussion in
have been advised of all the risks involved in it and all the a manner that makes it difficult for the patient later to refute,
alternatives to it. Although differing somewhat from state to in a “he said, she said” controversy, the version of the discus-
state, in most jurisdictions, the standard is objective rather sion that the physician may be rendering in the courtroom
than subjective. In other words, the risks and alternatives that under oath.
must be disclosed are those that a “reasonable patient, in An effective discussion of informed consent based on
similar circumstances”—not necessarily the plaintiff—would custom and habit is essential because of the slow pace of the
regard as material to the decision whether to undergo the legal system. In most jurisdictions, the statute of limitations
surgery in question. With procedures for which the statistical for bringing claims involving adult patients is 2 years. By the
incidence of risks has been published or is known, the physi- time the defendant physician’s pretrial deposition is taken,
cian has a duty to quantify for the patient the likelihood of another 1 to 3 years may have elapsed, and after that, even
the risk being realized. If the patient’s particular condition or more time passes before the conversation will have to be
situation is such that the likelihood of the risk occurring is relayed under oath if the claim goes to trial. It is exceedingly
higher than average, the physician has the duty to so inform rare that physicians can actually recall the informed consent
the patient. discussion in question at the time of the suit. However, the
Many physicians ignore another critical element in the content of the communication can be proved more reliably
required informed consent discussions: describing the range through custom and habit than through direct recollection,
of reasonable alternative procedures or modalities other than particularly when the elements of the discussion are corrobo-
the procedure in question that are available to the patient. rated with a comprehensive and clear form signed by the
The hazard that such omissions entail is illustrated by a case patient.
in which the physician performed a transesophageal balloon In some cases, physicians encourage the showing of a
dilatation of the esophagus to address achalasia that had patient education video that explains the intended procedure;
not responded to conservative medical therapy. The risk of such a video should also communicate the risks of the proce-
esophageal perforation was disclosed as part of informed dure. The use of educational videos can provide additional
consent, and the procedure was performed totally within the evidence to support the defense that the patient gave informed
standard of care, but the patient suffered perforation of the consent. Each version of the video should be labeled with the
esophagus with serious permanent and long-term disability. dates when it was routinely used and should not be discarded
Although an alternative approach, via thoracotomy, was a when it is replaced with updated versions. The patient’s chart
known option, it was not used at the defendant hospital, and should reflect that the patient watched the video and had no
the informed consent discussion therefore did not include questions after a review of its contents.
the surgical alternative. The defendants were forced to settle The physician who will perform the procedure, not the
the case for a significant amount of money, even though nurse or resident who will assist at it, has the duty to secure
there had been no negligence and the patient acknowledged the patient’s consent. However, information provided by
that the risk of esophageal perforation had been thoroughly other health care providers can be used by the defense as
disclosed. A breach of informed consent was easily estab- evidence.
lished because one of the reasonable alternatives was not
disclosed to the patient. The argument that a reasonable documentation
person would probably have rejected the surgical alternative Along with effective communication techniques and
had it been disclosed was not a valid defense; nondisclosure informed consent protocols, good documentation practices
of a reasonable alternative, in and of itself, created strict can minimize a surgeon’s risk of becoming a defendant in a
liability. medical malpractice suit, or at least provide a more effective
Some surgeons regard the informed consent discussion defense if litigation is commenced. Although the purpose of
as an inconvenient imposition on their time. However, the keeping medical records is to provide subsequent caregivers
few minutes needed for this discussion pale in comparison with important information relevant to the patient’s condition
with the time needed to defend a lawsuit involving a breach and treatment, in the context of litigation, medical records
of informed consent, either as the central claim or as an are used to demonstrate what care was or was not rendered.
ancillary one. In addition, given that the surgeon’s personal A standard question that plaintiffs’ attorneys ask defendants
interaction with a patient may be significantly limited in com- at pretrial depositions is whether the defendant agrees with
parison with that of the primary care physician, obstetrician, the adage, “If it is not documented, it wasn’t done.” Time
gynecologist, or medical specialist, the informed consent and time again, otherwise defensible cases are compromised
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CLAIMS — 5
because of inadequate documentation, such as failure to The appropriate way of handling such an error is to draw a
document an order, the time an order was given, a critical single line through the inaccurate information, record the
telephone call from the patient or patient’s family, a critical correct information, and initial and date the amendment.
informal consultation, or critical symptoms reported by a Clearly, a medical record should never be altered in an
patient during the course of an examination or clinic visit. attempt to cover up something. In the event of a suit, this act
Various tort provisions have been enacted with the inten- could lead to the loss of an otherwise defensible case.
tion of upgrading the quality of expert witnesses in some The following are guidelines for documentation:
states. Better qualified witnesses will generally be more
1. Time and date your notes.
objective, authoritative, and credible than less well-qualified
2. Write legibly.
witnesses. Such witnesses may nonetheless be influenced,
3. Record the information that is important to subsequent
sometimes to the defendant physician’s detriment, by the
caregivers. When an unusual treatment course is planned,
quality of the documentation provided. On the one hand, if
include a clear explanation.
the chart is well documented and the case is defensible, many
4. Record pertinent negative findings.
reputable experts will be loath to give an opinion stating that 5. Do not criticize colleagues in your notes. The record is not
substandard care was provided. On the other hand, absence a place to settle disputes.
of adequate documentation sometimes prejudices expert
case reviewers in favor of the plaintiff, even though subse- educating and informing office staff
quent deposition testimony may provide a cogent and More than ever before, every practicing surgeon must rec-
defensible explanation for how and why the adverse event or ognize that his or her office staff must also be well informed
complication occurred. and well educated about malpractice issues. In-service train-
It is crucial to ensure that telephone conversations are ing of office staff is pivotal to reducing the risk of being sued.
documented. Cases have been saved in the courtroom simply All office personnel should be well informed and educated
because a resident who received a call jotted a short note of on issues of confidentiality, including how to answer the tele-
the patient’s complaint and the advice given and pasted it phone, what kinds of conversations are inappropriate, and the
in the patient’s chart. All appointments, cancellations of dissemination of medical information. It is also critical to
appointments, and reasons for cancellations should be logged. maintain good relationships with patients; many avoidable
If printed images of bedside ultrasound scans are relevant, the lawsuits have arisen simply because a member of the physi-
printed copy should be stapled and placed into the progress cian’s office staff was rude to a patient on the telephone or
notes of the patient’s chart. If the surgeon provided the because the patient waited too long to see the doctor without
patient with a sketch to help explain an operative procedure, an explanation. Whenever patients or family members call
the sketch should be placed in the patient’s chart, with the or write to express displeasure with service they received—
date written on it. In one case involving an informed consent whether that service was provided by the surgeon, the resi-
issue, the defense was able to produce a sketch of the opera- dent, the clinic staff, or the nursing team—courtesy and
tion that the surgeon had made on the reverse side of a labo- common sense decree that the dissatisfied customers should
ratory report in the patient’s chart, thereby refuting the be contacted and allowed to vocalize their complaints, either
patient’s contention that no explanation of the procedure had over the telephone or in person. Willingness to listen to these
ever been given. If equipment malfunction was involved in an persons indicates a genuine interest in improving the delivery
adverse outcome, such as a death in which a postmortem of patient care and may well prevent some claims.
examination was conducted, the surgeon should insist that
the risk management office provide a secure place to store the additional strategies
specimen or equipment in question for later testing or use In the current malpractice climate, it is important to be
as a trial exhibit. If an anomalous condition contributed to vigilant for patients who tend to be inordinately dissatisfied,
an adverse outcome in a fatal case, efforts should be made to complain unreasonably, or to exhibit rudeness. Such
to ensure that the pathologist at least photographs the patients should receive the same high-quality medical care
abnormality at the time of the autopsy if the specimen is not as any other patient, but extra attention should be paid to
to be preserved for later use. documentation of missed appointments, telephone instruc-
Whenever an untoward outcome or event occurs, the event tions given, and the informed consent process. Paranoia is
should be documented in the chart in a purely factual manner, neither necessary nor helpful in dealing with these patients,
without resort to expressions of opinion or suggestions that but care should be taken to inform the staff of any concerns.
other health care providers are to blame. If additional relevant Litigious patients may feel short-changed by the medical
information subsequently becomes available, it can be helpful system because of past adverse experience with the medical
to make a late entry in the chart, with the time of the entry delivery system or economic pressures exacerbated by the
appropriately documented. Be cautious of using self-serving expense of testing and treatment, and when they are not
language in notes that are dictated or recorded after compli- given satisfactory explanations for a poor outcome or a thera-
cations have occurred, that is, the “late” operative report peutic failure, they may seek to elicit derogatory statements
that explains how “carefully” the surgeon operated to avoid about another physician’s advice or treatment. Accordingly,
complications. whereas dialogue and open discussion of adverse outcomes
If one realizes that an error in documentation has been with patients are essential, it is important to steer clear of
made in the patient’s chart (e.g., inaccurate information is criticizing another physician or health care provider. The
recorded), it is vital not to remove the page and start over and proper forum for constructive criticism of other health care
not to scratch out, write over, or “white out” the mistake. professionals with a view toward improvement is the peer
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CLAIMS — 6
review system, not a discussion with the patient or the any colleagues until legal counsel has become involved
patient’s family. If the critique is made in the context of because anyone who takes part in such discussions may be
peer review, the proceedings are shielded from discovery in asked to repeat the substance of the conversation at the time
litigation. of pretrial depositions. The available records should be
If you receive a complaint from a patient about his or her reviewed and a confidential summary of the case prepared;
care, it should be responded to promptly and respectfully. If this summary should be addressed only to legal counsel, with
the patient was hospitalized, turning to the hospital’s patient no copies to anyone. If the media are involved at the outset
representatives for guidance can be helpful. You should of the suit, under no circumstances should defendants attempt
investigate the complaint and communicate in a clear and to be spokespersons on their own behalf; this task should
sympathetic manner your findings. Make certain that you be left to others who are better equipped to determine
follow through. Although not every patient can be satisfied in how much information to provide to the media about the
this way, even minor complaints can escalate into lawsuits if controversy.
they are ignored. It is advisable to find out the name of the defense lawyer
With the enormous attention currently focused on mini- assigned to the case and arrange an initial meeting to familiar-
mizing health care expenditures, virtually all surgeons feel ize him or her with the relevant medical issues. Any medical
pressured to shorten the duration of hospitalization and research done to assist the defendant and legal counsel with
decrease the use of diagnostic tests and medications. the issues should be carried out with the understanding that
Such feelings, although completely understandable, should the research is performed in the context of communication
never be allowed to influence patient care decisions. Juries with counsel: all independent research that is conducted for
persuaded that treatment was withheld or delayed because the defendant’s own edification, rather than for communica-
of a lack of medical insurance have been known to award tion with counsel, is discoverable by the plaintiff. It is vital to
substantial punitive damages. In cases where denial of cover- take whatever time is necessary to educate the defense attor-
age by the health care plan is a particular problem, it can ney on the medical issues involved so that the attorney can
often be helpful to talk directly with the medical director of then gather more information effectively. The defendant can
the health plan. recommend and discuss with counsel certain fact-gathering
tasks to be done by counsel on the defendant’s behalf. Both
defendant and counsel can begin thinking about whom to
What Should Surgeons Do If Sued or If Threatened
engage as an outside expert to assist in identifying weak points
with a Suit?
or issues in the case before the defendant submits to a depo-
If you receive notice that a patient intends to file a suit or sition by the plaintiff’s lawyer. Once defendant and counsel
has actually filed a suit, you should immediately notify your have agreed on an expert, however, only counsel should
insurance carrier and follow its advice. Every state has unique approach or contact the expert.
standards and procedures that must be followed in response
to suits and claims that the insurance carrier can help you settling the claim versus trying the case
with. Most carriers have representatives who will handle Although many professional liability policies require the
the claim or suit and most often will arrange for you to consent of the insured before a settlement offer can be made,
have defense counsel appointed for you. Do not respond to a it still is usually possible for the insurer to settle the claim
lawyer representing a previous patient in a potential claim or over the objection of the insured physician after review and
suit without first contacting your insurance carrier or defense consideration of the objecting physician’s argument against
counsel. If the patient is currently under your care and wishes settlement. Nevertheless, the preferences of the defendant
to continue to have you care for him or her and you feel physician typically exert a heavy influence on the insurer’s
comfortable continuing to care for the patient, you can decision to try or settle the case. Defense attorneys’ recom-
usually continue to provide care. However, it is also appropri- mendations to the insurer are often affected by the degree of
ate to arrange for referral to another surgeon if necessary. rapport they enjoy with their physician client, the client’s
However, you should never speak directly to the patient about conviction (or lack of conviction) regarding whether he or
the claim or suit if you continue to provide care. If you receive she met the standard of care, and the level of the client’s
proper written authorization from the patient or his or commitment to defending the case in a jury trial.
her attorney, you should honor the request and provide a From the insurer’s standpoint, the decision to settle a case
complete copy of the record to them. If you suspect that is guided by a number of factors, such as (1) the strength and
the records are being requested because of a potential quality of the defense expert who has evaluated whether the
malpractice claim, you should notify your insurance carrier. standard of care has been met, (2) the reputation and ability
of the plaintiff’s trial counsel, (3) the likely verdict potential
measures for assisting in the defense
and the risk of an adverse verdict, (4) the general competence
First, all relevant records, telephone logs and messages, and demeanor of the defendant physician, and, of course, (5)
and e-mail correspondence or other notes should be assem- the costs of mounting a defense, which include defense attor-
bled, and every effort should be made to cooperate fully with ney fees, expert witness fees, expenses for daily transcripts
the claims representative of the insurer and the representative during trial, technology costs associated with the preparation
of the hospital risk management team if the hospital is and trial of the case, and the likelihood of an extended and
involved in the case. Under no circumstances should any expensive appeal by the losing party after the verdict. Insurers
records be altered, amended, or discarded when a suit is also consider the potentially beneficial longer-range impact of
initiated. The facts of the case should not be discussed with earning a reputation for defending their clients against all
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CLAIMS — 7
meritless claims, regardless of cost, on the assumption that Preparing for a Deposition
strong and successful defenses against such claims will dis- Depositions are part of the process of gathering evidence
courage future meritless claims against the physicians they and information in preparation for a malpractice trial. They
insure. are often held in an attorney’s office. State law controls
From the standpoint of an insured physician who is a depositions, so there is some variation, but, in general, they
named defendant, the risk of an adverse verdict is, or should follow similar guidelines. During a deposition, you will
be, an important consideration, as should the emotional wear usually be questioned by the plaintiff’s attorney first, with
and tear incurred in preparing for and enduring the stresses follow-up questions asked by your own counsel during cross-
of a trial; the time spent away from work and family; the examination. Additional questions by both attorneys are
degree to which a settlement, as opposed to a successful possible to further clarify points. The entire proceeding will
verdict, may affect future insurance premiums; and the extent be transcribed by a court reporter, and objections are allowed
to which a favorable jury verdict will result in clearing of in most states. It is important to prepare for your deposition
the physician’s good name and restoration of his or her pro- by reviewing the available records so that you are familiar
fessional reputation. How these considerations affect the with them. It is also important to take the time to understand
decision between settlement and trial is strongly influenced the questions that you are being asked and to answer them
by the psychological makeup of the defendant physician: a carefully. Depositions may be used at trial to demonstrate
physician with a strong emotional support structure who also inconsistencies in your answers to questions, so it is impor-
has a personality capable of standing up to the emotional tant to carefully consider answers before you give them. Your
stress and rigors of the courtroom is more suited to participa- attorney can help you in your preparation for the deposition
tion in a trial than a physician with a more fragile personality and is usually present while it is being taken.
who is intolerant of criticism and distrustful of the jury and
the legal system. A physician who favors going to trial over
settling the claim should be willing to become fully invested How Should Surgeons Act When They Are Defendants
in preparing the case for trial, should have a high degree or Witnesses in a Courtroom Trial?
of confidence in the preparation and skills of the defense Although the experience of a medical malpractice trial
attorney trying the case, and should be willing to spend the is not inevitable for all practicing physicians, it is a significant
time required to read the voluminous pretrial discovery depo- possibility for many. If the suit is held to have merit, no settle-
sitions, medical literature, and medical records associated ment has been arrived at and the case goes to trial, an under-
with the case. standing of what to expect at trial is helpful. In addition,
Many physicians would rather have professional negligence strategies for more effectively, credibly, and persuasively pre-
claims judged by other physicians than by laypersons from all senting the defense of a medical case to a jury of laypersons
walks of life and of different education levels. These attitudes charged with the duty to arrive at a verdict can be useful.
have their roots in the 19th century, when the judicial system Many witnesses who have to testify in court feel frightened
was struggling to resolve the claims of injured patients against or intimidated as they approach the witness stand to be sworn
a backdrop of inconsistent medical standards, relatively unso- in. Sometimes the truth that the witness is attempting to tell
phisticated scientific knowledge and information technology, is distorted because of this fear and because of the tactics of
and antiquated means of communicating medical concepts to the opposing lawyer. The perception and judgment of the
laypersons, many of whom were illiterate and lacked what jurors who listen to the witness are affected not only by what
would currently be considered a minimal education. Today, the witness says but also by the manner in which the testi-
the situation is different: jurors with college degrees are the mony is given, the degree to which the witness is acclimated
norm, rather than the exception, in many venues, and the to the facts of the case, and the demeanor of the witness on
expanded use of technology in the courtroom enables illustra- and off the witness stand. Rightly or wrongly, how the witness
tions, concepts, and documentation to be displayed clearly testifies is often more critical than what he or she actually
and effectively while witnesses discuss and interpret them for says. The jury members’ responsibility is to weigh the facts
the jury. Accordingly, it is likely that at least some of the that they are presented with and to come to a judgment. The
traditional suspicion of lay juries may be misplaced. As Struve trust that they have in the witnesses is a crucial element of
has noted, “Juries’ liability determinations in malpractice this process.
cases are not random; rather, studies find some degree of Preparation for an appearance in the courtroom is critical
correlation between jury outcomes and medical reviewers’ for any physician testifying in a trial to best use the opportu-
findings of negligence and causation.”11 The statistics released nity to present the facts in a fair and convincing light. Not
for the year 2005 demonstrate that in Pennsylvania, more surprisingly, under the stress of the moment, intelligent,
than 80% of the verdicts in malpractice trials courts continue experienced, and articulate witnesses often abandon their
to be rendered in favor of the defendant.12 habits of good judgment and solid common sense the moment
It is noteworthy that medical malpractice cases seem to they walk into a courtroom. The guidelines presented are
account for a far higher share of tort trials than other types of applicable to both physicians who are actual defendants in
tort actions do. For example, in Philadelphia County in 1996, a medical malpractice trial and those who are merely
malpractice accounted for only 3% of tort case filings but witnesses.
18.7% of tort trials. To make the comparison in another way,
about one of every eight malpractice filings went to trial, general preparation
compared with about one of every 100 automobile accident Most persons who have rarely or never been a witness in a
filings.13 trial are nervous and anxious at the thought of testifying in
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CLAIMS — 8
front of a jury. A major reason for this reaction is the fear this argument are demonstrated to the satisfaction of the
that one’s words will be twisted by the opposing lawyer judge during the questioning of the juror, the challenge is
or that the intended testimony will be unfairly distorted upheld; if not, it is denied.
or misrepresented as a result of deceptively phrased trick Ideally, before the selection process begins, you and your
questions. You can overcome, or at least alleviate, this counsel should spend some time discussing the qualities your
nervousness and anxiety by preparing painstakingly and team would like your jurors to have and developing a consen-
familiarizing yourself with the case well before the trial, as sus on what responses to questions should be considered
well as by concentrating on and paying close attention to the favorable and what responses should not. You should feel
content of any questions posed by opposing counsel during free to offer suggestions to your counsel regarding questions
your testimony. to ask the jurors, even if the questions you think of may seem
Defense counsel should discuss the key case issues with obvious. In some instances, your counsel may retain jury
you in detail before your appearance, but, obviously, not all consultants to assist in developing voir dire questions aimed
questions and answers can be (or should be) rehearsed. For at identifying positive or adverse jurors. In the last analysis,
your part, you should make sure that you are thoroughly jurors are generally selected on the basis of nothing more than
familiar with the portions of the medical records for which a hunch. Most of the time, decisions made during the selec-
you are responsible (either directly or in a supervisory capac- tion process are based mainly on a “gut feeling” derived from
ity). You should also read and study your pretrial deposition observing the jurors as they react to the lawyer’s questions
transcript to prevent inconsistencies in your trial testimony. during voir dire.
If possible, you should review the pretrial depositions of other During Lawyers’ Opening Statements
witnesses in the case. Stenographers are now able to generate
After the jury is empaneled, each side has the opportunity
word index transcripts that allow you to search the index
to make an opening statement to the jury before the evidence
of another witness’s deposition, quickly find all locations in
is actually presented. An effective opening statement can go
that deposition where the witness or the examiner mentions
a long way toward persuading the jury to accept one side’s
your name, and then focus on any portion of the testimony view of the case, even though the jury is cautioned by the
that has a bearing on you or your involvement in the case. judge to withhold judgment until all the evidence is heard. If
Currently available trial presentation software also allows you are not a named party to the case but merely a witness,
such searches to be linked to corresponding segments of the you should still try to be present during the opening state-
video portion of a videotaped deposition, with the written ments; doing so will help you quickly develop a feel for the
transcript appearing below the video as the witness testifies. case and will alert you to the issues you may face when you
This approach can be an extremely effective tool for a trial testify on the witness stand a few days later. In some instances,
lawyer during cross-examination, in that it facilitates demon- however, you may not have this option. Certain trial judges
stration of inconsistencies in a witness’s statements through may allow opposing counsel to obtain a sequestering order
verbal and visual comparison of trial testimony with a pretrial preventing witnesses (but not parties) from being present
deposition. during the opening statements or during the testimony of
Unless a sequestering order has been issued, you should other witnesses.
try, if possible, to come to court to watch other witnesses
testify before you. This will not only familiarize you with the During Presentation of Evidence
process of cross-examination but will also help you feel more Because the burden of proof is on the plaintiff, the plain-
comfortable with the courtroom environment as a whole by tiff’s case commences first, after the opening statements.
the time you testify. Of course, if you are a named defendant Sometimes the first witness called is not the plaintiff but the
in the case, you will have been there almost all the time defendant (or one of the defendants if the suit was brought
during all phases of the trial anyway. against multiple physicians). Plaintiffs’ lawyers like to use this
tactic early in the case, when the witnesses are likely to be
behavior at trial more nervous and have not yet had time to observe and warm
During Jury Selection up to the pace and facts of the case. By applying this tactic,
they hope to take advantage of the initial unfamiliarity with
If you are a named defendant, it is very important that you the testifying process, sometimes attempting to strong-arm a
be present during jury selection, a process known as voir dire, nervous or inexperienced witness or manipulate his or her
which is used in most states. At this time, you will first be testimony. Sometimes all the plaintiff’s attorney is trying to
introduced to the jurors who will be hearing the case. Some accomplish is simply to make the witness appear unsettled,
information is elicited from the potential jurors before the evasive, or defensive so as to prejudice the jury against that
selection process actually takes place. You will have an oppor- witness.
tunity to communicate with your counsel if you have any The upside of being called in the plaintiff’s case as one of
preferences or concerns about any individual potential juror. the first witnesses is that it gives you an excellent opportunity
Each party to the case generally has a limited number of to present the defense’s side before the plaintiff’s points
so-called peremptory challenges. This means that your are firmly established in the jurors’ minds. Although the
counsel can eliminate a preset number of potential jurors for questions asked in this situation are, of course, under the
virtually any reason. In addition, each party has an unlimited control of the plaintiff’s lawyer, they may—depending on how
number of so-called challenges for cause, which involve narrowly they are phrased—yield you an opening through
making the argument that a particular potential juror cannot which you can make the central points of the defense at the
sit on the case fairly and impartially. If the reasons underlying outset of the case.
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When being questioned by opposing counsel, you must well appear to you that the opposing attorney is “out of his
pay close attention to how the questions posed to you are (or her) league” in trying to play doctor, your interests are
phrased and whether improper assumptions and inaccurate not served by making this attitude apparent: the jury will
statements of fact are loaded into these questions before quickly identify with and side with a lawyer who is patronized
you answer. If the question contains an improper predicate or belittled because of a lack of technical knowledge or
or attempts to make you assume facts that are contested, mispronunciation of medical terms. If you are perceived as
you must point this out before you attempt to answer the defensive, sarcastic, or hostile toward opposing counsel, the
question. At the same time, you must never be evasive or fail jury may well dismiss the logical point you are making on the
to give a truthful and direct answer if the questions are witness stand out of a feeling of empathy for the examining
straightforward, fair, and simple. attorney, especially if that attorney has been polite to you
After you have been questioned by the plaintiff’s attorney during the questioning. Physician witnesses, particularly those
to establish the basic facts the plaintiff needs to prove, your who are professors and researchers, must be on their guard
defense counsel may cross-examine you in an effort to make, not to be seen as arrogant, ivory tower types who are out of
through your testimony, as many key points for the defense touch with the human, caring side of medicine (the side that
as the judge will then allow, even to the extent of assisting the jurors typically prefer to see). The jury generally wants to like
defense in introducing documents or exhibits that the jury you and understands that you are human. Building their trust
has not seen before. The defense thereby has a chance to is crucial.
place its case before the jury before the plaintiffs rest their You should refrain from humorous quips or anecdotes,
case. If all the key points for the defense can be established, especially if you are a defendant or a fact witness in the case.
it may not be necessary to call you back to the witness stand You should project your answers in a strong voice and
later, during the defense’s formal presentation of its case after look the examining attorney in the eye when questioned,
the plaintiff rests. The decision as to whether you will be but without appearing hostile in any way. If you do not know
recalled during the presentation of the defense is usually the answer to a question, the best response is simply to
made later in the trial, well after the defense has formally say so. You will get into difficulty if you continually try to
opened its case. Defense counsel should prepare you for outsmart the cross-examiner by trying to anticipate where
this possibility in advance of the trial so that you are aware the questioning is headed or giving equivocal or facetious
of the critical defense points that should be made in your answers.
subsequent testimony. When being examined by the plaintiff’s attorney, you
Many defense attorneys elect to defer this type of prode- should try not to look at your own counsel at the defense
fense cross-examination to the formal presentation of the table while the question is being asked, while you are answer-
defense, the rationale being that it may be best to hold the ing it, or right after you have given your answer. Looking
strong points of the defense in reserve until after the plaintiff back at the defense lawyers with whom you have associated
has taken his or her “best shots.” You should discuss this is a natural impulse, especially when the courtroom scene is
issue with your attorney in advance of the trial and decide on strange to you and you feel a need for reassurance or approval.
the strategy that works best for you. However, this impulse should be restrained because it sug-
demeanor as a witness gests to the jury that you are unsure about your testimony or,
even worse, that the testimony might never have been yours
General Recommendations to begin with. You should look at the defense attorneys only
Numerous trial lawyers, acting for plaintiffs and defendants when they are questioning you.
alike, have observed that it is better to have a poor case with When medical concepts must be explained to a jury, it
a client whom the jury likes than a good case with a client is important to avoid medical jargon. “Cause” is universally
whom the jury dislikes. The particular challenge for the understood; “etiology” is not. Generally speaking, most
physician acting as a witness is to avoid the appearance of medical concepts can be clearly explained with nonmedical
being disengaged, aloof, or, worse, arrogant. Therefore, when words, basic illustrations, or even crude diagrams. However,
testifying on the witness stand, you should always convey an the complexity level of your testimony and the extent to
attitude of caring, concern, and respect for the patient who is which you use technical medical language may vary depend-
the subject of the suit. As difficult as it may be, you should ing on the point in the trial at which your testimony is given.
always be polite and respectful toward the opposing counsel For example, if you are the last witness testifying and the
who will be cross-examining you. If, as sometimes occurs, jury has already heard three physicians explain a particular
the opposing attorney treats you with disrespect or ridicule, medical issue, you risk insulting the jurors if you talk to them
you should not respond by becoming defensive or overly as if they are in a seventh grade health class; you are better
aggressive. If you act respectfully, the jury will invariably served by using language that matches their current acquired
come to feel displeased with and offended by the attorney and understanding of the issue in question. You must use your
will resent the attorney for continuing in this manner in the own judgment as to what level of medical explanation is
face of your professionalism and politeness. This is true even appropriate at any given point in the trial, but it is important
if the attorney otherwise appears to be making some powerful that you are clearly understood.
points during the questioning. Most jurors are keenly interested in medical science
Above all, it is imperative to avoid the ever-present tempta- and human physiology. If you can respond to this interest
tion to condescend to or ridicule the plaintiff’s attorney by testifying in a clear and accurate manner, without conde-
during questioning on technical matters. Although it may scension, you have a better chance of ensuring that the
06/11
CLAIMS — 10
technical aspects of your testimony are remembered and clearly establish that the passage was taken out of context
understood long after you leave the witness stand. or misquoted. If, however, the examiner’s question was
fair and accurate, simply concede that the passage says
Strategy on Cross-examination at Trial what was represented in the question and wait for the next
The strategy that should govern your testimony at the trial question. Finally, if the judge denied your request to see
is quite different from the one that governed your testimony the document before you answer, you are then permitted
at the pretrial deposition. At the deposition, there was no to testify that because you cannot recall the exact wording
jury, and your counsel instructed you to answer all questions of the document referred to in the question, you are unable
concisely, without volunteering any information that would to answer the question.
lead to more questions. At the trial, it may be to your advan-
tage on occasion to play a more active role. For example, you Not surprisingly, witnesses who fail to follow these instruc-
may forcefully but politely correct a misimpression that is tions often find their testimony to be unfairly mischaracter-
being conveyed by the cross-examiner’s questions, or you ized and manipulated and sometimes discover that they have
may add another point that disputes a particular point the been tricked into conceding points that were untrue or unsub-
questioner is attempting to make. In doing so, however, you stantiated. A witness who does follow these instructions,
must maintain and convey a sense of balance and fairness however, will find, more often than not, that the examining
because it is certainly not to your advantage to dispute or attorney will abandon further attempts to misrepresent the
equivocate on obvious points. document with him or her and will adopt a more measured
and cautious approach to questioning.
Correction of Misleading Questions It is important not to quibble about well-established facts
If the cross-examining lawyer asks you a leading question or undisputed data that appear in medical records. A success-
that contains an unfair or improper assumption in the ful strategy is always to be on the side of facts that the jury
question itself, you should politely correct him or her and will most likely regard as true—even if some of those facts,
make it clear that you do not accept the assumption in the considered individually, do not appear to be favorable to the
question. defense.
Vulnerability to this sort of tactic is heightened when
the examining attorney uses deposition testimony or charac- Handling of Cross-examination Questions Based on Deposition
terizes a particular document during the formation of a ques- Transcript
tion. It is astounding how often witnesses feel compelled to Questions referring to your own pretrial deposition tran-
agree with the examiner’s characterization of the testimony script should be dealt with in precisely the same manner as
in a deposition or of the contents of a particular document, questions based on any other documents (see above). You
without even asking to see the portion of the deposition or should ask to see the transcript, you should review its context
document to which the examining attorney is referring in the before beginning your answer, and when you answer, you
question. Unless you know for certain that the portion of the should take the chance to correct any misleading assumptions
deposition or document used in the question is characterized or add crucial context. It is to your advantage that your cross-
accurately, we suggest that you do the following: examination testimony be consistent with your deposition
1. Always ask to see the deposition transcript or document referred insofar as this is possible. Unprepared trial attorneys some-
to in the question before beginning to answer. Quite often, the times make the mistake of trying to impeach a witness with
questioning attorney is taking the passage out of context, a document that, instead of contradicting the witness’s
is ignoring relevant passages immediately before or after testimony, turns out to be consistent with it, thereby strength-
the passage quoted, or, even worse, is directly misrepre- ening the very point under attack. This tactic can cause the
senting the content of the document or deposition passage lawyer to lose all credibility in front of a jury, especially when
in question. Most judges will accord a witness the courtesy the witness can politely explain why the previous testimony is
of being provided with the document if the witness requests consistent with the current testimony.
it. If, as sometimes happens, your request is not granted, Another unfortunate tactic some lawyers use with deposi-
this refusal may actually be to your advantage: jurors tion transcripts is to suggest that the witness just testified
are almost certain to be sympathetic to any witness who inconsistently because the in-court testimony did not appear
requests to see a document and is denied the opportunity in the deposition at all. For example, the examining lawyer
to see it. might say to the witness, “You just testified here in court that
2. Do not answer the question until you have received the ‘fact A’ occurred. Show me where in your deposition you
document you requested. When you are given the document, ever testified that ‘fact A’ occurred.” The witness should then
ask for a moment to see the passage that was the subject say something like the following: “At the deposition, I was
of the question but take a few extra seconds to examine the instructed to answer only the questions asked. I looked at my
paragraphs before and after the passage, both to confirm deposition before testifying today, and I do not believe that
your understanding of the context and to determine you ever asked me about ‘fact A’ in my deposition. If I am
whether the preceding and following passages help clarify mistaken, could you show me the point in my deposition
the passage in question. where you asked about that subject?”
3. If you then remember the question, answer it. If you do not
remember, ask the court reporter to read back the question Handling of Exhibits
after you have read the document. When you answer the When you are handed any exhibit, whether it is a demon-
question, correct any misrepresentation made in the strative exhibit or some other record in the case, you should
question or add anything you have found that would make a point of holding it and moving it with care and
06/11
CLAIMS — 11
respect. This nonverbal communication with the jury is or other emotions will be seen by the jury as contrived and
important because it is representative of your caring and self-serving and may cause you to be perceived as less objec-
respectful attitude toward the entire case. If you are asked to tive, factual, and trustworthy. You should also endeavor to
identify an exhibit, you should take the time to examine it distance yourself physically from other defense witnesses who
carefully before verbally identifying it. are in the room to avoid the appearance of collusion. If you
When you are asked to show the exhibit to the jury or to are a defendant or the physician whose care is being called
explain something while using the exhibit, you should first into question, you should not wave to or acknowledge any
ask for permission to step down from the witness box and other witnesses (including the defense expert) who may come
then place the exhibit on an easel or otherwise position it into the courtroom during the proceedings when the jury is
and yourself in such a way that you do not obstruct any in the room.
juror’s view of the exhibit as you are testifying. During your You should not stare or smile at the jurors: they will resent
testimony, you have an excellent opportunity to make eye any attempt, subtle or overt, to influence or curry favor with
contact with each juror and build a rapport. Sometimes, in them. Especially if you are sitting at the counsel table, it is a
dealing with an exhibit, you will have to face away from the good idea to take notes occasionally during the proceedings
court reporter. Therefore, you should make sure that you or to have something in front of you at the table to read. If
always speak loudly enough to be heard easily by the court you have a suggestion to make to your attorney during another
reporter so that the key portions of your testimony will not be witness’s testimony, you should write it down and hand the
interrupted by the court reporter’s requests for you to repeat note to the attorney or else discuss the matter during the next
a statement or to speak louder. recess.
During recesses, at lunch, in the elevator, or en route to or
Conduct While Not Testifying from the courtroom, you must be extremely careful not to
When your testimony is concluded, or when the judge discuss the case with anyone if there is a risk that you may
orders a pause, you should not attempt to communicate non- be overheard by a juror or a friend of the plaintiff. During
verbally with any of the attorneys, parties, or other witnesses. recess, when the jury is not in the courtroom, you may want
You should walk away from the witness chair with an erect to converse with courtroom personnel, witnesses, attorneys,
and confident posture and resume the seat you occupied or other persons in the courtroom. Once the bailiff has called
before you testified (unless you have been dismissed from the for the jurors, however, you should return to your seat
courtroom by the judge). promptly, before the jurors return to the courtroom. Again,
While other witnesses are testifying in the courtroom, you you should be careful not to stare at the jurors as they leave
must avoid any emotional facial expressions signaling either and enter.
approval or disapproval of the witnesses or the attorneys.
Facial expressions showing exasperation, disbelief, approval, Financial Disclosures: None Reported
References
1. Brennan TA, Sox CM, Burstin HR. Relation 6. Vincent C, Young M, Phillips A. Why 11. Struve CT. Expertise in medical malpractice
between negligent adverse events and the do people sue doctors? A study of patients litigation: special courts, screening panels,
outcomes of medical malpractice litigation. and relatives taking legal action. Lancet 1994; and other options. Project on Medical Liabil-
N Engl J Med 1996;335:1963–7. 343:1609–13. ity in Pennsylvania. 2003. Available at:
2. Brennan TA, Leape LL, Laird NM, et al. Inci- 7. Levinson W, Roter DL, Mullooly JP, et al. http://www.pewtrusts.org/uploadedFiles/
dence of adverse events and negligence in hospi- Physician-patient communication: the rela-
wwwpewtrustsorg/Reports/Medical_liability/
talized patients. N Engl J Med 1991;324: tionship with malpractice claims among
370–6. primary care physicians and surgeons. JAMA medical_malpractice_101603.pdf (accessed
3. Localio AR, Lawthers AG, Brennan TA, 1997;277:553–9. on April 5, 2011).
et al. Relations between malpractice claims 8. Hickson GB, Clayton EW, Githens PB, et al. 12. Medical malpractice jury verdicts: January
and adverse events due to negligence: results Factors that prompted families to file medical 2005 to December 2005. News release of the
of the Harvard Medical Practice Study III. malpractice claims following perinatal injuries. Administrative Office of Pennsylvania Courts.
N Engl J Med 1991;325:245–51. JAMA 1992;267:1359–63. April 25, 2006.
4. Hickson GB, Pichert JW, Federspiel CF, 9. Griffen FD. ACS closed claims study reveals 13. Bovbjerg RR, Bartow A. Understanding
et al. Development of an early identification critical failures to communicate. Bull Am Pennsylvania’s medical malpractice crisis:
and response model of malpractice prevention. Coll Surg 2007;92:11–6.
facts about liability insurance, the legal
Law Contemp Probl 1997;60:7. 10. Joint Commission for the Accreditation of
5. Beckman HB, Markakis KM, Suchman AL, Health Care Organizations. Comprehensive system, and health care in Pennsylvania. The
et al. The doctor-patient relationship and accreditation manual for hospitals: the official Project on Medical Liability in Pennsylvania
malpractice: lessons from plaintiff depositions. handbook. Chicago: Joint Commission (funded by The Pew Charitable Trusts).
Arch Intern Med 1994;154:1365–70. Resources; 2002. p. R1–10. June, 2003. p. 44.
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ELEMENTS OF CONTEMPORARY PRACTICE 10 SURGICAL PALLIATIVE CARE: CLINICAL AND ETHICAL
CONSIDERATIONS — 1
10 SURGICAL PALLIATIVE CARE:

CLINICAL AND ETHICAL
CONSIDERATIONS
Anne C. Mosenthal, MD, FACS, and Geoffrey Dunn, MD, FACS
The last 15 years have seen a renewed interest in and concern Evolution of Surgical Palliative Care
about the end of life and the care of the dying, both in The roots of surgical palliative care can be traced first to
American society and in the practice of medicine and surgery. the hospice movement founded by Dr. Cicely Saunders in the
This can be traced to the growth of the hospice movement, 1960s. She focused on the needs of the terminally ill, par-
patient-centered care, and the change in demographics per- ticularly their intense suffering from untreated pain at the end
mitting many more adults to live longer with chronic, life- of life. She defined the model of “Total Pain” and dis-
limiting illness. Simultaneously, it can also be seen as a tinguished “pain” from “suffering.” She described the four
reaction to the increasing emphasis of American medicine on dimensions of pain as physical, psychological, social/
technology, cure and prolongation of life at the expense of the economic, and spiritual, which lead to suffering. Hospice care
relief of suffering, humanism, and the “art” of medicine. The developed to treat all four aspects of pain, for both patient
last decades of the 20th century saw an unprecedented growth and family, at the end of life. This model focused initially on
in life-prolonging technology but also an increasing aware- those dying of cancer, where the trajectory of illness encour-
ness of the erosion of the doctor-patient relationship, the aged the aggressive treatment of suffering only when death
dehumanizing effect of much of medical care, and the shift was imminent or life-prolonging care had been exhausted.
from physician as healer to physician as technician and gate- During the 1980s and 1990s, palliative care extended this
keeper. The Study to Understand Prognoses and Preferences model of care to patients dying of other illnesses, such as
for Outcomes and Risks of Treatments (SUPPORT) in the dementia, cardiovascular disease, and organ failure, where
1990s observed that most Americans died in institutions, the trajectory of decline is long and unpredictable and the
usually on life support, with untreated pain and suffering,1,2 dichotomy of cure versus comfort is blurred. Concomitantly,
yet most Americans wish to die at home and fear untreated
other concepts of suffering, such as that proposed by Eric
pain and artificial extension of life.3 At the same time, ethical
Cassell, brought the realization that medical care itself might
and judicial decisions that emphasize patient autonomy pro-
be the cause of suffering rather than the relief. He described
vided the legal foundation for the care of the dying today,
suffering as arising from a threat to the integrity or wholeness
ensuring that physicians can both relieve suffering and avoid
of a person. Cassell noted that “the relief of suffering and
burdensome or futile treatments for their patients at the end
the cure of disease must be seen as twin obligations of a medi-
of life. The convergence of these developments has perhaps
cal profession that is truly dedicated to the care of the sick.
fostered the renewal of the twin goals of medicine and sur-
Physicians’ failure to understand the nature of suffering can
gery: the relief of suffering alongside life-prolonging, curative
result in medical intervention that (though technically ade-
therapy.
quate) not only fails to relieve suffering but becomes a source
Surgical palliative care has evolved in this context over the
last 10 years, drawing not only from the fields of hospice and of suffering itself.”4 Now palliative care has evolved to a
palliative medicine but also surgery itself. The emergence of model of interdisciplinary care that aims to relieve suffering
this field of surgery has in one sense reclaimed the long sur- and improve quality of life for patients with advanced illness
gical traditions of palliation and compassion from a time and their families. It is offered simultaneously with all other
when to bear witness and relieve suffering were all the appropriate medical treatment.
surgeon could offer, attributable in part to the limitations In 2010, surgical palliative care has evolved from these
of medical knowledge or surgical technique. Historically, trends in palliative care and long traditions in surgical care.
much of surgery and surgical care has focused not on cure Although the goal of cure is paramount in much of surgical
but on palliation of symptoms and restoration of quality of care, the relief of suffering and palliation of symptoms are
life, with burn care, vascular surgery, and surgical oncology equally important. The core values of surgical culture include
being prime examples. The contemporary practice of surgery ethical decision making, preservation of hope, nonabandon-
now includes the integration of technical competence ment, relief of suffering, and improvement in quality of life.
with knowledge and skill in relief of suffering, restoration of Certainly, surgeons have always prided themselves as being
quality-of-life, communication, and, when the end of life is the doctors of last resort, taking on the most difficult cases
near, appropriate decision making and withholding or with- and thereby maintaining hope and presence when others have
drawing of life support. The following chapter describes the “given up.” Coronary artery bypass graft for the treatment of
evolution of surgical palliative care, its ethical basis, and its angina, organ transplantation, and vascular surgery were
approach and clinical applications in surgical practice. developed as palliative procedures, with their primary goal to
DOI 10.2310/7800.SECPC10
09/10
improve quality of life as well as prolong it. Fields such as Table 2 Statement of Principles of Palliative Care
burn care, trauma, and critical care are examples of surgical
1. Respect the dignity and autonomy of patients, patients’
specialties that emphasize not only aggressive, technology- surrogates, and caregivers.
based, lifesaving care but also aggressive attention to pain 2. Honor the right of the competent patient or surrogate to
relief, rehabilitation, and quality of life. Both are considered choose among treatments, including those that may or may
equally important, neither is mutually exclusive, and usually not prolong life.
both are delivered simultaneously to patients.5,6 It is no sur- 3. Communicate effectively and empathically with patients,
their families, and caregivers.
prise, therefore, that surgical palliative care would be embraced 4. Identify the primary goals of care from the patient’s
as a specialty inasmuch as it is a renewal of core surgical perspective and address how the surgeon’s care can achieve
values and the adoption of other disciplines. the patient’s objectives.
Contemporary practice of end-of-life care was officially 5. Strive to alleviate pain and other burdensome physical and
nonphysical symptoms.
recognized in the surgical profession when the American 6. Recognize, assess, discuss, and offer access to services for
College of Surgeons endorsed its Statement of Principles Guid- psychological, social, and spiritual issues.
ing Care at the End of Life in 1998 [see Table 1].7 Over the next 7. Provide access to therapeutic support, encompassing the
decade, the principles of end-of-life care were integrated into spectrum from life-prolonging treatments through hospice
the surgical canon, and the palliative approach to care was care, when they can realistically be expected to improve the
quality of life as perceived by the patient.
moved upstream to include those patients with chronic, seri- 8. Recognize the physician’s responsibility to discourage
ous illness and the critically ill, not just those who are immi- treatments that are unlikely to achieve the patient’s goals
nently dying. In 2005, the American College of Surgeons and encourage patients and families to consider hospice
endorsed the Statement of Principles of Palliative Care [see Table care when the prognosis for survival is likely to be less than
a half-year.
2],8 thereby codifying a new discipline of surgery. Over the 9. Arrange for continuity of care by the patient’s primary
last 10 years, the field of surgical palliative care has grown, and/or specialist physician, alleviating the sense of
culminating in recognition by the American Board of Surgery abandonment patients may feel when “curative” therapies
and the American Board of Medical Specialties as a distinct are no longer useful.
discipline with board certification. 10. Maintain a collegial and supportive attitude toward others
entrusted with care of the patient.
Adapted from American College of Surgeons.8
Ethical and Legal Foundations of Palliative Care
The current practice of palliative and end-of-life care is
Table 3].10 Each clinical situation requires consideration of all
guided by bioethical principles and established judicial deci-
four principles for each patient; however, frequently, fulfill-
sions. The vast majority of deaths in America now occur in ment of one principle conflicts with fulfillment of others. For
hospitals and institutions, where active decisions must be example, a surgeon may perform a surgical procedure that
made to withhold or withdraw interventions to allow a “natu- can successfully remove a cancer (beneficence) but may cause
ral” death. Over 70% of patients dying in an intensive care pain or even death from complications (nonmaleficence).
unit have at least one intervention withheld or withdrawn Treatment of pain may be beneficial but can theoretically
prior to death.9 Surgeons must be familiar with the ethical hasten death in some cases. Patients may refuse lifesaving
principles and judicial decisions that form the basis of this surgery (autonomy) even if it means imminent death or dis-
practice. ability. The ethical principle of double effect allows the
Clinical decisions in palliative care are grounded in the surgeon to perform surgery and aggressively treat pain and
four ethical principles that guide all of modern medicine: suffering at the end of life if the intent is to do good, even
autonomy, beneficence, nonmaleficence, and justice [see though the side effect of the treatment may harm the
patient. The bad effect may be a foreseen, but not intended,
consequence or purpose of the treatment.
Table 1 American College of Surgeons Statement of In Western culture in general, and the United States in
Principles Guiding Care at the End of Life particular, the principle of autonomy has been codified and
Respect the dignity of both patient and caregivers. supported by the judicial and legal system as the prevailing
Be sensitive to and respectful of the patient’s and family’s ethical principle to guide medical decision making. Patient
wishes. autonomy is considered a fundamental right of Americans;
Use the most appropriate measures that are consistent with the this includes the right to be informed about medical illness,
choices of the patient or the patient’s legal surrogate. prognosis, and treatment options and the right to choose or
Ensure alleviation of pain and management of other physical
symptoms. refuse these options even if they are lifesaving. The Patient
Recognize, assess, and address psychological, social, and spiritual Self-Determination Act of 1990, passed by the US Congress,
problems. legally ensures that patients have the right to facilitate their
Ensure appropriate continuity of care by the patient’s primary own health care decisions, accept or refuse medical treat-
and/or specialist physician. ment, and create an advance directive. This allows patients
Provide access to therapies that may realistically be expected to
improve the patient’s quality of life. to determine their future health care decisions by completing
Provide access to appropriate palliative care and hospice care. a living will. Surgeons are ethically and legally bound to
Respect the patient’s right to refuse treatment. observe the wishes set forth in a living will in the event the
Recognize the physician’s responsibility to forego treatments that patient becomes incapable of making such decisions. In prac-
are futile. tice, however, this is complicated by the reality that specific
Adapted from the American College of Surgeons.7 clinical scenarios are rarely laid out in a living will, situations
09/10
Table 3 Common Ethical Issues in the Practice of Surgical Palliative Care

Issue Commentary
Disclosure of bad news Broad legal and ethical consensus supports disclosure of bad news when permitted by patient or
surrogate. Disclosure of bad news does not “take away hope” if conveyed with empathy in the
spirit of nonabandonment. Empathic truth telling fosters trust, which is the basis of hope.
Perioperative do-not-resuscitate The American College of Surgeons, the Association of Operating Room Nurses, and the American
(DNR) orders Society of Anesthesiologists support a policy of “required reconsideration” of DNR orders in
the perioperative period. This is a preoperative discussion between patient/surrogate and
anesthesiologist and surgeon to clarify goals and limits of care, with either revision or
continuation of the DNR order in the operating and recovery room.
Automatic rescinding of DNR orders during surgery is not recommended.
Withholding/withdrawal of life The withholding of medical treatments is considered legally and ethically equivalent to withdrawal.
support This is based on the principle of autonomy.
In practice, for both physicians and surrogates, it is more difficult to withdraw a life-supporting
treatment once it has been started than to withhold it. A surrogate’s persistent reluctance to
consider termination of life support is usually related to the fear that he or she will be “killing
the patient” or the fear that withdrawing life support will cause suffering.
Legally and ethically, termination of undesired medical treatment of the properly informed patient/
surrogate is not considered homicide, suicide, or euthanasia.
Aggressive symptom management Aggressive management of unbearable symptoms at the end of life is a moral imperative, even at
the risk of hastening or causing death, as long as causing death is not the intention of treatment.
The risk of hastening death is present with any surgical treatment for serious illness, including
attempts to cure.
The rule of double effect, broadly accepted by ethicists, is invoked:
• The act must be good or morally neutral.
• Bad effects are foreseen but not intended.
• A good end cannot justify a bad means.
• The risk/benefit ratio must be reasonable.
Donation after cardiac death Ethical and legal principles support DCD, invoking principles of autonomy and double effect.
(DCD) DCD should be considered for patients where withdrawal of life support is contemplated. The
Organ Procurement Organization personnel should be consulted prior to decision making to
evaluate feasibility and medical suitability before approaching this option.
arise that are unforeseen, and written documents cannot centered. Quality of life, relief of symptoms, and the oppor-
substitute for informed discussions between physician and tunity for spiritual comfort or closure at the end of life are
patient. This reality has led to reliance on surrogate decision more important measures of success in this discipline. This
makers and health care proxies to interpret a patient’s living constitutes a cultural shift in surgery, where the morbidity
will or advance directive in consultation with the physician. and mortality conference reinforces the notion that death is a
Although the Patient Self-Determination Act did not specifi- “failure” of the surgeon and brings “shame” on him or her.14
cally address the issue of surrogate decision maker or the It is not a large leap to see how this stigma would cause some
ethical basis of substituted judgment in medical decision surgeons to view end-of-life care as the sine qua non of
making, the legal and ethical basis has been clearly estab- “giving up” and therefore distinct from their aggressive, life-
lished by the Supreme Court decisions of the Karen Anne prolonging care. Surgical palliative care is currently moving
Quinlan and Nancy Cruzan cases.11–13 These two cases estab- away from this false dichotomy to an affirmative concept
lished that it is consistent with autonomy, beneficence, non- upstream in the patient’s care, when symptom control and
maleficence, and justice if a surrogate decision maker acts restoration of quality of life can be delivered alongside life-
based on the patient’s best interest and/or in accordance with prolonging surgery.
the patient’s previously expressed wishes. This provides the
legal basis for decisions to withhold or withdraw life support palliative care assessment
in patients who are incapacitated, as long as these principles The first goal of the assessment for palliative care is to
are maintained. gauge the level of overall distress. The assessment is, in a
sense, a “staging procedure” to determine the scope and
severity of palliative care needs. Palliative care assessment
The Practice of Surgical Palliative Care
includes the identification of the current illness, treatments,
Surgical palliative care is the treatment of suffering and the and likely prognosis; sources of pain in all dimensions; per-
restoration of quality of life for seriously ill or terminally ill sonal, social, and spiritual resources; and individual values
patients with surgical disease, regardless of the prognosis. and hopes. The patient’s decision-making capacity, advance
The surgeon brings all the tools in his or her armamentarium directives, and health care proxy should be identified as well.
to treat distress, not just disease. The measure of surgical Table 4, adapted from the American Medical Association
palliative skill in this context is not disease specific, such as Education for Physicians on End-of-Life Care Curriculum
complications, morbidity, or mortality, but rather patient (EPEC), describes the domains of palliative care assessment
09/10
Table 4 Ethical Principles in Palliative Care Scale score is a widely used scale for the assessment of func-
tion and prognosis in cancer patients.18 Patients with conges-
Principle Ethical Imperative
tive heart failure or chronic respiratory failure who may be
Autonomy Respect the capacity of individuals to make contemplating surgery have a more unpredictable trajectory
their own choices and act accordingly to death but will need prognostic information about the likely
Beneficence Relieve pain and suffering, foster the decline in quality of life over time, with or without surgery.
interests and well-being of other persons All therapy should be evaluated by both patient and sur-
and society
geon based on the goals of care established. Surgery or pro-
Nonmaleficence Do no harm; do not inflict pain or suffering cedures are weighed, not by their defined complications or
Justice Act fairly; distribute benefits and harms indications but by their benefits or burdens for the patient, in
equitably the context of his or her goals. Palliative surgery to relieve
malignant bowel obstruction should be considered based on
Adapted from Beauchamp TL and Childress JF.10
the likelihood of eating again and the relief of nausea, vomit-
ing, and pain (benefit) versus the likelihood of pain, open
with sample questions for each. Immediate relief of pressing wounds, infection, or death in the operating room or the
symptoms should be a priority and initiated concurrently with hospital (burdens). The patient’s decision will depend on his
the assessment if necessary. Further discussions around goals or her goals (“I want to die at home,” “I want to see my
of care cannot ensue if untreated symptoms are allowed to daughter’s wedding”), as well as the information the surgeon
persist. Who should be included in the discussions should provides about the surgery and alternatives. Each treatment
also be established at this time as the patient may or may not or therapy should be considered independent of other thera-
want family present. pies and based solely on its benefits or burdens. Patients
The assessment of physical symptoms is usually the first who want do-not-resuscitate (DNR) orders in the event of
priority in palliative care. This is focused on pain and non- cardiopulmonary arrest will still need symptom relief or
pain symptoms, that is, the patient’s subjective report, not simple, life-extending treatments. Surgery to relieve malig-
on disease processes or disease-based review of systems nant obstruction or antibiotics to treat pneumonia would still
(Table 5). The patient’s self-report is the gold standard. Val- meet their goals, even if they do not want cardiopulmonary
idated pain assessment tools using numeric scoring from 0 to resuscitation (CPR).
10 are the most common. Assessment tools are also available Establishing goals of care can be a difficult transition for
for nonpain symptoms but are generally validated for specific both patient and surgeon. The surgeon is often consulted as
disease or patient populations. The Edmonton Symptom the last hope and held up as the “rescuer,” bringing lifesaving
Assessment Scale (ESAS) is a validated tool for palliative care surgery or other “miracles.” It is not difficult to see that
patients and includes assessment for nonpain symptoms such changing the goals of care is, in a sense, breaking this “coven-
as fatigue, thirst, dyspnea, and nausea.15,16 Assessment should ant for cure”; the surgeon may feel that he or she is “taking
include not only the severity of the symptom but also away hope” or abandoning the patient by not performing
questions as to the level of distress the symptom causes. futile surgery that would only add burden, not benefit.14,19
goals of care Conversely, the surgeon may have a long relationship with a
patient, always focusing on aggressive, life-prolonging care,
The patient’s goals of care that emerge from this initial
but now the prognosis has shifted, and a transition to comfort
assessment and discussion should guide the scope of all fur-
and relief of suffering changes this role. This is further com-
ther surgery and treatments. The goals of care are generated
plicated if the patient’s condition has changed after surgery
by the patient’s preferences and wishes in the context of the
because of complications or iatrogenic events; this is fre-
medical realities and the prognosis. Goals may be fluid and
quently the case in the intensive care unit when unforeseen
evolve over time. Singer and colleagues identified five domains
postoperative events have changed the course or patients
of quality of life that patients with life-limiting illness hope
linger with multiple organ failure and uncertain prognosis.
for: adequate pain and symptom management, avoidance of
The ability of the surgeon to reflect on his or her own sense
inappropriate prolongation of dying, sense of control, relief of
burdens, and strengthening of relationships with loved ones.3 of failure or loss is the first step in making a transition in goals
More recent studies suggested that seriously ill patients weigh of care. The surgeon has the unique role of helping the patient
treatment options based on the treatment burden, treatment and family find new hope, whether it is hope for symptom
outcome, and likelihood of the outcome, with cognitive or relief or time with family. If likely outcomes are uncertain, the
severe functional impairment often considered more unac- surgeon can convey this range of possibilities, and goals of
ceptable outcomes than death.17 Although the surgeon must care can include a focus on relief of suffering alongside other
elicit preferences from the patient, he or she must provide the life-prolonging therapies, not in an either/or fashion.
medical information and prognosis to the patient, especially interdisciplinary team
likely and unlikely outcomes from contemplated therapy.
Physicians are notoriously poor at prognostication, but ranges The relief of “total pain” or suffering requires an interdis-
of life expectancy can be provided, keeping in mind that in ciplinary approach, particularly if suffering is extreme. The
some disease trajectories, death may be years away, but collaboration of pain medicine specialists, clinical pharma-
chronic, debilitating decline may be the life-limiting feature. cists, palliative medicine and nursing colleagues, and spiritual
Some trajectories are more predictable, such as cancer, and and psychosocial care providers is essential. Surgeons may
assessment of function, or progression of symptoms, is an not be familiar with nonsurgical alternatives for treatment of
indication of life expectancy. The Karnofsky Performance nonpain symptoms. Similarly, the best approach to breaking
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Table 5 Palliative Care Assessment

Domain Sample Questions to Ask the Patient
Illness/treatment summary Tell me what you know about your illness.
Could you give me an account about your illness and treatment you have had until now?
Tell me what stands out in your memory (about your illness, about treatment to date).
I will review (have reviewed) your medical history in your chart, but I am really interested in hearing about
it from your point of view.
Physical symptoms How long have you had (symptom)?
Are you having this (symptom) all the time or on and off?
How would you describe what you are feeling?
Is the (symptom) staying the same, getting better, or getting worse?
Using a scale (provide a scale), what is the lowest you have been in the past day? The highest? Where are
you now?
Does anything make the (symptom) better? Worse?
To what extent does the (symptom) interfere with what you want to do?
Is the (symptom) causing problems in your relations to others?
Have any treatments helped your (symptom)? How much?
What do you think is causing it (symptom)?
Does it (symptom) frighten you? Why?
Psychological symptoms Does everything happening make any sense to you?
What do you think will happen next?
How has your illness affected your life?
What do you see as the biggest problem facing you now?
What frightens you most about your illness?
How would you describe your mood?
How well do you think you are coping now?
Do you feel depressed?
Have you ever thought of taking your life? Do you have a plan?
Have you been sad? Frightened? Anxious?
Are you afraid of being a burden to others?
How have you handled tough times in your life previously?
Whom do you turn to for support in tough times?
Have you ever had problems with depression, alcohol, or other psychological difficulties before your illness?
Did you ever have treatment for these?
Are you afraid we won’t be there when you need us?
Spiritual issues Do you consider yourself a religious or spiritual person?
How important is your faith or belief in your life?
Do you belong to a community of faith?
What sustains your hope?
Do you have religious or spiritual beliefs that help you through difficulty?
What gives your life meaning?
Does your faith influence your feelings about your illness? Your surgery?
Do you see any possible conflicts between your health care and your beliefs?
Do you have any specific observances or rituals we should be mindful of during your care?
Social/cultural context Can you tell me about other people in your everyday life, at work, at home, etc.?
What language is spoken in your home or community?
Do you have a community or spiritual leader whom you would like to involve in your medical decisions?
Communication Is it your preference to be alone or have someone close to you present when we discuss important matters?
preferences Is there anyone with whom you would like me to discuss your care?
If I am approached by family members with questions about your situation, do I have your permission to
discuss it? To what extent?
Decision making Who will make decisions about your medical care if (when) you are not able to?
What would you like them to know?
Practical concerns Where do you hope to go after this hospitalization?
When you are ready for home, will your home be ready for you?
Are you concerned about being a financial burden on your family?
Anticipatory planning Have you given any thought of what comes after your hospitalization ?
What plans have you made for your future?
Are there things you need to know right now for planning for the future?
Would it be helpful for us to schedule a meeting with us and your family to plan your future treatment and
care?
Adapted from palliative care assessment in EPEC, American Medical Association’s Education for Physicians on End-of-life Care. 1999.
09/10
bad news, communication under conflict, or relief of existen- Table 6 SPIKES: A Six-Step Protocol for
tial pain may be beyond the scope of the usual surgical prac- Delivering Bad News
tice. In palliative care, the patient and family are considered Step 1: S – Setting Up the Interview
part of the unit of care. Attention to bereavement, grief, and Arrange for some privacy
the needs of family at the end of life is especially important. Involve significant others
Studies show that the nature of communication, access to the Sit down
dying patient, and the patient’s relief of distressing symptoms Make connection with the patient
Manage time constraints and interruptions
all affect the bereavement outcome of family members.20,21
Furthermore, the majority of hospitalized patients, particu- Step 2: P – Assessing the Patient’s Perception
larly in the intensive care unit, are incapacitated and cannot Step 3: I – Obtaining the Patient’s Invitation
make any medical or end-of-life decisions for themselves. Step 4: K – Giving Knowledge and Information to the Patient
Decision making generally falls on their surrogates, who are Avoid medical jargon
likely in crisis themselves because of the illness of a loved one. Give information in small amounts at a time
Emotional and educational support for their decision-making Step 5: E – Addressing the Patient’s Emotions with Empathetic
role is critical in avoiding conflict or prolonging the dying Responses
process, whether in the form of bereavement counselors, Allow time for expression of emotion
pastoral care, or other members of the palliative care team. Identify patient’s emotion
Identify cause of emotion
Studies clearly show that interdisciplinary communication,
Connect emotion with cause of emotion
whether in the form of family meetings, ethics, or palliative
care consultation, has a salutary effect on both patient and Step 6: S – Strategy and Summary
Discuss goals of care
family psychosocial outcomes.22–24 Surgeons may also benefit Treatment plans
from this team approach as they seek balance in the dual Future meetings
imperatives to rescue and to relieve suffering. The death of
Adapted from Baile WF et al.29
a patient is also a loss for the surgeon; reflection and the
ability to seek support are important steps for adapting to the
multiple roles of the surgeon in palliative care.
important when end-of-life decisions will be discussed; if
communication
initial communications are not clear and compassionate,
Shared decision making between the physician and the conflicts around withdrawal and withholding of life support
patient/family is the foundation of end-of-life care. Commu- can ensue. The timing of communication is important, par-
nication of bad news, along with treatment of distressing ticularly with families of critically ill or injured patients.
symptoms, is perhaps the fundamental “procedure” of pallia- Family meetings to discuss prognosis and end-of-life deci-
tive care. The emphasis on patient autonomy, the patient- sions in the intensive care unit are more effective if held
doctor relationship, and professionalism and the realization within 72 hours of admission.22,30
that clinical and litigation outcomes are improved now require
competency in communication skills in all aspects of surgical withdrawing and withholding of life support
practice. Although as late as the 1960s, most physicians did The vast majority of deaths in the United States, whether
not reveal a distressing diagnosis to their patients, it is now
in the hospital or at home, now occur in the setting of
the expectation and legal obligation that all medical informa-
withdrawing or withholding of life support. Although use of
tion be disclosed, no matter how upsetting. Communication
hospice during the last months of life has increased in the last
around death and dying can be one of the most stressful
decade, multiple studies suggest that the largest percentage of
aspects of practice. Surgical myths and fears abound: sur-
Centers for Medicare and Medicaid Services expenditures
geons are poor communicators or lack empathy, truth telling
will take away hope, talking is too time consuming—all fur- result from high-technology care in hospitals and intensive
ther compound these stressful encounters. In fact, good care units in the last 6 months of life.31 Death after end-of-life
communication is a skill. Increasing studies demonstrate that decision making and withholding or withdrawing of life sup-
patients and families’ satisfaction and understanding of the port have become the norm, and expertise in this area is now
illness are improved when physicians do less talking and more part of standard surgical practice.
listening, impart information clearly and simply, allow time The process of withholding or withdrawing life support is
and space for emotion, connect the emotional distress with based on shared decision making around end-of-life issues
its source (the medical information), and provide support.25–27 between patient, family, physician, and other health care pro-
Several communication protocols for delivering bad news viders. The decision should be based on patient preferences
or conducting a family meeting have been proposed and and goals, knowledge of the likely outcome of continuing life
studied.28,29 The SPIKES protocol developed by Baile and support versus withdrawing it, and the benefits and burdens
colleagues is one example, as shown in Table 6.29 All of of each option. Conducting these discussions requires skill
these emphasize preparation for the meeting, the appropriate in communication and knowledge of the ethical issues, symp-
setting, providing a “warning shot” for bad news, clear toms, and therapies available to treat them. There continues
delivery of information, empathic reflection of emotion, and to be misunderstanding around the difference between with-
concluding with recommendations for treatment. Following drawal of life support, euthanasia, and physician-assisted
these steps will provide support to the patient and family suicide. Families may worry that if they decide to withdraw
and allow for further communication. This is particularly the ventilator they “are killing the patient”; similarly, they
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fear that their loved one may “suffocate.” Part of the discus- aggressively treat dyspnea with opioids based on the principle
sion should include assurances that dyspnea, pain, and other of double effect. The fears of hastening death by administra-
symptoms can be treated successfully and that physicians will tion of opioids or benzodiazepines have not been borne out
not abandon the patient once a decision is made. The “DNR in several studies, where the time to death was equivalent for
discussion” can be particularly difficult; following available patients who did and did not receive these medications after
guidelines is helpful.32 These include the basic steps of good withdrawal of the ventilator.39,40
communication: preparation, appropriate setting, and reflect- The practice of withdrawing life support can be perceived
ing troubling emotions around difficult issues. It is helpful to as a conflict between the patient-centered goals of palliative
describe CPR as a procedure with certain indications, bene- care and societal goals of organ donation. In fact, the two are
fits, and burdens and to make a recommendation about not mutually exclusive. If the patient is likely to proceed to
whether or not to withhold it based on the medical prognosis brain death and organ donation is possible, efforts to stabilize
and condition. and support a patient can coincide with attention to patient’s
Confusion on the part of physicians still exists about their pain relief and comfort and family support until brain death
role in withholding and withdrawing life support. Many are protocols are completed. In other clinical situations near the
more comfortable withholding therapy rather than withdraw- end of life, once the surgeon contemplates withdrawing or
ing it because of unfounded fears that they may be causing withholding life support for a patient, the issue of organ
death, abandoning the patient, or vulnerable to litigation. donation must also be considered. With the advent of dona-
Historically, several studies have noted high variability in tion after cardiac death (DCD), it is theoretically possible for
physician practice around DNR orders, withdrawal, and patients to donate organs if cardiac death ensues after with-
withholding, with some preferring to withhold rather than drawal of the ventilator or pressors. For some families, the
withdraw, whereas others withdraw therapy in a particular prospect of organ donation is comforting in the face of other-
sequence or avoid withdrawal of the ventilator altogether.33–36 wise bad news. Organ Procurement Organization personnel
Ethical and legal precedents are clear that withdrawing is should be contacted prior to any communication with the
equivalent to withholding and the decision for each therapy family about this option to evaluate if medically appropriate.
should be based on patient’s preference (autonomy) and Any request for organ donation should be made by the organ
burdens and benefits.37 procurement organization, not the physician caring for the
Withdrawal of the ventilator deserves special consideration patient. The decision to withdraw life support should be
as it is a procedure that continues to cause anxiety among made before and separately from any consideration of organ
physicians. Several protocols have been developed for this donation. With DCD, organ donation may increasingly
procedure, which include family and patient preparation, use become part of the end-of-life decisions around withdrawal of
of terminal wean versus direct extubation, and guidelines life support.
for the use of opioids and benzodiazepines for the treatment
of refractory dyspnea.38 It is ethically and legally sound to Financial Disclosures: None Reported
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ELEMENTS OF CONTEMPORARY PRACTICE 11 BEDSIDE PROCEDURES FOR GENERAL SURGEONS — 1
11 BEDSIDE PROCEDURES FOR

GENERAL SURGEONS
M. Margaret Knudson, MD, FACS, and Ramin Jamshidi, MD
Innovative equipment and advances in pain management have The image seen on the screen while scanning in real time
helped to expand the number and types of procedures that can is produced by a series of echoes returning from the organ of
now be performed safely and comfortably at the bedside of the interest. Enhancement of this image requires adjustment of
surgical patient. However, success is unlikely unless the sur- the controls on the ultrasound console. Enhancement might
geon has detailed knowledge of the procedure, has assembled require brightening or darkening the entire picture on the
in advance all of the necessary equipment, and has a thorough screen (turning up or down the overall gain) or increasing or
appreciation for potential complications. Equally important is decreasing the gain in the area of interest only (near or far
preparation of the patient for what he or she will experience gain). It is helpful to adjust the gain such that a structure
and involvement of the responsible nurse prior to initiating any known to be anechoic (without echoes), such as blood within
procedure. This chapter focuses on these essential aspects for the heart or within a blood vessel, looks black to the observ-
each technique described. Additionally, we offer suggestions er’s eye. Adjusting the focus to concentrate on the target area
about training for and attaining competencies in these areas can also be easily accomplished. Because the ultrasound wave
for surgeons in various stages of their professional careers. becomes attenuated as it passes deep into the tissue, the
returning signal from the deepest region may require enhance-
ment by adjusting the time-gain compensation slide pots on
Ultrasound-Guided Procedures
the console. Magnification of the image is also possible. Once
ge n e ra l pr i n c i p l e s: i n st r um e n t a t i o n the desired image is obtained, it can be “frozen” to print or
a n d s ca n n ing t e c h n i q ue s store the image or to perform measurements. Annotation
Over the past several years, ultrasonography has emerged (e.g., labeling) is also performed on the frozen image. The
as an increasingly useful bedside imaging technique, offering series of images obtained just prior to freezing the image can
sharp two-dimensional and even three-dimensional imaging be reviewed using the cine-loop function in case the frozen
capabilities housed in smaller and more portable units. Thus, image missed the target. The initial images are usually dis-
a working knowledge of ultrasonography is essential for a played in grayscale (B-mode or brightness modulation), but
general surgeon and is now a requirement for all certified most machines have both color-flow and Doppler imaging
surgical training programs. Although a wide variety of excel- features as well, which can be added during real-time scan-
lent ultrasound machines are available from several manufac- ning and are essential for vascular procedures.
turers, the basic instrumentation and scanning techniques Traditionally, ultrasound examinations are performed with
that are common to all are reviewed here. the patient in a supine position. When the transducer is held
In general, obtaining an ultrasound image begins with pro- in a sagittal orientation (the transducer directional marker
viding a path for transmission of the sound wave between the
transducer and the object being scanned. This process, which
Table 1 Transducers and Their Applications
is termed coupling, is accomplished at the bedside by replacing
the air between the transducer and the skin with a gel surface Transducer Frequency (MHz) Application
(contact coupling). Standard ultrasound gels can be heated to 2–3.5 Abdominal
enhance imaging and improve patient comfort, but, most Cardiac
importantly, these gels should be applied liberally to the skin
Obstetrics
for optimal imaging. In fact, if the object of interest appears
dark on the screen, it is likely that the amount of contact gel 5.0 Neonates/pediatrics
is inadequate. The second major focus for the surgeon sonog- Peripheral vascular
rapher is choosing the correct transducer. The frequency of
Cerebrovascular
the transducer (measured in megahertz) determines the depth
of penetration in the tissues; a low-frequency transducer trav- Breast
els deep in the tissue but loses resolution. For sharper images Thyroid
on the surface, one would choose a high-frequency transducer, 10 Vein mapping
which penetrates only a few centimeters deep. Table 1 describes
the uses for transducers of various frequencies. Soft tissues
DOI 10.2310/7800.SECC11
04/09
toward the patient’s head), the left side of the screen is oriented array transducer (2.0–5.0 MHz) with a small footprint held in
toward the head, with the right side toward the feet. When the the subxiphoid position at 30º to the skin and aimed toward
marker is turned toward the patient’s right for transverse the left shoulder [see Figure 1]. Note that for all views, the
imaging, the patient’s right side is on the left side of the screen, marker groove points toward the left side of the screen. From
and the head would now be toward the top of the screen. this same position, the transducer is rotated transversely, and
Holding transducers incorrectly results in serious errors in a four-chamber view can be seen in most patients depending
interpretation of the images. Other tricks for obtaining the on body habitus. The third view is obtained from the left para-
best possible images (in addition to those listed above) include sternal area (long axis of the heart) with the transducer ori-
darkening the room as much as possible; sliding, tilting, and ented along a line between the right shoulder and the left hip.
rocking the transducer on the skin rather than picking it up Pleural effusions may be confused with pericardial effusions,
and moving it abruptly; using gentle but firm pressure; apply- but this is minimized in the subcostal view because there is no
ing graded compression when air is present; or repositioning pleural reflection between the liver and the heart. Addition-
the patient if needed. Most importantly, the surgeon sonogra- ally, intrapericardial fluid will conform to the contour of the
pher should take his or her time to obtain the best possible heart. Viewing the heart in more than one plane will also help
images under the circumstances. Rushing through an exami- reduce interpretation errors. Echocardiography can also be
nation is the most common source of error. used to detect the presence of cardiac motion when no blood
Although ultrasound technology has an excellent safety pressure is obtainable after trauma (pulseless electrical activity
profile, with the added benefit of high image quality and por- [PEA]). Following penetrating trauma, the detection of PEA
tability without radiation, there is still the possibility to inflict may be an indication for emergency department thoracotomy,
harm on a patient. Each unit must be well maintained and particularly in the presence of pericardial tamponade.
checked routinely to be sure that the ALARA principle (As The abdominal portion of the FAST examination begins in
Low As Reasonably Achievable) is adhered to, in reference to the right upper quadrant with the transducer placed in sagittal
power and exposure time while obtaining the necessary clini- orientation along the right anterior midaxillary line between
cal information. Tissues will heat up during lengthy examina- the 11th and 12th ribs. The liver, diaphragm, and right kidney
tions, and cavitation is also possible if the power is too high. are imaged and, in particular, the Morison pouch (between
Each transducer should be inspected regularly for breaks in the kidney and liver) is examined for fluid. In the supine posi-
the housing or cable that could potentially produce an electri- tion, this is the most likely spot for fluid or blood to accumu-
cal shock. After each examination, the transducers should be late [see Figure 2]. On the left side, the spleen and left kidney
thoroughly cleaned using a solution recommended by the are found in the posterior midaxillary line slightly higher
manufacturer so that blood or fluids are not transmitted from (between the ninth and 10th ribs). Once again, the trans-
one patient to the next. Surgeons must also be involved in ducer is oriented in a sagittal plane. It is extremely important
performance improvement programs where diagnostic deci- to examine not only the space between the spleen and the
sions and procedures performed using ultrasound are reviewed kidney but also the space between the left hemidiaphragm
for accuracy and patient safety. and the spleen, where many splenic injuries will manifest.
Because rib shadows may prevent full visualization of the
spleen, having a cooperative patient take a deep breath can
u se o f u l t ra s on og r a p h y i n t r a um a be helpful. The final abdominal image is of the pelvis. Here
The FAST Scan the bladder serves as an acoustic window and must contain
fluid to be seen. The transducer is oriented for transverse
The use of ultrasonography to query the pericardium and
sections over the pubis, aimed at the feet. If a Foley catheter
peritoneal cavity for blood has become standard in trauma cen-
is in place, fluid should be instilled into the bladder to facili-
ters. Referred to as the FAST examination (Focused Assess-
tate detection of pelvic fluid [see Figure 2].
ment for the Sonographic examination of the Trauma patient),
it has rapidly replaced diagnostic peritoneal lavage as the pre- Detection of Hemothorax
ferred method for detecting hemoperitoneum in the unstable
Other uses for ultrasonography following injury include
patient following blunt trauma.1 It is also appropriate for preg-
scanning for the presence of hemothorax, or pneumothorax,
nant and pediatric patients, for whom radiation exposure is
and in serial follow-up of intra-abdominal solid organ injuries
more dangerous. In penetrating trauma, the abdominal portion
being managed conservatively. Surgeons from Emory University
of the FAST examination is not always helpful, because the
were among the first to describe the evaluation of the pleural
amount of intra-abdominal fluid associated with hollow viscous
space using a standard 3.5 MHz transducer in the trauma
injuries (most likely to be injured in penetrating trauma) is often
room as part of the FAST examination.3 Briefly, the transducer
too small to detect with ultrasonography. On the other hand, a
is held in the sagittal position and advanced in the midaxillary
limited echocardiographic examination is extremely sensitive in
line from the 10th and 11th intercostal spaces (where the liver,
detecting penetrating injuries to the heart associated with peri-
diaphragm, and kidney are seen) cephalad until the supradia-
cardial fluid and has replaced all other noninvasive (e.g., central
phragmatic space is visualized. Fluid in the pleural space will
venous pressure [CVP], serial electrocardiograms) and invasive
appear as a black triangle above the hyperechoic (white)
(i.e., pericardial window) methods of initial evaluation.2
diaphragm [see Figure 3]. On the left side, the spleen and
Technique Sonographic detection of pericardial effusion kidney are first viewed at approximately the ninth or 10th
is straightforward, requiring no specialized knowledge of echo- intercostal space in the posterior axillary line, and the trans-
cardiographic cardiac anatomy. This echocardiographic ducer is simply advanced cephalad until the left hemidiaphragm
portion of the FAST examination is performed using a curved and the supradiaphragmatic space are identified. The 97.5%
04/09
a b
c d
Figure 1 (a) Transducer position for a subxiphoid view of

the heart. (b) Normal four-chamber view of the heart from
the subxiphoid position. (c) Transducer position for a
parasternal long view of the heart. Note orientation along a
line between the right shoulder and the left hip. (d ) Normal
parasternal long view. (e) Positive echocardiogram showing
pericardial fluid.
04/09
a b
c d
Figure 2 (a) Transducer position for the right upper quadrant (RUQ) portion of the FAST examination for trauma. (b) Normal
RUQ scan showing the liver and kidney. (c) Fluid seen in the Morison pouch in an RUQ scan (arrow). (d ) Transducer position
for the left upper quadrant (LUQ) portion of the FAST examination for trauma. Note the slightly higher position and more
posterior than that for the RUQ.
sensitivity and 99.7% specificity observed for thoracic ultraso- A comet tail artifact, manifested by hyperechoic streaks extend-
nography were similar to those for portable chest x-rays in the ing down from the visceral and the parietal pleural interface, is
trauma bay. The accuracy of this technique was only slightly also commonly seen when imaging a normal lung. In the
less when used in the critical care setting to detect pleural effu- absence of these two findings, a pneumothorax will be present
sion (94% accuracy).4 99% of the time.5,6 Visualizing of the lung slide can be enhanced
by using a linear array transducer (7.5 MHz) oriented for sagit-
Detection of Pnemothorax tal sections and applying power color Doppler mode (“power
Using ultrasonography to detect pneumothorax is slightly slide”).7 Although neither of these methods eliminates com-
more challenging as it requires recognition of the “absence” of pletely the need for a chest x-ray, they may be very useful in
the normal findings seen with an expanded lung. To perform situations such as the operating room, the intensive care unit
this examination, a 3.5 MHz phased array transducer is held in (ICU), or an austere environment when an x-ray is delayed or
a sagittal orientation in the second intercostal space in the unavailable.
midclavicular line. The examination is performed over several
respiratory cycles. A normal lung will demonstrate a “lung-sliding” Evaluation of Patients with Solid Organ Injuries
sign, seen as a to-and-fro motion at the interface between the The treatment of a stable patient with a solid organ injury
visceral and parietal pleura with respirations [see Figure 4 ]. (liver, spleen, kidney) identified on a computed tomographic
04/09
e f
g h
Figure 2 (e) Normal LUQ view showing the spleen and kidney. ( f ) Positive LUQ scan showing fluid around the spleen (arrow).
( g) Transducer position for a pelvic image of the FAST examination (sitting on the pubic bone and aimed toward the feet). (h)
Fluid in the pelvis using a full bladder as the acoustic window.
(CT) scan is most often observational. However, the need for u s e of u ltras onograp hy in the s u r gic al ic u
follow-up imaging to identify patients whose injuries have
progressed and/or those who have developed complications is Central Line Placement Using Ultrasound Guidance
controversial. Abdominal CT scanning, although extremely In the United States, an estimated 5 million central venous
accurate, is expensive and delivers additional radiation (of par- catheters are inserted annually for the purposes of monitoring
ticular concern in the management of pediatric trauma). We hemodynamic variables, administering fluids and medications,
hypothesized that surgeon sonographers could successfully or providing parenteral nutrition.9 Unfortunately, the use of
follow these injuries using ultrasonography. The surgeons central venous catheters is associated with a number of com-
involved in our study had considerable training and experience plications, which are both hazardous for the patient and expen-
in performing ultrasound examinations, but we were only able sive to treat. Mechanical complications occur in 5 to 19% of
to visualize the actual organ injury approximately one third of patients, infectious complications in 5 to 26%, and thrombotic
the time.8 However, we successfully detected 13 of the 15 events in 2 to 26%. Using ultrasound guidance during insertion
complications, including intra-abdominal abscesses, arterial of an internal jugular (IJ) catheter has been demonstrated to
pseudoaneurysms, and bilomas. More importantly, we were reduce the time required for insertion, the rates of unsuccessful
able to assess the amount of hemoperitoneum present during attempts, and the number of carotid artery punctures. A recent
serial examinations and thus determine more accurately than meta-analysis of 18 trials concluded that the use of ultrasonog-
by following hematocrits that patients were still bleeding. raphy to place central lines resulted in a significant reduction
04/09
a b
Figure 3 (a) Normal ultrasound view of the pleural space (arrow at diaphragm). (b) Ultrasound view of a hemothorax (arrow).
a b
Figure 4 (a) A 7.5 MHz transducer in the second intercostal space for evaluation of a potential pneumothorax. (b) Normal lung
markings. Note the “comet tail” effect from a normal air artifact. The interface between the parietal and visceral pleura is
marked with the upper arrow (point of observation for the “lung slide”).
in failure rates (risk difference ⫺12, 95% confidence interval using ultrasound guidance versus 425 patients using surface
[CI] ⫺0.18 to ⫺0.06), the number of attempts (risk reduction landmark techniques ( p < .001). The time for line placement
1.41, 95% CI 1.15 to 1.67), and arterial puncture rates (risk and the number of attempts were also significantly reduced in
difference ⫺0.07, 95% CI ⫺0.10 to ⫺0.03).10 Ultrasonongra- the ultrasound group. In the landmark group, hematoma for-
phy improved outcomes most convincingly for IJ vein cannula- mation occurred in 8.4%, hemothorax in 1.7%, pneumothorax
tion (as opposed to the subclavian vein) and when used by in 2.4%, and central venous catheter–associated bloodstream
clinicians less experienced at line placement. Karakitsos and infection in 18%, which were all significantly more common
colleagues performed a prospective comparison of the land- than in the ultrasound group ( p < .001).
mark technique versus real-time ultrasound-guided catheteriza-
tion of the IJ veins in critically ill patients.11 This randomized
study included 450 patients in each of the two study arms. Technique of Placing an IJ Catheter Under
There were no significant differences between the two groups Ultrasound Guidance
in gender, body mass index, previous catheterization, skeletal Step 1: Assemble the equipment listed in Table 2.
deformities, or other factors that could make line placement Step 2: Don personal protective gear and a sterile gown
difficult. The clinicians involved in the study had considerable and gloves.
experience in inserting central lines (10 years on average). Can- Step 3: Place the patient in the head-down position if
nulation of the IJ vein was accomplished in all 450 patients possible.
04/09
Table 2 Equipment Needed for Central Line Placement central venous catheter placement are arterial puncture,
hematoma formation, and pneumothorax. A chest radiograph
Standard commercial central catheter insertion kit
should be obtained immediately after any central venous
Large barrier drape catheterization attempt to evaluate for pneumothorax and to
Sterile gown/gloves confirm proper catheter position prior to its use. Arterial
puncture, which occurs in 6 to 9% of attempts, is more
Mask, eyewear, hat (personal protective gear)
common with IJ line placement than with subclavian cathe-
7.5 linear array transducer connected to standard ultrasound unit terization. If arterial puncture is recognized at the time of
Sterile conduction gel needle placement, it is managed by withdrawing the needle
Sterile plastic sheath/probe cover
and maintaining gentle pressure over the artery for several
minutes while observing for hematoma formation. If the
injury is recognized after the dilator is in place, it should be
Step 4: Standing at the head of the bed, identify the rel- left in place and a vascular surgeon consulted; removal of the
evant surface anatomy: the mastoid process, clav- catheter may require endovascular stenting or suture closure
icle, and clavicular and sternal heads of the ster- of the carotid artery. Pneumothorax (incidence of 0.2 to 1%
nocleidomastoid muscle. with IJ catheters) is slightly less likely than with subclavian
Step 5: Prepare the area widely with chlorhexidine and lines and is generally caused by advancing the needle too far
drape widely. in search of the vein instead of withdrawing to reassess the
Step 6: Insert the ultrasound transducer into the sterile position and course of the needle. Small pneumothoraces (<
sheath after placing conduction gel into the 10%) may be observed and reevaluated with chest imaging 6
bottom of the probe cover. hours later; larger or symptomatic pneumothoraces require
Step 7: Place a small amount of sterile conduction gel on tube thoracostomy.
the skin surface at the junction of the two heads
of the sternocleidomastoid muscle. Assessment of Volume Status in the ICU with Ultrasound
Step 8: Holding the transducer parallel to and just above Techniques
the clavicle, locate the IJ vein. It will be larger and Surgeons are beginning to use bedside ultrasonography to
flatter than the adjacent carotid artery, which is assess cardiac function and to estimate volume status in the
located medial to the vein [see Figure 5a]. A patent ICU. One simple measure is to note the relative collapse of
IJ vein should be compressible if it does not con- the right ventricle in a patient who is volume depleted.
tain thrombus. Rarely, color flow or Doppler Another method is to measure the diameter of the inferior
applications may be needed. Once the vein is vena cava (IVC) during resuscitation. Using a standard
located, orient the probe so that the vein appears abdominal transducer held for sagittal scanning, the antero-
on the right side of the screen (for right IJ vein posterior diameter of the IVC can be measured just below the
cannulation) or on the left side of the screen if the diaphragm in the hepatic segment.12 Given that the diameter
left IJ vein is used. This will minimize confusion will change with respiration, it should be measured in both
during the procedure. phases. A second measurement is taken in a transverse orien-
Step 9: Continue to visualize the vein holding the transducer tation [see Figure 6]. Yanagawa noted that the IVC diameter
with one hand while introducing the needle with the was significantly smaller (average 6.5 mm) in patients who
other hand. The direction of the needle must be at became hypotensive again after an initial response to fluid
right angles to the middle of the transducer and at resuscitation (so-called transient responders) as opposed to
an angle of 45º to the skin [see Figure 5b]. stabilized patients, in whom the IVC diameter averaged 10.7
Step 10: Once the needle is seen to enter the vein, aspirate mm.12 In a more advanced study, Gunst and colleagues mea-
back with a syringe to confirm free venous flow sured both stroke volume and IVC diameter using ultraso-
[see Figures 5c to 5e]. nography and compared their estimates of cardiac index
Step 11: Pass the guide wire through the needle, monitoring based on ultrasound data compared with the results found
for any cardiac arrhythmias (should they occur, with more directly measured indices using pulmonary artery
pull the guide wire back). The needle can now be catheterization.13 These surgeons were very accurate in esti-
withdrawn from the vein, leaving the wire intact. mating cardiac index and CVP; however, each of these inves-
Step 12: Using a blade, make a small skin incision at the tigators had completed 2 days of focused cardiac ultrasound
entrance of the wire and pass the catheter-dilator training and had 5 to 15 years of ultrasound training prior to
assembly over the wire into the vein. The catheter participating in this study. Nonetheless, it is clear that the
can also be visualized by ultrasonography. utility of bedside ultrasonography in estimating volume status
Step 13: Remove the dilator and wire together, then use a will continue to expand in the near future.
syringe to aspirate air from the catheter, confirm
venous return, and demonstrate that fluid can be Ultrasound-guided Thoracentesis
infused without excessive pressure. Pleural effusions can be easily diagnosed and aspirated under
Step 14: Suture the catheter securely in place. ultrasound guidance in the ICU.14 In one recent study of ultra-
Step 15: Confirm the position with x-ray. sound-guided thoracentesis in patients receiving mechanical
Complications associated with placement of an IJ ventilation, pneumothorax occurred in only 1.3% of the 232
catheter The most common immediate complications of patients who underwent this procedure.15 Pigtail catheters can
04/09
a b
c d
Figure 5 (a) A 7.5 MHz transducer in a sterile bag for real-

time imaging during placement of a central line. Note the
acoustic gel inside the bag and the rubber band occlusion
technique to avoid an air artifact. (b) Ultrasound image of the
right carotid artery and internal jugular (IJ) vein. (c) Internal
jugular vein collapsed with gentle pressure (normal).
(d ) Angle of the needle relative to the transducer. Note that
the needle aims for the middle of the transducer and must
enter at 90º to the transducer to be imaged on a sonogram.
(e) Needle seen on a sonogram in the internal jugular vein
(arrow).
04/09
a b
Figure 6 (a) Measurement of the inferior vena cava diameter (sagittal) at the level of the diaphragm (+ markings are calibers).
(b) Transverse measurement of the inferior vena cava at the same level.
Table 3 Equipment Needed for Thoracentesis / Paracentesis Step 8: If prolonged drainage is necessary, a larger cath-
eter can be advanced into this area using the
Standard central line insertion kit
Seldinger technique, attaching the catheter to a
Large barrier drape water-sealed drainage system.17
Sterile gown/gloves
Ultrasound and Paracentesis
Paracentesis is another useful technique that is also made safer
Caldwell needle (15 gauge) under ultrasound guidance. In the ICU, paracentesis can be
Sterile extension tubing used to sample abdominal fluid for diagnosis (blood, intestinal
contents, infection) or as a method of relieving pressure (ascites
Syringe
or secondary intra-abdominal hypertension following burns or
Scalpel overzealous resuscitation). The right and left lower quadrants
Local anesthetic are the most dependent locations and the easiest to access (gen-
erally above and medial to the superior iliac spine). Safe entry
also be inserted using ultrasonography.16 The equipment points for paracentesis that avoid the inferior epigastric vessels
needed for these procedures is outlined in Table 3. were mapped out recently by Saber and colleagues.18
Technique for Performing Ultrasound-Guided Thoracentesis Technique for Performing Ultrasound-Guided Paracentesis
Step 1: Position the patient either in the lateral decubitus Step 1: Assemble the equipment listed in Table 3.
(the affected side up) or the supine position. Ele- Step 2: The abdomen is scanned using a 3.5 MHz curved
vation of the head of the bed may also be useful. array transducer to locate the fluid collection(s).
Step 2: Perform the ultrasound examination (using a Step 3: Place the patient in a supine position of comfort.
3.5 MHz convex transducer) to locate the diaphragm, Step 4: Don personal protective gear, including a gown
liver (or spleen), and targeted pleural fluid. and gloves.
Step 3: If possible, switch to a 7.5 MHz linear probe to Step 5: Scrub the anterior abdominal wall with chlorhex-
visualize the ribs and vascular structures within idine solution and drape the region.
the chest. Step 6: Infiltrate the skin of the intended puncture site
Step 4: Choose a puncture site allowing at least one rib with local anesthetic.
space of fluid above and below. Step 7: Use the scalpel to make a nick in the skin to allow
Step 5: Mark the site, prepare the chest, and then inject passage of the needle.
the area generously with local anesthesia, includ- Step 8: Advance the Caldwell needle through the abdom-
ing the pleural surface. inal wall while aspirating with a syringe (note:
Step 6: Insert a 18- to 20-gauge sheath needle into the tar- ultrasonongraphy can be used to guide the needle
geted area, confirming the location of the needle into the fluid collection).
with ultrasonography, and perform the aspiration. Step 9: Once fluid is seen to enter the syringe, stop
Step 7: Once the fluid has been completely removed, with- advancing the needle. The drainage catheter
draw the needle while applying constant negative should be advanced over the needle into the fluid
pressure to minimize the chance of pneumothorax. and the needle removed.
04/09
Step 10: If prolonged drainage is required (as with tense Technique for Performing a Venous Ultrasound Examination
ascites), the catheter can be attached to a collec- Step 1: Position the patient in a supine and reversed
tion canister. Trendelenburg position (if possible), with the leg
Step 11: Observe the wound for ascetic leak and/or the abducted and externally rotated and the knee
development of a hematoma, and then dress it flexed.
with a transparent dressing. Step 2: Using a 7.5 MHz linear transducer held in a trans-
verse position, identify the common femoral vein
Complications of thoracentesis and paracentesis and artery at the level of the inguinal ligament.
The principal complications of thoracentesis are pneumotho- Step 3: The initial imaging should be done using the
rax and hemothorax. Drainage of very large effusions may B-mode (grayscale).
also lead to reexpansion pulmonary edema, although this is a Step 4: Focusing on the vein, apply pressure until the
rare entity. In one recent study of ultrasound-guided vein collapses. Follow the vein down in a trans-
thoracentesis in patients receiving mechanical ventilation, verse plane, using serial compression applied at 1
pneumothorax occurred in only 1.3% of the 232 patients who to 2 cm intervals.
underwent this procedure.15 As noted above with IJ cannula- Step 5: The vein will dive deep above the knee but can
tion, small pneumothoraces may be observed, but larger be visualized again posterior to the knee.
(> 10%) or symptomatic cases require tube thoracostomy. Step 6: Although the hallmark of DVT is a lack of com-
Hemothorax complicating thoracentesis is particularly trou- pressibility, occasionally, a thrombus will be visi-
bling because it suggests injury to an intercostal vessel, which ble within the lumen [see Figure 7].
may bleed significantly and potentially require operative liga- Step 7: Flow can be visualized within the vein by applying
tion. A routine chest radiograph should be obtained following color and Doppler imaging. With the transducer
the procedure, and attention should be paid to significant still in a transverse orientation, find the common
hematoma or oozing from the puncture site. femoral vein or artery and apply color flow. Keeping
Paracentesis may be complicated by abdominal wall hem- the vein in view, orient the transducer for longitudi-
orrhage and by hemodynamic instability resulting from fluid nal imaging. Once flow is visualized in the thigh,
shifts. Large-volume paracentesis leads to fluid and protein squeezing the calf muscles should increase the flow
losses with accompanying hypovolemia, hypotension, and signal. Clinically significant DVT below the level of
even acute renal insufficiency. Empiric replacement of pro- the thigh is unlikely if augmentation is present.
teinaceous solute by infusion of salt-poor albumin is generally Step 8: Repeat these same steps on the opposite side and
practiced (50 mL of 25% albumin for each liter of ascites compare images and results.
drained). If the puncture site is not carefully selected, inferior
epigastric vessel injury may occur, leading to expanding
abdominal wall hematoma and/or hemoperitoneum. If this Other Bedside Procedures
occurs and the hematoma does not tamponade the bleeding, p ercu taneou s tracheos tomy
exposure and ligation of the vessels will be necessary.
Operative tracheostomy has been performed for several cen-
turies, and the typical modern technique was standardized by
Detection of Venous Thrombosis with Duplex Ultrasonography Jackson in 1909. A percutaneous Seldinger technique was
Critically ill and injured patients are at high risk for poten- developed in the 1980s by Ciaglia and colleagues and has
tially lethal venous thromboembolism. Unfortunately, the gained popularity in recent years because of its suitability for
current methods of venous thromboembolism prophylaxis are performance at the bedside.20 Use of videobronchoscopic guid-
often contraindicated in the patients who are at greatest risk, ance has reduced immediate complications, but it should be
and surveillance for deep vein thrombosis (DVT) is frequently recognized that operative (“open”) tracheostomy remains the
used even in the absence of symptoms. Additionally, an gold standard as it allows for more control and has lower rates
immediate DVT scan can be helpful when pulmonary embo- of long-term complications, such as subglottic stenosis.21,22
lism is suspected in ICU patients. The sensitivity and speci- Indications for tracheostomy include orofacial trauma, resec-
ficity for duplex ultrasonography in symptomatic patients are tion of head or neck malignancy, and the need for prolonged
very high, and this study has now replaced venography as the mechanical ventilation. The timing of tracheostomy in critically
primary imaging procedure for the detection of DVT. Com- ill patients has long been debated, and ongoing clinical trials
pressibility under probe pressure is the most accurate test, strive to determine the optimal timing. The basic principle is to
reaching 97 to 100% sensitivity and 99% specificity for the perform the procedure early enough to facilitate subacute care
diagnosis of femoral and popliteal DVT.19 In contrast, the and reduce oropharyngeal, sinus, and pulmonary complications;
visibility of the thrombus as a fixed, echoic image within however, performing tracheostomy too early in a course of
the lumen has a sensitivity of only 50%. DVT should also be mechanical ventilation will lead to unnecessary procedures on
suspected when there is a lack of augmentation of flow above those patients who were nearing extubation at the time of oper-
the area being compressed. As with any ultrasound examina- ation. The TracMan clinical trial conducted at Oxford University
tion, the accuracy is highly dependent on the expertise of the randomized over 900 critically ill patients to early (days 1 to 4)
examiner, and we do not mean to imply that surgeons will versus late (day 10 or later) tracheostomy. This represents the
have the same excellent results as registered vascular techni- largest coordinated effort yet to determine the optimal timing of
cians. However, focused venous ultrasound examinations tracheostomy; recruitment completed in December 2008, and
should be within the skill set of a general surgeon. the results are expected to be reported in 2009.23
04/09
Figure 7 Ultrasound image of a femoral vein deep vein thrombosis (markers).
Tracheostomy is a clean-contaminated operation because a centimeter below the vocal folds. Maintain this
the respiratory tract is entered. These wounds are far from endoluminal view of the trachea.
sterile as there is considerable contamination by respiratory
secretions and saliva. However, infections are infrequent, and
there is no role for prolonged courses of antibiotic therapy Table 4 Equipment Needed for Percutaneous Tracheostomy
beyond a single preincision dose, as is the general recommen-
Large barrier drape
dation for clean-contaminated operations.
Sterile gown/gloves
Technique for Percutaneous Tracheostomy Mask, eyewear, hat (personal protective gear)
Step 1: Assemble the equipment listed in Table 4. Bronchoscope

Step 2: Position the patient so as to slightly raise the Laryngoscope and endotracheal tube
shoulder off the bed and extend the neck. Tracheostomy tube (at least two sizes)
Step 3: Don personal protective gear, including a sterile
Seldinger tracheostomy kit with dilator
gown and gloves.
Step 4: Scrub the anterior neck from the chin to the ster- Skin suture and needle holder
nal notch with chlorhexidine solution and place Ventilator tubing adapter for bronchoscope and accordion
sterile drapes. extension for tracheostomy
Step 5: Ask the bronchoscopist to advance the scope Scalpel
down the endotracheal tube and visualize the
carina and then withdraw the scope to a position Syringe
04/09
Step 6: Withdraw the endotracheal tube so that the tip is Step 13: Remove instruments for reprocessing and dispose
repositioned just distal to the bronchoscope tip. of sharp waste.
Step 7: Identify a point in the midline of the anterior
neck, midway between the cricothyroid mem- Complications of percutaneous tracheostomy
brane and sternal notch. Apply local anesthetic to Following tracheostomy, patients should initially be cared
this site and then use an 18-gauge needle attached for in an ICU owing to the potential severity of complica-
to a 10 mL syringe to puncture the trachea. It is tions. The site should be observed for bleeding, cellulitis,
critical that the puncture be visualized by the or development of subcutaneous emphysema. Dislodgment
bronchoscope and be in the midline of the ante- or misplacement of the tracheostomy tube must be imme-
rior trachea and not too close to the cricothyroid diately corrected as this will lead to death in short order. If
cartilage [see Figure 8]. possible, the tube should be reinserted, but often the safest
Step 8: Pass the guide wire through the needle into the approach is to resecure the airway by orotracheal intubation
trachea and remove the needle. and then convert to a formal (“open”) tracheostomy in the
Step 9: Make a 2 cm transverse skin incision centered on operating room. Significant bleeding around the tracheos-
the wire. Do not cut deep to the skin as bleeding tomy tube usually signifies injury to the thyroid parenchyma
from the thyroid or thyroid vessels can be prob- or one of its vessels; if this does not abate with hematoma
lematic and require operative repair. tamponade in a matter of minutes, this, too, requires oper-
Step 10: Apply generous sterile lubricant to the assembled ative intervention.
tracheostomy tube–dilator device, then pass it over A first tracheostomy tube change should be avoided at
the wire and twist it while pushing posteriorly to all costs during the first 10 days as there is the potential
dilate the tracheal puncture site and pass the trache- for fatal airway loss. Even after 10 days, any tracheostomy
ostomy tube. Once in the trachea (visualized by the tube change should be performed with airway rescue equip-
bronchoscope), immediately remove the dilator ment and supplemental oxygen available, an informed
while holding the tracheostomy tube in place. nurse at the bedside to assist as needed, knowledge of the
Step 11: Confirm proper ventilation through the tracheos- patient’s native anatomy by the surgeon (i.e., is the larynx
tomy tube and then remove the endotracheal tube. patent, thus permitting orotracheal intubation), and a
Step 12: Suture the faceplate of the tracheostomy tube to spare tracheostomy tube one size smaller than the one in
the adjacent skin and further secure it with a the patient’s airway. The presence of a respiratory thera-
necklace-type tie around the neck. pist is encouraged, especially for the first change.
Figure 8 Anatomic land markings of the neck. V = thyroid notch; box at the cricothyroid
membrane; broken line at the thyroid isthmus; solid line at the first tracheal ring; curved
line at the sternal notch.
04/09
t u be t hor a c o st o m y fastidious draping. It remains unclear whether presumptive or

Thoracostomy tubes (“chest drains” or “chest tubes”) prophylactic antibiotics prevent empyema related to chest
are placed to evacuate air or fluid in the pleural space and drain placement. Although the answer remains unclear, a
have become a primary treatment modality for pleural dis- recent multicenter trial in trauma patients failed to demon-
ease since first described by Hewett in 1876. Pneumotho- strate a benefit of antibiotic administration.25 If antibiotics are
rax may occur spontaneously, following injury, or as the administered, they should be given prior to beginning the
result of instrumentation, such as with percutaneous procedure and be limited to one dose of a first-generation
biopsy or thoracentesis. Pneumothoraces can be treated cephalosporin.
with standard chest tubes (of any size) or with pigtail cath- Technique for Tube Tracheostomy
eters inserted using a Seldinger technique. Fluid can accu-
Step 1: Assemble the equipment listed in Table 5. If the
mulate in the pleural space as a result of many different
patient is stable, consider administering an intra-
processes, including trauma, pneumonia, malignancy, and
venous narcotic.
congestive cardiac disease. Drains placed for simple fluid
Step 2: Position the patient with the affected side tilted
may be of smaller caliber, but those placed for hemothorax
up and the ipsilateral arm raised above the head
should be larger to prevent blockage by coagula (typically
[see Figure 9].
36 French for adults).
All hemothoraces should be promptly drained to prevent
fibrothorax and possible trapped lung. Failure to promptly
drain blood in the pleural space will render this technique Table 5 Equipment Needed for Tube Thoracostomy
ineffective, and formal decortications (i.e., via video-assisted Large barrier drape
thoracic surgery) will be required. Other fluid collections Sterile gown/gloves
should be drained and the underlying pathology addressed to
prevent recurrent accumulation. Special caution should be
taken when addressing malignant effusions because these Standard commercial central catheter insertion kit
have a tendency to reaccumulate after drain removal. If the Suitably sized chest tube
underlying disease is not going to be treated, the patient
Scalpel, large hemostat, needle driver
should generally either be treated with pleurodesis (to obliter-
ate the pleural space and prevent recurrence) or placement of Heavy silk or nylon suture
a chronic, tunneled pleural drain.24 Local anesthetic
These chest procedures must always be performed in as Drain trap/suction regulator
sterile a fashion as possible, although the immediacy of ten-
Occlusive dressing
sion physiology may sometimes require the surgeon to forgo
Figure 9 Correct position for placement of a chest tube. Note that the tube is directed
posterior and cephalad and the right arm is raised above the head.
04/09
Step 3: Don personal protective gear, including a sterile removal. Some prefer tube removal during forced expiration
gown and gloves. to increase intrapleural pressure and thus decrease the risk of
Step 4: Scrub the anterolateral chest wall with chlorhexi- recurrent pneumothorax. With this approach, however, some
dine solution and drape the region. patients suddenly gasp with surprise or pain, suddenly drop-
Step 5: Palpate the chest wall to identify an intercostal ping the intrapleural pressure and potentially drawing air in
space around the fifth rib. In men, the nipple is a through the tube tract. Another school of thought is to remove
useful surface landmark to indicate the height of the tube while the patient maintains maximal inspiration.
the dome of the diaphragm, below which one
should generally not stray. Principles and Process of Documenting
Step 6: Infiltrate the skin with local anesthetic and make Competency in Surgical Skills
a skin incision at the interspace below the intended Although documenting knowledge in surgery has been
thoracostomy site. Bluntly separate the subcuta- standardized by the American Board of Surgery, demonstra-
neous tissue and overlying muscle to arrive at the tion of skills has not as yet become part of the certification
rib and intercostal musculature. Infiltration of process. How one acquires, practices, and perfects a surgical
local anesthetic in the periosteum and pleura is a skill is an area of great interest to educators and the public
useful but often ignored step. alike. Although, certainly, the time spent learning and prac-
Step 7: Blunt spreading over the top of a rib allows punc- ticing will vary with the task, with each new skill, the essen-
ture through the pleura into the intercostal space, tials include the following:
after which the tube can be slid in while pointing
it superiorly and posteriorly. Creation of a proper 1. A period of didactic, hands-on instruction by an expert
subcutaneous tract and direction of the tube 2. A period of practice, often while being mentored
toward the thoracic apex decrease the likelihood 3. Demonstration of acquisition of the skill
of the tube entering a pulmonary fissure. 4. Continued practice-based learning including participation
Step 8: Secure the tube to the adjacent skin with a heavy in performance improvement programs and continued
suture of silk or nylon. education
Step 9: Connect the tube to the drain trap–suction device The Surgical Institutes, currently being developed through
and apply an occlusive dressing. the Education Division of the American College of Surgeons
Step 10: Remove instruments for reprocessing and dispose (ACS), will form the basis for development of a standard cur-
of sharp waste. riculum (including skills training) for each level of residency.
For a visual reference, readers are referred to the video Another group that has been very proactive in this arena is the
featured in the New England Journal of Medicine.26 Society of Gastrointestinal Surgeons (SAGES), which has
Traditionally, all chest drains were initially placed to suc- developed and propagated the “Fundamentals of Laparoscopic
tion (20 cm water) and subsequently transitioned to water Surgery” course. In ultrasonography, the ACS Ultrasound
seal (a one-way safety valve with no applied suction) as the Education Committee has developed a series of courses includ-
volume of output decreased. For many chest tube indica- ing Level I certification (attendance at the course), Level II
tions, a growing body of evidence supports placement of certification (passing a skill set), and Level III certification
chest drains to water seal from the outset. This has been (acquisition of skills under proctorship until reaching the expert
demonstrated to accelerate the resolution of air leaks and or instructor level). In particular, the skills-oriented postgradu-
duration of chest tubes.27 ate course “Ultrasound in the Surgical ICU” is an excellent
model for introducing bedside ultrasound techniques. Once
learned, how many examinations are necessary before profi-
Complications of tube thoracostomy The most ciency is attained is unclear but certainly varies with the nature
common immediate complication of this procedure is a mal- of the examination. In trauma, 25 FAST examinations per-
positioned tube, whether in an interlobar fissure, occluded by formed under supervision is generally considered adequate,
a kink, or even placed completely within the chest wall rather although it is important that some of those examinations include
than the pleural space. A chest radiograph should be obtained patients with positive findings. The American Society of Breast
after the placement of any chest drain to verify tube position Surgeons requires at least 100 breast ultrasound examinations
and to determine if the pleural air or fluid is beginning to prior to applying for credentialing. There has been limited suc-
drain properly. Inadequate tube position may sometimes be cess in using simulators to introduce ultrasound skills.28
addressed by sterile withdrawal and resuturing, but once a Recently, Hutton and Wong documented improvement in
tube has been placed, it should never be advanced. Much placement of chest tubes by junior house staff after practicing
more rarely, tube placement may cause injury to the pulmo- on a patient simulator.29 A recent systematic review concluded
nary parenchyma or bleeding from an intercostal or pulmo- that simulation-based training seems to be transferable to the
nary vessel. The latter should be suspected with persistent operating room.30 In this era of decreased time spent in training,
voluminous bloody output and/or any hemodynamic instabil- surgical educators are challenged to develop more efficient
ity after tube placement. Such vascular injuries require oper- methods of ensuring that general surgeons have acquired com-
ative intervention for definitive control. petency in both operative and bedside skills, with patient safety
Removal of chest tubes should be done with care not to and satisfaction as the ultimate measures of success.
allow air to entrain into the pleural space. This is primarily
accomplished by maintaining an occlusive dressing over the
tube site and asking the patient to cooperate with tube Financial Disclosures: None Reported.
04/09
References
1. Rozycki GS, Ballard RB, Feliciano DV, et al. 11. Karakitsos D, Labropoulos N, De Groot E, simple bedside procedure; preliminary report.
Surgeon-performed ultrasound for assess- et al. Real-time ultrasound-guided catheter- Chest 2005;128:816–20.
ment of truncal injuries: lessons learned ization of the internal jugular vein: a prospec- 21. Norwood S, Vallina VL, Short K, et al. Inci-
from 1540 patients. Ann Surg 1998;228: tive comparison with the landmark technique dence of tracheal stenosis and other late com-
557–67. in critical care patients. Crit Care 2008; plications after percutaneous tracheostomy.
2. Rozycki GS, Feliciano DV, Ochsner G, et al. 10:R162. Ann Surg 2000;232:233–41.
The roles of ultrasound in patients with possi- 12. Yanagawa Y, Sakamoto T, Okada Y. Hypo- 22. Raghuraman G, Rajan S, Marzouk JK, et al.
ble penetrating cardiac wounds: a prospective volemic shock evaluated by sonographic mea- Is tracheal stenosis caused by percutaneous
multicenter study. J Trauma 1999;46:543–51. surement of the inferior vena cava during tracheostomy different from that by surgical
3. Sisley AC, Rozycki GS, Ballard RB, et al. resuscitation in trauma patients. J Trauma tracheostomy? Chest 2005;127:879–85.
Rapid detection of traumatic effusion using 2007;63:1245–8. 23. TracMan. Tracheostomy management in
surgeon-performed ultrasonography. J Trauma 13. Gunst M, Ghaemmaghami V, Sperry J, et al. critical care. Available at: http://www.tracman.
1998;44:291–7. Accuracy of cardiac function and volume sta- org.uk (accessed December 2008).
4. Rozycki GS, Pennington SD, Feliciano DV. tus estimates using the bedside echocardio- 24. Trembly A, Michaud G. Single-center expe-
Surgeon-performed ultrasound in the critical graphic assessment in trauma/critical care. rience with 250 tunnelled pleural catheter
care setting: its use as an extension of the J Trauma 2008;65:509–16. insertions for malignant pleural effusion.
physical examination to detect pleural effu- 14. Bouhemad B, Zang M, Lu Q, Rouby JJ. Clin- Chest 2006;129:363–8.
sion. J Trauma 2001;50:636–42. ical review: bedside lung ultrasound in critical 25. Maxwell RA, Campbell DJ, Fabian TC, et al.
5. Dulchavsky SA, Schwarz KL, Kirkpatrick care practice. Crit Care 2007;11:205. Use of presumptive antibiotics following tube
AW, et al. Prospective evaluation of thoracic 15. Mayo PH, Goltz HR, Tafreshi M, Doelken P. thoracostomy for traumatic hemopneumothorax
ultrasound in the detection of pneumothorax. Safety of ultrasound-guided thoracentesis in in the prevention of empyema and pneumonia-a
J Trauma 2001;50:201–5. patents receiving mechanical ventilation. multi-center trial. J Trauma 2004;57:742–9.
6. Knudtson JL, Dort JM, Helmer SD, Smith Chest 2004;125:1059–62. 26. Nascimiento B, Simone C, Chien V. Videos
RS. Surgeon-performed ultrasound for pneu- 16. Liang SJ, Tu CY, Chen HJ, et al. Application in clinical medicine: chest-tube insertion.
mothorax in the trauma suite. J Trauma of ultrasound-guided pigtail catheter for N Engl J Med 2007;357:e15.
2004;56:527–30. drainage of pleural effusions in the ICU. 27. Cerfolio RJ, Bryant AS, Singh S, et al. The
7. Cunningham J, Kirkpatrick AW, Nicolaou S, Intensive Care Med 2009;35:350–4. management of chest tubes in patients with a
et al. Enhanced recognition of “lung sliding” 17. Nicolaou S, Talsky A, Khastoggi JD, et al. pneumothorax and an air leak after pulmo-
with power color Doppler imaging in the Ultrasound-guided interventional radiology in nary resection. Chest 2005;128:816–20.
diagnosis of pneumothorax. J Trauma critical care. Crit Care Med 2007;35:5186–97. 28. Knudson MM, Sisley AC. Training residents
2002;52:769–71. 18. Saber AA, Meslemani AM, Davis R, Pimentel using simulation technology: experience with
8. Rozycki GS, Knudson MM, Shackford SR, R. Safety zones for anterior abdominal wall ultrasound for trauma. J Trauma 2000;48:
Dicker R. Surgeon-performed bedside organ entry during laparoscopy: a CT scan mapping 659–65.
assessment with sonography after trauma of epigastric vessels. Ann Surg 2004;239: 29. Hutton IA, Wong C. Using simulation to
(BOAST): a pilot study from the WTA mul- 182–5. teach junior doctors how to insert chest tubes:
ticenter group. J Trauma 2005;59:1356–64. 19. Gaitini D. Current approaches and contro- a brief and effective teaching module. Intern
9. McGee DC, Gould MK. Preventing compli- versial issues in the diagnosis of deep vein Med J 2008;38:887–91.
cations of central venous catheterization. thrombosis via duplex Doppler ultrasound. J 30. Sturm LP, Wiindsor JA, Cosman PH, et al.
N Engl J Med 2003;348:1123–33. Clin Ultrasound 1996;34:289–97. A systematic review of skills transfer after sur-
10. Keenan SP. Use of ultrasound to place cen- 20. Ciaglia P, Firsching R, Syniec C. Elective gical simulation training. Ann Surg 2008;
tral lines. J Crit Care 2002;17:126–37. percutaneous dilational tracheostomy: a new 248:166–79.
04/09
1 BASIC SURGICAL AND PERIOPERATIVE CONSIDERATIONS 1 PREVENTION OF POSTOPERATIVE
INFECTION — 1
1 PREVENTION OF POSTOPERATIVE
INFECTION
Jonathan L. Meakins, MD, DSc, FACS
Epidemiology of Surgical Site Infection

Historically, the control of wound infection depended on
antiseptic and aseptic techniques directed at coping with the
infecting organism. In the 19th century and the early part of
the 20th century, wound infections had devastating conse- HOST
quences and a measurable mortality. Even in the 1960s, BACTERIA DEFENSE
before the correct use of antibiotics and the advent of modern MECHANISMS
preoperative and postoperative care, as much as one quarter
of a surgical ward might have been occupied by patients with
wound complications. As a result, wound management, in
itself, became an important component of ward care and of
medical education. It is fortunate that many factors have
intervened so that the so-called wound rounds have become
a practice of the past. The epidemiology of wound infection
has changed as surgeons have learned to control bacteria and SURGICAL
the inoculum and to focus increasingly on the patient (the SITE
host) for measures that will continue to provide improved
results.
The following three factors are the determinants of any
infectious process1:
1. The infecting organism (in surgical patients, usually Figure 1 In a homeostatic, normal state, the determinants of
bacteria) any infectious process—bacteria, the surgical site, and host
2. The environment in which the infection takes place (the defense mechanisms (represented by three circles)—intersect
at a point indicating zero probability of sepsis.
local response)
3. The host defense mechanisms, which deal systemically
with the infectious process classified into three categories: superficial incisional SSIs
(involving only skin and subcutaneous tissue), deep incisional
Wounds are particularly appropriate for analysis of infec- SSIs (involving deep soft tissue), and organ or space SSIs
tion with respect to these three determinants. Because many (involving anatomic areas other than the incision itself that
components of the bacterial contribution to wound infection are opened or manipulated in the course of the procedure)
now are clearly understood and measures to control bacteria [see Figure 2].2,3
have been implemented, the host factors become more appar-
ent. In addition, interactions between the three determinants
play a critical role, and with limited exceptions (e.g., massive
contamination), few infections will be the result of only one
factor [see Figure 1].
Definition of Surgical Site Infection

Wound infections have traditionally been thought of as
infections in a surgical wound occurring between the skin
and the deep soft tissues—a view that fails to consider the
operative site as a whole. As prevention of these wound infec-
tions has become more effective, it has become apparent that
definitions of operation-related infection must take the entire
operative field into account; obvious examples include sternal
and mediastinal infections, vascular graft infections, and
infections associated with implants (if occurring within 1 year
of the procedure and apparently related to it). Accordingly,
the Centers for Disease Control and Prevention currently Figure 2 Surgical site infections (SSI) are classified into three
prefers to use the term surgical site infection (SSI). SSIs can be categories, depending on which anatomic areas are affected.3
DOI 10.2310/7800.S01C01
06/08
INFECTION — 2
Epidemiology of Surgical Site Infection
Wound infection is caused by exogenous or endogenous bacteria;

infection is influenced not only by the source of the infecting inoculum
but also by the bacterial characteristics.
Ensure that prophylactic antibiotics, if indicated, are present in tissue

in adequate concentrations at beginning of operation.
Endogenous factors Bacterial characteristics of importance Exogenous factors

or sources of bacteria (virulence and antibiotic resistance) or sources of bacteria
Remote sites of Skin Bowel Nature and site Size of Operating Operating
infection of operation inoculum team–related room–related
required to
Postpone elective Is the operation produce • Comportment • Traffic control
operation if possible. • Clean infection • Use of • Cleaning
Treat remote infection • Contaminated impermeable • Air
appropriately. • Clean- Varies in drapes and
contaminated different gowns
• Dirty or clinical • Surgical scrub
infected situations. [see Sidebar
Preoperative
Preparation
of the
Operative Site]
Preventive measures to control bacteria
• Decontamination of patient's skin [see Sidebar Preoperative

Preparation of the Operative Site]
• Bowel preparation
• Prophylactic antibiotics
Right antibiotic
Correct timing
Right duration
[see Sidebar Antibiotic Prophylaxis of Infection and Table 7]
Surveillance and quality assurance
06/08
INFECTION — 3
HOST
DEFENSE
BACTERIA
MECHANISMS
Factors contributing to dysfunction of host defense mechanisms
can be related to surgical disease, to events surrounding the operation,
to the patient’s underlying disease, and to anesthetic management.
SURGICAL
SITE
Surgeon–related Patient–related Anesthesiologist–related

Factors influenced by the Patient-related factors • Normothermia
surgeon include include • Normovolemia
• Preoperative decisions • Presence of g3 • Pain control
• Timing of operation concomitant diagnoses • Tissue oxygenation
• Surgical technique • Underlying disease • Glucose control
• Transfusion • Age • Sterility of drugs
• Blood loss • Drug use
• Duration and extent • Preoperative nutritional
of operation status
• Glucose control • Smoking
• Tissue oxygenation
(mask)
Local factors influence the susceptibility of the wound environment by

affecting the size of the inoculum required to produce infection.
Operating team–related Patient–related
Factors influenced by the surgeon and operating team include • Age

• Duration of operation • Pao2
• Maintenance of hemostasis and perfusion • Abdominal procedure
• Avoidance of seroma, hematoma, necrotic tissue, wound • Tissue perfusion
drains • Presence of foreign body
• Tissue handling • Barrier function
• Cautery use • Diabetes
06/08
INFECTION — 4
Standardization in reporting will permit more effective sur- duration of the operation, and patient clinical status (three or
veillance and improve results, as well as offer a painless way more diagnoses on discharge).6 The National Nosocomial
of achieving quality assurance. The natural tendency to deny Infection Surveillance (NNIS) study reduced these four
that a surgical site has become infected contributes to the risk factors to three: wound classification, duration of the
difficulty of defining SSI in a way that is both accurate and operation, and American Society of Anesthesiologists (ASA)
acceptable to surgeons. The surgical view of SSI recalls one class III, IV, or V.7,8 Both risk assessments integrate the
judge’s (probably apocryphal) remark about pornography: “It three determinants of infection: bacteria (wound class), local
is hard to define, but I know it when I see it.” SSIs are usually environment (duration), and systemic host defenses (one
easy to identify. Nevertheless, there is a critical need for definition of patient health status), and they have been shown
definitions of SSI that can be applied in different institutions to be applicable outside the United States.9 However, the
for use as performance indicators.4 The criteria on which SENIC and NNIS assessments do not integrate other known
such definitions must be based are more detailed than the risk variables, such as smoking, tissue oxygen tension, glucose
simple apocryphal remark just cited; they are outlined more control, shock, and maintenance of normothermia, all of
fully elsewhere [see 1:8 Preparation of the Operating Room]. which are relevant for clinicians (although they are often hard
to monitor and to fit into a manageable risk assessment).
    
In addition, they do not incorporate a variety of other host
The National Academy of Sciences–National Research variables or operation characteristics derived from the Patient
Council classification of wounds [see Table 1], published in Safety in Surgery Study/National Surgical Quality Improve-
1964, was a landmark in the field.5 This report provided ment Program (NSQIP). These give high, medium, and
incontrovertible data to show that wounds could be classified low probabilities of SSI, which appear to be more accurate
as a function of probability of bacterial contamination but more complex to ascertain than NNIS prediction [see
(usually endogenous) in a consistent manner. Thus, wound Integration of Determinants below].10
infection rates could be validly compared from month to
month, between services, and between hospitals. As surgery
became more complex in the following decades, however, Bacteria
antibiotic use became more standardized and other risk Clearly, without an
variables began to assume greater prominence. In the early infecting agent, no
1980s, the Study on the Efficacy of Nosocomial Infection infection will result.
Control (SENIC) identified three risk factors in addition to Accordingly, most of
wound class: location of the operation (abdomen or chest), what is known about
bacteria is put to use
in major efforts directed at reducing their numbers by means
Table 1 National Research Council Classification of of asepsis and antisepsis. The principal concept is based on
Operative Wounds5 the size of the bacterial inoculum.
Clean (class I) Nontraumatic Wounds are traditionally classified according to whether
No inflammation encountered the wound inoculum of bacteria is likely to be large enough
No break in technique to overwhelm local and systemic host defense mechanisms
Respiratory, alimentary, or genitourinary
tract not entered and produce an infection [see Table 1]. One study showed
that the most important factor in the development of a wound
Clean-contaminated Gastrointestinal or respiratory tract entered
(class II) without significant spillage infection was the number of bacteria present in the wound at
Appendectomy the end of an operative procedure.11 Another quantitated this
Oropharynx entered relation and provided insight into how local environmental
Vagina entered factors might be integrated into an understanding of the
Genitourinary tract entered in absence of
infected urine problem [see Figure 3].12 In the years before prophylactic
Biliary tract entered in absence of infected antibiotics, as well as during the early phases of their use,
bile there was a very clear relation between the classification of
Minor break in technique the operation (which is related to the probability of a signifi-
Contaminated (class Major break in technique cant inoculum) and the rate of wound infection.5,13 This
III) Gross spillage from gastrointestinal tract relation is now less dominant than it once was; therefore,
Traumatic wound, fresh
Entrance of genitourinary or biliary tracts other factors have come to play a significant role.6,14
in presence of infected urine or bile
  
Dirty and infected Acute bacterial inflammation encountered,  
(class IV) without pus
Transection of “clean” tissue for the Endogenous bacteria
purpose of surgical access to a collection are a more important
of pus
Traumatic wound with retained cause of SSI than
devitalized tissue, foreign bodies, fecal exogenous bacteria. In
contamination, delayed treatment, or all clean-contaminated,
of these or from dirty source contaminated, and dirty-infected operations, the source and
06/08
INFECTION — 5
[see Sidebar Preoperative Preparation of the Operative Site],

may have specific roles in selected patients during epidemics
or in units with high infection rates. As a routine for all
patients, however, these techniques are unnecessary, time-
consuming, and costly in institutions or units where infection
rates are low.
The preoperative shave is a technique in need of reassess-
ment. It is now clear that shaving the evening before an
operation is associated with an increased wound infection
rate. This increase is secondary to the trauma of the shave
and the inevitable small areas of inflammation and infection.
If hair removal is required,15 clipping is preferable and should
be done in the OR or the preparation room just before the
operative procedure. Shaving, if ever performed, should not
be done the night before the operation.
In the past few years, the role of the classic bowel prepara-
tion [see Table 5] has been questioned [see Discussion, Infec-
tion Prevention in Bowel Surgery, below].16–21 The suggestion
has been made that selective gut decontamination (SGD)
may be useful in major elective procedures involving the
upper gastrointestinal (GI) tract and perhaps in other set-
tings. At present, SGD for prevention of infection cannot be
recommended in either the preoperative or the postoperative
Figure 3 The wound infection rate is shown here as a function
of bacterial inoculum in three different situations: a dry period.
wound with an adequate concentration of antibiotic When infection develops after clean operations, particu-
(cephaloridine > 10 µg/mL), a dry wound with no larly those in which foreign bodies were implanted, endoge-
antibiotic (placebo), and a wet wound with no antibiotic nous infecting organisms are involved, but the skin is the
(placebo, wound fluid hematocrit > 8%).12 primary source of the infecting bacteria. The air in the
operating room (OR) and other OR sources occasionally
become significant in clean cases; the degree of endogenous
contamination can be surpassed by that of exogenous con-
the amount of bacteria are functions of the patient’s disease tamination. Thus, both the operating team—surgeon, assis-
and the specific organs being operated on. tants, nurses, and anesthetists—and OR air have been
Operations classified as infected are those in which reported as significant sources of bacteria [see 1:8 Preparation
infected tissue and pus are removed or drained, providing a of the Operating Room]. In fact, personnel are the most impor-
guaranteed inoculum to the surgical site. The inoculum may tant source of exogenous bacteria.22–24 In the classic 1964
be as high as 1010 bacteria/mL, some of which may already be study by the National Academy of Sciences–National Research
producing an infection. In addition, some bacteria could be Council, ultraviolet light (UVL) was efficacious only in
in the growth phase rather than the dormant or lag phase and the limited situations of clean and ultraclean cases.5 There
thus could be more pathogenic. The heavily contaminated were minimal numbers of endogenous bacteria, and UVL
wound is best managed by delayed primary closure. This type controlled one of the exogenous sources.
of management ensures that the wound is not closed over a Clean air systems have very strong advocates, but they
bacterial inoculum that is almost certain to cause a wound also have equally vociferous critics. It is possible to obtain
infection, with attendant early and late consequences. excellent results in clean cases with implants without using
Patients should not have elective surgery in the presence these systems. However, clean air systems are here to stay.
of remote infection, which is associated with an increased Nevertheless, the presence of a clean air system does not
incidence of wound infection.5 In patients with urinary tract mean that basic principles of asepsis and antisepsis should
infections, wounds frequently become infected with the same be abandoned, because endogenous bacteria must still be
organism. Remote infections should be treated appropriately, controlled.
and the operation should proceed only under the best condi- The use of impermeable drapes and gowns has received
tions possible. If the operation cannot be appropriately considerable attention. If bacteria can penetrate gown and
delayed, the use of prophylactic and therapeutic antibiotics drapes, they can gain access to the wound. The use of imper-
should be considered [see Sidebar Antibiotic Prophylaxis of meable drapes may therefore be of clinical importance.25,26
Infection and Tables 2 through 4]. When wet, drapes of 140-thread-count cotton are permeable
Preoperative techniques of reducing patient flora, especially to bacteria. It is clear that some operations are wetter than
endogenous bacteria, are of great concern. Bowel prepara- others, but, generally, much can be done to make drapes
tion, antimicrobial showers or baths, and preoperative and gowns impermeable to bacteria. For example, drapes
skin decontamination have been proposed frequently. These of 270-thread-count cotton that have been waterproofed
techniques, particularly preoperative skin decontamination are impermeable, but they can be washed only 75 times.
06/08
INFECTION — 6
Antibiotic Prophylaxis of Infection

Selection Catheters for dialysis or nutrition, pacemakers, and shunts of
Spectrum. The antibiotic chosen should be active against the various sorts are prone to infection mostly for technical reasons,
most likely pathogens. Single-agent therapy is almost always and prophylaxis is not usually required. Meta-analysis indicates,
effective except in colorectal operations, small bowel proced- however, that antimicrobial prophylaxis reduces the infection rate
ures with stasis,emergency abdominal operations in the presen- in CSF shunts by 50%.115 Beneficial results may also be achiev-
ce of polymicrobial flora, and penetrating trauma; in such cases, able for other permanently implanted shunts (e.g., peritoneo-
a combination of antibiotics is usually used because anaerobic venous) and devices (e.g.,long-term venous access catheters
coverage is required. and pacemakers); however, the studies needed to confirm this
Pharmacokinetics. The half-life of the antibiotic selected must possibility will never be done, because the infection rates are low
be long enough to maintain adequate tissue levels throughout the and the sample sizes would have to be prohibitively large. The
operation. placement of such foreign bodies is a clean operation, and the
use of antibiotics should be based on local experience. A recent
Administration meta-analysis indicates that antibiotic prophylaxis (cefazolin)
Dosage, route, and timing. A single preoperative dose that is prevents SSI in breast surgery.116
of the same strength as a full therapeutic dose is adequate in CLEAN-CONTAMINATED CASES
most instances. The single dose should be given IV immediately
before skin incision. Administration by the anesthetist is Abdominal procedures. In biliary tract procedures (open or laparo-
most effective and efficient. scopic), prophylaxis is required only for patients at high risk: those
Duration. A second dose is warranted if the duration of the oper- whose common bile duct is likely to be explored (because of
ation exceeds either 3 hours or twice the half-life of the antibiotic. jaundice,bile duct obstruction, stones in the common bile duct,
No additional benefit has been demonstrated in continuing pro- or a reoperative biliary procedure); those with acute cholecystitis;
phylaxis beyond the day of the operation, and mounting data sug- and those older than 70 years. A single dose of cefazolin is
gest that the preoperative dose is sufficient. When massive hemo- adequate. In hepatobiliary and pancreatic procedures, antibiotic
rrhage has occurred (i.e., blood loss equal to or greater than blood prophylaxis is always warranted because these operations are
volume), a second dose is warranted. Even in emergency or clean-contaminated, because they are long, and because they are
trauma cases, prolonged courses of antibiotics are not justified abdominal, Prophylaxis is also warranted for therapeutic endosco-
unless they are therapeutic.79,114 pic retrograde cholangiopancreatography. In gastroduodenal
procedures, patients whose gastric acidity is normal or high and in
Indications whom bleeding, cancer, gastric ulcer, and obstruction are absent
are at low risk for infection and require no prophylaxis; all other
CLEAN CASES patients are at high risk and require prophylaxis. Patients under-
Prophylactic antibiotics are not indicated in clean operations going operation for morbid obesity should receive double the
if the patient has no host risk factors or if the operation does not usual prophylactic dose117; cefazolin is an effective agent.
involve placement of prosthetic materials. Open heart operation Operations on the head and neck (including the esophagus).
and operations involving the aorta of the vessels in the groin Patients whose operation is of significance (i.e., involves entry
require prophylaxis. into the oral cavity, the pharynx, or the esophagus) require
Patients in whom host factors suggest the need for prophylaxis prophylaxis.
include those who have more than three concomitant diagnoses, Gynecologic procedures. Patients whose operation is either
those whose operations are expected to last longer than 2 hours, high-risk cesarean section, abortion, or vaginal or abdominal
and those whose operations are abdominal.6 A patient who meets hysterectomy will benefit from cefazolin. Aqueous penicillin G
any two of these criteria is highly likely to benefit from prophylaxis. or doxycycline may be preferable for first-trimester abortions
When host factors suggest that the probability of a surgical site in patients with a history of pelvic inflammatory disease. In
infection is significant, administration of cefazolin at induction of
patients with cephalosporin allergy, doxycycline is effective
anesthesia is appropriate prophylaxis. Vancomycin should be
for those having hysterectomies and metronidazole for those
substituted in patients who are allergic to cephalosporins or who
are susceptible to major immediate hypersensitivity reactions to having cesarean sections. Women delivering by cesarean
penicillin. section should be given the antibiotic immediately after cord
When certain prostheses (e.g., heart valves, vascular grafts, clamping.
and orthopedic hardware) are used, prophylaxis is justified Urologic procedures. In principle, antibiotics are not
when viewed in the light of the cost of a surgical site infection to required in patients with sterile urine. Patients with positive
the patient’s health. Prophylaxis with either cefazolin or vanco- cultures should be treated. If an operative procedure is perfor-
mycin is appropriate for cardiac, vascular, or orthopedic patients med, a single dose of the appropriate antibiotic will suffice.
who receive prostheses. (continued)
Economics plays a role in the choice of drape fabric because of bacteria include the patient, the operating team (gowns,
entirely disposable drapes are expensive. Local institutional gloves with holes, wet drapes), the OR, and the equipment.
factors may be significant in the role of a specific type of In addition, the patient undergoing a longer operation
drape in the prevention of SSI. is likely to be older, to have other diseases, and to have
cancer of—or to be undergoing an operation on—a structure
   with possible contamination. A longer duration, even of
The probability of contamination is largely defined by the a clean operation, represents increased time at risk for
nature of the operation [see Table 1]. However, other factors contamination. These points, in addition to pharmacologic
contribute to the probability of contamination; the most considerations, suggest that the surgeon should be alert to the
obvious is the expected duration of the operative procedure, need for a second dose of prophylactic antibiotics [see Sidebar
which, whenever examined, has been significantly correlated Antibiotic Prophylaxis of Infection].
with the wound infection rate.6,11,13 The longer the procedure Abdominal operation is another risk factor not found in
lasts, the more bacteria accumulate in a wound; the sources the NNIS risk assessment.6,8 Significant disease and age are
06/08
INFECTION — 7
Antibiotic Prophylaxis of Infection (continued)

CONTAMINATED CASES particularly those resulting from trauma, contamination and tissue
destruction are usually so extensive that the wounds must be left
Abdominal procedures. In colorectal procedures, antibiotics
open for delayed primary or secondary closure. Appropriate
active against both aerobes and anaerobes are recommended.
timing of wound closure is judged at the time of débridement.
In appendectomy, SSI prophylaxis requires an agent or combin-
Antibiotics should be administered as part of resuscitation.
ation of agents against both aerobes and anaerobes; a single
Administration of antibiotics for 24 hours is probably adequate
dose of cefoxitin, 2 g IV, or, in patients who are allergic to β-lactam
if infection is absent at the outset. However, a therapeutic course
antibiotics, metronidazole, 500 mg IV, is effective. A combina-
of antibiotics is warranted if infection is present from the outset
tion of an aminoglycoside and clindamycin is effective if the
or if more than 6 hours elapsed before treatment of the wounds
appendix is perforated; a therapeutic course of 3 to 5 days is
was initiated.
appropriate but does not seem warranted unless the patient is
particularly ill. A laparotomy without a precise diagnosis is usu- Prophylaxis of Endocarditis
ally an emergency procedure and demands preoperative
prophylaxis. If the preoperative diagnosis is a ruptured viscus Studies of the incidence of endocarditis associated with den-
(e.g., the colon or the small bowel), both an agent active against tal procedures, endoscopy, or operations that may result in tran-
aerobes and an agent active against anaerobes are required. sient bacteremia are lacking. Nevertheless, the consensus is
Trauma. The proper duration of antibiotic prophylaxis for trauma that patients with specific cardiac and vascular conditions are
patients is a confusing issue—24 hours or less of prophylaxis is at risk for endocarditis or vascular prosthetic infection when
probably adequate, and more than 48 hours is certainly unwarr- undergoing certain procedures; these patients should receive
anted. When laparotomy is performed for nonpenetrating injuries, prophylactic antibiotics.118,119 A variety of organisms are dang-
prophylaxis should be administered. Coverage of both aerobes erous, but viridans streptococci are most common after dental
and anaerobes is mandatory. The duration of prophylaxis should or oral procedures, and enterococci are most common if the
be less than 24 hours. In cases of penetrating abdominal injury, portal of entry is the GU or GI tract. Oral amoxicillin now
prophylaxis with either cefoxitin or a combination of agents active replaces penicillin V or ampicillin because of superior absorp-
against anaerobic and aerobic organisms is required. The dur- tion and better serum levels. In penicillin-allergic patients,
ation of prophylaxis should be less than 24 hours, and in many clindamycin is recommended; alternatives include cephalexin,
cases, perioperative doses will be adequate. For open fractures, ceftriaxone, azithromycin, and clarithromycin. When there is a
management should proceed as if a therapeutic course were risk of exposure to bowel flora or enterococci, oral amoxicillin
required. For grade I or II injuries, a first-generation cephalosporin may be given. If an IV regimen is indicated, ampicillin may be
will suffice, whereas for grade III injuries, combination therapy is given, with gentamicin added if the patient is at high risk for
warranted; the duration may vary. For operative repair of fractures, endocarditis. In patients allergic to penicillin, vancomycin is
a single dose of cefazolin may be given preoperatively, with a appropriate,with gentamicin added in high-risk patients. These
second dose added if the procedure is long. Patients with major parenteral regimens should be reserved for high-risk patients
soft tissue injury with a danger of spreading infection will benefit undergoing procedures with a significant probability of
from cefazolin, 1 g IV every 8 hours for 1 to 3 days. bacteremia. [see Tables 3 and 4]
The new recommendations of the American Heart Association
have reduced the cardiac conditions needing prophylaxis and
DIRTY OR INFECTED CASES
the procedures that warrant antibiotics.118,119 There should be
Infected cases require therapeutic courses of antibiotics; a reduction in antibiotic use as a result.
prophylaxis is not appropriate in this context. In dirty cases,
additional factors that play a role in outcome; however, For some years, postoperative contamination of the
because the major concentrations of endogenous bacteria are wound has been considered unlikely. However, one report
located in the abdomen, abdominal operations are more likely of SSI in sternal incisions cleaned and redressed 4 hours
to involve bacterial contamination. postoperatively clearly shows that wounds can be contami-
Table 2 Parenteral Antibiotics Recommended for Prophylaxis of Surgical Site Infection
Antibiotic Dose Route of Administration

For coverage against aerobic gram-positive and Cefazolin 1g IV or IM (IV preferred)
gram-negative organisms
If patient is allergic to cephalosporins or if Vancomycin 1g IV
methicillin-resistant organisms are present
Combination regimens for coverage against Cefoxitin 1–2 g IV
gram-negative aerobes and anaerobes or
Cefazolin 1–2 g IV
plus
Metronidazole 0.5 g IV
or
Ampicillin/sulbactam 3g IV
Allergic to penicillin or cephalosporins Clindamycin 600 mg IV
plus
Gentamicin, ciprofloxacin, aztreonam
For single-agent coverage against gram-negative Cefoxitin 1–2 g IV
aerobes and anaerobes
06/08
INFECTION — 8
Table 3 Conditions and Procedures that Require Antibiotic Prophylaxis against Endocarditis118,119
Conditions that Warrant Prophylaxis

Prosthetic cardiac valve or prosthetic material used for cardiac valve repair
Previous infective endocarditis
Congenital heart disease (CHD)
Unrepaired cyanotic CHD, including palliative shunts and conduits
Complete repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention,
during the first 6 months after the procedure
Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit
endothelialization)
Cardiac transplantation recipients who develop cardiac valvulopathy
Procedures that Warrant Prophylaxis

Dental or oropharyngeal procedures that
1. manipulate gingival tissue or the periapical region of the teeth
2. perforate the oral mucosa
Incision and drainage, manipulation, or débridement of infected sites regardless of location
Gastrointestinal (GI) or genitourinary (GU) procedures for which antibiotics to prevent surgical site infection would be administered
Endoscopy of GI tract or uninfected GU tract prophylaxis is NO longer recommended
nated and become infected in the postoperative period.27 most obvious pathogenic bacteria in surgical patients are
Accordingly, use of a dry dressing for 24 hours seems gram-positive cocci (e.g., Staphylococcus aureus and strepto-
prudent. cocci). With modern hygienic practice, it would be expected
  that S. aureus would be found mostly in clean cases, with a
Not only is the size of wound infection incidence of 1 to 2%; however, it is, in fact,
the bacterial inoculum an increasingly common pathogen in SSIs. Surveillance can
important; the bacterial be very useful in identifying either wards or surgeons with
properties of virulence increased rates. Operative procedures in infected areas have
and pathogenicity are an increased infection rate because of the high inoculum with
also significant. The actively pathogenic bacteria.
Table 4 Antibiotics for Prevention of Endocarditis118,119
Prophylactic Regimen*
Manipulative Procedure Usual In Patients with Penicillin Allergy
Dental procedures likely to cause Oral Oral
gingival bleeding; operations or Amoxicillin 2 g 1 hr before procedure Clindamycin,† 600 mg 1 hr before procedure
instrumentation of the upper or
respiratory tract Cephaloxin,† 1 g 1 hr before procedure
or
Azithromycin or clarithromycin, 500 mg1 hr
before procedure
Parenteral Parenteral
Ampicillin, 2 g IM or IV 30 min before Clindamycin, 600 mg IV within 30 min before
procedure procedure
or or
Cefazolin or ceftriaxone 1 g IM or IV Cefazolin or ceftriaxone, 1 g IM or IV within
30 min before procedure
Infected gastrointestinal or Oral
genitourinary operation; abscess Amoxicillin, 2 g 1 hr before procedure
drainage
Parenteral Parenteral
Ampicillin, 2 g IM or IV within 30 min Vancomycin, 1 g IV infused slowly over 1 hr,
before procedure; if risk of endocarditis is beginning 1 hr before procedure; if risk of
considered high, add gentamicin, endocarditis is considered high, add
1.5 mg/kg (to maximum of 120 mg) IM or gentamicin, 1.5 mg/kg (to maximum of
IV 30 min before procedure 120 mg) IM or IV 30 min before procedure‡
*Pediatric dosages are as follows: oral amoxicillin, 50 mg/kg; oral or parenteral clindamycin, 20 mg/kg; oral cephalexin or cefadroxil, 50 mg/kg; oral azithromycin
or clarithromycin, 15 mg/kg; parenteral ampicillin, 50 mg/kg; parenteral cefazolin, 25 mg/kg; parenteral gentamicin, 2 mg/kg. The total pediatric dose should not exceed
the total adult dose.
†
Patients with a history of immediate-type sensitivity to penicillin should not receive these agents.
‡
High-risk patients should also receive ampicillin, 1 g IM or IV, or amoxicillin, 1 g PO, 6 hours after the procedure.
06/08
INFECTION — 9
deal with an inoculum, however small. Therefore, multiple

Preoperative Preparation of the Operative Site factors combine to transform the hospitalized preoperative
patient into a susceptible host. Same-day admission
The sole reason for preparing the patient's skin before an opera-
tion is to reduce the risk of wound infection. A preoperative should eliminate any bacterial impact associated with the
antiseptic bath is not necessary for most surgical patients, but preoperative hospital stay.
their personal hygiene must be assessed and preoperative Bacteria with multiple antibiotic resistance (e.g.,
cleanliness established. Multiple preoperative baths may pre- methicillin-resistant S. aureus [MRSA], Staphylococcus epider-
vent postoperative infection in selected patient groups, such as midis, and vancomycin-resistant enterococci [VRE]) can
those who carry Staphylococcus aureus on their skin or who
be associated with significant SSI problems. In particular,
have infectious lesions. Chlorhexidine gluconate is the recom-
mended agent for such baths.120 staphylococci, with their natural virulence, present an
Hair should not be removed from the operative site unless it important hazard if inappropriate prophylaxis is used.
physically interferes with accurate anatomic approximation of Many surgeons consider it inappropriate or unnecessary to
the wound edges.15 If hair must be removed, it should be clip- obtain good culture and sensitivity data on SSIs; instead of
ped in the OR.15 Shaving hair from the operative site, particul- conducting sensitivity testing, they simply drain infected
arly on the evening before operation or immediately before
wound incision in the OR, increases the risk of wound infection. wounds, believing that the wounds will heal. However, there
Depilatories are not recommended, because they cause have been a number of reports of SSIs caused by unusual
serious irritation and rashes in a significant number of patients, organisms24,27,28; these findings underscore the usefulness of
especially when used near the eyes and the genitalia.121 culturing pus or fluid when an infection is being drained.
In emergency procedures, obvious dirt, grime, and dried SSIs caused by antibiotic-resistant organisms or unusual
blood should be mechanically cleansed from the operative
pathogens call for specific prophylaxis, perhaps other infec-
site by using sufficient friction. In one study, cleansing of con-
taminated wounds by means of ultrasound débridement was tion control efforts, and, if the problem persists, a search for
compared with highpressure irrigation and soaking. Both a possible carrier or a common source.22–24,27,28
ultrasound débridement and high-pressure irrigation were
also effective in reducing the wound infection rate in expe-   
rimental wounds contaminated with a subinfective dose of The surgeon’s peri-
S. aureus and colloidal clay.122
For nonemergency procedures, the necessary reduction in operative rituals are
microorganisms can be achieved by using povidoneiodine designed to reduce or
(10% available povidoneiodine and 1% available iodine) or eliminate bacteria from
chlorhexidine gluconate both for mechanical cleansing of the the operative field.
intertriginous folds and the umbilicus and for painting the Many old habits are
operative site. Which skin antiseptic is optimal is unclear.
obsolete [see 1:8 Prepa-
The best option appears to be chlorhexidine gluconate or an
iodophor.123 The patient should be assessed for evidence of ration of the Operating
sensitivity to the antiseptic (particularly if the agent contains Room and Discussion,
iodine) to minimize the risk of an allergic reaction. What some Hand Washing, below].
patients report as iodine allergies are actually burns. Iodine Nonetheless, it is clear that surgeons can influence SSI rates.14
in alcohol or in water is associated with an increased risk of The refusal to use delayed primary closure or secondary clo-
skin irritation,96 particularly at the edges of the operative field,
where the iodine concentrates as the alcohol evaporates.
sure is an example. Careful attention to the concepts of asep-
Iodine should therefore be removed after sufficient contact time sis and antisepsis in the preparation and conduct of the oper-
with the skin, especially at the edges. Iodophors do not irritate ation is important. Although no single step in the ritual of
the skin and thus need not be removed. preparing a patient for the operative procedure is indispens-
able, it is likely that certain critical standards of behavior must
be maintained to achieve good results.
The preoperative hospital stay has frequently been found The measurement and publication of data about individu-
to make an important contribution to wound infection rates.13 als or hospitals with high SSI rates have been associated with
a diminution of those rates [see Table 6].13,14,29 It is uncertain
The usual explanation is that during this stay, either more
by what process the diffusion of these data relates to the
endogenous bacteria are present or commensal flora is
observed improvements. Although surveillance has unpleas-
replaced by hospital flora. More likely, the patient’s clinical
ant connotations, it provides objective data that individual
picture is a complex one, often entailing exhaustive workup surgeons are often too busy to acquire but that can contribute
of more than one organ system, various complications, and a to improved patient care. For example, such data can
degree of illness that radically changes the host’s ability to be useful in identifying problems (e.g., the presence of
MRSA, a high SSI incidence, or clusters), maintaining
Table 5 Effect of Surveillance and Feedback on Wound quality assurance, and allowing comparison with accepted
Infection Rates in Two Hospitals29 standards.
Period 1 Period 2*
Number of wounds 1,500 1,447 Environment: Local
Hospital A Factors
Wound infection rate 8.4% 3.7%
Local factors influ-
Number of wounds 1,746 1,939
Hospital B ence SSI development
Wound infection rate 5.7% 3.7% because they affect the
*Periods 1 and 2 were separated by an interval during which feedback on
size of the bacterial
wound infection rates was analyzed. inoculum that is required
06/08
INFECTION — 10
Table 6 Determinants of Infection and Factors that Influence Wound Infection Rates29
Variable Determinant of Infection

Bacteria Wound Environment (Local Host Defense Mechanisms (Systemic
Factors) Factors)
Bacterial numbers in wound a
Potential contamination a
Preoperative shave a
Presence of three or more diagnoses c
Age b c
Duration of operation a b c
Abdominal operation a b c
Relative value unit > 10
Emergency surgery
ASA class III, IV, or V c
O2 tension b
Glucose control c
Normothermia b c
Shock b c
Smoking b c
Diabetes10 b c
10
Dyspnea c
Steroid use10 b c
10
Serum albumin < 3.5 g/L c
Age g4010 c
10
Radiotherapy c
10
> 2 alcoholic drinks c
to produce an infection: in a susceptible wound, a smaller are the wound hematocrit and the presence of an antibiotic
inoculum produces infection [see Figure 2]. [see Figure 3]. In the absence of an antibiotic and in the
presence of wound fluid with a hematocrit of more than 8%,
 ’  10 bacteria yield a wound infection rate of 20%. In a techni-
Most of the local factors that make a surgical site favorable cally good wound with no antibiotic, however, 1,000 bacteria
to bacteria are under the control of the surgeon. Although produce a wound infection rate of 20%.12 In the presence of
Halsted usually receives, deservedly so, the credit for having an antibiotic, 105 to 106 bacteria are required.
established the importance of technical excellence in the OR
Drains
in preventing infection, individual surgeons in the distant past
achieved remarkable results by careful attention to cleanliness The use of drains varies widely and is very subjective. All
and technique.30 The halstedian principles dealt with hemo- surgeons are certain that they understand when to use a
stasis, sharp dissection, fine sutures, anatomic dissection, and drain. However, certain points are worth noting. It is now
the gentle handling of tissues. Mass ligatures, large or braided recognized that a simple Penrose drain may function as a
nonabsorbable sutures, necrotic tissue, and the creation of drainage route but is also an access route by which pathogens
hematomas or seromas must be avoided, and foreign materi- can reach the patient.31 It is important that the operative
als must be judiciously used because these techniques and site not be drained through the wound. The use of a closed
materials change the size of the inoculum required to initiate suction drain reduces the potential for contamination and
an infectious process. Logarithmically fewer bacteria are infection.
required to produce infection in the presence of a foreign Many operations on the gastrointestinal (GI) tract can be
body (e.g., suture, graft, metal, or pacemaker) or necrotic performed safely without employing prophylactic drainage.32
tissue (e.g., that caused by gross hemostasis or injudicious A review and meta-analysis from 2004 concluded that
use of electrocautery devices). (1) after hepatic, colonic, or rectal resection with primary
The differences in inoculum required to produce wound anastomosis and after appendectomy for any stage of appen-
infections can be seen in a model in which the two variables dicitis, drains should be omitted (recommendation grade A),
06/08
INFECTION — 11
and (2) after esophageal resection and total gastrectomy, intestinal tract to prevent bacteria, their toxins, or both from
drains should be used (recommendation grade D). Additional moving from the gut lumen into tissue at a rate too fast
randomized, controlled trials will be required to determine to permit clearance by the usual protective mechanisms. A
the value of prophylactic drainage for other GI procedures, variety of experimental approaches aimed at enhancing bowel
especially those involving the upper GI tract. barrier function have been studied; at present, however,
the most clinically applicable method of bowel protection is
Duration of Operation initiation of enteral feeding (even if the quantity of nutrients
In most studies, contamination certainly increases with provided does not satisfy all the nutrient requirements)
time (see above).6,11,13 Wound edges can dry out, become and administration of the amino acid glutamine [see 8:22
macerated, or in other ways be made more susceptible to Nutritional Support]. Glutamine is a specific fuel for entero-
infection (i.e., requiring fewer bacteria for development of cytes and colonocytes and has been found to aid recovery of
infection). Speed and poor technique are not suitable damaged intestinal mucosa and enhance barrier function
approaches; expeditious operation is appropriate. when administered either enterally or parenterally.
Electrocautery Advanced Age
The use of electrocautery devices (but not the harmonic Aging is associated with structural and functional changes
scalpel) has been clearly associated with an increase in the that render the skin and subcutaneous tissues more suscep-
incidence of superficial SSIs. However, when such devices tible to infection. These changes are immutable; however,
are properly used to provide pinpoint coagulation (for which they must be evaluated in advance and addressed by excellent
the bleeding vessels are best held by fine forceps) or to divide surgical technique and, on occasion, prophylactic antibiotics
tissues under tension, there is minimal tissue destruction, no [see Sidebar Antibiotic Prophylaxis of Infection]. SSI rates
charring, and no change in the wound infection rate.31 increase with aging until the age of 65 years, after which
  point, the incidence appears to decline.37
Local Blood Flow Host Defense

Local perfusion can Mechanisms
greatly influence the The systemic response
development of infec- is designed to control
tion, as is seen most and eradicate infection.
easily in the tendency of the patient with peripheral vascular Many factors can inhibit
disease to acquire infection of an extremity. As a local prob- systemic host defense
lem, inadequate perfusion reduces the number of bacteria mechanisms; some are related to the surgical disease and
required for infection, in part because inadequate perfusion others to the patient’s underlying disease or diseases and the
leads to decreased tissue levels of oxygen. Shock, by reducing events surrounding the operation.
local perfusion, also greatly enhances susceptibility to infec-
tion. Fewer organisms are required to produce infection - 
during or immediately after shock [see Figure 4]. There are a limited number of ways in which the surgeon
To counter these effects, the arterial oxygen tension can improve a patient’s systemic responses to surgery.
(PaO2) must be translated into an adequate subcutaneous Nevertheless, when appropriate, attempts should be made
oxygen level (determined by measuring transcutaneous to modify the host. The surgeon and the operation are
oxygen tension)33; this, together with adequate perfusion, will both capable of reducing immunologic efficacy; hence, the
provide local protection by increasing the number of bacteria operative procedure should be carried out in as judicious
required to produce infection. Provision of supplemental a manner as possible. Minimal blood loss, avoidance of
oxygen in the perioperative period may lead to a reduced SSI shock, and maintenance of blood volume, tissue perfusion,
rate, probably as a consequence of increased tissue oxygen and tissue oxygenation will minimize trauma and will reduce
tension,34 although the value of this practice has been ques- the secondary, unintended immunologic effects of major
tioned.35 If the patient is not intubated, a mask, not nasal procedures.
prongs, is required.36 Diabetes has long been recognized as a risk factor for infec-
tion and for SSI in particular. Three studies from the past
Barrier Function decade demonstrated the importance of glucose control for
Inadequate perfusion may also affect the function of other reducing SSI rates in both diabetic and nondiabetic patients
organs, and the resulting dysfunction will, in turn, influence who underwent operation,38,39 as well as in critically ill inten-
the patient’s susceptibility to infection. For example, sive care unit patients.40 Glucose control is required through-
ischemia-reperfusion injury to the intestinal tract is a frequent out the entire perioperative period. The beneficial effect
consequence of hypovolemic shock and bloodstream infec- appears to lie in the enhancement of host defenses. The sur-
tion. Inadequate perfusion of the GI tract may also occur gical team must also ensure maintenance of adequate tissue
during states of fluid and electrolyte imbalance or when oxygen tension33,34 and maintenance of normothermia.41
cardiac output is marginal. In experimental studies, altered When abnormalities in host defenses are secondary to
blood flow has been found to be associated with the break- surgical disease, the timing of the operation is crucial to out-
down of bowel barrier function—that is, the inability of the come. With acute and subacute inflammatory processes, early
06/08
INFECTION — 12
Figure 4 Animals exposed to

hemorrhagic shock followed by
resuscitation show an early decreased
resistance to wound infection. There
is also a persistent influence of shock
on the development of wound
infection at different times of
inoculation after shock. The impor-
tance of inoculum size (106/mL to
108/mL) and the effect of antibiotic on
infection rates are evident at all times
of inoculation.109
operation helps restore normal immune function. Deferral of operation being defined by the NNIS as one that is at or
definitive therapy frequently compounds problems. above the 75th percentile for operating time. Bacterial
contamination remains a risk factor, but the operative site is
  eliminated.8
Shock has an influence on the incidence of wound infection
Surgeons have always [see Figure 4]. This influence is most obvious in cases of
known that the patient trauma, but there are significant implications for all patients
is a significant variable in regard to maintenance of blood volume, hemostasis, and
in the outcome of opera- oxygen-carrying capacity. The effect of shock on the risk of
tion. Various clinical infection appears to be not only immediate (i.e., its effect on
states are associated with altered resistance to infection. In local perfusion) but also late because systemic responses are
all patients, but particularly those at high risk, SSI creates blunted as local factors return to normal.
not only wound complications but also significant morbidity Advanced age, transfusion, and the use of steroids and
(e.g., reoperation, incisional hernia, secondary infection, other immunosuppressive drugs, including chemotherapeutic
impaired mobility, increased hospitalization, delayed reha- agents, are associated with an increased risk of SSI.42,43 Often,
bilitation, or permanent disability) and occasional mortality.23 these factors cannot be altered; however, the proper choice of
SENIC has proposed that the risk of wound infection operation, the appropriate use of prophylaxis, and meticulous
be assessed not only in terms of probability of contamination surgical technique can reduce the risk of such infection by
but also in relation to host factors.6,7,9 According to this maintaining patient homeostasis, reducing the size of any
study, patients most clearly at risk for wound infection are infecting microbial inoculum, and creating a wound that is
those with three or more concomitant diagnoses; other likely to heal primarily.
patients who are clearly at risk are those undergoing a clean- Smoking is associated with a striking increase in SSI inci-
contaminated or contaminated abdominal procedure and dence. As little as 1 week of abstinence from smoking will
those undergoing any procedure expected to last longer than make a positive difference.44
2 hours. These last two risk groups are affected by a bacterial Pharmacologic therapy can affect host response as well.
component, but all those patients who are undergoing major Nonsteroidal anti-inflammatory drugs that attenuate the
abdominal procedures or lengthy operations generally have a production of certain eicosanoids can greatly alter the adverse
significant primary pathologic condition and are usually older, effects of infection by modifying fever and cardiovascular
with an increased frequency of concomitant conditions. The effects. Operative procedures involving inhalational anes-
NNIS system uses most of the same concepts but expresses thetics result in an immediate rise in plasma cortisol
them differently. In the NNIS study, host factors in the large concentrations. The steroid response and the associated
study are evaluated in terms of the ASA score. The duration immunomodulation can be modified by using high epidural
of the operation is measured differently as well, with a lengthy anesthesia as the method of choice; pituitary adrenal
06/08
INFECTION — 13
activation will be greatly attenuated. Some drugs that inhibit Discussion

steroid elaboration (e.g., etomidate) have also been shown to
be capable of modifying perioperative immune responses.    
Using this vast database of NSQIP, Neumayer and colleagues It is difficult to understand why antibiotics have not always
integrated most of these variables into an expanded risk prevented SSI successfully. Certainly, surgeons were quick
assessment [see Table 6].10 to appreciate the possibilities of antibiotics; nevertheless,
the efficacy of antibiotic prophylaxis was not proved until the
- late 1960s.12 Studies before then had major design flaws—
  principally, the administration of the antibiotic some time
A 2000 commentary after the start of the operation, often in the recovery room.
in The Lancet by Donal The failure of studies to demonstrate efficacy and the
Buggy considered the occasional finding that prophylactic antibiotics worsened
question of whether rather than improved outcome led in the late 1950s to pro-
anesthetic management found skepticism about prophylactic antibiotic use in any
could influence surgical wound healing.45 In addition to the operation.
surgeon- and patient-related factors already discussed The principal reason for the apparent inefficacy was inad-
(see above), Buggy cogently identified a number of equate understanding of the biology of SSIs. Fruitful study
anesthesiologist-related factors that could contribute to better of antibiotics and how they should be used began after phys-
wound healing and reduced wound infection. Some of these iologic groundwork established the importance of local blood
factors (e.g., pain control, epidural anesthesia, and autolo- flow, maintenance of local immune defenses, adjuvants, and
gous transfusion) are unproven but nonetheless make sense local and systemic perfusion.50
and should certainly be tested. Others (e.g., tissue perfusion, The key antibiotic study, which was conducted in guinea
intravascular volume, and—significantly—maintenance of pigs, unequivocally proved the following about antibiotics51:
normal perioperative body temperature) have undergone 1. They are most effective when given before inoculation of
formal evaluation. Very good studies have shown that dra- bacteria.
matic reductions in SSI rates can be achieved through careful 2. They are ineffective if given 3 hours after inoculation.
avoidance of hypothermia.41,46 Patient-controlled analgesia 3. They are of intermediate effectiveness when given between
pumps are known to be associated with increased SSI rates, these times [see Figure 5].
through a mechanism that is currently unknown.47 Infection
control practices are required of all practitioners; contamina- Although efficacy with a complicated regimen was demon-
tion of anesthetic drugs by bacteria has resulted in numerous strated in 1964,52 the correct approach was not defined until
small outbreaks of SSI.48,49 1969.12 Established by these studies are the philosophical and
As modern surgical practice has evolved and the variable practical bases of the principles of antibiotic prophylaxis of
of bacterial contamination has come to be generally well
managed, the importance of all members of the surgical team
in the prevention of SSI has become increasingly apparent.
The crux of Buggy’s commentary may be expressed as Staphylococcal Lesions
follows: details make a difference, and all of the participants 10
Mean 24-Hour Lesion Diameter (mm)
in a patient’s surgical journey can contribute to a continuing

decrease in SSI. It is a systems issue.
  
As operative infection rates slowly fall, despite the perfor-
mance of increasingly complex operations in patients at
greater risk, surgeons are approaching the control of infection
5 Staphylococcal Lesions + Antibiotic
with a broader view than simply that of asepsis and antisepsis.
This new, broader view must take into account many vari-
ables, of which some have no relation to bacteria, but all play
a role in SSI [see Table 6 and Figure 1].
To estimate risk, one must integrate the various determi-
nants of infection in such a way that they can be applied to
patient care. Much of this exercise is vague. In reality, Killed Staphylococcal Lesions
the day-to-day practice of surgery includes a risk assessment
that is essentially a form of logistic regression, although
–1 0 1 2 3 4 5 6
not recognized as such. Each surgeon’s assessment of the
probability of whether an SSI will occur takes into account Lesion Age at Time of Penicillin Injection (hr)
the determining variables: Figure 5 In a pioneer study of antibiotic prophylaxis,51 the
diameter of lesions induced by staphylococcal inoculation
Probability of SSI = 24 hours earlier was observed to be critically affected by the
x + a (bacteria) + b (environment: local factors) timing of penicillin administration with respect to bacterial
+ c (host defense mechanisms: systemic factors) inoculation.
06/08
INFECTION — 14
SSI in all surgical arenas12,51: that prophylactic antibiotics for prophylaxis is under consideration.63 If local results are
must be given preoperatively within 2 hours of the incision, poor, surgical practice should be reassessed before antibiotics
in full dosage, parenterally, and for a very limited period. are prescribed.
These principles remain essentially unchanged despite minor
modifications from innumerable subsequent studies.53–57 Antibiotic Selection and Administration
Prophylaxis for colorectal operations is discussed elsewhere When antibiotics are given more than 2 hours before oper-
[see Infection Prevention in Bowel Surgery, below]. ation, the risk of infection is increased.53,55 IV administration
in the OR or the preanesthetic room guarantees appropriate
Principles of Patient Selection levels at the time of incision. The organisms likely to be
Patients must be selected for prophylaxis on the basis of present dictate the choice of antibiotic for prophylaxis. The
either their risk for SSI or the cost to their health if an SSI cephalosporins are ideally suited to prophylaxis: their features
develops (e.g., after implantation of a cardiac valve or another include a broad spectrum of activity, an excellent ratio of
prosthesis). The most important criterion is the degree therapeutic to toxic dosages, a low rate of allergic responses,
of bacterial contamination expected to occur during the ease of administration, and attractive cost advantages. Mild
operation. The traditional classification of such contamina- allergic reactions to penicillin are not contraindications for
tion was defined in 1964 by the historic National Academy of the use of a cephalosporin.
Sciences–National Research Council study.5 The important Physicians like new drugs and often tend to prescribe
features of the classification are its simplicity, ease of under- newer, more expensive antibiotics for simple tasks. First-
standing, ease of coding, and reliability. Classification is generation cephalosporins (e.g., cefazolin) are ideal agents for
dependent on only one variable—the bacterial inoculum— prophylaxis. Third-generation cephalosporins are not: they
and the effects of this variable are now controllable by cost more, are not more effective, and promote emergence of
antimicrobial prophylaxis. Advances in operative technique, resistant strains.64,65
general care, antibiotic use, anesthesia, and surveillance have The most important first-generation cephalosporin for sur-
reduced SSI rates in all categories that were established by gical patients continues to be cefazolin. Administered IV in
this classification.6,13,14,51 the OR at the time of skin incision, it provides adequate tissue
In 1960, after years of negative studies, it was said, “Nearly levels throughout most of the operation. A second dose
all surgeons now agree that the routine use of prophylaxis in administered in the OR after 3 hours will be beneficial if the
clean operations is unnecessary and undesirable.”58 Since procedure lasts longer than that. Data on all operative site
then, much has changed: there are now many clean opera- infections are imprecise, but SSIs can clearly be reduced by
tions for which no competent surgeon would omit the use of this regimen. No data suggest that further doses are required
prophylactic antibiotics, particularly as procedures become for prophylaxis.
increasingly complex and prosthetic materials are used in Fortunately, cefazolin is effective against both gram-
patients who are older, sicker, or immunocompromised. positive and gram-negative bacteria of importance, unless
A separate risk assessment that integrates host and bacte- significant anaerobic organisms are encountered. The signifi-
rial variables (i.e., whether the operation is dirty or contami- cance of anaerobic flora has been disputed, but for elective
nated, is longer than 2 hours, or is an abdominal procedure colorectal surgery,66 abdominal trauma,67,68 appendicitis,69 or
and whether the patient has three or more concomitant other circumstances in which penicillin-resistant anaerobic
diagnoses) segregates more effectively those patients who are bacteria are likely to be encountered, coverage against both
prone to an increased incidence of SSI [see Integration of aerobic and anaerobic gram-negative organisms is strongly
Determinants of Infection, below]. This approach enables the recommended and supported by the data.
surgeon to identify those patients who are likely to require Despite several decades of studies, prophylaxis is not always
preventive measures, particularly in clean cases, in which properly implemented.53,55,69,70 Unfortunately, didactic educa-
antibiotics would normally not be used.6 tion is not always the best way to change behavior. Preprinted
The prototypical clean operation is an inguinal hernia order forms71 and a reminder sticker from the pharmacy72
repair. Technical approaches have changed dramatically over have proved to be effective methods of ensuring correct use.
the past 10 years, and most primary and recurrent hernias are The commonly heard decision “This case was tough; let’s
now treated with a tension-free mesh-based repair. The use give an antibiotic for 3 to 5 days” has no data to support
of antibiotics has become controversial. In the era of repairs it and should be abandoned. The extended duration is
under tension, there was some evidence to suggest that a associated with an increase in MRSA SSIs.73 Differentiation
perioperative antibiotic (in a single preoperative dose) was between prophylaxis and therapeusis is important. A thera-
beneficial.59 Current studies, however, do not support antibi- peutic course for perforated diverticulitis or other types of
otic use in tension-free mesh-based inguinal hernia repairs.60,61 peritoneal infection is appropriate. Data on casual contami-
On the other hand, if surveillance indicates that there is a nation associated with trauma or with operative procedures
local or regional problem62 with SSI after hernia surgery, anti- suggest that 24 hours of prophylaxis or less is quite
biotic prophylaxis (again in the form of a single preoperative adequate.74–76 Mounting evidence suggests that a single
dose) is appropriate. Without significantly more supportive preoperative dose is good care and that additional doses are
data, prophylaxis for clean cases cannot be recommended not required.
unless specific risk factors are present.
Data suggest that prophylactic use of antibiotics may con- Trauma Patients
tribute to secondary Clostridium difficile disease; accordingly, The efficacy of antibiotic administration on arrival in the
caution should be exercised when widening the indications emergency department as an integral part of resuscitation has
06/08
INFECTION — 15
been clearly demonstrated.77 The most common regimens

Table 7 Quality Improvement Objectives to Reduce
have been (1) a combination of an aminoglycoside and Surgical Site Infections80,83
clindamycin and (2) cefoxitin alone. These two regimens
or variations thereof have been compared in a number of Timeliness of antibiotics
studies.41,68,76,77 They appear to be equally effective, and either Appropriate selection of antibiotics
Correct duration of antibiotics
regimen can be recommended with confidence. For prophy- Preventing hyperglycemia
laxis, there appears to be a trend toward using a single drug: Maintaining normothermia
cefoxitin or cefotetan.56 If therapy is required because of Optimizing oxygen tension
either a delay in surgery, terrible injury, or prolonged shock, Avoidance of shaving surgical site
the combination of an agent that is effective against anaer-
obes with an aminoglycoside seems to be favored. Because
aminoglycosides are nephrotoxic, they must be used with care and a distinction between approaches to infection of the
in the presence of shock. wound, which is only part of the operative field, and
In many of the trauma studies just cited, antibiotic prophy- approaches to infections directly related to the operative site.
laxis lasted for 48 hours or longer. Subsequent studies, how- These developments will define more clearly the prophylaxis
ever, indicated that prophylaxis lasting less than 24 hours is requirements of patients whose operations are clean but
appropriate.75,76,78 Single-dose prophylaxis is appropriate for whose risk of wound or operative site infection is increased.
patients with closed fractures.79 A current issue of some concern is loss of infection surveil-
lance capability. Infection control units have been shown to
Complications offer a number of benefits in the institutional setting, such as
Complications of antibiotic prophylaxis are few. Although the following:
data linking prophylaxis to the development of resistant 1. Identifying epidemics caused by common or uncommon
organisms are meager, resistant microbes have developed in organisms24,27,57
every other situation in which antibiotics have been used, and 2. Establishing correct use of prophylaxis (timing, dose, dura-
it is reasonable to expect that prophylaxis in any ecosystem tion, and choice)53,56,74
will have the same result, particularly if selection of patients 3. Documenting costs, risk factors, and readmission
is poor, if prophylaxis lasts too long, or if too many late- rates86,87
generation agents are used. 4. Monitoring postdischarge infections and secondary conse-
A rare but important complication of antibiotic use is quences of infections88–90
pseudomembranous enterocolitis, which is induced most 5. Ensuring patient safety91
commonly by clindamycin, the cephalosporins, and ampicil- 6. Managing MRSA and VRE92
lin [see 8:16 Nosocomial Infection].63 The common denomina-
tor among different cases of pseudomembranous enterocolitis S. aureus—in particular, MRSA—is a major cause of SSI.92
is hard to identify. Diarrhea and fever can develop after Cross-infection problems are a concern, in a manner reminis-
administration of single doses of prophylactic antibiotics. The cent of the preantibiotic era. Hand washing (see below) is
condition is rare, but difficulties occur because of failure to coming back into fashion, consistent with the professional
make a rapid diagnosis. behavior toward cross-infection characteristic of the preanti-
biotic era. At present, hard evidence is lacking, but clinical
Current Issues observation suggests that S. aureus SSIs are especially trou-
The most significant questions concerning prophylaxis of blesome and destructive of local tissue and require a longer
SSIs already have been answered. time to heal than other SSIs do. When S. aureus SSIs occur
The problem has been the implementation of the strategies after cardiac surgery, thoracotomy, or joint replacement, their
known to work. Table 7 outlines seven measures known with consequences are significant. Prevention in these settings is
hard data to be important in the reduction of SSI. These important. When nasal carriage of S. aureus has been identi-
management approaches are integrated into the Surgical Care fied, mupirocin may be administered intranasally to reduce
Improvement Project80 and the Surgical Infection Prevention the incidence of S. aureus SSIs.93
Project.81 Single hospitals have used these criteria in ongoing The benefits of infection surveillance notwithstanding, as
quality improvement programs.82 More impressive is the the business of hospital care has become more expensive and
collaborative reported by Dellinger and colleagues in which financial control more rigid, the infection control unit is a
56 hospitals tracked, monitored, and internally fed back the hospital component that many administrators have come to
seven variables in Table 7 and demonstrated that as compli- consider a luxury and therefore expendable. Consequently,
ance increased, SSI rates came down.83 An important remain- surveillance as a quality control and patient safety mechanism
ing issue is the proper duration of prophylaxis in complicated has been diminished.
cases, in the setting of trauma, and in the presence of foreign It is apparent that SSIs have huge clinical and financial
bodies. No change in the criteria for antibiotic prophylaxis is implications [see Sidebar Patient Safety and Antibiotic Use].
required in laparoscopic procedures; the risk of infection is Patients with infections tend to be sicker and to undergo
lower in such cases.84,85 Cost factors are important and may more complex operations. Therefore, higher infection rates
justify the endless succession of studies that compare new translate into higher morbidity and mortality as well as higher
drugs in competition for appropriate clinical niches. cost to the hospital, the patient, and society as a whole. With
Further advances in patient selection may take place but increasingly early discharge becoming the norm, delayed
will require analysis of data from large numbers of patients diagnosis of postdischarge SSI and the complications thereof
06/08
INFECTION — 16
 
Patient Safety and Antibiotic Use
The purpose of cleansing the surgeon’s hands is to reduce
Prophylactic antibiotics have been considered to be a harmless
the numbers of resident flora and transient contaminants,
manner in which to prevent surgical site infections. The evidence
thereby decreasing the risk of transmitting infection. Although
is that a single dose of prophylactic antibiotics can precipitate
Clostridium difficile pseudomembraneous enterocolitis.63 These can the proper duration of the hand scrub is still subject to debate,
be as malignant as the same entity caused by therapeutic antibiotic evidence suggests that a 120-second scrub is sufficient,
regimens. provided that a brush is used to remove the bacteria residing
Although the principles of delivery of added prophylactic in the skin folds around the nails.94 The nail folds, the nails,
antibiotics and their duration have been established for a long and the fingertips should receive the most attention because
time, the evidence is clear that adherence to these principles is most bacteria are located around the nail folds and most
frequently poor. Two areas that are primarily at fault are the timing glove punctures occur at the fingertips. Friction is required
of administration of the first dose and whether it gets given and to remove resident microorganisms that are attached by
the duration of use of prophylactic antibiotics.43,70–72 The principles
adhesion or adsorption, whereas transient bacteria are easily
are (1) that the drug must be at the site of the wound at the
removed by simple hand washing.
time of incision and (2) a duration longer than 24 hours has no
positive impact on SSI and may have a negative one. The inability Solutions containing either chlorhexidine gluconate or
of hospitals around the world to ensure the short postoperative one of the iodophors are the most effective surgical scrub
duration of prophylaxis is a puzzle but is clear in all studies thus preparations and have the fewest problems with stability,
far performed. contamination, and toxicity.95 Alcohols applied to the skin
Although prophylactic antibiotics are not the only stimulus to are among the safest known antiseptics, and they produce
produce resistant microflora, their control and correct management the greatest and most rapid reduction in bacterial counts on
will contribute to decreasing the incidence of methicillin- clean skin.96 All variables considered, chlorhexidine gluconate
resistant Staphylococcus aureus (MRSA) and vancomycin-resistant followed by an iodophor appears to be the best option [see
enterococcus (VRE). MRSA, in particular, is now found in
Table 8].
community practice clearly as a result of excessive antibiotic use.
The purpose of washing the hands after surgery is to
The key to effective prophylactic antibiotics use and decreased
pressure for antibiotic resistance can be simplified to the right drug, remove microorganisms that are resident, that flourished in
the right timing, and the right duration The increased use of third- the warm, wet environment created by wearing gloves, or that
and fourth-generation antibiotics is to be strongly discouraged. reached the hands by entering through puncture holes in the
The new recommendations for the use of antibiotics in the gloves. On the ward, even minimal contact with colonized
prevention of infective endocarditis in association with either dental patients has been demonstrated to transfer microorganisms.97
or other operative procedures are clear. The number of conditions As many as 1,000 organisms were transferred by simply
has been reduced and clarified, and the recommendations regarding touching the patient’s hand, taking a pulse, or lifting the
procedures have been greatly simplified.118,119
patient. The organisms survived for 20 to 150 minutes,
All recommendations for prophylactic antibiotics, whatever
making their transfer to the next patient clearly possible.
the indication, suggest the use of first- or second-generation
cephalosporins, ampicillin or its derivatives, metronidazole, and A return to the ancient practice of washing hands between
first-generation erythromycins and aminoglycosides.56,118 each patient contact is warranted. Nosocomial spread of
numerous organisms—including C. difficile; MRSA, VRE,
and other antibiotic-resistant bacteria; and viruses—is a
constant threat.
Hand washing on the ward is complicated by the fact that
is a growing problem.88–90 Effective use of institutional overwashing may actually increase bacterial counts. Dry,
databases may contribute greatly to identification of this damaged skin harbors many more bacteria than healthy skin
problem.89 and is almost impossible to render even close to bacteria free.
Clearly, the development of effective mechanisms for Although little is known about the physiologic changes in
identifying and controlling SSIs is in the interests of all skin that result from frequent washings, the bacterial flora is
associated with the delivery of health care.91 The identifica- certainly modified by alterations in the lipid or water content
tion of problems by means of surveillance and feedback of the skin. The so-called dry hand syndrome was the impe-
can make a substantial contribution to reducing SSI rates tus behind the development of the alcohol-based gels now
[see Table 6].13,91 available. These preparations make it easy for surgeons to
Table 8 Characteristics of Three Topical Antimicrobial Agents Effective against Both Gram-Positive and Gram-Negative
Bacteria96
Agent Mode of Action Antifungal Activity Comments

Chlorhexidine Cell wall disruption Fair Poor activity against tuberculosis-causing organisms; can
cause ototoxicity and eye irritation
Iodine/iodophors Oxidation and substitution by Good Broad antibacterial spectrum; minimal skin residual
free iodine activity; possible absorption toxicity and skin irritation
Alcohols Denaturation of protein Good Rapid action but little residual activity; flammable
06/08
INFECTION — 17
clean their hands after every patient encounter with minimal One investigation demonstrated that silk sutures decrease
damage to their skin. the number of bacteria required for infection.107 Other inves-
tigators used a suture as the key adjuvant in studies of host
     manipulation,108 whereas a separate study demonstrated
At present, the best method of preventing SSIs after bowel persistent susceptibility to wound infection days after shock.109
surgery is, once again, a subject of debate. There have been The common variable is the number of bacteria. This relation
three principal approaches to this issue, involving mechanical may be termed the inoculum effect, and it has great relevance
bowel preparation in conjunction with one of the following in all aspects of infection control. Applying knowledge of this
three antibiotic regimens56,98–103: effect in practical terms involves the following three steps:
1. Oral antibiotics (usually neomycin and erythromycin),16–21,102 1. Keeping the bacterial contamination as low as possible via
2. Intravenous antibiotics covering aerobic and anaerobic asepsis and antisepsis, preoperative preparation of patient
bowel flora,16–21,56,100,101 or and surgeon, and antibiotic prophylaxis
3. A combination of regimens 1 and 2 (meta-analysis 2. Maintaining local factors in such a way that they can pre-
suggests that the combination of oral and parenteral vent the lodgment of bacteria and thereby provide a locally
antibiotics is best).103 unreceptive environment
3. Maintaining systemic responses at such a level that they
With respect to mechanical bowel preparation, there are can control the bacteria that become established
now many trials that in modern times have failed to be
supportive.16–19 Meta-analysis suggests no value in the preven- These three steps are related to the determinants of infec-
tion of infection and the possibility of increasing complication and their applicability to daily practice. Year-by-year
tions.16,21 The increased SSI and leak rates noted have been reductions in wound infection rates, when closely followed,
attributed to the complications associated with vigorous indicate that it is possible for surgeons to continue improving
bowel preparation, leading to dehydration, overhydration, or results by attention to quality of clinical care and surgical
electrolyte abnormalities. technique, despite increasingly complex operations.5,14,29–31 In
An observational study reported a 26% SSI rate in colorec- particular, the measures involved in the first step (control of
tal surgery patients.104 Intraoperative hypotension and body bacteria) have been progressively refined and are now well
mass index were the only independent predictive variables. established.
All patients underwent mechanical bowel preparation the The integration of determinants has significant effects [see
day before operation and received oral antibiotics and periop- Figures 3 and 4]. When wound closure was effected with a
erative IV antibiotics. Half of the SSIs were discovered after wound hematocrit of 8% or more, the inoculum required
discharge. Most would agree that the protocol was standard. to produce a wound infection rate of 40% was 100 bacteria
These and other results suggest that a fresh look at the [see Figure 3]. Ten bacteria produced a wound infection rate
infectious complications of surgery—and of bowel surgery in of 20%. The shift in the number of organisms required to
particular—is required. produce clinical infection is significant. It is obvious that this
inoculum effect can be changed dramatically by good surgical
     technique and further altered by use of prophylactic antibiot-
The significant advances in the control of wound infection ics. If the inoculum is always slightly smaller than the number
during the past several decades are linked to a better of organisms required to produce infection in any given
understanding of the biology of wound infection, and this link setting, the results are excellent. There is clearly a relation
has permitted the advance to the concept of SSI.2 In all tis- between the number of bacteria and the local environment.
sues at any time, there will be a critical inoculum of bacteria The local effect can also be seen secondary to systemic phy-
that would cause an infectious process [see Figure 3]. The siologic change, specifically shock. One study showed the low
standard definition of infection in urine and sputum has been local perfusion in shock to be important in the development
105 organisms/mL. In a clean dry wound, 105 bacteria proof an infection.105,106
duce a wound infection rate of 50% [see Figure 3].12 Effective One investigation has shown that shock can alter infection
use of antibiotics reduces the infection rate to 10% with the rates immediately after its occurrence [see Figure 4].109 Fur-
same number of bacteria and thereby permits the wound to thermore, if the inoculum is large enough, antibiotics will
tolerate a much larger number of bacteria. not control bacteria. In addition, there is a late augmentation
All of the clinical activities described are intended either of infection lasting up to 3 days after restoration of blood
to reduce the inoculum or to permit the host to manage volume. These early and late effects indicate that systemic
the number of bacteria that would otherwise be pathologic. determinants come into play after local effects are resolved.
One study in guinea pigs showed how manipulation of local These observations call for further study, but, obviously, the
blood flow, shock, the local immune response, and foreign combined abnormalities alter the outcome.
material can enhance the development of infection.105 This Systemic host responses are important for the control of
study and two others defined an early decisive period of infection. The patient has been clearly implicated as one
host antimicrobial activity that lasts for 3 to 6 hours after of the four critical variables in the development of wound
contamination.51,105,106 Bacteria that remain after this period infection.6 In addition, the bacterial inoculum, the location
are the infecting inoculum. Processes that interfere with this of the procedure and its duration, and the coexistence of
early response (e.g., shock, altered perfusion, adjuvants, or three or more diagnoses were found to give a more accurate
foreign material) or support it (e.g., antibiotics or total care) prediction of the risk of wound infection. The spread of risk
have a major influence on outcome. is defined better with the SENIC index (1 to 27%) than it
06/08
INFECTION — 18
is with the traditional classification (2.9 to 12.6%). The influence is very similar to that seen in other investigations.
importance of the number of bacteria is lessened if the other Whereas a PaO2 equivalent to a true fractional concentration
factors are considered in addition to inoculum. The inoculum of oxygen in inspired gas (FIO2) of 45% is not feasible,
effect has to be considered with respect to both the number maintenance, when appropriate, of an increased FIO2 in the
of organisms and the local and systemic host factors that are postoperative period may prove an elementary and effective
in play. Certain variables were found to be significantly tool in managing the inoculum effect.
related to the risk of wound infection in three important Modern surgical practice has reduced the rate of wound
prospective studies.6,11,13 It is apparent that the problem of infection significantly. Consequently, it is more useful to
SSI cannot be examined only with respect to the manage- think in terms of SSI, which is not limited to the incision
ment of bacteria. Host factors have become much more sig-
but may occur anywhere in the operative field; this concept
nificant now that the bacterial inoculum can be maintained
provides a global objective for control of infections associated
at low levels by means of asepsis, antisepsis, technique, and
with a surgical procedure. Surveillance is of great importance
prophylactic antibiotics.110
Important host variables include the maintenance of for quality assurance. Reports of recognized pathogens (e.g.,
normal homeostasis (physiology) and immune response. S. epidermidis and group A streptococci) and unusual organ-
Maintenance of normal homeostasis in patients at risk is one isms (e.g., Rhodococcus [Gordona] bronchialis, Mycoplasma
of the great advances of surgical critical care.110 The clearest hominis, and Legionella dumoffii) in SSIs highlight the impor-
improvements in this regard have come in maintenance of tance of infection control and epidemiology for quality assur-
blood volume, oxygenation, and oxygen delivery. ance in surgical departments.22–24,27,28 (Although these reports
One group demonstrated the importance of oxygen use the term wound infection, they are addressing what we now
delivery, tissue perfusion, and PaO2 in the development of call SSI.) The importance of surgeon-specific and service-
wound infection.111 Oxygen can have as powerful a negative specific SSI reports should be clear [see Table 6]13,14,113 and
influence on the development of SSI as antibiotics can.112 The their value in quality assurance evident.
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of preoperative warming on the incidence 65. Rotman N, Hay J-M, Lacaine F, et al. 83. Dellinger EP, Hausmann SM, Bratzler DW,
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laparoscopic cholecystectomy? J Am Coll surgery. Am J Surg 1988;155(Suppl 5A): wounds: the role of oxygen. New York:
Surg 1997;184:353. 71. Elsevier; 1987. p. 1.
85. Richards C, Edwards J, Culver D, et al. 99. Periti P, Mazzei T, Tonelli F, et al. Single 113. Olson MM, Lee JT Jr. Continuous, 10-year
Does using a laparoscopic approach to dose cefotetan versus multiple dose wound infection surveillance: results,
cholecystectomy decrease the risk of surgical cefoxitin—antimicrobial prophylaxis in advantages, and unanswered questions.
site infection? Ann Surg 2003;237:358. colorectal surgery. Dis Colon Rectum Arch Surg 1990;125:794.
1989;32:121.
86. Kirkland KB, Briggs JP, Trivette SL, et al. 114. Oreskovich MR, Dellinger EP, Lennard ES,
The impact of surgical-site infection in 100. Norwegian Study Group for Colorectal et al. Duration of preventive antibiotic
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of hospitalisation, and extra costs. Infect colorectal surgery include agents effective trauma. Arch Surg 1982;117:200.
Control Hosp Epidemiol 1999;20:725. against both anaerobic and aerobic micro-
115. Langely JM, Le Blanc JC, Drake J, et al.
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infections: the world coming together? placement of cerebrospinal fluid shunts:
Infect Control Hosp Epidemiol 2000;21: 101. Song J, Glenny AM. Antimicrobial meta-analysis. Clin Infect Dis 1993;17:98.
309. prophylaxis in colorectal surgery: a
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88. Weiss CA, Statz CL, Dahms RA, et al. Six trials. Br J Surg 1998;85:1232. Antibiotic prophylaxis for preventing wound
years of surgical wound infection surveillance infection after breast surgery: a systematic
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1999;134:1041. Efficacy of oral and systemic antibiotic 2006;203:729.
prophylaxis in colo-rectal operations. Arch
89. Sands K, Vineyard G, Livingston J, et al. Surg 1983;118:496. 117. Forse RA, Karam B, MacLean LD, et al.
Efficient identification of postdischarge Antibiotic prophylaxis for surgery in
surgical site infections: use of automated 103. Lewis RT. Oral versus systemic antibiotic morbidly obese patients. Surgery 1989;106:
pharmacy dispensing information, admini- prophylaxis in elective colon surgery: a 750.
strative data, and medical record infor- randomized study and meta-analysis send a
message from the 1990’s. Can J Surg 118. Wilson W. Taubert KA, Gewitz M, et al.
mation. J Infect Dis 1 1999;79:434. Prevention of infective endocarditis: guide-
2002;45:173.
90. Platt R. Progress in surgical-site infection lines from the American Heart Association.
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2002;23:361. Wound infection after elective colorectal
resection. Ann Surg 2004;239:599. 119. Major changes in endocarditis prophylaxis
91. Burke JP. Infection control—a problem for for dental, GI and GU procedures. Med
patient safety. N Engl J Med 2003;348:651. 105. Miles AA, Miles EM, Burke J. The value Lett Drug Ther 2007;49:99.
and duration of defence reactions of the skin
92. Simor AE, Ofner-Agostini M, Bryce E, et al. to the primary lodgement of bacteria. Br J 120. Hayek LJ, Emerson JM, Gardner AMN.
The evolution of methicillin-resistant Exp Pathol 1957;38:79. A placebo-controlled trial of the effect of
Staphylococcus aureus in Canadian hos- two preoperative baths or showers with
106. Miles AA. The inflammatory response in
pitals: 5 years of national surveillance. chlorhexidine detergent on postoperative
relation to local infections. Surg Clin North
CMAJ 2001;165:21. Am 1980;60:93. wound infection rates. J Hosp Infect
93. Perl TM, Cullen JJ, Wenzel RP, et al. 1987;10:165.
107. Alexander JW, Alexander WA. Penicillin
Intranasal mupirocin to prevent post- prophylaxis of experimental staphylococcal 121. Hamilton HW, Hamilton KR, Lone FJ.
operative Staphylococcus aureus infections. wound infections. Surg Gynecol Obstet Preoperative hair removal. Can J Surg 1977;
N Engl J Med 2002;346:1871. 1965;120:243. 20:269.
94. Lowbury EJL, Lilly HA, Bull JP. Methods 108. Polk HC Jr. The enhancement of host 122. McDonald WS, Nichter LS. Debridement
for disinfection of hands and operation sites. defenses against infection: search for the of bacterial and particulate-contaminated
Br Med J 1964;2:531. holy grail. Surgery 1986;99:1. wounds. Ann Plast Surg 1994;33:142.
95. Aly R, Maibach HI. Comparative 109. Livingston DH, Malangoni MA. An 123. Edwards PS, Lipp A, Holmes A. Preoperative
antibacterial efficacy of a 2-minute surgical experimental study of susceptibility to skin antiseptics for preventing surgical
scrub with chlorhexidine gluconate, infection after hemorrhagic shock. Surg wound infections after clean surgery.
povidone-iodine, and chloroxylenol sponge- Gynecol Obstet 1989;168:138. Cochrane Database Syst Rev (3):
brushes. Am J Infect Control 1988;16:173. CD003949, 2004.
110. Meakins JL. Surgeons, surgery and
96. Larson E. Guideline for use of topical immunomodulation. Arch Surg 1991;
antimicrobial agents. Am J Infect Control 126:494.
1988;16:253. Acknowledgment
111. Knighton D, Halliday B, Hunt TK. Oxygen
97. Casewell M, Phillips I. Hands as route of as an antibiotic: a comparison of the effects
transmission for Klebsiella species. Br Med of inspired oxygen concentration and Figures 3 and 4 Albert Miller.
J 1977;2:1315. antibiotic administration on in vivo bacterial The author would like to thank Byron J. Master-
98. Jagelman DG, Fabian TC, Nichols RL, clearance. Arch Surg 1986;121:191. son, MD, FACS for his contribution to a previous
et al. Single dose cefotetan versus multiple 112. Rabkin J, Hunt TK. Infection and oxygen. iteration of this chapter, on which the current
dose cefoxitin as prophylaxis in colorectal In: Davis JC, Hunt TK, editors. Problem version is partially based.
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1 BASIC SURGICAL AND PERIOPERATIVE CONSIDERATIONS 2 INFECTION CONTROL
IN SURGICAL PRACTICE — 1
2 INFECTION CONTROL IN
SURGICAL PRACTICE
Vivian G. Loo, MD, MSc, FRCPC
Surgical procedures, by their very nature, interfere with the understanding of host factors and have influenced other
6–11
normal protective skin barrier and expose the patient to aspects of surgical practice. Excessive use of and reliance
microorganisms from both endogenous and exogenous on antibiotics have led to the emergence of multidrug-
sources. Infections resulting from this exposure may not be resistant microorganisms, such as methicillin-resistant Staph-
limited to the surgical site but may produce widespread ylococcus aureus (MRSA), glycopeptide-intermediate S. aureus
systemic effects. Prevention of surgical site infections (SSIs) (GISA), multidrug-resistant Mycobacterium tuberculosis, and
12–15
is therefore of primary concern to surgeons and must be multidrug-resistant Enterococcus strains. Such complica-
addressed in the planning of any operation. Standards of pre- tions reemphasize the need to focus on infection control as
vention have been developed for every step of a surgical an essential component of preventive medicine.
procedure to help reduce the impact of exposure to micro- Besides the impact of morbidity and mortality on patients,
1–3
organisms. Traditional control measures include steriliza- there is the cost of treating nosocomial infections, which is
tion of surgical equipment, disinfection of the skin, use of a matter of concern for surgeons, hospital administrators,
prophylactic antibiotics, and expeditious operation. insurance companies, and government planners alike. Efforts
The Study on the Efficacy of Nosocomial Infection Control to reduce the occurrence of nosocomial infections are now
(SENIC), conducted in US hospitals between 1976 and a part of hospital cost-control management programs.
16,17
1986, showed that surgical patients were at increased risk for The challenge to clinicians is how to reduce cost while main-
all types of infections. The nosocomial, or hospital-acquired, taining control over, and preventing spread of, infection. A
infection rate at that time was estimated to be 5.7 cases out review of 30 studies published between 1990 and 2003
4
of every 100 hospital admissions. These infections included reported that approximately 20% of nosocomial infections
surgical site infections (SSIs), as well as bloodstream, urinary, were preventable.18
and respiratory infections. Today, the increased use of
minimally invasive surgical procedures and early discharge
5
from the hospital necessitates postdischarge surveillance The Surgical Wound and Infection Control
in addition to in-hospital surveillance for the tracking of
nosocomial infections. With the reorganization of health      
care delivery programs, nosocomial infections will appear Nosocomial infections are defined as infections acquired in
more frequently in the community and should therefore be the hospital. There must be no evidence that the infection
considered a part of any patient care assessment plan. was present or incubating at the time of hospital admission.
The Joint Commission on Accreditation of Healthcare Usually, an infection that manifests 48 to 72 hours after
Organizations (JCAHO) strongly recommends that the admission is considered to be nosocomially acquired. An
reduction of healthcare associated infections be prioritized as infection that is apparent on the day of admission is usually
a national patient safety goal (http://www.jointcommission. considered to be community acquired, unless it is epidemio-
org/PatientSafety/InfectionControl). Effective infection con- logically linked to a previous admission or to an operative
trol and prevention require an organized, hospital-wide procedure at the time of admission.
program aimed at achieving specific objectives. The program’s SSIs account for 14 to 16% of all nosocomial infections.
purpose should be to obtain relevant information on the They occur in 2 to 5% of patients undergoing clean proce-
occurrence of nosocomial infections among both patients and dures and in as many as 20% of patients undergoing intra-
employees. The data should be documented, analyzed, and abdominal operations.19 To encourage a uniform approach
communicated along with a plan for corrective measures. among data collectors, the Centers for Disease Control and
Such surveillance activities, combined with education, form Prevention (CDC) has suggested three categories of SSIs,
the basis of an infection control program. supplying definitions for each category [see Table 1].20 The
Data relating to host factors are an integral part of infection CDC defines an incisional SSI as an infection that occurs at
data analysis. Documentation of host factors has made for a the incision site within 30 days after surgery or within 1 year
better appreciation of the associated risks and has allowed if a prosthetic implant is in place. Infection is characterized
comparative evaluation of infection rates. Development of by redness, swelling, or heat with tenderness, pain, or dehis-
new surgical equipment and technological advances have cence at the incision site and by purulent drainage. Other
influenced the impact of certain risk factors, such as the indicators of infection include fever, deliberate opening of the
length of an operation and the duration of a hospital wound, culture-positive drainage, and a physician’s diagnosis
stay. Clinical investigations have helped improve the of infection with prescription of antibiotics. The category of
DOI 10.2310/7800.2008.S01C02
05/08
Table 1 Surgical Site Infections (SSIs)20 Table 2 American Society of Anesthesiologists Physical
Status Scale
Superficial SSIs
Skin Class Patient Description
Deep incisional SSIs
Fascia 1 A normally healthy individual
Muscle layers 2 A patient with mild systemic disease
Organ or space SSIs
Body organs A patient with severe systemic disease that is
3
Body spaces not incapacitating
A patient with incapacitating systemic disease
4
that is a constant threat to life
organ or space SSI was included to cover any part of the A moribund patient who is not expected to
5
survive 24 hr with or without operation
anatomy other than the incision (ie, organs or spaces) that
might have been opened or manipulated during the operative E Added for emergency procedures
procedure. This category would include, for example, arterial
and venous infections, endometritis, disk space infections,
20
and mediastinitis. hair removal (and likelihood of consequent skin injury),
There should be collaboration between the physician or inappropriate use of antimicrobial prophylaxis, duration of
nurse and the infection control practitioner to establish the the operation, and wound classification. The influence of
presence of an SSI. The practitioner should complete the hair removal methods on SSI has been examined by many
surveillance with a chart review and document the incident investigators. Infection rates were reported to be lower with
6,7
in a computer database program for analysis. The data must depilatory agents and electric clippers than with razors.
be systematically recorded; many commercial computer pro- Antimicrobial prophylaxis is used for all operations that
grams are available for this purpose. One group reported that involve entry into a hollow viscus. Antimicrobial prophylaxis
their experience with the Health Evaluation through Logical is also indicated for clean operations in which an intra-
Processing system was useful for identifying patients at high articular or intravascular prosthetic device will be inserted
21
risk for nosocomial infections. and for any operation in which an SSI would have a high
22
morbidity. A comprehensive study determined that there
    is considerable variation in the timing of administration
The risk of development of an SSI depends on host factors, of prophylactic antibiotics, but that administration within
8
perioperative wound hygiene, and the duration of the surgical 2 hours before surgery reduces the risk of SSI.
procedure. Identification of host and operative risk factors Operative wounds are susceptible to varying levels of bac-
can help determine the potential for infection and point terial contamination, by which they are classified as clean,
toward measures that might be necessary for prevention and clean-contaminated, contaminated, or dirty.25 In most insti-
control. tutions, the responsibility for classifying the incision site is
assigned to the operating room circulating nurse; one assess-
Host Risk Factors ment suggests that the accuracy of decisions made by this
26
Host susceptibility to infection can be estimated according group is as high as 88%.
to the following variables: older age, severity of disease,
physical-status classification (see below), prolonged preoper- Composite Risk Indices
ative hospitalization, morbid obesity, malnutrition, immuno- The CDC established the National Nosocomial Infections
suppressive therapy, smoking, preoperative colonization with Surveillance (NNIS) system in 1970 to create a national
22
S. aureus, and coexistent infection at a remote body site. database of nosocomial infections.27 The NNIS system has
A scale dividing patients into five classes according to been used to develop definitions of infections and indices for
their physical status was introduced by the American Society predicting the risk of nosocomial infection in a given patient.
of Anesthesiologists (ASA) in 1974 and tested for precision The NNIS system has been integrated into the National
23
in 1978. The test results showed that the ASA scale is Healthcare Safety Network (NHSN).28
a workable system, though it lacks scientific definition
[see Table 2]. NNIS Basic Risk Index NNIS developed a composite
Significant differences in infection rates have been shown risk index composed of the following criteria: ASA score,
in patients with different illnesses. In one prospective study, wound class, and duration of surgery. Reporting on data
the severity of underlying disease (rated as fatal, ultimately collected from 44 US hospitals between 1987 and 1990,
fatal, or nonfatal) was shown to have predictive value for NNIS demonstrated that this risk index is a significantly
endemic nosocomial infections; the nosocomial infection rate better predictor for development of SSI than the traditional
in patients with fatal diseases was 23.6%, compared with wound classification system alone.29,30 The NNIS risk index
24
2.1% in patients with nonfatal diseases. is a useful method of risk adjustment for a wide variety of
procedures.
Operative Risk Factors The NNIS risk index assigns patients scores of 0, 1, 2,
Several factors related to the operative procedure may be or 3. A patient’s score is determined by counting the number
associated with the risk of development of an SSI [see 1:1 of risk factors present from among the following: an ASA
Prevention of Postoperative Infection]. These include method of score of 3, 4, or 5; a surgical wound that is classified as
05/08
contaminated or dirty/infected; and an operation lasting the focus of improvement in a 1-year collaborative project
longer than T hours (where T represents the 75th percentile that included 56 hospitals and 43 Medicare quality improve-
of distribution of the duration of the operative procedure ment organizations.36 Other performance measures included
being performed, rounded to the nearest whole number of maintenance of patient normothermia, use of supplemental
hours). oxygenation, maintenance of euglycemia and appropriate hair
removal. In this collaborative project, hospitals reported a
Modified NNIS Basic Risk Index for Procedures 27% mean reduction in their SSI rates.36
Using Laparoscopes For cholecystectomy and colon The Surgical Care Improvement Project (SCIP) was
surgery procedures, the use of a laparoscope lowered the risk developed in 2003 and evolved from the SIP project.35 This
of SSI within each NNIS risk index category.31 Hence, for initiative is a national partnership of organizations (including
these procedures, when the procedure is performed laparo- the American College of Surgeons [ACS]) that is committed
scopically, the risk index should be modified by subtracting 1 to the reduction of postoperative complications in four
from the basic NNIS risk index score. With this modification, areas: (1) prevention of SSIs, (2) prevention of venous throm-
the risk index has values of M (or −1), 0, 1, 2, or 3. For boembolism, (3) prevention of adverse cardiac events, and
appendectomy and gastric surgery, use of a laparoscope (4) prevention of respiratory complications.35
affected SSI rates only when the NNIS basic risk index was
0, thereby yielding five risk categories: 0—Yes, 0—No, 1, 2, Hand Hygiene
and 3, where Yes or No refers to whether the procedure was Although hand hygiene is considered the single most
performed with a laparoscope.31 important measure for preventing nosocomial infections,
poor compliance is frequent.37 Role modeling is important in
Operation-Specific Risk Factors It is likely that positively influencing this behavior. One study showed that
operation-specific logistic regression models will increasingly a hand-washing educational program contributed to a
be used to calculate risk. For example, in spinal fusion reduction in the rate of nosocomial infections.38 Good hand-
surgery, Richards and colleagues identified diabetes mellitus, washing habits can be encouraged by making facilities (with
ASA score greater than 3, operation duration longer than sink, soap, and paper towels) visible and easily accessible
4 hours, and posterior surgical approach as significant inde- in patient care areas [see 1:1 Prevention of Postoperative
pendent predictors of SSI.32 Other logistic regression models Infection].
have been developed for craniotomy and cesarean section.33,34 Agents used for hand hygiene include plain nonantimicro-
These models should permit more precise risk adjustment. bial soaps, antimicrobial soaps, and waterless alcohol-based
hand antiseptics. Plain soaps have very little antimicrobial
  activity: they mainly remove dirt and transient flora.39 Com-
In any surgical practice, policies and procedures should be pared with plain soaps, antimicrobial soaps achieve a greater
in place pertaining to the making of a surgical incision and log reduction in eliminating transient flora and have the
the prevention of infection. These policies and procedures additional advantage of sustained activity against resident
should govern the following: (1) skin disinfection and hand- hand flora.39 Alcohol-based hand antiseptics have an excellent
washing practices of the operating team, (2) preoperative spectrum of antimicrobial activity and rapid onset of action,
preparation of the patient’s skin (e.g., hair removal and use dry rapidly, and do not require the use of water or towels.40
of antiseptics), (3) the use of prophylactic antibiotics, (4) Therefore, they are recommended for routine decontamina-
techniques for preparation of the operative site, (5) manage- tion of hands during patient care, except when hands are
ment of the postoperative site if drains, dressings, or both visibly soiled. Emollients are often added to alcohol-based
are in place, (6) standards of behavior and practice for the waterless hand antiseptics because of these antiseptics’
operating team (e.g., the use of gown, mask, and gloves), (7) tendency to cause drying of the skin.40
special training of the operating team, and (8) sterilization
Sterilization and Disinfection
and disinfection of instruments.
Spaulding proposed in 1972 that the level of disinfection
Surgical Infection Prevention and Surgical Care Improvement and sterilization for surgical and other instruments be deter-
Projects mined by classifying the instruments into three categories
In 2002, the Centers for Medicare and Medicaid Services, according to the degree of infection risk involved in their use:
in collaboration with the CDC, implemented the National critical, semicritical, and noncritical.41
Surgical Infection Prevention (SIP) Project.35 The goal of Critical items include objects or instruments that directly
the SIP Project is to decrease the morbidity and mortality enter the vascular system or sterile areas of the body. These
associated with postoperative SSI by advocating appropriate items should be sterilized by steam under pressure, dry heat,
selection and timing of prophylactic antibiotics. Three per- ethylene oxide, or other approved methods. Flash steriliza-
formance measures were developed: (1) the percentage of tion is the process by which surgical instruments are sterilized
patients who receive parenteral antimicrobial prophylaxis for immediate use should an emergency situation arise (e.g.,
within 1 hour before incision (within 2 hours for vancomycin an instrument that was accidentally dropped). This is usually
or fluoroquinolone), (2) the percentage of patients who are achieved by leaving instruments unwrapped in a container
given a prophylactic antimicrobial regimen consistent with and using a rapid steam cycle.42 Instruments must still be
published guidelines, and (3) the percentage of patients manually cleaned, decontaminated, inspected, and properly
whose prophylactic antimicrobial is discontinued within 24 arranged in the container before sterilization. Implantables
hours after surgery. These three performance measures were should not be flash sterilized. Flash sterilization is not intended
05/08
to replace conventional steam sterilization of surgical with MRSA have been traced to MRSA carriers among health
instruments or to reduce the need for adequate instrument care workers.48 Screening of personnel to identify carriers is
inventory.42 undertaken only when an outbreak of nosocomial infection
Semicritical items are those that come into contact with occurs that cannot be contained despite implementation of
mucous membranes or skin that is not intact (eg, broncho- effective control measures and when a health care worker is
scopes and gastroscopes). Scopes have the potential to cause epidemiologically linked to cases.
infection if they are improperly cleaned and disinfected. Protecting the health care team from infection is a constant
Transmission of infection has been documented after endo- concern. Preventive measures, such as immunizations and
scopic investigations, including infection with Salmonella typhi preemployment medical examinations, should be undertaken
and Helicobacter pylori.43,44 Semicritical items generally require at an employee health care center staffed by knowledgeable
high-level disinfection that kills all microorganisms except personnel.49 Preventable infectious diseases, such as chicken-
bacterial spores.45 Glutaraldehyde 2% is a high-level disinfec- pox and rubella, should be tightly controlled in hospitals that
tant that has been used extensively in flexible endoscopy. serve immunocompromised and obstetric patients. It is highly
Before disinfection, scopes should receive a thorough manual recommended that a record be maintained of an employee’s
cleaning to eliminate gross debris. To achieve high-level immunizations. Knowledge of the employee’s health status
disinfection, the internal and external surfaces and channels on entry to the hospital helps ensure appropriate placement
should come into contact with the disinfecting agent for a and good preventive care.
minimum of 20 minutes.45 Glutaraldehyde has certain dis- When exposure to contagious infections is unavoidable,
advantages. In particular, it requires activation before use; susceptible personnel should be located, screened, and given
moreover, it is irritating to the skin, eyes, and nasal mucosa, prophylactic treatment if necessary. In collaboration with the
and thus, its use requires special ventilation or a ducted fume occupational health department, infection control personnel
hood.45 An alternative to glutaraldehyde is orthophthaldehyde should define the problem, establish a definition of contact,
(OPA), a newer agent that is approved by the Food and Drug and take measures to help reduce panic.
Administration (FDA) for high-level disinfection. OPA is
Isolation Precautions
odorless and nonirritating and does not require activation
before use.46 CDC guidelines have been developed to prevent the trans-
Noncritical items are those that come in contact with intact mission of infections.50 These isolation guidelines promote
skin (e.g., blood pressure cuffs). They require only cleaning two levels of isolation precautions: standard precautions and
with a detergent and warm water or disinfection with an transmission-based precautions.
intermediate-level or low-level germicide for 10 minutes.
The reuse of single-use medical devices has become a topic Standard Precautions The standard precautions, which
of interest because of the implied cost savings. The central incorporate the main features of the older universal precau-
concerns are the effectiveness of sterilization or disinfection tions and body substance isolation guidelines, were developed
according to category of use, as well as maintenance of the to reduce the risk of transmission of microorganisms for
essential mechanical features and the functional integrity of all patients, regardless of their diagnosis.50,51 Standard pre-
the item to be reused. The FDA has issued regulations gov- cautions apply to blood, all body fluids, secretions and
erning third-party and hospital reprocessors engaged in repro- excretions, and mucous membranes.
cessing single-use devices for reuse. These regulations are
available on the FDA’s Web site (http://www.fda.gov/cdrh/ Transmission-Based Precautions Transmission-based
reprocessing/index.html). precautions were developed for certain epidemiologically
important pathogens or clinical presentations. These pre-
Hair Removal cautions comprise three categories, based on the mode of
An infection control program should have a hair-removal transmission: airborne precautions, droplet precautions,
policy for preoperative skin preparation [see 1:1 Prevention of and contact precautions.50 Precautions may be combined for
Postoperative Infection]. certain microorganisms or clinical presentations (e.g., both
contact and airborne precautions are indicated for a patient
Operating Room Environment with varicella).
Environmental controls in the OR have been used to reduce Airborne precautions are designed to reduce transmission
the risk of SSI [see 1:8 Preparation of the Operating Room]. The of microorganisms spread via droplets that have nuclei 5 µm
OR should be maintained under a positive pressure of at least in size or smaller, remain suspended in air for prolonged
2.5 Pa in relation to corridors and adjacent areas. In addition, periods of time, and have the capability of being dispersed
there should be 20 to 25 air changes per hour for ceiling widely.50 Airborne precautions include wearing an N95 respi-
heights between 9 and 12 feet.47 rator, placing the patient in a single room that is under a
negative pressure of 2.5 Pa in relation to adjacent areas, keep-
       ing the door closed, providing a minimum of 6 to 12 air
The health care team has a primary role in the prevention changes per hour, and exhausting room air outside the build-
of infection. Continued education and reinforcement of poli- ing and away from intake ducts or, if recirculated, through
cies are essential: the team must be kept well informed and a high-efficiency particulate air (HEPA) filter.50 Airborne
up to date on concepts of infection control. Inadvertently, precautions are indicated for patients with suspected or
team members may also be the source of, or the vector in, confirmed infectious pulmonary or laryngeal tuberculosis;
transmission of infection. Nosocomial infection outbreaks measles; varicella; disseminated herpes zoster; and Lassa,
05/08
Ebola, Marburg, and other hemorrhagic fevers with pneumo- pose a major risk. It is estimated that in the United States,
nia. Varicella, disseminated herpes zoster, and hemorrhagic about 1.25 million people have chronic HBV infection, and
fevers with pneumonia also call for contact precautions (see more than 4 million have chronic HCV infection. Transmis-
below). sion of these infections to health care workers continues to
Droplet precautions are designed to reduce the risk of occur, and each year, approximately 250 health care workers
transmission of microorganisms spread via large-particle die of chronic HBV infection alone.57 Hepatitis B vaccination
droplets that are greater than 5 µm in size, do not remain has proved safe and protective and is highly recommended
suspended in the air for prolonged periods, and usually travel for all high-risk employees; it should be made available
1 m or less.50 No special ventilation requirements are required through the employee health care center.
to prevent droplet transmission. A single room is preferable, Despite the efficacy of the vaccine, many surgeons and
and the door may remain open. Examples of patients for other personnel remain unimmunized and are at high risk
whom droplet precautions are indicated are those with influ- for HBV infection.57 Whereas younger surgeons have been
enza, rubella, mumps, and meningitis caused by Haemophilus
routinely immunized, an estimated 25 to 30% of surgeons
influenzae and Neisseria meningitidis.
who have been in practice for longer than 10 to 15 years
Contact precautions are designed to reduce the risk of
remain at substantial risk.57 HBV is far more easily transmit-
transmission of microorganisms by direct or indirect contact.
ted than HIV and continues to have a greater impact on the
Direct contact involves skin-to-skin contact resulting in phys-
morbidity and mortality of health care personnel.53 The risk
ical transfer of microorganisms.50 Indirect contact involves
contact with a contaminated inanimate object that acts as an of seroconversion is at least 30% after percutaneous exposure
intermediary. Contact precautions are indicated for patients to blood from a hepatitis B e antigen–seropositive source.53
colonized or infected with Clostridium difficile and multidrug- Given that a patient’s serostatus may be unknown, it is impor-
resistant bacteria that the infection control program judges to tant that health care workers follow standard precautions for
be of special clinical and epidemiologic significance.50 all patients.
Exposure to Bloodborne Pathogens Hepatitis C Virus The average incidence of seroconver-

The risk of transmission of HIV and hepatitis B virus sion after percutaneous exposure from an HCV-positive
(HBV) from patient to surgeon or from surgeon to patient source is 1.8% (range, 0 to 7%).53,58,59 Mucous membrane
has resulted in a series of recommendations governing con- exposure to blood rarely results in transmission, and no trans-
tact with blood and body fluids.52–54 The risk of acquiring a mission has been documented from exposure of intact or
bloodborne infection (e.g., HBV, hepatitis C virus [HCV], nonintact skin to blood.53 There is no recommended postex-
or HIV) depends on three factors: type of exposure to the posure prophylaxis regimen for HCV. The use of immuno-
bloodborne pathogen, prevalence of infection in the popula- globulin has not been demonstrated to be protective.53 There
tion, and the rate of infection after exposure to the blood- are no antiviral medications recommended for postexposure
borne pathogen.52–54 Postexposure management has been prophylaxis.53
discussed in CDC guidelines (http://www.cdc.gov/mmwr/
pdf/rr/rr5011.pdf).52 Management of occupational exposures Human Immunodeficiency Virus Exposure to blood
to HIV was updated in 2005 (http://www.cdc.gov/mmwr/ and body substances of patients who have AIDS or who are
preview/mmwrhtml/rr5409a1.htm).54 seropositive for HIV constitutes a health hazard to hospital
Protection of the face and hands during the operative pro- employees. The magnitude of the risk depends on the degree
cedure is important. A study of 8,502 operations found that
and method of exposure [see 8:21 Acquired Immunodeficiency
the rate of direct blood exposure was 12.4%, whereas the rate
Syndrome].54 Because screening for HIV infection is not
of parenteral exposure via puncture wounds and cuts was
mandatory among patients, the CDC recommends following
2.2%. Parenteral blood contacts were twice as likely to occur
the same guidelines for all patients undergoing invasive pro-
among surgeons as among other OR personnel.55 These find-
cedures that one would use in cases of known HIV-infected
ings support the need for OR practice policies and the choice
of appropriate personal protective equipment for the OR patients [see Table 3].52
staff. OR practice policy should give particular attention to There have been isolated reports of transmission of HIV,
methods of using sharp instruments and to ways of reducing HBV, and HCV from healthcare workers to patients. It is
the frequency of percutaneous injuries: sharp instruments imperative to prevent transmission of these bloodborne
should be passed in a metal dish, cautery should be used, and pathogens from surgeons to patients. Accordingly, the CDC
great care should be taken in wound closures. It is important has developed specific guidelines for health care workers
that face shields and masks protect the operating team from and exposure-prone activities [see Table 3].52 Similarly, the
splashes and aerosolized fluids. For optimal protection, a ACS has issued additional recommendations regarding the
mask should be fluid-capture efficient and air resistant.56 surgeon’s role in the prevention of hepatitis transmission and
For invasive surgical procedures, double gloving has HIV [see Table 4].52,57,60
become routine. However, there are recognized differences
among the gloves available. Latex allergy is an important Exposure to Tuberculosis
issue; nonlatex alternatives are available for those who are In studies of health care workers, the incidence of positive
allergic. results on tuberculin skin testing have ranged from 0.11
to 10%.61,62 Health care workers who are immunocompro-
Hepatitis B Virus For active surgeons and other mised are at high risk for the development of disease after
members of the health care team, HBV infection continues to exposure.61
05/08
Table 3 CDC Recommendations for Prevention of HIV and Table 4 ACS Recommendations for Preventing
HBV Transmission during Invasive Procedures52 Transmission of Hepatitis57
Health care workers with exudative lesions or weeping dermatitis Surgeons should continue to utilize the highest standards of
should cover any unprotected skin, or they should not provide infection control, involving the most effective known sterile
patient care until the damaged skin has healed. barriers, universal precautions, and scientifically accepted
Hands should be washed after every patient contact. measures to prevent blood exposure during every operation.
Health care workers should wear gloves when contact with blood This practice should extend to all sites where surgical care is
or body substances is anticipated; double gloves should be used rendered and should include safe handling practices for needles
during operative procedures; hands should be washed after and sharp instruments.
gloves are removed. Surgeons have the same ethical obligations to render care to
Gowns, plastic aprons, or both should be worn when soiling of patients with hepatitis as they have to render care to other
clothing is anticipated. patients.
Mask and protective eyewear or face shield should be worn if Surgeons with natural or acquired antibodies to HBV are
aerosolization or splattering of blood or body substances is protected from acquiring HBV from patients and cannot
expected.
transmit the disease to patients. All surgeons and other
Resuscitation devices should be used to minimize the need for
mouth-to-mouth resuscitation. members of the health care team should know their HBV
Disposable containers should be used to dispose of needles and immune status and become immunized as early as possible in
sharp instruments. their medical career.
Avoid accidents and self-wounding with sharp instruments by Surgeons without evidence of immunity to HBV who perform
following these measures: procedures should know their HBsAg status and, if this is
• Do not recap needles. positive, should also know their HBeAg status. In both
• Use needleless systems when possible. instances, expert medical advice should be obtained and all
• Use cautery and stapling devices when possible. appropriate measures taken to prevent disease transmission to
• Pass sharp instruments in metal tray during operative patients. Medical advice should be rendered by an expert
procedures. panel composed and convened to fully protect practitioner
confidentiality. The HBeAg-positive surgeon and the panel
In the case of an accidental spill of blood or body substance on should discuss and agree on a strategy for protecting patients at
skin or mucous membranes, do the following: risk for disease transmission.
• Rinse the site immediately and thoroughly under water.
On the basis of current information, surgeons infected with HCV have
• Wash the site with soap and water.
no reason to alter their practice but should seek expert medical advice
• Document the incident (i.e., report to Occupational Safety and
Health Administration or to the Infection Control Service). and appropriate treatment to prevent chronic liver disease.
Blood specimens from all patients should be considered hazardous HBeAg = hepatitis B e antigen; HBsAg = hepatitis B surface antigen; HCV =
hepatitis C virus
at all times.
Prompt attention should be given to spills of blood or body
substances, which should be cleaned with an appropriate 2. Surveillance by objective, or targeted surveillance, in
disinfectant. which a specific goal is set for reducing certain types of
CDC = Centers for Disease Control and Prevention; HBV = hepatitis B infection. This concept is priority directed and can be
virus. further subdivided into two distinct activities:
a. The setting of outcome objectives, in which the
The CDC recommendations for tuberculosis prevention objectives for the month or year are established and all
place emphasis on a hierarchy of control measures, including
efforts are applied to achieving a desired rate of infec-
administrative engineering controls and personal respiratory
tion. As with the hospital-wide approach, a short-term
protection (http://www.cdc.gov/mmwr/PDF/rr/rr5417.pdf).63
plan would be made to monitor, record, and measure
The following measures should be considered:
infections and to provide feedback on the results.
1. The use of risk assessments and development of a written b. The setting of process objectives, which incorporates
tuberculosis control protocol. the patient care practices of doctors and nurses as
2. Early identification, treatment, and use of airborne they relate to outcome (e.g., wound infections and their
precautions for persons who have tuberculosis. control).
3. Tuberculosis screening and respiratory protection 3. Periodic surveillance: intensive surveillance of infections
programs for health care workers. and patient-care practices by unit or by service at different
4. Training and education. times of the year.
5. Evaluation of tuberculosis infection control programs.63 4. Prevalence survey: the counting and analysis of all active
infections during a specified time period. This permits
Activities of an Infection Control Program identification of nosocomial infection trends and problem
areas.
 5. Outbreak surveillance: the identification and control of
The cornerstone of an infection control program is surveil- outbreaks of infection. Identification can be made on the
lance. This process depends on the verification, classification, basis of outbreak thresholds if baseline bacterial isolate
analysis, reporting, and investigation of infection occurrences, rates are available and outbreak thresholds can be
with the intent of generating or correcting policies and developed. Problems are evaluated only when the number
procedures. Five surveillance methods can be applied64,65: of isolates of a particular bacterial species exceeds outbreak
thresholds.
1. Total, or hospital-wide, surveillance: collection of com-
prehensive data on all infections in the facility, with the Surveillance techniques include the practice of direct
aim of correcting problems as they arise. This is labor patient observation and indirect observation by review of
intensive. microbiology reports, nursing Kardex, or the medical record
05/08
to obtain data on nosocomial infections.6,64 The sensitivity such as Foley catheters, ventilators, and intravascular lines
of case finding was found to be 33 to 65% with microbiology can be illustrated as device-associated risks according to site,
reports, 85% with Kardex, and 90% with total chart as follows:
review.64 These methods may be used either separately or in
(Number of device-associated infections of a site/
combination to obtain data on clinical outcomes.
Number of device days)x1,000
The increasing practice of same-day or short-stay surgical
procedures has led to the need for postdischarge surveillance. Reporting
This may be done by direct observation in a follow-up clinic, One use of surveillance data is to generate information for
by surveying patients through the mail or over the telephone, individual surgeons, service chiefs, and nursing personnel
by reviewing medical records, or by mailing questionnaires as an indicator of their progress in keeping infections and
directly to surgeons. The original CDC recommendation of diseases under control. Infection notification to surgeons has
30 days for follow-up was used by one hospital to randomly been shown to have a positive influence on clean-wound
screen post–joint arthroplasty patients by telephone. This infection rates.6,7 This technique was used by Cruse and
screening identified an infection rate of 7.5%, compared with Foord in 1980 to show a progressive decrease in the infection
2% for hospitalized orthopedic patients.66 Results from rates of clean surgical wounds to less than 1% over 10 years.7
another medical center suggested that 90% of cases would be In other settings, endemic rates of bloodstream, respiratory,
captured in a 21-day postoperative follow-up program.5 The and urinary tract infection were corrected and reduced by
use of prosthetic materials for implants requires extending the routine monitoring and reporting to medical and nursing
follow-up period to 1 year. staff.24
In a medical setting, Britt and colleagues also reported a
Verification and Definition of Infection
reduction in endemic nosocomial infection rates for urinary
The CDC provides definitions for specific nosocomial infec- tract infections, from 3.7% to 1.3%, and for respiratory tract
tions (http://www.cdc.gov/ncidod/dhqp/pdf/nnis/NosInfDefi- infections, from 4.0% to 1.6%, simply by keeping medical
nitions.pdf).67 The use of standardized definitions is critical personnel aware of the rates.24
for consistency, particularly if interhospital comparisons
are made. A complete assessment should include clinical Outbreak Investigation
evaluation of commonly recognized sites (e.g., wound, respi- There are 10 essential components to an outbreak investi-
ratory system, urinary tract, and intravenous access sites) for gation:
evidence of infection, especially when no obvious infection is
1. Verify the diagnosis and confirm that an outbreak exists.
seen at the surgical site. Laboratory and radiologic data
This is an important step, because other factors may
should complement the clinical information. Microbiologic
account for an apparent increase in infections. These
evaluation should aim at identification of the microorganism
factors may include a reporting artifact resulting from a
(which depends on an adequate specimen for Gram’s staining
change in surveillance methodology, a laboratory error or
and culture).
change in laboratory methodology, or an increase in the
Use of Denominators denominator of the formula used for data analysis (if this
increase is proportionate to the rise in the numerator, the
The choice of denominators depends on the patients at risk
infection rate has not changed).
of acquiring nosocomial infections and on the ease or diffi-
2. Formulate a case definition to guide the search for
culty of collecting the data for denominators. Commonly
potential patients with disease.
used denominators include the number of admissions, the
3. Draw an epidemic curve that plots cases of the disease
number of patient-days, and the number of procedures. For against time of onset of illness. This curve compares the
device-related infections, the appropriate denominator is the number of cases during the epidemic period with the
number of days of device exposure; this variable takes into baseline. In addition, the epidemic curve helps to deter-
account the differences in the risks experienced by the moni- mine the probable incubation period and how the disease
tored patient. is being transmitted (i.e., a common source versus person
Data Analysis to person).
4. Review the charts of case patients to determine demo-
The original practice of presenting overall hospital-wide graphics and exposures to staff, medications, therapeutic
crude rates provided little means for adjustment of variables modalities, and other variables of importance.
(e.g., risk related to the patient or to the operation). The 5. Perform a line listing of case patients to determine
following three formulas, however, are said to offer more whether there is any common exposure.
precision than traditional methods68: 6. Calculate the infection rate. The numerator is the number
(Number of nosocomial infections/Service operations) of infected patients, and the denominator is the number
x100 of patients at risk.
[Number of site-specific nosocomial infections/Specific 7. Formulate a tentative hypothesis to explain the reservoir
and the mode of transmission. A review of the literature
operations (e.g., number of inguinal hernias)]x100
on similar outbreaks may be necessary.
[Number of nosocomial infections/Hospital
8. Test the hypothesis, using a case-control study, cohort
admissions (patient-days)]x1,000
study, prospective intervention study, or microbiologic
Data on infections of the urinary tract, respiratory system, study. A case-control study is usually used, because it
and circulatory system resulting from exposure to devices is less labor intensive. For a case-control study, control
05/08
subjects should be selected from an uninfected surgical Strategies for preventing and controlling the emergence
population of patients who were hospitalized at the and spread of antimicrobial-resistant microorganisms have
same time as those identified during the epidemic period been developed (http://www.cdc.gov/ncidod/dhqp/pdf/ar/
and matched for age, gender, service operation, operation mdroGuideline2006.pdf). These guidelines include opti-
date, and health status (ASA score). Two or three control mizing antimicrobial prophylaxis for surgical procedures;
patients are usually selected for every case patient. optimizing the choice and duration of empirical therapy;
The cases and controls are then compared with respect improving antimicrobial prescribing patterns by physicians;
to possible exposures that may increase the risk of dis- monitoring and providing feedback regarding antibiotic resis-
ease. Patient, personnel, and environmental microbiologic tance; formulating and using practice guidelines for antibiotic
isolates (if any) should be kept for fingerprinting (e.g., usage; developing a system to detect and report trends in
with pulsed-field gel electropheresis or random amplified antimicrobial resistance; ensuring that caregivers respond
polymorphic DNA polymerase chain reaction). rapidly to the detection of antimicrobial resistance in indi-
9. Institute infection control measures. This may be done at
vidual patients; incorporating the importance of controlling
any time during the investigation. The control measures
antimicrobial resistance into the institutional mission and
should be reviewed after institution to determine their
climate; increasing compliance with basic infection control
efficacy and the possible need for changing them.
policies and procedures; and developing a plan for identify-
10. Report the incident to the infection control committee,
and submit a report at the completion of the investiga- ing, transferring, discharging, and readmitting patients
tion. The administrators, physicians, and nurses involved colonized or infected with specific antimicrobial-resistant
should be informed and updated as events change.69 microorganisms.76
-  Clostridium difficile

C. difficile is recognized as the leading cause of nosocomial
Staphylococci infectious diarrhea.80 The best-described C. difficile virulence
Hospitals and communities worldwide are facing the factors are toxins A and B.81 The most important risk factor
challenge posed by the spread of antimicrobial-resistant for C. difficile–associated infection (CDI) is previous antibio-
microorganisms. Strains of MRSA are increasing in hospitals tic use.80 After exposure to C. difficile, some patients remain
and are an important cause of nosocomial infections; in a asymptomatic, whereas others experience illnesses ranging
sample of intensive care units in the United States in 2003, from mild diarrhea to fulminant colitis.80 The incidence of
approximately 59.5% of S. aureus isolates were resistant to severe disease leading to death, colectomy, or the need for
methicillin or oxacillin.28 MRSA strains not only replace intensive care is usually no more than 1 to 5%.
methicillin-susceptible strains as a cause of hospital-acquired In the past few years, CDI outbreaks characterized by
infections but also actually increase the total burden of increased morbidity and mortality have been reported in the
nosocomial infections.70 Moreover, there are reports that United States, Canada, and Europe. These outbreaks have
MRSA is becoming a community-acquired pathogen.71,72 A been attributed to the emergence of a hypervirulent strain of
population-based surveillance of invasive MRSA infections in C. difficile, which is now referred to as the North American
the United States performed from July 2004 to December pulsed-field type 1 (NAP1) or PCR ribotype 027.82–84 Com-
2005 determined that 85% were healthcare associated and pared with control strains, the NAP1 strain produces 16-fold
14% were community associated; 1% could not be classi- greater quantities of toxin A and 23-fold greater quantities of
fied.72 A proactive approach to controlling MRSA at all levels toxin B.85
of health care can result in decreased MRSA infection For control of CDI outbreaks, a multifaceted approach is
rates.73,74 required, including close attention to hand hygiene, use of
Strains of GISA, an emerging pathogen first isolated in contact precautions when providing care to CDI patients,
1996 in Japan,75 exhibit reduced susceptibility to vancomycin environmental disinfection, antibiotic restriction, and rapid
and teicoplanin. DNA fingerprinting suggests that these laboratory diagnosis.86
GISA strains evolved from preexisting MRSA strains that
infected patients in the months before the GISA infection.  
Contact precautions are indicated for patients infected or
Control of the microbial reservoir of the patient’s immedi-
colonized with GISA; infection control guidelines to prevent
ate environment in the hospital is the goal of an infection
the spread of GISA are available.76
control program. Environmental control begins with design
Enterococci of the hospital’s physical plant. The design must meet the
Vancomycin-resistant Enterococcus (VRE) accounts for functional standards for patient care and must be integrated
38.2% of all enterococci in the ICUs participating in the into the architecture to provide traffic accessibility and con-
NNIS program.28 Transmission usually occurs through trol. Since the 1960s, the practice of centralizing seriously ill
contact with the contaminated hands of a health care worker. patients in intensive care, dialysis, and transplant units has
The environment is an important reservoir for VRE, but it is accentuated the need for more careful analysis and planning
not clear whether the environment plays a significant role of space. The primary standards for these special care units
in transmission.77 Risk factors for VRE acquisition include a and ORs require planning of floor space, physical surfaces,
prolonged hospital stay, liver transplantation, the presence of lighting, ventilation, water, and sanitation to facilitate easy
feeding tubes, dialysis, and exposure to cephalosporins.78 cleaning and disinfecting of surfaces, sterilization of instru-
Contact precautions are indicated for patients infected or ments, proper food handling, and garbage disposal. These
colonized with VRE.76,79 activities should then be governed by practical policies that
05/08
are understandable to the staff. Preventive maintenance Benefits of an Infection Control Program
should be a basic and integral activity of the physical plant The establishment of an infection control program can
department. greatly benefit a hospital. An infection control program sup-
Surveillance of the environment by routine culturing of ports patient safety and is a means for continuous quality
OR floors and walls was discontinued in the late 1970s. improvement in the care that is given, in addition to being an
Autoclaves and sterilization systems should, however, be accreditation requirement. In Canada and the United States,
continuously monitored with quality control indicators. The the need for infection control programs is supported by
results should be documented and records maintained. all governing agents, including the Canadian Council on
Investigations of the physical plant should be reserved
Hospital Accreditation, JCAHO, the American Hospital
for specific outbreaks, depending on the organism and its
Association (AHA), the Canadian Hospital Association, the
potential for causing infection. This was demonstrated by
Association for Practitioners in Infection Control (APIC), the
an outbreak of sternal wound Legionella infections among
Society of Hospital Epidemiologists of America (SHEA) Joint
post–cardiovascular surgery patients after they were exposed
Commission Task Force, and the Community and Hospital
to tap water during bathing.87 The CDC provides guidelines
Infection Control Association–Canada (CHICA-Canada).
for infection control issues related to the environment.88,89
The effectiveness of infection surveillance and control pro-
Hospital-acquired aspergillosis is caused by another ubiqui-
grams in preventing nosocomial infections in US hospitals
tous microorganism that is often a contaminant of ambient
was assessed through the SENIC Project.91 In a representative
air during construction. The patients most at risk are usually
sample of US general hospitals, infection control programs
immunosuppressed (i.e., neutropenic). It is recommended
with a trained infection control physician or microbiologist
that preventive measures be instituted for these patients when
and at least one infection control nurse per 250 beds were
construction is being planned.90 The provision of clean (i.e.,
associated with a 32% lower rate of four infections studied
HEPA-filtered) air in positive pressure–ventilated rooms,
(central venous catheter–associated bloodstream infections,
with a minimum of 12 air exchanges per hour, is the basic
ventilator-associated pneumonias, catheter-related urinary
requirement for these patients.47
tract infections, and SSIs).
A comprehensive review of environmental infection control
Reductions in nosocomial infections have a substantial
in health care facilities is available at the CDC Web site
impact on morbidity, mortality, length of stay, and cost.92 In
(http://www.cdc.gov/ncidod/dhqp/pdf/guidelines/Enviro_
one study, for example, the extra costs associated with treat-
guide 03.pdf). This review contains recommendations for
ing bloodstream infections in an intensive care setting were
preventing nosocomial infections associated with construc-
tion, demolition, and renovation.89 estimated to be $40,000 per survivor.93 Accomplishing a
high-quality infection control program requires organization
 and the dedicated service of all health care employees.
A strategy for routine training of the health care team is
necessary at every professional level. The process may Organization of an Infection Control Program
vary from institution to institution, but some form of com-
munication should be established for the dissemination of   
information about the following:
The chair of the infection control committee should have
1. Endemic infection rates. an ongoing interest in the prevention and control of infec-
2. Endemic bacterial trends. tions. Members should represent administration, infectious
3. Updates on infection prevention measures (especially diseases, microbiology, nursing, the OR, central supply,
during and after an outbreak). medicine, surgery, pharmacy, and housekeeping. This multi-
4. Updates on preventive policies pertaining to hand hygiene, disciplinary group becomes the advocate for the entire hospi-
isolation precautions, and other areas of concern. tal. The members work with the infection control service
Although members of the infection control team are the to make decisions in the following areas: (1) assessing the
responsible resource persons in the hospital system, each effectiveness and pertinence of infection control policies
member of the health care team also has a responsibility to and protocols in their areas and (2) raising infection
help prevent infection in hospitalized patients. control–related concerns.
        

According to existing public health acts, certain infectious Collecting surveillance data on nosocomial infections and
diseases must be reported by law. Differences exist between taking actions to decrease nosocomial infections are the prin-
the reporting systems of one country and those of another, cipal functions of the infection control service. This service
but on the whole, diseases such as tuberculosis, sexually usually consists of a trained hospital epidemiologist, infection
transmitted diseases, and meningococcal meningitis are control practitioners (ICPs), and secretarial and informatics
reported for community follow-up. support. The scope of the ICPs’ responsibilities has expanded
Open communication with community hospitals and in keeping with the increasing complexity of health care. It is
other health care facilities provides for better management currently recommended that there be 0.8 to 1.0 ICP for every
of patients with infections, allowing for notification and plan- 100 occupied acute care beds.94 Training programs to assist
ning for additional hospitalization or convalescence as the with the professional and organizational development of ICPs
patient moves to and from the community and hospital. are available through SHEA (http://www.shea-online.org),
05/08
APIC (http://www.apic.org), and CHICA-Canada (http:// nursing units. Methods for collecting, editing, storing, and
www.chica.org), and the APIC certification program sup- sharing data should be based on the CDC’s NSHN system,
ports continuous professional improvement. A viable and which promotes the use of high-quality indicators for
useful program for surveillance requires a computer future monitoring and comparison among health care
database program networked to microbiology, the OR, and institutions.28
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on the surgeon and HIV infection. 2004. 78. Boyce JM. Vancomycin-resistant enterococ-
Available at: www.facs.org/fellows_info/ cus: detection, epidemiology, and control Acknowledgment
statements/st-13.html. measures. Infect Dis Clin North Am 1997;
61. McKenna MT, Hutton MD, Cauthen G, 11:367. The author would like to thank A. Peter McLean,
et al. The association between occupation 79. Recommendations for preventing the spread MD, FACS for his contributions to a previous
and tuberculosis: a population based survey. of vancomycin resistance: recommendations iteration of this chapter on which the current
Am J Respir Crit Care Med 1996;154:587. of the Hospital Infection Control Practices version is partially based.
05/08
1 BASIC SURGICAL AND PERIOPERATIVE CONSIDERATIONS 3 PERIOPERATIVE CONSIDERATIONS FOR
ANESTHESIA — 1
3 PERIOPERATIVE CONSIDERATIONS
FOR ANESTHESIA
Steven B. Backman, MDCM, PhD, FRCPC, Richard M. Bondy, MDCM, Alain Deschamps, MD, PhD,
Anne Moore, MD, and Thomas Schricker, MD, PhD
Advancements in modern surgical care are complemented by associated with general or regional anesthesia (see below)
alterations in anesthetic management to provide maximum should be discussed in an informative and reassuring manner;
patient benefit. During the last two decades, anesthesia prac- a well-conducted preoperative anesthesia interview plays an
tice has changed enormously—with the proliferation of airway important role in alleviating anxiety.
devices; the routine employment of patient-controlled anal- The medications the patient is taking can have a substantial
gesia; the wider popularity of regional anesthesia, including impact on anesthetic management. Generally, patients should
thoracic epidural anesthesia and peripheral nerve blocks; the continue to take their regular medication up to the time
development of computer-controlled devices for infusing of the operation. It is especially important not to abruptly
short-acting drugs; the discovery and use of quickly reversible discontinue medications that may result in withdrawal or
inhalational drugs, opiates, and muscle relaxants; the avail- rebound phenomena (e.g., beta blockers, alpha antagonists,
ability of online monitoring of central nervous system (CNS) barbiturates, and opioids). With some medications (e.g., oral
function; and the increased application of transesophageal hypoglycemics, insulin, and corticosteroids), perioperative
echocardiography, to name but a few examples. Our aim dosage adjustments may be necessary [see 8:10 Endocrine
in this chapter is to offer surgeons a current perspective on Problems]. Angiotensin-converting enzyme inhibitors have
perioperative considerations for anesthesia to facilitate dia- been associated with intraoperative hypotension and may
logue between the surgeon and the anesthesiologist and be withheld at the discretion of the anesthesiologist.3 Drugs
thereby ensure optimum care for our patients. The primary that should be discontinued preoperatively include mono-
focus is on the adult patient: the special issues concerning amine oxidase inhibitors (MAOIs) and oral anticoagulants
pediatric anesthesia are beyond the scope of our review. In [see Table 1].
Many surgical patients are taking antiplatelet drugs.
addition, the ensuing discussion is necessarily selective; more
Careful consideration should be given to the withdrawal of
comprehensive discussions may be found elsewhere.1,2
these agents in the perioperative period [see Table 1] because
of the possibility that discontinuance may lead to an acute
Perioperative Patient Management coronary syndrome. Patients with recently placed coronary
artery drug-eluting stents (< 1 year) may be at particular risk,
Preoperative medical evaluation is an essential component
so elective surgery should be postponed.4 If surgery is neces-
of preoperative assessment for anesthesia. Of particular
sary, and patients are deemed to be at increased risk for
importance to the anesthesiologist is any history of personal
medication-related bleeding during surgery, the longer-acting
or family problems with anesthesia. Information should be
agents (e.g., aspirin, clopidogrel, and ticlopidine) can be
sought concerning difficulty with airway management or
replaced with nonsteroidal antiinflammatory drugs (NSAIDs)
intubation, drug allergy, delayed awakening, significant post-
that have shorter half-lives. Typically, these shorter-acting
operative nausea and vomiting (PONV), unexpected hospital
drugs are given for 10 days, stopped on the day of surgery,
or intensive care unit (ICU) admission, and post–dural punc- and then restarted 6 hours after operation. Platelet transfu-
ture headache (PDPH). Previous anesthetic records may be sion can be considered if there is a very high potential for
requested. significant bleeding.5
The airway must be carefully examined to identify patients The increasing use of herbal and alternative medicines has
at risk for difficult ventilation or intubation [see Special led to significant morbidity and mortality as a consequence
Scenarios, Difficult Airway, below], with particular attention of unexpected interactions with traditional drugs. Because
paid to teeth, caps, crowns, dentures, and bridges. Patients many patients fail to mention such agents as part of their
must be informed about the risk of trauma associated with medication regimen during the preoperative assessment, it is
intubation and airway management. Anesthetic options [see advisable to question all patients directly about their use.
Choice of Anesthesia, below] should be discussed, including Particular attention should be given to Chinese herbal teas,
the likelihood of postoperative ventilation and admission to which include organic compounds and toxic contaminants
the hospital or ICU. When relevant, the possibility of blood that may produce renal fibrosis or failure, cholestasis, hepati-
product administration should be raised [see 1:4 Bleeding and tis, and thrombocytopenia. Specific recommendations exist
Transfusion], and the patient’s acceptance or refusal of trans- for the discontinuance of many of these agents [see Table 1].
fusion should be carefully documented. Postoperative pain Prophylactic administration of perioperative beta blockers
management [see 1:6 Postoperative Pain] should be addressed, in patients with or at risk for atherosclerotic disease under-
particularly when a major procedure is planned. The risks going noncardiac surgery is controversial and merits specific
DOI 10.2310/7800.S01C03
11/08
ANESTHESIA — 2
Table 1 Recommendations for Preoperative Discontinuance of Drugs and Medicine68–81

Type of Agent Pharmacologic Effects Adverse Effects Discontinuance Recommendations
Drug
MAOIs Isocarboxazid Irreversible inhibition of Potentiation of sympathomimetic Elective surgery: discontinue at least
Phenelzine monoamine oxidase amines, possible hypertensive crisis 2 wk in advance; consider potential
Pargyline with the resultant May prolong and intensify effects of for suicidal tendency—mental
Tranylcypromine increase in serotonin, other CNS depressants health specialist should be involved
Selegiline norepinephrine, Severe idiopathic hyperpyrexic Emergency surgery: avoid meperidine;
epinephrine, dopamine, reaction with meperidine and consider regional anesthesia
and octamine possibly other narcotics
neurotransmitters Potential catastrophic interaction
with tricyclic antidepressants,
characterized by high fever and
excessive cerebral excitation and
hypertension
Oral Warfarin Inhibition of vitamin K– Bleeding Elective surgery: discontinue 5–7 days
anticoagu- dependent clotting in advance; replace with heparin if
lants factors II, VII, IX, X necessary
Aspirin and Inhibition of May increase intraoperative and Primary hemostasis normalizes in
NSAIDs thromboxane A2 postoperative bleeding but not 48 hr in healthy persons; platelet
Aspirin 80% of platelets must be transfusion requirement activity fully recovered in 8–10 days
Fenoprofen inhibited for therapeutic Perioperative hemorrhagic complica- Patients on long-term aspirin therapy
Ibuprofen effect tions increase with increasing for coronary or cerebrovascular
Sodium Susceptibility to aspirin half-life of drug pathology should not discontinue
meclofenamate varies between patients drug in perioperative period unless
Tolmetin hemorrhagic complications of
Indomethacin procedure outweigh risk of acute
Ketoprofen thrombotic event
Diflunisal
Naproxen
Sulindac
Piroxicam
Antiplatelet Thienopyridines Inhibition of platelet Synergistic antithrombotic effect with Discontinue ticlopidine 2 wk in
agents Ticlopidine aggregation aspirin advance; discontinue clopidogrel
Clopidogrel Inhibition of platelet 7–10 days in advance
ADP–induced amplifi- Patients with coronary artery stents
cation may receive aspirin plus ticlopidine
for prolonged period after angio-
plasty; stopping therapy consider-
ably increases risk of coronary
thrombosis; elective surgery should
be delayed for 1–3 mo
Antiglycoprotein Competitive inhibition of Literature (mainly from cardiac Discontinue at least 12 hr in advance
agents GPIIb/IIIa receptors to surgery) shows increased hemor- Transfuse platelets only if needed to
Eptifibatide prevent platelet rhagic risk if surgery undertaken correct clinically significant bleeding
Tirofiban aggregation < 12 hr after discontinuance of
Abciximab Rapid onset of action abciximab
Short half-lives Individual variability in recovery time
Often combined with of platelet function
aspirin and/or heparin
Herbal Chaparral Used as an alternative Hepatotoxicity As soon as possible
medicines anticancer agent
This herbal agent should
be considered as
dangerous
Coltsfoot Used as an antitussive and Carcinogenic As soon as possible
demulcent agent
Considered dangerous
Comfrey Used as a general healing Hepatotoxicity, liver failure As soon as possible
agent
Ephedra/ma Noncatecholamine Dose-dependent increase in HR and Discontinue at least 24 hr in advance
huang sympathomimetic agent BP, with potential for serious
(Ephedra with a1, b1, and b2 cardiac and CNS complications
sinica) activity; both direct and Possible adverse drug reactions:
indirect release of MAOIs (life-threatening hyperten-
endogenous catechol- sion, hyperpyrexia, coma), oxytocin
amines (hypertension), digoxin and volatile
anesthetics (dysrhythmias),
guanethedine (hypertension,
tachycardia)
11/08
ANESTHESIA — 3
Table 1 Continued
Type of Agent Pharmacologic Effects Adverse Effects Discontinuance Recommendations
Drug
Herbal Echinacea Immunostimulatory effect Hepatotoxicity Discontinue as far in advance as
medicines (Echinacea Allergic potential possible in any patient with hepatic
purpurea) dysfunction or surgery with possible
hepatic blood flow compromise
Feverfew May increase bleeding especially in At least 7 days
patients already on anticlotting
medications
Garlic (Allium Irreversible dose- Increased bleeding may potentiate Discontinue at least 7 days in advance
sativum) dependent inhibition of other platelet inhibitors
platelet aggregation
Germander Choleretic, antiseptic Hepatotoxicity As soon as possible
properties
Used in weight control
Ginkgo (Ginkgo Inhibition of platelet- Increased bleeding Discontinue at least 36 hr in advance
biloba) activating factor May potentiate other platelet
Modulation of neurotrans- inhibitors
mitter receptor activity
Ginger (Zingiber Potent inhibitor of Increased bleeding Discontinue at least 36 hr in advance
officinale) thromboxane synthase May potentiate effects of other
anticoagulants
Ginseng (Panax Inhibition of platelet Prolonged PT and PTT Discontinue at least 7 days in advance
ginseng) aggregation, possibly Hypoglycemia
irreversibly Reduced anticoagulation effect of
Antioxidant action warfarin
Antihyperglycemic action Possible additive effect with other
“Steroid hormone”–like stimulants, with resultant
activity hypertension and tachycardia
Goldenseal May worsen swelling and/or high BP At least 7 days
Kava (Piper Dose-dependent potentia- Potentiation of sedative anesthetics,
methysticum) tion of GABA- including barbiturates and
inhibitory neurotrans- benzodiazepines
mitter with sedative, Possible potentiation of ethanol
anxiolytic, and effects
antiepileptic effects
Licorice Hypertension
(Glycyrrhiza Hypokalemia
glabra) Edema
Contraindicated in chronic liver and
renal insufficiency
Lobelia Used as an antinausea and Respiratory depression, tachycardia, As soon as possible
mild expectorant hypotension, hallucinations, coma,
Considered dangerous death
Sassafras Stimulant, antispasmodic Carcinogenic As soon as possible
Saw palmetto May interfere with other hormone At least 7 days
therapies
St. John’s wort Inhibits reuptake of Possible interaction with MAOIs Discontinue on day of surgery; abrupt
(Hypericum serotonin, norepine- Evidence for reduced activity of withdrawal in physically dependent
perforatum) phrine, and dopamine cyclosporine, warfarin, calcium patients may produce benzodiaz-
by neurons Increases channel blockers, lidocaine, epine-like withdrawal syndrome
metabolism of some midazolam, alfentanil, and NSAIDs
P-450 isoforms
Valerian Dose-dependent Possible potentiation of sedative Discontinue at least 24 hr in advance
(Valeriana modulation of GABA anesthetics, including barbiturates
officinalis) neurotransmitter and and benzodiazepines
receptor function
Vitamin E May increase bleeding, especially in
patients taking anticlotting agents
May affect thyroid function in
otherwise healthy patients
In doses greater than 400 IU per day,
further increase in BP may be seen
in already hypertensive patients
Yohimbe Aphrodisiac, sexual Hypertension, tachycardia, paralysis, As soon as possible
stimulant death
ADP = adenosine diphosphate; BP = blood pressure; CNS = central nervous system; GABA = b-aminobutyric acid; GP = glycoprotein; HR = heart rate;
MAOIs = monoamine oxidase inhibitors; NSAIDs = nonsteroidal antiinflammatory drugs; PT = prothrombin time; PTT = partial thromboplastin time.
11/08
ANESTHESIA — 4
consideration. Although a subgroup of patients may benefit Table 3 Fasting Recommendations* to Reduce Risk of
from such treatment with respect to decreased cardiac mor- Pulmonary Aspiration83
bidity, overall, an increased risk of death, stroke, and clini- Ingested Material Minimum Fasting Period† (hr)
cally significant hypotension and bradycardia has been
‡
reported.6 As such, it is anticipated that guidelines regarding Clear liquids 2
Breast milk 4
the role for beta blockers in the perioperative setting will con- Infant formula 6
tinue to evolve.7 Nonhuman milk§¤ 6
Light meal|| 8
Inpatient versus Outpatient Surgery *These recommendations apply to healthy patients undergoing elective proce-
dures; they are not intended for women in labor. Following the guidelines does
An ever-increasing number of operations are performed on not guarantee complete gastric emptying.
†
These fasting periods apply to all ages.
an ambulatory basis [see ECP:5 Patient Safety in Surgical Care: ‡
Examples of clear liquids include water, fruit juices without pulp, carbonated
A Systems Approach]. Operations considered appropriate for beverages, clear tea, and black coffee.
§
an ambulatory setting are associated with minimal physiologic Because nonhuman milk is similar to solids in gastric emptying time, the
amount ingested must be considered in determining the appropriate fasting
trespass, low anesthetic complexity, and uncomplicated period.
recovery.8,9 The design of the ambulatory facility may impose ||
A light meal typically consists of toast and clear liquids. Meals that include
limitations on the types of operations or patients that can be fried or fatty foods or meat may prolong gastric emptying time. Both
the amount and type of foods ingested must be considered in determining the
considered for ambulatory surgery. Such limitations may be appropriate fasting period.
secondary to availability of equipment, recovery room nursing
expertise and access to consultants, and availability of ICU or
hospital beds. Patients who are in class I or class II of the intraoperative and postoperative opioid requirements and
American Society of Anesthesiologists (ASA) physical status accelerate patient discharge. Use of a laryngeal mask airway
scale are ideally suited for ambulatory surgery; however, a rather than an endotracheal tube is ideal in the outpatient
subset of ASA class III patients may be at increased risk for setting because lower doses of induction agent are required
prolonged recovery and hospital admission [see Table 2]. to blunt the hypertension and tachycardia associated with its
Premedication to produce anxiolysis, sedation, analgesia, insertion; in addition, it is associated with a decreased inci-
amnesia, and reduction in PONV and aspiration may be dence of sore throat and does not require muscle paralysis for
considered for patients undergoing outpatient procedures, insertion. On the other hand, a laryngeal mask airway may
as it may for those undergoing inpatient procedures. Such not protect against aspiration.12,13
premedication should not delay discharge. Fasting guidelines The benefits of regional anesthesia [see Regional Anesthesia
[see Table 3] and intraoperative monitoring standards for Techniques, below] may include decreases in the incidence of
ambulatory surgery are identical to those for inpatient aspiration, nausea, dizziness, and disorientation. Spinal and
procedures [see Patient Monitoring, below]. epidural anesthesia may be associated with headache (dural
A number of currently used anesthetics (e.g., propofol, puncture) and backache. Compared with spinal anesthesia,
sevoflurane, desflurane), narcotics (e.g., alfentanil, fentanyl, epidural anesthesia takes more time to perform, has a slower
sufentanil, and remifentanil), and muscle relaxants (e.g., onset of action, and may not produce as profound a block;
succinylcholine, atracurium, mivacurium, and rocuronium) however, the duration of an epidural block can readily be
demonstrate rapid recovery profiles. Nitrous oxide also has extended intraoperatively or postoperatively if necessary.
desirable pharmacokinetic properties, but it may be associ- Care should be exercised in choosing a local anesthetic for
ated with increased PONV. Titration of anesthetics to indices neuraxial blockade: spinal lidocaine may be associated with
of CNS activity (e.g., the bispectral index) may result in a transient radicular irritation, and bupivacaine may be
decreased drug dosages, faster recovery from anesthesia, associated with prolonged motor block; narcotics may pro-
and fewer complications.10,11 Multimodal analgesia (involving duce pruritus, urinary retention, nausea and vomiting, and
the use of local anesthetics, ketamine, alpha2-adrenergic ago- respiratory depression. Various dosing regimens, including
nists, beta blockers, acetaminophen, or NSAIDs) may reduce minidose spinal techniques, have been proposed as means of
minimizing these side effects.14–17
Monitored anesthesia care [see Choice of Anesthesia, below]
Table 2 Association between Preexisting Medical achieves minimal CNS depression, so the airway and sponta-
Conditions and Adverse Outcomes82 neous ventilation are maintained and the patient is able
Medical Associated Adverse Outcome to respond to verbal commands. Meticulous attention to
Condition
monitoring is required to guard against airway obstruction,
Congestive heart 12% prolongation of postoperative stay arterial desaturation, and pulmonary aspiration.
failure
Hypertension Twofold increase in risk of intraoperative In the recovery room, the anesthetic plan is continued until
cardiovascular events discharge. Shorter-acting narcotics and NSAIDs are admin-
Asthma Fivefold increase in risk of postoperative istered for pain relief, and any of several agents may be given
respiratory events for control of nausea and vomiting. Criteria for discharge
Smoking Fourfold increase in risk of postoperative
respiratory events
from the recovery room have been established [see Table 4].
Obesity Fourfold increase in risk of intraoperative and Recovery of normal muscle strength and sensation (including
postoperative respiratory events proprioception of the lower extremity, autonomic function,
Reflux Eightfold increase in risk of intubation-related and ability to void) should be demonstrated after spinal or
adverse events epidural anesthesia. Delays in discharge are usually the result
11/08
ANESTHESIA — 5
Table 4 Postanesthetic Discharge Scoring System definitive surgical treatment must not be unduly delayed by
(PADSS)84 attempts to “get a line.”
Category Score* Explanation
Vital signs 2 Within 20% of preoperative value Choice of Anesthesia
1 Within 20 to 40% of preoperative
Anesthesia may be classified into three broad categories:
value
0 Within 40% of preoperative value (1) general anesthesia, (2) regional anesthesia, and (3) moni-
tored anesthesia care. General anesthesia can be defined as a
Activity, mental 2 Oriented and steady gait
state of insensibility characterized by loss of consciousness,
status 1 Oriented or steady gait
0 Neither amnesia, analgesia, and muscle relaxation. This state may be
achieved either with a single anesthetic or, in a more balanced
Pain, nausea, 2 Minimal
fashion, with a combination of several drugs that specifically
vomiting 1 Moderate
0 Severe induce hypnosis, analgesia, amnesia, and paralysis.
There is, at present, no consensus as to which general
Surgical bleeding 2 Minimal
anesthetic regimen best preserves organ function. General
1 Moderate
0 Severe anesthesia is employed when contraindications to regional
anesthesia are present or when regional anesthesia or moni-
Intake/output 2 Oral fluid intake and voiding
1 Oral fluid intake or voiding
tored anesthesia care fails to provide adequate intraoperative
0 Neither analgesia. In addition, a few situations specifically mandate
general anesthesia and controlled ventilation: the need for
*Total possible score is 10; patients scoring g9 are considered fit for discharge
home.
abdominal muscle paralysis, lung isolation, and hyperventila-
tion; the presence of serious cardiorespiratory instability; and
the lack of sufficient time to perform regional anesthesia.
Alternatives to general anesthesia should be considered for
of pain, PONV, hypotension, dizziness, unsteady gait, or lack
patients who are susceptible to malignant hyperthermia
of an escort.18
(MH), for those in whom intubation is likely to prove difficult
or the risk of aspiration is high, and for those with pulmonary
Elective versus Emergency Surgery compromise that may worsen after intubation and positive
pressure ventilation.
Surgical procedures performed on an emergency basis may
Regional anesthesia is achieved by interfering with afferent
range from relatively low priority (e.g., a previously cancelled
or efferent neural signaling at the level either of the spinal
case that was originally elective) to highly urgent (e.g., a
cord (neuraxial blockade) or of the peripheral nerves. Neur-
case of impending airway obstruction). For trauma, specific
axial anesthesia (i.e., epidural or spinal administration of
evaluation and resuscitation sequences have been established
local anesthetics) is commonly employed as the sole anes-
to facilitate patient management [see 7:1 Initial Management
thetic technique for procedures involving the lower abdomen
of Life-Threatening Trauma]. The urgency of the situation
and the lower extremities; it also provides effective pain relief
dictates how much time can be allotted to preoperative patient
after intraperitoneal and intrathoracic procedures. Combin-
assessment and optimization. When it is not possible to ing regional and general anesthesia has become increasingly
communicate with the patient, information obtained from popular.19 Currently, some physicians are using neuraxial
family members and paramedics may be crucial. Information blockade as the sole anesthetic technique for procedures such
should be sought concerning allergies, current medications, as thoracotomy and coronary artery bypass grafting, which
significant past medical illnesses, nihil per os (NPO) status, are traditionally thought to require general anesthesia and
personal or family problems with anesthesia, and recent endotracheal intubation.20
ingestion of alcohol or drugs. Any factor that may complicate Neuraxial blockade has several advantages over general
airway management should be noted (e.g., trauma to the anesthesia, including better dynamic pain control, shorter
face or the neck, a beard, a short and thick neck, obesity, or duration of paralytic ileus, reduced risk of pulmonary
a full stomach). When appropriate, blood samples should be complications, and decreased transfusion requirements; it is
obtained as soon as possible for typing and cross-matching, also associated with a decreased incidence of renal failure
as well as routine blood chemistry, complete blood count, and myocardial infarction [see 1:6 Postoperative Pain].21–24
and toxin screen. Arrangements for postoperative ICU Contrary to conventional thinking, however, the type of anes-
monitoring, if appropriate, should be instituted early. thesia used (general or neuraxial) is not an independent risk
Clear communication must be established between the factor for long-term cognitive dysfunction.25 Neuraxial block-
surgical team and anesthesia personnel so that an appropriate ade is an essential component of multimodal rehabilitation
anesthetic management plan can be formulated and any programs aimed at optimization of perioperative care and
specialized equipment required can be mobilized in the oper- acceleration of recovery [see ECP:3 Perioperative Considerations
ating room (OR). The induction of anesthesia may coincide for Anesthesia].26,27
with resuscitation. Accordingly, the surgical team must be For short, superficial procedures, a variety of peripheral
immediately available to help with difficult intravenous nerve blocks may be considered.28 With procedures on the
(IV) access, emergency tracheostomy, and cardiopulmonary upper or lower extremity, an IV regional (Bier) block with
resuscitation. Patients in shock may not tolerate standard diluted lidocaine may be useful. Anesthesia of the upper
anesthetics, which characteristically blunt sympathetic extremity and shoulder may be achieved with the brachial
outflow. The anesthetic dose must be judiciously titrated, and plexus block. Anesthesia of the lower extremity may be
11/08
ANESTHESIA — 6
achieved by blocking the femoral, obturator, and lateral fem- are advocated by some as measures of hypnosis to guide the
oral cutaneous nerves (knee surgery) or the ankle and popli- administration of anesthetics.32,33 However, their effectiveness
teal sciatic nerves (foot surgery). Anesthesia of the thorax in preventing intraoperative awareness remains controversial,
may be achieved with intercostal or intrapleural nerve blocks. particularly when anesthesia is maintained by inhalational
Anesthesia of the abdomen may be achieved with celiac drugs.34 CNS function may also be assessed by measurement
plexus and paravertebral blocks. Anesthesia of the head and of cerebral blood flow, using transcranial Doppler, jugular
neck may be achieved by blocking the trigeminal, supraor- bulb venous oxygen saturation, and cerebral oximetry
bital, supratrochlear, infraorbitral, and mental nerves and the monitoring techniques. Although there is growing clinical
cervical plexus. Local infiltration of the operative site may experience with these noninvasive intraoperative neurologic
provide intraoperative and postoperative analgesia. monitors, randomized, prospective, and adequately powered
Unlike the data on neuraxial blockade, the data on studies to support and guide their use are currently lacking.
peripheral nerve blockade neither support nor discourage its
use as a substitute for general anesthesia. Generally, however,
General Anesthesia Techniques
we favor regional techniques when appropriate: such
approaches maintain consciousness and spontaneous breath- An ever-expanding armamentarium of drugs is available
ing while causing only minimal depression of the CNS and for premedication and for induction and maintenance of
the cardiorespiratory systems, and they yield improved pain anesthesia. Selection of one agent over another is influenced
control in the immediate postoperative period. by the patient’s baseline condition, procedure, local standard
Monitored anesthesia care involves the use of IV drugs of practice, and predicted duration of hospitalization.
to reduce anxiety, provide analgesia, and alleviate the dis-
premedication
comfort of immobilization. This approach may be combined
with local infiltration analgesia provided by the surgeon.29 Preoperative medications are given primarily to decrease
Monitored anesthesia care requires monitoring of vital signs anxiety, to reduce the incidence of nausea and vomiting,
and the presence of an anesthesiologist who is prepared and to prevent aspiration. Other benefits include sedation,
to convert to general anesthesia if necessary. Its benefits amnesia, analgesia, drying of oral secretions, and blunting of
are substantially similar to those of regional anesthesia. These undesirable autonomic reflexes.
benefits are lost when attempts are made to overcome surgi-
Sedatives and Analgesics
cal pain with excessive doses of sedatives and analgesics.
Benzodiazepines produce anxiolysis, sedation, hypnosis,
amnesia, and muscle relaxation; they do not produce analge-
Patient Monitoring sia. They may be classified as short acting (midazolam), inter-
Patient monitoring is central to the practice of anesthesia. mediate acting (lorazepam), or long acting (diazepam).
A trained, experienced physician is the only truly indispens- Adverse effects [see Table 5] may be marked in debilitated
able monitor; mechanical and electronic monitors, although patients. Their central effects may be antagonized with
useful, are, at most, aids to vigilance. Wherever anesthesia is flumazenil.
administered, the proper equipment for pulse oximetry, blood Muscarinic antagonists (e.g., scopolamine and atropine)
pressure measurement, electrocardiography, and capnogra- were commonly administered at one time; this practice is not
phy should be available. At each anesthesia workstation, as popular today. They produce, to varying degrees, sedation,
equipment for measuring temperature, a peripheral nerve amnesia, lowered anesthetic requirements, diminished nausea
stimulator, a stethoscope, and appropriate lighting must and vomiting, reduced oral secretions, and decreased gastric
be immediately available. A spirometer must be available hydrogen ion secretion. They blunt the cardiac parasym-
without undue delay. pathetic reflex responses that may occur during certain
Additional monitoring may be indicated, depending on the procedures (e.g., ocular surgery, traction on the mesentery,
patient’s health, the type of procedure to be performed, and and manipulation of the carotid body). Adverse effects include
the characteristics of the practice setting. Cardiovascular
monitoring, including measurement of systemic arterial,
Table 5 Benzodiazepines: Doses and Duration of Action85
central venous, pulmonary arterial, and wedge pressures;
cardiac output; and continuous arterial and mixed venous Dose (for Elimination
Benzodiazepine Comments
Sedation) Half-Life
oximetry, is covered in detail elsewhere [see 8:3 Shock].
Additional information about the cardiovascular system may Midazolam 0.5–1.0 mg, 1.7–2.6 hr Respiratory
repeated depression,
be obtained by transesophageal echocardiography.30 Practice excessive
guidelines for this technique have been developed.31 It may sedation,
be particularly useful in patients who are undergoing valve hypotension,
repair or who have persistent severe hypotension of unknown bradycardia,
anticonvulsant
etiology. activity
The effects of anesthesia on the CNS may be assessed (withdrawal)
by monitoring electroencephalographic (EEG) activity that is Lorazepam 0.25 mg, 11–22 hr See midazolam
either spontaneous (raw or processed) or evoked (e.g., repeated Venous
somatosensory, auditory, or visual). Commercially available thrombosis
devices that employ spectral analysis of spontaneous EEG Diazepam 2.0 mg, 20–50 hr See midazolam
activity (e.g., bispectral index) are relatively easy to use and repeated and lorazepam
11/08
ANESTHESIA — 7
tachycardia, heat intolerance, inhibition of gastrointestinal pharmacologic treatment may be helpful [see Table 7]. H2
(GI) motility and micturition, and mydriasis. receptor antagonists (e.g., cimetidine, ranitidine, and famoti-
Opioids are used when analgesia, in addition to sedation dine) and proton pump inhibitors (e.g., omeprazole) reduce
and anxiolysis, is required. With morphine and meperidine, gastric acid secretion, thereby raising gastric pH without
the time of onset of action and the peak effect are unpredict- affecting gastric volume or emptying time. Nonparticulate
able. Synthetic opioids (e.g., fentanyl) have a more rapid antacids (e.g., sodium citrate) neutralize the acidity of gastric
onset and a predictable time course, which make them contents. Metoclopramide promotes gastric emptying (by
more suitable for premedication immediately before surgery. stimulating propulsive GI motility) and decreases reflux (by
Adverse effects [see Table 6] can be reversed with full increasing the tone of the esophagogastric sphincter); it may
(naloxone) or partial (nalbuphine) antagonists. also possess antiemetic properties.
The alpha2-adrenergic agonists clonidine and dexmedeto- In all patients at risk for aspiration who require general
midine are sympatholytic drugs that also exert sedative, anesthesia, a rapid sequence induction is traditionally consid-
anxiolytic, and analgesic effects. They reduce intraoperative ered a standard of practice, although this has been recently
anesthetic requirements, thus allowing faster recovery, and questioned.37 A rapid sequence induction is achieved through
attenuate sympathetic activation secondary to intubation adequate preoxygenation, administration of drugs to produce
and surgery, thus improving intraoperative hemodynamic rapid loss of consciousness and paralysis, and exertion of
stability. Major drawbacks are hypotension and bradycardia; pressure on the cricoid cartilage (the Sellick maneuver) as
rebound hypertensive crises may be precipitated by their loss of consciousness occurs to occlude the esophagus and so
discontinuance.35,36 limit reflux of gastric contents into the pharynx. An alterna-
tive is the so-called modified rapid sequence induction, which
Prevention of Aspiration permits gentle mask ventilation during the application of
Aspiration of gastric contents is an extremely serious cricoid pressure (thereby potentially reducing or abolishing
complication that is associated with significant morbidity insufflation of gas into the stomach). The advantages of the
and mortality. Fasting helps reduce the risk of this complica- modified approach are that there is less risk of hypoxia and
tion [see Table 3]. When the likelihood of aspiration is high, more time to treat cardiovascular responses to induction
Table 6 Opioids: Doses and Duration of Action86

Agent Relative Dose Time to Duration of Comments
Induction Analgesic Peak Action
Potency Induction or Maintenance Effect
Maintenance Loading
Morphine 1 1 mg/kg 0.05–0.2 mg/kg/hr 5–20 min 2–7 hr Respiratory depression, nausea,
For perioperative vomiting, pruritus, constipa-
analgesia: tion, urinary retention, biliary
0.1 mg/kg IV, spasm, neuroexcitation
IM Pseizure, tolerance
Cough suppression, relief of
dyspnea-induced anxiety
(common to all opioids)
Histamine release, orthostatic
hypotension, prolonged
emergence
Meperidine 0.1 For perioperative NA 2 hr (oral); 2–4 hr See morphine
analgesia: 1 hr Orthostatic hypotension,
0.5–1.5 mg/kg (SC, myocardial depression, dry
IV, IM, SC IM) mouth, mild tachycardia,
mydriasis, histamine release
Attenuates shivering; to be
avoided with MAOIs
Local anesthetic–like effect
Remifentanil 250–300 1 µg/kg 0.25–0.4 µg/kg/min 3–5 min 5–10 min See morphine
Awareness, bradycardia, muscle
rigidity
Ideal for infusion; fast recovery,
no postoperative analgesia
Alfentanil 7.5–25 50–300 µg/kg 1.25–8.0 µg/kg/min 1–2 min 10–15 min See morphine
Awareness, bradycardia, muscle
rigidity
Fentanyl 75–125 5–30 µg/kg 0.25–0.5 µg/kg/min 5–15 min 30–60 min See morphine and alfentanil
Sufentanil 525–625 2–20 µg/kg 0.05–0.1 µg/kg/min 3–5 min 20–45 min See morphine and alfentanil
Ideal for prolonged infusion
IM = intramuscular; IV = intravenous; MAOI = monoamine oxidase inhibitor; NA = not applicable; SC = subcutaneous.
11/08
ANESTHESIA — 8
Table 7 Pharmacologic Prevention of Aspiration87,88

Agent Dose Timing of Administration Comments
before Operation
H2 receptor antagonists 1–3 hr Hypotension, bradycardia, heart block, increased airway
Cimetidine 300 mg, PO resistance, CNS dysfunction, reduced hepatic metabolism
Ranitidine 50 mg IV of certain drugs
Famotidine 20 mg IV Bradycardia
Rare CNS dysfunction
Sodium citrate 30 mL PO 20–30 min Increased gastric fluid volume
Omeprazole 40 mg IV 40 min Possible alteration of GI drug absorption, hepatic metabolism
Metoclopramide 10 mg IV 15–30 min Extrapyramidal reactions, agitation, restlessness (large doses);
to be avoided with MAOIs, pheochromocytoma, bowel
obstruction
CNS = central nervous system; GI = gastrointestinal; IV = intravenous; MAOI = monoamine oxidase inhibitor; PO = oral.
agents before intubation. Regardless of which technique is hyperreactive airway disease). Inhalation induction is also
used, consideration should be given to emptying the stomach popular for ambulatory surgery when paralysis is not required.
via an orogastric or nasogastric tube before induction. Sevoflurane is well suited for this application because it is not
irritating on inhalation, as are most other volatile agents, and
induction it produces rapid loss of consciousness. Sevoflurane has
Induction of general anesthesia is achieved by administer- mostly replaced halothane as the agent of choice for inhala-
ing drugs to produce unconsciousness. It is one of the most tion induction because it is less likely to cause dysrhythmias
crucial and potentially dangerous moments for the patient and is not hepatotoxic.
during general anesthesia because of the precipitous depres-
sion of the cardiorespiratory systems and airway protective maintenance
mechanisms. Various agents can be used for this purpose; the Balanced general anesthesia is produced with a variety of
choice depends on the patient’s baseline medical condition drugs to maintain unconsciousness, prevent recall, and pro-
and fasting status, the state of the airway, the surgical proce- vide analgesia. Various combinations of volatile and IV agents
dure, and the expected length of the hospital stay. The agents may be employed to achieve these goals. The volatile agents
most commonly employed for induction are propofol, sodium isoflurane, desflurane, and sevoflurane are commonly used
thiopental, ketamine, and etomidate [see Table 8]. The opi- for maintenance [see Table 9]. Nitrous oxide is a strong anal-
oids alfentanil, fentanyl, sufentanil, and remifentanil may also gesic and a weak anesthetic agent that possesses favorable
be used for this purpose; they are associated with a very stable pharmacokinetic properties (fast onset, fast offset). Because
hemodynamic profile during induction and surgery but only of its relatively high blood:gas partition coefficient compared
invariably produce unconsciousness [see Table 6]. with nitrogen, nitrous oxide rapidly difuses into and expands
Volatile agents [see Table 9] may be employed for induction air-filled cavities. Thus, it should be avoided in situations in
of general anesthesia when maintenance of spontaneous ven- which expansion of such cavities is undesirable (e.g., pneu-
tilation is of paramount importance (e.g., with a difficult mothorax, air embolism, bowel obstruction, and middle ear
airway) or when bronchodilation is required (e.g., with severe surgery). It cannot be used as the sole anesthetic agent unless
Table 8 Induction Agents: Doses and Duration of Action85

Agent Induction Time to Duration Comments
Dose Peak of Action
(mg/kg) Effect (s) (min)
Propofol 1.0–2.5 90–100 5–10 Hypotension, apnea, antiemetic (low dose), sexual fantasies and hallucinations,
convulsions Pseizures (rare), pain on injection, thrombophlebitis
Thiopental 2.5–4.5 60 5–8 Hypotension, apnea, emergence delirium, prolonged somnolence,
anaphylactoid reaction, injection pain, hyperalgesia
Anticonvulsant effect
Contraindicated with porphyria
Ketamine 0.5–2 30 10–15 Analgesia; increased BP, HR, CO; lacrimation and salivation; bronchial
dilatation; elevated ICP
Dreaming, illusions, excitement
Preservation of respiration (apnea possible with high doses)
Etomidate 0.2–0.6 60 4–10 Minor effects on BP, HR, CO
Adrenocortical suppression, injection pain and thrombophlebitis, myoclonus,
nausea and vomiting
BP = blood pressure; CO = cardiac output; HR = heart rate; ICP = intracranial pressure.
11/08
ANESTHESIA — 9
Table 9 Volatile Drugs89,90 hydrolysis of remifentanil, its administration may be labor

†
intensive, necessitating frequent administration of boluses
Agent Oil/Gas MAC Blood/Gas Rank
Coefficient* (atm) Coefficient‡ Order
and constant vigilance. Its short half-life also limits its useful-
(FA/FI)§ ness as an analgesic in the postoperative period and may even
contribute to acute opioid intolerance. To help circumvent
Halothane 224 0.0074 2.5 6
these problems, various dosing regimens have been proposed
Enflurane 96.5 0.0168 1.8 5 in which the patient is switched from remifentanil to a
Isoflurane 90.8 0.0115 1.4 4 longer-acting narcotic.
Desflurane 18.7 0.060 0.45 2 neuromuscular blockade
Sevoflurane 47.2 0.0236 0.65 3 The reversible paralysis produced by neuromuscular block-
Nitrous 1.4 1.04 0.47 1 ade improves conditions for endotracheal intubation and
oxide facilitates surgery. Neuromuscular blocking agents are classi-
FA/FI = alveolar concentration of gas/inspired concentration; MAC = mini- fied as either depolarizing (succinylcholine) or nondepolariz-
mum alveolar concentration to abolish purposeful movement in response to ing (pancuronium, rocuronium, vecuronium, atracurium,
noxious stimulation in 50% of patients.
*Lipid solubility correlates closely with anesthetic potency (Meyer-Overton
cisatracurium, and mivacurium) and may be further differen-
rule). tiated on the basis of chemical structure and duration of
†
Correlates closely with lipid solubility. action [see Table 10]. The blocking effect of nondepolarizing
‡
Relative affinity of an anesthetic for blood compared to gas at equilibrium.
The larger the coefficient, the greater the affinity of the drug for blood and muscle relaxants is enhanced by volatile drugs, hypothermia,
hence the greater the quantity of drug contained in the blood. acidosis, certain antibiotics, magnesium sulfate, and local
§
Rise in alveolar anesthetic concentration toward the inspired concentration is anesthetics and is reduced by phenytoin and carbamazepine.
most rapid with the least soluble drugs and slowest with the most soluble.
Patients with weakness secondary to neuromuscular disorders
(e.g., myasthenia gravis and Eaton-Lambert syndrome) may
it is administered in a hyperbaric chamber; it is usually be particularly sensitive to nondepolarizing muscle relax-
administered with at least 30% oxygen to prevent hypoxia. ants.
Nitrous oxide is commonly used in combination with other
volatile agents. Potent volatile agents can trigger malignant emergence
hyperthermia in susceptible patients. General anesthesia is terminated by cessation of drug
The IV drugs currently used to maintain general anesthesia, administration, reversal of muscle paralysis, and extubation
whether partially or entirely, feature a short, context- (or removal of an upper airway device). During this poten-
sensitive elimination half-life; thus, pharmacologically signifi- tially dangerous period, close scrutiny of the patient is essen-
cant drug accumulation during prolonged infusion is avoided. tial, and all OR personnel must coordinate their efforts to
Such agents (including propofol, midazolam, sufentanil, help ensure a smooth and safe emergence from general anes-
and remifentanil) are typically administered via computer- thesia. In this phase, patients may demonstrate hemodynamic
controlled infusion pumps that use population-based instability, retching and vomiting, respiratory compromise
pharmacokinetic data to establish stable plasma (and CNS (including laryngospasm), and, occasionally, uncooperative
effector site) concentrations. Because of the extremely rapid or aggressive behavior.38
Table 10 Neuromuscular Blocking Agents: Doses and Duration of Action91
Agent Dose Duration of Metabolism Elimination Comments

(mg/kg) Action (min)
Succinylcholine 0.7–2.5 5–10 Plasma cholinesterase Renal < 2%, Fasciculations, elevation of serum potassium,
chloride hepatic 0% increased ICP, bradycardia, MH trigger;
prolonged effect in presence of atypical
pseudocholinesterase
Pancuronium 0.04–0.1 60–120 Hepatic 10–20% Renal 85%, Muscarinic antagonist (vagolytic), prolonged
hepatic 15% paralysis (long-term use)
Rocuronium 0.6–1.2 35–75 None Renal < 10%, Minimal histamine release
hepatic > 70%
Vecuronium 0.08–0.1 45–90 Hepatic 30–40% Renal 40%, Prolonged paralysis (long-term use)
hepatic 60%
Atracurium 0.3–0.5 30–45 Hoffman elimination, Renal 10–40%, Histamine release; laudanosine metabolite (a
nonspecific ester hepatic 0% CNS stimulant)
hydrolysis
Cisatracurium 0.15–0.2 40–75 Hoffman elimination Renal 16%, Negligible histamine release; laudanosine
hepatic 0% metabolite
Mivacurium 0.15–0.2 15–20 Plasma cholinesterase Renal < 5%, Histamine release; prolonged effect in presence
hepatic 0% of atypical pseudocholinesterase
CNS = central nervous system; ICP = intracranial pressure; MH = malignant hyperthermia.
11/08
ANESTHESIA — 10
Reversal of neuromuscular blockade is achieved by admin- the headrest used in the prone position.41 The relationship
istering anticholinesterases such as neostigmine or edropho- between postoperative cognitive dysfunction (POCD) and
nium. These drugs should be given in conjunction with a anesthesia per se remains unclear and may occur in patients
muscarinic antagonist (atropine or glycopyrrolate) to block who receive general (intravenous or inhalational) or regional
their unwanted parasympathomimetic side effects. Neostig- anesthesia. POCD does not seem to be associated with intra-
mine is more potent than edrophonium in reversing profound operative hypoxemia, hypotension, or acid-base disturbances.
neuromuscular blockade. It is imperative that paralysis be Certain procedures, such as cardiac and orthopedic surgery,
sufficiently reversed before extubation to ensure that sponta- have been associated with this disorder, and a common
neous respiration is adequate and that the airway can be etiology (air, particulate, or fat microemboli) is implicated.
protected. Reversal can be clinically verified by confirming There is a growing appreciation that even with other types of
the patient’s ability to lift the head for 5 seconds. Reversal can surgery, POCD can occur, with elderly patients (more than
also be assessed by muscle contraction response to electrical 60 years) being at particular risk during the first week after
nerve stimulation. the procedure. Presently, there is little evidence that POCD
Causes of failure to emerge from anesthesia include persists longer than 6 months.42
residual neuromuscular blockade, a benzodiazepine or opioid
overdose, the central anticholinergic syndrome, an intraop-
Regional Anesthesia Techniques
erative cerebrovascular accident, preexisting pathophysiologic
conditions (e.g., CNS disorders, hepatic insufficiency, and Neuraxial (central) anesthesia techniques involve continu-
drug or alcohol ingestion), electrolyte abnormalities, acidosis, ous or intermittent injection of drugs into the epidural or
hypercarbia, hypoxia, hypothermia, and hypothyroidism. intrathecal space to produce sensory analgesia, motor block-
As noted, the effects of narcotics and benzodiazepines can ade, and inhibition of sympathetic outflow. Peripheral nerve
be reversed with naloxone and flumazenil, respectively. blockade involves inhibition of conduction in fibers of a single
Physostigmine may be given to reverse the reduction in peripheral nerve or plexus (cervical, brachial, or lumbar) in
consciousness level produced by general anesthetics. Electro- the periphery. Intravenous regional anesthesia involves IV
lyte, glucose, blood urea nitrogen, and creatinine levels should administration of a local anesthetic into a tourniquet-occluded
be measured; liver and thyroid function tests should be extremity. Perioperative pain control may be facilitated
performed; and arterial blood gas values should be obtained. by administering local anesthetics, either infiltrated into the
Patients should be normothermic. Unexplained failure wound or sprayed into the wound cavity. Procedures per-
to emerge from general anesthesia warrants immediate formed solely under infiltration may be associated with patient
consultation with a neurologist. dissatisfaction caused by intraoperative anxiety and pain.43,44
contraindications
Risk and General Anesthesia Strong contraindications to regional (particularly neurax-
Determining the risk(s) attributed solely to anesthesia is ial) anesthesia include patient refusal or inability to cooperate
difficult because of the confounding variables of patient during the procedure, elevated intracranial pressure, antico-
characteristics, concurrent medications, and the surgical agulation, vascular malformation or infection at the needle
procedure itself, including context (e.g., elective versus emer- insertion site, severe hemodynamic instability, and sepsis.
gency). Prospective, unbiased studies sufficiently powered to Preexisting neurologic disease is a relative contraindication.
reveal the frequency of rare events are lacking, and reliance
on self-reporting of negative outcomes likely results in an anticoagulation and bleeding risk
underestimation of risk. Given these limitations, attempts Although hemorrhagic complications can occur after any
have been made to define the risks associated with anesthesia, regional technique, bleeding associated with neuraxial block-
based on extensive and critical literature reviews [see ade is the most serious possibility because of its devastating
Table 11].39 Perioperative mortality associated with consequences. Spinal hematoma may occur as a result of
anesthesia increases with age, ASA status, and emergency vascular trauma from placement of a needle or catheter into
procedures. Factors contributing to anesthesia-related the subarachnoid or epidural space. Spinal hematoma may
mortality include inadequate assessment, preparation and also occur spontaneously, even in the absence of antiplatelet
resuscitation, inappropriate anesthetic technique, inadequate or anticoagulant therapy. The actual incidence of spinal cord
perioperative monitoring, lack of supervision, and poor postinjury resulting from hemorrhagic complications is unknown;
operative care. Morbidity ranges from major permanent the reported incidence is estimated to be less than 1 in
disability to relatively minor events without long-term conse- 150,000 for epidural anesthesia and 1 in 200,000 for spinal
quence. Peripheral nerve injury, although rare, may have seri- anesthesia [see Table 12].45 With such low incidences, it is
ous disability. The etiology includes direct injury from nee- difficult to determine whether any increased risk can be
dles, instruments, suturing, injection of toxic substances, and attributed to anticoagulant use [see Table 13] without data
thermal insults. Less obvious but more frequent events involve from millions of patients, which are not currently available.
mechanical factors such as nerve compression or stretch. Much of our clinical practice is based on small surveys and
Ischemia associated with a low cardiac output state is often expert opinion.
implicated.40 Great caution must be used during patient posi-
tioning, with careful attention to proper padding. Loss of Antiplatelet Agents
vision is a rare but catastrophic event that may be associated There is no universally accepted test that can guide
with compression of the eye by a facemask or by padding of antiplatelet therapy. Antiplatelet agents can be divided into
11/08
ANESTHESIA — 11
Table 11 Predicted Incidence of Complications of Anesthesia39

Mortality and Morbidity Approximate Incidence Rate per 10,000 Remarks
Population
Total perioperative deaths 1:200 (elective surgery) 50
(within 30 days) 1:40 (emergency surgery) 250
x2 (60–79 yr)
x5 (80–89 yr)
x7 (> 90 yr)
Death related to anesthesia 1:50,000 (anesthesia related) 0.2
1:100,000 (ASA physical status I and II) 0.1
Cardiac arrest 1:10,000–1:20,000 (general anesthesia) 0.5–1.0 Mortality ≈ 1:15,000–1:150,000
1:3,000 (local anesthesia) 3
1:1,500 (spinal: 25% fatal) 7
Myocardial reinfarction 1:20 (0–3 mo after myocardial infarction 500
1:40 (4–6 mo after myocardial
infarction) 250
Respiratory complications
Aspiration during general 1:3,000 3 x4 in emergencies
anesthesia 1:60,000 (death) 0.16 x3 in obstetrics
Difficult intubation 1:50 200
Failure to intubate 1:500 20 Obstetrics ≈ 1:250
Failure to intubate and 1:5,000 2
ventilate
Postoperative cognitive 1:4 at 1 wk 2,500 Regional anesthesia
dysfunction 1:10 at 3 mo 1,000 General anesthesia
(> 60 yr) 1:100 permanent 100
Postoperative delirium 1:7 (general surgery) 1,400 x3 >75 yr
Up to 1:2 for elderly fractures of neck 5,000 x3 if requiring intensive care
or femur
Drowsiness 1:2 5,000 Day surgery
Dizziness 1:5 2,000 Day surgery
Headache 1:5 2,000
Cerebrovascular accident 1:50 if previous stroke 200 46% mortality
(CVA) 1:100 general surgery 100 60% mortality if previous CVA
(≈ 1:700 in the nonsurgical
population)
Carotid endarterectomy (CVA 1:15 if symptomatic 700
+ death) 1:25 if asymptomatic 400
Disabling CVA + death
Awareness
With pain 1:3,000 3 2/3 with neuromuscular blockade
Without pain 1:300 30 1/3 without neuromuscular blockade
Total intravenous 1:500 20
anesthesia 1:10,000 1
Anaphylaxis 1:10,000 1
Deafness
“Idiopathic” (general 1:10,000 1 ≈ 1:1,000 cardiac surgery
anesthesia)
Transient after spinal 1:7 1,500
anesthesia
Loss of vision 1:125,000 0.08
1:100 (cardiac surgery) 100
Pain ~1:3 (moderate) 3,000
After major surgery 1:10 (severe) 1,000
Day surgery 1:2 5,000
Postoperative nausea and 1:4 2,500 2/3 nausea and 1/3 vomiting
vomiting Female:male 3:1
11/08
ANESTHESIA — 12
Table 11 Continued
Mortality and Morbidity Approximate Incidence Rate per 10,000 Remarks
Population
Sore throat 1:2 (if tracheal tube) 5,000
1:5 (if laryngeal mask) 2,000
1:10 (if facemask only) 1,000
Dental damage
Requiring intervention 1:5,000 2
All dental damage 1:100 100
All oral trauma after tracheal 1:20 500
intubation
Peripheral nerve injury 1:300 ulnar neuropathy 30
General anesthesia 1:1,000 (other nerves) 10
Thrombophlebitis 1–2:20 (water-soluble drugs) 500–1,000
1:4 (propylene glycol based) 2,500
Arterial cannulation <1:100 (permanent) < 100
complication
Pulmonary artery perforation 1:2,000 5
Arterial puncture (during central venous cannulation)
Internal jugular vein 1:35 350
cannulation
Subclavian vein cannulation 1:200 50
four major classes: (1) aspirin and related cyclooxygenase during a 5-year period. LMWH should be stopped at least 24
inhibitors (NSAIDs); (2) ticlopidine and selective adenosine hours before regional blockade, and the first postoperative
diphosphate antagonists; (3) direct thrombin inhibitors (e.g., dose should be given no sooner than 24 hours afterward.47
hirudin); and (4) glycoprotein IIb/IIIa inhibitors. Only with
aspirin is there sufficient experience to suggest that it does complications
not increase the risk of spinal hematoma when given at clini- Drug Toxicity
cal dosages.46 Caution should, however, be exercised when
Systemic toxic reactions to local anesthetics primarily
aspirin is used in conjunction with other anticoagulants.47
involve the CNS and the cardiovascular system [see Table 14].
Oral Anticoagulants The initial symptoms are light-headedness and dizziness,
followed by visual and auditory disturbances. Convulsions
Therapeutic anticoagulation with warfarin is a contraindi-
and respiratory arrest may ensue and necessitate treatment
cation to regional anesthesia.48 If regional anesthesia is
and resuscitation.
planned, oral warfarin can be replaced with IV heparin (see
The use of neuraxial analgesic adjuncts (e.g., opioids,
below).
clonidine, epinephrine, and neostigmine) decreases the dose
Heparin of local anesthetic required, speeds recovery, and improves
the quality of analgesia. The side effects of such adjuncts
There does not seem to be an increased risk of spinal bleed-
include respiratory depression (opiods), urinary retention
ing in patients receiving subcutaneous low-dose (5,000 U)
(opiods), tachycardia (epinephrine), hypotension (clonidine),
unfractionated heparin [see 6:6 Venous Thromboembolism] if
and nausea and vomiting (neostigmine, opioids).
the interval between administration of the drug and initiation
of the procedure is greater than 4 hours.49 Higher doses, Neurologic Complications
however, are associated with increased risk. If neuraxial The incidence of neurologic complications ranges from 2
anesthesia or epidural catheter removal is planned, heparin in 10,000 to 12 in 10,000 with epidural anesthesia and from
infusion must be discontinued for at least 6 hours, and 0.3 in 10,000 to 70 in 10,000 with spinal anesthesia.49,50 The
the partial thromboplastin time should be measured. Recom- most common serious complication is neuropathy, followed
mendations for standard heparin cannot be extrapolated to by cranial nerve palsy, epidural abscess, epidural hematoma,
low-molecular-weight heparin (LMWH), because the bio- anterior spinal artery syndrome, and cranial subdural hema-
logic actions of LMWH are different and the effects cannot toma [see Table 12]. Vigilance and routine neurologic testing
be monitored by conventional coagulation measurements. of sensory and motor function are of paramount importance
After the release of LMWH for general use in the United for early detection and treatment of these potentially disas-
States in 1993, more than 40 spinal hematomas were reported trous complications.
11/08
ANESTHESIA — 13
Table 12 Predicted Incidence of Complications of Regional Anesthesia39

Complication Incidence Rate per 10,000 Remarks
Population
Paraplegia ≈ 1:100,000 0.1
Permanent nerve injury
Spinal 1–3:10,000 1–3
Epidural 0.3–10:10,000 0.03–10
Peripheral nerve block ≈ 1:5,000 2 2% brachial plexus neuropraxia lasting
> 3 mo
Epidural hematoma ≈ 1:150,000 (epidural) 0.07 ≈ 1:1,000,000 (spontaneous)
≈ 1:14,000 (USA)
≈ 1:200,000 (spinal) 0.05 ≈ 1:2,250,000 (Europe)
≈ 1:10,000 (spontaneous)
Epidural abscess 1:2,000–1:7,500 0.7–5.0
Transient neural complications 1:1,000–1:10,000 (epidural) 1–10 (epidural)
1:125–1:2,500 (spinal) 4-80 (spinal)
Transient radicular irritation Up to 1:3 (heavy lidocaine and 3,000
(spinal) mepivacaine)
Cardiac arrest ≈ 1:1,500 (spinal) 5 (spinal)
≈ 1:3,000 (local anesthesia) 3 (local anesthesia)
≈ 1:10,000 (epidural) 1 (epidural)
≈ 1:10,000 (regional blocks) 1 (regional)
Post–dural puncture headache ≈ 1:100 100 80% following inadvertent dural tap
≈ 1:10 (day surgery) 1,000 Blood patch 70–100%
Immediate success, but headaches
recur in 30–50%
Backache < 1 hr surgery ≈ 20% 2,000 GA = LA
> 4 hr surgery ≈ 50% 5,000
Urinary dysfunction ≈ 1:50 200
Pneumothorax ≈ 1:20 (supraclavicular blocks) 500
Systemic LA toxicity ≈ 1:10,000 (epidural) 1
≈ 1:1,500 (regional blocks) 7
Cerebral seizures ≈ 1:4,000 (intravenous regional 2.5 Axillary ≈ 1:1,000
anesthesia)
≈ 1:500 (brachial plexus) 20 Supraclavicular ≈ 1:125
Eye blocks
Retrobulbar hemorrhage 1:250–1:20,000 0.5–40
Brainstem anesthesia ≈ 1:700 15
Globe perforation ≈ 1:10,000 1
Ptosis—transient after eye ≈ 1:2 at 24 hr 5,000
block
≈ 1:5 at 1 mo 2,000
Diplopia—transient after eye 8–70% 800–7,000
block
GA = general anesthesia; LA = local anesthesia.
Transient Neurologic Symptoms described after intrathecal use of all local anesthetics but
The term transient neurologic symptoms (TNSs) refers to are most commonly noted after administration of lidocaine,
backache with pain radiating into the buttocks or the lower in the ambulatory surgical setting, and with the patient in
extremities after spinal anesthesia. It occurs in 4 to 33% of the lithotomy position during operation. Discomfort from
patients, typically 12 to 36 hours after the resolution of spinal TNSs is self-limited and can be effectively treated with
anesthesia, and lasts for 2 to 3 days.51 TNSs have been NSAIDs.
11/08
ANESTHESIA — 14
Table 13 Pharmacology of Anticoagulant Agents anesthesia. Patients requiring hemodynamic or respiratory

support may be admitted to the PACU if rapid improvement
Drug Coagulation Time to Time to
Tests Peak Effect Normal
is expected and appropriate monitoring and personnel are
Hemostasis available. Hemodynamic instability, the need for prolonged
INR PTT after Discon- respiratory support, and poor baseline condition mandate
tinuance admission to the ICU. Common complications encountered
Heparin in the PACU include postoperative pulmonary insufficiency,
cardiovascular instability, acute pain, and nausea and
IV < (( min 4–6 hr
vomiting [see Table 15]. These complications are discussed in
SC < ( 1 hr 4–6 hr greater detail elsewhere [see 8:5 Pulmonary Insufficiency, 8:2
LMWH < < 2–4 hr 12 hr Acute Cardiac Dysrhythmia, 1:6 Postoperative Pain, and ECP:5
Warfarin (( < 2–6 days 4–6 days Patient Safety in Surgical Care: A Systems Approach].
Aspirin < < hr 5–8 days

Special Scenarios
Thrombolytic < (( min 1–2 days
agents (t-PA, difficult airway
streptokinase)
Airway management is a pivotal component of patient care
((= clinically significant increase; ( = possibly clinically significant increase; <
= clinically insignificant increase or no effect; INR = international normalized
because failure to maintain airway patency and ventilation
ratio; LMWH = low-molecular-weight heparin; PTT = partial thromboplastin can lead to permanent disability, brain injury, or death. The
time; t-PA = tissue plasminogen activator. difficult airway should be managed in accordance with
contemporary airway guidelines, such as the protocols estab-
lished by the ASA, to reduce the risk of adverse outcomes
Post–Dural Puncture Headache during attempts at ventilation and intubation. (The ASA
Use of small-gauge pencil-point needles for spinal anesthe- protocols may be accessed on the organization’s Web site:
sia is associated with a 1% incidence of PDPH. The inci- http://www.asahq.org/Newsletters/2005/11-05/2003Trauma
dence of PDPH after epidural analgesia varies substantially Algorithm.html). The emphasis on preserving spontaneous
because the risk of inadvertent dural puncture with a Tuohy ventilation and the focus on awake intubation options
needle is directly dependent on the anesthesiologist’s train- are central themes whose importance cannot be
ing. PDPH is characteristically aggravated by upright posture overemphasized.
and may be associated with photophobia, neck stiffness, It is crucial that all patients who are undergoing difficult or
nausea, diplopia, and tinnitus. Meningitis should be consid- prolonged airway instrumentation be appropriately treated
ered in the differential diagnosis. Although PDPH is not with topical anesthesia, sedation, and monitoring so as
life-threatening, it carries substantial morbidity in the form of to ensure adequate ventilation and to attenuate, detect,
restricted activity. Medical treatment with bed rest, IV fluids, and treat harmful neuroendocrine responses that can cause
NSAIDs, and caffeine is only moderately effective. An epidu-
ral blood patch is the treatment of choice: the success rate is
approximately 70%. Table 15 Pharmacologic Treatment of Postoperative
Nausea and Vomiting8
Agent Dose Comments
Recovery
Propofol 10 mg IV, [See Table 8]
Admission to the postanesthetic care unit (PACU) is repeated dose
appropriate for patients whose vital signs are stable and
whose pain is adequately controlled after emergence from Ondansetron 4.0–8.0 mg IV Highly effective, costly;
headache, constipation,
transiently increased
LFTs
Table 14 Local Anesthetics for Infiltration Anesthesia: Dexamethasone 4.0–8.0 mg IV Adrenocortical suppression,
Maximum Doses* and Duration of Action delayed wound healing,
With Epinephrine fluid retention, electro-
Without Epinephrine lyte disturbances,
(1:200,000)
psychosis, osteoporosis
Drug Duration Duration
Maximum Maximum Droperidol 0.5–1.0 mg IV Sedation, restlessness,
of Action of Action
Dose (mg) Dose (mg) dysphoria, dysrhythmia
(min) (min)
(?)
Chloroprocaine 800 15–30 1,000 3–90
Lidocaine 300 30–60 500 120–360 Metoclopramide 10–20 mg IV Avoid in bowel obstruction,
Mepivacaine 300 45–90 500 120–360 extrapyramidal reactions
Prilocaine 500 30–90 600 120–360
Bupivacaine 175 120–240 225 180–420 Scopolamine 0.1–0.6 mg SC, Muscarinic side effects,
Etidocaine 300 120–180 400 180–420 IM, IV somnolence
Dimenhydrinate 25–50 mg IV Drowsiness, dizziness
*Recommended maximum dose can be given to healthy, middle-aged, normal-
sized adults without toxicity. Subsequent doses should not be given for at least IM = intramuscular; IV = intravenous; LFT = liver function test; SC =
4 hours. Doses should be reduced during pregnancy. subcutaneous.
11/08
ANESTHESIA — 15
myocardial ischemia, bronchospasm, and intracranial hyper- and resuscitation is extremely difficult. Cardiorespiratory
tension. Extubation is stressful as well and may be associated compromise may be attenuated by effective postoperative
with intense mucosal stimulation and exaggerated glottic pain control that permits early ambulation and effective
closure reflexes, resulting in laryngospasm and, possibly, ventilation. Surgical site infection and dehiscence may result
pulmonary edema secondary to vigorous inspiratory efforts in difficult reoperation and prolonged hospitalization.
against an obstructed airway. Laryngeal incompetence and
aspiration can also occur after extubation. Removal of an malignant hyperthermia
endotracheal tube from a known or suspected difficult airway MH is a rare but potentially fatal genetic condition charac-
should ideally be performed over a tube exchanger so as to terized by life-threatening hypermetabolic reactions in
facilitate emergency reintubation. susceptible individuals after the administration of volatile
Alternatives to standard oral airways, masks, introducers, anesthetics or depolarizing muscle relaxants.55 Abnormal
exchangers, laryngoscopes, and endotracheal tubes now exist function of the sarcoplasmic reticulum calcium release
that offer more options, greater safety, and better outcomes. channel in skeletal muscle has been identified as a possible
It would be naive to believe that any single practitioner could underlying cause.
master every new airway protocol and device. To keep up In making the diagnosis of MH, it is important to consider
with technical and procedural advances, university hospital other possible causes of postoperative temperature elevation.
program directors should consider incorporating technical Such causes include inadequate anesthesia, equipment prob-
skill laboratories and simulator training sessions into their lems (e.g., misuse or malfunction of heating devices, ventila-
curricula. tors, or breathing circuits), local or systemic inflammatory
responses (either related or unrelated to infection), transfu-
morbid obesity sion reaction, hypermetabolic endocrinopathy (e.g., thyroid
Morbid obesity represents the extreme end of the over- storm or pheochromocytoma), neurologic catastrophe (e.g.,
weight spectrum and is usually defined as a body mass index intracranial hemorrhage), and reaction to or abuse of a
higher than 40 kg/m2 [see 5:7 Surgical Treatment of Morbid drug.
Obesity].52 It poses a formidable challenge to health care Immediate recognition and treatment of a fulminant MH
providers in the OR, the postoperative recovery unit, and the episode are essential for preventing morbidity and mortality.
ICU. The major concerns in the surgical setting are the Therapy consists of discontinuing all triggers, instituting
possibility of a difficult airway, the increased risk of known or aggressive cooling measures, giving dantrolene in an initial
occult cardiorespiratory compromise, and various serious dose of 2.5 mg/kg, and administering 100% oxygen to com-
technical problems related to positioning, monitoring, vascu- pensate for the tremendous increase in oxygen use and carbon
lar access, and transport. Additional concerns are the poten- dioxide production. An indwelling arterial line, central venous
tial for underlying hepatic and endocrine disease and the access, and bladder catheterization are indispensable for
effects of altered drug pharmacokinetics and pharmacody- monitoring and resuscitation. Acidosis, hyperkalemia, and
namics. For the morbidly obese patient, there is no such malignant dysrhythmias must be rapidly treated, with the
thing as minor surgery. caveat that calcium channel blockers are contraindicated in
Initial management should be based on the assumptions this setting. Maintenance of adequate urine output is of par-
that (1) a difficult airway is likely; (2) the patient will be pre- amount importance and may be facilitated by the clinically
disposed to hiatal hernia, reflux, and aspiration; and (3) rapid significant amounts of mannitol contained in commercial
arterial desaturation will occur with induction of anesthesia dantrolene preparations. When the patient is stable and the
as a consequence of decreased functional residual capacity surgical procedure is complete, monitoring and support are
and high basal oxygen consumption. Often the safest option continued in the ICU, where repeat doses of dantrolene may
is an awake fiberoptic intubation with appropriate topical be needed to prevent or treat recrudescence of the disease.55
anesthesia and light sedation. In expert hands, this technique
is extremely well tolerated and can usually be performed in massive transfusion
less than 10 minutes.53 Morbidly obese patients often are Massive blood transfusion, defined as the replacement of a
hypoxemic at rest and have an abnormal alveolar-arterial patient’s entire circulating blood volume in less than 24
oxygen gradient caused by ventilation-perfusion mismatch- hours, is associated with significant morbidity and mortality.
ing. The combination of general anesthesia and the supine Management of massive transfusion requires an organized
position exacerbates alveolar collapse and airway closure. multidisciplinary team approach and a thorough understand-
Mechanical ventilation, weaning, and extubation may be ing of associated hematologic and biochemical abnormalities
difficult and dangerous, especially in the presence of signifi- and subsequent treatment options.
cant obstructive sleep apnea. Postoperative pulmonary Patients suffering from shock as a result of massive blood
complications (e.g., pneumonia, aspiration, atelectasis, and loss often require transfusions of packed red blood cells,
emboli) are common.54 platelets, fresh frozen plasma, and cryoprecipitate to optimize
Morbid obesity imposes unusual loading conditions on oxygen-carrying capacity and address dilutional and con-
both sides of the heart and the circulation, leading to the sumptive loss of platelets and clotting factors [see 8:3 Shock
progressive development of insulin resistance, atherogenic and 1:4 Bleeding and Transfusion]. Transfusion of large
dyslipidemias, systemic and pulmonary hypertension, amounts of blood products into a critically ill patient can
ventricular hypertrophy, and a high risk of premature coro- lead to coagulopathies, hyperkalemia, acidosis, citrate intoxi-
nary artery disease and biventricular heart failure. Peri- cation, fluid overload, and hypothermia.56 Therapy should
operative cardiac morbidity and mortality are therefore be guided by vital signs, urine output, pulse oximetry,
significant problems. Untoward events can happen suddenly, electrocardiography, capnography, invasive hemodynamic
11/08
ANESTHESIA — 16
monitoring, serial arterial blood gases, biochemical profiles, hypothermia with these techniques should be continued as
and bedside coagulation screens. Fluids should be adminis- necessary. Shivering may also be reduced by means of drugs
tered through large-bore cannulas connected to modern such as meperidine, nefopam, tramadol, physostigmine,
countercurrent warming devices. Shed blood should be ketamine, methylphenidate, and doxapram.63
salvaged and returned to the patient whenever possible. In
intraoperative awareness
refractory cases, transcatheter angiographic embolization
techniques should be considered for control of bleeding. One of the goals of anesthesia is to produce a state of
Hemostatic agents, such as procoagulants (desmopressin, unconsciousness during which the patient neither perceives
recombinant factor VIIa) and antifibrinolytics (aprotnin, nor recalls noxious surgical stimuli. When this objective is not
tranexamic acid, e-aminocaproic acid), have been used met, awareness occurs, and the patient will have explicit or
extensively in surgical procedures associated with consider- implicit memory of intraoperative events. In some instances,
able blood loss (e.g., solid organ transplantation, cardiac and intraoperative awareness develops because human error,
orthopedic surgery [see 1:4 Bleeding and Transfusion].57 machine malfunction, or technical problems result in an
Although they are effective at reducing blood loss, a serious inappropriately light level of anesthesia. In others (e.g., when
concern is the increased risk for thrombosis. Aprotinin, a the patient is severely hemodynamically unstable or efforts
serine protease inhibitor with unique antifibrinolytic and are being made to avoid fetal depression during cesarean
hemostatic properties, very effectively decreases blood loss section), the light level of anesthesia may have been inten-
and transfusion requirements, as well as attenuates poten- tionally chosen. Regardless of the cause, intraoperative aware-
tially harmful inflammatory responses and minimizes reperfu- ness is a terrifying experience for the patient and has been
sion injury. However, recent evidence indicates that it may associated with serious long-term psychological sequelae.64
be associated with increased morbidity58 (renal failure) and Prevention of awareness depends on regular equipment
mortality,59 so its availability has been suspended.60 Recom- maintenance, meticulous anesthetic technique, and close
binant factor VIIa was originally approved for hemophiliacs observation of the patient’s movements and hemodynamic
who developed antibodies against either factor VIII or factor responses during operation. CNS monitoring may reduce
the risk of intraoperative awareness, particularly when anes-
IX. It may prove useful for managing hemorrhage deriving
thesia is maintained exclusively by intravenous drugs (total
from trauma or surgery when standard interventions have
intravenous anesthesia).34
failed.61
anaphylaxis
hypothermia
Allergic reactions range in severity from mild pruritus and
Significant decreases in core temperature are common
urticaria to anaphylactic shock and death. Inciting agents
during anesthesia and surgery as a consequence of exposure
include, but are not limited to, antibiotics, contrast agents,
to a cold OR environment and of disturbances in normal pro-
blood products, volume expanders, protamine, aprotinin,
tective thermoregulatory responses. Patients lose heat through
narcotics, induction agents, muscle relaxants, latex,65 and,
conduction, convection, radiation, and evaporation, espe-
rarely, local anesthetic solutions. Many drug additives and
cially from large wounds and during major intracavitary pro- preservatives have also been implicated.
cedures. Moreover, effective vasoconstrictive reflexes and True anaphylaxis presents shortly after exposure to an
both shivering and nonshivering thermogenesis are severely allergen and is mediated by chemicals released from degranu-
blunted by anesthetics.62 Neonates and the elderly are lated mast cells and basophils. Manifestations usually include
particularly vulnerable. dramatic hypotension, tachycardia, bronchospasm, arterial
Hypothermia may confer some degree of organ preserva- oxygen desaturation, and cutaneous changes. Laryngeal
tion during ischemia and reperfusion. For example, in cardiac edema can occur within minutes, in which case, the airway
surgery, hypothermic cardiopulmonary bypass is a common should be secured immediately. Anaphylaxis can mimic heart
strategy for protecting the myocardium and the CNS. Inten- failure, asthma, pulmonary embolism, and tension pneumo-
tional hypothermia has also been shown to improve neuro- thorax. Treatment involves withdrawing the offending
logic outcome and survival in comatose victims of cardiac substance and administering oxygen, fluids, and epinephrine,
arrest. Perioperative hypothermia can have significant delete- followed by IV steroids, bronchodilators, and histamine
rious effects as well, however, including myocardial ischemia, antagonists. Prolonged intubation and ICU monitoring may
surgical site infection, increased blood loss and transfusion be required until symptoms resolve. Appropriate skin and
requirements, and prolonged anesthetic recovery and hospital blood testing should be done to identify the causative agent.
stay.
The sensation of cold is highly uncomfortable for the perioperative dysrhythmias
patient, and shivering impedes monitoring, raises plasma cat- In 2005, current scientific developments in the acute treat-
echolamine levels, and exacerbates imbalances between ment of cerebrovascular, cardiac, and pulmonary disease
oxygen supply and demand by consuming valuable energy were merged with the evolving discipline of evidence-based
for involuntary muscular activity. It is therefore extremely medicine to produce the most comprehensive set of resuscita-
important to measure the patient’s temperature and maintain tion standards ever created: a 14-part document from the
thermoneutrality. Increasing the ambient temperature of the American Heart Association entitled “2005 American Heart
OR and applying modern forced-air warming systems are Association Guidelines for Cardiopulmonary Resuscitation
the most effective techniques available. In addition, all IV and Emergency Cardiovascular Care.”66 This document
and irrigation fluids should be heated. After the patient addresses a wide array of key issues in both in-hospital and
has been transferred from the OR, aggressive treatment of out-of-hospital resuscitation, including a recommendation for
11/08
ANESTHESIA — 17
confirmation of tube position after endotracheal intubation Table 16 Cardiac Conditions Associated with Risk of
and a warning about the danger associated with unintentional Adverse Outcome from Endocarditis for Which
massive auto–positive end-expiratory pressure. Prophylaxis Is Reasonable67
As regards the impact the new guidelines have on the man- Prosthetic cardiac valve or prosthetic material used for cardiac
agement of cardiopulmonary resuscitation, an increase in valve repair
ratios of compression to ventilation ratios (to 30:2) and an Previous infective endocarditis
emphasis on effective chest compressions (“push hard, push Congenital heart disease (CHD)*
Unrepaired cyanotic CHD, including palliative shunts and
fast”) are suggested. In addition, early chest compressions conduits
before defibrillation, a one-shock sequence for defibrillation Completely repaired congenital heart defect with prosthetic
as opposed to a three-shock sequence, and avoidance of pro- material or device, whether placed by surgery or by catheter
longed interruption of chest compressions are recommended. intervention, during the first 6 months after the procedure†
Repaired CHD with residual defects at the site or adjacent to the
For wide QRS dysrhythmias, amiodarone continues to be the site of a prosthetic patch or prosthetic device (which inhibit
drug of choice. It may also be administered for ventricular endothelialization)
fibrillation or for pulseless ventricular tachycardia that does Cardiac transplant recipients who develop cardiac valvulopathy
not respond to cardiopulmonary resuscitation, cardioversion, *Except for the conditions listed above, antibiotic prophylaxis is no longer
and a vasopressor. recommended for any other form of CHD.
†
Amiodarone is a complex, powerful, and broad-spectrum Prophylaxis is reasonable because endothelialization of prosthetic material
occurs within 6 months after the procedure.
agent that inhibits almost all of the drug receptors and
ion channels conceivably responsible for the initiation and
propagation of cardiac ectopy, irrespective of underlying antibiotic prophylaxis
ejection fraction, accessory pathway conduction, or anatomic Recently, the Americal Heart Association has revised the
substrate. It does, however, have potential drawbacks, such guidelines for administration of antiobiotic drugs prophylacti-
as its relatively long half-life, its toxicity to multiple organs, cally to prevent infective endocarditis.67 Infective endocarditis
and its complicated administration scheme. Furthermore, prophylaxis is no longer recommended for mitral valve pro-
amiodarone is a potent noncompetitive alpha and beta lapse or for the stenotic or regurgitant cardiac lesions associ-
blocker, which has important implications for anesthetized, ated with rheumatic heart disease [see Table 16]. A suggested
mechanically ventilated patients who may be debilitated antibiotic regimen is provided in Table 17.
and experiencing volume depletion, abnormal vasodilation,
myocardial depression, and fluid, electrolyte, and acid-base
abnormalities. That said, no other drug in its class has ever Table 17 Antibiotic Protocol67
demonstrated a significant benefit in randomized trials Situation Agent Regimen: Single Dose
30–60 min before
addressing cardiac arrest in humans.
Procedure
Amiodarone is effective in both children and adults, and it
Adults Children
can be used for prophylaxis and treatment. The recom-
mended cardiac arrest dose is a 300 mg IV bolus. In less Oral Amoxicillin 2g 50 mg/kg
acute situations (e.g., wide-complex tachycardia), an initial Unable to take Ampicillin or 2 g IM or IV 50 mg/kg
oral cefazolin or IM or IV
150 mg dose should be administered slowly over 10 minutes,
medication ceftriaxone 1 g IM or IV
and one or two additional boluses may be given similarly. A 50 mg/kg
loading regimen is then initiated, first at 1 mg/min for 6 hours IM or IV
and then at 0.5 mg/min for 18 hours. Allergic to Cephalexin*† or 2g 50 mg/kg
Vasopressin (antidiuretic hormone) continues to be listed penicillins or clindamycin or 600 mg 20 mg/kg
as an alternative to epinephrine in the ventricular tachycar- ampicillin azithromycin or 500 mg 15 mg/kg
oral clarithromycin
dia/ventricular fibrillation protocol. Vasopressin is an integral
component of the hypothalamic-pituitary-adrenal axis and Allergic to Cefazolin or 1 g IM or IV 50 mg/kg
penicillins or ceftriaxone† or IM or IV
the neuroendocrine stress response. The recommended dose ampicillin clindamycin 600 mg IM 20 mg/kg
for an adult in fibrillatory arrest is 40 units in a single bolus. and unable or IV IM or IV
For vasodilatory shock states associated with sepsis, hepatic to take oral
failure, or vasomotor paralysis after cardiopulmonary bypass, medication
infusion at a rate of 0.01 to 0.04 units/min may be particu- IM = intramuscular; IV = intravenous.
larly useful. Vasopressin is neither recommended nor forbid- *Or other first- or second-generation oral cephalosporin in equivalent adult or
pediatric dosage.
den in cases of pulseless electrical activity or asystolic arrest, †
Cephalosporins should not be used in a person with a history of anaphylaxis,
and it may be substituted for epinephrine. angioedema, or urticaria with penicillins or ampicillin.
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1 BASIC SURGICAL AND PERIOPERATIVE CONSIDERATIONS 4 BLEEDING AND TRANSFUSION — 1
4 BLEEDING AND TRANSFUSION

Garth H. Utter, MD, MSc, FACS, Robert C. Gosselin, MT, and John T. Owings, MD, FACS
Approach to the Patient with Massive Hemorrhage
A surgeon is frequently one of the first people to be called bleeding should be considered when the patient is at appre-
when a patient experiences massive hemorrhage. “Massive ciable risk of death; these apply even if the hemorrhage
hemorrhage” is usually not hard to recognize in practice, but developed during an elective procedure. For example, right
it can be defined as hemorrhage requiring at least 10 units nephrectomy may be warranted to afford exposure of the
of cellular blood products within 24 hours. To treat such a infrahepatic inferior vena cava, or deliberate division of a
patient appropriately, the surgeon must rapidly and simulta- common iliac artery may be necessary to expose bleeding
neously accomplish three tasks: identify the source or cause from the corresponding common iliac vein. Temporary vas-
of the bleeding, stop or limit the bleeding, and restore the cular shunts may be helpful to rapidly restore blood flow to
patient’s circulation. ischemic limbs if it is still possible to salvage the limb. How-
Causes fall into two main categories: (1) conditions involv- ever, reperfusion of a large volume of ischemic tissue in the
ing loss of vascular integrity, such as a patient with bleeding setting of shock can cause severe systemic problems, so expert
from a peptic ulcer or a trauma patient with a severe liver judgment is necessary to decide whether to try to preserve or
laceration, and (2) conditions involving a derangement of the amputate the limb in such situations.
hemostatic process. Typically, massive hemorrhage begins Sometimes, the best option to control massive hemorrhage
with a loss of vascular integrity, but derangements of hemo- is not necessarily an open operation. Increasingly, interven-
stasis frequently develop as a secondary problem and play a tional radiologic and endovascular techniques are serving
major role in the exacerbation of such hemorrhage. In this important roles: although long used for control of bleeding
section, we focus on the immediate concerns to keep the from sites not easily managed with open procedures, such
patient alive with particular attention to how to address as pelvic fractures, they have recently become an accepted
the associated coagulopathy. We consider derangements approach for some problems traditionally managed with open
of hemostasis that are not associated with massive hemor- procedures, such as ruptured abdominal aortic aneurysms,1
rhage in the next section, “Approach to the Patient with a because of the speed of access by an experienced interven-
Derangement of Hemostasis.” tionalist. However, the surgeon should be actively involved in
decisions to use minimally invasive techniques and should
never hesitate to operate if that is the best option in a given
Control of the Source
situation. Surgeons must individualize their approach to each
of Bleeding
patient based on their expertise, available resources, and the
If a coagulopathy most current standards of care but be willing to use all tools
develops as a result of in their armamentarium.
uncontrolled hemor-
rhage from loss of vascu-
lar integrity, attempting Restoration of the Blood Volume
to treat the coagulopathy Just as massive hemorrhage should lead the surgeon to
without controlling the reprioritize the goals of an operation, it should also prompt a
source is an exercise in futility. Other sections of this text major shift in the fluid resuscitation strategy. Initially, when
address the anatomic and technical considerations involved there is massive hemorrhage that can be addressed with an
in controlling different sites of bleeding [see subcategories operation, resuscitation with blood products and other intra-
under “Bleeding” in the Index]. However, in contrast to the venous (IV) fluids should be implemented only as an adjunct
routine conduct of operations, control of the source of while attempts are made to stop the loss of blood. Although
massive bleeding requires a fundamentally different mindset. surgeons continue to debate the merits of “permissive hypo-
The goals of operative conduct change from definitive tension” (the concept that fluid resuscitation before control
management of all issues to “damage control,” in which the of hemorrhage should be minimized because it will lead to
salient objective is to address immediately life-threatening increased bleeding2), attempts at fluid resuscitation should
problems: restoration of vascular integrity and, to the extent not delay procedures to control massive hemorrhage, even
necessary and prudent, restoration of the circulation of the temporarily.
viscera and limbs. Other goals, such as reestablishment of When massive bleeding exists and direct control of the site
intestinal continuity or closure of the wound, become second- of bleeding is under way, the decision to transfuse should be
ary and can be addressed later if the patient survives. Even based primarily on hemodynamic status rather than on the
selected, more drastic maneuvers for exposure of the site of hemoglobin or hematocrit level. These laboratory values do
Indicates the text is tied to a SCORE learning objective. Please see the DOI 10.2310/7800.2019
HTML version online at www.acssurgery.com.
12/11
Approach to the Patient with Hemorrhage
Patient experiences ongoing bleeding
First, assess whether bleeding is massive
Bleeding is massive
Assess whether there is an anatomic source.
Anatomic source identified No specific anatomic source identified

Immediately initiate an effort to stop or
limit the bleeding with a damage-control
operation (or other lifesaving
interventional procedure).
Support the patient’s circulation

and correct the coagulopathy
(1) Administer blood transfusion along

with early plasma and platelet transfusions
to maintain a 1:1:1 ratio.
(2) Administer a fibrinolytic agent
(e.g., tranexamic acid 1 g IV, followed
by 1 g over 8 hours).
(3) Warm the patient to a core
temperature of 36°C.
° C.
(4) Consider administering rVIIa.
Monitor progress of resuscitation
Check CBC, INR, and aPTT.

Consider returning to the operating room Patient has family history of bleeding disorder
if bleeding persists or recurs.
Initiate directed testing and therapy.
Patient has normal INR and aPTT Patient has normal INR and prolonged aPTT
Consider platelet dysfunction. Consider drug effects (heparin, lepirudin), acquired factor
Give platelets and initiate directed therapy. deficiency, and vWD.
Give protamine (to reverse heparin), replace factors, or
initiate directed therapy for vWD.
12/11
Bleeding is not massive
Assess whether there is an anatomic source.
Patient has unligated vessel or unrecognized injury No technical cause of bleeding is apparent
Control bleeding vessel. Draw blood for laboratory tests.

Check temperature.
Temperature is normal Temperature is low
Warm patient.
Bleeding continues Bleeding stops
Assess platelet status and coagulation parameters.
Platelet status or coagulation parameters are abnormal Platelet status or coagulation parameters are normal
Look for family history of specific bleeding disorder. DIC is not present.
Reconsider possibility of unligated vessel [see above].
Patient has no family history of bleeding disorder
Continue evaluation guided by laboratory test results.
Patient has increased INR and normal aPTT Patient has increased INR and prolonged aPTT
Consider drug effects (warfarin), hepatic failure, and If D-dimer level is elevated, assume DIC and treat accordingly.
malnutrition. If D-dimer level is normal, consider end-stage renal disease
Give IV vitamin K, FFP, or rVIIa as appropriate; treat and multifactor deficiency.
cirrhosis-related variceal bleeding. Give FFP and initiate directed therapy.
12/11
not reflect acute hemorrhage because there is a time lag The concept of liberal, early use of plasma and platelets
before these levels equilibrate from fluid shift between the developed in large part from the recent US-led military cam-
extravascular and vascular compartments and from adminis- paigns in Iraq and Afghanistan. Initially in those conflicts,
tration of IV fluids. The goals of transfusion are therefore as the lack of a reliable supply of blood products near the scene
much to increase the intravascular volume as to prevent the of injury—and platelets especially—led to the use of fresh
development of profound deficits in oxygen-carrying capac- whole blood transfusion. Although fresh whole blood would
ity. Stabilized patients who are at high risk for recurrent be impractical in the civilian setting because of logistical
bleeding (e.g., those with a massive liver injury or gastroin- issues and the risk of transmitting transfusion-related infec-
testinal (GI) hemorrhage from an unknown source) should tions, the perception of improved outcomes associated
receive transfusions up to a level at which, should bleeding with its use prompted military surgeons to advocate 1:1:1
recur, enough reserve oxygen-carrying capacity would be transfusion.
available to allow diagnosis and correction of the hemorrhage Proponents of this approach argue that it restores
without significant compromise of oxygen delivery (we advo- hemostatic capacity and helps limit hemorrhage, leading to
cate a target hematocrit of roughly 30% during this phase). improved survival. Indeed, observational studies suggest that
The standard restrictive transfusion strategy used in stable mortality is reduced.3 However, the ratios examined in these
intensive care unit (ICU) patients [see Approach to the studies typically have been calculated retrospectively over
Patient with Anemia, below] warrants modification in these relatively long (e.g., 12- or 24-hour) time periods after hem-
circumstances because of the higher likelihood of occult orrhage. Critics emphasize that patients who do not survive
active hemorrhage. long enough to receive early plasma and platelets bias such
observational comparisons (i.e., they are classified as receiv-
ing a large ratio of RBCs to plasma or platelets because they
Management of the died early) and that plasma and platelets carry theoretical
Coagulopathy harms of transfusion-related acute lung injury and bacterial
It is true that coagu- infection, respectively. Despite some uncertainty about the
lopathy may promote actual merits of the 1:1:1 approach, given that military con-
massive hemorrhage flicts have frequently spurred advances in transfusion medi-
and that massive hem- cine, it appears likely that the approach will be adopted more
orrhage causes a coagu- widely if the availability of blood products does not limit its
lopathy. As a rule, the application. In the absence of sufficient availability of blood
massively hemorrhaging patient has a coagulopathy out of products to allow a 1:1:1 approach, aggressive correction
of abnormalities of the INR, aPTT, and platelet count are
proportion to the abnormalities reflected with in vitro labora-
warranted for patients with massive hemorrhage.
tory tests such as the prothrombin time (PT, commonly
More convincing information supports the use of antifibri-
expressed as an international normalized ratio [INR]) or acti-
nolytic agents in the setting of massive hemorrhage. Apro-
vated partial thromboplastin time (aPTT). Coagulopathy
tinin, tranexamic acid, and e-aminocaproic acid (Amicar) are
most typically occurs when there is massive hemorrhage in
known to reduce transfusion requirements in the setting of
concert with injury to a large volume of tissue. Although the
elective operations (primarily cardiac procedures). Further-
nature of this coagulopathy is not precisely defined, it prob-
more, a recent large randomized trial, the CRASH-2 trial,
ably involves a number of factors: (1) platelet dysfunction
showed that patients with or at risk for significant bleeding
and diminished availability of platelets at the interface between
(i.e., hypotension or tachycardia) from traumatic injury had
the vascular endothelium and luminal flow; (2) dysfunctional
decreased all-cause and bleeding-related mortality when they
formation of thrombi in the setting of acidosis and hypother- received tranexamic acid within 8 hours of injury.4 In this
mia; (3) accelerated thrombolysis (attributable to dysfunc- study, tranexamic acid was administered intravenously as a
tional thrombosis); and, eventually, (4) consumption of 1 g loading dose, followed by an infusion of an additional
clotting factors. 1 g over 8 hours. Tranexamic acid did not increase the
Increased recognition of this coagulopathy has prompted likelihood of major vascular occlusion events (myocardial
enthusiasm for administration of plasma and platelets early in infarction, stroke, and pulmonary embolism).
the treatment of the patient with massive hemorrhage. This Recombinant activated factor VII (rVIIa) is approved for
practice, frequently incorporated into a massive transfusion the treatment of hemophilia in the United States. It has also
protocol, is described as “1:1:1 transfusion” because the goal been advocated for off-label use early in the course of uncon-
is to transfuse one unit of plasma and one of platelets along trolled hemorrhage5 and intracranial hemorrhage. Although
with each unit of red blood cells (RBCs) such that the ratio rVIIa can be a rapid and highly specific form of treatment in
stays balanced throughout the resuscitation phase. (Adjust- certain instances of bleeding (e.g., traumatic brain injury in a
ment of these ratios is necessary for centers that use pooled patient on warfarin), the rationale for its use is not as highly
quantities of plasma and/or platelets.) The rationale is that targeted in the setting of massive hemorrhage, during which
patients are already extensively coagulopathic by the time factor deficiencies are not typically an early abnormality. Two
they manifest thrombocytopenia or prolongation of the INR sponsor-initiated international randomized trials of rVIIa in
or aPTT. Thus, during the first several hours during and severely injured trauma patients have been performed, and
after massive hemorrhage, plasma and platelets are necessary their results—although neither had overwhelming power to
independent of the laboratory tests and help address a detect improved survival—suggest that rVIIa decreases blood
significant contributing factor for persistent hemorrhage. transfusions but does not reduce mortality.6,7 One recent
12/11
report suggested that off-label use of rVIIa in certain popula- of 37°C (98.6°F). The resulting coagulopathy cannot be
tions significantly increased the risk of arterial thromboem- detected by laboratory tests because the laboratory warms the
bolic complications.8 In the absence of better designed sample to 37°C to run the coagulation assays (INR and
and conducted studies of patients with massive bleeding, aPTT). Thus, bleeding hypothermic patients should be
surgeons will need to decide whether use of rVIIa is war- rewarmed, and active measures are warranted if the core
ranted despite its costs and incompletely understood efficacy temperature is 34.5°C (94.1°F) or lower.11
and safety profile in this setting. Consensus recommenda- Relatively new agents have been promulgated to facilitate
tions have attempted to define appropriate use in light of hemostasis at sites of focal bleeding. QuikClot (Z-Medica,
insufficient evidence.9 Newington, CT), a granular substance containing the
There is relatively little controversy over the management mineral zeolite, and HemCon (HemCon, Inc., Portland,
of hypothermia. As a series of chemical reactions, the coagu- OR), a chitosan-based dressing, have been used in the setting
lation cascade slows with decreasing temperature.10 Thus, a of military trauma. Preliminary information suggests that
patient with a temperature lower than 35°C (95°F) clots whereas QuikClot appears to cause superficial burns, HemCon
more slowly and less efficiently than one with a temperature may carry few disadvantages.12
Approach to the Patient with a Derangement of Hemostasis
Not infrequently, surgeons encounter patients with actual frequently disastrous. For these reasons, in all cases of ongo-
or suspected derangements of hemostasis short of massive ing bleeding, the first consideration must always be to exclude
hemorrhage. These situations range from the preoperative a surgically correctable cause.
assessment of asymptomatic patients potentially at risk for Ongoing bleeding may be surprisingly difficult to diagnose.
coagulopathic bleeding to the postoperative management Healthy young patients can usually maintain a normal blood
of patients with an observed bleeding diathesis. Although it is pressure until their blood loss exceeds 40% of their blood
still important to rule out the possibility of technical causes volume (roughly 2 L). If the bleeding is from a laceration to
of bleeding, surgeons should also be able to recognize coagu- an extremity, it will be obvious; however, if the bleeding is
lopathic bleeding and know how to prevent it when possible occurring internally, there may be few physiologic signs until
or evaluate and manage its most common etiologies when the patient is at high risk for death.
it occurs. Even when a technical cause of bleeding has seemingly
Coagulopathies are varied in their causes, treatments, and been excluded, the possibility should be reconsidered
prognoses. Although specialized hematologic tests exist to periodically throughout assessment. Patients who are either
identify rare congenital or acquired clotting abnormalities, unresuscitated or underresuscitated undergo vasospasm that
our goal in this section is to outline a practical, effective results in decreased bleeding. As resuscitation proceeds, the
approach to the coagulopathies surgeons see most frequently. catecholamine-induced vasospasm subsides and bleeding
The vast majority of these coagulopathies can be diagnosed
may recur. Only when the surgeon is confident that a missed
by means of a brief patient and family history, a review of
injury or unligated vessel is not the cause of the bleeding
medications, physical examination, and commonly used labo-
should other potential causes be investigated.
ratory studies—in particular, PT (commonly expressed as an
INR), aPTT, complete blood count (CBC), and D-dimer
assay. Initial Assessment
In the Discussion section later in this chapter, we present of Potential
an overview of the physiology of hemostasis and consider Coagulopathy
some of the rarer conditions and theoretical considerations in
The first step in the
greater detail.
assessment of a stable
patient with a potential
Exclusion of coagulopathy is to draw
Technical Causes of a blood sample. The
Bleeding blood should be drawn
It is critical to empha- into a tube containing ethylenediaminetetraacetic acid
size that the most (EDTA) for a CBC and into a citrated tube for coagulation
common causes of post- analysis (these tubes commonly have purple and blue tops,
operative bleeding, even respectively).
when it is not massive, Concomitant with these laboratory tests, it is essential to
are technical: an unli- obtain a personal and family history of bleeding tendencies.
gated vessel or an unrecognized injury is much more likely to A patient who has had dental extractions without major
be the cause of a falling hematocrit than either a drug effect problems or who had a normal adolescence without any
or an endogenous hemostatic defect. Furthermore, if an history of bleeding dyscrasias is very unlikely to have a
unligated vessel is treated as though it were an endogenous congenital or hereditary bleeding disorder.13 Alternatively,
hemostatic defect (i.e., with transfusions), the outcome is previous bleeding events and a familial history of bleeding are
12/11
both suggestive of a congenital coagulopathy and warrant fur- Newer platelet-blocking agents have been found to be
ther testing to diagnose and treat the disorder [see Discussion, effective in improving outcome after coronary angioplasty.17
Bleeding Disorders, below]. Mucosal and superficial bleeding These drugs function through different mechanisms. Some,
is suggestive of platelet abnormalities, and deep bleeding is such as abciximab (ReoPro), eptifibatide (Integrilin), and
suggestive of a factor deficiency. A thorough medication tirofiban (Aggrastat), block the platelet surface receptor
inventory is necessary to assess the possible impact of drugs glycoprotein (GP) IIb-IIIa, which binds platelets to fibrino-
on laboratory and clinical presentations. In the patient history gen. Others, such as clopidogrel, ticlopidine (Ticlid), and
query, it is advisable to ask explicitly about nonprescription prasugrel (Effient), target the P2Y12 receptor (also known
drugs—using expressions such as “over-the-counter drugs,” as the adenosine diphosphate [ADP] receptor). Clopidogrel,
“cold medicines,” and “Pepto-Bismol”—because unless spe- the most commonly used among this group, permanently
cifically reminded, patients tend to equate the term “medica- prevents the association of P2Y12 receptors into functional
tions” with prescription drugs. If this is not done, many drugs oligomeric complexes. As a result, there is no way to inacti-
that are capable of influencing hemostasis in vivo and in vitro vate this medication if the patient experiences bleeding during
(e.g., salicylates, cold and allergy medicines, and herbal its therapeutic window, which typically lasts about 5 days
supplements) may be missed. from the last dose. In the face of life-threatening bleeding
during this interval, it is reasonable to administer platelets
Interpretation of Co- based on the rationale that, in large-enough quantities, they
agulation Parameters may eventually bind all of the active metabolite. Some of the
newest drugs in the P2Y12 inhibitor class (which have not yet
normal inr, normal been evaluated for use in the United States), for example,
aptt ticagrelor, are reversible, which may help avoid such
Patients with a normal difficulties in the future.
INR and a normal aPTT von Willebrand disease (vWD), although sometimes asso-
who exhibit unexpected ciated with a slight prolongation of the aPTT (as a result of
bleeding may have im- decreased factor VIII activity), most commonly shows no
paired platelet activity. Inadequate platelet activity is fre- abnormalities with both the INR and the aPTT. The clinical
quently manifested as persistent oozing from wound edges expression is variable, but von Willebrand factor (vWF) levels
or as low-volume bleeding. Such bleeding is rarely the cause of less than 30% are more likely associated with clinically
important bleeding. Confirmation of the diagnosis can be
of exsanguinating hemorrhage, although it may be life-
obtained by specialized tests [see Discussion, Bleeding
threatening when it occurs in certain locations (e.g., inside
Disorders, below]. Correction is accomplished by administer-
the cranium or the pericardium). Inadequate platelet activity
ing desmopressin, directed therapy (vWF/factor VIII), or
may be attributable to an insufficient number of platelets,
cryoprecipitate.
platelet dysfunction, or a platelet inhibitor. In the absence of
In patients with platelet dysfunction caused by an inhibitor
a major surgical insult or concomitant coagulopathy, a plate-
of platelet function, such as an elevated blood urea nitrogen
let count of 20,000/µL or higher is usually adequate for
(BUN) level or aspirin, 1-desamino-8-D-arginine vasopressin
normal coagulation.14,15 There is some disagreement regard-
(desmopressin) is capable of significantly improving the plate-
ing the threshold for platelet transfusion in the absence of
let dysfunction.18 The mechanism of this effect is not entirely
active bleeding. Patients undergoing procedures in which
understood but appears to involve more complex changes
even small-vessel oozing is potentially life-threatening (e.g.,
than simply increased release of factor VIII and vWF.
craniotomy) should be maintained at a higher platelet count Supratherapeutic effects of the low-molecular-weight hepa-
(i.e., > 20,000/µL). Patients without ongoing bleeding who rins (LMWHs) may also manifest with a normal INR and
are not specifically at increased risk for major complications aPTT [see Normal INR, Prolonged aPTT, below for a discus-
from low-volume bleeding may be safely watched with sion of both unfractionated heparin and the LMWHs].
platelet counts as low as 10,000/µL.16 Less common causes of bleeding in patients with a normal
Oozing in a patient who has an adequate platelet count and INR and a normal aPTT include factor XIII deficiency,
normal coagulation parameters may be a signal of platelet hypofibrinogenemia or dysfibrinogenemia, and derangements
dysfunction. The now-routine administration of acetylsali- in the fibrinolytic pathway [see Discussion, Mechanics of
cylic acid (aspirin) and clopidogrel (Plavix) to reduce the Hemostasis, below].
risk of myocardial infarction and stroke has led to a rise in
the incidence of drug-induced platelet dysfunction. Aspirin normal inr,
causes irreversible platelet dysfunction through the cyclooxy- prolonged aptt
genase pathway. It takes approximately 10 days for sufficient In the absence of a
numbers of new platelets to be formed such that the effect of history of significant
aspirin lapses; however, because the half-life of aspirin is on bleeding, patients with a
the order of 2 to 5 hours, new platelet transfusions should normal INR and an
be unaffected if at least a day has passed since the last use abnormal aPTT are
of aspirin. The platelet dysfunction caused by other likely to have a drug-
nonsteroidal antiinflammatory drugs (e.g., ibuprofen) is induced coagulation de-
reversible and consequently does not generally last as long fect. The agent most commonly responsible is unfractionated
as that caused by aspirin. heparin. Reversal of the heparin effect, if desired, can be
12/11
accomplished by administering protamine sulfate. Protamine inhibitors is that the effects are not reversible; if thrombin
should be given with caution, however, because it may induce inhibition is no longer desired, FFP should be given to
both hyper- and hypocoagulable states.19 Protamine should attempt to correct the aPTT. Because the inhibitor that is
also be used with caution because of the potential for allergic circulating but not bound at the time of FFP administration
reactions, including anaphylaxis. Patients can become sensi- will bind the prothrombin in the FFP, the amount of FFP
tized to impurities in protamine if they have previously required to correct the aPTT may be greater than would be
received it. Also, diabetic patients have been described to needed with a simple factor deficiency.
become sensitized through their exposure to similar impuri- Hemophilia is also associated with prolongation of the
ties in protamine-containing insulin formulations (e.g., neu- aPTT. It can cause spontaneous bleeding or prolonged bleed-
tral protamine Hagedorn, or “NPH,” insulin).20 ing after a surgical or traumatic insult. As noted, hemophilia
Importantly, the aPTT does not detect the anticoagulant is rare in the absence of a personal or family history of the
activity of LMWHs. Because such heparins exert much of disorder. Although hemophilia can occur as an acquired
their anticoagulant effect by potentiating antithrombin to autoimmune condition with production of antibodies against
inactivate factor Xa rather than factor IIa, an assay that mea- clotting factors, the most common forms of hemophilia are
sures anti-Xa activity is needed to measure the anticoagulant inherited and involve deficiencies of factors VIII, IX, and
effect. However, the anti-Xa effect of the LMWHs may not XI (hemophilia A, hemophilia B [Christmas disease], and
be as effectively reversed by protamine as the anti-IIa effect hemophilia C, respectively). As X-linked recessive disorders,
of unfractionated heparin. It is currently unclear which agent hemophilias A and B occur almost exclusively in males. The
is best for reversal of LMWHs, but both protamine and rVIIa clinical presentations of hemophilia A and hemophilia B are
have been advocated. Whether or not bleeding has occurred, similar: hemarthroses are the most common clinical manifes-
because the standard coagulation tests do not detect the tations, ultimately leading to degenerative joint deformities.
effect of the LMWHs, suspicion for a supratherapeutic effect Spontaneous bleeding may also occur, resulting in intracra-
should be aroused if there is a concern that excessive doses nial hemorrhage, large hematomas in the muscles of extrem-
have been administered or clearance has decreased (e.g., ities, hematuria, and GI bleeding. Certain types of vWD can
renal insufficiency). result in a deficiency of factor VIII and thus present like
hemophilia A. Factor XI deficiency is relatively common in
One nuance of the anti-Xa laboratory assay is that it may
Jewish persons but rarely results in spontaneous bleeding.
not truly measure the degree of anticoagulation in vivo;
Such deficiency may result in bleeding after oral operations
rather, anti-Xa results for some of the available assays should
and trauma; however, a number of major procedures (e.g.,
be interpreted merely as the concentration of LMWH in
cardiac bypass surgery) do not result in postoperative
plasma. Because heparins (including LMWHs) function to a
bleeding in this population.23
large extent by catalyzing the activity of antithrombin, the
In contrast to depletion of natural anticoagulants such
therapeutic effect of heparin is critically dependent on ade-
as antithrombin and protein C, depletion of procoagulant
quate antithrombin levels. In fact, acquired antithrombin
factors rarely gives rise to significant manifestations until it is
deficiency (as occurs with trauma and other critical illnesses)
relatively severe. Typically, no laboratory abnormalities result
is the most common reason for LMWH to have an inade-
from depletion of procoagulant factors until factor activity
quate effect. The anti-Xa laboratory assay may not account
levels fall below 40% of normal, and clinical abnormalities
for in vivo antithrombin levels, because some methods involve
are frequently absent even when factor activity levels fall to
the addition of antithrombin to the test sample as a reagent.
only 10% of normal. This tolerance for subcritical degrees of
Consequently, the results of this assay may not be a reliable depletion is a reflection of the built-in redundancies in the
guide to the patient’s coagulation status. procoagulant pathways.
An additional crucial point is that the administration of If hemophilia is suspected, specific factor analysis is
plasma (e.g., fresh frozen plasma [FFP]) will not correct indicated. Appropriate therapy involves administering the
the anticoagulant effect of either unfractionated heparin or deficient factor or factors. Hemophiliac patients who have
LMWHs. In fact, given that plasma contains antithrombin undergone extensive transfusion therapy may pose a particu-
and that both unfractionated heparin and LMWHs act by lar challenge: massive transfusions frequently lead to the
potentiating antithrombin, administration of FFP could development of antibodies that make subsequent transfusion
actually enhance the heparins’ anticoagulant effect. or even directed therapy impossible. Accordingly, several
A variety of direct thrombin inhibitors (e.g., bivalirudin alternatives to transfusion or directed factor therapy (e.g.,
[Hirulog], lepirudin, argatroban, and dabigatran) are cur- rVIIa) have been developed for use in this population.
rently available in Europe, Asia, and North America.21 Many Other conditions may also have an isolated effect on the
of them cause prolongation of the aPTT. Dabigatran is a new aPTT. Drotrecogin alfa (i.e., activated protein C), a medica-
oral direct thrombin inhibitor that has been recently approved tion approved for treatment of certain subgroups of patients
for use in the United States for atrial fibrillation. As an oral with sepsis, may prolong the aPTT. Its use is contraindicated
alternative to warfarin that does not require frequent labora- in the presence of active hemorrhage, but if bleeding should
tory tests to monitor its anticoagulant effect, dabigatran may arise during its use, cessation of the infusion should suffice as
become widely used. It has a variable impact on coagulation a result of its short half-life. Lupus anticoagulant and contact
assays: the aPTT is typically elevated but may be only mod- factor deficiency can also cause prolongation of the aPTT;
erately prolonged with supratherapeutic levels of dabigatran.22 however, these phenomena do not clinically result in a
One disadvantage shared by most of the direct thrombin hypocoagulable state.
12/11
increased inr, Generally, factor replacement should be instituted with FFP,

normal aptt but use of rVIIa is reasonable in the setting of active hemor-
An increased INR rhage or any intracranial hemorrhage. Although to date there
in association with a is little information on its efficacy in this particular setting,
normal aPTT is poten- the administration of rVIIa, 20 to 40 µg/kg, would be a rea-
tially a more ominous sonable approach. If the bleeding is a manifestation of portal
finding in a patient with hypertension (as in variceal bleeding), emergency portal
a coagulopathy. Any of decompression—typically via transjugular intrahepatic porto-
a number of causes, all systemic shunting—should be considered. Modest elevations
centering on factor deficiency, may be responsible. of the INR in patients with cirrhosis who are not actively
An elevated INR occurs with the administration of vitamin bleeding, have not recently undergone operation, and are not
K antagonists (e.g., warfarin), with variable effects on the specifically at increased risk for life-threatening hemorrhage
aPTT. If the aPTT is normal, this usually demonstrates that may be observed without correction.
warfarin was only recently started (usually < 3 days of treat- increased inr,
ment) or has been underdosed. Such a coagulopathy is the prolonged aptt
result of a pure factor deficiency, and its degree is propor-
tional to the prolongation of the INR. Because warfarin Increases in both the
acts by disrupting vitamin K metabolism, the coagulopathy INR and the aPTT may
may be corrected by giving vitamin K [see Table 1], but this be the most problematic
process takes several hours for additional proteins to be finding of all. When
synthesized.24 If the patient is actively bleeding, vitamin K both assays show
should still be given, but the primary corrective measures increases, the patient is
should be to administer FFP and/or rVIIa. FFP should be likely to have multiple
administered in an amount proportional to the patient’s size factor deficiencies; possible causes include disseminated
and the relative increase in the INR, whereas rVIIa should be intravascular coagulation (DIC), severe hemodilution, and
administered at a dose of 15 to 90 µg/kg. The INR should renal failure with severe nephrotic syndrome. However, when
subsequently be rechecked to ensure that correction has been dramatic elevations of the aPTT and the INR occur that are
achieved. Because rVIIa has a relatively short half-life, in out of proportion to the patient’s clinical status, the problem
general, it should be used as an adjunct to FFP rather than may simply be that the specimen tube was not adequately
a replacement for it. Aside from the time delay involved, filled. If a life-threatening coagulopathy seems unlikely, the
the main potential disadvantage of vitamin K replacement blood sample should be redrawn and the tests repeated.
therapy is that if the patient is to be reanticoagulated with Hemodilution and nephrotic syndrome result in a coagu-
warfarin in the near future, dosing will be difficult because lopathy that is attributable to decreased concentration of
the patient will exhibit resistance to warfarin for a variable coagulation proteins. Dilutional coagulopathy may occur
period. when a patient who is given a large volume of packed RBC
Cirrhosis is arguably the most serious of the causes of an units is not also given coagulation factors.25 Because of the
elevated INR. It is a major problem not so much because of tremendous redundancy of the hemostatic process, pure
the coagulopathy itself but because of the associated deficits dilutional coagulopathy is rare. It is considered an unlikely
in wound healing and immune function that result from diagnosis until after one full blood volume has been replaced
dysfunction of reticuloendothelial cells and hepatocytes. (as when a patient requires 10 units of packed RBCs to
Table 1 Management of the Patient with an Increased International Normalized Ratio

Indication Recommended Treatment
No significant INR above therapeutic range Lower or hold the next dose
bleeding but < 5.0
INR > 5.0 but < 9.0
Rapid reduction of INR In the absence of additional risk factors for bleeding, withhold next 1–2 doses;
is not required alternatively, withhold next dose and give vitamin K, 1.0–2.5 mg orally
Rapid reduction of INR Give vitamin K, 1.0–2.0 mg p.o.; expected reduction of INR should occur within
is required 24 hr
INR > 9.0 Give vitamin K, 3.0–5.0 mg p.o.; expected reduction of INR should occur within
24 hr
Serious bleeding Any elevation of INR Give vitamin K, 10 mg IV, supplemented with FFP, prothrombin complex
concentrate, or rVIIa; further vitamin K supplementation may be required every
12 hr
Life-threatening Any elevation of INR Give FFP, prothrombin complex concentrate, or rVIIa supplemented with vitamin
bleeding K 10 mg IV, repeated as necessary
FFP = fresh frozen plasma; INR = international normalized ratio; rVIIa = recombinant activated factor VII.
12/11
maintain a stable hematocrit). Nephrotic syndrome is associ- Table 2 Coagulopathy (DIC) Score
ated with loss of plasma proteins (including coagulation
INR aPTT Platelets Fibrinogen D-Dimer
factors) from the kidneys. Score (s) (s) (1,000/µL) (mg/dL) (ng/mL)
Both hemodilution and nephrotic syndrome should be
distinguished from DIC (which is a consumptive rather than 0 < 1.2 < 34 > 150 > 200 < 1,000
1 > 1.2 > 34 < 150 < 200 < 2,000
a dilutional process26), although, on occasion, this distinction 2 > 1.4 > 39 < 100 < 150 < 4,000
is a difficult one to make. A blood sample should be sent for 3 > 1.6 > 54 < 60 < 100 > 4,000
D-dimer assay. If the D-dimer level is low (< 1,000 ng/mL),
aPTT = activated partial thromboplastin time; DIC = disseminated intravas-
DIC is unlikely; if it is very high (> 2,000 ng/mL) and there cular coagulopathy; INR = international normalized ratio.
is no other clear explanation (e.g., a complex pelvic fracture),
DIC is more likely than dilutional coagulapathy. Treatment
of dilutional coagulopathy should be directed at replacement
of lost factors. FFP should be given first, followed by cryo- (e.g., antithrombin and protein C) have been used. Despite
precipitate, calcium, and platelets. Transfusion should be improvements in laboratory measures with some of these
continued until the coagulation parameters are corrected and agents, they do not appear to improve survival. One interpre-
the bleeding stops. tation of the PROWESS trial27 that evaluated drotrecogin alfa
The term “DIC” refers to the phenomenon of diffuse, (recombinant activated protein C) as treatment for sepsis is
disorganized activation of the clotting cascade within the vas- that the observed improvement in survival resulted from con-
cular space. It does not occur as an isolated process; rather, tainment of intravascular coagulation. However, the mortality
it is always secondary to an underlying problem. It typically benefit in that study has not been replicated in other trials
results either from an overwhelming clotting stimulus (e.g., and may not apply to patients undergoing operations.
massive crush injury, overwhelming infection, or transfusion Currently, the most appropriate treatment of severe DIC is
reaction) or from a more moderate clotting stimulus in the removal of the clotting stimulus and aggressive transfusion to
context of shock. The underlying problem that manifests as restore blood loss and clotting factor deficits. The high mor-
DIC has a range of severity, with mild and moderate cases tality associated with severe DIC probably relates more to the
represented by anything from a subclinical process to the underlying pathology than to the hematologic derangement
development of organ dysfunction. One school of thought is per se.
that the systemic inflammatory response syndrome and DIC An increased INR with a prolonged aPTT may also be
are simply different manifestations of the same process. How- caused by various isolated factor deficiencies of the common
ever, severe cases are what surgeons traditionally think of as pathway. Congenital deficiencies of factors X and V and
DIC: bleeding in the context of fibrinolysis and consumption prothrombin are very rare. Acquired factor V deficiencies
of coagulation factors. Severe DIC arises when congestion of have been observed in patients with autoimmune disorders.
the microvasculature with thrombi occurs, resulting in large- Acquired hypoprothrombinemia has been documented in a
scale activation of the fibrinolytic system. This fibrinolytic small percentage of patients with lupus anticoagulants who
activity results in breakdown of clot at previously hemostatic exhibit abnormal bleeding. Factor X deficiencies have been
sites of microscopic injury (e.g., endothelial damage) and noted in patients with amyloidosis.
macroscopic injury (e.g., IV catheter sites, fractures, or Several anticoagulant medications can affect both the INR
surgical wounds), as well as degradation of fibrinogen sys- and the aPTT. Patients receiving large doses of unfractioned
temically. Bleeding and reexposure to tissue factor stimulate heparin may have a prolonged INR, depending on the spe-
activation of factor VII with increased coagulation activity; cific reagents used in the test, and the related oral anti-Xa
thus, microthrombi are formed, and the vicious circle inhibitors (e.g., rivaroxaban) may also prolong both the INR
continues. and the aPTT.28 The oral direct thrombin inhibitors typically
Beyond recognition and correction of the underlying prolong the aPTT but can also affect the INR. Stabilized
problem causing DIC and the associated coagulopathy, the warfarin therapy will increase both the INR and the aPTT.
diagnosis of DIC represents something of an academic exer- Several rodenticides in the vitamin K antagonist class with
cise because there is no specific treatment for the condition. warfarin (e.g., brodifacoum) exert the same effect; however,
Scoring systems that assess the severity of DIC are most because they have a considerably longer half-life than warfa-
useful for distinguishing DIC from other causes of coagu- rin, the reversal of the anticoagulation effect with vitamin K
lopathy (e.g., hypothermia, dilution, and drug effects) [see or FFP may be correspondingly longer.29 Animal venoms
Table 2]. Heparin, antifibrinolytic agents, and antithrombotics may also increase the INR and the aPTT.
Approach to the Patient with Anemia
Anemia is common among hospitalized surgical patients. In condition or to the operation, (2) serial blood draws (totaling,
large prospective cohort studies, the average hemoglobin level on average, approximately 40 mL/day in the ICU),30 and (3)
in surgical ICU patients was 11.0 g/dL,30 and 55% of surgical diminished erythropoiesis related to the primary illness.
ICU patients received transfusions.31 Anemia results from Treatment of anemia has evolved over the past few decades.
at least three factors: (1) blood loss related to the primary Cellular transfusions have long been a common, available
12/11
means to treat anemia in the perioperative and critical care benefit from a more liberal transfusion strategy. To date,
setting, but recognition in the 1980s that blood products relatively few such patients have been included in the
were transmitting fatal viral infections changed the risk- randomized trials on this topic.
benefit analysis. The blood-banking community in the United
States and most developed countries adapted and systema-
Acute Coronary Artery Ischemic Syndromes
tically reduced the risk of transmission of the most likely
infectious agents by restricting the eligible donor pool and Currently, there is no consensus regarding the most appro-
routinely testing blood products for serologic and nucleic acid priate transfusion strategy for patients with acute coronary
evidence of pathogens.32 Currently, the possibility that an artery ischemic syndromes, such as active myocardial infarc-
unpredictable new pathogen might emerge, such as a novel tion and unstable angina. The results of observational studies
or mutated virus, is thought to pose a greater risk to the safety have been mixed,35,36 and no clinical trial has yet addressed
of the blood supply than such recognized pathogens as HIV, this specific subgroup of patients. Some distinction should
hepatitis B virus (HBV), and hepatitis C virus (HCV). These be drawn between patients who have acute coronary artery
latter viruses are now so rarely transmitted in developed ischemic syndromes and those who merely have a history of
countries that the incidence of transfusion-related infection is coronary artery or other atherosclerotic disease. Although the
difficult to quantify. TRICC trial did not enrol patients admitted after a routine
Transfusion of allogeneic blood products has also been cardiac surgical procedure,34 it included enough patients with
associated with significant dysfunction of the immune system cardiovascular disease to allow a sizable subgroup analysis.37
and inflammatory processes. These immunomodulatory This post hoc analysis suggested that in patients with cardio-
effects are presumably much more frequent than rare cases of vascular disease as a primary diagnosis or an important
viral transmission, but it is not clear whether they are causally comorbid condition, survival was essentially the same regard-
related to poorer outcomes [see Discussion, Mechanism and less of whether a liberal transfusion protocol or a restrictive
Significance of Transfusion-Related Immunomodulation, one was followed. In patients with confirmed ischemic heart
disease, however, a nonsignificant decrease in survival was
below]. Furthermore, transfusion also may not augment
noted, generating some concern that adverse cardiovascular
oxygen delivery as assumed as a result of a variety of changes
events (e.g., myocardial infarction and stroke) might increase
that occur with red cell storage.
in frequency at lower hemoglobin levels. Consequently,
Moreover, randomized trials comparing a restrictive RBC
a target hemoglobin of 10 g/dL is generally considered
transfusion protocol (hemoglobin concentration maintained
acceptable for patients with acute coronary artery ischemic
at 7.0 to 9.0 g/dL) with a more liberal protocol (hemoglobin
syndromes or significant coronary artery disease.
maintained at 10.0 to 12.0 g/dL) for critically ill patients have
not demonstrated harm with the restrictive approach.33 In
fact, as suggested by the Transfusion Requirements in Criti- Neurologic Conditions
cal Care (TRICC) study, the restrictive approach may even Some have argued that just as the heart may be sensitive to
improve survival for younger or less severely ill patients.34 decreases in oxygen-carrying capacity, the injured central
Thus, for a variety of reasons, the conventional wisdom is nervous system may be vulnerable to further damage from
to try to limit blood transfusions when possible. The decision anemia because anemia may limit the delivery of oxygen to
whether to transfuse should be based on the patient’s current damaged tissue. According to this view, patients with
and predicted need for additional oxygen-carrying capacity traumatic brain injury, stroke, or spinal cord injury may be
[see Figure 1]. First, it is important to determine whether vulnerable to anemia-related damage; however, as yet, the
significant hypovolemia or active bleeding is present. In such clinical evidence—mostly from observational studies with
patients, liberal transfusion is indicated as a means of increas- significant methodological weaknesses—is insufficient either
ing intravascular volume and preventing the development of to support or to refute liberal transfusion of such patients.38
profound deficits in oxygen-carrying capacity [see Approach
to the Patient with Massive Hemorrhage, above].
In a hemodynamically stable but critically ill patient with- Symptomatic Anemia
out evidence of active hemorrhage, it is appropriate to take An additional consideration in the decision to transfuse
a more restrictive approach and administer transfusion only blood is the oxygen-carrying capacity that is necessary to
when the hemoglobin concentration is less than 7.0 g/dL prevent patient fatigue or discomfort. Typical symptoms of
(hematocrit 21%). Less acutely ill patients can even be anemia include lightheadedness, tachycardia, and tachypnea
followed for hemoglobin concentrations below 7.0 g/dL, either during activity or at rest. Clearly, some degree of tachy-
especially if they are asymptomatic and at minimal risk for cardia is to be expected in any patient who has undergone a
hemorrhage. In the absence of transfusion, iron supplementa- major operation or sustained a serious injury. The key judg-
tion should be considered, particularly for menstruating ment to make in deciding whether to treat symptomatic
women. There is no specific hemoglobin concentration or anemia with transfusion is whether the anemia is truly com-
hematocrit (i.e., transfusion trigger) at which all patients promising the patient’s health or recovery. It is not always
should receive transfusions. easy, however, to determine whether symptoms or signs
The above approach should apply to most patients, but attributed to anemia will actually improve as a result of trans-
there are two groups for whom a more aggressive RBC transfusion. For example, a liberal transfusion approach does not
fusion policy should be considered. Although opinion is appear to lead to earlier discontinuation of mechanical venti-
divided, patients who have acute coronary artery ischemic lation.39 A major randomized trial that is near completion, the
syndromes and those with acute neurologic conditions may Functional Outcomes in Cardiovascular Patients Undergoing
12/11
Patient is anemic
Assess whether bleeding is active
Patient is actively bleeding Patient is not actively bleeding

Transfuse without regard for the hematocrit if the Determine whether the patient is experiencing an
patient is unstable acute cardiac or central nervous system event
(e.g., myocardial infarction, stroke, traumatic
brain injury)
Monitor progress of resuscitation
Maintain a hematocrit of 30% until the situation
has been stabilized for at least 24 hours
Patient is experiencing an acute cardiac No acute cardiac or central nervous

or central nervous system event system event
Consider transfusing to a hematocrit of 30% Evaluate whether the patient is
(or remains) critically ill
The patient is critically ill The patient is not critically ill

Transfuse to maintain a hematocrit of 21% Consider transfusion if the patient
is symptomatic
Figure 1 Algorithm depicting the decision-making process for transfusion in anemic patients.
Surgical hip fracture repair (FOCUS) study, is addressing the used. First, steps should be taken to minimize additional
issue of functional recovery. Its primary aim is to determine iatrogenic blood loss. Laboratory tests should be restricted to
whether liberal transfusion improves walking ability among those that are most likely to benefit the patient and should be
anemic patients with a history of cardiovascular disease who conducted with the smallest amount of blood possible (e.g.,
undergo operative repair of a hip fracture.40 pediatric specimen tubes). Nonemergency operations that are
likely to involve appreciable blood loss should be postponed
if possible. Second, any impediments to native erythropoiesis
Observation of Anemia
should be removed: iron should be supplemented (orally if
Although it is now standard practice to observe patients possible), and the administration of recombinant erythropoi-
with hemoglobin concentrations of 6 to 7 g/dL, data suggest etin should be considered. Third, 100% oxygen should be
that the benefits of transfusion probably outweigh the risks administered because oxygen dissolved in plasma contributes
below this level. a significant proportion of oxygen delivery at very low
For all patients, if the hemoglobin level drops low enough, hemoglobin levels. Fourth, in extreme cases, consideration
cellular metabolism cannot be sustained and death becomes should be given to decreasing oxygen demand. Because the
a certainty. Followers of certain religious faiths who decline mechanical work of respiration itself becomes a significant
blood transfusion even when death is the probable or certain contributor to oxygen demand in severely anemic patients,
consequence have provided valuable observational data on mechanical ventilation and even neuromuscular blocking
the effects of severe anemia that would otherwise be unethical agents should be considered to reduce oxygen demand from
to obtain. Such cases have challenged surgeons and intensive skeletal muscle. The metabolic rate can be further reduced by
care physicians to find techniques for supporting life at inducing hypothermia.
extremely low hemoglobin concentrations and have helped For decades, efforts have been in progress to augment
define the limits beyond which anemia may be fatal. Reviews oxygen-carrying capacity using RBC substitutes. Various dif-
of patients who have refused transfusion suggest that a ferent substitutes have been evaluated, some of which remain
hemoglobin below 5 g/dL results in substantial increases under investigation. None have been approved for routine
in mortality, especially in elderly persons and patients with use by the US Food and Drug Administration (FDA), largely
cardiovascular disease.41 because of significant adverse effects. The main categories of
When RBC transfusion is not possible (whether because substitutes are those based on hemoglobin and those based
the patient declines transfusion or because compatible blood on perfluorocarbons. Unmodified, acellular hemoglobin is
is unavailable), a number of temporizing measures can be nephrotoxic, so hemoglobin-based blood substitutes involve
12/11
either attempts to modify the hemoglobin molecule or encap- production and storage as well as adverse effects with their
sulate hemoglobin within synthetic membranes. Even with use.44 Thus, although blood substitutes promise a number of
such modifications, however, these substitutes appear to advantages (increased shelf life, availability that is not limited
increase the risk of death and myocardial infarction.42,43 Per- by donor supply, and reduced or eliminated risk of incompat-
fluorocarbon-based substitutes have attempted to take advan- ibility reactions and pathogen transmission), the extent to
tage of the high solubility of oxygen in these liquids, but their which they will ever be a suitable treatment for anemia in
development has been impeded by practical hurdles in their surgical patients is unclear.
Discussion
Mechanics of Hemostasis the Weibel-Palade bodies of endothelial cells causes platelets

to adhere to their surface. The presence of interleukin-1b
Hemostasis is the term for the process by which cellular
(IL-1b), tissue necrosis factor (TNF), interferon gamma, and
and plasma components interact in response to vessel injury
thrombin also promotes expression of TF on the endothe-
to maintain vascular integrity and promote wound healing.
lium.46,47 TF activates factors X and VII, and these activated
The initial response to vascular injury (primary hemostasis)
factors generate additional thrombin, which increases both
involves the recruitment and activation of platelets, which
fibrin formation and platelet aggregation.
then adhere to the site of injury. Subsequently, plasma pro-
The endothelium also acts in numerous ways to downregu-
teins, in concert with cellular components, begin to generate
late coagulation.48 Heparan sulfate and thrombomodulin are
thrombin, which causes further activation of platelets and
both downregulators of thrombin formation. In the presence
converts fibrinogen to fibrin monomers that polymerize into
of thrombin, the endothelium responds by expressing or
a fibrin clot (secondary hemostasis). The final step is the
releasing (1) membrane-bound thrombomodulin, which
release of plasminogen activators that induce clot lysis and
forms a complex with thrombin to activate protein C; (2)
tissue repair.
endothelium-derived relaxing factor (i.e., nitric oxide49) and
The cellular components of hemostasis include endothe-
prostacyclin, which have vasodilating and platelet aggregation-
lium, subendothelial cells and substrate, white blood cells
inhibiting effects, respectively; and (3) tissue plasminogen
(WBCs), RBCs, and platelets. The plasma components
activator (t-PA) or urokinase-type plasminogen activator
include a number of pro- and anticoagulant proteins that,
(u-PA), either of which converts the zymogen plasminogen
once activated, can accelerate or downregulate thrombin
to its active form, plasmin, that degrades fibrin and fibrino-
formation or clot lysis to facilitate wound healing. In normal
gen.47,50 Heparan sulfate, on the endothelium wall, forms
individuals, these hemostatic components are in a regulatory
a complex with plasma antithrombin to neutralize thrombin.
balance; thus, any abnormality involving one or more of
The endothelium is also the source of tissue factor pathway
these components can result in a pathologic state, whether
inhibitor (TFPI), which downregulates TF-VIIa-Xa
of uncontrolled clot formation (thrombosis) or of excessive
complexes.
bleeding (hemorrhage). These pathologies can result from
either hereditary or acquired causes. Erythrocytes and Leukocytes
cellular components The nonplatelet cellular components of blood play indirect
roles in hemostasis. RBCs contain thromboplastins that are
Endothelium and Subendothelial Tissue potent stimulators of various procoagulant proteins. In addi-
The endothelium has both procoagulant and anticoagulant tion, in the setting of laminar flow, a sufficient concentration
properties. At baseline, in its normal, undamaged state, the of RBCs within the bloodstream (i.e., the hematocrit) assists
endothelial surface is covered with endogenous antithrombins in primary hemostasis by physically forcing the platelets
(antithrombin III, heparan sulfate, dermatan sulfate, and toward the endothelial surfaces. When the RBC count is low
others) that protect against pathologic coagulation, thus pro- enough, there is a reduction in this force, which results in
viding a barrier between prothrombotic factors in the plasma inadequate endothelium-platelet interaction and subsequently
and thrombogenic subendothelial factors. However, when a bleeding diathesis.
vascular injury occurs, the endothelium and subendothelial Leukocytes have several functions in the hemostatic
tissues serve as a nidus for recruitment, adhesion, and aggre- process. The interaction between the adhesion molecules
gation of platelets. Disruption of the endothelium exposes expressed on both leukocytes and endothelium results in
collagen fibrils, to which platelets adhere, and tissue factor cytokine production, initiation of inflammatory responses,
(TF), which serves as an integral, potent clotting stimulus [see and degradation of extracellular matrix to facilitate tissue
Procoagulants, below]. TF is pervasive on the cell surfaces healing. In the presence of thrombin and other stimuli, mono-
of subendothelial tissue and especially concentrated on such cytes express TF, potentiating coagulation. Neutrophils and
tissue as vascular adventitia, cerebral cortex, lung paren- activated monocytes bind to stimulated platelets and endo-
chyma, visceral organ capsules, and epidermis.45 Damaged or thelial cells that express P-selectin. Adhesion and rolling of
activated endothelial cells express adhesion molecule recep- neutrophils, mediated by fibrinogen and selectins on the
tors (E-selectin and P-selectin), and release of vWF from endothelium, appear to help restore vessel integrity but may
12/11
also lead to inflammatory responses.51,52 Lymphocytes also pathways but rather on the different roles contact factors
adhere to endothelium via adhesion molecule receptors (part of the intrinsic cascade) and TF play in coagulation.
and appear to be responsible for cytokine production and The main role of the contact factors (factor XII, prekalli-
inflammatory responses. krein, and high-molecular-weight kininogen) appears to be in
downregulation of coagulation rather than the generation of
Platelets thrombin. Even in patients completely lacking these factors,
Platelets facilitate hemostasis and subsequent fibrin who have a markedly prolonged aPTT, abnormal bleeding
formation both by generating the initial platelet plug and by does not occur. However, the contact factors activate the
providing a phospholipid surface on which the activation bradykinin (BK) pathway, which exerts profibrinolytic effects
of coagulation factors is localized. Activation of platelets by by stimulating endothelial release of plasminogen activators.
agonists such as adenosine triphosphate (ATP), ADP, epi- It also stimulates endothelial production of nitric oxide and
nephrine, thromboxane A2, collagen, and thrombin causes prostacyclin, which play vital regulatory roles in vasodilation
platelets to undergo morphologic changes and degranulation. and regulation of platelet activation.55
Degranulation releases procoagulants (e.g., thrombospondin, The key initiator of plasma procoagulant formation is the
vWF, fibrinogen, ADP, ATP, and serotonin) that promote expression of TF on cell surfaces.46,56 TF activates factor VII
further platelet adhesion and aggregation and surface and binds with it to form the TF-VIIa complex, which acti-
expression of P-selectin, which induces cellular adhesion. vates factors X and IX. Factor Xa enhances its own produc-
Platelet degranulation also results in the release of b- tion by activating factor IX, which in turn converts more
thromboglobulin, platelet factor 4 (which has antiheparin factor X to Xa. Factor Xa also produces minimal amounts
properties), various growth factors, and calcium, as well as of thrombin by cleaving the prothrombin molecule. The
the formation of platelet microparticles. Plasminogen activa- thrombin generated from this process cleaves the coagulation
tor inhibitor–1 (PAI-1) released from degranulated platelets cofactors V and VIII to enhance production of the
neutralizes the fibrinolytic pathway by forming a complex factor complexes IX-VIIIa (intrinsic tenase) and Xa-Va
with t-PA. (prothrombinase), which dramatically catalyzes conversion of
On exposure to vascular injury, platelets adhere to the prothrombin to thrombin [see Figure 2].57
exposed endothelium via binding of vWF to the GPIb-IX-V Thrombin has numerous effects, including pro- and
complex.53 Conformational changes in the GPIIb-IIIa com- antithrombotic functions. Its procoagulant properties include
plex on the activated platelet surface enhance fibrinogen cleaving fibrinogen, activating the coagulation cofactors V
binding, which results in platelet-to-platelet aggregation and VIII, inducing platelet aggregation, inducing expression
and complex morphologic changes. The end result of these of TF on cell surfaces, and activating factor XIII. In cleaving
changes is a platelet plug with such dense adherence of fibrinogen, thrombin causes the release of fibrinopeptides A
platelets and such dramatic changes in platelet shape that, on and B (fibrin monomer). The fibrin monomer undergoes
electron microscopy, each platelet resembles a piece within a conformational changes that expose the a and b chains of the
three-dimensional jigsaw puzzle. The phospholipid surface of molecule, which then polymerize with other fibrin monomers
the membranes of activated platelets then anchors activated to form a fibrin mesh. Activated factor XIII cross-links the
IXa-VIIIa and Xa-Va complexes, thereby localizing thrombin polymerized fibrin (between the a chains and the c chains) to
generation.54 stabilize the fibrin clot and delay fibrinolysis.
plasma components
Fibrin(ogen)olysis
Procoagulants Plasminogen is the primary fibrinolytic zymogen that circu-
In primary hemostasis, circulating plasma vWF—in addi- lates in plasma. In the presence of t-PA or u-PA (released
tion to the vWF secreted by endothelial cells in response to from the endothelium), plasminogen is converted to the
injury—facilitates adhesion of platelets to the endothelium. active form, plasmin. Plasmin cleaves fibrin (or fibrinogen)
Plasma vWF also serves as the carrier protein for factor VIII, between the molecule’s D and E domains, causing the for-
preventing its neutralization by the protein C regulatory mation of X, Y, D, and E fragments from fibrinogen degrada-
pathway. tion, and D-dimers from polymerized fibrin degradation.
Secondary hemostasis involves numerous plasma compo- The secondary function of the fibrinolytic pathway is the acti-
nents. Traditional diagrams of the coagulation cascade depict vation by u-PA of matrix metalloproteinases that degrade the
two distinct pathways, the intrinsic and extrinsic pathways, extracellular matrix.58
that join in a final common pathway. The historical reason
Endogenous Antithrombotic Factors
for depicting the coagulation cascade this way is to emphasize
differences between the aPTT test (which is prolonged in the In persons with normal coagulation status, downregulation
absence of sufficient quantities of components in the intrinsic of hemostasis occurs simultaneously with the production of
pathway: factor XII, prekallikrein, and high-molecular-weight procoagulants (e.g., activated plasma factors, stimulated
kininogen) and the INR (which measures clotting time in endothelium, and stimulated platelets). In addition to their
response to the extrinsic stimulus, TF). In vivo, however, the procoagulant activity, both thrombin and contact factors
primary stimulus for secondary hemostasis is the exposure of stimulate downregulation of the coagulation process. Throm-
TF (i.e., the extrinsic pathway), and the thrombin generated bin forms a complex with endothelium-bound thrombomod-
from this process activates factor VIII, effectively bypassing ulin to activate protein C, which inhibits factors Va and VIIIa.
the initial steps in the intrinsic pathway. Accordingly, our The thrombin-thrombomodulin complex also regulates the
focus is not on the standard view of intrinsic and extrinsic fibrinolytic pathway by activating a circulating plasma protein
12/11
VII VIII
Platelet TF
Aggregation VIIIa
IXa
XIIIa V
VIII IXa AT
AT
TF-VIIa Va aPC
AT Xa
V
XIII TFPI Thrombomodulin
VIIIa PS
IX X
PC
Thrombin Thrombin
IXa Xa
Xa
Va Va
Fibrinogen II AT
II
Platelet
Fibrin Fibrin TAT

Polymer Monomer
Figure 2 Schematic representation of the procoagulant pathways. aPC = activated protein C; AT = antithrombin;
PC = protein C; PS = protein S; TAT = thrombin-antithrombin; TF = tissue factor; TFPI = tissue factor pathway inhibitor.
known as thrombin-activatable fibrinolysis inhibitor (TAFI), increased risk of bleeding as a consequence of dysfunctional
which appears to suppress conversion of plasminogen to plas- fibrinolysis, concomitant platelet dysfunction, or coagulation
min.59 Contact factors are known to be required for normal factor deficiencies.65
surface-dependent fibrinolysis, and there is some evidence Abnormalities of RBCs and WBCs may promote thrombo-
that contact factor deficiencies can lead to thromboembo- sis (e.g., decreased blood flow from polycythemia vera,
lism. Another plasma protein responsible for regulation of leukocytosis, and sickle cell anemia) but usually do not
fibrinolysis is a2-antiplasmin, which binds to circulating and cause major bleeding unless there is an associated severe
bound plasmin to limit breakdown of fibrin. thrombocytopenia.
Circulating downregulating proteins include antithrombin The most common heritable disease associated with bleed-
(a serine protease inhibitor of activated factors—especially ing is vWD, with some countries having a prevalence as high
factors IXa, Xa, and XIa—and thrombin45), proteins C and as 1 to 2%. This condition is characterized by a variety of
S (regulators of factors VIIIa and Va60), C1 inhibitor (a qualitative and quantitative abnormalities of vWF. There are
regulator of factor XIa), TFPI (a regulator of the TF-VIIa-Xa three main categories of vWD [see Table 3]: reduced concen-
complex61), and a2-macroglobulin (a thrombin inhibitor—the tration of normal vWF (type 1), dysfunctional vWF (type 2),
primary thrombin inhibitor in neonates62). Limitation of and the absence of vWF altogether (type 3). Type 2 vWD is
platelet activation occurs secondarily as a result of decreased classified into four subtypes (A, B, M, and N) based on the
levels of circulating agonists and endothelial release of nature of the dysfunction. Type 1 is most common, account-
prostacyclin [see Figure 2]. ing for 70 to 80% of cases of vWD, and varies in severity,
with most affected individuals manifesting only a mild bleed-
ing tendency. Diagnosis of vWD is based on a combination
Bleeding Disorders of the patient history and laboratory parameters. Patients
with vWD typically experience bleeding from the mucous
inherited coagulopathies
membranes. Because the most prevalent forms of vWD are
Numerous congenital abnormalities of the coagulation inherited in an autosomal dominant fashion, careful ques-
system have been identified. These include abnormalities of tioning typically reveals affected relatives. Laboratory tests to
plasma proteins (e.g., hemophilia and vWD), platelet recep- confirm the diagnosis and determine the subtype of vWD
tors (e.g., Glanzmann thrombasthenia and Bernard-Soulier include vWF antigen tests, functional assays (e.g., the risto-
syndrome), and endothelium (e.g., telangiectasia). Abnor- cetin cofactor assay), vWF multimer assays, ristocetin-induced
malities can involve abnormal protein synthesis resulting in a platelet aggregation assays, platelet count, and factor VIII
dysfunctional coagulation protein (a “defect”) or decreased levels. The ratio of activity:antigen (ristocetin cofactor assay
protein production (a “deficiency”). result relative to vWF antigen level) is typically approximately
Most of the coagulation defects associated with the endo- 1 for vWF type 1 vWD and less than 0.6 for type 2 vWD.
thelium are closely related to thrombosis or atherosclerosis. Appropriate treatment depends on which type of vWD the
Defects or deficiencies of thrombomodulin, TFPI, and t-PA, patient has. Desmopressin is typically sufficient prophylaxis
albeit rare, are associated with thrombosis.63,64 Vascular or treatment for patients with type I vWD but is not always
defects (e.g., hemorrhagic telangiectasias) may carry an effective, and tachyphylaxis can occur. vWF/factor VIII
12/11
Table 3 Classification and Management of von Willebrand Disease

Proportion
Type of von among All
Willebrand Cases of
Disease Pathology vWD Diagnostic Evaluation Primary Treatment
1 Deficiency in the amount of vWF 70–80% Decreased vWF Ag and vWF RCo Desmopressin
produced (vWF/factor VIII
concentrate if
unresponsive to
desmopressin)
2A Failure of mutant vWF to form 10% Normal or decreased vWF Ag; vWF RCo vWF/factor VIII
appropriate multimers or substantially decreased; vWF MM with concentrate
increased proteolysis of mutant high- and high/medium-molecular-
vWF weight forms absent
2B Increased binding of mutant vWF 5% Similar to type 2A, but thrombocytopenia, vWF/factor VIII
to platelet glycoprotein Ib increased RIPA (even with low dose of concentrate, platelet
receptor, resulting in decreased ristocetin), and increased vWF binding transfusion
circulating vWF to normal platelets
2M Abnormal vWF binding site for Rare Normal or decreased vWF Ag; vWF RCo vWF/factor VIII
platelet glycoprotein Ib substantially decreased; vWF MM concentrate
receptor, leading to decreased normal and decreased vWF binding to
affinity between vWF and normal platelets
platelets
2N Abnormal vWF binding site for Rare Normal vWF Ag, vWF RCo, and vWF vWF/factor VIII
factor VIII, leading to MM; decreased factor VIII level and concentrate
decreased circulating factor factor VIII binding to vWF
VIII levels
3 Complete absence of vWF Very rare Absent vWF Ag, vWF RCo, and vWF vWF/factor VIII
MM concentrate
Platelet type Increased binding of vWF to Rare Similar to type 2B except that, as with Platelet transfusion
mutant platelet glycoprotein Ib normal individuals, vWF does not bind
receptor, resulting in decreased to normal platelets
circulating vWF
RIPA = ristocetin-induced platelet aggregation (not the same as vWF RCo); vWF = von Willebrand factor; vWF Ag = von Willebrand factor antigen test; vWF
MM = von Willebrand factor multimer analysis; vWF Rco = von Willebrand factor ristocetin cofactor assay.
concentrate is necessary for patients with type 1 who are not of factor V, factor VII, factor X, prothrombin, and fibrinogen
responsive to desmopressin and for patients with types 2 may become apparent in the neonatal period (presenting, for
and 3 who undergo operations or experience major bleeding. example, as umbilical stump bleeding); later in life, they
Desmopressin may be contraindicated for patients with type result in clinical presentations such as epistaxis, intracranial
2B vWD because it can exacerbate the thrombocytopenia bleeding, GI bleeding, deep and superficial bruising, and
that they typically experience.66 menorrhagia.
There are rare inherited defects of the platelet surface, Defects or deficiencies in the fibrinolytic pathway are
including Glanzmann thrombasthenia (a defect in the GPIIb- also rare and are most commonly associated with thrombo-
IIIa complex), Bernard-Soulier syndrome (a defect in the embolic events. a2-Antiplasmin deficiencies and primary
GPIb-IX complex), and Scott syndrome (a defect in the fibrin(ogen)olysis are rare congenital coagulopathies with
platelet’s activated surface that promotes thrombin forma- clinical presentations similar to those of factor deficiencies. In
tion).67 Intracellular platelet defects (storage pool diseases) primary fibrin(ogen)olysis, failure of regulation of t-PA and
are also rare but do occur; examples are gray platelet syn- u-PA leads to increases in circulating plasmin levels, which
dromes (e.g., alpha granule defects), Hermansky-Pudlak result in rapid degradation of clot and fibrinogen.68,69
syndrome, dense granule defects, Wiskott-Aldrich syndrome,
acquired coagulopathies
and various defects in intracellular production and
signaling (involving defects of cyclooxygenase synthase and A wide range of clinical conditions may cause deficiencies
phospholipase C, respectively). of the primary, secondary, or fibrinolytic pathways. Acquired
Numerous pathologic states are also associated with coagulopathies are very common, but most do not result in
deficiencies or defects of plasma procoagulants. Hemophilias spontaneous bleeding.
A, B, and C were previously discussed [see Interpretation of As noted, coagulopathies related to the endothelium are
Coagulation Parameters, Normal INR, Prolonged aPTT, primarily associated with thrombosis rather than bleeding.
above]. Inherited deficiencies of the other coagulation factors A number of disorders may cause vascular injury, including
are very rare. Factor XIII deficiencies result in delayed post- sickle cell anemia, hemolytic-uremic syndrome, and throm-
operative or posttraumatic bleeding. Congenital deficiencies botic thrombocytopenic purpura.
12/11
Acquired platelet abnormalities, both qualitative (i.e., IX, factor X, prothrombin, and proteins C and S. Newer
dysfunction) and quantitative (i.e., decreases in absolute drugs that may also cause factor deficiencies include direct
numbers), are common occurrences. Many acquired throm- thrombin inhibitors (e.g., lepirudin and bivalirudin74) and
bocytopathies are attributable to medications (e.g., aspirin, fibrinogen-degrading drugs (e.g., ancrod75).
ibuprofen, other nonsteroidal antiinflammatory drugs, vari- Isolated acquired factor deficiencies are relatively rare.
ous antibiotics, certain antihistamines, and phenytoin). Newer Clinically, they present in exactly the same way as inherited
classes of antiplatelet drugs function by inhibiting platelet factor deficiencies, except that there is no history of earlier
receptors [see Interpretation of Coagulation Parameters, bleeding. In some cases, there is a secondary disease (e.g.,
Normal INR, Normal aPTT, above].70 Thrombocytopenia lymphoma or an autoimmune disorder) that results in the
can be primary or secondary to a number of clinical con- development of antibody to a procoagulant (e.g., factor V,
ditions. Primary bone disorders (e.g., myelodysplastic or factor VIII, factor IX, vWF, prothrombin, or fibrinogen).
myelophthisic syndromes) and spontaneous bleeding may
arise when platelet counts fall below 10,000/µL. Disseminated Intravascular Coagulation
Thrombocytopenia can be associated with immune causes DIC is a complex coagulation process that involves massive
(e.g., immune thrombocytopenic purpura and heparin- activation of the coagulation system with deposition of fibrin
induced thrombocytopenia) or such conditions as a deficiency in the microvasculature that causes the subsequent activation
in the plasma metalloproteinase ADAMTS13 (a disintegrin of the fibrinolytic pathway. The overwhelming microvascular
and metalloproteinase with a thrombospondin type 1 motif, fibrin deposition is the cause of both the activation of the
member 13) (thrombotic thrombocytopenic purpura). fibrinolytic system (which promotoes more bleeding) and
Acquired platelet dysfunction (e.g., acquired vWD) that is eventually multiple organ dysfunction syndrome (MODS).
not related to dietary or pharmacologic causes has been The activation occurs at all levels, including platelets, endo-
observed in patients with immune disorders or cancer. thelium, and pro- and anticoagulants. It is crucial to empha-
Multifactorial coagulopathies are common as well. Patients size that DIC is an acquired disorder that occurs secondary
with severe renal disease typically exhibit platelet dysfunction to an underlying clinical event (e.g., child birth complicated
(from excessive amounts of uremic metabolites), factor by amniotic fluid embolism, severe gram-negative infection,
deficiencies associated with impaired protein synthesis and shock, severe traumatic brain injury, polytrauma, severe
protein loss (as with increased urinary excretion), or throm- burns, or cancer). As noted [see Interpretation of Coagulation
bocytopenia (from diminished thrombopoietin produc- Parameters, Increased INR, Prolonged aPTT, above], there
tion).71,72 Patients with severe hepatic disease commonly
is some controversy regarding the best approach to therapy,
have impairment of coagulation factor synthesis, increases in
but there is no doubt that treating the underlying cause of
circulating levels of paraproteins, and splenic sequestration of
DIC is paramount to patient recovery.
platelets.
DIC is not always clinically evident: low-grade DIC may
Massive cellular transfusion can dilute the levels of clotting
lack clinical symptoms altogether and manifest itself only
factors if more than 10 packed RBC units are given within a
through laboratory abnormalities, even when thrombin gen-
short period without plasma supplementation. In addition,
eration and fibrin deposition are occurring. In an attempt to
because RBC units contain citrate as an anticoagulant, mas-
facilitate recognition of DIC, the disorder has been divided
sive transfusion can induce a coagulopathy from hypocalce-
into three phases, distinguished on the basis of clinical and
mia. Immunologic reactions to ABO/Rh mismatches can
induce immune-mediated hypercoagulation. Acquired multi- laboratory evidence. In phase I DIC, there are no clinical
factorial deficiencies associated with extracorporeal circuits symptoms, and the routine screening tests (i.e., INR, aPTT,
(e.g., cardiopulmonary bypass, hemodialysis, and continuous fibrinogen level, and platelet count) are within normal limits.76
venovenous dialysis) can arise as a consequence of hemodilu- Secondary testing (i.e., measurement of antithrombin, pro-
tion from circuit priming fluid or activation of procoagulants thrombin fragment, thrombin-antithrombin complex, and
after exposure to thrombogenic surfaces. Thrombocytopenia soluble fibrin levels) may reveal subtle changes indicative of
can result from platelet destruction and activation caused thrombin generation. In phase II DIC, there are usually clin-
by circuit membrane exposure or can be secondary to the ical signs of bleeding around wounds, suture sites, IV sites,
presence of heparin antibody. or venous puncture sites, and decreased function is noted in
Animal venoms can be either pro- or antithrombotic. The specific organs (e.g., lung, liver, and kidneys). The INR is
majority of the poisonous snakes in the United States (rattle- increased, the aPTT is prolonged, and the fibrinogen level
snakes in particular) have venom that works by activating and platelet count are decreased. Other markers of thrombin
prothrombin, but cross-breeding has produced a number generation and fibrinolysis (e.g., D-dimer level) show sizable
of new venoms with different hemostatic consequences. The elevations. In phase III DIC, MODS is observed, the INR
clinical presentation of coagulopathies associated with snake- and the aPTT are markedly increased, the fibrinogen level is
bites generally mimics that of consumptive coagulopathies.73 markedly depressed, and the D-dimer level is dramatically
Drug-induced factor deficiencies are common, particularly increased. A peripheral blood smear shows large numbers
as a result of anticoagulant therapy. The most commonly of schistocytes, indicating RBC shearing from fibrin
used anticoagulants are heparin and warfarin. Heparin does deposition.
not cause a factor deficiency; rather, it accelerates production The activation of the coagulation system seen in DIC
of antithrombin, which inhibits factor IXa, factor Xa, and appears to be primarily caused by TF. The brain, the
thrombin, thereby prolonging clot formation. Warfarin placenta, and solid tumors are all rich sources of TF. Gram-
reduces procoagulant potential by inhibiting vitamin K syn- negative endotoxins also induce TF expression. The exposure
thesis, thereby reducing carboxylation of factor VII, factor of TF on cellular surfaces causes activation of factors VII and
12/11
IX, which ultimately leads to thrombin generation. Circulat-

Measurement of coagulation parameters
ing thrombin is rapidly cleared by antithrombin. Moreover,
the coagulation pathway is downregulated by activated Determine INR and aPTT.
protein C and protein S. However, constant exposure of TF
(as a result of underlying disorders) results in constant gen-
eration of thrombin, and these regulator proteins are rapidly
consumed. TAFI and PAI also contribute to fibrin deposition
INR is normal INR is increased
by restricting fibrinolysis and subsequent fibrin degradation
and clearance. Finally, it is likely that release of cytokines
(e.g., IL-6, IL-10, and TNF) may play some role in
causing the sequelae of DIC by modulating or activating the aPTT is aPTT is aPTT is aPTT is
coagulation pathway. normal prolonged normal prolonged
Determine Consider vWD, Consider Consider
Laboratory Assessment of Bleeding fibrinogen hemophilia, liver disease, multiple factor
level. factor deficiency effects of deficiencies,
Patients with massive or life-threatening hemorrhage should with or without drugs, and DIC, and
be treated presumptively and without a delay to obtain the inhibitor, and factor VII effects of
results of laboratory tests [see Approach to the Patient with effects of drugs. deficiency. drugs.
Massive Hemorrhage, above]. However, these tests serve an
integral role in the diagnostic algorithm for patients with
more modest bleeding. If the patient is not experiencing Fibrinogen level Fibrinogen level is abnormal
massive or life-threatening hemorrhage, blood samples for is normal
coagulation testing should be drawn before administering Measure levels of fibrin
Determine factor degradation products (FDPs).
blood products or medication intended to promote coagula-
XIII level.
tion. The CBC (including platelet count and differential
count), the INR, and the aPTT tests should be the primary
laboratory tests for differentiating coagulopathies [see FDP level is
FDP level is normal
Figure 3]. Technological advances have made it possible to abnormal
perform these and other diagnostic laboratory tests outside Consider hypofibrinogenemia
the confines of the clinical laboratory (“near-care” or “point- and dysfibrinogenemia. Consider state
of-care” testing). Whatever tests of coagulation are employed, of abnormal
it is important to recognize their limitations. fibrin(ogen)olysis.
Several technical factors can influence the results of the
INR and aPTT. These tests involve adding activators, Factor XIII level is normal Factor XIII level
phospholipids, and calcium to plasma in a test tube (or the is abnormal
Coagulation factor deficiency
equivalent) and determining the time to clot formation. Time
is unlikely. Patient has factor
to clot formation is a relative value in that it is compared with Consider causes associated XIII deficiency.
the time in a normal population, and each laboratory must with platelets or vasculature.
periodically adjust the reference range accordingly. Poor
sampling techniques (e.g., hemolysis, inadequately filled Figure 3 Algorithm depicting the use of coagulation
coagulation tubes, excessive tourniquet time, and clotted or parameters in assessment of coagulopathies. aPTT =
activated samples) can influence the results. Hemolysis from activated partial thromboplastin time; DIC = disseminated
poor phlebotomy technique can release thromboplastins from intravascular coagulation; INR = international normalized
RBC membranes that initiate the coagulation process. An ratio; vWD = von Willebrand disease.
elevated hematocrit or inadequately filled specimen tube can
prolong test results because the excess citrate chelates the
calcium added in the assay. Hemolysis, jaundice, and lipemia do not detect low fibrinogen levels. In this chapter, we have
can all interfere with the optical systems that modern instru- assumed that the methods used with the INR and aPTT tests
ments use to detect clot. In addition, factor VIII in particular result in abnormalities when factor activity levels fall below
is relatively labile, so failure to process and run coagulation 0.4 IU/mL.
samples expeditiously can prolong the aPTT. Assessment of platelets also involves certain pitfalls.
Not all coagulation tests are functionally equivalent: differ- Platelet count and platelet function should be considered as
ent laboratory methods may yield differing results.77 For most completely independent metrics [see Figure 4]. Patients with
laboratories, coagulation reagents have been selected in such congenital thrombocytopathies often have normal platelet
a way as to ensure that the tests are sensitive to factor counts; therefore, assessment of platelet function is required
VIII and IX deficiencies (i.e., diagnosis and monitoring of as well. Historically, the bleeding time has been used to assess
hemophilia) and the effects of warfarin and heparin. As a platelet function. However, this test is grossly insensitive,
consequence, a normal aPTT in a patient with an abnormal yielding normal results in as many as 50% of patients with
INR may not exclude the possibility of common pathway congenital thrombocytopathies.78,79 Numerous rapid tests of
deficiencies (e.g., deficiencies of factors X, V, and II), and platelet function are currently available that can be used to
most current methods of determining the INR and the aPTT screen for platelet defects; although the accuracy and clinical
12/11
Assessment of platelet status Table 4 Tests of Platelet Function

Product
Platelet count and platelet function should (Manufacturer) Method
be considered as independent variables.
PFA-100 (Dade Measures time required to occlude
Behring) aperture after exposure to platelet
agonists (collagen/epinephrine and
collagen/ADP) at shear rates
Platelet count is normal Platelet count is abnormal
hemoSTATUS Measures modified activated clotting
Assess platelet function. Assess platelet function. (Medtronic) time with platelet-activating factor
as the platelet agonist
Whole Blood Measures changes in impedance
Aggregometers after addition of platelet agonist(s)
Platelet Platelet Platelet Platelet (Chronolog
function is function is function is function Corporation)
normal abnormal normal is abnormal
Ultegra Analyzer Used primarily for measuring the
Platelet-related Determine Consider Consider (Accumetrics) effect of platelet glycoprotein
cause is whether hemodilution Bernard- blockers (e.g., abciximab and
unlikely. patient has and immune Soulier eptifibatide), aspirin, or P2Y12
Consider a history causes. syndrome. inhibitors
vascular of bleeding.
causes and Platelet Works (Helena Compares platelet counts before and
plasma Laboratories) after addition of agonists (collagen
factor deficits. and ADP)
Impact Cone and Measures platelet aggregates after
Plate(let) Analyzer exposure of whole blood to shear
(Diamed) forces in a spinning cone
Patient has a Patient has no
history of bleeding history of bleeding Multiplate function Measures changes in impedance after
analyzer (Verum addition of platelet agonist with
Consider vWD Consider liver disease, Diagnostica GmbH) four-channel impedance technol-
and Glanzmann uremia, MDS, and ogy
thrombasthenia. effects of drugs. Thromboelastometry TEG analyzer with platelet mapping
protocol, CSA and ROTEM with
Figure 4 Algorithm depicting the use of platelet count and platelet function assessment [see
platelet functional status in assessment of coagulopathies. Laboratory Assessment of
Bleeding, above]
MDS = myelodysplastic syndrome; vWD = von Willebrand
disease. ADP = adenosine diphosphate.
utility of these tests have not been thoroughly evaluated, they

can be considered in the diagnostic approach to the bleeding
patient [see Table 4]. better directed therapy. The trauma surgery community in
The role of point-of-care testing appears to be expanding. particular has generated enthusiasm for thromboelastography
The activated clotting time (ACT) has been used in the set- to allow real-time monitoring of coagulopathic acutely injured
ting of cardiopulmonary bypass to monitor anticoagulation patients. The main strength of the test may be to identify
when such high levels of unfractionated heparin are used hyperfibrinolysis in a more timely fashion than traditional
that no clotting would occur with the aPTT. A newer class laboratory methods do, assisting clinicians in selecting patients
of tests, commonly referred to as thromboelastography, for antifibrinolytic therapy (e.g., e-aminocaproic acid).
measure viscoelastic changes in whole blood as it clots. In this At present, there are no laboratory or ex vivo methods
technique, a pin is suspended from a torsion wire into a cup capable of directly measuring the physiologic properties of
containing blood. The cup rotates periodically, and, as clot the endothelium. Indirect assessments of endothelial damage
forms and later lyses over time, the device detects changes in can be obtained by measuring levels of several laboratory
torque transmitted to the immersed pin. The most commonly parameters (e.g., vWF, the soluble cytokines endothelin-1
reported device is the thromboelastograph (TEG, Haemo- and E-selectin, and thrombomodulin), but such measure-
scope Corporation, Niles, IL), but other devices using related ments have no clinical utility in the assessment of a bleeding
methods include the rotational thromboelastogram (ROTEM, patient.
TEM International GmbH, Munich, DE) and the Sonoclot
(Sienco Inc, Arvada, CO). The TEG and ROTEM report
similar parameters [see Figure 5], but the values are not Mechanism and Significance of Transfusion-Related
directly comparable. Modifications of the basic sample cup Immunomodulation
allow users to isolate specific abnormalities. Although certain Although a unit of packed RBCs is an exceedingly complex
patterns may reflect specific abnormalities, software applica- biologic substance, blood is used frequently and somewhat
tions have made graphs easier to interpret. Although these casually, compared with many pharmaceutical agents that
methods lack specificity and clinical outcome studies are not have undergone extensive regulatory review. A unit of alloge-
yet available, graphically depicted abnormalities may lead to neic transfused blood contains antigenic RBCs, WBCs, and
12/11
(correlated with clot strength)

Instrument signal (mm) c
C
D E Normal
0
A B
20 mm
Coagulopathy/anticoagulants
Long R time
Clot Formation Clot Lysis
0 10 20 30 40 50 60 Reduced platelet function

Low MA
Time (minutes
b
Parameter Nomenclature Process Primary fibrinolysis
TEG ROTEM High LY30
CT (clotting time): Initiation of thrombin
r: time to start time to start of generation and start
A of clotting clotting of clot polymerization
k: time from CFT (clot

start of clotting formation time): Hypercoagulable
B time from start Rate of clot
to amplitude formation, fibrin Short R time, High MA
of 20 mm of clotting to
amplitude to 20 mm polymerization and
crosslinking with
αo: slope between platelet interaction
amplitudes αo: angle of
C measured at the tangent at 20 mm DIC
ends of the r and k amplitude Stage 1 - hypercoagulable state
periods with secondary fibrinolysis
MA (maximum MCF (maximum
Stabilization of clot DIC
D amplitude): clot firmness):
maximum amplitude maximum amplitude by platelets and Stage 2 - hypocoagulable state
of instrument signal of instrument signal factor XIII
CL45, CL60 (lysis LY30, LY 45, Measures the degree

E after 45 and 60 or ML: Lysis at of fibrinolysis after
minutes): amplitude 30 or 45 minutes, a set amount of time
at specified times maximum lysis
Figure 5 Schematic thromboelastogram (a), description of common thromboelastometry parameters (b), and illustration of
selected abnormalities of coagulation (c). DIC = disseminated intravascular coagulation.
platelets; an array of antigenic or immunologically active sub- of donor leukocytes, but leukoreduction, typically through
stances in plasma (including both substances from donor prestorage filtration techniques, removes more than 99.9% of
plasma and substances that accumulate during storage); and, donor leukocytes. Although leukoreduction has not been
potentially, viral, bacterial, and parasitic pathogens. How- required by the FDA, it is required in Canada and several
ever, the specific transfusion-related factors that result in European countries and has been adopted by many blood
dysregulation of the innate or adaptive immune responses, as banks in the United States, in part because it reduces the
well as the clinical consequences of this immunomodulation, frequency of febrile transfusion reactions, cytomegalovirus
remain inadequately defined. transmission, and alloimmune platelet refractoriness.
Interest in the immunosuppressive effect of blood transfu- Although donor leukocytes appear to be the most likely
sion stemmed in part from the observation by Opelz and mediators of transfusion-related immunomodulation, donor
colleagues in 1973 that recipients of cadaveric renal trans- erythrocytes or antibodies could also play a role. With
plants experienced longer graft survival if they had undergone increased storage time, donor erythrocytes develop a “storage
allogeneic blood transfusion before transplantation.80 A lesion,” including morphologic changes that could impair
number of different strategies for mitigating this immunosup- their flow through the capillary microcirculation. A recent
pressive effect have been considered, including restrictive observational study of patients transfused in the setting of
criteria for transfusion, administration of autologous blood a cardiac operation found an association between older
products, and reduction of the quantity of donor leukocytes (i.e., greater than 14 days since donation) units of blood
in units of blood. Buffy-coat reduction removes 70 to 80% and increased postoperative complications and mortality.81
12/11
However, this study has been criticized for several methodo- another (e.g., autologous versus allogeneic and leukoreduced
logic issues, and many consider the issue unsettled. Transfu- versus nonleukoreduced). The literature is extensive, but
sion-related acute lung injury (which some define very broadly many methodologic issues have been identified that limit
to include underrecognized cases of immunomodulation) the validity of the studies.83 Accordingly, the evidence appears
appears to be caused in some cases by donor antibodies to to be insufficient to establish a causal connection between
recipient leukocyte antigens. This has led some blood centers allogeneic blood transfusion and either increased cancer
to exclude individuals likely to have such antibodies (e.g., recurrence or postoperative infection. Nonetheless, the
previously pregnant women) from plasma donation.82 heterogeneity of the study results and the finding of a major
A plethora of observational studies and some randomized randomized trial, the TRICC trial, that a restrictive transfu-
trials have attempted to evaluate the role of blood transfusion sion policy may improve survival in some patients continue
in the recurrence of resected malignancies and postoperative to fuel debate over whether the avoidance or modification
infection. Most of the observational studies have compared of allogeneic blood transfusion may improve patient
the outcomes of transfused cohorts with those of nontrans- outcomes.
fused cohorts. The randomized trials, however, have mostly
evaluated different kinds of blood transfusions against one Financial Disclosures: None Reported
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74. Eriksson BI, Kalebo P, Ekman S, et al. Direct
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Selective cellular expression of tissue factor inhibitor that inhibits the factor VII-tissue Disseminated intravascular coagulation: clin-
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N Engl J Med 1990;323:27–36. 64. Korninger C, Lechner K, Niessner H, et al. 80. Opelz G, Sengar DP, Mickey MR, Terasaki
49. Ignarro LJ, Buga GM, Wood KS, et al. Endo- Impaired fibrinolytic capacity predisposes PI. Effect of blood transfusions on subse-
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Proc Natl Acad Sci U S A 1987;84:9265–9. 65. Shovlin CL. Molecular defects in rare 81. Koch CG, Li L, Sessler DI, et al. Duration
of red-cell storage and complications after
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1229–39.
disease. Thromb Haemost 1997;78:415–9. 145–50. 82. Triulzi DJ, Kleinman S, Kakaiya RM, et al.
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inhibited by platelet-released mediators, role based diagnosis and management guidelines, donors: implications for a transfusion-related
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damage. Thromb Haemost 1999;82:787–93. 68. Lind B, Thorsen S. A novel missense muta-
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Acknowledgments
85–90. 69. Minowa H, Takahashi Y, Tanaka T, et al.
54. Michelson AD, Barnard MR. Thrombin- Four cases of bleeding diathesis in children Figures 1, 3, and 4 Marcia Kammerer
induced changes in platelet membrane glyco- due to congenital plasminogen activator Figure 2 Seward Hung
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1 BASIC SURGICAL AND PERIOPERATIVE CONSIDERATIONS 5 POSTOPERATIVE MANAGEMENT
OF THE HOSPITALIZED PATIENT — 1
5 POSTOPERATIVE MANAGEMENT
OF THE HOSPITALIZED PATIENT
Deborah L. Marquardt, MD, FACS, Roger P. Tatum, MD, FACS, and Dana C. Lynge, MD, FACS
At the beginning of the modern era of surgery, operative 2. The operative procedure to be performed
procedures commonly took place in an operating theater, 3. The course and duration of the operative procedure
performed by plainclothes surgeons in aprons for audiences 4. The patient’s clinical status at the completion of the
of students and other onlookers. Afterward, patients were procedure, as managed with the help of anesthesia
typically cared for at home or in a hospital ward, with scarcely colleagues
any monitoring and little to help them toward recovery
besides their own strength and physiologic reserve. In the The initial phase of disposition planning begins preopera-
current era, surgery is a high-tech, rapid-paced field, with tively. After a full history has been obtained and a complete
new knowledge and technological advances seemingly appear- physical examination carried out, the procedure to be
ing around every corner. Many of these new discoveries have performed is decided on. This decision then initiates a
allowed surgeons to work more efficiently and safely, and as discussion of the complexity and potential complications
a result, a number of operations have now become same-day associated with the procedure, as well as of the concerns and
procedures. In addition, some very complex operations that special needs related to any comorbid conditions that may be
were once thought to be impossible or to be associated with present. If, as is often the case, the surgeon requires some
unacceptably high morbidity and mortality have now become
assistance with planning the operation around the patient’s
feasible thanks to advances in surgical technique, anesthesia,
other health problems, input from appropriate medical and
postoperative management, and critical care. The focus of
surgical colleagues can be extremely helpful. Key factors to
our discussion is on the postoperative considerations that
have become essential for successful recovery from surgery. take into consideration include the potential complications
Each patient is unique, and each patient’s case deserves related to the procedure and the urgency of their treatment;
thoughtful attention; no two patients can be managed in the level of monitoring the patient will require with respect to
exactly the same way. Nevertheless, certain basic categories vital signs, neurologic examination, and telemetry; and the
of postoperative care apply to essentially all patients who degree of care that will be necessary with respect to treat-
undergo surgical procedures. Many of these categories are ments, use of drains, and wound care. Relatively few
discussed in greater detail elsewhere in ACS Surgery. Our published references describe specific criteria for the various
objective in this chapter is to provide a complete yet concise disposition categories; however, most hospitals and surgery
overview of each pertinent topic. centers will have developed their own policies specifying a
standard of care to be provided for each category.
Disposition same-day surgery
The term disposition refers to the location and level of
Same-day surgery is appropriate for patients who (1) have
care and monitoring to which the patient is directed after the
few or no comorbid medical conditions and (2) are undergo-
completion of the operative procedure. Although disposition
is not often discussed as a topic in its own right, it is an ing a procedure that involves short-duration anesthesia or
essential consideration that takes into account many impor- local anesthesia plus sedation and that carries a low likelihood
tant factors. It may be classified into four general categories of urgent complications. Operations commonly performed on
as follows: a same-day basis include inguinal or umbilical hernia repair,
simple laparoscopic cholecystectomy, breast biopsy, and
1. Home or same-day surgery via the recovery room small subcutaneous procedures.
2. The intensive care unit (ICU), with or without a stay in
The growth in the performance of minor and same-day
the recovery room
procedures has led to the development of various types of
3. The surgical floor via the recovery room
short-stay units or wards. The level of care provided by a
4. The telemetry ward via the recovery room
short-stay ward is generally equivalent to that provided by a
The disposition category that is appropriate for a given regular nursing ward; however, the anticipated duration of
patient is determined by considering the following four care is substantially shorter, typically ranging from several
factors: hours to a maximum of 48 hours. Short-stay wards also
1. The patient’s preoperative clinical status (including both undergo some modifications to facilitate the use of stream-
the condition being treated and any comorbid conditions), lined teaching protocols designed to prepare patients for
as indicated by the history, the physical examination, and home care. Many hospitals now have short-stay units, as do
the input of other medical practitioners some independent surgery centers.
DOI 10.2310/7800.2020
09/11
surgical floor gastric secretions when an ileus is anticipated or offloading of

The vast majority of patients receive the postoperative care the upper GI tract when a fresh anastomosis is located close
they require on the surgical floor (or regular nursing ward). by. Although NG tubes have often been placed routinely after
Assessment of vital signs, control of pain, care of wounds, abdominal surgery, the current literature cites a number of
management of tubes and drains, and monitoring of intake reasons why routine use is inadvisable and selective use is
and output are addressed every 2 to 8 hours (depending on preferable. For example, significantly earlier return of bowel
the variable). Assignment of the patient to the regular nursing function, a trend toward fewer pulmonary complications, and
ward presupposes that he or she is hemodynamically stable enhanced patient comfort and decreased nausea are reported
and does not need continuous monitoring. when NG tubes are not routinely placed or when they are
The telemetry ward is a variant of the regular nursing ward. removed within 24 hours after operation.2
The care provided in the telemetry ward is generally equiva- When postoperative placement of an NG tube is consid-
lent to that provided on other floor wards except that patients ered appropriate, an order from a physician is required, along
undergo continuous cardiac monitoring. Patients commonly with direction regarding the method of drainage. Sometimes
assigned to the telemetry ward after operation include (1) NG tubes are placed to low continuous suction; more often,
those with a known medical history of arrhythmias that may however, they are placed to low intermittent suction to
necessitate intervention, (2) those with intraoperative arrhyth- eliminate the chance of continuous suction against a visceral
mias or other electrocardiographic (ECG) changes who are wall and to promote generalized drainage. If large volumes of
not believed to require ICU monitoring but who do need secretions are not expected, continuous gravity may be used
this form of cardiac follow-up, and (3) those making the instead of suction. A key concern with NG tubes is mainte-
transition from the ICU to a regular ward who are hemody- nance of the patency of both the main port and the sump
namically stable but who require ongoing follow-up of a port. Should either port become blocked, the tube will be
cardiac issue. rendered ineffective. This concern should be discussed with
the nursing staff. At times, it may be necessary to issue
intensive care unit
specific orders to ensure that this concern is appropriately
When early postoperative complications may necessitate addressed. As a rule, surgical nurses are well acquainted with
urgent intervention and close observation is therefore essen- tube maintenance; however, if thick secretions are expected,
tial, patients should be admitted to the ICU for postoperative orders for routine flushing may be indicated. When the tube
care. Postoperative ICU admission may also be appropriate is no longer indicated, its removal may be ordered.
for patients who are clinically unstable after the procedure;
these patients often require ongoing resuscitation, intrave- urinary catheters
nous (IV) administration of vasoactive agents, ventilatory Urinary catheters can serve a large variety of purposes. In
support, or continuous telemetry monitoring for dysrhyth- the setting of bladder or genitourinary surgery, they are often
mias. In addition, admission to the ICU should be considered employed to decompress the system so that it will heal more
for patients in whom the complexity of drain management, readily. After general surgical procedures—and many other
wound care, or even pain control may necessitate frequent
surgical procedures as well—they are used to provide accu-
postoperative monitoring that is not available on a regular
rate measurements of volume output and thus, indirectly, to
nursing ward. At present, there is no single set of accepted
give some indication of the patient’s overall volume and
guidelines directing ICU admission. There are, however,
resuscitation status. Furthermore, after many procedures,
published sources that can provide some guidance. For
patients initially find it extremely difficult or impossible to
example, a 2003 article supplied recommendations for the
mobilize for urination, and a urinary catheter may be quite
various services to be provided by differing levels of ICUs.1
helpful during this time.
Published recommendations of this sort may be adopted
or modified by individual hospitals and surgery centers as Their utility and importance notwithstanding, urinary
necessary. catheters are associated with the development of nosocomial
urinary tract infections (UTIs). As many as 40% of all hospi-
tal infections are UTIs, and 80 to 90% of these UTIs are
Care Orders associated with urinary catheters [see Postoperative Compli-
Nurses and other ancillary personnel provide the bulk of cations, below]. Accordingly, when catheterization is no longer
the care received by patients after a surgical procedure; deemed necessary, prompt removal is indicated. As a rule,
accordingly, it is essential that they receive clear and ample orders specifically pertaining to urinary catheter care are few,
instructions to guide their work. Such instructions generally typically including gravity drainage, flushing to maintain
take the form of specific postoperative orders directed to each patency (if warranted), and removal when appropriate. At
ancillary service. Services for which such orders may be times, irrigation is employed after urologic procedures or for
appropriate include nursing, respiratory therapy, physical the management of certain infectious agents.
therapy (PT), occupational therapy (OT), and diet and
oxygen therapy
nutrition. In what follows, we briefly outline some of the
common tasks that require orders to be directed toward these Supplemental administration of oxygen is often necessary
services. after a surgical procedure. Common indicators of a need
for postoperative oxygen supplementation include shallow
nasogastric tubes breathing and pain, atelectasis, operative manipulation in the
Nasogastric (NG) tubes are commonly placed after gastro- chest cavity, and postoperative impairment of breathing
intestinal (GI) operations, most frequently for drainage of mechanics. Because supplemental oxygen is considered a
09/11
medication, a physician’s order is required before it can be the presence of severe inflammation leads the surgeon to
administered. In many cases, oxygen supplementation is conclude that dissection poses too high an operative risk.
ordered on an as-needed basis with the aim of enabling the Particularly in the latter setting, delayed elective cholecystec-
patient to meet specific peripheral oxygen saturation criteria. tomy may be appropriate; if so, the cholecystostomy tube
In other cases, it is ordered routinely in the setting of known may be removed at the time of the operation.
preoperative patient oxygen use. Nasobiliary tubes are placed endoscopically in the course
An important factor to keep in mind is that oxygen supple- of biliary endoscopy. They are used to decompress the CBD
mentation protocols may vary from one nursing unit to in some settings. They are usually placed to gravity and
another. Different units may place different limitations on the otherwise are managed in much the same way as NG
amount of supplemental oxygen permitted, depending on tubes.7
their specific monitoring and safety guidelines. Another
important factor is that patients with known obstructive wound care
pulmonary disease and carbon dioxide retention are at The topic of wound care is a broad one. Here we focus on
increased risk for respiratory depression with hyperoxygen- initial postoperative dressing care, traditional wet-to-dry
ation; accordingly, particular care should be exercised in dressings, and use of a vacuum-assisted closure device (e.g.,
ordering supplemental oxygen for these patients. VAC Abdominal Dressing System, Kinetic Concepts, Inc.,
San Antonio, TX). These and other components of wound
drains care are discussed in more detail elsewhere.
Drains and tubes are placed in a wide variety of locations Initial wound management after an operative procedure
for a number of different purposes—in particular, drainage generally entails placement of a sterile dressing to cover the
of purulent materials, serum, or blood from body cavities. incision. The traditional recommendation has been to keep
Several types are commonly used, including soft gravity this dressing in place and dry for the first 48 hours after
drains (e.g., Penrose), closed-suction drains (e.g., Hemovac, operation; because epithelialization is known to take place
Jackson-Pratt, and Blake), and sump drains, which draw air within approximately this period, the assumption is that this
into one lumen and extract fluid via a companion lumen. measure will reduce the risk of wound infection. Although
Traditionally, surgeons have often made the decision to place most surgeons still follow this practice, especially in general
a drain on the basis of their surgical training and practice surgical cases, supporting data from randomized clinical
habits rather than of any firm evidence that drainage is studies are lacking. In addition, several small studies that
warranted. Multiple randomized clinical trials have now dem- evaluated early showering with closed surgical incisions found
onstrated that routine use of drains after elective operations— no increases in the rate of infection or dehiscence.8,9 It should
including appendectomies and colorectal, hepatic, thyroid, be kept in mind, however, that these small studies looked
and parathyroid procedures—does not prevent anastomotic primarily at soft tissue and other minor skin incisions that did
and other complications (although it does reduce seroma not involve fascia. Thus, even though the traditional approach
formation). Consequently, it is recommended that drains, to initial dressing management is not strongly supported, the
like NG tubes, be employed selectively.3–5 Once a drain is in data currently available are insufficient to indicate that it
place, specific orders must be issued for its maintenance. should be changed.
These include use of gravity or suction (and the means by Wet-to-dry dressings are used in a variety of settings. In a
which suction is to be provided if ordered), management and surgical context, they are most often applied to a wound that
measurement of output, stripping, and care around the drain cannot be closed primarily as a consequence of contamina-
exit site. tion or inability to approximate the skin edges. Wet-to-dry
Biliary tract drains include T tubes, cholecystostomy tubes, dressings provide a moist environment that promotes granu-
percutaneous drains of the biliary tree, and nasobiliary drains. lation and wound closure by secondary intention. Moreover,
Daily site maintenance, flushing, and output recording are their removal and replacement cause débridement of excess
performed by the nursing staff. Most biliary tract drains are exudate or unhealthy superficial tissue. Postoperative orders
removed by the practitioner or other trained midlevel staff should specify the frequency of dressing changes and the
members. solution used to provide dampness. For most clean open
T tubes are generally placed after operative exploration or incisions, twice-daily dressing changes using normal saline
repair of the common bile duct (CBD). The long phalanges solution represent the most common approach. If there is
are left within the CBD, and the long portion of the tube is excess wound exudate to be débrided, dressing changes may
brought out to the skin for drainage. The tube is left in place be performed more frequently. If there is particular concern
until the CBD is properly healing and there is evidence of about wound contamination or superficial colonization of
adequate distal drainage (signaled by a decrease in external organisms, substitution of dilute Dakin solution for normal
drainage of bile). Before the T tube is removed, a cholangio- saline may be considered.
gram is recommended to document distal patency and rule A new era of wound management arrived in the late 1990s
out retained gallstones or leakage.6 with the introduction of negative-pressure wound therapy
Cholecystostomy tubes are placed percutaneously— (NPWT). In NPWT, a vacuum-assisted wound closure
typically under ultrasonographic guidance and with local device places the wound under subatmospheric pressure con-
anesthesia—to decompress the gallbladder. Generally, they ditions, thereby encouraging blood flow, decreasing local
are used either (1) when cholecystectomy cannot be wound edema and excess fluid (and consequently lowering
performed, because concomitant medical problems make bacterial counts and encouraging wound granulation), and
anesthesia or the stress of operation intolerable, or (2) when increasing wound contraction.10,11 Since the first published
09/11
animal studies, NPWT has been successfully employed for a anastomoses after gastric resection, the more tenuous nature
multitude of wound types, including complex traumatic and of a esophagojejunostomy after total gastrectomy, and the
surgical wounds, skin graft sites, and decubitus wounds. delayed gastric conduit emptying, aspiration risk, and anasto-
Before vacuum-assisted closure is used, however, it is neces- motic stress seen after esophagectomy or resection—have led
sary to consider whether and to what extent the wound is to the current practice of instituting NG drainage and placing
contaminated, the proximity of the wound to viscera or the patient on NPO status postoperatively until evidence of
vascular structures, and the potential ability of the patient to the return of bowel function is apparent, as well as, in some
tolerate dressing changes. Wounds that are grossly contami- cases, investigating the anastomosis for possible leakage by
nated or contain significant amounts of nonviable tissue means of contrast fluoroscopy. There are no clinical trial data
probably are not well suited to an occlusive dressing system to support this approach. In fact, many surgeons routinely
of this type given that frequent evaluation and possibly remove the NG tube within 24 hours after gastric resection
débridement may be needed to prevent ongoing tissue and early feeding without incurring increased complications.
infection and death. Furthermore, the suction effect of the However, there are also no clinical trial data indicating that
standard vacuum sponge may cause serious erosion of the current approach is potentially ineffective or harmful.
internal viscera or exposed major blood vessels. Some Consequently, traditional management methods after upper
silicone-impregnated nonadherent sponges are available GI procedures still are often endorsed in the literature.13,14
that may be suitable in this setting, but caution should be
exercised in using them. Finally, because of the adherence of enteral nutrition
the sponge and the occlusive adhesive dressing, some patients Enteral nutrition may be delivered via several routes. Most
may be unable to tolerate dressing changes without sedation patients who have undergone an operation are able to take in
or anesthesia. an adequate amount of calories orally. When they are unable
to do so, whether because of altered mental status, impaired
Nutrition pulmonary function, or some other condition, the use of
enteral feeding tubes may be indicated. In the acute setting,
The patient’s nutritional status has a significant effect
NG and nasojejunal feeding tubes are the types most com-
on postoperative morbidity and even mortality. After most
monly employed to deliver enteral solutions into the GI tract.
operative procedures that do not involve the alimentary tract
Either type is appropriate for this purpose; the two types are
or the abdomen and do not affect swallowing and airway
equivalent overall as regards their ability to provide adequate
protection, the usual practice is to initiate the return to full
nutrition, and there are no significant differences in outcome
patient-controlled oral nutrition as soon as the patient is fully
or complications. In cases where prolonged inability to take
awake. In these surgical settings, therefore, it is rarely neces-
in adequate calories orally is expected, the use of an indwell-
sary to discuss postoperative nutrition approaches to any
ing feeding tube, such as a gastrostomy or jejunostomy tube,
great extent.
After procedures that do involve the alimentary tract or the may be indicated. These tubes must be placed either at the
abdomen, however, the situation is different. The traditional time of operation or subsequently via surgical or percutane-
practice has been to institute a nihil per os (NPO) policy, ous means, and there is some potential for complications.
with or without NG drainage, after all abdominal or alimen- The specific indications for the use of such tubes are
tary tract procedures until the return of bowel function, as patient derived; they are not routinely associated with the
evidenced by flatus or bowel movement, is confirmed. The performance of specific procedures.
routine application of this practice has been challenged, how- total parenteral nutrition
ever, especially over the past 15 years. Data from prospective
studies of high statistical power are lacking, but many smaller Total parenteral nutrition (TPN) is a surrogate form of
studies evaluating early return to enteral nutrition after nutrition in which dextrose, amino acids, and lipids are
alimentary tract procedures have yielded evidence tending to delivered via a central venous catheter. It is a reliable method
favor more routine use of enteral intake within 48 hours after in that it delivers nutrients and calories regardless of whether
such procedures. the patient’s gut is functioning. Nevertheless, multiple studies
Issues related to postoperative nutritional support are over the past 20 years have shown that when the patient has
discussed further and in greater detail elsewhere. a functioning intestinal tract, enteral feeding is clearly prefer-
able to TPN. Although the specific mechanisms are not fully
npo status understood, enteral nutrition is known to foster gut mucosal
In the setting of elective colorectal surgery, it is well- integrity, to support overall immune function, and to be asso-
accepted practice to initiate a return to patient-controlled ciated with lower complication rates and shorter hospital
enteral-oral feeding within 24 to 48 hours after operation; this stays. In contrast, TPN is known to be associated with altered
practice yields no increase in the incidence of postoperative immune function, an increased rate of infectious complica-
complications (e.g., anastomotic leakage, wound and intra- tions, and, in some studies, a higher incidence of anastomotic
abdominal infection, and pneumonia) or the length of hospi- complications after GI surgery. Moreover, there are as yet no
tal stay and, according to some reports, may even decrease data to indicate that acute use of TPN during short periods
them.12 In the setting of upper GI surgery (specifically, gastric of starvation benefits patients who are adequately nourished
resection, total gastrectomy, and esophagectomy), the situa- preoperatively. TPN may, however, be lifesaving in patients
tion is less clear-cut. Traditional concerns—in particular, the who are malnourished and who do not have functioning
need to avoid distention stress on gastric or gastrojejunal GI tracts (e.g., those with short gut syndrome, severe gut
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dysmotility or malabsorption, mesenteric vascular insuffi- space. They may be further classified into two subcategories:
ciency, bowel obstruction, high-output enteric fistulas, or crystalloids and colloids.
bowel ischemia).15
Crystalloids
caloric goals Crystalloid solutions are water-based solutions to which
Once a route of nutritional support has been decided on, electrolytes (and, sometimes, organic molecules such as
overall goals for caloric and protein intake may be established dextrose) have been added. The crystalloid solutions used for
on the basis of the patient’s ideal body weight (IBW) and resuscitation are generally isotonic to blood plasma and
expected postoperative metabolic state. One approach is to include such common examples as 0.9% sodium chloride,
rely on a general estimate; a commonly used formula is lactated Ringer solution, and Plasma-Lyte (Baxter Health-
25 kcal/kg IBW. Another approach is to calculate a basal care, Round Lake, IL). The choice to use one solution over
energy requirement by using the Harris-Benedict equation. another is usually inconsequential, but there are a few notable
This calculation is separate from the calculation of protein exceptions. For example, in the setting of renal dysfunction,
needs. A daily protein intake goal may be calculated on there is a risk of hyperkalemia when potassium-containing
the basis of the patient’s estimated level of physical stress. solutions such as lactated Ringer solution and Plasma-Lyte
A well-nourished unstressed person requires a protein intake are used. As another example, the administration of large
of approximately 1.0 g/kg IBW/day. A seriously ill patient volumes of 0.9% sodium chloride, which has a pH of 5.0 and
under ongoing severe physical stress, however, may require a chloride content of 154 mmol/L, can lead to hyperchlore-
2.0 g/kg IBW/day; in some settings (e.g., extensive burns), mic metabolic acidosis. Regardless of which crystalloid solu-
a protein intake as high as 3.0 g/kg IBW/day may be tion is used, large volumes may have to be infused to achieve
recommended. Once the patient’s specific needs have been a significant increase in the circulating intravascular volume.
calculated, the amount and type of nutrient solution to be Only one third to one quarter (250 to 330 mL/L) of the fluid
provided enterally or via TPN are determined. If the patient administered stays in the intravascular space; the rest migrates
is on a full oral diet, a calorie count or recording of the by osmosis into the interstitial tissues, producing edema
percentage of items eaten at each meal or snack may be made
and potential impairment of tissue perfusion (the latter is a
by the nursing staff and used to estimate the patient’s intake,
theoretical consequence whose existence has not yet been
with nutritional supplementation provided as needed.16
directly demonstrated).17
Patients who require assistance with nutritional intake
should be monitored to determine whether the interventions Colloids
being carried out are having the desired effect. The most
Colloid solutions are composed of microscopic particles
common method of monitoring patients’ nutritional status
dispersed in a second substance in such a way that they are
with nutritional supplementation is to measure the serum
suspended and do not separate by normal filtration. Colloids
albumin and prealbumin (transthyretin) concentrations.
are derived from three main forms of semisynthetic mole-
Albumin has a half-life of approximately 14 to 20 days and
cules: gelatins, dextrans, and hydroxyethyl starches. All of the
thus serves as a marker of longer-term nutritional status.
commonly used synthetic colloids are dissolved in crystalloid
A value lower than 2.2 g/dL is generally considered to repre-
solution. Nonsynthetic colloids also exist, including human
sent severe malnutrition, but even somewhat higher values
(< 3.0 g/dL) have been associated with poorer outcomes after albumin solutions, fresh frozen plasma, plasma-protein
elective surgery. Although the serum albumin concentration fraction, and immunoglobulin solutions. Compared with
is a commonly used marker, it is not always a reliable one. crystalloid solutions, colloid solutions increase the circulating
Because of albumin’s relatively long half-life, the serum intravascular volume to a much greater degree per unit of
concentration does not reflect the patient’s more recent volume infused. In this respect, the various colloids may be
nutritional status. In addition, the measured concentration thought of as a single group; however, in practice, they are
can change quickly in response to the infusion of exogenous most often given selectively on the basis of secondary charac-
albumin or to the development of dehydration, sepsis, and teristics other than their volume-increasing action, such as
liver disease despite adequate nutrition. Prealbumin is a effect on hemostasis, risk of allergic reaction, and cost.
separate serum protein that has a half-life of approximately
Crystalloids versus Colloids
24 to 48 hours and thus can serve as a marker of current and
more recent nutritional status. Like the albumin concentra- The debate over whether crystalloids or colloids are supe-
tion, the prealbumin concentration can be affected by liver rior for resuscitation has been going on for at least 30 years.
and renal disease. Overall, however, it is more immediately Although multiple randomized, controlled trials have com-
reliable in following the effects of nutritional intervention. pared the two types of solutions in a variety of settings,
including sepsis, trauma, burns, and surgery, the evidence
accumulated to date has not established that one is clearly
Fluid Management better than the other in terms of overall outcome. Supporters
IV fluids may be classified into two main categories: resus- of crystalloid resuscitation cite the risk of altered hemostasis,
citation and maintenance. Supplemental fluids constitute a the increased likelihood of drug interactions and allergic reac-
third category. tions, the potential for volume overload, and the relatively
high cost as factors arguing against the use of colloids.
resuscitation fluids Supporters of colloid resuscitation cite the large volume of
Resuscitation fluids maintain tissue perfusion in the setting crystalloid needed to produce significant volume effects, the
of hypovolemia by restoring lost volume to the intravascular subsequent tissue edema, and the potential for impaired
09/11
tissue perfusion and oxygenation as factors arguing against status. Bringing the patient closer to the baseline sensory
the use of crystalloids. Current recommendations favor state by reducing pain allows him or her to engage in activi-
crystalloid for resuscitation, with colloid an acceptable ties that promote healing and prevent complications, includ-
substitute when its secondary effects are desired in specific ing mobilization to help prevent deep vein thrombosis (DVT)
situations.17,18 and deep breathing and coughing to help prevent pneumonia.
Common methods of pain relief include IV infusion of
maintenance fluids narcotics, epidural analgesia using local anesthetics with or
Maintenance fluids provide required daily amounts of free without narcotics, oral administration of narcotics, and the
water and electrolytes (e.g., sodium, potassium, and chloride) use of nonnarcotic oral medications such as nonsteroidal
to balance expected daily losses and maintain homeostasis. A antiinflammatory drugs (NSAIDs) and acetaminophen (see
basic rule of thumb used by many practitioners to calculate below). These and other issues related to postoperative pain
the infusion rate for maintenance IV fluids is the so-called 4, control are discussed in greater detail elsewhere.
2, 1 rule:
iv narcotic analgesia
• 4 mL/kg/hr for the first 10 kg of body weight
IV narcotics may be administered either by the medical
• 2 mL/kg/hr for the next 10 kg of body weight and
staff or, if patient-controlled analgesia (PCA) is feasible, by
• 1 mL/kg/hr for every 1 kg of body weight above 20 kg
the patient. In most cases, with the exception of brief hospital
Generally accepted maintenance requirements include 30 stays (< 48 hours) and ICU settings where the patient may
to 35 mL/kg/day for free water, 1.5 mEq/kg/day for chloride, not be alert enough to manage a patient-controlled system,
1 mEq/kg/day for sodium, and 1 mEq/kg/day for potassium. PCA is now generally considered preferable to as-needed
In the setting of starvation or poor oral intake, dextrose 5% nurse-administered IV narcotic analgesia. Numerous studies
is often added to maintenance fluids to inhibit muscle break- and reviews have shown that PCA is safe and is no more
down. In regular practice, however, these specific values are likely to cause side effects (e.g., oversedation, overdose,
not commonly used; more often, a rough estimate is made of itching, and nausea) than nurse-administered IV narcotic
expected daily fluid requirements, and solutions are ordered analgesia is. In addition, the use of PCA improves patients’
in accordance with this estimate. Although this practice subjective perceptions of the efficacy of pain relief and the
is unlikely to cause noticeable harm in the majority of post- timeliness of drug administration.22
operative patients, there are situations where inaccurate
epidural analgesia
calculations can lead to dehydration and volume overload.
Three studies from the early 2000s evaluated patients under- Epidural analgesia usually makes use of a local anesthetic
going elective colorectal surgery with the aim of determining (e.g., bupivicaine) with or without the addition of a narcotic
whether providing higher volumes of fluid perioperatively had (e.g., fentanyl). The anesthetic solution is instilled into the
an impact on outcome.19–21 In all three, the data supported epidural space, bathing the nerve roots in a given region and
the use of smaller fluid volumes perioperatively, which thereby providing pain relief. Until the past decade or so,
was shown to result in earlier return of gut function after epidural analgesia was considered a more dangerous method
operation, shorter hospital stays, and overall decreases in of pain relief and was not routinely employed outside the
cardiopulmonary and tissue-healing complications. ICU. With time and further observation has come the
recognition that epidural analgesia is safe and effective
supplemental fluids for postoperative pain control in a routine floor setting if
Supplemental fluids are given to replace any ongoing fluid managed by the proper supporting team of physicians.
loss beyond what is expected to occur via insensible loss and There has been some debate regarding whether epidural
excretion in urine and stool. They are most commonly analgesia leads to earlier return of bowel function after GI
required by patients with prolonged NG tube output, entero- surgery or reduces the incidence of pulmonary complications;
cutaneous fistulas, diarrhea, high-output ileostomies, or large at present, this debate remains unresolved. There is clear
open wounds associated with excessive insensible fluid loss. evidence, however, that patients subjectively experience less
In each case, the amount of fluid lost daily should be calcu- pain with epidural analgesia, both at rest and in the course of
lated, and replacement fluid should be given in a quantity activities such as mobilization and coughing. Moreover, in
determined by this measurement (either as a whole or in part) patients who have sustained traumatic rib fractures, early use
and by the patient’s overall intravascular volume status. The of epidural analgesia in place of IV narcotic analgesia has
particular solution to be used depends on the characteristics been shown to reduce the incidence of associated pneumonia
of the fluid loss. The components and volume of the fluids and shorten the time for which mechanical ventilation is
produced in the GI tract are different at different sites [see required.23 Epidural analgesia does have certain drawbacks,
Table 1]. including an increased incidence of orthostatic episodes and
a need for more frequent adjustments of the medication
dosage. Nevertheless, it can be highly effective and can be
Pain Control a reasonable option when judged appropriate by the
The topic of postoperative pain control covers a broad anesthesiologist and agreed to by the patient.24,25
spectrum of possible interventions that serve a wide range
of purposes. The most obvious purpose is simply to relieve oral administration of narcotics
the suffering and stress associated with postoperative pain. Oral administration of narcotics is one of the oldest
Another is to improve the patient’s overall postoperative methods of providing postoperative pain relief. Numerous
09/11
Table 1 Electrolyte Content and Rate of Production of Fluids Secreted in the Gastrointestinal Tract
Electrolyte Concentration (mEq/L)
+
Source of Secretion Na K+ Cl– HCO3– H+ Rate of Production (mL/day)
Salivary glands 50 20 40 30 100–1,000
Stomach
Basal 100 10 140 30 1,000
Stimulated 30 10 140 100 4,000
Bile 140 5 100 60 500–1,000
Pancreas 140 5 75 100 1,000
Duodenum 140 5 80 100–2,000
Ileum 140 5 70 50 100–2,000
Colon 60 70 15 30
different narcotic agents are now available for use in this than 2 g/day in patients with normal hepatic function and
setting. When deciding which narcotic to prescribe, however, even lower in those with impaired hepatic function. It is
physicians typically do not select freely from the entire avail- particularly important to keep these dose limits in mind when
able range; rather, they tend to choose from a small subset of narcotic-acetaminophen combinations are prescribed on an
agents that they know well and are comfortable with. A key as-needed basis; in this situation, safe dosage limits may well
point to keep in mind is that in some formulations, narcotics be exceeded if sufficient care is not taken.
are combined with other compounds (e.g., acetaminophen or
aspirin), and these added medications can have side effects of
Glycemic Control
their own if taken in excessively high doses. Such formula-
tions may require more careful titration than narcotics alone Over the last decade, blood glucose control in the post-
would. Another key point is that many narcotics are available operative period has become a topic of great interest. Many
in both short-acting and long-acting versions. In patients who studies, beginning with that of Van den Berghe and colleagues
are experiencing substantial postoperative pain, a combina- in 2001,26 have found that strict glucose control reduces
tion of long-acting agents and short-acting agents may yield morbidity and mortality in critically ill surgical ICU patients.
more sustained and predictable pain relief than either type Although most of the data currently available are derived
alone would. from ICU patients rather than from the surgical population
Finally, for patients who have a history of chronic pain as a whole, the principle of tight glycemic control has been
conditions and who regularly used pain medications preop- generalized to apply to most postoperative patients.
eratively, the assistance of an acute pain service management The target glucose range has been the subject of debate,
team may be invaluable in treating pain postoperatively. with most institutions using a range of 80 to 140 mg/dL. The
ability to achieve this target range and the means of achieving
nsaids and acetaminophen it vary according to the level of nursing care that is provided.
NSAIDs are available both by prescription and over the Options include continuous IV insulin infusion and combina-
counter. They not only provide effective analgesia for pain tions of subcutaneous injections that use various long- and
from minor procedures but also may be a powerful adjunct short-acting insulin formulations. Episodes of hypoglycemia
to narcotics in more acute hospital settings. Their major dis- are an ever-present risk with tight glucose control; accord-
advantages, which in some contexts are substantial enough to ingly, the use of standard dosage regimens and careful moni-
limit their use, include their propensity to cause gastric irrita- toring are recommended to reduce the risk of such episodes.
tion and ulceration; their antiplatelet effects, which increase The debate over the specifics of glycemic control notwith-
the tendency toward bleeding; and their potential nephro- standing, it is generally well accepted that this issue should
toxic effects in some formulations. When employed in be addressed in all patients who have undergone major
settings where these disadvantages are not considered to pose operative procedures, regardless of whether they carry a
a high risk, NSAIDs can be a useful addition to narcotics, preoperative diagnosis of diabetes mellitus.26,27
both by providing further pain relief and by reducing
the required narcotic doses (and thus the incidence of
narcotic-related side effects). Postoperative Complications
Like the NSAIDs, acetaminophen provides minor pain Numerous complications may arise in the postoperative
relief and is an antipyretic, but unlike the NSAIDs, it has no period. Many of these are specific to particular operative
antiinflammatory effect. Acetaminophen also is often added procedures and hence are best discussed in connection with
to narcotic regimens or formulations to reduce the need for those procedures. Many others, however, may develop after
narcotics. Its greatest potential side effect is hepatic toxicity virtually any operation and thus warrant a general discussion
with excessive use. Accordingly, the dosage should be less in this chapter (see below). Prompt discovery and treatment
09/11
of these latter complications rely heavily on a sufficiently high views, if possible) and sputum cultures, sometimes accompa-
index of suspicion. nied by CT scanning of the chest and, possibly, bronchos-
copy with bronchoalveolar lavage (which may be useful
postoperative fever in directing antibiotic therapy when sputum cultures are non-
Postoperative temperature elevations are quite common, diagnostic). Empirical broad-spectrum antibiotic therapy is
occurring in nearly one third of patients after surgery. Only a typically initiated before the causative organism is identified;
relatively small number of these are actually caused by infec- this practice has been shown to reduce mortality. Piperacillin-
tion. Fevers that are caused by infections (e.g., pneumonias, tazobactam, which is effective against Pseudomonas aeruginosa,
wound infections, or UTIs) tend to reach higher tempera- is commonly used for this purpose; however, when Gram
tures (> 38.5°C [101.3°F]), usually are associated with staining of the sputum identifies gram-positive cocci, vanco-
moderate elevation of the white blood cell (WBC) count 3 mycin or linezolid may be used initially instead.30 Once the
or more days after operation, and typically extend over con- causative organism is identified, specific antibiotic therapy
secutive days. Noninfectious causes of postoperative fevers directed at that organism is indicated, as in treatment of other
include components of the inflammatory response to surgical infectious processes. Drainage of parapneumonic effusions
intervention, reabsorption of hematomas, and (possibly) may also be necessary, and this measure may be helpful in
atelectasis.28 diagnosing or preventing the development of empyema.
Beyond checking the WBC count, a shotgun approach to
the workup of postoperative fever probably is not warranted. surgical site infection
A focused approach based on well-directed questioning and Surgical site infection (SSI) is one of the most common
a careful physical examination is more likely to obtain the postoperative complications and may occur after virtually any
highest diagnostic yield. Coughing, sputum production, and type of procedure. Rates of infection vary widely (from less
respiratory effort should be noted, and the lungs should be than 1% to approximately 20%) depending on the procedure
auscultated for rales. All incisions should be inspected for performed, the classification of the operative wound (clean,
erythema and drainage, and current and recent IV sites clean-contaminated, contaminated, or dirty), and a host of
should be checked for evidence of cellulitis. If a central line patient-related and situation-specific factors. The majority
has been placed, particularly if it has been in place for several of SSIs, regardless of site, are caused by skin-based flora,
days, the possibility of a line infection should be considered. most commonly gram-positive cocci (e.g., staphylococci).
Patients who have undergone prolonged NG intubation Gram-negative infections are also commonly seen after GI
may have sinusitis, which is most readily diagnosed through procedures, and anaerobes may be present after pharyngo-
computed tomography (CT) of the sinuses. Further workup esophageal procedures.31 With SSI, as with other postopera-
for fever may include, as indicated, chest x-ray, sputum tive infectious complications, prompt recognition of the signs
cultures, urinalysis, blood cultures, or CT of the abdomen and symptoms is the key to successful management. Hence,
(after procedures involving laparotomy—especially bowel regular examination of the wound, particularly in the setting
resections—where intra-abdominal abscess is a possible of postoperative fever, is critical. Erythema and induration
complication). (indicative of cellulitis) are obvious signs of SSI, as is active
drainage of pus from the wound. A more subtle sign is pain
pneumonia that is greater than expected, especially when the pain seems
Respiratory infections in the postoperative period are to be increasing several days after operation.
generally considered nosocomial pneumonias and, as such, In most cases, it is necessary to open and drain the wound
are potentially serious complications. The estimated inci- (which is easily done at the bedside or in the clinic in most
dence of postoperative pneumonia varies significantly, with cases) and allow it to heal via secondary intention. Generally,
many estimates tending to run high. A 2001 study of more wet-to-dry dressing changes with saline are employed;
than 160,000 patients undergoing major noncardiac surgery however, larger wounds may benefit from NPWT [see Care
provided what may be a reasonable overall figure, finding the Orders, Wound Care, above]. Success with NPWT has been
incidence of postoperative pneumonia to be approximately widely reported, and this technique has been used to treat
1.5%.29 In the 2,466 patients with pneumonia, the 30-day difficult wounds such as exposed vascular grafts and sternot-
mortality was 21%. Thoracic procedures, upper abdominal omy infections.32,33 The use of antibiotics depends on the
procedures, abdominal aortic aneurysm repair, peripheral presence and degree of cellulitis. The initial choice of an
vascular procedures, and neurosurgical procedures were all agent should be guided by the likelihood that particular
identified as placing patients at significantly increased risk for organisms will be present, which is estimated on the basis
pneumonia. Patient-specific risk factors included age greater of the site of the operation and the type of procedure being
than 60 years, recent alcohol use, dependent functional performed. Whenever possible, any purulent material in the
status, long-term steroid use, and a 10% weight loss in the SSI should be cultured; this step may permit more targeted
6 months preceding the operation.29 antimicrobial therapy.
The diagnosis of postoperative pneumonia is based on the
usual combination of index of suspicion, findings from the deep vein thrombosis and pulmonary embolism
history and physical examination (e.g., fever, shortness of In the absence of appropriate prophylaxis, the incidence
breath, hypoxia, productive cough, and rales on lung auscul- of DVT may be as high as 30% in abdominal and thoracic
tation), imaging, and laboratory evaluation. Appropriate surgery patients and that of fatal pulmonary embolism (PE)
workup, directed by the clinical findings, typically starts with may be as high as 0.9%. Thus, prophylaxis against thrombo-
chest x-rays (preferably in both posteroanterior and lateral embolism is clearly of high importance in the postoperative
09/11
care of many patients. Major risk factors for DVT and PE in Atrial fibrillation and atrial flutter account for the majority of
this setting include the operation itself, physical immobility, SVTs.38 Ventricular rate control may be achieved pharmaco-
advanced age, the presence of a malignancy, obesity, and a logically by infusing diltiazem. Digoxin has long been used
history of smoking.34 for this purpose but is less effective in acute settings than
DVT should be suspected postoperatively whenever a diltiazem is. Amiodarone, which is used to treat ventricular
patient complains of lower-extremity pain or one leg is notice- dysrhythmias, may also be used to restore sinus rhythm
ably more swollen than the other. The gold standard for postoperatively in some cases, especially after cardiac
diagnosis remains a venous duplex examination, which has procedures.39 When pharmacologic rate control is not
a sensitivity of 97% for detecting DVT of the femoral and possible, particularly in hypotensive patients, cardioversion is
popliteal veins.35 In most cases, treatment involves starting a indicated.
heparin infusion (typically without a loading bolus in the Approximately one third of patients who undergo noncar-
postoperative setting), targeting a partial thromboplastin time diac surgery in the United States have some degree of
(PTT) that is double to triple the normal PTT (i.e., approx- coronary artery disease and thus are at increased risk for
imately 60 to 80 seconds), and then switching to warfarin perioperative MI. The incidence of coronary artery disease is
therapy when the patient is stable and able to tolerate oral even higher in certain subpopulations, such as patients who
medications. undergo major vascular procedures.40,41 In the perioperative
PE should be suspected whenever a postoperative patient setting, however, the pathophysiology of coronary ischemia
experiences a decrease in oxygen saturation or shortness of is different from that in nonsurgical settings, where plaque
breath; this decrease may be accompanied by chest pain, rupture is the most common cause of MI. Approximately
tachycardia, and diaphoresis, all of which may also be seen 50% of all MIs occurring in surgical patients are caused
in the setting of myocardial infarction (MI). When PE is by increased myocardial oxygen demand in the face of
suspected, it may be appropriate to start heparin therapy even inadequate supply resulting from factors such as fluid shifts,
before the diagnosis has been confirmed, depending on the physiologic stress, hypotension, and the effects of anesthesia.
degree of suspicion and the relative risk anticoagulation The majority of cardiac ischemic events occur in the first
may pose to the patient. Currently, the principal means of 4 days of the postoperative period.41
diagnosing acute PE is spiral CT. This modality has relatively
Perioperative beta blockade for patients at risk for MI is
wide availability, can be performed fairly rapidly, and has a
now routine. Multiple trials and meta-analyses have demon-
sensitivity of 53 to 100% and a specificity of 81 to 100%. In
strated that this practice yields significant risk reductions in
addition, it is readily usable in most critically ill patients,
terms of both cardiac morbidity and mortality42,43 and that
including those undergoing mechanical ventilation (although
these risk reductions are achieved regardless of the type
the amount of IV contrast material it requires may limit its
of surgery being performed. Although there has been some
use in patients with renal insufficiency). Greater diagnostic
variation in the protocols used by these trials and the results
yield may be obtained by combining spiral CT with a lower-
reported, there is general agreement that beta blockade should
extremity venous duplex examination.36 For most patients
be initiated preoperatively, delivered at the time of surgery,
with postoperative PE, anticoagulation is administered in the
and continued postoperatively for up to 1 week.42
form of heparin. Low-molecular-weight heparins (LMWHs)
Diagnosis of postoperative MI is complicated by the fact
are also generally safe and effective; however, because their
that as many as 95% of patients who experience this compli-
effect cannot be turned off in the same way as that of IV
unfractionated heparin, they may be less useful in the period cation may not present with classic symptoms (e.g., chest
after operation.37 In patients with massive PE, surgical embo- pain). Identification of MI may be further hindered by the
lectomy or suction-catheter embolectomy may be considered ECG changes brought on by the stress of the perioperative
as conditions warrant. Thrombolytic therapy is generally period (including dysrhythmias). Ultimately, the most useful
contraindicated in the postoperative setting. signal of an ischemic cardiac event in the postoperative period
is a rise in the levels of cardiac enzymes, particularly troponin
cardiac complications I. Accordingly, cardiac enzyme activity should be assessed
Cardiac dysrhythmias may occur after a wide variety of whenever there is a high index of suspicion for MI or a patient
surgical procedures; as one might imagine, they are most is considered to be at significant perioperative risk for MI.40
common after cardiac operations. Predisposing factors and Treatment of postoperative MI focuses on correcting any
possible causes are numerous and various, including underly- factors contributing to or exacerbating the situation that led
ing cardiac disease, perioperative systemic stress, electrolyte to the event (e.g., hypovolemia or hypotension). Typically,
and acid-base imbalances, hypoxemia, and hypercarbia. although antiplatelet agents (e.g., aspirin) are sometimes
Thus, controlling such conditions to the extent possible both given, thrombolytic therapy is avoided because of concerns
preoperatively and postoperatively is an important part of about postoperative bleeding. Acute percutaneous coronary
preventing and managing postoperative cardiac dysrhythmias. intervention is also associated with an increased risk of bleed-
Treatment generally involves first achieving hemodynamic ing but has nonetheless been used successfully in the peri-
stability and then converting the rhythm back to sinus if operative setting and is recommended by some physicians.44
possible. Beta blockade is often advocated as a means of treating
Supraventricular tachycardias (SVTs) are the dysrhythmias postoperative MI, although it is probably more effective when
most commonly seen in the postoperative period, occurring used both preoperatively and perioperatively as a means of
after approximately 4% of noncardiac major operations. preventing MI.40
09/11
Discharge addressing it as early as possible in the postoperative period

Planning for discharge from the hospital is clearly an essen- is extremely valuable not only for ensuring an appropriate
tial part of perioperative care. In the best of circumstances, length of stay but also for maintaining the satisfaction and
discharge planning starts before admission for elective comfort of both patient and family. Specific issues should be
surgery and is discussed with the patient and family as part addressed at this point as needed, including the home
of preoperative patient education. Starting the process early resources and support available to the patient, wound care,
enables the provider to estimate the patient’s probable needs ostomy care, management of feeding tubes and drains, IV
at the end of acute hospitalization and thus to make prelimi- antibiotic therapy, and physical rehabilitation. Thus, as soon
nary arrangements as needed. For example, if it appears likely as it appears that a patient is on track either for discharge
that the patient will have to stay in a skilled nursing or home or for transfer to a rehabilitation or skilled nursing facil-
extended care facility or will require prolonged physical ity, a discussion with the appropriate social work or discharge
therapy and rehabilitation, these matters can be addressed to planning personnel should be scheduled. PT/OT evaluations
the mutual satisfaction of both patient and physician in early in the postoperative course can also be of great assis-
advance of hospital discharge. In this way, delays in discharge tance in determining a patient’s needs on discharge, and such
and unnecessary days of acute hospitalization can be avoided, evaluations are essential for any patient who may need a stay
at least in some instances. in an inpatient rehabilitation facility. Typically, it requires at
Criteria for discharge or transfer from acute hospital care least 1 day to set up services such as home health care and
vary widely depending on the procedure, the provider, and outpatient PT, and it may take this long or longer to obtain
the patient; rarely are they codified. For example, in a 2005 a bed at an appropriate rehabilitation or skilled nursing facil-
survey of 16 surgeons performing open colorectal resections ity. Consequently, the earlier these plans are made, the better.
within one hospital, only two factors—absence of complica- For many surgical patients, formal discharge planning and
tions and reported postoperative bowel movement—were PT/OT evaluations are not actually necessary. Brief discus-
considered criteria for early discharge by most (but not all) sions with the patient, the family, or the nursing staff caring
of the surgeons.45 There was wide disagreement on all other for the patient will assist in determining which surgical
criteria, including postoperative mobility and the ability to patients are most likely to benefit from this approach.
tolerate a general diet. Given such variation in discharge
criteria for even one category of procedure, it is clear that a
discussion of specific criteria for each type of surgery is well Current Controversies in Postoperative Management
beyond the scope of this chapter. It is worth pointing out, obstructive sleep apnea
however, that the various discharge criteria now in use,
despite their differences, have a common basis—namely, the Obstructive sleep apnea (OSA) has rapidly become the
idea that at discharge, the patient should ideally be able to most prevalent sleep disorder over the last 20+ years. At
manage basic self-care activities (e.g., feeding, wound care, present, estimates suggest that it affects 9% of women and
and mobility) without advanced assistance and that the likeli- 24% of men in the United States. Additionally, estimates also
hood of readmission should be minimized to the extent suggest that as many as 82% of men and 92% of women
possible. Identification, investigation, and control of factors affected do not carry the formal diagnosis of OSA.50,51 Despite
such as nausea, pain, fever, deconditioning, and fatigue are the large percentage of the population affected, no well-vetted
important in determining whether a patient is at risk for a specific guidelines are present in the current literature. That
return to the hospital in the postoperative period.46 being said, there is a wealth of discussion of the issue from
Over the past two decades, critical pathways, which are which several more general guidelines may be drawn.
organized plans that outline the sequence of patient care and Preoperative screening for OSA is the first and most critical
discharge, have been increasingly used in managing post- step in management. As a majority of affected patients have
operative care after a variety of procedures from all disci- not been formally diagnosed, this allows the operative team
plines. They have been shown to reduce hospital stays and the opportunity to detect the greatest number of patients at
maintain safety in patients undergoing common procedures risk and to adjust their operative plan of care accordingly.52
(e.g., colectomy), patients undergoing complex procedures Most commonly, screening is done by anesthesiology in the
(e.g., esophagectomy),47 and patients with high comorbid- preanesthesia setting using one of a number of available
ity.48 Individual pathways are typically specific to a hospital screening tools. In addition to this, it is important for the
or health care system; thus, the discharge criteria are those surgeon to also consider the potential presence of OSA as this
agreed on by the providers involved in the care of eligible may significantly affect the choice of surgical setting and
patients at that particular institution. Critical pathways can postoperative setting planned.53 Although, again, there are no
be helpful not only by standardizing care and improving the set guidelines provided in the literature dictating criteria
relative appropriateness of postoperative discharge but also, for outpatient versus inpatient surgical settings, for patients
in many cases, by decreasing the overall length of postopera- with known or suspected OSA requiring significant sedation
tive hospitalization.46 In a 2003 study of 27 postoperative or general anesthesia, using a setting with access to difficult
critical pathways used at the Johns Hopkins Hospital, airway carts, advanced respiratory care, and the option of a
the authors found that seven (27%) of the pathways were prolonged postanesthesia recovery unit (PACU) observation
associated with significant (5 to 45%) decreases in length of is recommended.54
stay.49 The two greatest issues in postoperative management are
Regardless of whether critical pathways are implemented, the level of monitoring provided and the use of sedatives
if discharge planning is not addressed preoperatively, and narcotic analgesics. The choice of surgical/postoperative
09/11
setting is best made after consideration of known or potential Multiple strategies have been employed in attempts to
OSA, any associated comorbidities, and the type of surgery decrease the length of postoperative ileus, such as early
to be performed. Patients with severe OSA generally require feeding, the use of chewing gum, and pharmacologic agents
inpatient monitoring postoperatively. Outside of known particularly directed at blocking the GI effects of narcotics.
severe OSA, the time observed in the PACU may also pro- Feeding patients early (i.e., before evidence of return of bowel
vide further information on which to base ongoing care or function) after abdominal surgery has been demonstrated to
discharge.51 Any patient who currently uses a home continu- be generally safe and forms an element of many postoperative
ous positive airway pressure (CPAP) or bilevel positive airway pathways. However, various studies comparing early feeding
pressure (BiPAP) device should use this in the immediate with awaiting return of bowel function have yielded mixed
postoperative period.55 In the inpatient setting, the use results, and no clear recommendation for early feeding can be
of continuous pulse oximetry and telemetry should be made across all procedures.56,58 Chewing gum is thought to
considered, and supplemental oxygen should be used with represent a sham-feeding condition that may have benefit in
caution.53,55 stimulating GI motility after abdominal surgery. It is safe; has
Anesthetics and sedatives depress the central nervous few, if any, significant risks; and is well tolerated by patients.
system, inhibit respiration, depress skeletal muscle tone, and A recent meta-analysis of seven randomized, controlled trials
relax the upper airway.55 Opiate drugs can depress respiratory comparing chewing gum with no gum after abdominal
drive and rate, decrease tidal volume, and lead to decreased surgery concluded that gum leads to a clinically significant
sensitivity to arousal. Thus, the use of sedatives postopera- improvement in return of bowel function as represented by a
tively should be avoided or used with great caution. Narcotic sooner return of flatus.59 However, not all individual trials
agents need to be titrated to adequate pain relief but should have demonstrated a benefit.56 Of the pharmacologic agents
be used only when nonnarcotic agents are ineffective. Addi- that have been investigated in the treatment of postoperative
tionally, the need for opiates may be significantly decreased ileus, alvimopan, which is a selective antagonist of the periph-
with the use of nonnarcotic agents such as acetaminophen, eral opioid mu receptor, appears to confer the most signifi-
centrally acting agents such as tramadol hydrochloride, cant benefit and was recently approved by the Food and
NSAIDs, or topical anesthetics when appropriate.53 Drug Administration for this indication. The recommended
The prevalence of OSA is only likely to increase given dose is 12 mg orally given twice daily for up to 7 days.57,60,61
current trends in associated comorbidities such as obesity. Alvimopan was shown to reduce the return to GI tract
Further prospective data are needed for more definitive function after bowel resection by 12 hours compared with
future recommendations, particularly regarding postoperative placebo in a meta-analysis of five randomized, controlled
monitoring and admission status. trials involving a total of 1,877 patients.62 Further, it does not
appear to have serious side effects.
postoperative ileus Postoperative ileus remains a major factor in determining
Ileus, or the cessation of bowel function and transit in the the length of hospital stay after abdominal surgery, particu-
absence of mechanical obstruction, is a common postopera- larly after bowel resection. Both chewing gum and alvimopan
tive phenomenon particularly after abdominal surgery and appear to provide some benefit in reducing the time to bowel
occurs in virtually all patients undergoing bowel resection. Its recovery after surgery, with the former being the most simple
causes are multifactorial, including an overall increase in and cost-effective to implement. None of these measures
sympathetic tone, the inflammatory response to bowel as a eliminate the effects of surgical intervention on GI motility
result of direct manipulation, and the well-known effects of entirely, however, and this will continue to be an area of
narcotic analgesics on GI motility.56 Although the typical active investigation in improving the care of the postoperative
duration of postoperative ileus averages around 3 days, in patient.56–62
up to 32% of patients, return of bowel function may be
particularly delayed.57 Financial Disclosures: None Reported
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1 BASIC SURGICAL AND PERIOPERATIVE CONSIDERATIONS 6 POSTOPERATIVE PAIN — 1
6 POSTOPERATIVE PAIN
Spencer S. Liu, MD, and Henrik Kehlet, MD, PHD, FACS (Hon)
Clinical Approach to the Patient with Postoperative Pain
Postoperative pain con- Guidelines for Postoperative Pain Treatment

sists of a constellation of In the past few years, efforts have been made to develop
unpleasant sensory, emo- procedure-specific perioperative pain management guide-
tional, and mental experi- lines. The impetus for these efforts has been the realization
ences associated with that the analgesic efficacy may be procedure dependent
autonomic, psychological, and that the choice of analgesia in a given case must also
and behavioral responses precipitated by the surgical injury. depend on the benefit-to-risk ratio, which varies among
Pain management has received increasing attention, and mul- procedures. In addition, it is clear that some analgesic
tiple government agencies and medical specialty organiza- techniques will be considered only for certain specific
tions have now created guidelines for treatment of operations (e.g., peripheral nerve blocks and intraperito-
postoperative pain.1 In 2001, the Joint Commission on neal local anesthesia).6–8 At present, these procedure-
Accreditation of Healthcare Organizations (JCAHO) intro- specific guidelines are still largely in a developmental state
duced standards for pain management,2 stating that patients and are available for laparoscopic cholecystectomy, open
have the right to appropriate evaluation and management and colon surgery, hysterectomy, inguinal hernia repair, thora-
that pain must be assessed. cotomy, mastectomy, hemorrhoidectomy, and knee and
Postoperative pain relief has two practical aims. The first hip replacement.9,10
is provision of subjective comfort, which is desirable for
humanitarian reasons. The second is inhibition of trauma- thoracic
induced nociceptive impulses to blunt autonomic and procedures
somatic reflex responses to pain and to enhance subsequent Pain after thoracotomy
restoration of function by allowing the patient to breathe, is severe, and pain therapy
cough, and move more easily. Because these effects reduce should therefore include a
pulmonary, cardiovascular, thromboembolic, and other combination regimen,
complications, they may lead secondarily to improved post- preferably comprising epidural local anesthetics and opi-
operative outcome. oids11 combined with systemic nonsteroidal antiinflammatory
drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors
Inadequate Treatment of Pain (depending on risk factors) [see algorithm]. If the epidural
regimen is not available, then comparable analgesia may be
A common misconception is that pain, no matter how
achieved with continuous thoracic paravertebral block, with
severe, can always be effectively relieved by opioid analgesics.
It has repeatedly been demonstrated, however, that in a high
proportion of postoperative patients, pain is inadequately Table 1 Contributing Causes of Inadequate Pain
treated.3,4 This discrepancy between what is possible and Treatment
what is practiced can be attributed to a variety of causes [see Insufficient knowledge of drug pharmacology among surgeons and
Table 1], which to some extent can be ameliorated by increased nurses
teaching efforts. Recent evidence also indicates that overreli- Uniform (p.r.n.) prescriptions
ance on opioid therapy may be inherently limiting because of
development of both acute tolerance and opioid-induced Lack of concern for optimal pain relief
hyperalgesia.5 The ability of opioids in high doses or with Failure to give prescribed analgesics
chronic administration to potentially induce pain illustrates Fear of side effects
the importance of using multimodal analgesic regimens that
Fear of addiction
target multiple analgesic pathways.
DOI 10.2310/7800.S01C06
01/09
Combine complementary alternative medicine with pharmalogic

and other interventions to treat postoperative pain
• Consider recommended multimodal combination regimens.

• Acetaminophen is recommended as a basic component of
multimodal analgesia in any of the settings listed below.
Thoracic Abdominal
Cardiac Noncardiac Major Open
Give systemic opioids Give epidural analgesia or Give epidural analgesia

with NSAIDs or COX-2 continuous paravertebral with NSAIDs or COX-2
inhibitors. block with NSAIDs or inhibitors.
Consider epidural COX-2 inhibitors. Secondary Choice:
analgesia or parasternal Secondary Choice: Give systemic PCA
wound catheter with local Give systemic PCA opioids with NSAIDs or
anesthetic. opioids with NSAIDs or COX-2 inhibitors.
COX-2 inhibitors.
COX-2 = cyclooxygenase-2, NSAIDs = nonsteroidal antiinflammatory drugs; PCA = patient-controlled analgesia.
01/09
Clinical Approach to the Patient

with Postoperative Pain
Pelvic Peripheral
Prostatectomy Gynecologic Vascular Major Joint Procedures
Give epidural analgesia Give systemic PCA Give epidural local Give continuous or single-
or systemic PCA opioids opioids with NSAIDs or anesthetics with NSAIDs dose perineural analgesia
with NSAIDs or COX-2 COX-2 inhibitors. or COX-2 inhibitors. (femoral or lumbar plexus)
inhibitors. Secondary Choice: Secondary Choice: with NSAIDs or COX-2
Give epidural analgesia. Give systemic opioids inhibitors.
with NSAIDs or COX-2 Secondary Choice:
inhibitors. Give systemic PCA or
single-dose spinal opioids
with NSAIDs or COX-2
inhibitors. Consider single-
dose perineural analgesia.
01/09
the potential for lesser incidence of urinary retention and Pain relief after major joint procedures (e.g., hip and knee
postoperative nausea and vomiting.12 Although comparable, operations)10 may involve an epidural regimen in certain high-
the continuous paravertebral technique may be more techni- risk patients because such regimens have been shown to reduce
cally difficult. If neither regional analgesic technique is thromboembolic complications and intraoperative blood loss
available, then the inferior regimen of NSAIDs and systemic and to improve physical rehabilitation when compared with
opioids may be used. Cryoanalgesia is not recommended as systemic opioid regimens.17,18 However, the severe pain noted
it is less effective.10 Acetaminophen is recommended as a after knee replacement is probably best treated with peripheral
basic analgesic for multimodal analgesia. Pain after cardiac nerve blocks.10,19 Most of the benefit of continuous femoral
operation with sternotomy is less severe, and systemic opi- nerve analgesia may also be achieved with a single-injection
oids plus NSAIDs are recommended. The combined regi- femoral nerve block.20 Total hip replacement is a less painful
men of epidural local anesthetics and opioids or parasternal procedure, but when pain is severe, a continuous lumbar
wound catheters with continuous administration of local plexus or femoral nerve block can be used.10,21 Alternatively
anesthetics13 is recommended when more effective pain and with less technical expertise, a single intrathecal dose of
relief is necessary, and it may reduce cardiopulmonary mor- local anesthetic and low-dose morphine will provide effective
bidity and perhaps length of stay.14 analgesia for the first 8 to 16 hours,10 after which NSAIDs or
COX-2 inhibitors may be added. Acetaminophen is provided
abdominal as a basic analgesic for multimodal analgesia.
procedures
Pain after major and Treatment Modalities
upper open abdominal
operations is severe, and a complementary and alternative medicine
combined regimen of epi- interventions
dural local anesthetics and opioids is recommended because Cognitive, behavioral, alternative, or social interventions
it has proved to be superior to systemic opioids and to have should be used in combination with pharmacologic therapies to
few and acceptable side effects.10,11,15 Furthermore, the epidu- prevent or control acute pain, with the goal of such interven-
ral regimen will reduce postoperative pulmonary complications being to guide the patient toward partial or complete self-
tions and ileus compared with treatment with systemic control of pain.22,23 A recent survey by the American Hospital
opioids.16 Systemic NSAIDs or COX-2 inhibitors are added Association indicated that 27% of member hospitals offered
when needed. Acetaminophen is recommended as a basic complementary and alternative medications (CAMs).24 Use of
analgesic for multimodal analgesia. nonpharmacologic adjunctive analgesics has been endorsed by
After gynecologic lower abdominal or pelvic operations,10 advisory bodies such as the Anesthesia Patient Safety Founda-
systemic opioids plus NSAIDs or COX-2 inhibitors are rec- tion and Institute of Healthcare Improvement.25,26
ommended except in patients in whom more effective pain Psychological preparation in patients with postoperative pain
relief is desirable. In such patients, the combined regimen of has been demonstrated to shorten hospital stay and reduce
epidural local anesthetics and opioids is preferable. Acet- postoperative narcotic use [see Table 2].27 Guided imagery,
aminophen is recommended as a basic analgesic for multi- relaxation, and music techniques have been demonstrated to
modal analgesia. reduce postoperative opioid use and affective pain.22 Acupunc-
Pain following prostatectomy is usually not severe and may ture and acupressure has been successfully used as an adjunct
be treated with systemic opioids combined with NSAIDs or for postoperative analgesia and reduces pain scores, anxiety
COX-2 inhibitors and acetaminophen. However, blood loss levels, and postoperative nausea.28 Alternative techniques
and thromboembolic complications are reduced when epidu-
ral local anesthetics are administered. This method is there-
fore recommended intraoperatively and continued in selected Table 2 Psychological Preparation of Surgical Patients
high-risk patients for pain relief after open prostatectomy and Procedural information
transurethral resection. In low-risk patients, systemic opioids Give a careful and relevant description of what will take place.
with NSAIDs or COX-2 inhibitors and acetaminophen allevi-
Sensory information
ate postoperative pain. Describe the sensations that will be experienced either during or
after the operation.
peripheral Pain treatment information
procedures Outline the plan for administering sedative and analgesic medi-
cation and encourage patients to communicate concerns and
After vascular proce- discomforts.
dures, postoperative pain
Instructional information
control is probably best
Teach patients postoperative exercises, such as leg exercises,
achieved with epidural and show them how to turn in bed or move so that pain is
local anesthetic–opioid mixtures, combined with systemic minimal.
NSAIDs or COX-2 inhibitors.11 Acetaminophen is recom- Reassurance
mended as a basic analgesic for multimodal analgesia. This Reassure those who are mentally, emotionally, or physically
regimen will be effective, and the increase in peripheral blood unable to cooperate that they are not expected to take an active
flow that is documented to occur with epidural local anes- role in coping with pain and will still receive sufficient analgesic
treatment.
thetics may lower the risk of graft thrombosis.
01/09
Table 3 Opioid Receptor Types and Physiologic Actions

Prototypical Ligand
Receptor Type Endogenous Exogenous Physiologic Actions
1
Mu ß-Endorphin Morphine Supraspinal analgesia
2
Mu ß-Endorphin Morphine Respiratory depression
Delta Enkephalin — Spinal analgesia
Kappa Dynorphin Ketocyclazocine Spinal analgesia, sedation, visceral analgesia
should be combined with pharmacologic or other interven- administration of an agonist-antagonist with a complete agonist
tions, but care must be taken to ensure that the pharmacologic may cause a reduction in the effect of the complete agonist.29
treatment does not compromise the mental function necessary
for the success of the planned psychological intervention. Agents
Morphine Morphine is the opioid with which the most
systemic opioids clinical experience has been gained. Sufficient pharmacoki-
Mechanisms of Action netic and pharmacodynamic data are available. Use of this
Opioids produce analgesia and other physiologic effects by agent is recommended; it may be given orally, intravenously
binding to specific receptors in the peripheral and central ner- (IV), or intramuscularly (IM).
vous system (CNS) [see Table 3]. These receptors normally Meperidine Detailed and sufficient pharmacokinetic
bind a number of endogenous substances called opioid pep- and pharmacodynamic data on meperidine are available. It is
tides. These receptor-binding interactions mediate a wide array less suitable than morphine as an analgesic because its active
of physiologic effects.29 Three types of opioid receptors and
their subtypes have been discovered: mu, delta, and kappa Table 4 Intrinsic Activity of Opioids
receptors. The most commonly used opioids bind to mu recep-
tors. The mu1 receptor is responsible for the production of Opioid Mu Kappa Delta
opioid-induced analgesia, whereas the mu2 receptor appears to Agonists
be related to the respiratory depression, cardiovascular effects, Morphine Agonist —
and inhibition of GI motility commonly seen with opioids.
Meperidine Agonist —
The discovery of peripheral opioid receptors has led to (Demerol)
investigation into potential clinical applications. Phase III
studies with alvimopan (a peripheral opioid antagonist that Hydromorphone Agonist
(Dilaudid)
does not cross the blood-brain barrier) have demonstrated
reduced ileus and hospitalization after abdominal surgery.30 Oxymorphone Agonist
(Numorphan)
Other studies have also investigated the analgesic effects of
applying opioids to wound sites in an attempt to provide Levorphanol Agonist
peripheral analgesia without central side effects. Unfortunately, (Levo-
Dromoran)
neither incisional31 nor intra-articular32 opioid administration
has demonstrated significant beneficial effect.30 This finding Fentanyl Agonist
may be attributable to the need for chronic inflammatory medi- (Duragesic)
ators to facilitate expression of peripheral opioid receptors.33 Sufentanil Agonist
The relation between receptor binding and the intensity of (Sufenta)
the resultant physiologic effect is known as the intrinsic activ- Alfentanil (Alfenta) Agonist
ity of an opioid. Most of the commonly used opioid analge- Methadone Agonist
sics are agonists. An agonist produces a maximal biologic (Dolophine)
response by binding to its receptor. Other opioids, such as
Agonist-Antagonists
naloxone, are termed antagonists because they compete with
agonists for opioid receptor-binding sites. Still other opioids Buprenorphine Partial
(Buprenex) agonist
are partial agonists because they produce a submaximal
response after binding to the receptor. (An excellent example Burtorphanol Antagonist Agonist Agonist
of a submaximal response produced by partial agonists is (Stadol)
buprenorphine’s action at the mu receptor.) Nalbuphine Antagonist Partial Agonist
Drugs such as nalbuphine, butorphanol, and pentazocine are (Nubain) agonist
known as agonist-antagonists or mixed agonist-antagonists.29 Pentazocine Antagonist Agonist Agonist
These opioids simultaneously act at different receptor sites: their (Talwin)
action is agonistic at one receptor and antagonistic at another Dezocine (Dalgan) Partial
[see Table 4]. The agonist-antagonists have certain pharmaco- agonist
logic properties that are distinct from those of the more common Antagonists
mu agonists: (1) they exhibit a ceiling effect and cause only
submaximal analgesia compared with mu agonists and (2) Naloxone (Narcan) Antagonist Antagonist Antagonist
01/09
metabolite, normeperidine, can accumulate, even in patients about 30% of the time during any 4-hour dosing interval.
with normal renal clearance, and this accumulation can result The optimal means to treat moderate to severe postoperative
in CNS excitation and seizures.29 Other agents should be pain with systemic opioids is via IV patient-controlled anal-
used before meperidine is considered. Like morphine, meper- gesia (PCA). This delivery system compensates for the wide
idine can be given orally, IV, or IM. inter- and intraindividual variability in analgesic needs and
blood levels after opioid administration. Self-delivery helps
Side Effects produce timely titration of analgesia and reduces administra-
By depressing or stimulating the CNS, opioids cause a tive delay from conventional delivery (e.g., p.r.n.). Systematic
number of physiologic effects in addition to analgesia. The reviews have noted that IV PCA delivery of opioids reduces
depressant effects of opioids include analgesia, sedation, and pain scores and improves patient satisfaction over conven-
altered respiration and mood; the excitatory effects include tional delivery.34 Typical regimens are provided in Table 5.
nausea, vomiting, and miosis. Recent advances in iontophoretic technology have led to
All mu agonists produce a dose-dependent decrease in the commercial release of a transdermal fentanyl iontophoretic
responsiveness of brainstem respiratory centers to increased PCA system. This system delivers 40 µ g fentanyl over
carbon dioxide tension (Pco2). This change is clinically man- 10 minutes after patient demand. Onset is rapid because of
ifested as an increase in resting Pco2 and a shift in the CO2 the active electrical current driving the fentanyl transder-
response curve. Agonist-antagonist opioids have a limited mally. The system deactivates after 24 hours or 80 adminis-
effect on the brainstem and appear to elicit a ceiling effect on trations. Several clinical trials have reported equivalence
increases in Pco2. between the fentanyl system and IV PCA opioid.35 One
Opioids also have effects on the gastrointestinal (GI) tract. pooled analysis suggested less analgesic gaps with the fentanyl
Nausea and vomiting are caused by stimulation of the che- system because of fewer technical failures and administrative
moreceptor trigger zone of the medulla. Opioids enhance delays than the IV PCA device36; however, the role of this
sphincteric tone and reduce peristaltic contraction. Delayed fentanyl system remains to be fully defined.
gastric emptying is caused by decreased motility, increased
antral tone, and increased tone in the first part of the duode- epidural and subarachnoid opioids
num. Delay in passage of intestinal contents because of
Opioids were first used in the epidural and subarachnoid
decreased peristalsis and increased sphincteric tone leads to
spaces in 1979. Since that time, they have become the main-
greater absorption of water, increased viscosity, and desicca-
stay of postoperative management for severe pain. Epidural
tion of bowel contents, which cause constipation and contrib-
opioids may be administered in a single bolus or via continu-
ute to postoperative ileus. Opioids also increase biliary tract
ous infusions. They are usually combined with local anesthet-
pressure. Finally, opioids may inhibit urinary bladder func-
ics in a continuous epidural infusion to enhance analgesia.37
tion, thereby increasing the risk of urinary retention.
Several long-acting, slow-release oral opioids are currently
available, but their role (in particular, their safety) in the set- Mechanisms of Action
ting of moderate to severe postoperative pain remains to be Opioids injected into the epidural or subarachnoid space
established. In addition, modern principles of treatment cause segmental (i.e., selective, spinally mediated) analgesia
increasingly emphasize the use of opioid-sparing analgesic by binding to opioid receptors in the dorsal horn of the spinal
approaches to enhance recovery (see below). cord.38 The lipid solubility of an opioid, described by its par-
tition coefficient, predicts its behavior when introduced into
clinical application of systemic opioids the epidural or subarachnoid space. Opioids with low lipid
Traditional IM dosing of opioids is a suboptimal means of solubility (i.e., hydrophilic opioids) have a slow onset of
analgesia.34 IM dosing does not result in consistent blood action and a long duration of action. Opioids with high lipid
levels, because opioids are absorbed at a variable rate from solubility (i.e., lipophilic opioids) have a quick onset of action
the vascular bed of muscle. Moreover, administration of tra- but a short duration of action. This is attributable to more
ditional IM regimens results in opioid concentrations that rapid diffusion across the dura into the spinal cord but
exceed the concentrations required to produce analgesia only also more rapid systemic uptake and clearance via uptake into
Table 5 Typical Intravenous Patient-Controlled Analgesia Regimens

Drug Concentration Size of Bolus Lockout Interval (min)
Agonists
Morphine (1 mg/mL)
Adult 0.5–2.5 mg 5–10
Pediatric 0.01–0.03 mg/kg (max. = 0.15 mg/kg/hr) 5–10
Fentanyl (0.01 mg/mL)
Adult 10-20 ug 4–10
Pediatric 0.5–1 µ g/kg (max. = 4 µ g/kg/hr) 5–10
Hydromorphone (0.2 mg/mL)
Adult 0.05–0.25 mg 5–10
Pediatric 0.003–0.005 mg/kg (max. = 0.02 mg/kg/hr) 5–10
01/09
epidural and spinal cord blood vessels. In fact, current Naloxone reverses the depressive respiratory effects of spinal
evidence suggests that a major site of action of spinal lipo- opioids. In an apneic patient, 0.4 mg IV will usually restore
philic opioids is not the spinal cord but the brain via systemic ventilation. If a patient has a depressed respiratory rate but is
uptake.39 Thus, lipophilic opioids as sole epidural analgesic still breathing, small aliquots of naloxone (0.2 to 0.4 mg) can
agents are becoming less frequently recommended. be given until the respiratory rate returns to normal.
Subarachnoid opioids should be used when the required Nausea and vomiting are caused by transport of opioids to
duration of analgesia after surgery is relatively short (< 24 hours) the vomiting center and the chemoreceptor trigger zone in
because of typical single-injection delivery. When protracted the medulla via CSF flow or the systemic circulation. Nausea
analgesia is required, epidural administration is preferred; can usually be treated with antiemetics or, if severe, with nal-
repeated injections may be given through epidural catheters, or oxone (in 0.2 mg increments, repeated if necessary).
continuous infusions may be used. Smaller doses of subarach- Pruritus is probably the most common side effect of the
noid opioids are generally required to produce analgesia. Ordi- spinal opioids. Although not fully defined, the mechanism
narily, no more than 0.1 to 0.25 mg of morphine should be used likely involves activation of “itch-specific” opioid receptors
to provide 12 to 24 hours of analgesia. These doses, which are on spinal sensory neurons.45 Although pruritus is commonly
about 10 to 20% of the size of comparably effective epidural treated with antihistamines, there is minimal evidence for
doses, provide reliable pain relief with few side effects.40 Fen- mechanism-specific effectiveness. An alternative and proba-
tanyl has also been extensively used in the subarachnoid space bly superior treatment is use of a mixed opioid agonist antag-
in a dose range of 6.25 to 25 µ g to provide 3 to 6 hours of onist to directly block the opioid receptor–induced itching
analgesia. Recently, an extended duration formulation of epidu- while maintaing opioid analgesias. Doses of 5 mg of nalbu-
ral morphine has been commercially released.41–43 phine IV or 2 to 4 mg of butorphanol intranasally or IV every
This formulation consists of morphine encased in multive- 6 hours is commonly used.45
sicular lipid with predictable sustained release. Clinical stud- The mechanism of spinal opioid–induced urinary retention
ies have overall supported the efficacy and general safety of involves inhibition of volume-induced bladder contractions
this formulation (10–15 mg doses) without demonstrating and blockade of the vesical reflex. Naloxone administration is
marked superiority over conventional central neuraxial opioid the treatment of choice, although bladder catheterization is
therapy. Thus, the role of this preparation remains to be sometimes required.
determined.
clinical application of epidural and
Side Effects subarachnoid opioids
The chief side effects associated with epidural and As stated earlier, subarachnoid opioids are limited in the
subarachnoid opioids are respiratory depression, nausea and duration of analgesia because of typical single-injection deliv-
vomiting, pruritus, and urinary retention.38,40,44 The poor lipid ery. Epidural administration allows prolonged delivery of opi-
solubility of morphine is responsible for its protracted dura- oids, and typical regimens are listed in Table 6. However,
tion of action but also allows morphine to undergo cephalad side effects from opioids are common, and it is better to com-
migration in the cerebrospinal fluid (CSF). This migration bine epidural opioids with local anesthetics to obtain multi-
can cause delayed respiratory depression, with a peak inci- modal and synergistic analgesia. This allows smaller doses of
dence 3 to 10 hours after an injection. The high lipid solubil- both agents to be used with better analgesia and fewer side
ity of lipophilic opioids such as fentanyl allows them to be effects. Typical regimens are listed in Table 7.
absorbed into lipids close to the site of administration. Con-
sequently, the lipophilic opioids do not migrate rostrally in epidural local anesthetics and other
the CSF and cannot cause delayed respiratory depression. Of regional blocks
course, the high lipid solubility of lipophilic opioids allows Local anesthetic neural blockade is unique among available
them to be absorbed into blood vessels, which may cause analgesic techniques in that it may offer sufficient afferent
early respiratory depression, as is commonly seen with sys- neural blockade, resulting in relief of pain; avoidance of seda-
temic administration of opioids. Overall, the typical incidence tion, respiratory depression, and nausea; and, finally, efferent
of respiratory depression is similar to that seen with systemic sympathetic blockade, resulting in increased blood flow to the
opioids at approximately 0.2%.44 region of neural blockade.46
Table 6 Typical Dosing of Neuraxial Opoids

Intrathecal or Subarachnoid
Drug Single Dose Epidural Single Dose Epidural Continuous Infusion
Fentanyl 5–25 µ g 50–100 µ g 25–100 µ g/hr
Sufentanil 2–10 µ g 10–50 µ g 10–20 µ g/hr
Morphine 0.1–0.3 mg 1–5 mg 0.1–1 mg/hr
Hydromorphone — 0.5–1 mg 0.1–0.2 mg/hr
Meperidine 10–30 mg 20–60 mg 10–60 mg/hr
Lower doses may be effective when administered to the elderly or when injected in the cervical or thoracic region. Units vary across agents for single dose (mg
versus µ g) and continuous infusion (mg/hr versus µ g/hr).
01/09
Table 7 Typical Patient-Controlled Epidural Analgesia Regimens

Analgesic Solution Continuous Rate (mL/hr) Demand Dose (mL) Lockout Interval (min)
0.0625–0.125% bupivacaine + 2–5 µ g/mL 4–6 3–4 10–15
fentanyl
0.125–0.125% bupivacaine + 2–5 µ g//mL 3–5 2–3 12
sufentanil
0.1–0.2% ropivacaine + 2–4 µ g//mL 3–5 2–5 10–20
fentanyl
Mechanism of Action clinical application of continuous epidural

Local anesthetic neural blockade is a nondepolarizing block analgesia
that reduces the permeability of cell membranes to sodium Typical regimens are listed in Table 7. As is similar with
ions.47 Whether different local anesthetics have different IV PCA, patient-controlled epidural analgesia (PCEA) has
effects on different nerve fibers is debatable. been demonstrated to provide superior analgesia, decreased
analgesic consumption, and decreased side effects.51 The
Choice of Drug safety of PCEA regimens for hospital wards has been well
For optimal management of postoperative pain, the anes- documented.52 As all epidural analgesic agents are deliber-
thetic agent should provide excellent analgesia of rapid onset ately segmental (limited in anatomic spread) in nature, it is
and long duration without inducing motor blockade. The important for the vertebral site of epidural placement to
various local anesthetic agents all meet one or more of these match the site of surgery. For example, lumbar epidurals
criteria; however, the ones that come closest to meeting all of offer inferior analgesia to thoracic epidurals for thoracic sur-
the criteria are bupivacaine, ropivacaine, and levobupivacaine. gery. Suggested epidural sites are also listed in Table 9.
This should not preclude the use of other agents, because
their efficacy has also been demonstrated. Ropivacaine and other regional analgesia techniques
levobupivacaine may have a better safety profile, but the Intraperitoneal administration of local anesthetics cannot
improvement may be relevant only when high intraoperative be recommended for typical postoperative analgesia,
doses are given.47 because they are not efficacious,53 except in laparoscopic
cholecystectomy.8,10 Intraincisional administration of bupi-
Side Effects
vacaine or other long-acting local anesthetics, which has
The main side effects of epidural local anesthesia are hypo- negligible side effects and demands little or no surveillance,
tension caused by sympathetic blockade, vagal overactivity, is recommended for patients undergoing relatively minor
and decreased cardiac function (during a high thoracic block). procedures.
Under no circumstances should epidural local anesthetics be Continuous administration of local anesthetics into the
used before a preexisting hypovolemic condition is treated. wound via a catheter directly placed at the end of surgery is
Hypotension may be treated with ephedrine, 10 to 15 mg IV, a simple and efficacious means to provide postoperative
and fluids, with the patient tilted in a head-down position. analgesia. A recent systematic review noted that wound
Atropine, 0.5 to 1.0 mg IV, may be effective during vagal catheters improved postoperative analgesia, reduced opioid
overactivity.
Urinary retention occurs in 20 to 100% of patients, and
urinary catheterization is typically used during epidural anal-
Table 8 Procedures for Maintenance of Epidural
gesia. Motor blockade may delay mobilization; however, its Anesthesia for Longer than 24 Hours
incidence can be reduced by using the weakest concentration
1. Administer appropriate drug in appropriate dosage at selected
of local anesthetic that is compatible with adequate sensory
infusion rate as determined by physician
blockade.
The routine complications associated with the epidural 2. Nurse evaluates vital signs and intake and output as required
for a postoperative patient
catheter are minimal when proper nursing protocols are fol-
lowed [see Table 8]. The decision to employ epidural local 3. Nurse checks infusion pump hourly to ensure that it is function-
anesthetics in such patients should be made only after the ing properly, that infusion rate is proper, and that alarm is on
risks44,48 are carefully compared with the documented advan- 4. Nurse also assesses
tages of such anesthetics.49,50 • Bladder—for distention, if patient is not catherized
Spinal hematoma attributable to the combination of epidu- • Lower extremities—for status of motor function
ral analgesia and anticoagulants is rare, but the risk may be • Central nervous system—for signs of toxicity or respiratory
depression
increased by specific agents. Guidelines on the use of epidural • Skin integrity on back (breakdown may occur if motor func-
analgesia and anticoagulation are currently listed on the tion is not present)
American Society of Regional Anesthesia and Pain Medicine • Tubing and dressing (disconnection of tubing or dislodg-
Web site.48 Most anticoagulants can be safely managed with ment of catheter may occur)
epidural analgesia; however, special care must be taken with 5. Every 48 hr, the catheter dressing should be removed, the cath-
thrombolytics, low-molecular-weight heparins, and newer eter entrance site cleaned, and topical antibiotic applied (much
antiplatelet, antithrombin, and anti–factor Xa agents. as in care of a central venous catheter)
01/09
Table 9 Recommended Location of Catheter Insertion for Surgical Procedures

Congruent Epidural Catheter
Location of Incision Examples of Surgical Procedures Placement
Thoracic Lung reduction, radical mastectomy, thoracotomy, thymectomy T4–8
Upper abdominal Cholecystectomy, esophagectomy, gastrectomy, hepatic section, Whipple T6–8
procedure
Middle abdominal Cystoprostatectomy, nephrectomy T7–10
Lower abdominal Abdominal aortic aneurysm repair, colectomy, radical prostatectomy, T8–11
total abdominal hysterectomy
Lower extremity Femoropopliteal bypass, total hip or total knee replacement L1–4
L = lumbar; T = thoracic.
use, and decreased opioid-related side effects in a variety of any agent or agents over the others, and selection therefore
procedures.13 However, there is still a need for more may depend on the convenience of delivery, duration, and
procedure-specific data before general recommendations can cost.66 All of the NSAIDs have potentially serious side effects:
be made as a wide variety of surgical procedures, catheter GI and surgical site hemorrhage, renal failure, impaired bone
locations, and analgesic regimens were included in the sys- healing, and asthma. The endoscopically verified superficial
tematic review. ulcer formation seen within 7 to 10 days after the initiation
Continuous peripheral nerve blocks are growing in popular- of NSAID therapy is not seen with selective COX-2 inhibitor
ity, and the analgesic treatment may be continued after dis- treatment in volunteers. The clinical relevance of these find-
charge.54,55 A systematic review has documented multiple ings for perioperative treatment remains to be established,
benefits from the use of continuous perineural analgesia versus however, given that acute severe GI side effects (bleeding,
systemic opioids, such as reduced pain scores at rest and with perforation) are extremely rare in elective cases.
activity, reduced opioid use, reduced opioid-related side Because prostaglandins are important for regulation of
effects, and increased patient satisfaction.54 Use of outpatient water and mineral homeostasis by the kidneys in the dehy-
perineural analgesia is also growing in popularity, and studies drated patient, perioperative treatment with NSAIDs, which
have observed that this form of analgesia reduces unplanned inhibit prostaglandin synthesis, may lead to postoperative
hospital admission after ambulatory procedures, improves renal failure. So far, specific COX-2 inhibitors have not been
patients quality of life at home, and may facilitate conversion demonstrated to be less nephrotoxic than conventional
of hospital procedures to short-stay procedures (e.g., total NSAIDs.62,67 Although little systematic evaluation has been
knee replacement).56 A growing body of literature surveying done, extensive clinical experience with NSAIDs suggests
the use of thousands of perineural catheters for postoperative that the renal risk is not substantial.68 Nonetheless, conven-
analgesia documents a low incidence of complications and tional NSAIDs and COX-2 inhibitors should be used with
overall safety of this technique.57 More recently, a high-volume caution in patients who have preexisting renal dysfunction.62
infiltration technique with dilute concentrations of local anes- Although conventional NSAIDs prolong bleeding time and
thetics with or without adjuvants seems promising because of inhibit platelet aggregation, there generally does not seem to
its apparent efficacy, simplicity, and safety.58,59
nsaids, cox-2 inhibitors, and acetaminophen Table 10 Typical Dosing for Common NSAIDs, COX-2
Inhibitors, and Acetaminophen
NSAIDs and COX-2 inhibitors are modest analgesics that
have both peripheral and central analgesic mechanisms and Typical Dose for Maximum
Postoperative Recommended
antiinflammatory effects [see Table 10]. Although these agents
Drug Analgesia Dose (mg/day)
are typically less effective as sole analgesic agents than opi-
oids,60 they have an excellent efficacy to safety profile and are Acetaminophen 650–1,000 mg q 6 hr 4,000
generally recommended after all kinds of operations for low- Celecoxib 100–200 mg q 12 hr 400
risk patients.61,62 Several reviews and systematic reviews report Diclofenac 50 mg q 8 hr 150
that NSAIDs and COX-2 inhibitors decrease systemic mor-
Ibuprofen 400 mg q 6 hr 3,200
phine use by approximately 13 to 18 mg over a 24-hour
period.61,62 More importantly, these reviews indicate that Indomethacin 25–50 mg q 8 hr 200
NSAIDs decrease pain scores by approximately 1 cm on a 10 cm Ketorolac 10 mg q 4–6 hr 40
visual analogue scale pain score and reduce opioid-related side
Ketorolac 15–30 mg q 6 hr 120
effects of sedation and nausea by approximately 30%. Conven- (intravenous)
tional NSAIDs inhibit both COX-1 and COX-2. Selective
Meloxicam 7.5–15 mg q day 15
COX-2 inhibitors, which do not inhibit COX-1, have the
potential to achieve analgesic efficacy comparable to that of Naproxen 250 mg q 6–8 hr 1,375
conventional NSAIDs but with fewer minor side effects.63–65 Paracetamol 1,000 mg q 6 hr 4,000
Only a few of the NSAIDs may be given parenterally. The (intravenous)
data now available on the use of NSAIDs for postoperative COX-2 = cyclooxygenase; NSAIDs = nonsteroidal antiinflammatory
pain are insufficient to allow definitive recommendation of drugs.
01/09
be a clinically significant risk of increased bleeding. However, of serotonin and norepinephrine.78 It can be used as an intra-
in some procedures for which strict hemostasis is critical venous analgesic but is less potent than opioids (morphine,
(e.g., tonsillectomy, cosmetic surgery, and eye surgery), these meperidine)79 and is a poor sole agent for control of postop-
drugs have been shown to increase the risk of bleeding com- erative pain.80
plications and should therefore be replaced with COX-2 Several systematic reviews have suggested that some anal-
inhibitors, which do not inhibit platelet aggregation.69 The gesic and perioperative opioid-sparing effects can be achieved
observation that prostaglandins are involved in bone and by adding an N-methyl-d-aspartate (NMDA) receptor
wound healing has given rise to concern about potential side antagonist (e.g., ketamine), gabapentin, or pregabalin [see
effects in surgical patients. Although there is experimental Combination Regimens, below].34,81
evidence that both conventional NSAIDs and COX-2 inhib-
itors can impair bone healing,70 the clinical data available at transcutaneous electrical nerve stimulation
present are insufficient to document increased wound or Transcutaneous electrical nerve stimulation (TENS) is the
bone healing failure with these drugs.71 This is a particularly application of a mild electrical current through the skin sur-
important issue for future study in that many orthopedic surface to a specific area, such as a surgical wound, to achieve
geons remain reluctant to use NSAIDs. pain relief; the exact mechanism whereby it achieves this
Currently, there is widespread concern about the increased effect is yet to be explained but may involve spinal gating and
risk of cardiovascular complications associated with long-term activation of opioid receptors. Although several randomized
treatment with selective COX-2 inhibitors. Generally, such controlled trials have reported efficacy after inguinal herni-
side effects have appeared only after 1 to 2 years of treatment otomy,82 thoracotomy,83 and other procedures,84 the specific
and led to the withdrawal of rofecoxib in 2004 and valdecoxib values and the proper uses of the various stimulation frequen-
in 2005 from the US market.72 In the past few years, however, cies, waveforms, and current intensities have not been deter-
two studies of patients undergoing coronary artery bypass mined. In addition, blinding of subjects is difficult with TENS
grafting (CABG) found that the risk of cardiovascular com- studies, and this effect of bias is difficult to assess. Overall,
plications was increased significantly (two- to threefold) in the effect of TENS on acute pain is too imprecise to warrant
this setting and led to the label change for COX-2 inhibitors a recommendation for routine use.85
and NSAIDs indicating that these agents are contraindicated
in CABG patients.72 The larger question is whether these combination regimens
drugs should also be contraindicated for perioperative use, or Because no single pain treatment modality is optimal, com-
at least used with caution, in high-risk cardiovascular patients bination regimens (e.g., balanced analgesia or multimodal
who are undergoing procedures other than CABG. At pres- treatment) offer major advantages over single-modality regi-
ent, the data are insufficient to allow final conclusions; none- mens, whether by maintaining or improving analgesia, by
theless, reviews suggest that the benefits of short-term use of reducing side effects, or by doing both.86 Combinations of
these agents in patients without cardiovascular risk factors epidural local anesthetics and morphine,15,44 of NSAIDs and
probably outweigh the potential (low) risk of complications. opioids,66,87,88 of NSAIDs and acetaminophen,73,74 of acet-
Until further studies are performed, use in patients with car- aminophen and opioids,89 of acetaminophen and tramadol,90
diovascular risk factors should be cautious.72 and of a selective COX-2 inhibitor and gabapentin91 or pre-
Acetaminophen also possesses analgesic capability, both gabalin81 have been reported to have additive effects. At pres-
peripherally and centrally. Its analgesic effect is somewhat (about ent, information on other combinations (involving ketamine,
20 to 30%) weaker than those of conventional NSAIDs and clonidine, glucocorticoids, and other agents) is too sparse to
COX-2 inhibitors. For example, use of acetaminophen typically allow firm recommendations; however, multimodal analgesia
reduces morphine consumption by approximately 9 mg over a is undoubtedly promising, and multidrug combinations
24-hour period,61 which may be insufficient to significantly should certainly be explored further.
reduce opioid-related side effects or dramatically improve anal- The potential of combination regimens is especially intrigu-
gesia. However, acetaminophen lacks the side effects typical of ing with respect to the concept of perioperative opioid-sparing
NSAIDs.62 Combining acetaminophen with NSAIDs may analgesia. The use of one or several nonopioid analgesics in
improve analgesia, especially in smaller and moderate-sized such regimens may enhance recovery in that the concomitant
operations73,74; accordingly, this agent is recommended as a reduction in the opioid dosage will lead to decreased nausea,
basic component of multimodal analgesia in all operations. vomiting, and sedation.92–95 Both the adverse events associated
with postoperative opioid analgesia and the relatively high costs
other analgesics of such analgesia argue for an opioid-sparing approach.96,97 The
Glucocorticoids are powerful antiinflammatory agents and ability to reduce opioid-related and non–opioid-related side
have proven analgesic value in less extensive procedures,75,76 effects by use of multimodal analgesia may become especially
especially dental, laparoscopic, and arthroscopic operations. attractive for several reasons. First, there is growing evidence
In addition, they have profound antiemetic effects.77 Con- that the use of opioids as sole analgesics can lead to opioid-
cerns about possible side effects in the setting of perioperative induced hyperalgesia, whereby overstimulation of opioid recep-
administration have not been borne out by the results of ran- tors creates a nociceptive state (i.e., opioids increase sensitivity
domized studies.75,76 to painful stimuli).98 Also, in light of the JCAHO pain initiative
Tramadol is a weak analgesic that has several relatively and overall increased focus on reducing pain,1 a concern exists
minor side effects (e.g., dizziness, nausea, and vomiting) and that these initiatives may precipitate increased use of opioids
possesses weak opioid agonist activity and inhibits reuptake and thereby an increased risk of side effects.99,100
01/09
Discussion
Physiologic Mechanisms of Acute Pain or augmentation of this descending system enhances analgesia.
The noxious stimuli from iatrogenic surgical injury or Epidural-intrathecal administration of alpha-adrenergic agonists
accidental trauma set a cascade of events in motion cumu- (e.g., clonidine) or of anticholinesterases (e.g., neostigmine)
lating in the perception of “pain.” Many interrelated com- works in this manner to provide pain relief.94
ponents contribute to the processing of nociceptive stimuli.
spinal reflexes
Clinicians should recognize that the neurobiology of noci-
ception is extremely complex, with multiple levels of redun- Nociception may be enhanced by spinal reflexes that affect
dancy, such that there is no “hardwired” or “final common” the environment of the nociceptive nerve endings. Thus,
pathway for the process of nociception of acute pain. The tissue damage may provoke an afferent reflex that causes
basic mechanisms are (1) afferent transmission of nocicep- muscle spasm in the vicinity of the injury, thereby increasing
tive stimuli through the peripheral nervous system after nociception. Similarly, sympathetic reflexes may cause
tissue damage, (2) modulation of these injury signals by decreased microcirculation in injury tissue, thereby generat-
control systems in the dorsal horn, and (3) modulation of ing smooth muscle spasm, which amplifies the sensation.
the ascending transmission of pain stimuli by a descending
control system originating in the brain [see Figure 1].101–103 postinjury changes in peripheral and
central nervous systems
peripheral pain receptors and neural
After an injury, the afferent nociceptive pathways undergo
transmission to the spinal cord
physiologic, anatomic, and chemical changes.102,103 These changes
Peripheral pain receptors (nociceptors) can be identified by include increased sensitivity on the part of peripheral nociceptors,
function but cannot be distinguished anatomically. The as well as the growth of sprouts from damaged nerve fibers that
responsiveness of peripheral pain receptors may be enhanced become sensitive to mechanical and alpha-adrenergic stimuli and
by endogenous analgesic substances (e.g., prostaglandins, eventually begin to fire spontaneously. Moreover, excitability
serotonin, bradykinin, nerve growth factor, and histamine), may be increased in the spinal cord, which leads to expansion of
as well as by increased efferent sympathetic activity.101 Anti- receptive fields in dorsal horn cells. Such changes may lower pain
dromic release of substance P may amplify the inflammatory thresholds, may increase afferent barrage in the late postinjury
response and thereby increase pain transmission. The periph- state, and, if normal regression does not occur during convales-
eral mechanisms of visceral pain are different from somatic or cence, may contribute to a chronic pain state.102
neuropathic nociception and likely involve transient receptor Neural stimuli have generally been considered to be the
potential vanilloid 1 receptors, acid-sensing ion channels, and main factor responsible for initiation of spinal neuroplasticity;
tachykinins.104 Peripheral opioid receptors have been demon- however, it now appears that such neuroplasticity may also be
strated to appear in inflammation on the peripheral nerve mediated by cytokines released as a consequence of COX-2
terminals but probably have little clinical relevance.31–33 induction.103 Improved understanding of the mechanisms of
Somatic nociceptive input is transmitted to the CNS through pain may serve as a rational basis for future drug development
A-delta and C fibers, which are small in diameter and either and may help direct therapy away from symptom control and
unmyelinated or thinly myelinated. Visceral pain is transmit- toward mechanism-specific treatment.107
ted through afferent sympathetic pathways; the evidence that In experimental studies, acute pain behavior or hyperexcit-
afferent parasympathetic pathways play a role in visceral noci- ability of dorsal horn neurons may be eliminated or reduced if
ception is inconclusive.104,105 the afferent barrage is prevented from reaching the CNS. Pre-
injury neural blockade with local anesthetics or opioids can
dorsal horn control systems and modula- suppress excitability of the CNS; this is called preemptive anal-
tion of incoming signals gesia. Although this has been a consistent finding in laboratory
All incoming nociceptive traffic synapses in the gray matter of studies, clinical studies have been less dramatic. A critical anal-
the dorsal horn (Rexed laminae I to IV). Several substances may ysis of controlled clinical studies that compared the efficacy of
be involved in primary afferent transmission of nociceptive stimuli analgesic regimens administered preoperatively with the effi-
in the dorsal horn: substance P, enkephalins, somatostatin, neu- cacy of the same regimens administered postoperatively con-
rotensin, g-aminobutyric acid (GABA), glutamic acid, angiotensin cluded that preemptive analgesia does not always provide a
II, vasoactive intestinal polypeptide (VIP), and cholecystokinin clinically significant increase in pain relief.108,109 Nonetheless, it
octapeptide (CCK-8).102,106 From the dorsal horn, nociceptive is important that pain treatment be initiated early to ensure
information is transmitted through the spinothalamic tracts to the that patients do not wake up with high-intensity pain.
hypothalamus, through spinoreticular systems to the brainstem
and reticular formation, and finally to the cerebral cortex.
Effects of Pain Relief
descending pain control system
s elected p hys iologic res p ons es to oper ation
A descending control system for sensory input originates in
the brainstem and reticular formation and in certain higher brain Cardiovascular
areas. The main neurotransmitters in this system are norepi- It has traditionally been thought that an imbalance of myo-
nephrine, serotonin, acetylcholine, and enkephalins. Stimulation cardial oxygen supply and demand, such as an increase in
01/09
Perception of Pain
Trauma
Capillary
To the Limbic System Descending Inhibitory Pathway

Neurotransmitters at
Dorsal Horn Level:
Norepinephrine Release of
Serotonin Substance P
Enkephalins Histamine
Serotonin
Primary Afferent
Bradykinin
Neurotransmitter
Prostaglandins
Candidates
Substance P
Spinothalamic Tract L-Glutamate
GABA Release of
VIP
CCK-8 Sensory Nerve Norepinephrine
Somatostatin
Muscle
Motor of other Efferent Nerve
Segmental Reflexes:
Increased Skeletal Muscle Tension
Decreased Chest Compliance
More Nociceptive Input
Increased Sympathetic Tone
Decreased Gastric Mobility
IIeus, Nausea, Vomiting
Figure 1 Shown are the major neural pathways involved in nociception. Nociceptive input is transmitted from the periphery to
the dorsal horn via A-delta and C fibers (for somatic pain) or via afferent sympathetic pathways (for visceral pain). It is then
modulated by control systems in the dorsal horn and sent via the spinothalamic tracts and spinoreticular systems to the
hypothalamus, to the brainstem and reticular formation, and eventually to the cerebral cortex. Ascending transmission of
nociceptive input is also modulated by descending inhibitory pathways originating in the brain and terminating in the dorsal horn.
Nociception may be enhanced by reflex responses that affect the environment of the nociceptors, such as smooth muscle spasm.
CCK = cholecystokinin-octapeptide; GABA = γ -aminobutyric acid; VIP = vasoactive intestinal peptide.
demand (e.g., increase in heart rate or blood pressure) or a uncontrolled postoperative pain may be especially detrimen-
decrease in supply (e.g., decreased coronary blood flow to the tal and contribute to cardiac morbidity through activation of
vulnerable subendocardial areas), may contribute to periop- the sympathetic nervous system, other surgical stress
erative cardiac events, particularly in patients with decreased responses, and the coagulation cascade. Increased sympa-
cardiac reserve.110 Although many factors may contribute to thetic nervous system activity can increase myocardial oxygen
an imbalance of myocardial oxygen supply and demand, demand by increasing heart rate, blood pressure, and
01/09
contractility or even decrease myocardial oxygen supply, other functions, including tissue repair, autoimmune
which, in turn, may lead to angina, dysrhythmias, and areas regulation, arteriosclerosis, and tumor growth and metasta-
of myocardial infarction.110 In addition, sympathetic activa- sis.114 Nevertheless, the primary components of the coagula-
tion may enhance perioperative hypercoagulability, which tion systems comprise cellular (e.g., platelets, endothelial
may contribute to perioperative coronary thrombosis or vaso- cells, monocytes, and erythrocytes) and molecular (e.g.,
spasm, thus reducing myocardial oxygen supply.111 coagulation factors and inhibitors, fibrinolysis factors and
inhibitors, adhesive and intercellular proteins, acute-phase
Pulmonary proteins, immunoglobulins, phospholipids, prostaglandins,
The pathophysiology of pulmonary dysfunction after sur- and cytokines) components.114 The normal process of coag-
gery is multifactorial. Relevant factors include disruption of ulation involves several steps, including initiation (damaged
normal respiratory muscle activity, which may result from vascular endothelium expresses tissue factor, which ulti-
either surgery or anesthesia, reflex inhibition of phrenic nerve mately leads to generation of thrombin), amplification (aug-
activity with subsequent decrease in diaphragmatic function, mentation of the effects of thrombin), propagation (formation
and uncontrolled postoperative pain, which may contribute of clot), and stabilization (formation of a stable fibrin mesh-
to voluntary inhibition of respiratory activity, or splinting.112 work that protects clot from fibrinolytic attack).114 However,
Although the pathophysiology of breathing and respiratory following surgery, the normal process of coagulation may
muscle function following surgery is complex, it is clear that become unbalanced, which may result in a tendency toward
anesthetic or analgesic agents administered in the periopera- thrombosis. Immediately after surgical incision, there are
tive period affect the central regulation of breathing and increases in the levels of tissue factor, tissue plasminogen
activities of respiratory muscles. This incoordination of respi- activator, plasminogen activator inhibitor–1, and von Will-
ratory muscle function (which may last well into the postop- ebrand factor, which contribute to a hypercoagulable and
erative period) will impair lung mechanics, increasing the risk hypofibrinolytic state postoperatively.114 Many of these det-
of hypoventilation, atelectasis, and pneumonia. Visceral stim- rimental responses may be reduced by excellent postopera-
ulation may decrease phrenic motoneuron output, which tive analgesia and in particular by the sympathetic and
results in a decrease in diaphragmatic descent and lung afferent block provided by thoracic epidural analgesia with
volumes.112 local anesthetics.
Gastrointestinal postoperative morbidity

Although decreased GI motility is expected after abdomi- Despite excellent theoretical reasons why high-quality
nal surgery, return of GI function usually occurs within sev- analgesia should improve postoperative physiology and out-
eral days postoperatively. Some patients will develop paralytic comes, the effects of nociceptive blockade and pain relief
ileus, a protracted and more severe state of GI immotility. on postoperative morbidity remain controversial.16 There
Although the pathophysiology of postoperative ileus and are several likely reasons why these effects are difficult to
decreased GI motility is multifactorial, the primary mecha- assess. Primarily, surgical techniques and perioperative care
nisms include neurogenic (spinal, supraspinal adrenergic are constantly evolving and improving, with subsequent
pathways), inflammatory (i.e., local inflammatory responses reduction in baseline morbidity and mortality. Thus, the
initiate neurogenic inhibitory pathways), and iatrogenic positive effects of analgesia on outcomes may be apparent
pharmacologic (e.g., opioids) mechanisms.113 In the acute only on selected high-risk patients or procedures. Several
postoperative phase, neurogenic (spinal and supraspinal) systematic reviews have examined this question and have
mechanisms are primary mediators of decreased GI motil- reached the following conclusions. For open major vascular
ity.113 Activation of splanchic afferents and increased sympa- and thoracic procedures, there is good evidence from sys-
thetic outflow, along with the possible use of opioids, are the tematic reviews and large randomized controlled trials that
predominant mechanisms for decreased GI motility immedi- thoracic epidural analgesia may reduce cardiovascular and
ately following surgery. However, over the subsequent post- pulmonary morbidity when compared with systemic opi-
operative days, a prolonged phase of postoperative ileus oids.16 There is good evidence from meta-analyses that
occurs. The presumed etiology of the latter is distinct and intraoperative spinal or epidural local anesthetics in lower-
involves an enteric molecular inflammatory response that body procedures reduce estimated blood loss by about
impairs local neuromuscular function and activates neuro- 30%.17,115 Finally, the duration of postoperative ileus is
genic inhibitory pathways.113 Our understanding of the reduced by approximately 24 to 36 hours with the use of
mechanisms of postoperative ileus is not complete, and it is epidural analgesia with local anesthetic–containing solu-
likely that these three mechanisms are not discrete phenom- tions after major open abdominal procedures.16 This effect
ena but interrelated. may be of major significance in that reduction of ileus
allows earlier oral nutrition,50 which has been demonstrated
Coagulation to improve outcome.
It is recognized that hypercoagulability occurs in associa- Another key feature in the difficulties assessing the impact
tion with surgical procedures. Although the pathophysiology of postoperative analgesia is that most studies to date have
of coagulation-related events (e.g., formation of deep vein focused on the effects of a single factor (i.e., epidural analge-
thrombosis has essentially been unchanged since Virchow’s sia) on overall postoperative morbidity. In current medical
initial description of the triad of stasis, blood vessel injury, practice, this is probably too simplistic an approach as overall
and hypercoagulability, our current understanding of the postoperative outcome is known to be determined by multi-
coagulation system is that it is a complex system with many ple factors.116–118 Besides postoperative pain relief, reinforced
01/09
psychological preparation of the patient, reduction of stress nists, and anticonvulsant analgesia adjuncts such as gabapen-
by performing neural blockade or opting for minimal invasive tin.61,124,125 Future studies will need to define optimal strategies
procedures, and enforcement of early oral postoperative feed- for high-risk procedures and patients.
ing and mobilization may all play a significant role in deter-
mining outcome.118 Prevention of intraoperative hypothermia, barriers to effective postoperative analgesia
avoidance of fluid overloading, and avoidance of hypoxemia In general, multiple advisory and supervisory organizations
may be important as well.118,119 Therefore, although adequate (e.g., JCAHO, World Health Organization) recognize the
pain relief is obviously a prerequisite for good outcome, the importance of adequate pain control.1 Partially in response to
best results are likely to be achieved by combining analgesia these initiatives, there has been a marked increase in the cre-
with all of the aforementioned factors in a multimodal reha- ation and requirement of acute pain treatment services within
bilitation effort. hospitals across the world.126 Work continues on attempting
to create efficient and simple delivery techniques and tech-
development and prevention of chronic nologies for postoperative analgesia. In addition to economic
postoperative pain constraints, significant concerns regarding potential for opioid
Although not all nociceptive input results in a pathologic tolerance and addiction remain as a barrier.1 Continued expo-
process, a substantial percentage of patients who undergo sure of an opioid receptor to high concentrations of opioid will
certain surgical procedures will exhibit prolonged central cause tolerance. Tolerance is the progressive decline in an
sensitization and chronic pain [see Table 11]. Pathologic opioid’s potency with continuous use, so higher and higher
nociceptive input may cause central sensitization, which is concentrations of the drug are required to cause the same
marked by hyperexcitable spinal neurons that exhibit a analgesic effect. Physical dependence refers to the production
decreased threshold for activation, increased and prolonged of an abstinence syndrome when an opioid is withdrawn. It is
response to noxious input, expansion of receptive fields, defined by the World Health Organization as follows:
possible spontaneous activity, and activation by normally
A state, psychic or sometimes also physical, resulting from
non-noxious stimuli.120
interactions between a living organism and a drug, char-
Induction and maintenance of central sensitization empha-
acterized by behavioural and other responses that always
size different receptor-neurotransmitter combinations, includ-
include a compulsion to take the drug on a continuous or
ing NMDA receptors, prostaglandins, and neuropeptides
periodic basis in order to experience its psychic effects,
(substance P, calcitonin gene–related peptide, neurokinin A).121
and sometimes to avoid discomfort from its absence.127
Ultimately, transcriptional changes (including induction of
genes), structural changes in synaptic connections (e.g., con- This definition is very close to the popular concept of addic-
tact between low-threshold afferent and nociceptive neurons), tion. It is important, however, to distinguish addiction (imply-
and loss of inhibitory interneurons may result in a persistent ing compulsive behavior and psychological dependence) from
state of central sensitization.122 tolerance (a pharmacologic property) and from physical
Multiple studies and reviews have noted that more severe dependence (a characteristic physiologic effect of a group of
acute postoperative pain is a risk factor for development of drugs). Physical dependence does not imply addiction. More-
chronic postoperative pain.61,123 Although optimal strategies over, tolerance can occur without physical dependence; the
for prevention of chronic pain have not been identified, converse does not appear to be true. The possibility that the
promising modalities include preemptive regional analgesia medical administration of opioids could result in a patient
such as thoracic epidural local anesthetics, NMDA antago- becoming addicted has generated much debate about the use
Table 11 Approximate Incidences and Risk Factors for Development of Postoperative Chronic Pain
Surgical Procedure Incidence of Chronic Pain (%) Risk Factors
Thoracotomy 30–70 Increased acute pain
Open vs thoracoscopic
Not using thoracic epidural analgesia with local anesthetics
Intercostal nerve injury
Mastectomy 11–60 Increased acute pain
Increased acute opioid consumption
Immediate adjuvant radiation therapy
Axillary dissection vs sentinel node biopsy
Inguinal hernia repair 0–37 Increased acute pain
Preoperative pain
Female gender
Surgery for recurrent hernia
Open vs laparoscopic
01/09
of opioids. In a prospective study of 12,000 hospitalized treatment techniques, the risks attendant on the procedures
patients receiving at least one strong opioid for a protracted under consideration, and the cost to the patient. It is to be
period, there were only four reasonably well-documented hoped that our growing understanding of basic pain mecha-
cases of subsequent addiction, and in none of these was there nisms and appropriate therapy, combined with the promising
a history of previous substance abuse.128 Thus, the iatrogenic data supporting the idea that adequate inhibition of surgically
production of opioid addiction is very rare. It is hoped that induced nociceptive stimuli may reduce postoperative mor-
continued physician and patient education will reduce this bidity, will stimulate more surgeons to turn their attention to
barrier to high-quality postoperative analgesia. this area. Effective control of postoperative pain, combined
with a high degree of surgical expertise and the judicious use
of other perioperative therapeutic interventions within the
Conclusion context of multimodal postoperative rehabilitation, is certain
The choice of therapeutic intervention for acute postopera- to improve acute and long-term patient outcomes.
tive pain is determined largely by the nature of the patient’s
problem, the resources available, the efficacy of the various Financial Disclosures: None Reported
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Analg 2005;100:162–8. ologist. Anesthesiology 2000;92:1467–72. and chronic pain after breast surgery for can-
100. Taylor S, Voytovich AE, Kozol RA. Has the 113. Bauer AJ, Boeckxstaens GE. Mechanisms of cer. Anesth Analg 2005;101:1427–32.
pendulum swung too far in postoperative postoperative ileus. Neurogastroenterol 126. Werner MU, Soholm L, Rotboll-Nielsen P,
pain control? Am J Surg 2003;186:472–5. Motil 2004;16 Suppl 2:54–60. Kehlet H. Does an acute pain service
101. Kidd BL, Urban LA. Mechanisms of inflam- 114. Bombeli T, Spahn DR. Updates in periop- improve postoperative outcome? Anesth
matory pain. Br J Anaesth 2001;87:3–11. erative coagulation: physiology and manage- Analg 2002;95:1361–72.
102. Carr DB, Goudas LC. Acute pain. Lancet ment of thromboembolism and haemorrhage. 127. World Health Organization. WHO expert
1999;353:2051–8. Br J Anaesth 2004;93:275–87. committee on drug dependence. Sixteeth
103. Woolf CJ, Salter MW. Neuronal plasticity: 115. Rodgers A, Walker N, Schug S, et al. Reduc- Report. World Health Organ Tech Rep Ser
increasing the gain in pain. Science tion of postoperative mortality and morbid- 1969;407:1–28.
2000;288:1765–9. ity with epidural or spinal anaesthesia: results 128. Porter J, Jick H. Addiction rare in patients
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105. Chen SL, Wu XY, Cao ZJ, et al. Subdia- gies to improve surgical outcome. Am J Surg
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Liver Physiol 2008;294:G1441–9. and challenges in postoperative recovery.
106. Julius D, Basbaum AI. Molecular mechanisms Lancet 2003;362:1921–8.
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Acknowledgments
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2004;140:441–51. the anesthesiologist in fast-track surgery: from Figure 1 Carol Donner.
01/09
1 BASIC SURGICAL AND PERIOPERATIVE CONSIDERATIONS 7 ACUTE WOUND CARE — 1
7 ACUTE WOUND CARE

Stephen R. Sullivan, M.D., Loren H. Engrav, M.D., F.A.C.S., and Matthew B. Klein, M.D.
Approach to Acute Wound Management
Acute wounds are the result of Wound Preparation

local trauma and may be asso-
ciated with severe life-threaten- ANESTHESIA
ing injuries. The approach to a Adequate general or local
patient with an acute wound anesthesia, preceded by care-
begins with assessment of the ful motor and sensory exami-
ABCs (Airway, Breathing, and nation, must be instituted
Circulation). Management of before examination and treat-
any life-threatening injuries present is addressed first; only after ment of the wound can begin. General anesthesia in the OR is
more urgent problems have been ruled out or corrected is manage- employed if the patient is unable to tolerate local anesthesia; ade-
ment of the wound itself addressed. A complete history is obtained quate pain control cannot be achieved with a local block; the
and a thorough physical examination performed, with special wound requires significant debridement, exploration, or repair;
attention paid to both local and systemic wound environment fac- bleeding is difficult to control; or the local anesthetic dose required
tors that may affect healing. Information about the cause of injury for adequate pain control exceeds the maximum dose that can be
is sought. In the case of a hand injury, the patient’s hand domi- safely delivered. Local anesthesia is usually sufficient for debride-
nance and occupation are determined. All patients with acute ment and closure of most small traumatic wounds. Often, the local
wounds should be assessed for malnutrition, diabetes, peripheral anesthetic may be injected directly into wounded tissue. However,
vascular disease, neuropathy, obesity, immune deficiency, autoim- direct wound injection may be less reliable in inflamed or infected
mune disorders, connective tissue diseases, coagulopathy, hepatic tissue or may distort important anatomic landmarks used to align
dysfunction, malignancy, smoking practices, medication use that wound edges. In these situations, regional nerve blocks directed at
could interfere with healing, and allergies. The local wound envi- specific sensory nerves outside the injured field may be employed
ronment should be evaluated to determine the extent and com- instead.
plexity of injury, the tissues involved, the presence or absence of The main injectable anesthetics can be broadly divided into
contamination by microorganisms or foreign bodies, and the amides and esters [see Table 1]. (An easy way of remembering
degree of any damage related to previous irradiation or injury to which category an agent belongs to is to recall that the amides all
surrounding tissues. have two Is in their generic name, whereas the esters have only
Gloves and a shielded mask are worn to protect the practition- one.) Lidocaine, an amide, is the most commonly used local anes-
er from exposure to body fluids. Gloves must be powder free, as thetic. Its advantages include its rapid onset of action (< 2 min-
well as latex free (to prevent allergic reactions to latex).1 The utes), its extended duration of action (60 to 120 minutes), its rel-
wound is carefully examined, with particular attention paid to ative safety in comparison with more potent anesthetics (e.g.,
size, location, bleeding, arterial or venous insufficiency, tissue bupivacaine), and its availability in multiple forms (e.g., liquid,
temperature, tissue viability, and foreign bodies.The possibility of jelly, and ointment) and concentrations (e.g., 0.5%, 1.0%, and
damage to vessels, nerves, ducts, cartilage, muscles, or bones in 2.0%). In addition, lidocaine rarely causes allergic reactions,
proximity to the injury is assessed. X-rays and a careful motor whereas ester anesthetics (e.g., tetracaine) are metabolized to
and sensory examination may be required to rule out such coex- para-aminobenzoic acid, to which some persons are allergic.
isting injuries.While these tests are being performed, moist gauze Cocaine, an ester, is an excellent local anesthetic for wounds in
should be applied to wounds. For thorough assessment of
injuries, it may be necessary to probe ducts (e.g., the parotid duct
or the lacrimal duct). Table 1—Common Injectable Anesthetics3
At this point, decisions must be made about acute wound care.
The goal of acute wound management is a closed, healing wound Amides Esters
that will result in the best functional and aesthetic outcome. In
what follows, we address the key considerations in management of Lidocaine (Xylocaine) Procaine (Novocain)
Bupivacaine (Marcaine) Chloroprocaine (Nesacaine)
the acute wound, including anesthesia, choice of repair site (i.e.,
Mepivacaine (Carbocaine) Tetracaine (Pontocaine)
operating room or emergency department), debridement, irriga-
Prilocaine (Citanest) Benzocaine (multiple brands)
tion, hemostasis, closure materials, timing and methods of closure, Etidocaine (Duranest) Propoxycaine (Ravocaine)
appropriate closure methods for specific wound types, dressings, Phenocaine Cocaine
adjunctive treatment (e.g., tetanus and rabies prophylaxis, antibi- Dibucaine (Nupercainal)
otics, and nutritional supplementation), postoperative wound Ropivacaine (Naropin)
care, and potential disturbances of wound healing. Finally, we Levobupivacaine (Chirocaine)
briefly review the physiology of wound healing.
Patient presents with acute wound Initial measures are complete, and wound care is initiated
Prepare wound:
Obtain complete history, and perform thorough physical
examination. Life-threatening conditions take priority • Anesthesia: use local anesthesia in most cases. Use general
over wound care. anesthesia if local anesthesia cannot be tolerated, if pain cannot be
controlled with local anesthesia, if wound requires significant repair,
Examine local wound environment, look for local and
if bleeding is hard to control, or if local anesthetic dose needed
systemic factors that may impair healing, and identify
would be unsafe.
wounded structures.
• Debridement: debride necrotic tissue, and remove foreign bodies.
Consider antibiotic prophylaxis for clean or clean-
If there is significant questionably viable tissue, defer debridement
contaminated wounds if factors likely to impair wound
until status is clarified, and initiate dressing changes.
healing [see Table 7] are present. Initiate antibiotic
prophylaxis for contaminated and dirty wounds and • Irrigation: use only nontoxic irrigants, avoiding antibiotics and strong
for wounds with extensive devitalized tissue. antiseptics. Low pressure is preferable to high pressure (but bulb
syringe is inadequate).
• Hemostasis: use pressure, cauterization, or ligation (but do not
ligate lacerated arteries proximal to amputated part). Place drain if
there is risk of hematoma or fluid collection.
Abrasion Laceration Crush injury
Remove foreign bodies to prevent Close immediately if patient presents with Severity of injury is not always
traumatic tattooing. clean wound within 8 hr of injury (or 24 hr for apparent.
Allow healing by secondary closure. simple facial injury). Otherwise, delay closure Monitor for compartment syndrome,
Tape or glue may be used. or allow wound to heal without closure. and treat on urgent basis.
Close deep laceration in layers.
Puncture wound Complex wound Extravasation injury
Leave wound open, and Inform patient of potential for poor aesthetic Conservative management (i.e., elevation,
allow healing by outcome, and discuss alternatives. ice, and monitoring) suffices in most cases.
secondary closure. Close immediately if wound is clean and tissue Injury involving high volume, high osmolarity,
viable. Delay closure if wound is contaminated or chemotherapeutic agent may necessitate
or there is significant nonviable or questionably additional measures (e.g., hydrocortisone,
viable tissue. incision and drainage, hyaluronidase, saline,
Perform primary closure if possible. Severe injury or aspiration).
may necessitate delayed primary closure,
secondary closure, skin grafting, or tissue transfer.
Consider tetanus treatment, antibiotic

prophylaxis, or both.
Apply dressings as appropriate
for individual wound type.
Abrasion Laceration, complex wound closed primarily, injection injury,

high-velocity wound, bite wound, or sting
Use occlusive dressings (impregnated
gauze may be used for small superficial
Consider three-layer dressings for open draining wound, with inner
wounds). Avoid dry dressings.
nonadherent layer, middle absorbent layer, and outer binding layer.
Consider ointment if there is minimal drainage.
Wound is ready for closure
Select closure materials: sutures, tapes, staples, or adhesives.

Determine timing and methods of closure:
• Immediate primary closure: clean wound without contraindications
to closure
• Delayed primary closure: contaminated wound, wound with
questionably viable tissue, or patient who cannot tolerate immediate
closure Approach to
• Secondary closure (allowing wound to heal by itself): wound with
contamination or contraindication to closure, patient who cannot
Acute Wound Management
tolerate closure, or wound for which closure is not needed for
aesthetic result
• Skin grafting: large superficial wound
• Tissue transfer: large wound with exposed vital structure
Formulate specific closure approach suitable for individual wound type.
Injection injury Bite wound
Wound appearance is often deceptively benign. Take into account risks of rabies, bacterial and other viral
Examine wound area carefully and obtain infections, and envenomation.
appropriate radiographs. Treat with exploration, irrigation, and debridement.
Treat aggressively with incision, wide exposure, Close immediately if wound is clean and tissue viable. Delay
debridement, and removal of foreign bodies. closure if wound is contaminated or there is significant nonviable
Allow healing by secondary closure. or questionably viable tissue.
Perform primary closure if possible. Severe injury may necessitate
secondary closure, skin grafting, or tissue transfer.
Consider rabies treatment, rabies prophylaxis, or both.
High-velocity wound Sting
Wound appearance is often deceptively Take into account risk of envenomation.

benign; foreign bodies are frequently present. Symptoms may be local or systemic.
Examine wound area carefully and obtain Treatment is usually directed toward local
appropriate radiographs. symptoms. For systemic reactions,
Debride wound extensively and identify epinephrine, diphenhydramine, and
all injured tissue. supportive airway and BP care may be
Avoid immediate primary closure. Perform required.
delayed primary closure or allow healing by
secondary closure.
Complex wound left open or closed after delay Extravasation injury or crush injury
Generally, use wet-to-dry dressings; use wet-to-wet Avoid compression dressings.

dressings if wound bed contains tendons, arteries,
nerves, or bone. Avoid compression dressings.
Consider NPWT for large open wound.
mucous membrane (e.g., those in the nose or the throat). It is sive bacterial contamination. To reduce the risk of infection in an
unique among local anesthetics in that it causes vasoconstriction, acute wound, necrotic tissue and foreign bodies must be re-
which helps reduce hemorrhage.Typically, cocaine is applied top- moved.11 The wound and the surrounding local tissue must be
ically by soaking gauze or pledgets in a solution. exposed so that necrotic tissue can be identified and debrided.
Vasoconstriction can also be produced by adding epinephrine to Hair may be trimmed with scissors or an electric clipper or re-
a local anesthetic, usually in a dilution of 1:100,000 or 1:200,000 tracted with an ointment or gel to facilitate exposure, debride-
(5 to 10 μg/ml). Through vasoconstriction, epinephrine prolongs ment, and wound closure. Close shaving with a razor should be
the anesthetic agent’s duration of action, allows a larger dose to be avoided, however, because it potentiates wound infections.12 Clip-
safely administered, and aids in hemostasis.2 Traditionally, local ping of eyebrows should also be avoided, both because the eye-
anesthetics with epinephrine have not been used in finger and toe brows may not grow back and because the hair is necessary for
wounds, because of the theoretical risk of ischemia and tissue loss; proper alignment.
however, these adverse effects have not yet been reported clinically Some wounds contain a significant amount of questionably
or documented by any prospective studies.3 viable tissue. If there is enough questionably viable tissue to pre-
Local anesthetics can cause systemic toxicity when injected clude acute debridement, dressing changes may be initiated.When
intravascularly or given in excessive doses. Manifestations of sys- all tissue has been declared to be either viable or necrotic and
temic toxicity begin with central nervous system effects (e.g., verti- when the necrotic tissue has been debrided surgically or by means
go, tinnitus, sedation, and seizures) and may progress to cardiovas- of dressing changes, the wound can be closed.
cular effects (e.g., hypotension, cardiac conduction abnormalities, Most foreign bodies are easily removed from wounds either by
and cardiovascular collapse).Treatment for systemic toxicity is sup- hand or via surgical debridement. Abrasion injuries or gunpowder
portive, with oxygen, airway support, and cardiovascular bypass (if explosions can cause small foreign body fragments to be embed-
necessary) provided until the anesthetic has been metabolized by ded in and beneath the skin. These small foreign bodies are often
the liver.The maximum safe dose of lidocaine is 3 to 5 mg/kg with- difficult to extract but should be removed as soon after the injury
out epinephrine and 7 mg/kg with epinephrine. Doses as high as 55 as possible. Irrigation usually suffices for removal of loose foreign
mg/kg have been used without toxicity for tumescent anesthesia in bodies, but surgical debridement with a small drill, a sharp instru-
patients undergoing liposuction4; however, in this scenario, some of ment, or a brush may be required for removal of more firmly
the anesthetic is aspirated by the liposuction, which means that the embedded foreign material. If the interval between injury and
effective dose is lower. The lidocaine doses used for local wound treatment exceeds 1 to 2 days, the wounds will begin to epithelial-
injection should be substantially smaller than those used in liposuc- ize and the embedded material will be trapped in the skin, result-
tion.The maximum safe dose of cocaine is 2 to 3 mg/kg.To prevent ing in traumatic tattooing.
local anesthesia from causing systemic toxicity, the recommended
IRRIGATION
safe doses of the anesthetics should not be exceeded, and aspiration
should be performed before injection into the wound to ensure that After debridement of necrotic tissue and foreign bodies, the
the agent will not be injected intravascularly. next step is irrigation of the wound.This may be accomplished by
The pain associated with injection of the local anesthetic can be means of several different methods, including bulb syringe irriga-
minimized by using a small-caliber needle (27 to 30 gauge), warm- tion, gravity flow irrigation, and pulsatile lavage. These methods
ing the anesthetic, injecting the agent slowly, using a subcutaneous can be further divided into high-pressure (35 to 70 psi) and low-
rather than an intradermal injection technique,5 providing coun- pressure (1 to 15 psi) delivery systems. High-pressure pulsatile
terirritation, buffering the anesthetic with sodium bicarbonate to lavage reduces bacterial concentrations in the wound more effi-
reduce acidity (in a 1:10 ratio of sodium bicarbonate to local anes- ciently than low-pressure and bulb syringe irrigation do,13 but it
thetic),6 and applying a topical local anesthetic before injection. also causes considerable disruption to soft tissue structure14 and
Topical local anesthetics (e.g., TAC [tetracaine, adrenaline (epi- results in deeper penetration and greater retention of bacteria in
nephrine), and cocaine] and EMLA [a eutectic mixture of lido- soft tissue than low-pressure lavage does.15 In general, low-pres-
caine and prilocaine]) are as effective as injectable anesthetics when sure systems should be employed for acute wound irrigation,
applied to an open wound.7 EMLA requires approximately 60 though merely running saline over a wound is of little value. To
minutes to induce sufficient anesthesia for open wounds; TAC obtain continuous irrigation with pressures as low as 5 to 8 psi,
requires approximately 30 minutes.8 EMLA is more effective than one group recommended using a saline bag in a pressure cuff
TAC for open wounds of the extremity. Benzocaine 20% (in gel, inflated to 400 mm Hg and connected to I.V. tubing with a 19-
liquid, or spray form) can also be used for topical anesthesia and is gauge angiocatheter.16
frequently employed before endoscopic procedures. It is poorly Only nontoxic solutions (e.g., 0.9% sterile saline, lactated
absorbed through intact skin but well absorbed through mucous Ringer solution, sterile water, and tap water) should be used for
membranes and open wounds. A 0.5- to 1-second spray is usually wound irrigation.17 Irrigation with an antibiotic solution appears
recommended, though even with a standardized spray duration, to offer no advantages over irrigation with a nonsterile soap solu-
the delivered dose can vary considerably.9 A 2-second spray results tion, and the antibiotic solution may increase the risk of wound-
in a statistically, though not clinically, significant increase in methe- healing problems.18 Strong antiseptics (e.g., povidone-iodine,
moglobin levels.10 Methemoglobinemia is a rare but life-threaten- chlorhexidine, alcohol, sodium hypochlorite, and hydrogen perox-
ing complication of benzocaine spray use. If symptoms of methe- ide) should not be placed directly into the wound, because they
moglobinemia develop (e.g., cyanosis or elevated methemoglobin are toxic to the tissues and impede healing. The surrounding skin
levels on cooximetry), prompt treatment with intravenous methyl- should be prepared with an antibacterial solution, and a sterile
ene blue, 1 to 2 mg/kg, is indicated.9 field created to limit contamination.
DEBRIDEMENT HEMOSTASIS
Normal healing can proceed only if tissues are viable, if the In most wounds, hemorrhage can be readily controlled with
wound contains no foreign bodies, and if tissues are free of exces- pressure, cauterization, or ligation of vessels. Lacerated arteries
proximal to amputated parts such as fingers or ears, however, increase the risk of infection. Monofilament sutures hold knots less
should not be ligated, because an intact vessel is necessary for well than multifilament sutures, requiring five knots for security;
microsurgical replantation. Packing, wrapping, and elevating can multifilament sutures are easier to handle and require only three
help control hemorrhage temporarily. If necessary (though the knots.With all sutures, the knots must be square to be secure and
need should be rare), a tourniquet may be applied to an injured must be only tight enough to coapt the wound edges.To minimize
extremity. Hemostasis prevents hematoma formation, which in- foreign body bulk, buried suture knot ends should be cut right on
creases the risk of infection and wound inflammation. If there ap- the knot. In terms of absorbability, either absorbable or nonab-
pears to be a potential risk of hematoma or fluid collection, drains sorbable sutures may be appropriate, depending on the situation.
should be placed. Although drains may help prevent accumulation Absorbable sutures are generally used for buried sutures to approx-
of blood or serum in the wound, they are not a replacement for imate deep tissues (e.g., dermis, muscle, or fascia). Absorption of
meticulous hemostasis. Drains facilitate approximation of tissues, synthetic suture material occurs by hydrolysis and causes less tis-
particularly under flaps; however, they also tend to potentiate bac- sue reaction than absorption of natural suture material, which
terial infections and should therefore be removed from the wound occurs by proteolysis. Nonabsorbable sutures (e.g., those made of
as soon as possible.19 silk, nylon, polyester, or polybutester) are most commonly used for
As a rule, drains can be safely removed when drainage reaches wounds in the skin, from where they will eventually be removed, or
levels of 25 to 50 ml/day. If a hematoma or seroma forms, the sub- for wounds in deeper structures that require prolonged support
sequent course of action depends on the size of the fluid collec- (e.g., abdominal wall fascia, tendons, nerves, and blood vessels).
tion. Small hematomas and seromas usually are reabsorbed and Staple closure is less expensive and significantly faster than
thus can be treated conservatively. Larger hematomas and sero- suture closure, and it offers a slightly, though not significantly, bet-
mas provide a significant barrier to healing, and treatment may ter cosmetic outcome when used to close scalp wounds.22,23 Con-
require reopening the wound and placing drains. Intermittent taminated wounds closed with staples have a lower incidence of
sterile aspirations, followed by application of a compressive dress- infection than those closed with sutures.24 In addition, staple clo-
ing, may be indicated for seromas. If this approach fails to elimi- sure eliminates the risk that a health care provider will experience
nate the seroma, a drain may be reintroduced. a needle stick, which is a particularly important consideration in
caring for a trauma patient with an unknown medical history.
The tapes used for wound closure either are rubber-based or
Wound Closure employ an acrylate adhesive. Rubber-based tapes (e.g., athletic
tape) are a potential irritant to skin, degrade with exposure to
MATERIALS
heat, light, and air, and are occlusive, thereby preventing transepi-
Once the appropriate dermal water loss. Tapes that include acrylate adhesives (e.g.,
preparatory measures have Micropore and Steri-Strip), however, are hypoallergenic, have a
been taken (see above), the long shelf life, and are porous, thereby allowing water to evapo-
wound is ready to be closed. rate.25 Linear wounds in areas with little tension are easily approx-
The first step is to choose the imated with tape alone, whereas wounds in areas where the skin is
material to be used for wound closure. The materials currently more taut (e.g., the extremities) generally require that tape skin
available for this purpose include sutures, staples, tapes, and glues. closure be supplemented by dermal sutures.The use of tape alone
Selection of the appropriate material is based on the type and loca- is desirable when feasible, in that it spares the patient the discom-
tion of the wound, the potential for infection, the patient’s ability to fort associated with suture removal, prevents suture puncture
tolerate closure, and the degree of mechanical stress imposed by scars, and avoids the emotional upset that may attend suture clo-
closure. The selected material must provide wound edge approxi- sure of small facial wounds on children.25 Tape closure has some
mation until the tensile strength of the wound has increased to the significant advantages: it immobilizes wound edges, permits early
point where it can withstand the stress present. suture removal, is easy to perform and comfortable for the patient,
The majority of wounds are closed with sutures. A suture is a leaves no marks on the skin, and yields a lower infection rate in
foreign body by definition, and as such, it may generate an inflam- contaminated wounds than suture closure does.26 It also has a few
matory response, interfere with wound healing, and increase the disadvantages: patients may inadvertently remove the tapes, and
risk of infection. Accordingly, the number and diameter of sutures wound edge approximation is less precise with tapes alone than
used to close a wound should be kept to the minimum necessary with sutures. In addition, tape will not adhere to mobile areas
for coaptation of the edges. under tension (e.g., the plantar aspects of the feet) or to moist
Sutures are categorized on the basis of material used, tensile areas (e.g., mucous membranes and groin creases), and wound
strength, configuration, absorbability, and time to degradation [see edema can lead to blistering at the tape margins and to inversion
Table 2]. Suture material may be either natural or synthetic; natur- of taped wound edges.
al fibers (e.g., catgut and silk) cause more intense inflammatory The use of tissue adhesives (e.g., octylcyanoacrylate) is a fast,
reactions than synthetic materials (e.g., polypropylene) do.20 The strong, and flexible method of approximating wound edges. Com-
tensile strength of suture material is defined as the amount of pared with sutures, staples, and tapes, adhesives provide a faster
weight required to break a suture divided by the suture’s cross-sec- closure and are essentially equivalent in terms of cosmetic out-
tional area. It is typically expressed in an integer-hyphen-zero form, come, infection rate, and dehiscence rate.27 Adhesives can be used
whereby larger integers correspond to smaller suture diameters on most parts of the body and have been employed to close
(e.g., 3-0 sutures have a greater diameter and more tensile strength wounds ranging from 0.5 to 50 cm in length. Their advantages
than 5-0 sutures do).21 Closure of acute wounds rarely requires include reduced cost, ease of application, and the absence of any
sutures larger than 4-0. In terms of configuration, suture material need for needles or suture removal; their major disadvantage is
may be composed either of a single filament or of multiple fila- lack of strength.28 They must not be applied to tissues within
ments. Multifilament suture material may be twisted or braided, wounds but, rather, should be applied to intact skin at wound
and the interstices created by braiding may harbor organisms and edges, where they serve to hold injured surfaces together. In addi-
Table 2—Types and Characteristics of Suture Material Used for Wound Closure
Tensile
Method of Time to
Suture Type Material Comment Configuration Strength at
Absorption Degradation
2 Wk
Plain catgut (bovine intestinal serosa) Natural; high tissue reactivity Monofilament Proteolysis 0% 10–14 days
Chromic catgut (bovine intestinal Natural; stronger, less reactive, and

serosa treated with chromic acid) longer-lasting than plain catgut Monofilament Proteolysis 0% 21 days
Fast-absorbing catgut Natural Monofilament Proteolysis 0% 7–10 days
Polyglytone 6211 (Caprosyn) Synthetic Monofilament Hydrolysis 10% 56 days
Glycomer 631 (Biosyn) Synthetic Monofilament Hydrolysis 75% 90–110 days

Absorbable
Polyglycolic acid (Dexon) Synthetic Monofilament/ Hydrolysis 20% 90–120 days
multifilament
Polyglactic acid (Vicryl) Synthetic Multifilament Hydrolysis 20% 60–90 days
Polyglyconate (Maxon) Synthetic Monofilament Hydrolysis 81% 180–210 days
Polyglycolide (Polysorb) Synthetic Multifilament Hydrolysis 80% 56–70 days
Polydioxanone (PDS) Synthetic Monofilament Hydrolysis 74% 180 days
Polyglecaprone 25 (Monocryl) Synthetic Monofilament Hydrolysis 25% 90–120 days
Polyglactin 910 (Vicryl RAPIDE) Synthetic Multifilament Hydrolysis 0% 7–14 days
Synthetic; low tissue reactivity; Monofilament

Polybutester (Novafil) — High —
elastic; good knot security
Synthetic; low tissue reactivity;

Nylon (Monosof, Dermalon, Ethilon) memory effect necessitates Monofilament — High
more knots —
Nylon (Nurolon) Synthetic; low tissue reactivity Multifilament — High —
Synthetic; silicon coated; low tissue

Nylon (Surgilon) Multifilament — High —
reactivity
Polypropylene (Prolene, Surgilene, Synthetic; low tissue reactivity; Monofilament — High —

Surgipro) slippery
Polyethylene (Dermalene) Synthetic Monofilament — High —
Lowest tissue reactivity of all

Nonabsorbable sutures; poor handling; creates Monofilament/
Stainless steel — Highest —
artifact on CT scan; moves with multifilament
MRI
Cotton Natural Multifilament — — —

Natural; high tissue reactivity; good Multifilament
Silk (Sofsilk) — Poor —
knot security
Synthetic; uncoated; high

Polyester (Dacron, Mersilene, friction; low tissue reactivity; poor Multifilament — High —
Surgidac) knot security
Synthetic; silicon coated; low

Polyester (Ticron) tissue reactivity; good knot Multifilament — High —
security
Synthetic; polybutylate coated;

Polyester (Ethibond) low tissue reactivity; good knot Multifilament — High —
security
Synthetic; Teflon coated; low Multifilament —

Polyester (Ethiflex, Tevdek) tissue reactivity; good knot High —
security
tion, they should not be used for wounds in mucous membranes, nylon sutures under loupe or microscope magnification. For ische-
contaminated wounds, deep wounds, or wounds under tension. mic or amputated tissues (e.g., an ear, a digit, or a limb), vessel re-
Adhesives are particularly useful for superficial wounds or wounds pair is performed with 8-0 to 10-0 monofilament nylon sutures
in which the deep dermis has been closed with sutures. under magnification.
In subcutaneous fat, suture placement should be avoided
TIMING AND METHODS
whenever possible; if sutures in this location are absolutely neces-
Appropriate materials having been selected, the next issue to sary, they should be placed at the fat-fascia junction or the fat-der-
address is the timing of wound closure. The choices are (1) to mis junction, not in fat alone. Fat cannot hold sutures by itself,
close the wound at the time of initial presentation, (2) to delay clo- and because it has a poor blood supply, suturing may lead to fat
sure until after a period of healing or wound care, and (3) to allow necrosis. The deeper fascial layers that contribute to the structur-
the wound to heal on its own.The best choice in a given situation al integrity of areas such as the abdomen, the chest, and the galea
depends whether the patient is stable and able to undergo wound should be closed as a separate layer to prevent hernias, structural
repair, whether hemorrhage is under control, whether necrotic deformities, and hematomas.
material has been adequately debrided and foreign bodies At the skin level, the deep dermis is responsible for the strength
removed, whether and to what degree bacterial contamination is of the acute wound closure. Deep dermal repair is performed with
present, and what the expected aesthetic outcome of immediate 4-0 absorbable suture material (e.g., polyglactin 910) and a cutting
closure might be in comparison with that of delayed closure or needle. The sutures are buried and placed 5 to 8 mm apart, with
secondary healing. care taken to evert the skin edges. Buried dermal sutures are often
The timing of wound closure determines the method that will used in conjunction with tapes (e.g., Steri-Strips), fine epidermal
be employed. The closure methods available include (1) primary sutures, or adhesives to facilitate precise alignment. Skin edges
closure by direct approximation; (2) delayed primary closure, in should be coapted and everted with 4-0 to 6-0 nylon or polypropy-
which the wound is closed after a healing period; (3) secondary lene sutures placed in the superficial dermis and the epidermis.The
closure, in which the wound is allowed to heal on its own; (4) skin graft- distance between the sutures and the distance between the wound
ing; and (5) the use of local or distant flaps. The ideal wound clo- edge and the suture insertion point should be equal to the thick-
sure method would support the wound until it has nearly reached ness of the skin (epidermis and dermis combined).
full strength (i.e., about 6 weeks), would not induce inflammation, Several different skin suturing methods may be used, depend-
would not induce ischemia, would not penetrate the epidermis and ing on the nature of the wound. Simple interrupted sutures are
predispose to additional scars, and would not interfere with the useful for irregular wounds.Vertical mattress sutures are good for
healing process. Unfortunately, no existing method accomplishes either thick (e.g., scalp) or thin (e.g., eyelid) skin. Horizontal mat-
all of these goals in all cases; some sort of compromise is virtually tress sutures can lead to ischemia and thus must be applied loose-
always necessary. In the acute wound setting, the simplest method ly; they may look untidy early after repair, but they generally
that will achieve a good closure is preferred. achieve good wound-edge eversion and long-term healing. Half-
Primary closure provides optimal wound healing when two per- buried horizontal and vertical mattress sutures are used for flap
pendicular, well-vascularized wound edges are approximated with- edges to minimize ischemia. A continuous intradermal or subcu-
out tension. Closure should proceed from deep to superficial.The ticular suture is easy to remove and relatively inconspicuous visu-
initial step is to identify landmarks and line up tissues, using skin ally. A simple continuous suture should be used only for linear
hooks or fine forceps to keep from causing wound edge trauma. wounds; it is quick to place but tends to invert the wound edges.
Although wound closure is usually a straightforward process, situ- Flap tips should be sutured with a three-point method to prevent
ations occasionally arise in which special caution is necessary. For strangulation [see Figure 1]. For children, suture removal can be
instance, when a wound crosses tissues with different characteris- both emotionally and physically traumatic; accordingly, when
tics (e.g., at the vermilion border of the lip, the eyebrow, or the hair- suturing is employed for skin closure in a pediatric patient, the use
line of the scalp), particular care must be taken to align the dam- of fast-absorbing suture material (e.g., plain catgut) or a pullout
aged structures accurately. In the repair of soft tissue, it is critical to continuous subcuticular suturing method should be considered.
handle tissue gently with atraumatic surgical technique, to place Primary direct approximation of wounds is not always indicat-
sutures precisely, and to minimize tension and contamination. ed. In cases where obvious bacterial contamination is present,
The next step is tissue-specific repair, which may require the there is a substantial amount of questionably necrotic tissue, or
consultation of an experienced surgeon. Bone fractures are re- the patient is unstable and unfit to undergo primary repair at the
duced and repaired with plates, rods, or external fixation devices. time of presentation, delayed primary closure is performed.
Muscle lacerations should be repaired because muscle is capable Delayed primary closure involves direct approximation of wound
of a significant degree of regeneration. A completely lacerated edges after a period (usually 4 to 5 days) of wound hygiene. This
muscle that is properly repaired recovers approximately 50% of its closure method markedly diminishes the incidence of wound
ability to produce tension and 80% of its ability to shorten, where- infection in patients with contaminated wounds.
as a partially lacerated muscle that is properly repaired recovers Secondary closure, in which the wound is left open and allowed
approximately 60% of its ability to produce tension and 100% of to heal on its own, is also sometimes chosen. Secondary closure
its ability to shorten.29 Tendon lacerations should be meticulously depends on contraction of the surrounding tissue and epithelializa-
approximated to allow gliding and restore tensile strength. Either tion from the wound margins.When this approach is followed, cau-
4-0 multifilament polyester or monofilament polypropylene is a tion and close observation are essential because the process of tis-
reasonable choice for muscle and tendon repair.30 Early active sue contraction can sometimes lead to contracture, a pathologic
mobilization promotes the restoration of tensile strength in mus- scar deformity. Secondary closure can, however, yield acceptable
cles and tendons. Penetrating nerve trauma is treated with ten- results with specific wound types and at specific anatomic sites.
sion-free coaptation at the time of wound closure by primary With puncture wounds, for example, secondary closure is pre-
repair or repair with a nerve graft or nerve tube. Epineurial coap- ferred because it diminishes the likelihood of infection. For both
tation is typically achieved by placing 8-0 to 10-0 monofilament abrasions and puncture wounds, the functional and aesthetic
Figure 1 Shown is the method for inserting three-point sutures, along with three different applications
of this method.
results of secondary closure are generally as good as or better than proving quite difficult to remove. Complete debridement of these
those obtained by primary or delayed primary closure. For wounds embedded foreign bodies within 24 to 48 hours of injury is crucial
on anatomically concave surfaces (e.g., the medial canthal region, in preventing so-called traumatic tattooing. In the early postinjury
the nasolabial region, or the perineum), secondary wound healing period, surgical debridement with a small drill, a sharp instru-
generally yields excellent results.31 Secondary closure should also ment, or a scrub brush may suffice for removal of the foreign
be considered for severely contaminated wounds, infected wounds, material causing the traumatic tattoo; later, dermabrasion will be
wounds with significant amounts of devitalized tissue, wounds with necessary.34,35 Once the wound is adequately debrided, semiocclu-
foreign bodies, lacerations older than 24 hours, wounds in patients sive dressings should be applied to optimize epithelialization.
who are in shock, and high-velocity wounds.32
Occasionally, an acute wound is so large that neither primary Puncture Wounds
nor secondary closure will suffice. Such wounds must be covered Puncture wounds should be
with skin grafts or transferred tissue (i.e., flaps) [see 3:3 Open examined for foreign bodies,
Wound Requiring Reconstruction and 3:7 Surface Reconstruction which must be removed when
Procedures]. Local or distant flaps must be considered for wounds found. They are typically left
that involve exposed bone denuded of periosteum, cartilage open, treated with wound
denuded of perichondrium, tendon denuded of paratenon, or care, and allowed to heal by
nerve denuded of perineurium. secondary intention. With
puncture wounds, secondary closure reduces the risk of infection
CLOSURE OF SPECIFIC TYPES OF WOUNDS
and generally yields excellent aesthetic results.
Wounds may be divided into 10 main types: abrasions, puncture
wounds, lacerations, complex wounds, crush injuries, extravasation Lacerations
injuries, injection injuries, high-velocity wounds, bite wounds, and The type of wound most
stings. In addition, the American College of Surgeons (ACS) has commonly encountered by
divided wounds into four major categories: clean, clean-contami- surgeons is a superficial or
nated, contaminated, and dirty [see Table 3].The likelihood of infec- deep acute traumatic or surgi-
tion after any surgical procedure is correlated with the ACS wound cal wound that is suitable for
category: class I and II wounds have infection rates lower than 11%, primary closure by direct
whereas wounds in class IV have infection rates as high as 40%.33 approximation of the wound
edges. In this setting, the goal is to provide the best possible chance
Abrasions for uncomplicated healing. If the wound is to be closed, primary
Abrasions are superficial closure at the time of evaluation is preferred if it is feasible. As a
wounds caused by scraping. rule, closure should be completed within 6 to 8 hours of the injury,
They involve only the epider- though simple noncontaminated wounds of the face can be safely
mis and a portion of the der- closed as long as 24 hours after the injury. Primary closure is gen-
mis and frequently heal secon- erally desirable in that it eliminates the need for extensive wound
darily within 1 to 2 weeks. If an care, allows the wound to heal more quickly, and minimizes
abrasion is to be closed pri- patient discomfort. However, lacerations containing foreign bod-
marily, tape or glue may be used for epidermal approximation to ies or necrotic tissue that cannot be removed by irrigation or
prevent suture mark scars (which could be worse than the actual debridement and lacerations with excessive bacterial contamina-
wound scar). In some patients who have experienced abrasion tion should not be closed primarily, nor should wounds in which
injuries (e.g., motorcycle accidents in which victims slide along hemostasis is incomplete. Hematomas,36 necrotic tissue,37 and for-
asphalt) or blast injuries (e.g., firework explosions), small foreign eign bodies38 all promote bacterial growth and place a mechanical
body fragments become embedded in and beneath the skin, often barrier between healing tissues.
Complex Wounds Table 3—Classification and Infection

The term complex wounds Rates of Operative Wounds
includes stellate wounds and
those caused by degloving,
avulsion, and mutilation. The Infection Rate
Classification Wound Characteristics
(%)
goals of treatment include
achieving closure within 6 to 8 Atraumatic, uninfected; no entry of
Clean (class I) 1.5–5.1
hours of the injury, providing GU, GI, or respiratory tract
treatment in a manner consistent with the patient’s general health,
Minor breaks in sterile technique;
keeping bacterial counts at a low level, protecting tissues from des- Clean-contaminated
7.7–10.8 entry of GU, GI, or respiratory
(class II)
iccation, applying only nonnoxious agents, and supplying adequate tract without significant spillage
permanent coverage. In addition, it is important to discuss with the Traumatic wounds; gross spillage
patient the particular treatment difficulties posed by these wounds. Contaminated
15.2–16.3 from GI tract; entry into infected
(class III)
Often, a patient with a complex wound must be treated in the OR tissue, bone, urine, or bile
under general anesthesia because the injury is extensive or because Drainage of abscess; debridement
Dirty (class IV) 28.0–40.0
there is a need for exploration of tissues, removal of foreign bodies, of soft tissue infection
and debridement of nonviable tissue.
Stellate wounds can be approximated with careful placement of
interrupted and three-point sutures. Severely injured tissue may sure) is less than or equal to 30 mm Hg, compartment syndrome
have to be removed as an ellipse, with the resulting defect closed. is considered to be present. If clinical symptoms develop or the
Degloving refers to circumferential elevation of skin and fat delta pressure is below 30 mm Hg, appropriate therapeutic mea-
from muscle; the skin flap created by this process rarely survives. sures should be taken, including restoration of normal blood pres-
In the acute setting, questionably viable flaps of tissue may be sure in the hypotensive patient, removal of all constrictive dress-
evaluated by administering fluorescein, up to 15 mg/kg I.V., and ings, and maintenance of the limb at heart level.1 If the delta pres-
observing the flap for fluorescence under an ultraviolet lamp after sure remains below 30 mm Hg, clinical symptoms and signs per-
10 to 15 minutes have elapsed.39 Viable flap tissue fluoresces sist despite conservative measures, or both, fasciotomies should be
green.Tissue that is determined to be devascularized, on the basis performed within 6 hours.41 Hyperbaric oxygen therapy may also
of either physical examination or fluorescein testing, should be be beneficial in cases of crush injury with compartment syndrome
debrided. If the viability of a tissue segment is in doubt, the seg- in an extremity.43 Compartment syndrome with muscle damage
ment may be sewn back into its anatomic location and allowed to can also lead to rhabdomyolysis and renal failure. If an elevated
define itself as viable or nonviable over time. serum creatine kinase concentration is reported, intravascular vol-
Large open wounds resulting from avulsion can be either left to ume is stabilized, and urine flow is confirmed, a forced mannitol-
heal by secondary intention or treated with delayed skin grafting.32 alkaline diuresis should be initiated as prophylaxis against hyper-
Mutilating wounds caused by machinery (e.g., farm equip- kalemia and acute renal failure.44
ment) are often contaminated by a mixture of gram-positive and
Extravasation Injuries
gram-negative organisms, though not always excessively so.40 When
such a wound is grossly contaminated, antibiotic therapy (prefer- In some patients with arter-
ably with an agent or combination of agents that offers broad-special or venous catheters in place,
trum coverage) is indicated. Contaminated wounds closed with a vessel may become occluded
either tape or staples have a lower incidence of infection than those or a catheter dislodged from
closed with sutures.24,26 the intravascular space, leading
to extravasation injury, where-
Crush Injuries by solutions or medicines are
A notable feature of crush delivered into the interstitial space. The majority of acute extrava-
injury is that the severity of the sation injuries are quickly diagnosed and heal without complica-
wound is not always readily tions, and in most cases, conservative management (i.e., elevation
apparent. In many cases, no of the limb, application of ice packs, and careful monitoring) is ade-
external laceration can be quate.45 However, extravasation injuries involving high fluid vol-
seen, even though deep tissue umes, high-osmolar contrast agents, or chemotherapeutic drugs can
damage may be extensive. have more serious effects, resulting in skin ulceration and extensive
Ultrasonography or magnetic resonance imaging may help identi- soft tissue necrosis.Treatment of these injuries is not standardized;
fy a hematoma that is amenable to evacuation.32 Deep tissue it may include conservative management, hydrocortisone cream,
injury can lead to compartment syndrome and subsequent incision and drainage, hyaluronidase injection, saline injection, and
extremity loss. Early diagnosis is the key to successful treatment. aspiration by means of liposuction.45-47
Generally, the diagnosis can be made on the basis of physical signs
Injection Injuries
and symptoms, including increasing pain that is out of proportion
to the stimulus, altered sensation, pain on passive stretching of the Wounds caused by injection
affected muscle compartment, muscle weakness, and palpable of foreign materials (e.g.,
tenseness of the compartment.41 paint, oil, grease, or dirty
If compartment syndrome is suspected, the intracompartmen- water) can be severe. Injection
tal pressure should be measured.42 If the intracompartmental injuries usually result from the
pressure exceeds 30 mm Hg or if the so-called delta pressure (i.e., use of high-pressure spray
the diastolic blood pressure minus the intracompartmental pres- guns (600 to 12,000 psi) and
often occur on the nondominant hand.48,49 On initial examination, obic and anaerobic organisms commonly found in cat-bite wounds
the injury may appear deceptively benign, with only a punctate are similar to those found in dog-bite wounds, and antibiotic pro-
entry wound visible; however, foreign material is often widely dis- phylaxis with amoxicillin-clavulanate is appropriate.57 Acute regional
tributed in the deeper soft tissues. Radiographs are obtained to lymphadenitis after a cat scratch is known as cat-scratch disease
identify any fractures present and, in some cases, to determine the and is caused by Bartonella henselae58; it is treated by administer-
extent to which the injected material is distributed. Injection ing azithromycin.59
wounds must be treated aggressively with incision, wide exposure, Dog-bite wounds are at lower (16%) risk for infection than
debridement, and removal of foreign bodies to prevent extensive human-bite or cat-bite wounds and tend to be less severely con-
tissue loss and functional impairment. The functional outcome is taminated with bacteria. The aerobic species commonly isolated
determined by the time elapsed between injury and treatment and from such wounds include Pasteurella (P. canis), Streptococcus,
by the type of material injected. Oil-based paint is more damaging Staphylococcus, Moraxella, and Neisseria; common anaerobic iso-
to tissues than water-based paint, oil, grease, water, or air.50,51 lates include Fusobacterium, Bacteroides, Porphyromonas, and
Prevotella.57 Prophylactic treatment with a combination of a β-lac-
High-Velocity Wounds tam antibiotic with a β-lactamase inhibitor (e.g., amoxicillin-
High-velocity wounds from clavulanate) is appropriate.57,60
explosions or gunshots cause
extensive tissue damage as a Venomous animals Snake bites. Four types of poisonous
consequence of the release of snakes are native to the United States: the coral snakes (Micrurus
kinetic energy. Small entry and Micruroides species), from the family Elapidae, and three species
wounds are common, but the of pit vipers, from the family Viperidae (rattlesnakes [Crotalus
seemingly benign appearance species], copperheads [Agkistrodon tortortrix], and cottonmouths
of such a wound often belies the actual severity of injury: the exit or water moccasins [Agkistrodon piscivorus]).61-63 Pit vipers can be
wound and interspace may contain large areas of ischemic and identified by the pit between the eye and the nostril on each side
damaged tissue that affect critical structures (e.g., bone and blood of the head, the vertical elliptical pupils, the triangle-shaped head,
vessels). Clothing and dirt may also be transmitted into the deep the single row of subcaudal plates distal to the anal plate, and the
spaces. Radiographs may identify radiopaque foreign bodies (e.g., two hollow fangs protruding from the maxillae that produce the
metal objects or pieces of leaded glass).52 Treatment of wounds cre- characteristic fang marks.64 Coral snakes have rounder heads and
ated by high-velocity missiles involves extensive debridement and eyes and lack fangs; they are identified by their characteristic color
identification of injured tissue.Wounds should be left open to heal by pattern, consisting of red, yellow, and black vertical bands.
secondary or delayed primary closure.32 Patients bitten by any of the pit vipers must be examined for
massive swelling and pain, which, in conjunction with fang marks,
Bite Wounds suggest envenomation. Local pain and swelling typically develops
Treatment of bite wounds within 30 minutes of the bite, though in some cases, these manifes-
involves thorough exploration, tations may take up to 4 hours to appear. Erythema, petechiae, bul-
irrigation, and debridement. X- lae, and vesicles are sometimes seen. Severe envenomation may
rays must be obtained and induce systemic reactions, including disseminated intravascular
wounds explored to evaluate coagulation (DIC), bleeding, hypotension, shock, acute respiratory
the patient for fractures or open distress syndrome (ARDS), and renal failure. Patients bitten by
joint injuries. If a joint capsule coral snakes, on the other hand, show no obvious local signs when
has been violated, the joint must be thoroughly cleaned. Because of envenomation has occurred. Consequently, the physician must
the infection risk, wounds may be allowed to heal by secondary or look for systemic signs, such as paresthesias, increased salivation,
delayed primary closure; primary closure is also possible if thor- fasciculations of the tongue, dysphagia, difficulty in speaking, visu-
ough debridement is performed.32 Rabies prophylaxis treatment al disturbances, respiratory distress, convulsions, and shock.These
should be considered for patients who have been bitten by wild ani- symptoms may not develop until several hours after the bite.
mals [see Adjunctive Wound Treatment, Rabies Prophylaxis, below]. If signs or symptoms suggestive of envenomation are found,
appropriate laboratory tests (hematocrit, fibrinogen level, coagula-
Humans and nonvenomous animals Most human bite tion studies, platelet count, urinalysis, and serum chemistries)
wounds are clenched fist wounds sustained by young men.53 should be ordered. Laboratory tests should be repeated every 8 to
Human bite wounds are considered infected from the moment of 24 hours for the first 1 to 3 days to determine whether envenoma-
infliction and must be treated with antibiotics.54,55 The antibiotic tion is progressing. Severe envenomation can cause decreased fib-
regimen should be selected on the basis of the bacterial species rinogen levels, coagulopathy, bleeding, and myoglobinuria.
believed to be present. Common isolates from bite wounds Treatment of venomous snake bites includes immobilization
includes Streptococcus anginosus, Staphylococcus aureus, Eikenella and elevation. If envenomation is suspected or confirmed, anti-
corrodens, Fusobacterium nucleatum, Prevotella melaninogenica, and venin should be administered intravenously and as early as possi-
Candida species.53 To cover these species, a broad-spectrum ble. Antivenins commonly used in the United States include Anti-
antibiotic or combination of antibiotics (e.g., amoxicillin-clavu- venin (Crotalidae) Polyvalent (ACP) (Wyeth Pharmaceuticals,
lanate or moxifloxacin) should be administered.53 Collegeville, Pennsylvania) and Crotalidae Polyvalent Immune
Nonhuman primates can cause viral infection, most commonly Fab (Ovine) (CroFab; Protherics Inc., Nashville, Tennessee).65
with cercopithecine herpesvirus type 1. If left untreated, such in- Fab antivenom (FabAV) is less allergenic and more potent than
fection can lead to meningoencephalitis, which carries a 70% mor- ACP and thus has largely supplanted it in the United States.65,66
tality. Accordingly, acyclovir prophylaxis is recommended.56 Patients are treated with a loading dose of four to six vials of
Wounds caused by cat bites or scratches are at high (80%) risk FabAV, followed by three two-vial maintenance doses at 6, 12, and
for infection, usually attributable to Pasteurella multocida. The aer- 18 hours to prevent recurrence of symptoms. If symptoms
progress despite antivenin treatment, an additional four to six vials throughout the northwestern United States, they live in low places
of FabAV are given twice more; if symptoms continue to progress, and build funnel-shaped webs in dark spaces. Hobo spiders have
consideration should be given to using ACP. ACP remains the been reported to inflict painful bites that lead to wound ulcera-
most effective antivenin for patients with coral snake bites and tion, dermonecrosis, and a persistent headache, though the accu-
those who do not respond to FabAV. Before ACP is administered, racy of such reports has been debated.69,72,73 A slow-healing ulcer
the patient must be tested for sensitivity. The major complication that leaves a central crater has been described.Treatment consists
of antivenin therapy is serum sickness. This complication occurs of local wound care.
in approximately 50% to 75% of patients treated with ACP but in
only 16% of those treated with FabAV.65,67 Stings
Compartment syndrome is a rare but severe complication of a Scorpions Stings from
snake bite. Fasciotomy is sometimes required to relieve extremity most of scorpion species found
compartment syndrome, but it is not necessary for prophylactic in the United States cause only
purposes. Tourniquets, incision and suction, cryotherapy, and limited local reactions that can
electric shock treatment are of little value for snake bites and may be managed conservatively;
increase complication rates.There is no clear evidence to support however, stings from Centru-
antibiotic prophylaxis in this setting.64 roides sculpturatus, which is
found in California and many
Spider bites. The bites of most spiders found in the United southern states, may be more severe. Centruroides has a sting that
States cause little to no wound or local reaction; however, there are causes envenomation with a neurotoxin. Erythema, edema, and
three types that are capable of injecting venom with skin-penetrat- ecchymosis at the site of the sting are evidence that envenomation
ing bites. Brown recluse spiders (Loxosceles reclusa) can be identi- did not take place. Instead, envenomation is indicated by an
fied by a violin-shaped dorsal mark. They are nocturnal, live in immediate and intense burning pain at the wound site.74 The ini-
dark and dry places, and are found in the central and southern tial local pain may then be followed by systemic symptoms such
United States. The venom is a phospholipase enzyme that acts as as muscle spasm, excess salivation, fever, tachycardia, slurred
a dermal toxin and almost always causes a local reaction.68 Local speech, blurry vision, convulsions, or death.68 Treatment consists
signs and symptoms may be limited to minor irritation, though of icing and elevation of the wounded area, followed by adminis-
they may also progress to extreme tenderness, erythema, and tration of barbiturates for control of neuromuscular activity and
edema.The onset of local signs and symptoms may be delayed for institution of supportive therapy with antihistamines, cortico-
as long as 8 hours after a bite, and tissue necrosis may then devel- steroids, and analgesics.74
op over the following days to weeks. Systemic reactions may
include mild hemolysis, mild coagulopathy, and DIC, though Centipedes Centipedes are slender, multisegmented, and
severe intravascular hemolytic syndrome and death have also been multilegged arthropods that range in size from 1 to 30 cm and in
reported.68,69 Oral administration of dapsone (50 to 100 mg/day) color from bright yellow to brownish black. The first pair of legs
to minimize tissue necrosis has been advocated by some70; howev- are modified into sharp stinging structures that are connected to
er, this treatment is of uncertain efficacy, and no prospective data venom glands. Centipedes prefer dark, damp environments and
currently support its use. Moreover, dapsone can cause a serious may be found throughout the southern United States. Local
unwanted side effect, hemolytic anemia.69 If systemic symptoms symptoms associated with centipede stings include pain, erythe-
develop, systemic corticosteroid therapy and supportive measures ma, edema, lymphangitis, lymphadenitis, weakness, and paresthe-
are indicated. Brown recluse antivenin is not available in the sia. Skin necrosis may occur at the envenomation site. Systemic
United States. symptoms may include anxiety, fever, dizziness, palpitations, and
Black widow spiders (Latrodectus mactans) can be identified by nausea.75 Treatment consists of symptomatic pain control, infiltra-
a red-hourglass ventral mark.63 They live in dark, dry, and protect- tion of local anesthetics, administration of antihistamines, and
ed areas and are distributed widely throughout the continental local wound care.75
United States.The venom is a neurotoxin that produces immedi-
ate and severe local pain. Local signs and symptoms include two Hymenoptera The order Hymenoptera includes wasps,
fang marks, erythema, swelling, and piloerection.68 Systemic reac- bees, and ants. Wasps, which are found across the United States,
tions with neurologic signs may develop within 10 minutes and live in small colonies and may attack in groups when provoked.
may include muscle pain and cramps starting in the vicinity of the Honeybees (Apis mellifera) and bumblebees (Bombus species), also
bite, abdominal pain, vomiting, tremors, increased salivation, found across the United States, are generally docile and rarely
paresthesias, hyperreflexia, and, with severe envenomation, shock. sting unless provoked. Africanized honeybees (Apis mellifera scutel-
Systemic symptoms may last for days to weeks. High-risk persons lata, also referred to as killer bees), found primarily in the south-
(e.g., those who are younger than 16 years, the elderly, pregnant western states, are far more aggressive than other bees. Fire ants
women, hypertensive patients, or persons who continue to show (Solenopsis invicta and Solenopsis richteri) are wingless, ground-
symptoms despite treatment) may experience paralysis, hemoly- dwelling arthropods that are found in many southern states and
sis, renal failure, or coma. Treatment includes 10% calcium glu- that attack in an aggressive swarm.
conate I.V. for relief of muscle spasm, methocarbamol or diaze- Although Hymenoptera stingers are small, they can evoke se-
pam for muscle relaxation, and a single dose of antivenin. Anti- vere local and systemic reactions.The local response to a Hymen-
venin causes serum sickness in as many as 9% of patients; conse- optera sting is a painful, erythematous, and edematous papule that
quently, its use is controversial except in cases where the patient is develops within seconds and typically subsides in 4 to 6 hours.
at high risk.71 Some stingers are barbed and must be removed with a scraping,
Hobo spiders (Tegenaria agrestis) can be identified by their long rather than pinching, motion to prevent the injection of more
hairy legs and a cephalothorax that is marked by two stripes and venom. Systemic reactions occur in about 5% of the population
butterfly markings dorsally and two stripes ventrally. Found and may lead to anaphylaxis with syncope, bronchospasm, hypo-
tension, and arrhythmias. Wounds and local reactions are treated With sutured wounds, dressings are required only until
with ice, elevation, and analgesics. Systemic reactions are treated drainage from the wound ceases.With nondraining wounds, dress-
with subcutaneous epinephrine, diphenhydramine, and support- ings may be removed after 48 hours, by which time epithelial cells
ive airway and blood pressure care.68 Persons with a history of sys- will have sealed the superficial layers of the wound. An alternative
temic reactions to insect stings should carry epinephrine kits. method of treating minimally draining incisional wounds is to
apply an antibacterial ointment [see Adjunctive Wound Treatment,
DRESSINGS FOR SPECIFIC
Topical Antimicrobials, below]. Such ointments are occlusive and
TYPES OF WOUNDS
maintain a sterile, moist environment for the 48 hours required for
Generally, the functions of a epithelialization. In anatomic areas that are difficult to dress (e.g.,
wound dressing include pro- the scalp), it may be reasonable to forgo a dressing and simply
tection, antisepsis, pressure, apply ointments or allow a scab to form on the wound surface.
immobilization, debridement, Operative incisional wounds are also sometimes covered with an
provision of a physiologic envi- occlusive dressing to optimize epithelialization [see Abrasions,
ronment, absorption, packing, above]. Some of these dressings are transparent, allowing observa-
support, information, comfort, and aesthetic appearance. More tion of the wound.The disadvantage of occlusive dressings is their
specifically, the functions of a dressing should be tailored to the limited absorptive capacity, which allows drainage from the wound
wound type, and the purpose of the dressing must be carefully to collect underneath.
considered before application.
Complex Wounds
Abrasions For complex wounds containing questionably necrotic tissue,
Abrasions heal by epithelialization, which is accelerated by the foreign bodies, or other debris that cannot be removed sharply,
warm, moist environment created by an occlusive dressing.76,77 wet-to-dry dressings are effective, simple, and inexpensive. A sin-
Such an environment not only promotes epithelialization but also gle layer of coarse wet gauze is applied to a wound, allowed to dry
enhances healing, both because of the moisture itself and because over a period of 6 hours, and removed. Necrotic tissue, granula-
of the low oxygen tension that promotes the inflammatory phase.78 tion tissue, debris, and wound exudate become incorporated with-
A variety of dressings are suitable for treatment of abrasions, in- in the gauze and are removed with the dressing.The disadvantages
cluding biologic dressings, hydrogels, hydrocolloids, and semiper- of wet-to-dry dressings are pain and damage to or removal of some
meable films.These dressings need not be changed as long as they viable tissue. If the wound bed contains tendons, arteries, nerves,
remain adherent. Small, superficial wounds also heal readily when or bone, wet-to-wet dressings should be used to prevent desicca-
dressed with impregnated gauze dressings (e.g., Xeroform and tion of these critical structures.
Scarlet Red [Kendall, Mansfield, Massachusetts]), which allow Wet-to-wet dressings, which are not allowed to dry, cause less
exudates to pass through while maintaining a moist wound bed.78 tissue damage than wet-to-dry dressings but do not produce as
These less adherent dressings must be changed more regularly.79 much debridement. Most wet-to-wet dressings are kept moist with
Dry dressings (e.g., gauze) should be avoided with abrasions saline. Wounds with significant bacterial contamination may be
because they facilitate scab formation. Scabs slow epithelialization, treated with dressings that contain antibacterial agents (e.g.,
in that advancing cells must enzymatically debride the scab- mafenide, silver sufadiazine, silver nitrate, or iodine).
wound interface in order to migrate.80 Wounds covered with a scab Biologic and semipermeable films also maintain a moist wound
also tend to cause more discomfort than wounds covered with bed, but they are difficult to use on deep or irregular wounds and
occlusive dressings. wounds with a great deal of drainage. Consequently, wet-to-wet
dressings with agents such as silver sulfadiazine are often used for
Lacerations these types of wounds. Enzymatic agents can debride wounds
For sutured deep wounds, the specific purposes of a dressing effectively and are a reasonable alternative to wet-to-dry or wet-to-
are to prevent bacterial contamination, to protect the wound, to wet dressings for wounds that contain necrotic tissue.82
manage drainage, and to facilitate epithelialization. Dressings used
on such wounds usually consist of three basic layers. The inner
(contact) layer is chosen to minimize adherence of the dressing to Table 4—Recommendations for
the wound and to facilitate drainage through itself to the overlying Tetanus Immunization89,90
layers. Common choices for this layer include fine-mesh gauze,
petrolatum gauze, Xeroform or Xeroflo (Kendall, Mansfield,
Tetanus Immunization History Tt* TIG
Massachusetts) gauze, and Adaptic (Johnson & Johnson, New
Brunswick, New Jersey).These substances should be applied only Unknown Yes Yes
as a single layer; in multiple layers, they become occlusive. The
middle layer is chosen for absorbency and ability to conform to > 10 yr since last booster Yes Yes
shape of the wound area. It is usually composed of fluffs, Kerlix ≥ 5 and ≤ 10 yr since last booster Yes No
(Kendall, Mansfield, Massachusetts), or wide-mesh gauze, all of
< 5 yr since last booster No No
which facilitate capillary action and drainage.81 The middle layer
must not be allowed to become soaked, because if it is, exudate Note: Tetanus toxoid (Tt) and tetanus immune globulin (TIG) should be administered with
will collect on the wound surface, and maceration and bacterial separate syringes at different anatomic sites. Tetanus and diphtheria toxoids are contraindi-
cated for the wounded patient if there is a history of a neurologic or severe hypersensitivity
contamination may occur. The outer (binding) layer serves to reaction after a previous dose. Local side effects alone do not preclude continued use. If a
systemic reaction is suspected of representing allergic hypersensitivity, immunization should
secure the dressing. Common choices for this layer include Kling be postponed until appropriate skin testing is performed. If a contraindication to a Tt-con-
(Johnson & Johnson, New Brunswick, New Jersey), ACE ban- taining preparation exists, TIG alone should be used.
*For patients younger than 7 years, diphtheria-tetanus-pertussis vaccine (DTP) (or tetanus
dages (BD Medical, Franklin Lakes, New Jersey), and Coban (3M, St. and diphtheria toxoids, if pertussis vaccine is contraindicated) is preferable to Tt alone. For
Paul, Minnesota). patients 7 years of age or older, Tt alone may be given.
Some wounds are difficult to dress and require special consid- wound before an occlusive dressing does not reduce the infection
eration. For wounds with flaps or questionably viable tissue, com- rate and may promote antibiotic resistance.85 For uncomplicated
pression dressings should not be used, because they may cause traumatic wounds, however, application of bacitracin and neomy-
ischemia. Wounds that cross joints are best dressed with plaster cin ointment results in a significantly lower infection rate than ap-
splints for temporary immobilization; semipermeable films are plication of petrolatum.86 Neomycin-containing ointments reduce
flexible and may also be used in this setting.Wounds with high lev- bacterial counts in partial-thickness wounds in animals, but many
els of exudates may be dressed with hydrocolloids, hydrogels, or other over-the-counter antibiotic ointments are not effective at re-
alginates.78 For large or irregular wounds, negative-pressure ducing bacterial counts in wounds.87
wound therapy (NPWT) with the VAC system (Kinetic Concepts Wounds contaminated by bacteria can be treated with dressings
Inc., San Antonio, Texas) is recommended; VAC dressings con- that contain antibacterial agents such as mafenide, silver nitrate,
form well and remain adherent. Additionally, NPWT uses subat- silver sulfadiazine, or iodine. Mafenide penetrates eschar well, but
mospheric pressure to remove excess wound fluid, stimulates the it can cause pain and has the potential to induce metabolic acido-
formation of granulation tissue, improves peripheral blood flow sis through inhibition of carbonic anhydrase. Silver has microbici-
and tissue oxygenation, and reduces the size of the wound.83,84 dal effects on common wound contaminants and may also be
Use of the VAC system is contraindicated in wounds with exposed affective against methicillin-resistant S. aureus (MRSA).84 Silver
blood vessels or bowel. nitrate does not cause pain, but it can cause hypochloremia, and
it stains fingernails and toenails black. Silver sulfadiazine is fre-
quently used because of its broad antibacterial spectrum, its rela-
Adjunctive Wound Treatment tively low side effect profile (transient leukopenia is occasionally
seen), and its ability to maintain a moist wound environment
PROPHYLACTIC SYSTEMIC ANTIBIOTICS
(thereby speeding healing and epithelialization).88
For most wounds, antibiotic prophylaxis is not indicated.When
TETANUS PROPHYLAXIS
it is called for, the agent or agents to be used should be selected
on the basis of the bacterial species believed to be present. The Tetanus is a nervous system disorder that is caused by Clostri-
anatomic location of a wound may also suggest whether oral flora, dium tetani and is chacracterized by muscle spasm. In the past,
fecal flora, or some less aggressive bacterial contaminant is likely wounds were classified as either tetanus-prone or non–tetanus-
to be present. Gram staining can provide an early clue to the prone on the basis of their severity. It is now clear, however, that
nature of the contamination. Ultimately, the choice of a prophy- wound severity is not directly correlated with tetanus susceptibil-
lactic antibiotic regimen is based on the clinician’s best judgment ity; tetanus has been associated with a wide variety of injury types
regarding which agent or combination of agents will cover the over a broad spectrum of wound severity.89 Accordingly, all wounds,
pathogens likely to be present in the wound on the basis of the regardless of cause or severity, must be considered tetanus prone,
information available. and the patient’s tetanus immunization status must always be con-
As a rule, clean and clean-contaminated wounds are adequately sidered.Tetanus wound prophylaxis should be provided as appro-
treated with irrigation and debridement.There are, however, some priate [see Table 4].89,90
local factors (e.g., impaired circulation and radiation injury) and
RABIES PROPHYLAXIS
systemic factors (e.g., diabetes, AIDS, uremia, and cancer) that
increase the risk of wound infection; in the presence of any of these Rabies is an acute progressive encephalitis that is caused by
factors, prophylactic antibiotics should be considered. In addition, viruses from the family Rhabdoviridae. The rabies virus can be
prophylactic antibiotics should be given to patients with extensive transmitted by any mammal, but viral reservoirs are found only in
injuries to the central area of the face (to prevent spread of infec- carnivores and bats. In North America, raccoons, skunks, bats,
tion through the venous system to the meninges), patients with and foxes are the animals most commonly responsible for trans-
valvular disease (to prevent endocarditis), and patients with pros- mission.91 Bite wounds in which the animal’s saliva penetrates the
theses (to reduce the risk of bacterial seeding of the prosthesis). dermis are the most common cause of exposure.
Lymphedematous extremities are especially prone to cellulitis, and Postexposure treatment consists of wound care, infiltration of
antibiotics are indicated whenever such extremities are wounded. rabies immune globulin into the wound, and administration of
Contaminated and dirty wounds are associated with a higher vaccine.91,92 Wound care involves washing with soap and water, as
risk of infection and are therefore more likely to necessitate anti- well as the use of iodine- or alcohol-based virucidal agents.93
biotic prophylaxis. Human bite wounds, mammalian bite wounds, Guidelines for postexposure prophylaxis have been established
and wounds contaminated with dirt, bodily fluids, or feces are [see Table 5]. The vaccination regimen is determined by the
all prone to infection and must be treated with antibiotics.54,55 patient’s previous vaccination status [see Table 6].
Prophylactic administration of a combination of a β-lactam
antibiotic with a β-lactamase inhibitor (e.g., amoxicillin-clavu-
lanate) is appropriate.57,60 Antibiotic prophylaxis is also indicated Postoperative Wound Care
for mutilating wounds with extensive amounts of devitalized tis- Closed wounds should be kept clean and dry for 24 to 48
sue. Such wounds are often contaminated by a mixture of gram- hours after repair. Epithelialization begins within hours after
positive organisms and gram-negative organisms.40 When antibi- wound approximation and forms a barrier to contamination.
otics are indicated for these injuries, broad-spectrum coverage is Gentle cleansing with running water will help remove bacteria
appropriate. and crusting.The patients should not place tension on the wound
or engage in strenuous activity until the wound has regained suf-
TOPICAL ANTIMICROBIALS
ficient tensile strength. In the first 6 weeks after repair, the
Topical antimicrobials (e.g., antibiotic ointments, iodine prepa- wound’s tensile strength increases rapidly; after this period, ten-
rations, and silver agents) are commonly used to prevent wound sile strength increases more slowly, eventually reaching a maxi-
infection. Application of mupirocin ointment to a clean surgical mum of 75% to 80% of normal skin strength [see Figure 2].
Table 5—Recommendations for Postexposure Rabies Prophylaxis91-93
Animal Type Animal Disposition and Evaluation Prophylaxis
If animal is healthy and available, it is confined for Start vaccination if animal exhibits rabies
10 days of observation symptoms*
If animal is rabid or suspected of being rabid, no

Dogs, cats, ferrets observation is indicated Provide immediate vaccination
If animal’s rabies status is unknown, consultation

Consult public health official
is indicated
Bats, skunks, raccoons, foxes, bobcats, coyotes, Animal is regarded as rabid unless brain laboratory Provide immediate vaccination unless brain labora-
mongooses, and most carnivores tests are negative tory tests are negative
Livestock, small rodents (e.g., squirrels, chipmunks,

rats, hamsters, gerbils, guinea pigs, and mice), Each case is considered indivdually; rabies report- Consult public health officials; almost never require
large rodents (e.g., woodchucks and beavers), ed in large rodents in some areas antirabies treatment
rabbits, hares, and other mammals
*If the isolated animal shows symptoms of rabies, postexposure prophylaxis is started immediately, and the animal is euthanized for laboratory testing. Vaccination prophylaxis is stopped
if laboratory tests are negative for rabies.
Wounds at risk for infection should be assessed by a medical trunk) should remain in place longer, as should sutures in wounds
provider within 48 hours of care. In addition, the patient should sustained by patients who have a condition that hinders healing
be taught to look for signs of infection (e.g., erythema, edema, (e.g., malnutrition). In such cases, suture-mark scars are consid-
pain, purulent drainage, and fever). ered acceptable. The appropriate method of removing a suture is
The timing of suture or staple removal is determined by balanc- first to cut it, then to pull on the knot parallel to or toward, rather
ing the requirements for optimal cosmesis against the need for than away from, the wound.
wound support. On one hand, it is clear that for optimal cosmesis, After suture removal, numerous methods are employed to
sutures should be removed early, before inflammation and epithe- minimize unsightly scar formation. The cosmetic outcome of a
lialization of suture tracts. An epithelialized tract will develop scar is largely determined by the nature and severity of the
around a suture or staple that remains in the skin for longer than wound, which are outside the surgeon’s control. The greatest
7 to 10 days; once the suture or staple is removed, the tract will be impact a surgeon can have on cosmetic outcome is derived from
replaced by scar.94 On the other hand, it takes a number of weeks providing meticulous care when the acute wound is initially
for the wound to gain significant tensile strength, and early encountered. Postoperative wound care measures employed to
removal of wound support can lead to dehiscence of wounds that optimize cosmetic outcome include massage, the use of silicone
are under substantial tension. Early suture removal is warranted bandages or pressure garments, and the application of lotions.
for some wounds. For example, sutures in aesthetically sensitive These interventions appear to help, but prospective trials are
areas (e.g., the face) may be removed on day 4 or 5, and sutures needed to confirm their efficacy and establish treatment guide-
in areas under minimal tension (e.g., in wounds parallel to skin lines.The healing wound is fragile, and topical application of oint-
tension lines) may be removed on day 7. Sutures in wounds sub- ments to achieve an improved scar appearance may actually
ject to greater stress (e.g., wounds in the lower extremities or the achieve the opposite result. For example, vitamin E, which is
commonly applied to healing wounds, can induce contact der-
matitis and cause scars to look worse.95
Table 6—Recommendations for
Postexposure Rabies Vaccination91-93 Factors That May Hinder Wound Healing
Despite a surgeon’s best efforts, healing does not always occur
Dosage in an undisturbed fashion: sometimes, a closed wound dehisces. If
Vaccine No Previous Previous the dehiscence is sudden, the wound is clean, and only skin and
Vaccination Vaccination superficial tissues are involved, then the wound should be
reclosed, and the cause of the dehiscence should be corrected if
Full dose of 20 IU/kg infil- possible. If the dehiscence is slow and the wound is contaminated
trated around wound(s)
Human rabies immune at initial presentation; or infected, then the wound should be allowed to heal secondari-
Not administered
globulin (HRIG) use separate syringe ly, with dressing changes and scar revision to be performed at a
and anatomic site from later date.
vaccine
There are a number of local and systemic factors [see Table 7]
Human diploid cell vaccine that can interfere with wound healing (see below). Accordingly, it
(HDCV), rabies vaccine
1.0 ml IM on days 0, 3, 7,
is essential for clinicians to be aware of and knowledgeable about
adsorbed (RVA), or 1.0 ml IM on
purified chick embryo 14, and 28* days 0 and 3* these factors and, whenever possible, to take appropriate mea-
cell vaccine (PCECV) sures to improve the chances for optimal healing. The use of
nutrients and growth factors to stimulate wound healing may be
*Vaccine administration site for adults is the deltoid; for children, the anterolateral thigh may considered; this measure is currently the subject of extensive
be used. To prevent sciatic nerve injury and reduce adipose depot delivery, the gluteus is
never used. research.
800 that show no perfusion on fluorescein testing is ischemic. Ques-

tionably viable tissue should be monitored closely and debrided
Tensile Strength (g/mm2)
600
when declared nonviable.
Hematoma and Seroma
400 Hematomas and seromas increase the risk of infection and the
likelihood of wound dehiscence. To prevent their formation,
hemostasis at the time of wound closure must be meticulous, and
200 bleeding diatheses must be corrected. Because the rubbing of
wound edges against one another is associated with the formation
of hematomas and seromas, wound edge movement should be
0
1 2 3 4 5 6 7 8 9 10 11 12 minimized and immobilization employed as necessary.Wounds at
Weeks after Wounding significant risk for hematoma or seroma formation should be
closed over a drain.
Figure 2 The tensile strength of skin wounds increases rapidly
for approximately 6 weeks after wounding; it then continues to Large hematomas or seromas that are recognized early, before
increase slowly for 6 to 12 months after wounding, though it never infection develops, should be evacuated, and the wound should be
reaches the tensile strength of unwounded tissue. Collagen is reclosed. Small hematomas or seromas can usually be treated con-
remodeled and replaced with highly cross-linked collagen along servatively until they are reabsorbed, but close observation is
tissue stress lines. The process of collagen replacement and scar required. If a hematoma or seroma is not recognized until late,
remodeling continues for years. when infection has already set in, the wound should be opened,
drained, and allowed to heal secondarily; scar revision may be car-
ried out at a later point.
LOCAL FACTORS
Trauma
Tension
Tissue injury is obviously associated with external trauma, but
Tension—whether from inherent skin tension, poor surgical it can also be iatrogenic. Rough handling of tissue edges with for-
technique, movement of joints, or inadequate wound support— ceps produces minute crush injuries, which promote wound infec-
may lead to separation of wound edges. It should be minimized tion. It is preferable to handle wound edges with hooks, using gen-
by undermining the wound edges during closure to allow easy tle surgical technique.
coaptation.Tissue ellipses from complex wound edges should be
kept as narrow as possible and should be created along relaxed Edema
skin tension lines. Adequate support of the wound after suture Edema results from the accumulation of fluid in the interstitial
removal is critical; many surgeons keep tapes (e.g., Steri-Strips) space. It may occur as an acute process, in which tissue injury
over a wound for 3 weeks, until the strength of the wound equals leads to histamine release, leaky capillaries, and inflammation, or
that of the deep sutures and tapes. Wounds over joints should be as a chronic process, in which venous insufficiency, lymphatic
splinted to reduce tension. insufficiency, and a low plasma oncotic pressure may cause fluid
to collect in the interstitium. In both cases, edema raises tissue
Foreign Body
pressure and inhibits perfusion and healing. The proteinaceous
All foreign bodies that contaminate a wound should be re- and fibrin-rich fluid also forms clot and fibrous tissue, which hin-
moved at the time of initial debridement and before wound clo- der the supply of oxygen and inflammatory cells.97 Clearance of
sure. Retained foreign bodies may cause failed healing, infection, wound edema is necessary for healing and may be successfully
or traumatic tattooing. Iatrogenic foreign bodies may also interfere accomplished by means of compression therapy98 or NPWT with
with wound healing and promote infection. Suture material is a a VAC device.83
foreign body; thus, the number and size of sutures placed in a
wound should be kept to the minimum necessary for coaptation
of the wound edges.
Table 7—Local and Systemic Factors
Infection That Impair Wound Healing
All traumatic wounds are contaminated and should therefore
be irrigated to remove organisms. Infection occurs when bacteria
Local Factors Systemic Factors
are too numerous (>105 organisms/g tissue) or virulent for local
tissue defenses to be able to control them.96 As noted [see Tension Inherited connective tissue disorders
Adjunctive Wound Care, Prophylactic Antibiotics, above], local Foreign body Hypothermia
factors (e.g., impaired circulation and radiation injury) increase Infection Oxygen
the risk of infection, as do various systemic diseases (e.g., diabetes, Ischemia Tobacco smoking
AIDS, uremia, and cancer). Wound cultures should be obtained, Hematoma and seroma Malnutrition
and broad-spectrum antibiotic therapy should be started when Edema Jaundice
infection is diagnosed. The antibiotic regimen is adjusted on the Irradiation Age
basis of culture results and sensitivities. Diabetes mellitus
Uremia
Ischemia Steroids
Chemotherapeutic agents
Ischemic wound tissue readily becomes infected and therefore Other drugs
must be debrided. Tissue with dermal edges that do not bleed or
Irradiation Oxygen
Irradiation damages the skin and can cause wounds to heal Tissue oxygenation is necessary for aerobic metabolism, fibro-
slowly. It also induces chronic skin changes: previously irradiated blast proliferation, collagen synthesis, and the antimicrobial oxida-
tissues demonstrate delayed healing when wounded.99 Irradiated tive burst of inflammatory cells.Transcutaneous oxygen tension is
tissue is characterized by a thickened and fibrotic dermis, a thin directly correlated with wound healing.109 Wound tissue oxygena-
epidermis, pigment changes, telangiectasia, decreased hair, and tion is determined by blood perfusion, hemoglobin dissociation,
increased dryness (as a consequence of damage to sebaceous and local oxygen consumption, fraction of inspired oxygen (FIO2), oxy-
sweat glands). The microvasculature of the skin is obliterated, gen-carrying capacity (as measured by hemoglobin content), arte-
leading to tissue ischemia and impaired healing. Keratinocytes, rial oxygen tension (PaO2), circulating blood volume, cardiac func-
which are necessary for wound epithelialization, exhibit impaired tion, arterial inflow, and venous drainage.106,110 Each of these vari-
mitotic ability and slow progressive desquamation (as a conse- ables should be addressed in promoting wound healing.
quence of their superficial location and high replication rate).97 Supplemental administration of oxygen (inspired or hyperbar-
Collagen bundles become edematous and fibrotic. Fibroblasts, ic) has beneficial effects on wound healing.The incidence of infec-
which are necessary for collagen synthesis, also show diminished tion in surgical wounds can be reduced by improving the FIO2 with
migration and proliferation.100 supplemental oxygen.111 In a study of patients undergoing colon
Because irradiated skin is irreversibly damaged, tissue transfer surgery, for example, the wound infection rate was 50% lower
may be required for repair of wounds in areas subjected to radia- when an FIO2 of 0.8 was maintained intraoperatively and for 2
tion. Vitamin A supplementation can lessen the adverse effects of hours postoperatively than when an FIO2 of 0.3 was maintained.112
irradiation on wound healing.101 Hyperbaric oxygen therapy (i.e., the delivery of oxygen in an envi-
ronment of increased ambient pressure) has been used for treat-
SYSTEMIC FACTORS ment of many types of wounds in which tissue hypoxia may impair
healing.43 It increases tissue oxygen concentrations tenfold while
Inherited Connective Tissue Disorders also causing vasoconstriction, which results in decreased posttrau-
Several inherited connective tissue disorders are known to inter- matic edema and decreased compartment pressures.113 The ele-
fere with normal wound healing. Ehlers-Danlos syndrome exists as vated pressure and hyperoxia induced by hyperbaric oxygen ther-
multiple types that exhibit certain differences, but in general, the apy may promote wound healing; for patients with an acute
syndrome leads to deficient collagen cross-linking, which results in wound, this modality may be a useful adjunct in treating limb-
lax and fragile skin, lax joints, and impaired wound healing. For threatening injury, crush injury, and compartment syndrome.43
Circulating volume can be improved by administering crystal-
example, an Ehlers-Danlos patient who undergoes an elective her-
loids or blood. However, anemia alone is not associated with
nia repair or facelift may have a poor outcome as a consequence of
impaired wound healing unless it is severe enough to limit circu-
deficient collagen formation and poor wound healing.102,103 Osteo-
lating blood volume.114 The vasculature may be compromised
genesis imperfecta is a procollagen formation disorder that is clini-
either systemically (e.g., by diabetes mellitus or peripheral vascu-
cally manifested by brittle bones, increased laxity of ligaments and
lar disease) or locally (e.g., by trauma or scar). Vascular bypasss
skin, bone deformities, and impaired wound healing.104 Marfan syn-
may be necessary to improve tissue oxygenation in patients with
drome is an autosomal dominant disorder characterized by deficient
poor arterial inflow.97
synthesis of fibrillin, which is a key component in elastin formation.
Patients with this syndrome have long extremities and hyperex- Tobacco Smoking
tendable joints; those who are seriously affected have lax ligaments, Tobacco smoking reduces tissue oxygen concentrations, impairs
dissecting aneurysms, dislocated eye lenses, pectus excavatum, and wound healing, and contributes to wound infection and dehis-
scoliosis. Surgical repair of aneurysms and hernias is usually suc- cence.115,116 The effects of smoking are attributable to vasocon-
cessful in this population, though healing difficulties may be en- striction (caused by nicotine), displacement of oxygen binding
countered.103 Cutis laxa is a disease in which an elastase inhibitor (resulting from the high affinity of carbon monoxide for hemoglo-
deficiency gives rise to defective elastic tissue. Patients with this dis- bin), increased platelet aggregation,117 impairment of the inflam-
ease have thick, coarse, and drooping skin, along with hernias, matory cell oxidative burst,118 endothelial damage, and the devel-
aneurysms, heart disease, and emphysema. Unlike patients with the opment of atherosclerosis.115,116,119 All acutely injured patients
other heritable diseases mentioned, cutis laxa patients often show should stop smoking, and ideally, all noninjured patients sched-
no impairment of wound healing.105 uled to undergo surgery should stop smoking at least 3 weeks before
Hypothermia an elective surgical wound is made.118,120 Like smoked tobacco,
transcutaneous nicotine patches alter the inflammatory cell oxida-
Hypothermia may develop as a consequence of administration tive burst and cause vasoconstriction; accordingly, they too should
of anesthetic drugs, exposure to cold, or redistribution of body not be used when a wound is present.118
heat; it leads to peripheral vasconstriction and impaired wound
oxygen delivery.106 Wound tensile strength increases more slowly Malnutrition
when healing occurs in a cold environment. Prevention or correc- On average, hospitalized patients show a 20% increase in ener-
tion of hypothermia reduces the wound infection rate and increas- gy expenditure, and this increase calls for appropriate nutritional
es collagen deposition in patients undergoing abdominal surgery.107 compensation.97 Good nutritional balance and adequate caloric
Preoperative systemic and local warming also reduces the wound intake (including sufficient amounts of protein, carbohydrates, fatty
infection rate in patients undergoing elective operations.108 A warm acids, vitamins, and other nutrients) are necessary for normal
body temperature must be maintained in all wounded patients to wound healing.121
reduce subcutaneous vasoconstriction and maximize wound heal- All patients who have sustained wounds should undergo nutri-
ing potential. tional assessment,122 which typically includes measuring serum
levels of albumin, protein, prealbumin, transferrin, and insulinlike wounds; this measure will improve collagen synthesis, though it
growth factor–1 (IGF-1).97 The serum albumin level is one of the may not have any appreciable effect on the healing rate.143
best predictors of operative mortality and morbidity.123 A value
lower than 2.5 g/dl is considered severely depressed, and a value Age
lower than 3.4 g/dl is associated with higher perioperative mortal- Aging has a deleterious effect on the capacity for wound heal-
ity.124,125 Protein provides an essential supply of the amino acids ing.145 Increasing age is associated with an altered inflammatory
used in collagen synthesis, and hypoproteinemia results in im- response, impaired macrophage phagocytosis, and delayed heal-
paired healing; consequently, it is not surprising that protein ing.146 Nevertheless, even though the wound healing phases begin
replacement and supplementation can improve wound heal- later in elderly persons, proceed more slowly, and often do not
ing.126,127 In particular, supplementation specifically with the amino reach the same level that they would in younger persons, elderly
acids arginine, glutamine, and taurine (which are essential for ana- patients are still able to heal most wounds with ease.147
bolic processes and collagen synthesis) is known to enhance wound
healing.128-130 Glutamine is the most abundant free amino acid in Diabetes Mellitus
the body, and under catabolic conditions, it is released from mus- Diabetes mellitus is associated with poor wound healing and an
cle unless provided as a supplement. increased risk of infection. Diabetic neuropathy leads to sensory
Vitamins C, A, K, and D are essential for normal healing. loss (typically in the extremities) and diminished ability to detect
Vitamin C (ascorbic acid) hydroxylates the amino acids lysine and or prevent injury and wounding. Once present, wounds in diabet-
proline during collagen synthesis and cross-linking. A deficiency ic patients heal slowly. The etiology of this healing impairment is
of this vitamin causes scurvy, marked by failed healing of new multifactorial. Diabetes is associated with impaired granulocyte
wounds and dehiscence of old wounds. Vitamin C supplementa- function and chemotaxis, depressed phagocytic function, altered
tion (100 to 1,000 g/day) can improve wound healing.97,130 Vitamin humoral and cellular immunity, peripheral neuropathy, peripher-
A (retinoic acid) is essential for normal epithelialization, proteo- al vascular disease, and various immunologic disturbances, any of
glycan synthesis, and normal immune function.131-133 Retinoids which may hinder wound healing.148-151 In addition, it is associat-
and topical tretinoin may help foster acute wound healing by ed with a microangiopathy that can limit perfusion and delivery of
accelerating epithelialization of full- and partial-thickness wounds, oxygen, nutrients, and inflammatory cells to the healing wound.152
activating fibroblasts, increasing type III collagen synthesis, and Diabetes-induced impairment of healing, as well as the attendant
decreasing metalloprotease activation.134,135 Oral retinoid treat- morbidity and mortality, may be reduced by tightly controlling
ment significantly increases the decreased hydroxyproline con- blood sugar levels with insulin.153 Diabetic patients must also
tent, tumor growth factor–β (TGF-β) level, and IGF-1 concentra- closely monitor themselves for wounds and provide meticulous
tion associated with corticosteroids.134 In addition, all aspects of care for any wounds present.
corticosteroid-impaired healing—other than wound contrac-
tion—can be reversed by providing supplemental oral vitamin A Uremia
at a recommended dosage of 25,000 IU/day.136 The retinoic acid Uremia and chronic renal failure are associated with weakened
derivative isotretinoin (13-cis-retinoic acid), however, impairs host defenses, an increased risk of infection, and impaired wound
wound epithelialization and delays wound healing.137 Vitamin K is healing.154 Studies using uremic animal models show delayed
a cofactor in the synthesis of coagulation factors II, VII, IX, and healing of intestinal anastomoses and abdominal wounds.155
X, as well as thrombin. Consequently, vitamin K is necessary for Uremic serum also interferes with the proliferation of fibroblasts
clot formation and hemostasis, the first step in acute wound heal- in culture.103,155 Treatment of this wound healing impairment
ing. Vitamin D is required for normal calcium metabolism and includes dialysis.
therefore plays a necessary role in bone healing. Uremic patients with wounds may experience bleeding compli-
Dietary minerals (e.g., zinc and iron) are also essential for cations. In this situation, appropriate evaluation includes determin-
normal healing. Zinc is a necessary cofactor for DNA and RNA ing the prothrombin time (PT), the activated partial thromboplas-
synthesis. A deficiency of this mineral can lead to inhibition cell tin time (aPTT), the platelet count, and the hematocrit. Treat-
proliferation, deficient granulation tissue formation,138 and ment includes dialysis without heparin; administration of desmo-
delayed wound healing.139 Zinc replacement and supplementa- pressin (0.3 μg/kg), cryoprecipitate, conjugated estrogens (0.6
tion can improve wound healing.130 However, daily intake mg/kg/day I.V. for 5 days),156 and erythropoietin; and transfusion
should not exceed 40 mg of elemental zinc, because excess zinc of red blood cells to raise the hematocrit above 30%.157,158
can immobilize macrophages, bind copper, and depress wound Uremic patients with hyperparathyroidism may also exhibit the
healing.140 Iron is also a cofactor for DNA synthesis, as well as uremic gangrene syndrome (calciphylaxis), which involves the
for hydroxylation of proline and lysine in collagen synthesis.97 spontaneous and progressive development of skin and soft tissue
However, iron deficiency anemia does not appear to affect wounds, usually on the lower extremities. Patients with this syn-
wound strength.141 drome typically are dialysis dependent and have secondary or ter-
tiary hyperparathyroidism.Wound biopsies demonstrate fat necro-
Jaundice sis, tissue calcification, and microarterial calcification.159
The effect of jaundice on wound healing is controversial. Treatment includes local wound care, correction of serum phos-
Jaundiced patients appear to have a higher rate of postoperative phate levels with oral phosphate binders,160 correction of calcium
wound healing complications,142 as well as a lower level of collagen levels with dialysis, and subtotal parathyroidectomy.159
synthesis.143 However, obstructive jaundice does not affect healing
of blister wounds in humans.143 Jaundiced animals show a signifi- Drugs
cant delay in collagen accumulation within the wound, but no sig- Steroids Corticosteroids are anti-inflammatory agents that
nificant reduction in the mechanical strength of the wound.144 inhibit all aspects of healing, including inflammation, macrophage
Biliary drainage may be considered in jaundiced patients with migration, fibroblast proliferation, protein and collagen synthesis,
development of breaking strength, wound contraction, and epithe- reduce the synthesis of collagen by fibroblasts, and delay wound
lialization.103,136,161 In the setting of an acute wound that fails to contraction.97 Some cytotoxic drugs (e.g., methotrexate and dox-
heal, corticosteroid doses may be reduced, vitamin A administered orubicin) substantially attenuate the early phases of wound repair
topically or systemically, and anabolic steroids given to restore and reduce wound tear strength.165 The magnitude of these effects
steroid-retarded inflammation.103,136 is influenced by the timing of the chemotherapeutic agent’s deliv-
Unlike corticosteroids, anabolic steroids accelerate normal col- ery in relation to the time when the wound is sustained.
lagen deposition and wound healing. Oxandrolone is an oral ana- Preoperative delivery has a greater adverse effect on healing; for
bolic steroid and testosterone analogue that is employed clinically example, doxorubicin impairs wound healing to a greater extent if
to treat muscle wasting, foster wound healing, and mitigate the given before operation than if treatment is delayed until 2 weeks
catabolism associated with severe burn injury. Supplementation after operation.166 Chemotherapy also results in myelosuppression
with this agent leads to significant improvements in the wound and neutropenia that can decrease resistance to infection, allowing
healing rate.162 In burn patients treated with oral oxandrolone, small wounds to progress to myonecrosis and necrotizing soft tis-
hospital length of stay is significantly reduced, and the number of sue infections.167 In all acutely wounded patients who have recent-
necessary operative procedures is decreased.163 In ventilator- ly been treated with, are currently taking, or will soon begin to take
dependent surgical patients receiving oxandrolone, however, the chemotherapeutic agents, the wounds must be closely observed
course of mechanical ventilation is longer than in those not treat- for poor healing and complications.
ed with oxandrolone. It has been suggested that the very ability of
oxandrolone to enhance wound healing may increase collagen Other drugs Many other commonly used drugs affect wound
deposition and fibrosis in the later stages of ARDS and thereby healing and thus should be avoided in the setting of an acute
prolong recovery.164 Acute elevation of liver enzyme levels has wound. Nicotine, cocaine, ergotomine, and epinephrine all cause
been seen in some patients treated with oxandrolone; accordingly, vasocontriction and tissue hypoxia. Nonsteroidal anti-inflammato-
hepatic transaminase concentrations should be intermittently ry drugs (e.g., ibuprofen and ketorolac) inhibit cyclooxygenase pro-
monitored in all patients treated with this agent.163 duction and reduce wound tensile strength. Colchicine decreases
fibroblast proliferation and degrades newly formed extracellular
Chemotherapeutic agents Both wound healing and tumor matrix. Antiplatelet agents (e.g., aspirin) inhibit platelet aggregation
growth depend on metabolically active and rapidly dividing cells. and arachidonic acid–mediated inflammation. Heparin and war-
Consequently, chemotherapeutic anticancer drugs that hinder farin impair hemostasis by virtue of their effects on fibrin forma-
tumor growth can also impair wound healing.These agents (which tion.84,168,169 As noted [see Malnutrition, above], isotretinoin inhibits
include adrenocorticosteroids, alkylating agents, antiestrogens, wound epithelialization and delays wound healing.137 Vitamin E (α-
antimetabolites, antitumor antibodies, estrogen, progestogens, tocopherol) impairs collagen formation, inflammation, and wound
nitroureas, plant alkaloids, and random synthetics) attenuate the healing170; topical application of this agent can causes contact der-
inflammatory phase of wound healing, decrease fibrin deposition, matitis and worsen the cosmetic appearance of scars.95
Discussion
Physiology of Wound Healing nephrine and norepinephrine) and prostaglandins (e.g., prosta-
Wound healing is not a single event but a continuum of glandin F2α [PGF2α] and thromboxane A2 [TXA2]). As vessels
processes that begin at the moment of injury and continue for contract, platelets aggregate and adhere to the blood vessel colla-
months. These processes take place in much the same way gen exposed by the injury. Aggregating platelets release alpha-
throughout the various tissues of the body and, for the purposes granule proteins, resulting in further platelet aggregation and trig-
of description, may be broadly divided into three phases: (1) gering cytokine release.The cytokines involved in cutaneous wound
inflammation, (2) migration and proliferation, and (3) maturation healing include epidermal growth factors, fibroblast growth fac-
[see Figure 3]. Humans, unlike (for instance) salamanders, lack the tors, transforming growth factor–β, platelet-derived growth factor,
ability to regenerate specialized structures; instead, they heal by vascular endothelial growth factor (VEGF), tumor necrosis fac-
forming a scar that lacks the complex and important skin struc- tor–α (TNF-α), interleukin-1 (IL-1), IGF-1, granulocyte colony-
tures seen in unwounded skin [see Figure 4]. stimulating factor, and granulocyte-macrophage colony-stimulat-
ing factor.171 Some of these cytokines have direct effects early in
INFLAMMATORY PHASE the healing process; others are bound locally and play critical roles
The inflammatory phase of wound healing begins with hemo- in later healing phases. The use of specific cytokines to reverse
stasis, followed by the arrival first of neutrophils and then of ma- healing deficits or promote wound healing appears to be a promis-
crophages.This response is most prominent during the first 24 hours ing clinical tool and is currently the subject of ongoing basic scien-
after a wound is sustained. Signs of inflammation (i.e., erythema, tific and clinical research.172
edema, heat, and pain) are apparent, generated primarily by changes The coagulation cascade also contributes to hemostasis. The
in the venules on the distal side of the capillary bed. In clean extrinsic pathway is essential to hemostasis and is stimulated by
wounds, signs of inflammation dissipate relatively quickly, and few the release of tissue factor from injured tissue; the intrinsic cascade
if any inflammatory cells are seen after 5 to 7 days. In contaminat- is not essential and is triggered by exposure to factor XII. Both
ed wounds, inflammation may persist for a prolonged period. coagulation pathways lead to the generation of fibrin, which acts
Because wounds bleed when blood vessels are injured, hemo- with platelets to form a clot in the injured area [see 1:4 Bleeding and
stasis is essential. In the first 5 to 10 minutes after wounding, vaso- Transfusion]. Fibrin both contributes to hemostasis and is the pri-
constriction contributes to hemostasis, and the skin blanches as a mary component of the provisional matrix [see Migratory and
result. Vasoconstriction is mediated by catecholamines (e.g., epi- Proliferative Phase, Provisional Matrix Formation, below].
Figure 3 Depicted are the phases of wound healing. In the inflammatory phase (top, left), platelets adhere to collagen
exposed by damage to blood vessels to form a plug. The intrinsic and extrinsic pathways of the coagulation cascade gener-
ate fibrin, which combines with platelets to form a clot in the injured area. Initial local vasoconstriction is followed by
vasodilatation mediated by histamine, prostaglandins, serotonin, and kinins. Neutrophils are the predominant inflammato-
ry cells (a polymorphonucleocyte is shown here). In the migratory and proliferative phase (top, right; bottom, left), fibrin
and fibronectin are the primary components of the provisional extracellular matrix. Macrophages, fibroblasts, and other
mesenchymal cells migrate into the wound area. Gradually, macrophages replace neutrophils as the predominant inflam-
matory cells. Angiogenic factors induce the development of new blood vessels as capillaries. Epithelial cells advance across
the wound bed. Wound tensile strength increases as collagen produced by fibroblasts replaces fibrin. Myofibroblasts induce
wound contraction. In the maturational phase (bottom, right), scar remodeling occurs. The overall level of collagen in the
wound plateaus; old collagen is broken down as new collagen is produced. The number of cross-links between collagen mol-
ecules increases, and the new collagen fibers are aligned so as to yield an increase in wound tensile strength.
Vasoconstriction and hemostasis are followed by vasodilatation, tissue and bacteria and digest them. After neutrophils phagocy-
which is associated with the characteristic signs of erythema, edema, tose damaged material, they cease to function and often release
heat, and pain.Vasodilatation is mediated by prostaglandins (e.g., lysosomal contents, which can contribute to tissue damage and a
PGE2 and PGI2 [prostacyclin]), histamine, serotonin, and ki- prolonged inflammatory response. Macrophages, however, are
nins.173,174 As the blood vessels dilate, the endothelial cells separate essential to wound healing and do not cease to function after
from one another, thereby increasing vascular permeability. In- phagocytosing bacteria or damaged material.176 In the wound envi-
flammatory cells initially roll along the endothelial cell lining, sub- ronment, macrophages also secrete collagenase, elastase, and
sequently undergo integrin-mediated adhesion, and finally trans- matrix metalloproteinases (MMPs) that break down damaged tis-
migrate into the extravascular space.175 sue. Macrophages also produce cytokines that mediate wound-
For the first 48 to 72 hours after wounding, neutrophils are the healing processes, as well as IL-1 (which can lead to a systemic
predominant inflammatory cells in the wound. About 48 to 96 response, including fever) and TNF-α.171
hours after wounding, however, monocytes migrate from nearby
MIGRATORY AND PROLIFERATIVE PHASE
tissue and blood and transform into macrophages, and eventual-
ly, macrophages become the predominant inflammatory cells in The migratory and proliferative phase is marked by the attrac-
the wound. Both neutrophils and macrophages engulf damaged tion of epidermal cells, fibroblasts, and endothelial cells to the
Lymphatic
Pacinian Vessel Sweat Gland
Corpuscle and Duct
Meissner
Corpuscle
Hair
Epidermis Sebaceous
Gland
Papillary Dermis
Hair Follicle
Reticular Dermis Approximate

Border of Cone
Blood Vessel
Hypodermis
Fascia
Nerve Fiber
Figure 4 Shown are the key anatomic
components of the skin.
Fat Dome
wound. Cells migrate along the scaffolding of fibrin and fibroblasts and other cells to the provisional extracellular matrix.180 By
nectin. This process involves the upregulation of integrin receptor influencing cellular attachment, fibronectin helps modulate cell mi-
sites on the cell membranes, which allows the cells to bind at dif- gration into the wound.181 In addition, the fibrin-fibronectin lattice
ferent sites in the matrix and pull themselves through the scaffold- binds various cytokines that are released at the time of injury and
ing. Migration through the provisional matrix is facilitated by pro- serves as a reservoir for these factors in the later stages of healing.182
teolytic enzymes. Cytokines and growth factors then stimulate the Fibroblasts then replace the provisional extracellular matrix
proliferation of these cells.171,176 with a collagen matrix, and the wound gains strength. The rate of
collagen synthesis increases greatly after the initial 3 to 5 days and
Epithelialization continues at an increased rate for 21 days before gradually declin-
Within approximately 24 hours of injury, epidermal cells from ing.183 Of the many types of collagen, the ones that are of primary
the wound margin and skin appendages begin to migrate into the importance in the skin are types I and III. Approximately 80% to
wound bed. These migrating epidermal cells dissect the wound, 90% of the collagen in the skin is type I collagen; the remaining
separating desiccated eschar from viable tissue.80 At 24 to 48 hours 10% to 20% is type III.The percentage of type III collagen is high-
after wounding, epidermal cells at the wound margin begin to pro- er in embryonic skin and in skin that is in the early stages of wound
liferate, producing more migrating cells.171 As epidermal migration healing.
is initiated, the desmosomes that link epidermal cells together and Collagen molecules are synthesized by fibroblasts. Lysine and
the hemidesmosomes that link the epidermal cells to the basement proline residues within the collagen molecule become hydroxylat-
membrane disappear.177 Migrating epidermal cells express integrin ed after being incorporated into polypeptide chains. This process
receptors that allow interaction with extracellular matrix proteins, requires specific enzymes, as well as various cofactors (i.e., oxygen,
laminin, collagen, and fibrin clot.178 When epidermal cells migrat- vitamin C, α-ketoglutarate, and ferrous iron).The result is procol-
ing from two areas meet, contact inhibition prevents further migra- lagen, which is released into the extracellular space. Individual col-
tion.The cells making up the epidermal monolayer then differenti- lagen molecules then align and associate with one another to form
ate, divide, and form a multilayer epidermis. fibrils. Covalent cross-links form between various combinations of
the hydroxylated residues (lysine and hydroxylysine) in aligned
Provisional Matrix Formation collagen fibrils, with the strongest links occurring between hydrox-
Formation of the provisional matrix and granulation tissue begins ylysine and hydroxylysine. These cross-links are essential to the
approximately 3 to 4 days after wounding. Fibroblasts synthesize tensile strength of the wound. Cofactor deficiencies (e.g., vitamin
an extracellular matrix of fibrin, fibronectin, and proteoglycans that C deficiency in scurvy) and the use of corticosteroids can lead to
supports epidermal and endothelial cell migration and prolifera- the synthesis of weak, underhydroxylated collagen that is inca-
tion.178,179 Proteoglycans (e.g., dermatan sulfate, heparin, heparan pable of generating strong cross-links.
sulfate, keratan sulfate, and hyaluronic acid) consist of a protein
core that is linked to one or more glycosaminoglycans; they anchor Angiogenesis
proteins and facilitate the alignment of collagen into fibrils. The growth of new blood vessels, which is necessary to support
Fibrin becomes coated with vitronectin and fibronectin, which the wound tissue, begins 2 to 3 days after wounding.This process
are glycoproteins that facilitate the adhesion of migrating fibro- of angiogenesis may be stimulated by the hypoxic and acidic
wound microenvironment, as well as by cytokines (e.g., VEGF) highest at anatomic sites with redundant tissue. Excessive contrac-
derived from epidermal cells and macrophages.171,184 Endothelial tion can lead to contracture, a pathologic scarring that impairs the
cells from surrounding vessels express fibronectin receptors and function and appearance of the scar.
grow into the provisional matrix.These migrating endothelial cells
create paths in the matrix for developing capillaries by releasing Scar Remodeling
plasminogen activator, procollagenase, heparanase, and MMPs, Collagen remodeling begins approximately 3 weeks after wound-
which break down fibrin and basement membranes.171,185 The ing. Collagen synthesis is downregulated, the rates at which colla-
budding capillaries join and initiate blood flow. As the wounded gen is synthesized and broken down reach equilibrium,and the wound
area becomes better vascularized, the capillaries consolidate to becomes less cellular as apoptosis occurs. During this process, the
form larger blood vessels or undergo apoptosis.186 extracellular matrix, including collagen, is continually remodeled
and synthesized in a more organized fashion along stress lines.183
MATURATIONAL PHASE
Collagen breakdown is mediated by MMPs.189 The number of
cross-links between collagen fibers increases,183 and the realigned,
Wound Contraction highly cross-linked collagen is much stronger than the collagen
Myofibroblasts are specialized fibroblasts containing alpha– produced during the earlier phases of healing.The tensile strength
smooth muscle actin microfilaments that contribute to wound of the wound increases rapidly for 6 weeks after injury; accordingly,
contraction.187,188 The wound edges are pulled together by the con- during this period, heavy lifting and any other activity that applies
tractile forces supplied by the myofibroblast. Wound contraction stress across the wound should be avoided. After the initial 6
generally begins in the 4- to 5-day period after wounding and con- weeks, tensile strength increases more slowly for a further 6 to 12
tinues for 12 to 15 days or until the wound edges meet.The rate at months, though it never reaches the tensile strength of unwound-
which contraction occurs varies with the laxity of the tissue and is ed tissue [see Figure 2].
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United States. Am Surg 53:198, 1987 87. Davis SC, Cazzaniga AL, Eaglstein WH, et al: Tissue oxygen tensions during controlled hemor-
64. Lawrence WT, Giannopoulos A, Hansen A: Pit Over-the-counter topical antimicrobials: effective rhage. Surg Forum 18:3, 1967
viper bites: rational management in locales in which treatments? Arch Dermatol Res 297:190, 2005 111. Hopf HW, Hunt TK, Rosen N: Supplemental oxy-
copperheads and cottonmouths predominate. Ann 88. Kucan JO, Robson MC, Heggers JP, et al: gen and risk of surgical site infection. JAMA 291:
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66. Dart RC, Seifert SA, Boyer LV, et al: A randomized 89. Rhee P, Nunley MK, Demetriades D, et al: surgical-wound infection. Outcomes Research
multicenter trial of crotalinae polyvalent immune Tetanus and trauma: a review and recommenda- Group. N Engl J Med 342:161, 2000
113. Bird AD,Telfer AB: Effect of hyperbaric oxygen on 137. Zachariae H: Delayed wound healing and keloid 1976
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1974 138. Fernandez-Madrid F, Prasad AS, Oberleas D: 162. Demling RH, Orgill DP: The anticatabolic and
115. Jensen JA, Goodson WH, Hopf HW, et al: Effect of zinc deficiency on nucleic acids, collagen, wound healing effects of the testosterone analog
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Surg 126:1131, 1991 sue. J Lab Clin Med 82:951, 1973 15:12, 2000
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Med 93:22S, 1992 in wound healing. Adv Wound Care 12:137, 1999 of oxandrolone on outcome measures in the se-
117. Birnstingl MA, Brinson K, Chakrabarti BK: The 140. Posthauer ME: Do patients with pressure ulcers verely burned: a multicenter prospective random-
effect of short-term exposure to carbon monoxide benefit from oral zinc supplementation? Adv Skin ized double-blind trial. J Burn Care Res 27:131,
on platelet stickiness. Br J Surg 58:837, 1971 Wound Care 18:471, 2005 2006
118. Sorensen LT, Nielsen HB, Kharazmi A, et al: 141. Macon WL, Pories WJ: The effect of iron deficien- 164. Bulger EM, Jurkovich GJ, Farver CL, et al:
Effect of smoking and abstention on oxidative burst cy anemia on wound healing. Surgery 69:792, 1971 Oxandrolone does not improve outcome of venti-
and reactivity of neutrophils and monocytes. 142. Grande L, Garcia-Valdecasas JC, Fuster J, et al: lator dependent surgical patients. Ann Surg
Surgery 136:1047, 2004 Obstructive jaundice and wound healing. Br J Surg 240:472, 2004
119. Sackett DL, Gibson RW, Bross ID, et al: Relation 77:440, 1990 165. Bland KI, Palin WE, von Fraunhofer JA, et al:
between aortic atherosclerosis and the use of ciga- 143. Koivukangas V, Oikarinen A, Risteli J, et al: Effect Experimental and clinical observations of the
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279:1413, 1968 lization, skin collagen synthesis, and serum colla- wound healing. Ann Surg 199:782, 1984
120. Kuri M, Nakagawa M,Tanaka H, et al: Determin- gen propeptide levels in patients with neoplastic pan- 166. Lawrence WT,Talbot TL, Norton JA: Preoperative
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tion to improve wound healing after head and neck 144. Greaney MG,Van Noort R, Smythe A, et al: Does amycin): which is better for wound healing?
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plete and partial starvation on the rate of fibropla- 145. Lindstedt E, Sandblom P: Wound healing in man: tissue infections in the neutropenic pediatric
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122. Gray D, Cooper P: Nutrition and wound healing:
what is the link? J Wound Care 10:86, 2001 146. Swift ME, Burns AL, Gray KL, et al: Age-related 168. Karukonda SR, Flynn TC, Boh EE, et al: The
alterations in the inflammatory response to dermal effects of drugs on wound healing—part II.
123. Gibbs J, Cull W, Henderson W, et al: Preoperative Specific classes of drugs and their effect on healing
serum albumin level as a predictor of operative injury. J Invest Dermatol 117:1027, 2001
wounds. Int J Dermatol 39:321, 2000
mortality and morbidity: results from the National 147. Eaglstein WH: Wound healing and aging. Clin
VA Surgical Risk Study. Arch Surg 134:36, 1999 Geriatr Med 5:183, 1989 169. Karukonda SR, Flynn TC, Boh EE, et al: The
effects of drugs on wound healing: part 1. Int J
124. Reinhardt GF, Myscofski JW, Wilkens DB, et al: 148. Nolan CM, Beaty HN, Bagdade JD: Further char- Dermatol 39:250, 2000
Incidence and mortality of hypoalbuminemic acterization of the impaired bactericidal function
patients in hospitalized veterans. JPEN J Parenter of granulocytes in patients with poorly controlled 170. Ehrlich HP,Tarver H, Hunt TK: Inhibitory effects
Enteral Nutr 4:357, 1980 diabetes. Diabetes 27:889, 1978 of vitamin E on collagen synthesis and wound
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125. Stack JA, Babineau TJ, Bistrian BR: Assessment of 149. Fahey TJ 3rd, Sadaty A, Jones WG 2nd, et al:
nutritional status in clinical practice. Gastroenter- Diabetes impairs the late inflammatory response 171. Singer AJ, Clark RA: Cutaneous wound healing. N
ologist 4:S8, 1996 to wound healing. J Surg Res 50:308, 1991 Engl J Med 341:738, 1999
126. Jeschke MG, Herndon DN, Ebener C, et al: 150. Bagdade JD, Root RK, Bulger RJ: Impaired leuko- 172. Robson MC: Cytokine manipulation of the wound.
Nutritional intervention high in vitamins, protein, cyte function in patients with poorly controlled Clin Plast Surg 30:57, 2003
amino acids, and omega3 fatty acids improves pro- diabetes. Diabetes 23:9, 1974 173. Williams TJ, Peck MJ: Role of prostaglandin-
tein metabolism during the hypermetabolic state 151. Greenhalgh DG:Wound healing and diabetes mel- mediated vasodilatation in inflammation. Nature
after thermal injury. Arch Surg 136:1301, 2001 litus. Clin Plast Surg 30:37, 2003 270(5637):530, 1977
127. Chernoff R: Physiologic aging and nutritional sta- 152. Duncan HJ, Faris IB: Skin vascular resistance and 174. Ryan GB, Majno G: Acute inflammation: a review.
tus. Nutr Clin Pract 5:8, 1990 skin perfusion pressure as predictors of healing of Am J Pathol 86:183, 1977
128. Soeters PB, van de Poll MC, van Gemert WG, et ischemic lesion of the lower limb: influences of dia- 175. Ley K: Leukocyte adhesion to vascular endotheli-
al: Amino acid adequacy in pathophysiological betes mellitus, hypertension, and age. Surgery um. J Reconstr Microsurg 8:495, 1992
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specialized amino acid mixture on human collagen Intensive insulin therapy in the critically ill antimacrophage serum. Am J Pathol 78:71, 1975
deposition. Ann Surg 236:369, 2002 patients. N Engl J Med 345:1359, 2001 177. Gipson IK, Spurr-Michaud SJ, Tisdale AS:
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Treatment with supplementary arginine, vitamin C patients with chronic renal failure. Infect Dis Clin appear synchronously during development and
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ised controlled trial. Clin Nutr 24:979, 2005 155. Colin JF, Elliot P, Ellis H: The effect of uraemia 178. Clark RA, Lanigan JM, DellaPelle P, et al: Fibro-
131. Freiman M, Seifter E, Connerton C, et al:Vitamin upon wound healing: an experimental study. Br J nectin and fibrin provide a provisional matrix for
A deficiency and surgical stress. Surg Forum 21:81, Surg 66:793, 1979 epidermal cell migration during wound reepithe-
1970 156. Vigano G, Gaspari F, Locatelli M, et al: Dose- lialization. J Invest Dermatol 79:264, 1982
132. Shapiro SS, Mott DJ: Modulation of glycosamino- effect and pharmacokinetics of estrogens given to 179. Greiling D, Clark RA: Fibronectin provides a con-
glycan biosynthesis by retinoids. Ann NY Acad Sci correct bleeding time in uremia. Kidney Int duit for fibroblast transmigration from collagenous
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134. Wicke C, Halliday B, Allen D, et al: Effects of uremia and liver disease. Curr Opin Hematol vivo. J Invest Dermatol 76:181, 1981
steroids and retinoids on wound healing. Arch 6:329, 1999 181. Clark RA, Folkvord JM,Wertz RL: Fibronectin, as
Surg 135:1265, 2000 159. Kane WJ, Petty PM, Sterioff S, et al: The uremic well as other extracellular matrix proteins, mediate
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102:1667, 1998 thyroidectomy. Plast Reconstr Surg 98:671, 1996 182. Wysocki AB, Grinnell F: Fibronectin profiles in
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vitamin A on reversing the inhibitory effect of cor- Calciphylaxis in man: a syndrome of tissue necro- 1990
tisone on healing of open wounds in animals and sis and vascular calcification in 11 patients with 183. Madden JW, Peacock EE Jr: Studies on the biolo-
man. Ann Surg 170:633, 1969 chronic renal failure. Arch Intern Med 136:1273, gy of collagen during wound healing: 3. Dynamic
metabolism of scar collagen and remodeling of dermal wounds. Ann Surg 188. Desmouliere A, Chaponnier C, Gabbiani G: Tissue repair, contraction, and the
174:511, 1971 myofibroblast. Wound Repair Regen 13:7, 2005
184. Detmar M, Brown LF, Berse B, et al: Hypoxia regulates the expression of vascu- 189. Riley WB Jr, Peacock EE Jr: Identification, distribution, and significance of a col-
lar permeability factor/vascular endothelial growth factor (VPF/VEGF) and its lagenolytic enzyme in human tissues. Proc Soc Exp Biol Med 124:207, 1967
receptors in human skin. J Invest Dermatol 108:263, 1997
185. Nadav L, Eldor A,Yacoby-Zeevi O, et al: Activation, processing and trafficking of
extracellular heparanase by primary human fibroblasts. J Cell Sci 115:2179, 2002
186. Ilan N, Mahooti S, Madri JA: Distinct signal transduction pathways are utilized Acknowledgments
during the tube formation and survival phases of in vitro angiogenesis. J Cell Sci
111:3621, 1998 Figures 1 and 4 Thom Graves.
187. Gabbiani G, Ryan GB, Majne G: Presence of modified fibroblasts in granulation Figure 2 Janet Betries.
tissue and their possible role in wound contraction. Experientia 27:549, 1971 Figure 3 Carol Donner.
1 BASIC SURGICAL AND PERIOPERATIVE CONSIDERATIONS 8 PREPARATION OF THE OPERATING
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8 PREPARATION OF THE OPERATING

ROOM
T. Forcht Dagi, MD, MPH, FACS, FCCM, and William Schecter, MD, FACS, FCCM
This chapter concentrates on the general principles of operat- area of the cubital tunnel must be well padded to avoid injury
ing room (OR) design and operation. The OR is designed to the ulnar nerve. The surgeon generally stands on the
to permit sterile, safe, painless, and effective surgical inter- patient’s right and the assistant on the left. For pelvic proce-
vention to improve the lives of patients. Advances in science dures, the right-handed surgeon may elect to stand on the
and technology have significantly increased the complexity patient’s left. The scrub nurse stands next to the instrument
of the OR environment. With further advances, the OR will tray placed on a Mayo stand over the patient’s legs. The back
continue to evolve. table containing additional instruments is placed at the foot
The basic aspects of OR design have not changed since the of the bed (Figure 1A).
late 19th century, except for changes necessitated by the Two sets of ceiling lights are positioned over the field. In
introduction of complex surgical imaging and monitoring many cases, a head light worn by the surgeon provides addi-
equipment. Effective integration of this equipment into the tional focused illumination. For pelvic procedures, access to
confined OR space is essential. This chapter focuses on the perineum is either helpful or essential. The patient should
general principles of planning and operation rather than the be placed in the Lloyd-Davies position. The patient’s legs are
specific requirements of individual surgical specialties. placed in well-padded leg holders attached to the side of the
Efficient operation of the OR depends on many individu- OR table. The distal portion of the table is lowered to form
als, some seldom seen, whose skills are essential. They are a right angle with the proximal table. The patient is moved
rarely acknowledged and easily overlooked. Continuous, distally so that the sacrum is positioned adjacent to the table
respectful communication is essential for safe and successful brake. Care is taken to protect the airway, arms, and legs
outcomes. during repositioning. A foam pad is placed between the
sacrum and the OR table. The leg holders are positioned to
avoid abduction of the hips. Care is taken to ensure padding
General Principles of OR Design and Construction in the area of the peroneal nerves, feet, and calves. Peroneal
physical layout nerve palsy and compartment syndrome attributable to
prolonged pressure are risks. Morbid obesity is a relative
The basic physical design of the OR is determined first by contraindication to the Lloyd-Davies position because of the
requirements for patient positioning, illumination, anesthesia, risk of a traction injury to the sciatic nerve.
and instrumentation and second by considerations of storage,
patient and staff movement, and communication. Basic OR Thoracotomy
design has not changed substantially over the past century. The patient is placed in the full lateral position. A bean bag
More recently, however, advances in minimally invasive is a useful device to hold the patient in position. It holds its
surgery, intraoperative imaging, patient monitoring, surgical shape when a suction device is applied. An axillary roll, either
navigation, surgical robotics, and data connectivity have a rolled sheet or an IV bag, is placed to protect the brachial
stimulated surgeons and architects to rethink the layout of the plexus. Alternatively, a large pillow may be placed under the
OR. axilla and chest. Pillows are useful for supporting the legs.
The bottom leg should be slightly flexed and the top leg
Positioning the Patient extended. The position should be secured by the application
The anesthesia machine is positioned at the head of the of 2-inch tape to the area of the iliac crest. Care must be
table so that the anesthesiologist has an unimpeded view of taken to protect the skin from the tape to avoid blister
the machine, monitors, airway, and intravenous (IV) fluids. formation. The arms are extended in front of the patient.
The suction tubing and electrocautery cords are usually They may rest on an arm board protected by pillows or
brought off the field toward the feet. However, they may be sheets. Alternatively, the top arm may be supported by a
brought off the side or head of the patient in selected cases well-placed “airplane splint.” As in laparotomy, the surgeon
depending on equipment location and room orientation. and assistant stand on either side of the patient and the scrub
nurse stands toward the feet. Two lights are positioned over
Laparotomy the patient. The use of a head light by the operating surgeon
The patient is positioned supine on the operating table. is routine in many situations (Figure 1B).
The arms may be tucked in at the patient’s sides or placed on
well-padded arm boards at 90° angles to the table. Care must Thyroidectomy and Parathyroidectomy
be taken to avoid hyperextending the arms to avoid injury to Thyroidectomy and parathyroidectomy are the most
the brachial plexus. If the arms are tucked in at the side, the common neck procedures performed by general surgeons.
DOI 10.2310/7800.S01C08
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a b
Figure 1 Patient positioning: (a) laparotomy,

(b) thoracotomy, and (c) thyroidectomy.
Preoperative evaluation should include assessment of cervical such as the Occupational Safety and Health Administration
spine mobility. The patient is positioned supine on the OR (OSHA) and the Nuclear Regulatory Commission.2–5
table. After endotracheal intubation, a sheet roll is placed Numerous articles and books discuss the various aspects
posterior to the scapula. The head is extended and placed on of OR design.6–10 The American Institute of Architects has
a foam “donut” pad, avoiding excess tension on the cervical published a comprehensive set of guidelines for health care
spine. Extension of the head should be avoided in the pres- facility design that includes a detailed discussion of OR
ence of limited cervical spine mobility. The head of the table design.11 Along with such guidelines and recommendations
is elevated to reduce venous pressure. Two ceiling lights are obtained from specialty surgical, anesthesiology, biomedical
positioned over the neck. Most surgeons use a head light to engineering and nursing associations, the design of new ORs
provide additional focused illumination. The scrub nurse must consider local needs and perspectives. The design of a
stands next to the Mayo stand holding the instrument tray new OR should be a collaborative effort reflecting the efforts
over the patient’s feet (Figure 1C). of clinical services, support services, and administration.
A similar position is employed for neck explorations. For
unilateral neck exploration, the patient‘s head is turned away design process and considerations
from the side of the planned incision. Designs must accommodate work flow and patient move-
ment. Important considerations include the mix of inpatient
design standards and outpatient surgery, the design of the hospital or institu-
Standards for new construction and major remodeling of tion (including proximity to clinical services such as radiology
ORs in the United States generally fall under the jurisdiction and pathology), the surgical specialties to be served, accessi-
of state and local agencies. These agencies, in turn, often bility to perioperative care units, accessibility of supplies,
incorporate guidelines published by the Department of Health and removal of waste materials. The need for intraoperative
and Human Services,1 as well as other groups and agencies, fluoroscopy and sectional imaging, shielding, ceiling-mounted
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microscopes, and surgical robotics and similar advanced including nuclear, biological, chemical, and radiation
technologies will be influential. It is important to allow for incidents, are not addressed in this chapter.
flexibility and to anticipate the introduction of new
technologies over the life of the design. Time motion studies, physical requirements
simulations, and models may prove helpful and contribute to The fundamental model for OR design is a quadrangular
OR efficiency long term. Balancing flexibility and cost is a room with minimum dimensions of 20 × 20 ft or 7 × 7 m.
continuing challenge.12 More often, the dimensions are closer to 30 × 30 ft or
The geography and physical relationship of clean and less 10 × 10 m, so as to accommodate more specialized cardiac,
clean areas in the operating suite determine many other neurosurgical, minimally invasive, orthopedic, and multiteam
aspects of the OR suite. There are two designs in common procedures. Smaller rooms are generally adequate for minor
use. The first involves one or more clean hubs. The ORs are surgery and for procedures such as cystoscopy and eye
situated centrifugally in spokelike fashion. Clean and sterile surgery.
equipment and supplies that must be on hand for immediate Ceiling height should be at least 10 ft or 3.5 m to allow
use are stored in the hub. A peripheral corridor typically ceiling mounting of operating lights, microscopes, robots,
affords access to perioperative care units, instrument and navigational systems, and other equipment. An additional 1
anesthesia workrooms, clean storage, staff lounges, and other to 2 ft or 0.5 to 0.75 m of ceiling height may be advisable if
facilities. Entry and egress from the suite and access to the x-ray or other boom equipment is to be permanently mounted.
OR front desk and reception area also involve the peripheral In ORs designed to accept intraoperative sectional imaging
corridor. In the simplest embodiment, four ORs surround a devices (computed tomography [CT] and magnetic reso-
hub. The number can be greater or smaller. Controlled nance imaging [MRI]), the floors may be elevated to accom-
movement through the hub or hubs drives this design. modate cabling and wiring for power and data connections.
The second model uses corridors rather than hubs and When floors are elevated, the overall height of the OR has to
spokes. Supply rooms are typically situated between adjacent be increased.
rooms. A less common variation builds a separate supply Some institutions design or redesign the entire OR suite
with the potential to accommodate oversized equipment as
room next to each individual OR. Older ORs were designed
well as conduits and cables in both the ceiling and floor.
with one door only. Current design favors two, one connect-
Others prefer to customize individual rooms.
ing to the more sterile area and the other to the less sterile
OR and perioperative facilities may be specially constructed
area.
to withstand environmental hazards such as earthquakes,
The OR must balance the restrictions on access needed for
tornadoes, and floods or hardened to contend with hostile
safety and efficiency with freedom of movement for personnel
military or terrorist attack. Standards and specifications
and patients. This balance is equally important in emergency
for this type of construction fall outside the scope of this
situations and during complex and lengthy operations.
chapter.
Should ORs be dedicated to specific surgical specialties?
There are practical and logistical advantages to dedicated computerization, communication, and data
rooms, especially in cardiac surgery, neurosurgery, trauma, exchange: voice, video, and data
and ophthalmology. However, specialty-specific rooms can Computers, telephones, imaging, and other systems for
limit scheduling flexibility. Although it is hard to imagine data capture, analysis, and exchange should be integrated
justifying a room so narrowly designed that it absolutely into the OR design. The ubiquitous deployment of radiology
cannot be used for more than one specialty, dedicated rooms Picture Archiving and Communication Systems (PACS) and
might be emphasized in one institution and versatility in the potential of digital pathology to improve surgical pathol-
another. Each approach has its advocates. Design and ogy services mandate the installation of high-speed broad-
equipment should ultimately reflect expected and projected band connections. Two-way audio with teleconferencing
case mix. capabilities enables teleconsultation and teaching from and
Finally, the design of the OR suite must facilitate cleaning, in the OR.
disinfection and efficient turnover, and the installation and Effective communication systems capable of connecting
maintenance of installed equipment. the OR team, the OR front desk, and the rest of the hospital
storage must be accessible. Emergency communication channels
must be tested at regular intervals. Most importantly, systems
The OR design must provide adequate storage space for for communication, data exchange, and data storage retrieval
urgently required supplies. Storage in hallways and inside the must be available, preferably off-site. Off-site data storage
OR can create obstructions and hazards. backup is essential for hospitals likely to respond to mass
casualty events or subject to environmental hazards.
critical devices and emergency equipment
Critical devices, as well as emergency supplies and instru- assimilating new technologies
ments, must be prepared and positioned for immediate Advances in the medical device and information technol-
deployment. Accessories should be stored next to the ogy (IT) sectors stimulate a constant stream of innovation.
instruments that need them. Nevertheless, the undisciplined introduction of new technol-
Some hospitals have mass casualty response as part of their ogies can be distracting, contraproductive, and expensive.
mission. These institutions will have special requirements for ORs should be focused on measurable benefit and integration
versatility, equipment, storage, and supplies. The specific rather than novelty. The introduction of new technologies
design requirements for response to mass casualty events, should reduce complexity and tangibly increase therapeutic
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benefits and options for patients in ways that have been The risks associated with malpositioning deserve further
recognized for more than a decade.13 comment. Any bony prominence is subject to injury from
The OR of the future will be characterized by increasing excessive pressure. The fragile skin of infants and older
dependence on technology. Although it is essential to track patients may be injured by dragging rather than lifting into
new technologies, they should be assessed and introduced position. The American Society of Anesthesiologists (ASA)
in a disciplined manner. Technology acquisition should be practice advisory on the prevention of perioperative periph-
strategic. A full discussion of technology assessment in eral neuropathies recommends that when practical, patients
surgery is outside the purview of this chapter, but the central should be placed in the intended position before induction of
principles are straightforward. First, the magnitude of unmet anesthesia to test for comfort.25 Uncomfortable positions
needs should be detailed and quantified. Second, the should be modified. This is especially important with older
cost-effectiveness of a new technology should be assessed. patients or patients with degenerative spine and joint disease
Next, competitive solutions, including substitutes for the or skeletal instability.
candidate technology acquisition, should be considered. Two major preventable consequences of malpositioning
Last, the marginal benefits and burdens of new technology are neuropathy or plexopathy and skin burns or ulceration.
introduction should be quantified. Approximately 80% of surgical procedures are performed
with patients in the supine position. Ulnar neuropathy and
brachial plexopathy are the two most common complications
Patient Safety, OR Efficiency, and Quality in this position and constitute 28% and 20% of claims,
Improvement respectively, in recent closed claims studies.26–31 Padding of
The OR is a high-stress environment with inherent risk in the precondylar groove of the humerus and tucking of the
arms or, at the least, restriction of abduction to less than 90°
which members of multiple disciplines temporarily congre-
help prevent this problem.25
gate to treat surgical patients. The potential for error and
The lithotomy position is used in approximately 9% of
inefficiency is great. Conversion of this group of individuals
cases and is the next most commonly used position.27,29
from disciplines with differing professional cultures and skill
Damage to the obturator, sciatic, lateral femoral cutaneous,
sets into a smoothly functioning surgical team is the key and peroneal nerves has been observed. These injuries
to increasing patient safety and efficiency.14 Surgical team account for 5% of claims for nerve damage in the Closed
training is an effective method to achieve a “team culture” Claims Data Base. They represent a small but not insignifi-
resulting in improved communication and decreased risk cant risk.26 Other patient positions have also been associated
of error.15 The use of perioperative care protocols reduces with malpositioning injuries.
failures of communication.16
The Joint Commission Universal Protocol became effective occupational injury to the health care team
on July 1, 2004. The key principles of the Universal Protocol Professionals engaged in perioperative and surgical care
are (1) the preoperative verification process, (2) marking the are exposed to biologic, ergonomic, chemical, physical, and
correct surgical site, (3) taking a “time-out” prior to surgery, psychosocial occupational risks.
and (4) adapting the requirements to non-OR settings. The
elements of the time-out concept are evolving and may Biologic Risks
include introduction of team members; patient identification; These risks include (1) parenteral and mucocutaneous
review of the patient’s history, risk factors, medications, and exposure to pathogens, (2) respiratory tract exposure to
allergies; availability of appropriate images and equipment; pathogens, (3) exposure to the biologic components of surgi-
goals of surgery; and potential intra- and postoperative cal smoke, and (4) exposure to allergens in latex gloves.32
problems. The role of a discussion of planned postoperative Strategies to reduce mucocutaneous exposure to pathogens
care at the completion of the surgical procedure prior to the include double-gloving, blunt suture needles, a neutral zone
emergence from anesthesia is not clear at the present time.17 for passage of sharps, and engineered sharps injury preven-
The use of a protocol during the hand-over of surgical tion devices.33 The use of N-95 respirator masks reduces the
patients to intensive care results in improved care.18 Extend- risk of occupational exposure to aerosolized Mycobacterium
tuberculosis and particulate matter greater than 1 micron in
ing the team concept to postanesthesia care has resulted in
size.34 Health care workers with allergies to latex should avoid
improved quality of care as measured by intubation times and
contact with latex gloves and tubing.
hospital stay following cardiac surgery.19 The use of specialty
teams during surgery to improve communication and effi- Ergonomic Risks
ciency is logical, but at present, there is a paucity of studies Health problems related to ergonomics, especially back
documenting its efficacy. Continuous monitoring is essential pain, are common. These problems are associated with
to maintain quality.20 awkward posture at the operating table, standing for long
Patient safety21 begins with protection of patients from periods of time, and back injury incurred by lifting patients.
misidentification, physical and chemical hazards, medication The OR table, monitors, imaging screens, and equipment
error, operative error, and improper positioning.22 The sur- should be positioned so that the OR team’s posture and posi-
geon is responsible for positioning the patient and preventing tion are as comfortable as possible within the limits of patient
positioning injury.23 The OR team is responsible for procur- safety. Lifting injury can be minimized by using proper patient
ing and maintaining the equipment for proper positioning transfer techniques and obtaining additional assistance when
and monitoring the patient intraoperatively. The entire team moving patients in the OR. Repetitive motion injury is a less
is responsible for preventing falls.24 common but not insignificant risk.32
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Chemical Risks Another study considered risks to the fetus of the pregnant
Health care workers are exposed to numerous potentially surgeon. This risk is of particular importance early in gesta-
hazardous chemicals in the OR, including anesthetic gases, tion, before the pregnancy is recognized. In this study, the
disinfecting and sterilizing chemicals, specimen preservatives, calculated accumulative dose received intraoperatively
and chemotherapeutic drugs.32 Scavenger systems are exceeded the threshold dose for the induction of radiation
deployed broadly and have significantly reduced exposure to injury by at least two orders of magnitude. Approximately
anesthetic gases.35 Protective gowns and gloves prevent 2100 hours of fluoroscopy are required to reach this
exposure to other chemicals in the OR. threshold.
Childhood cancer is another documented risk of low-dose
Physical Risks fetal radiation exposure. The extent of this risk remains
Physical risks to patients and the OR team include controversial. Nevertheless, the ICRP has recommended a
fire, electrocution, radiation exposure, and laser energy maximum dose of 2 mSv and preferably less than 1 mSv
exposure.32 during the declared pregnancy. With the protection afforded
by a 0.5 mm lead-equivalent apron, however, the calculated
Fire The first principle of fire prevention is control of expected cumulative fetal dose is less than 0.37 mSv, a
the three elements of the fire triangle: oxygen, fuel, and an figure that extrapolates to a significantly lower dose, and
ignition source.36 Air/oxygen mixtures should be adjusted to consequently a lower risk, than that derived from natural
reduce the fraction of inspired oxygen (FiO2) to the lowest background radiation.
level consistent with patient safety and satisfactory hemoglo- Surgeons exposed to intraoperative ionizing radiation may
bin oxygen saturation.36 Light, heat, and electrical sources of avail themselves of several protective strategies. A 1 mm lead-
ignition should be carefully monitored and kept away from equivalent whole-body shield or apron provides 99% protec-
paper drapes. The use of alcohol-based skin preparation tion. A 0.5 mm lead-equivalent free-standing shield reduces
solutions should be minimized if possible.37 The use of the exposure by 90%. A neck (thyroid) shield with 0.25 mm lead
electrocautery or laser energy in the airway or in the unpre- equivalence reduces exposure by 60%. Radiation-protective
pared intestinal lumen in the presence of high concentrations gloves reduce dosage to the hand by up to 40%.37,41
of oxygen increases the risk of fire. Maintaining distance is also protective. Radiation attenu-
ates with the square of the distance. For any given distance
Radiation exposure Exposure to ionizing radiation is from the source of radiation, if the intensity of the radiation
inherently dangerous. For this reason, the extent of exposure
at a distance of d = 1, the intensity at any other distance is
must be minimized through the use of all protective means
equal to 1/d2. Intensity diminishes as a function of the square
available. Although the hazards of radiation were witnessed
of distance.
early in the 20th century, how exposure was to be calculated
The effects of distance are manifested quickly. Staff
and what acute and cumulative doses were dangerous could
exposure at 1 m distance from a C arm is 1/1000th that of
not be determined until later. In 1928, the International
the patient, even without shielding. In a model of femoral
Commission on Radiological Protection (ICRP) was formed
fracture, moving from the treated hip side of a patient to the
to study and set standards for radiation protection. The
contralateral side reduces exposure by a factor of 57 for
National Council on Radiation Protection (NCRP) was estab-
the surgeon, 13 for the nurse, and 21 for the anesthetist. If
lished in the United States to help set US policy on radiation
the surgeon remains ipsilateral to the operative site but moves
protection.37 Until recently, guidelines for radiation exposure
as little as 0.5 m away (cephalad) from the beam, the dose is
have been based on annual exposure limits (maximal permis-
sible yearly dose). The historical means of dosimetry under- reduced by a factor of 13, and at 1.5 m away, by a factor of
estimated exposure because of technical limitations and 26. At 2 m from the source of radiation, the scattered radia-
sampling error. For this reason, guidelines now focus on life- tion received by staff is very small.42 Nevertheless, because of
time accumulated exposure as a more useful surrogate for the the problem of accumulated lifetime exposure, no degree of
real risks in those with chronic or prolonged exposure. exposure is ever deemed truly innocuous.
Concessions to higher annual dose limits were made Image-guided surgery now plays a major role in many sur-
for workers allowed higher radiation exposure because of gical disciplines, including orthopedics, vascular surgery, and
occupational responsibilities. These were called “classified” urology. The cumulative radiation exposure associated with
workers, and they were subjected to strict monitoring and image guidance may be hazardous. The use of radionuclides
regular examination. Radiologists have been considered for identification of sentinel nodes and intraoperative brachy-
classified workers, but not surgeons. Classified workers were therapy for the treatment of certain malignancies also creates
permitted more than three times the annual dose than the potential for radiation exposure.43
nonclassified.38 Exposure to radiation comes from background radioactiv-
Empirical data suggest that the typical spinal surgeon per- ity and from radiation sources in the workplace. The ICRP
forming fluoroscopically guided procedures may receive as has established recommended yearly limits of radiation expo-
much as 1.3-fold the annual whole-body radiation dose allow- sure for these two categories [see Table 1].44 Recent studies of
able for radiologists, although the level of thyroid exposure is OR staff indicate that radiation exposure during surgical
less than 10% of the applicable limit specified by the NCRP.39 procedures employing radiation imaging techniques are well
A study of endovascular surgeons, in contrast, showed that within the ICRP limits.45–47
their radiation exposure fell well within these limits, as well All OR personnel should wear radiation safety badges to
as the limits established by the ICRP.40 allow monitoring of radiation exposure on a monthly basis.
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Table 1 ICRP-Recommended Radiation Dose Limits44 OR Design

Advances in videoendoscopic surgery and endoluminal
Dose Limit
vascular surgery since 1990 have led to the introduction of
Occupational Public many complex electronic devices into an OR environment
Effective dose 20 mSv/yr averaged over 1 mSv/yr designed at the end of the 19th century. The promise of
defined periods of 5 yr widespread robotics use in the future may further complicate
Annual equivalent dose in equipment and use of space within the OR. At the same time,
Lens of the eye 150 mSv 15 mSv the importance of IT in both the performance of surgery
Skin 500 mSv 50 mSv and its documentation will only increase. These changes
Hands and feet 500 mSv —
will inevitably require design adaptations in the OR to
ICRP = International Commission on Radiological Protection; mSv = ensure adequate power and communication infrastructure
millisievert.
support.56
The ideal OR of the future will have videoendoscopic
monitors, light sources, and CO2 insufflators mounted on
OR personnel should wear protective lead aprons (0.25– booms that can be introduced or withdrawn from patient care
0.5 mm in thickness) with thyroid shields during procedures without moving heavy carts or reconnecting cables and power
in which fluoroscopy is used. Personnel frequently exposed to sources. ORs with ceiling- or floor-mounted fluoroscopy
radiation should wear lead-containing lenses for eye protec- permit efficient use of catheter-based endoluminal and intra-
tion. A mobile shield is useful for additional protection during vascular techniques during surgical care. Boom-mounted
cine runs. equipment can be easily moved, permitting more rapid room
OR personnel should stand as far away from the x-ray turnover between cases.
beam as possible to limit exposure. Even a distance of several Designing rooms with the flexibility for multidisciplinary
feet can significantly reduce exposure. Equipment emitting use may be more cost effective for many hospitals. In the long
ionizing radiation should be maintained and monitored to run, however, team training for subspecialty fields employing
ensure proper function.48 The use of pulsed fluoroscopy and complex imaging equipment and catheter-based therapy may
prove to be a more important factor for patient safety and
effective collimation of images will help minimize the dose
efficiency than any particular OR design.57 This is a key
of radiation. Excessive and unnecessary imaging should be
element in program development. Hospital administration
eliminated.
must also commit the capital necessary to complete such
a project before proceeding with program development.
Laser exposure Surgical lasers are class 4 lasers that
Balancing OR efficiency, new technology, and cost is a
have the potential to irreparably damage the eye and burn the continuous challenge.
skin. A class 4 laser beam is 1 billion times brighter than a
100 W light bulb.49 All OR personnel must wear protective
glasses with lenses designed specifically for the wavelength of Environmental Issues in the OR
the specific laser being used. Glasses should be inspected
temperature and humidity
prior to use to ensure that there are no scratches on the lens
that could render the wearer vulnerable to an eye injury. The In Europe and North America, the OR is typically main-
windows of the room should be shielded to protect individu- tained at 18° to 26°C (64.4° to 78.8°F). A higher tempera-
als passing by. The number of personnel in a laser therapy ture is necessary during operations on infants and burn
room should be kept to a minimum. patients to conserve body heat. Fully gowned surgeons prefer
the lower temperature of 18°C (64.4°F), but anesthesiologists
Noise and light exposure General environmental prefer 21.5°C (70.7°F).58 The optimum ambient temperature
in the OR reflects a compromise between the comfort of
hazards include high levels of noise and intense levels of
gowned and ungowned staff. The ubiquitous deployment of
light.50–52 These hazards are of equal significance to patients
patient warming devices has all but eliminated the problem
and to staff. One early study has indicated that elevated noise
of hypothermia in the adult during elective surgery.
levels during orthopedic procedures (above the recommended
Recent publications have indicated neurologic benefits
limits of 110 dBA) were associated with significant hearing from controlled hypothermia in the region of 34°C (93.2°F)
loss in orthopedic surgeons.51 Noise, excessive chatter, in certain cases of asystole, cardiopulmonary arrest, and
and even music can also pose a hazard to the patient by resuscitation.59–61 The equipment required for therapeutic
distracting the attention of OR personnel. hypothermia can be cumbersome.
Humidity in the OR is generally maintained between 50
Psychosocial risks Perhaps the most underappreciated and 60%. Humidity greater than 60% may cause condensa-
risks to the perioperative professional are psychosocial. Long tion on cool surfaces. Humidity less than 50% may not
hours and nighttime emergencies lead to fatigue. The high suppress static electricity. Static electricity can adversely
level of responsibility, the consequences of error, and the affect the function of modern computers and smart medical
level of oversight have led to high levels of stress and burn- devices.
out.53 Unfortunately, violence in the health care workplace,
both verbal and physical, is common.54 Stress reduction can lighting
be achieved by team training.15 Hospitals should have zero ORs are no longer provided with skylights and northern
tolerance for workplace violence.55 exposure to maximize the benefit of natural illumination.
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ROOM — 7
Nevertheless, effective lighting remains an important factor in interface as a function of resistance to the flow of current.
reducing stress by providing clear views of the operative field, The vaporization of intracellular water content leads to disin-
the anesthesia and monitoring systems, and the nursing tegration of the cell. Heat leads to the coagulation of proteins
area. and hemostasis. Cellular debris is aerosolized. The smoke
The standards for OR illumination were outlined by Dr. that is generated is comparable to that accompanying laser
William Beck and the Illuminating Engineering Society.62,63 A use. The smoke and its particulate content may be carcino-
general illumination brightness of up to 200 footcandles (ft-c) genic, allergenic, inflammatory, and infectious. There is little
is desirable in new construction. The lighting sources should difference between laser plume and electrosurgical smoke.65
be free of glare and nonreflective.64 The electrosurgical instrument requires close supervision.66
The amount of light required during an operation varies It is very easy to become complacent in its use. The unit
with the surgeon and the operative site. Quantities of light generates an electrical arc. In the past, these have been asso-
can be measured as a function of the amount beamed on a ciated with explosions. This risk has been lessened because
subject (incident light) or the amount reflected (reflected explosive anesthetic agents are no longer used. Nevertheless,
light). In one study, general surgeons operating on the explosion of hydrogen and methane gases in the large bowel
common bile duct found 300 ft-c sufficient because the remains a threat, especially when surgery must be performed
reflectance of this tissue area is 15%. The corresponding inci- on an unprepared bowel.67 Because the unit and its arc
dent light level would be 2,000 ft-c.21 Surgeons performing generate a broad and unfiltered band of radiofrequencies,
coronary bypass operations require an incident level of electrosurgical units may interfere with monitoring devices,
3,500 ft-c.21 Whether changes in the color of light can improve most notably the electrocardiographic (ECG) monitor.
discrimination of different tissues is unknown. Interference with cardiac pacemaker activity may occur.68
The powerful lights installed for surgery generate heat Skin burns are the most frequently reported complication
through the projection of infrared energy. This is an in use. Rarely are they fatal, but they are painful and may
inefficient but inevitable byproduct of most forms of light require skin grafts, raising the possibility of litigation. The
appropriate for the OR. Much of the infrared energy can burn site can be at the dispersive electrode, ECG monitoring
be eliminated by filtration or by heat-diverting dichroic leads, esophageal or rectal temperature probes, or areas of
reflectors. body contact with grounded objects. The dispersive electrode
There are several types of overhead lighting designs. For should be firmly attached to a broad area of dry, hairless skin,
preferably over a large muscle mass.67,68
small ORs, a single large overhead light with one or two small
Alcohol-based hair care products should be avoided during
satellites may suffice. Larger ORs may benefit more from
head and neck surgery because the risk of combustion during
several large lights with broader orbits. The larger the OR,
the use of electrocautery.
the more important the installation of multiple light sources
Preparation of the OR should include verification of the
that can concentrate light in different areas of the operating
proper function and grounding of the unit and proper place-
field. This consideration is of particular importance where
ment of the dispersive electrode. Smoke evacuators are highly
large body areas are exposed or where multiple sites are
recommended. The National Institute for Occupational
accessed simultaneously.
Safety and Health (NIOSH) recommends a system that can
The illumination provided by overhead lighting can be
pull 50 cubic feet per minute with a capture velocity of 100
usefully amplified and improved with headlights. Headlights
to 150 feet per minute at the inlet nozzle and positioned
have substituted for mobile lights in many OR suites, but within 2 inches of the surgical site.69 Filters should be installed
both have their place. When headlights are used, spare bulbs to capture the contents of the smoke. Used filters are deemed
must be kept on hand and cabling examined for damage and biohazardous. Routine, unfiltered suction is not adequate for
properly stored after each use. this purpose.69
During microsurgical and laparoscopic procedures, the
surgical field is illuminated primarily by dint of the instru- lasers and laser safety
ments used for visualization. The importance of ambient Lasers generate focused energy. They have been implicated
lighting for the remainder of the OR must not be forgotten. in skin burns, retinal injuries, endotracheal tube fires,
All ORs should be equipped with battery-powered backup pneumothorax, and damage to viscera and the vasculature.70
illumination and flashlights for emergency use. Both patients and staff have suffered injuries.
or equipment The laser-safe OR requires specific modifications. The OR
should not have windows. Walls, ceilings, and equipment
The modern OR is replete with medical devices designed should be nonreflective. Equipment used in the operative
to facilitate the work of the surgical team and to support, field should be nonreflective and nonflammable. A sign
position, and protect the patient [see Table 2]. The equipment warning personnel that a laser is in use should be posted.
in the OR must be chosen and maintained with three Anesthetic technique should also take the use of lasers into
concerns in mind: patient safety, surgical efficiency, and consideration. When lasers are used in the vicinity of the face,
reduction of occupational hazards. airway, or chest cavity, the concentration of O2 and N2O in
the inhaled gases should be reduced to decrease the possibil-
electrosurgical devices
ity of fire. Personnel should wear appropriate eye protection.
The common electrosurgical device is a 500 W radiofre- A smoke evacuator will improve visualization, reduce objec-
quency generator used to cut and coagulate tissue. A current tionable odor, and decrease the potential for papillomavirus
passes from the cutting or coagulating surgical instrument infection or ingestion of toxic fumes from the laser smoke
to a dispersion electrode. Heat is generated at the tissue plume.65,71–74
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Table 2 Devices Used in the Operating Room
Function Device
Support of patient Anesthesia delivery devices
Ventilator
Physiologic monitoring devices
Warming devices
IV fluid warmers and infusers
Support of surgeon Sources of mechanical, electrical, and internal power, including power tools and electrocautery, as well as
laser and ultrasound instruments
Mechanical retractors
Lights mounted in various locations
Suction devices and smoke evacuators
Electromechanical and computerized assistive devices, such as robotic assistants
Visualization equipment, including microscopes, endoscopic video cameras, and display devices such as
video monitors, projection equipment, and head-mounted displays
Data, sound, and video storage and transmission equipment
Diagnostic imaging devices (e.g., for fluoroscopy, ultrasonography, MRI, and CT)
Support of OR team Surgical instruments, usually packaged in case carts before each operation but occasionally stored in
nearby fixed or mobile modules
Tables for display of primary and secondary surgical instruments
Containers for disposal of single-use equipment, gowns, drapes, etc.
Workplace for charting and record keeping
Communication equipment
CT = computed tomography; IV = intravenous; MRI = magnetic resonance imaging; OR = operating room.
powered devices Improperly balanced instruments have been known to twist

The surgical table must be properly positioned and adjusted or fall, causing injury to patients and staff.
to ensure the safety of the patient and the efficient work of Many commercial microscope drapes are available. Where
the surgical team. Manually adjustable tables are simple, but the laser is mounted to the microscope, it is essential to
those with electrical controls are easier to manage. OR table confirm that the drape is out of the line of fire to avoid
attachments, such as the arm boards and leg stirrups used to contamination, melting, or kindling.
position patients, must be properly maintained and secured intraoperative imaging and navigation
to prevent injuries to patients or staff. During transfer to and
from the OR table, care must be taken to ensure that the The advent of less invasive surgery requires accurate intra-
patient is not injured and that life support, monitoring, and operative confirmation of surgical anatomy through the use
intravenous (IV) systems remain connected. Proper transfer of x-ray, CT, MRI, and ultrasonography. These modalities
technique, adequate staff, and the use of assistive devices are increasingly accompanied by and aligned with the use of
such as rollers will help prevent musculoskeletal injuries to surgical navigation systems. Intraoperative ultrasonography
the OR staff during this maneuver. Patients with fragile skin, requires a high-quality portable ultrasound unit and special-
including infants, small children, the ill, and the elderly, ized probes. Depending on the procedure and the training of
should be lifted and not dragged into position. the surgeon, the presence of a radiologist and an ultrasound
Other powered surgical instruments common in the OR technician may be requested.
include those used to obtain skin grafts, open the sternum The ultrasound unit should be positioned near the patient,
and the cranium, and perform orthopedic procedures. and the surgical team must be able to view the image
Powered saws and drills can aerosolize body fluids, thereby comfortably. In some cases, the image may be displayed on
creating a potential infection and contamination hazard for OR monitors by means of a video mixing device. Ultrasound
OR personnel.75 units may also be used to modify the reference image in real
time in surgical navigation systems.76
operating microscope Fluoroscopic and x-ray units may be portable or dedicated.
Microsurgery is a routine part of many surgical specialties, Open radiologic units are usually installed either in the OR
including neurosurgery, plastic surgery, hand surgery, gyne- proper or immediately adjacent to the OR to permit intraop-
cologic surgery, and ophthalmology. Microscopes may be erative imaging of the selected body area. Intraoperative angi-
moved into the OR on wheeled stands or mounted on the ography and MRI devices are typically installed in dedicated
ceiling, wall, or floor. Built-in microscopes are best employed ORs.77 Intraoperative CT for neurosurgery, for example, may
in dedicated ORs.46 All controls and displays must be involve either portable or fixed devices.78
properly positioned at or below the user’s line of sight to The use of sequential compression stockings has become
allow comfortable and unobstructed viewing. the standard of care for the prevention of venous thrombo-
Modern operating microscopes are servo controlled and embolism in the majority of operations for which direct access
counterbalanced. The sequence for properly balancing a to the lower extremities is not required [see 6:6 Venous
microscope should be carefully followed prior to every Thromboembolism].79 The air pump often must be placed near
procedure and each time accessories are added or removed. the patient on the floor or on a nearby cart. The pressure
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tubing from the stockings to the pump must be carefully use a foot pedal to select various imaging and recording
routed so as not to interfere with surgical access. modes and to play back selected images and sequences.
Suction devices are ubiquitous in the OR. A typical suction Unlike fixed systems, which require patients to be moved
apparatus consists of a set of canisters on a wheeled base on a floating table to change the field of view, C-arm systems
receiving suction from a wall- or ceiling-mounted source. The require the image intensifier to be moved from station to
surgeon’s aspirating cannula is connected sterilely to these station over a fixed patient. Although more cumbersome than
canisters. Suction tubing is a common tripping hazard in the fixed systems, the newest C-arms have increased mobility
OR. In some procedures, the suction canisters may require and maneuverability. Patients must be placed on a special
repeated changing. nonmetallic carbon fiber table. To provide a sufficient field of
view and permit panning from head to toe, the tables must
equipment be supported at one end and completely clear beneath.
Although these tables do not flex, they are sufficient for most
Imaging Equipment
operations. Furthermore, they are mobile and may be replaced
Imaging equipment for endovascular surgery can be fixed with conventional operating tables when the endovascular
to the ceiling or portable. The fixed system is also employed suite is being used for standard open surgical procedures.
in catheterization laboratories and dedicated interventional
radiology suites. Portable systems use C-arms with dedicated Interventional Equipment
vascular software packages designed for optimal endovascular The performance of endovascular procedures in the OR
imaging. Each of these systems has advantages and disadvan- requires familiarity with a wide range of devices that may
tages. be unfamiliar to OR personnel. These include guidewires,
Fixed ceiling-mounted systems have higher power output sheaths, specialized catheters, angioplasty balloons, stents,
and smaller focal spot size and provide the highest-quality and stent grafts [see Table 3]. In a busy endovascular OR,
images. Larger image intensifiers (up to 16 in.) make possible much of this equipment must be stocked for everyday use,
larger visual fields for diagnostic arteriograms. Fewer runs are with the remainder ordered on a case-by-case basis. The
necessary, with the advantage of reducing the quantity of expense of establishing the necessary inventory of equipment
contrast injected and radiation exposure. can be substantial and can place a considerable burden on
Fixed systems are accompanied by floating angiography smaller hospitals that are already spending sizable amounts
tables, which allow the surgeon to move the patient easily on stocking similar devices for their catheterization laborato-
beneath the fixed image intensifier. The variable distance ries and interventional suites. Fortunately, many companies
between the x-ray tube and the image intensifier allows the are willing to supply equipment on a consignment and case
basis, allowing hospitals to pay for devices as they are used
intensifier to be placed close to the patient if desired, thereby
and reducing the volume of devices stocked.
improving image quality and decreasing radiation scatter.
It is generally accepted that such systems afford the surgeon ORs in Other Specialties
the most control and permit the most effective imaging of
Specialty equipment is generally available for permanent
patients. installation in ophthalmologic, orthopedic, trauma, neurosur-
Fixed ceiling-mounted systems are quite expensive (typi- gical, and urologic ORs. The observations offered regarding
cally $1 to $1.5 million), and major structural renovations are microscopes, imaging devices and lasers, storage, and physi-
often required for installation in a typical OR. These systems cal layout are broadly applicable. The cardiovascular OR and
are not particularly flexible. The floating angiography tables the neurosurgical OR often have complex needs that are more
and the immobility of the image intensifiers render the rooms difficult to fill simply by equipping a general-purpose OR.
unsuitable for most conventional open surgical procedures. Thus, a neurosurgical OR may need to be equipped for
As a result, fixed imaging systems are generally restricted to neuronavigation, laser and microsurgery, intraoperative angi-
high-volume centers where use rates justify the construction ography, neurointerventional surgery, and pediatric surgery.
of dedicated endovascular ORs. In addition, it may need shielding for neurophysiologic
The imaging capability and versatility of portable digital recordings necessary for cranial electrostimulation. The pres-
C-arms have increased dramatically. State-of-the-art portable ence of fixed or mounted instrumentation per se rarely poses
C-arms are considerably less expensive than fixed systems an insurmountable difficulty in adapting a general-purpose
($175,000 to $225,000) while retaining many of their advan- OR to specialty use, but the reverse is not the case.
tages. The variable image intensifier size (from 6 to 12 in.)
offers valuable flexibility, with excellent resolution at the Surgeon’s Control of Equipment: Touch Panels, Voice
smaller end and an adequate field of view at the larger end. Activation, and Robotics
With some portable C-arm systems, it is possible to vary the Inherent shortcomings in the design of OR equipment have
distance between the image intensifier and the x-ray tube, as been exacerbated by the spread of minimally invasive proce-
with a fixed system (see above). Pulsed fluoroscopy, image dures. Because most of the equipment needed for minimally
collimation, and filtration are standard features for improving invasive surgery resides outside the sterile field, the circulat-
imaging and decreasing radiation exposure. Sophisticated ing nurse becomes the point person for critical control. Often
software packages allow high-resolution digital subtraction the circulating nurse is out of the room at the precise moment
angiography, variable magnification, road mapping (i.e., the important equipment adjustments must be made.
superimposition of live fluoroscopy over a saved digital Surgeons grow frustrated at the inevitable delays that
arteriogram), image fusion, and a number of other useful follow, and nurses often weary of these additional and some-
features. Improvements in C-arm design allow the surgeon to times distracting responsibilities. As a result, there is great
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Table 3 Standard Equipment for Endovascular Operating Rooms
Diagnostic arteriography Entry needle (16-gauge beveled)

Entry wire (J wire or floppy-tip wire)
Arterial sheath (5 Fr)
Catheters
Multipurpose nonselective (pigtail, tennis racquet, straight, etc.)
Selective (cobra head, shepherd’s crook, etc.)
Guidewires (floppy, steerable, angled, hydrophilic, etc.)
Contrast agent (nonionic preferred)
Power injector
Balloon stent angioplasty Sheaths (various lengths and diameters)
Guide catheters
Balloons (various lengths and diameters)
Stents
Balloon expandable (various lengths and diameters)
Self-expanding (various lengths and diameters)
Inflation device
Endovascular aneurysm repair Large-caliber sheaths (12–24 Fr)
Super-stiff guidewires
Endovascular stent grafts
Main body and contralateral iliac limb
Aortic and iliac extension grafts
Endovascular arterial coils
interest in improving the interface of surgical devices with the provides the OR team with critical information about the pro-
surgeon. Sterile touchscreens offered the first solution, but gress of the operation. To operate a device, the surgeon must
many two-handed surgical procedures still make it difficult take approximately 20 minutes to train the recognition system
for a surgeon to control ancillary equipment manually. Voice to his or her voice patterns and must wear an audio headset
activation technology offers a potential solution. to relay commands. The learning curve for voice control is
Development of voice activation began in the late 1960s. minimal (two or three cases, on average). Devices that can
The goal was a simple, safe, and universally acceptable voice now be controlled by voice activation software include
recognition system that flawlessly carried out the verbal cameras, light sources, digital image capture and documenta-
requests of the user. However, attempts to construct a system tion devices, printers, insufflators, OR ambient and surgical
capable of accurately recognizing a wide array of speech lighting systems, operating tables, and electrocauteries.
patterns faced formidable technological hurdles that are only
now beginning to be overcome. Infection Control in the OR
In 1998, the first Food and Drug Administration (FDA)- Infection control is a major concern in health care in
approved voice activation system, Hermes (Computer general, but it is a particularly important issue in the sterile
Motion, Santa Barbara, CA), was introduced into the OR. environment of the OR, where patients undergo surgical
Designed to provide surgeons with direct access and control procedures and are at significant risk for perioperative
of surgical devices, Hermes is operated via either a handheld nosocomial infection. Even the best OR design will not
pendant or voice commands from the surgeon. The chal- compensate for improper surgical technique or failure to pay
lenges of advanced laparoscopic surgery provide a fertile attention to infection prevention.
ground for demonstrating the benefits of voice activation [see Surgical site infection (SSI) is a major cause of patient
Table 4]. morbidity, mortality, and health care costs. In the United
Voice activation offers surgeons immediate access to States, according to the Centers for Disease Control and
and direct control of surgical devices. At the same time, it Prevention (CDC), approximately 2.9% of nearly 30 million
Table 4 Benefits of Voice Activation Technology in the Laparoscopic Operating Room
Benefits to surgical team Gives surgeons direct and immediate control of devices
Frees nursing staff from dull, repetitive tasks
Reduces miscommunication and frustration between surgeons and staff
Increases OR efficiency
Alerts staff when device is malfunctioning or setting off alarm
Benefits to hospital Saves money, allowing shorter, more efficient operations
Contributes to better OR use and, potentially, performance of more surgical procedures
Lays foundation for expanded use of voice activation in ORs
Allows seamless working environment
Benefit to patient Reduces operating time, which—coupled with improved optics, ergonomics, and
efficiency—leads to better surgical outcome
OR = operating room.
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operations are complicated by SSIs each year. This percent- of surgical gloves rather than a single pair provides an addi-
age may, in fact, be an underestimate, given the known tional barrier and further reduces the risk of contamination.
inherent problems with surgeons’ voluntary self-reporting of A 2002 Cochrane Review concluded that wearing two pairs
infections occurring in the ambulatory surgical setting.80 Each of latex gloves significantly reduced the risk of hand exposure.
infection is estimated to increase total hospital stay by several The rate of single-glove perforations is approximately 15%.
days and add materially to costs and charges. The rate of inner glove perforation when two pairs of gloves
SSIs pose an increasingly difficult problem for institutions are worn is approximately 5%.86
with a large Medicare population. Recently, the Centers OSHA requires that personal protective equipment be
for Medicare and Medicaid Services (CMS) published the available in the health care setting, and these requirements
Inpatient Prospective Payment System (IPPS) FY 2009 final are specified in the OSHA standard on occupational exposure
rule expanding the list of hospital-acquired conditions (HACs) to bloodborne pathogens, which went into effect in 1992.
that will reduce Medicare payments. A number of SSIs figure Among the requirements is the implementation of the CDC’s
prominently on this list.81 State Medicaid directors have also universal precautions, designed to prevent transmission of
been authorized to deny payment for certain HACs. HIV, hepatitis B virus, and other bloodborne pathogens.87
The epidemiology and management of SSIs in older adults These precautions dictate the use of protective barriers (e.g.,
are receiving increasing attention.82 SSIs have been divided gloves, gowns, aprons, masks, and protective eyewear) to
by the CDC into three broad categories: superficial incisional reduce the risk that the health care worker’s skin or mucous
SSI, deep incisional SSI, and organ or space SSI [see Table 5 membranes will be exposed to potentially infectious
and 1:1 Prevention of Postoperative Infection].83 materials.
Factors that contribute to the development of SSI include Performance standards for protective barriers are the
responsibility of the FDA’s Center for Devices and
(1) the patient’s health status, (2) the physical environment
Radiological Health. FDA standards define the performance
where surgical care is provided, and (3) clinical interventions
properties that these products must exhibit, including mini-
that increase the patient’s inherent risk. Careful patient
mum strength, barrier protection, and fluid resistance. The
selection and preparation, including judicious use of antibi-
current CDC recommendation is to use surgical gowns
otic prophylaxis, can decrease the overall risk of infection,
and drapes that resist liquid penetration and remain effective
especially after clean-contaminated and contaminated
barriers when wet.
operations.
These standards are intuitively appealing, but few studies
hand hygiene address the comparative benefits of specific types of drapes.
A meta-analysis of over 5,000 surgical cases indicated that
Hand antisepsis plays a significant role in preventing noso- adhesive drapes increase the risk of SSI (relative risk = 1.23;
comial infections. When outbreaks of infection occur in the p = .03) and iodine-impregnated drapes had no effect.88
perioperative period, careful assessment of the adequacy of Compliance with universal precautions and barrier
hand hygiene among OR personnel is important. Agents protection is a challenge. Educational efforts aimed at OR
used for surgical hand scrubs should substantially reduce personnel improved compliance significantly, particularly
microorganisms on intact skin, contain a nonirritating antimi- with regard to the use of protective eyewear and double-
crobial preparation, possess broad-spectrum activity, and be gloving. These efforts were associated with a reduced
fast-acting and persistent.84 The CDC offers the following incidence of blood and body fluid exposure.89
guidelines85:
antimicrobial prophylaxis
• Surgical hand antisepsis using either an antimicrobial
SSIs are established several hours after contamination.90
soap or an alcohol-based hand rub with persistent activity
There is a well-recognized “golden period” during which
is recommended before donning sterile gloves when
prophylactic antibiotics can be effective. Administration of
performing surgical procedures (evidence level IB).
antibiotics before contamination reduces the risk of infection
• When performing surgical hand antisepsis using an antimi-
but is subsequently of little value.91 Selective use of short-
crobial soap, scrub hands and forearms for the length of
duration, narrow-spectrum antibiotic agents should be con-
time recommended by the manufacturer, usually 2 to 6 sidered for appropriate patients to cover the usual pathogens
minutes. Long scrub times (e.g., 10 minutes) are not isolated from SSIs [see Table 6].92
necessary (evidence level IB). Recommendations for antibiotic prophylaxis are addressed
• When using an alcohol-based surgical hand-scrub product in more detail elsewhere [see 1:1 Prevention of Postoperative
with persistent activity, follow the manufacturer’s instruc- Infection]. In brief, the principles of optimal surgical
tions. Before applying the alcohol solution, prewash hands antimicrobial prophylaxis include (1) appropriate choice of
and forearms with a nonantimicrobial soap and dry hands an antimicrobial agent, (2) proper timing of antibiotic admin-
and forearms completely. After application of the alcohol- istration before incision, and (3) limited duration of antibiotic
based product, allow hands and forearms to dry thoroughly administration after operation.
before donning sterile gloves. When a preoperative antibiotic is indicated, a single dose
of therapeutic strength, administered shortly before incision,
gloves and protective barriers
usually suffices.93 The dose may have to be increased if the
There is a high risk of pathogen transfer during surgery. patient is morbidly obese.94 A second dose is indicated if the
This is a risk from which both the patient and the surgical procedure is longer than two half-lives of the drug or if exten-
team must be protected. The risk can be reduced by using sive blood loss occurs. Continuation of prophylaxis beyond
protective barriers, such as surgical gloves. Wearing two pairs 24 hours is not recommended.
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Table 5 Criteria for Defining a Surgical Site Infection83
Superficial incisional SSI

Infection occurs within 30 days after the operation, and infection involves only skin or subcutaneous tissue of the incisions, and at least
one of the following:
1. Purulent drainage, with or without laboratory confirmation, from the superficial incision
2. Organisms isolated from an aseptically obtained culture of fluid or tissue from the superficial incision
3. At least one of the following signs or symptoms of infection: pain or tenderness, localized swelling, redness, or heat; and superficial
incision is deliberately opened by surgeon, unless incision is culture negative
4. Diagnosis of superficial incisional SSI by the surgeon or attending physician
Do not report the following conditions as SSI:
1. Stitch abscess (minimal inflammation and discharge confined to the points of suture penetration)
2. Infection of an episiotomy or newborn circumcision site
3. Infected burn wound
4. Incisional SSI that extends into the fascial and muscle layers (see deep incisional SSI)
Note: Specific criteria are used for identifying infected episiotomy and circumcision sites and burn wounds.
Deep incisional SSI
Infection occurs within 30 days after the operation if no implant* is left in place or within 1 yr if an implant is in place and the infection
appears to be related to the operation, and infection involves deep soft tissues (e.g., fascial and muscle layers) on the incision, and at
least one of the following:
1. Purulent drainage from the deep incision but not from the organ/space component of the surgical site
2. A deep incision spontaneously dehisces or is deliberately opened by a surgeon when the patient has at least one of the following
signs or symptoms: fever (> 38°C [100.4°F]), localized pain, or tenderness, unless the site is culture negative
3. An abscess or other evidence of infection involving the deep incision is found on direct examination, during reoperation, or by
histopathologic or radiologic examination
4. Diagnosis of a deep incisional SSI by a surgeon or attending physician
Notes
1. Report infection that involves both superficial and deep incision sites as deep incisional SSI
2. Report an organ/space SSI that drains through the incision as a deep incisional SSI
Organ/space SSI
Infection occurs within 30 days after the operation if no implant* is left in place or within 1 yr if an implant is in place and the infection
appears to be related to the operation, and infection involves any part of the anatomy (e.g., organs or spaces), other than the incision,
which was opened or manipulated during an operation, and at least one of the following:
1. Purulent drainage from a drain that is placed through a stab wound† into the organ/space
2. Organisms isolated from an aseptically obtained culture of fluid or tissue in the organ/space
3. An abscess or other evidence of infection involving the organ/space that is found on direct examination, during reoperation, or by
histopathologic or radiologic examination
4. Diagnosis of an organ/space SSI by a surgeon or attending physician
SSI = surgical site infection.
*National Nosocomial Infection Surveillance definition; a non–human-derived implantable foreign body (e.g., prosthetic heart valve, nonhuman vascular graft,
mechanical heart, or hip prosthesis) that is permanantly placed in a patient during surgery.
†
If the area around a stab wound becomes infected, it is not an SSI. It is considered a skin or soft tissue infection, depending on its depth.
The provision of prophylactic antibiotics, where indicated, published in 2001, determined that warming patients before
has been accepted as a measure of surgical quality aimed at short-duration clean procedures (breast, varicose vein, or
a reduction in SSIs.95,96 A strong economic case has been hernia) reduced infection (p = .001) and reduced wound
made for infection control, including prophylactic antibiotics, scores (p = .007) in this setting as well.104
benefiting the hospital as well as the patient.97 The perio- The safest and most effective way of protecting patients
perative nursing team has a central role, together with the from hypothermia is to use forced-air warmers with special-
anesthesiologist, in monitoring the administration of ized blankets placed over the upper or lower body. Alterna-
preoperative prophylactic antibiotics.98–100 tives include placing a warming water mattress under the
patient and draping the patient with an aluminized blanket.
nonpharmacologic preventive measures Second-line therapy involves warming all IV fluids. Any
Several studies have confirmed that certain nonpharmaco- irrigation fluids used in a surgical procedure should be at or
logic measures, including maintenance of perioperative slightly above body temperature before use. Radiant heating
normothermia and provision of supplemental perioperative devices placed above the operative field may be especially
oxygen, are efficacious in preventing SSIs.101 useful during operations on infants. Use of a warmer on
the inhalation side of the anesthetic gas circuit can also
Perioperative Normothermia help maintain the patient’s body temperature during an
A 1996 study showed that warming patients during colorec- operation.
tal surgery reduced infection rates.102 This finding was
confirmed in a subsequent observational cohort study that Supplemental Perioperative Oxygen
reported a significantly increased incidence of SSI with Destruction by oxidation, or oxidative killing, is the body’s
hypothermia.103 A randomized, controlled trial of 421 patients, most important defense against surgical pathogens. This
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Table 6 Distribution of Pathogens Isolated from Surgical Site Infections: National Nosocomial Infections Surveillance
System, 1986–199683
Pathogen Percentage of Isolates*

1986–1989 (N = 16,727) 1990–1996 (N = 17,671)
Staphylococcus aureus 17 20
Coagulase-negative staphylococci 12 14
Enterococcus species 13 12
Escherichia coli 10 8
Pseudomonas aeruginosa 8 8
Enterobacter species 8 7
Proteus mirabilis 4 3
Klebsiella pneumoniae 3 3
Other Streptococcus species 3 3
Candida albicans 2 3
Group D streptococci (nonenterococci) — 2
Other gram-positive aerobes — 2
Bacteroides fragilis — 2
*Pathogens representing less than 2% of isolates are excluded.
defensive response depends on oxygen tension in contami- decrease in mortality rate generally in critically ill patients.111,112
nated tissue. An easy method of improving oxygen tension in The effects are not restricted to diabetics. In fact, there is
adequately perfused tissue is to increase the FiO2. Supple- evidence to conclude that nondiabetics enjoy more protection
mental perioperative oxygen (i.e., an FiO2 of 80% instead of than diabetics.113
30%) significantly overcomes the decrease in phagocytosis Some questions remain about just how tight control must
and bacterial killing usually associated with anesthesia and be to have an effect. There is a small but measurable risk
surgery (and significantly reduces postoperative nausea and of hypoglycemia with intensive IV insulin therapy, but this
vomiting). Oxygen tension in wound tissue has been found to risk can be mitigated with continuous or near-continuous
be a good predictor of SSI risk.105 glucometry or dynamic scale nomograms.114
Avoidance of Blood Transfusion

Housekeeping Procedures
The association between blood transfusion and increased
perioperative infection rates is well documented. In a 1997 floors and walls
study, geriatric hip fracture patients undergoing surgical
Despite detailed recommendations for cleaning the OR [see
repair who received blood transfusion had significantly higher
Table 7], the procedures that are optimal to provide a clean
rates of perioperative infection than those who did not (27%
environment while still being cost-effective have not been
versus 15%), and this effect was confirmed on multivariate
critically analyzed.115
analysis.106 Another study yielded similar findings in colorec-
Only a few studies have attempted to correlate surface
tal cancer: the relative risk of infection was 1.6 for transfusion contamination of the OR with SSI risk. In one randomized,
of one to three units of blood and 3.6 for transfusion of more
controlled study, for example, the control rooms were cleaned
than three units.107
with a germicidal agent and wet-vacuumed before the first
A large prospective cohort study published in 2003 evalu-
case of the day and between cases, whereas in the experimen-
ated the association between anemia, blood transfusion, and
tal rooms, cleaning consisted only of wiping up grossly visible
perioperative infection.108 Regression analysis confirmed that
contamination after clean and clean-contaminated cases.116
intraoperative transfusion of packed red blood cells was an
Both rooms had complete floor cleanup after contaminated
independent risk factor for perioperative infection (odds ratio
1.06; confidence interval 1.01 to 1.11; p > .0001). Further- or dirty and infected cases. Bacterial colony counts obtained
more, transfusion of more than four units of packed red blood directly from the floors were lower in the control rooms, but
cells was associated with a ninefold increased risk of infection counts obtained from other horizontal surfaces did not differ
(confidence interval 5.74 to 15.00; p < .0001). between the two OR groups. Wound infection rates were the
same in the control rooms and the experimental rooms and
Tight Glycemic Control were comparable with rates reported in other series.
Hyperglycemia is common under conditions of physiologic Another study found that floor disinfectants decreased
stress, in the intensive care unit (ICU) and in the OR. Tight bacterial concentration on the floor for 2 hours only. Colony
glycemic control using intensive insulin therapy and continu- counts return to pretreatment levels as personnel walked
ous glucose monitoring has been shown to reduce infection about.117
in the ICU and is emerging as a standard in surgical critical Even when an OR floor is contaminated, the rate of redis-
care and intraoperatively.109,110 It has been associated with a persal of bacteria into the air is low, and the clearance rate is
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Table 7 Operating Room Cleaning Schedules
Areas requiring daily cleaning Surgical lights and tracks

Fixed ceiling-mounted equipment
Furniture and mobile equipment, including wheels
OR and hall floors
Cabinet and push-plate handles
Ventilation grills
All horizontal surfaces
Substerile areas
Scrub and utility areas
Scrub sinks
Areas requiring routinely scheduled cleaning Ventilation ducts and filters
Recessed tracks
Cabinets and shelves
Walls and ceilings
Sterilizers, warming cabinets, refrigerators, and ice machines
OR = operating room.
high. It seems unlikely, therefore, that bacteria from the floor development of numerous and costly rituals of OR cleanup.
contribute to SSI. Consequently, routine disinfection of the However, there are no prospective studies and no large body
OR floor between clean or clean-contaminated cases appears of relevant data to support the usefulness of such rituals.
to be unnecessary. In fact, one study found no significant difference in environ-
According to CDC guidelines for the prevention of SSI, mental bacterial counts after clean cases than after dirty
when visible soiling of surfaces or equipment occurs during ones.119 Numerous authorities have recommended that there
an operation, an Environmental Protection Agency (EPA)- be only one standard of cleaning the OR after either clean or
approved hospital disinfectant should be used to decontami- dirty cases.115,119,120 This recommendation is reasonable
nate the affected areas before the next operation.83 This because of two important considerations:
statement is in keeping with the OSHA requirement that
all equipment and environmental surfaces be cleaned and • Any patient may be a source of contamination caused by
decontaminated after contact with blood or other potentially unrecognized bacterial or viral infection.
infectious materials. • The second major source of OR contamination is the
Disinfection after a contaminated or dirty case and after personnel who work there.
the last case of the day is probably a reasonable practice, Rituals applied to dirty cases include placing a germicide-
although it is not supported by directly pertinent data. Wet- soaked mat outside the OR door, allowing the OR to stand
vacuuming of the floor with an EPA-approved hospital disin- idle for an arbitrary period after cleanup of a dirty procedure,
fectant should be performed routinely after the last operation and using two circulating nurses, one inside the room and
of the day or night. one outside. None of these practices has a sound theoretical
dirty cases or factual basis.
By tradition, dirty cases are scheduled after all of the
Operations are classified or stratified into four groups in clean cases of the day have been completed. This restriction,
relation to the epidemiology of SSIs [see 1:1 Prevention of however, reduces the efficiency with which operations can be
Postoperative Infection]118: scheduled and may unnecessarily delay emergency cases.
• Clean operations are those elective cases in which the gas- There are no data to support special cleaning procedures or
trointestinal (GI) tract or the respiratory tract is not entered the closing of an OR after a contaminated or dirty operation
and there are no major breaks in technique. The infection has been performed.121 Mats placed outside the entrance to
rate in this group should be less than 3%. the OR suite show neither a reduction in the number of
• Clean-contaminated operations are those elective cases in organisms on shoes and stretcher wheels nor a reduction in
which the respiratory or the GI tract is entered or during SSI risk.122
which a break in aseptic technique has occurred. The
infection rate in such cases should be less than 10%.
Data Management in the OR
• Contaminated operations are those cases in which a fresh
traumatic wound is present or gross spillage of GI contents Regular analysis of OR data is essential to monitor effi-
occurs. ciency and correct deficiency.123 OR efficiency is maximized
• Dirty or infected operations include those in which bacte- by adherence to several basic principles:
rial inflammation occurs or in which pus is present. The
1. The number of ORs available should be matched to the
infection rate may be as high as 40% in a contaminated or
number required to achieve good use.
dirty operation.
2. Nurses and anesthesiologists rather than attending
Fear that bacteria from dirty or heavily contaminated cases surgeons should control access to the surgical schedule.
could be transmitted to subsequent cases has resulted in the 3. Surgeons should be allowed to follow themselves.
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4. Block time should be provided to surgeons. industries. In the future, such technology may be a useful
5. Systems should be established to enable and enforce adjunct to computerized OR scheduling.127
efficient turnover between cases.124
quality improvement
The distinction between efficiency and effectiveness is
The key to increased OR efficiency is increased productiv-
important. Measures of effectiveness relate achievements to
ity. Standardization of internal procedures reduces bottle-
goals. Measures of efficiency relate achievements to cost. The
OR must be both efficient and effective. necks. Computerization speeds the flow of information
Data must be both available and rapidly accessible. so that continuous improvement of the system becomes
Automation of OR data is critical and must integrate with the possible. Before a desired improvement can be implemented,
institutional health information system (HIS).125 Hospital- the proposed change must be tested quickly so that its effect
wide data regarding work flow, staffing, referral patterns, and can be determined, ideally through a small-scale pilot imple-
even parking may yield useful information for improvements mentation. This requires a collaborative effort, in which the
in OR efficacy and efficiency.126 group involved in the change learns how to “plan, do, check,
and act.” These are the elements of the so-called “PDCA
or scheduling cycle,” a classic quality initiative method. During the PDCA
OR scheduling systems should be designed to track all cycle, teams are encouraged to strategize and communicate
of the operational aspects of the OR, including patients, about various solutions and look for changes that can be
resources, rooms, and staff. They should be fully integrated made. A change is tested, quickly evaluated, and adopted
into the institutional HIS while also interfacing with key if efficacious. The PDCA cycle depends on integrated surgi-
elements located in other parts of the hospital (or ambulatory cal teams with open communication and mutual respect.
center), including finance, materials management, electronic Such teams remain the key to a safe, efficient, and effective
medical records, radiology, pathology, nursing, the emer- OR.89
gency room, labor and delivery, the blood bank, and the
pharmacy.
One of the most important purposes of a good OR schedul- Dr. Dagi is a director for Acela, Inc. and IntelliDx, Inc. His
ing system is to allow informed case substitution. Informed personal investment portfolio includes pharmaceutical and medical
case substitution is critical because surgical scheduling must device companies, none of whose products have been mentioned in
contend with frequent last-minute case cancellations.127 Dif- this chapter. He chairs the Scientific Advisory Board for Dupont
ferent specialties differ widely in their scheduling practices. life sciences. He has received neither financial nor research support
An understanding of these practices allows the OR to use from any of these entities.
resources to maximum efficiency.128 Dr Schecter has no significant financial or other relationships
Information systems that predict and fill unexpected open- with pharmaceutical, medical device, or biologics companies
ings already exist in the transportation and manufacturing relevant to this chapter.
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dosing before primary hip and knee replace- research. Clin Anaesthesiol 2008;22: analysis to estimate how many months of
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96. Schoen D. Antibiotic dosing before primary gical critical care. Curr Probl Surg 2008;45: increase productivity. Anesth Analg 2002;
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performance measure. Orthopaed Nurs 111. Langley J, Adams G. Insulin-based regimens 127. Surgery teams make strides on OR delays.
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97. Perencevich E, Stone P, Wright S, et al. patients: a systematic review. Diabetes 128. Dexter F, Traub RD. How to schedule elec-
Raising standards while watching the Metab Res Rev 2007;23:184–92. tive surgical cases into specific operating
bottom line: making a buisness case for 112. Vanhorebeek I, Langouche L, Van den rooms to maximize the efficiency of use of
infection control. Infect Control Hosp Berghe G. Tight blood glucose control: operating room time. Anesth Analg 2002;
Epidemiol 2007;28:1121–33. what is the evidence? Crit Care Med 2007; 94:933.
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Acknowledgment
and administration of perioperative antibiot- 114. Meijering S, Corstjens AM, Tulleken JE,
ics: a survey of the American Association of et al. Towards a feasible algorithm for tight The authors wish to acknowledge Rene Lafrenière,
Clinical Directors. Surv Anesthesiol 2007; glycaemic control in critically ill patients: a MD, CM, FACS, Ramon Berguer, MD, FACS,
51:218. systematic review of the literature. Crit Care Patricia C. Seifert, RN, Michael Belkin, MD,
100. Wiener-Kronish JP. Infection control for 2006;10(1):R19. FACS, Stuart Roth, MD, PhD, Karen S.
the anesthesiologist: is there more than 115. Peers JG. Cleanup techniques in the Williams, MD, Eric J. De Maria, MD, FACS,
handwashing? ASA Referesher Courses in operating room. Arch Surg 1973;107:596. and Lena M. Napolitano, MD, FACS, FCCM,
Anesthesiology. 2007;35:219–25. 116. Weber DO, Gooch JJ, Wood WR, et al. who wrote and edited this chapter for the previ-
101. Sessler DI, Akca O. Nonpharmacological Influence of operating room surface ous version of ACS Surgery. This chapter has
prevention of surgical wound infections. contamination on surgical wounds: a pro- drawn heavily on their work and generally follows
Clin Infect Dis 2002;35:1397. spective study. Arch Surg 1976;111:484. their outline and concept of the subject discussed.
102. Kurz A, Sessler DI, Lenhardt R. Periopera- 117. Daschner F. Patient-oriented hospital Russell Stewart contributed to the research and
tive normothermia to reduce the incidence hygiene. Infection 1980;39 Suppl:243. bibliography.
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1 BASIC SURGICAL AND PERIOPERATIVE CONSIDERATIONS 9 FAST TRACK INPATIENT AND
AMBULATORY SURGERY — 1
9 FAST TRACK INPATIENT AND

AMBULATORY SURGERY
Liane Feldman, MD, FACS, FRCS, and Franco Carli, MD, PhD, FRCA, FRCPC
Fast track (also known as accelerated recovery, accelerated in the traditional surgical practice concerning the use of
rehabilitation, enhanced recovery, or multimodal rehabilita- drains, tubes and catheters.
tion) surgery involves the use of a coordinated, multidisci-
Some of these individual elements may be part of evidence-
plinary perioperative care plan to reduce complications,
based modern surgical care, but there remains a great deal
facilitate earlier discharge from the hospital, and permit faster
of variability among surgeons and institutions.8 Introduction
recovery of the ability to carry out daily activities after elective
of one or more components in isolation may improve some
surgery.1 This approach is the result of advancements in
specific outcomes, but the underlying hypothesis in fast track
anesthetic techniques, improved understanding of periopera-
surgery is that a multimodal approach to care will enhance
tive organ dysfunction, and the introduction of minimally
outcomes further.4 Although few data are available, the
invasive surgery (MIS). Attenuation of the stress response
existing evidence is encouraging and suggests that fast track
to surgery (endocrine, metabolic and immunologic) and
programs are associated with reductions in hospital stay
consequent prevention of some of its negative effects (e.g.,
and morbidity.6 Successful implementation of a formal fast
increased cardiac demands, decreased gastrointestinal [GI]
track program at the institutional level, however, requires
motility, and pain) underlie many of the benefits of fast track
significant resources and time and involves an organized and
surgery.2
coordinated effort on the part of a motivated multidisciplinary
A unifying theme in the development and implementation
team that includes anesthesiologists, surgeons, nurses, phys-
of fast track surgery is the quest to understand and address
iotherapists, social workers, nutritionists, and patients. This
the factors that keep patients hospitalized after major surgery
represents a shift from conventional surgical practice, in
and impede their return to baseline performance and func-
which perioperative management is primarily dictated by the
tion.3 These interrelated factors include the need for paren-
surgeon’s preference.
teral analgesia, the requirement for intravenous (IV) fluids,
In this chapter, we describe the constituent elements of
and lack of mobility.4 Whereas some of these factors have
a fast track surgery program. We review the organizational
a physiologic basis (e.g., decreased GI motility from the
steps required to set up such a program and provide specific
sympathetic response to surgery), others are related to tradi-
examples of care plans in digestive surgery.
tions or cultural aspects of the care of surgical patients (e.g.,
waiting for GI motility to return before introducing oral
intake). The goal is to combine a variety of individual Preoperative Issues
evidence-based elements of perioperative care, each of which
may have only modest benefits when used in isolation, into a physical optimization
coordinated effort that can be expected to have a synergistic Evaluation and Optimization of Preexisting Organ Function
beneficial effect on surgical outcomes.5 The term fast track
has contributed to the misconception that the primary goal of Postoperative complications are related to preoperative
this approach is cost containment through the reduction of comorbid conditions,9 including inadequate nutrition.10
hospital stay; however, the primary goals are in fact to shorten Classification of functional capacity and optimization of
recovery time, decrease morbidity, and improve efficiency.6,7 organ function are expected to reduce cardiovascular and
The principles of fast track surgery are applicable to both other complications. The preoperative evaluation is also an
outpatient and inpatient procedures: many procedures that opportunity to improve long-term health apart from surgical
once necessitated hospitalization are now routinely performed considerations—for example, by counseling patients who
in an ambulatory or short-stay setting. may benefit from long-term beta blockade, smoking cessa-
A fast track surgery program encompasses preoperative, tion, or tightened glycemic control. A substantive discussion
intraoperative, and postoperative phases. The principal ele- of cardiopulmonary risk assessment and reduction is beyond
ments are as follows. the scope of this chapter; however, various current guidelines
and algorithms are available for assessment and reduction of
1. Preoperative patient education and preparation for surgery perioperative risk related to cardiac disease,11 pulmonary
(“prehabilitation”). complications,12 obesity,13 and diabetes.14
2. Newer anesthetic, analgesic, and surgical techniques, The perioperative period provides smokers with a good
whose aim is to decrease the surgical stress response, pain opportunity to quit. Smoking increases the risk of cardiac,
and discomfort, and postoperative nausea and vomiting. respiratory, and wound complications,15 and abstinence
3. Aggressive postoperative rehabilitation, including early reduces complications.16,17 Although reduction of pulmonary
enteral feeding and ambulation. This also includes changes complications requires an abstinence period of weeks to
DOI 10.2310/7800.S01C09
08/08
months, cardiac and wound complications are reduced after juice) up to 2 hours preoperatively increases gastric fluid
shorter periods.15 Smokers should be advised to quit and volume or exacerbates the risk of aspiration in otherwise
referred to resources that will help them do so. healthy adults.27,28 Current preoperative fasting guidelines
for adult patients undergoing elective surgery recommend a
Assessment and Optimization of Nutritional Status 2-hour fast for liquids and a 6-hour fast for solids.29 These
Poor nutritional status is an independent risk factor for recommendations do not apply to patients with delayed
complications after surgery. Patients with moderate and gastric emptying (e.g., from gastroparesis, GI obstruction, or
severe preoperative undernutrition benefit from preoperative upper GI tract malignancy).
nutritional support, preferably via the enteral route, for
at least 7 days preoperatively.10,18 Patients with less severe Preoperative Ingestion of Oral Carbohydrate Drink
malnutrition, including those with diminished oral intake as That it is safe to administer fluids up to 2 hours before
a consequence of their underlying disease, generally benefit surgery enables the use of high-carbohydrate drinks imme-
from the addition of oral nutritional supplements to their diately before operation. Emerging evidence suggests that it
normal diet. may be beneficial to provide a drink containing 100 g of
carbohydrate the evening before surgery and a second drink
Improvement of Physical Fitness containing a further 50 g 2 to 3 hours before induction of
The perioperative period may be associated with rapid anesthesia. This measure improves preoperative feelings of
physical deconditioning, requiring a period of recovery during thirst, hunger, and anxiety30; reduces postoperative insulin
which patients are fatigued and quality-of-life and activities resistance; and reduces the catabolic stress response to sur-
are curtailed. Given that patients with poor baseline exercise gery.31 Compared with control subjects, patients receiving
tolerance and physical conditioning are at increased risk preoperative oral carbohydrate drinks had less muscle loss32
for serious perioperative complications11,19 and prolonged dis- and better whole-body protein balance33 after major abdomi-
ability,20,21 it seems reasonable to hypothesize that improving nal surgery and had shorter hospital stays after colorectal
functional capacity by increasing physical activity before surgery.34 Preoperative carbohydrate drinks reduced nausea
surgery may be protective.22 Physical fitness can potentially and vomiting after laparoscopic cholecystectomy in one trial35
be improved significantly while patients are waiting for sched- but not in another.36
uled procedures: modest improvements in aerobic capacity
may be seen in older adults after training only 1 hour a day, patient education
four times a week, for 4 weeks.23 The strategy of augmenting Preoperative patient education is an essential component
physical capacity in anticipation of an upcoming stressor is of fast track surgery. For many patients, impending major
termed prehabilitation—as opposed to rehabilitation, which surgery represents a significant psychological stress. Greater
begins only after the injury or operation has taken place. preoperative emotional distress, depression, and anxiety are
Preliminary evidence supports the use of exercise pre- associated with poorer operative outcomes, including
habilitation before surgery. In one study, adults randomly increased pain, higher complication rates, poorer wound
assigned to exercise for 1 month showed faster healing of a healing, longer hospital stays, slower return to normal daily
punch-biopsy site than control subjects did.24 In another, activities, and reduced patient satisfaction.37,38 There is
a preoperative exercise program carried out by patients evidence that emotional distress delays wound healing by
awaiting lung cancer surgery improved exercise capacity to a altering endocrine and inflammatory responses.39,40 The
degree that mitigated the expected postsurgical decline.25 In results from meta-analyses suggest that preoperative patient
yet another study, patients receiving twice-weekly exercise education and preparation have positive effects on certain
training while waiting for coronary artery bypass graft surgery outcomes (e.g., pain, psychological distress, and indexes of
(CABGS) had shorter hospital stays and better preoperative recovery, including hospital stay), even if the intervention is
and postoperative quality of life than control subjects; the relatively brief and not individualized.40 For example, patients
quality-of-life differences remained for up to 6 months after who watched a video involving an actor outlining aspects of
surgery.26 Observational data suggest that simply instructing perioperative care after inguinal hernia surgery experienced
patients to walk 30 minutes daily in the perioperative period improved quality of life and faster resumption of baseline
may be beneficial, without the need for a formal individual- activities in comparison with control subjects.41
ized exercise program (F. Carli and associates, unpublished Patient expectation may also play a role in determining
data). postoperative outcome.42 Because the fast track recovery
program may differ from patients’ and caregivers’ expecta-
Preoperative Fasting tions for and previous experiences with hospitalization and
To reduce the risk of tracheal aspiration of gastric contents surgery, it is important to specify the active role the patient is
at the induction of general anesthesia, patients have tradition- expected to play. Such specification includes providing
ally had to refrain from oral ingestion of both solids and explicit written information about the benefits of the
liquids (nil per os [NPO]) from midnight of the night before program, the goals for daily nutritional intake and ambulation
the operation. This standard approach is convenient and in the early postoperative period, the discharge criteria,
easy to follow, but it requires patients to spend a long period and the expected hospital stay. Information about sensory
without hydration or nutrition, especially for operations experiences (e.g., pain, nausea and vomiting, and fatigue) are
scheduled in the afternoon. Solids may present a risk, but included in the discussion and the written materials, as well
there is no evidence that oral intake of water and other clear as guidelines regarding what to expect once they leave the
fluids (e.g., tea, coffee, apple juice, and pulp-free orange hospital.
08/08
premedication subjects and has been shown to facilitate the recovery period
In the past, preanesthetic medication was administered and decrease hospital admission after ambulatory surgical
with the intent of providing sedation and reducing anxiety. procedures.
Today, with the advent of same-day admission and fast track
surgery, premedication may play additional roles, including Intraoperative Issues
modulation of intraoperative hemodynamics and attenuation
of postoperative side effects.43 attenuation of surgical stress response
Benzodiazepines are excellent anxiolytics that possess Surgery initiates a series of metabolic and inflammatory
rapid onset of action and are flexible in use, being available responses that are involved in the pathogenesis of postopera-
in both IV and oral forms. Doses as small as 2 mg effectively tive morbidity and can slow the recovery process. These
reduce anxiety and anxiety-related complications.44 They
responses induce a transient but reversible state of insulin
also reduce the amount of anesthetic required and provide
resistance, the magnitude of which is linked to the invasive-
comfort. Opioids such as morphine and meperidine are no
ness of the surgical procedure. This state is characterized by
longer for premedicants in outpatient settings, because of
a decrease in peripheral glucose uptake and a concomitant
the prolonged duration of action and the high incidence of
increase in endogenous glucose production. The magnitude
side effects. Fentanyl has a better profile for fast track surgery
of this noxious response can be reduced by perioperative
and facilitates early hospital discharge. Acetaminophen and
cyclooxygenase-2 (COX-2) inhibitors (e.g., celecoxib) can be interventions that modify the catabolic response. These
administered either orally or rectally up to 1 hour before interventions can be classified as pharmacologic (high-dose
surgery and possess significant perioperative opioid-sparing opioids, neural blockade with local anesthetics, beta
effects.45 blockers, glucocorticoids, alpha2 agonists, nonsteroidal anti-
Anticholinergics (e.g., atropine and scopolamines) are inflammatory drugs [NSAIDS]), hormonal (insulin, growth
rarely used today, except for procedures such as laryngoscopy hormone, estrogens), physical (normothermia, MIS), and
or bronchoscopy, in which reduction of secretions is required. nutritional. Among these interventions, intraoperative and
These compounds are not given to elderly patients, because postoperative blockade of afferent neural nociceptive stimuli
they may trigger delirium; rather, glycopyrrolate (0.3 mg IV), by epidural and spinal block using local anesthetics has
which does not cross the blood-brain barrier, is preferred. been shown to be the most powerful modulator of the meta-
Beta blockers and alpha2 agonists can be used as adjuvants bolic and endocrine stress response. To be effective, however,
to fast track anesthetic techniques. With their anesthetic the neural blockade must be established before surgery and
and analgesic-sparing effects,46–49 these medications maintain continued for a minimum of 48 hours.56
perioperative hemodynamic stability and reduce postopera- For postoperative pain relief, epidural block achieved with
tive pain, thus facilitating the early recovery process. Beta a mixture of local anesthetics and opioids provides excellent
blockers (e.g., propanolol, atenolol, labetalol, esmolol) atten- postoperative analgesia at rest and during movement com-
uate the intraoperative rise in circulating concentrations of pared with systemic opioids,57 thus facilitating resumption of
catecholamines, promote hemodynamic stability during dietary intake and utilization of nutrients,58 attenuating the
emergence from anesthesia and in the early postoperative loss of body mass, and allowing earlier resumption of exer-
period, and prevent perioperative cardiovascular events in cise.59 Epidural block also affects insulin resistance, attenuat-
elderly patients undergoing noncardiac surgery50 and patients ing the hyperglycemic response, facilitating the oxidative
with preexisting coronary artery disease.51,52 In addition, utilization of exogenous glucose,60 and thereby preventing the
preliminary evidence that beta blockers possess anticatabolic postoperative loss of aminoacids and saving almost 100 g of
properties and anesthetic and analgesic-sparing effects sug- lean body mass daily.61 The extent of protein sparing has
gests that they may play a role in accelerating the recovery been found to be greater than that previously achieved with
process.53 Alpha2 agonists (e.g., clonidine or dexmedetomi- hormonal and nutritional interventions. Epidural block has
dine) have also been used as premedicants with the goal
anticatabolic effects, and patients can be rendered anabolic
of reducing the need for opioid analgesics and attenuating
with the concomitant administration of glucose and amino-
sympathoadrenergic and hypothalamopituitary responses.
acids62 or aminoacids alone; the advantage of the latter is
Clonidine shortens the duration of paralytic ileus after
that it is not associated with hyperglycemia.63–65 Preoperative
colorectal procedures54 and decreases the incidence of post-
oral or IV carbohydrate administration also reduces postoper-
operative nausea and vomiting (PONV). Both clonidine and
dexmedetomidine have been shown to reduce the incidence ative insulin resistance, thus decreasing postoperative catabo-
of myocardial ischemia.55 lism and resulting in less fatigue.66–68
Antacids and H2-receptor antagonists can be administered A single dose of glucocorticoids given at induction of anes-
before surgery in subjects at risk for gastric aspiration (e.g., thesia decreases the inflammatory response without causing
those who are diabetic, obese, or pregnant; have gastroesoph- any significant side effects. Beta blockers also reduce cardiac
ageal reflux disease; or have sustained a stroke). H2-receptor demands and sympathetic stimulation and have been shown
antagonists are given the evening before surgery and in to attenuate catabolism in burn patients.53 MIS attenuates the
the morning to decrease the volume and acidity of gastric inflammatory response but not the endocrine one. Although
content. A nonparticulate antacid (e.g., sodium citrate) is it is not clear to what extent MIS modulates catabolism,
given 1 hour before surgery to raise the gastric pH. the administration of dextrose after laparoscopic colon
Administration of anti-PONV medications such as dexa- surgery results in a significant suppression of endogenous
methasone and odansetron before or during the induction glucose production (an index of gluconeogenesis), with no
and maintenance of anesthesia is recommended in high-risk protein-sparing capacity.69 This implies enhanced whole-body
08/08
glucose uptake and greater utilization and oxidation of exo- reducing postoperative respiratory complications as a result
genous glucose. Insulin, growth hormones, and anabolic ste- of residual muscle paralysis.
roids have been shown to improve wound healing, directing In summary, short-acting anesthetic drugs and adjuvants
aminoacids toward anabolic pathways to enhance lean tissue minimize postoperative side effects and enhance the ability to
synthesis. fast track patients after both ambulatory and major inpatient
surgical procedures. Not surprisingly, combining short-acting
anesthetic techniques
anesthetic techniques with an educational program has been
General Anesthesia reported to increase fast tracking significantly in ambulatory
centers. Although a majority of adults can be fast-tracked
After general anesthesia for fast track surgery, the patient
after ambulatory surgery under general anesthesia, minimiz-
should be able to walk out of the hospital with minimal
ing patient discomfort and anxiety is critically important for
side effects. Therefore, the choice of anesthetic agents
establishing a successful fast track surgery program for all
should include fast-acting IV drugs and less soluble volatile
types of elective surgery.
anesthetics, along with adjuvants to minimize the side
effects. Regional Anesthesia
Propofol is the IV agent of choice for induction of fast track
Regional anesthetic techniques (spinal, epidural, and
anesthesia.70 For maintenance of anesthesia, highly soluble
peripheral nerve blocks) have several advantages over general
volatile anesthetic agents, such as desflurane and sevoflurane,
anesthesia—including improved pulmonary function,
offer advantages over propofol and isoflurane, in that they
decreased cardiovascular demand, a lower incidence of ileus,
facilitate early recovery.71–73 Nitrous oxide (50–70%) remains
and good quality of analgesia at rest and on ambulation—
a popular adjuvant during the maintenance period because
both when used in place of GA and when used as adjuvants.
of its anesthetic- and analgesic-sparing effects, low cost,
The appropriate combination of a local anesthetic with an
and favorable pharmacokinetic profile;74 however, it is not
adjuvant will facilitate readiness for discharge. Consequently,
recommended in subjects at risk for PONV, nor is it suitable
epinephrine should not be added to spinal local anesthetics,
for laparoscopic surgery when the operating time is longer
because it might delay time to micturition; however, fentanyl
than 1 hour. Prolonged use of nitrous oxide causes bowel
in small doses does not interfere with bladder function.88,89
distention (the so-called gas effect) and predisposes to
PONV. When general anesthesia is maintained with volatile Faster recovery of sensory and motor function results when
anesthetic agents, there is an increased risk of PONV in minidose lidocaine (10–30 mg), bupivacaine (3.5–7 mg), or
the early postoperative period; accordingly, it is suggested ropivacaine (5–10 mg) spinal anesthetic techniques are com-
that low-dose droperidol (0.625 mg) and dexamethasone bined with a potent opioid analgesic (e.g., fentanyl [10–25 µg]
(4–8 mg) should be sued to provide effective antiemetic or sufentanil [5–10 µg]).90,91 However, postoperative side
prophylaxis.75 Titration of both IV and inhaled anesthetics effects (e.g., pruritus, nausea) are increased when intrathecal
using cerebral monitoring devices may also facilitate the opioids are used.
fast track process,76–79 except in spontaneously breathing Thoracic epidural blockade is the most effective technique
patients.80 for postoperative analgesia. Whether in the form of a con-
With regard to opioids, fentanyl remains a good choice, tinuous infusion or of patient-controlled analgesia (PCA),
though infusion of the ultra–short-acting opioid remifentanil epidural analgesia results in better static and dynamic pain
(0.05–0.15 µg/kg/min) is an increasingly popular alternative relief than IV opioid–based PCA delivery systems.92 Epidural
for short and painful conditions. Whereas intraoperatively block with local anesthetics reduces the endocrine and meta-
administered fentanyl can maintain some residual effect bolic responses to surgery, improves pulmonary outcome
during the postoperative period, remifentanil is rapidly after major abdominal and thoracic operations (e.g., aortic
metabolized; thus, one must remember that as soon as the surgery93 and thoracoabdominal esophagectomy),94 and facil-
remifentanil infusion ends, the patient can be in serious pain. itates the return of bowel function, while resulting in better
Long-acting opioids must therefore be administered in due preservation of perioperative nutritional profiles, higher
time. The use of nonopioid analgesics (e.g., NSAIDs, [includ- health-related quality-of-life scores, and improved exercise
ing COX-2 inhibitors], acetaminophen, alpha2 agonists, capacity after colon surgery59; however, it has not been found
glucocorticoids, ketamine, and local anesthetics in the wound) to affect the duration of hospitalization. Over the past
are recommended as part of a multimodal analgesic regimen 20 years, several randomized controlled studies and meta-
aimed at reducing opioid-related side effects.81,82 Adjuvants analyses have been conducted to study the effect of spinal
such as beta blockers and lidocaine have had some success in and epidural block on postoperative outcome. One large
reducing opioid use during and after laparoscopic surgery. meta-analysis reported that morbidity and mortality were
These compounds represent an alternative to short-acting significantly lower with spinal and epidural analgesia than
opioids in controlling for any associated acute autonomic with general anesthesia and systemic opioid analgesia,95 but
responses.83–85 these benefits could not be demonstrated in several subse-
Short- or intermediate-acting muscle relaxants are used quent randomized, controlled trials. However, these studies
for fast track surgery because they often do not need to were not controlled for factors that might influence the
be reversed. A novel agent, sugammadex (a cyclodextrin stress response, including hypothermia, immunosuppression,
compound),86 has been shown to provide faster reversal of hypoxemia, perioperative surgical and nursing care, infection,
nondepolarizing muscle relaxants without anticholinergic and the use of drains and tubes. One might therefore
side effects,87 thus facilitating earlier tracheal extubation and assume that the beneficial effects of regional anesthesia on
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postoperative mortality and morbidity are most apparent maintenance of normothermia

when it is used as part of a multimodal therapeutic regimen During major surgery, body temperature falls by approxi-
in which all evidence-based therapeutic strategies have been mately 1° to 2°C as a result of loss of body heat and inhibition
put in place. of the thermoregulatory response. Whereas a small drop in
With regard to some biologic outcome measures, thoracic core temperature is not a cause for concern in fit and healthy
epidural analgesia with a local anesthetic and administration persons, it can be detrimental in elderly, malnourished, or
of opioids reduce ileus and lead to faster discharge after frail persons with cardiorespiratory and metabolic instability.
colonic surgery in patients enrolled in a fast track program Mild hypothermia elicits a stress response during the recovery
(i.e., in patients being treated with multimodal techniques period while the patient attempts to regain normothermia by
that include preoperative preparation, attenuation of the means of shivering and vasoconstriction. It results in increased
intraoperative stress response, multimodal analgesia, early cardiovascular demands, elevated oxygen consumption,
oral feeding and mobilization, and early removal of drains hypoxia, and impaired coagulation and leukocyte formation.
and tubes).6,96 A role for epidural analgesia as part of a Maintenance of intraoperative normothermia with the use
multimodal analgesia technique has also been suggested of active and passive warming devices in conjunction with
in the setting of fast track cardiac anesthesia,97–100 in which aggressive postoperative management of shivering and resid-
epidural local anesthetics have been associated with earlier ual hypothermia decreases the incidence of wound infections,
tracheal extubation, decreased pulmonary complications and blood loss, myocardial ischemia, and protein breakdown.114
cardiac dysrhythmias, reduced postoperative pain and opioid fluid management
analgesic requirements, shorter stays in the intensive care
Intraoperative fluid management strategy remains contro-
unit (ICU), and faster recovery of bowel and bladder func-
versial, in that adverse outcomes may be associated with
tion.101–103 However, with advances in MIS, the perioperative
both inadequate and excessive fluid administration.115–117
use of mu-receptor antagonists and other analgesia adjuvants, Inadequate fluid administration can lead to a reduction in
and the advent of fast track accelerated recovery programs effective circulating volume, with diversion of blood towards
in which all surgical, anesthetic, and nursing care elements the brain and heart and away from the gut, skin, and kidneys.
are revised according to scientific evidence, the role of Liberal (as opposed to restrictive) IV fluid administration
thoracic epidural technique in some types of surgery must be improves gut perfusion and increases left ventricular stroke
reconsidered.104 volume. In contrast, excessive IV fluid administration may
result in adverse effects. Excess fluid in the intravascular
Incisional Local Anesthesia
compartment leads to increased venous pressure and pulmo-
Infiltration of local anesthetics into the surgical wound is nary and peripheral edema that may compromise peripheral
an effective analgesia technique for minor surgical procedures oxygenation. Two studies have suggested that excessive
(e.g., hernia repair, anal surgery, and breast procedures). hydration can increase postoperative morbidity and lengthen
When possible, local infiltration should be performed before the hospital stay after major abdominal surgery.118,119 In these
the surgical incision is made and should be a component studies, perioperative water and salt restriction reduced car-
of all balanced fast track anesthetic techniques.105,106 Better diopulmonary and tissue healing complications and prevented
analgesia results when the infiltration of local anesthetics is hyperchloremic metabolic acidosis after abdominal surgery.
supplemented with a peripheral nerve block (e.g., ileoinguinal On the other hand, after laparoscopic cholecystectomy, large
block for inguinal hernia repair).106 Compared with neuro- volumes of intraoperative fluid have been associated with
axial or general anesthetic techniques, local anesthetic reduced side effects (e.g., pulmonary dysfunction, dizziness,
infiltration techniques reduce the risk of postoperative urinary drowsiness, thirst, and PONV) and a shorter hospital stay.120
retention associated with anorectal surgery107 and inguinal Although aggressive crystalloid administration during colorec-
herniorrhaphy.108,109 The instillation of local anesthetics on tal surgery improves tissue oxygenation,117 it does not reduce
the visceral peritoneum during laparoscopy has only weak the risk of surgical site infection (SSI).121
Perioperative fluid administration should take into account
and short-lasting analgesic effects.110
preoperative dehydration resulting from fasting and bowel
Continuous wound infusion with local anesthetics has been
preparation, replacement of blood loss and secretions, and
used for abdominal, gynecologic, and thoracic operations,
maintenance hydration. The volume and composition of the
and many studies have shown it to yield improved analgesia,
fluid, together with the type of surgery performed and the
greater patient satisfaction with pain management, reduced patient’s hemodynamic requirements, influence the duration
PONV, and shorter hospital stay.111 Continuous infusion and magnitude of intravascular volume expansion. Intra-
of bupivacaine at the median sternotomy incision site after operative esophageal Doppler monitoring can facilitate goal-
cardiac surgery not only provides good postoperative pain directed fluid administration by targeting specific values for
relief but also allows patients to ambulate earlier, leading to the cardiac index. Several studies have been conducted on
a shorter hospital stay.112,113 A systematic review of random- different types of surgical procedures, and the outcomes have
ized trials of the efficacy of continuous wound irrigation with been positive (shorter length of hospital stay, lower incidence
local anesthetics for postoperative analgesia demonstrated of admission to ICU, and fewer complications) when fluid
good analgesia and opioid-sparing, with reduced side effects.111 administration was guided by a predetermined stroke volume
Nevertheless, the quality of analgesia can be highly variable and filling pressure.122,123 Therefore, strategies that avoid both
even in a given patient or a given type of surgery, which hypovolemia and postoperative fluid overload are important
highlights the difficulty of interpreting the results. in facilitating the fast track recovery process.
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minimization of incision size and use of mis The use of peripheral nerve blocks and conduction block-
The size and orientation of the surgical incision are dic- ade for major and minor surgical procedures in combination
tated primarily by the location and extent of the pathology, with adjuvants provides excellent analgesia, though not
always consistently. One reason for partial analgesic failures
the need for exposure, the requirement for stoma placement
might be that too often, the analgesia regimen has not been
(if applicable), the likelihood of further abdominal surgery,
optimized for a specific procedure. Accordingly, various
and the patient’s body habitus. The incision should be as
procedure-specific analgesic regimens have been developed.
small as possible while allowing adequate exposure. Trans-
On the basis of published evidence, the addition of either
verse incisions are used when possible by some fast track NSAIDs or regional analgesia and beta blockers to opioids
colorectal groups (though not by all). A meta-analysis found enhances the quality of analgesia and exerts significant
clinical outcomes after transverse or midline incisions to be opioid-sparing effects.145 At present, the evidence does not
similar overall.124 support adding acetaminophen to an opioid; however, the
Laparoscopic techniques are used when possible. In com- combination of acetaminophen with an NSAID provides
parison with conventional open surgery, laparoscopic surgery better analgesia than either drug alone. More work is needed
is associated with better preservation of systemic immune to verify whether the combination of several nonopioid
function,125,126 less pulmonary compromise,127 a lower inci- analgesics could produce good analgesia with minimal
dence of ileus,128 a shorter hospital stay, and earlier resump- side effects.81 In the meantime, the current strategy for
tion of regular activities.129–134 In addition, the risk of SSI,135 postoperative analgesia involves a combination of regional
incisional hernia,136,137 and small-bowel obstruction138 may be and local anesthesia, MIS, and nonopioid pharmacologic
reduced with laparoscopic approaches. interventions.
In the setting of colorectal surgery, it is unclear at present
postoperative nausea and vomiting
whether the laparoscopic approach further improves on the
short-term recovery benefits already seen with multimodal PONV continues to be a common complication of surgery,
rehabilitation programs; benefits have been reported in some with an overall estimated incidence of 20 to 30%. PONV
studies138,139 but not in others.140,141 delays discharge from the postanesthesia care unit (PACU)
and is the leading cause of unanticipated hospital admission
in ambulatory surgical patients. Vomiting increases the risk of
Postoperative Issues aspiration and has been associated with suture dehiscence.
Nausea and vomiting remain the most common reasons for
pain management
poor patient satisfaction during the postoperative period. In
Pain remains the most common reason for delaying one study, a simplified risk factor chart was developed that
discharge after ambulatory surgery,142 while good analgesia identified four main risk factors for PONV: female sex,
accelerates restoration of function and improves recovery [see nonsmoking status, a history of PONV, and opioid use.146
1:6 Postoperative Pain].143 Although there is no direct relation The incidence of PONV in patients with none, one, two,
between analgesic techniques and postoperative morbidity three, or all four of these risk factors was approximately 10%,
and mortality,144 optimal pain control, in combination with 20%, 40%, 60%, and 80%, respectively. In a large study of
other interventions, remains a priority for the physician in the 18,000 ambulatory patients, general anesthesia was associ-
perioperative period. The pathophysiology of postoperative ated with an 11-fold higher incidence of PONV than regional
pain is characterized by a combination of nociceptive stimuli or local anesthesia was.147 The risk of PONV has also been
from the wound, inflammation and sensitization of peripheral shown to increase with longer operating times.
somatic and visceral nerve terminals and central neurons, and Consensus guidelines for managing PONV recommend
inhibition of central descending control. It is therefore neces- intraoperative pharmacologic strategies designed to compen-
sary to approach pain in a multidisciplinary fashion, whereby sate for baseline risk factors and modify the incidence of this
different treatment modalities complement each other with complication. Currently available antiemetics may act at the
the aim of improving analgesia while minimizing the side cholinergic (muscarinic), dopaminergic (D2), histaminergic
(HI), or serotonergic (5-HT3) receptors. NK-1–receptor
effects associated with each treatment.
antagonists are also being investigated. A 2000 study intro-
Opioids remain the most successful compounds for post-
duced the concept of a multimodal approach to management
operative pain control, but they are associated with several
of PONV in high-risk patients, utilizing total IV anesthesia
important side effects (e.g., acute opioid tolerance, hypoven-
(TIVA) with propofol and remifentanil, ketorolac, no nitrous
tilation, sedation, ileus, nausea and vomiting, and urinary oxide, no neuromuscular blockade, IV hydration, ondanse-
retention), any of which may delay hospital discharge. Accord- tron, droperidol, and dexamethasone.148 This approach
ingly, it is sensible to consider multimodal analgesia as the resulted in a 98% complete response rate (i.e., no PONV
next step in providing optimal pain control. In this approach, and no antiemetic rescue). A subsequent study comprising
the synergistic or additive effects of a variety of analgesics 5,000 patients employed a multifactorial design to evaluate
are exploited, allowing the individual doses to be reduced three antiemetic interventions (ondansetron [4 mg], droperi-
and thereby minimizing individual drug-related side effects. dol [1.25 mg], and dexamethasone [4 mg]) and three anes-
Intraoperative use of adjuvants such as ketamine, clonidine, thetic interventions (TIVA with propofol, omission of nitrous
dexmedetomidine, adenosine, gabapentine, dexamethasone, oxide, and substitution of remifentanil for fentanyl) for PONV
lidocaine, beta blockers, magnesium, and neostigmine has prophylaxis.149 Each antiemetic reduced the risk of PONV
an opioid-sparing effect during the whole perioperative by approximately 26%. The efficacy of the interventions
period. was dependent on the patient’s baseline risk. The greatest
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absolute risk reduction from the intervention was achieved patients.10 After colorectal surgery, feeding before complete
in the patients at high risk for PONV. Consensus guidelines return of peristalsis is tolerated by most patients.159 Meta-
for management of PONV do not currently recommend analysis of randomized trials comparing early enteral or oral
prophylaxis for patients at low risk for PONV. For those at feeding with fasting after various types of elective GI surgery
moderate risk, combination therapy with two antiemetic found no obvious advantages to keeping patients on NPO
agents is recommended. For those at high risk, combination status, with several studies suggesting that early feeding
therapy with three antiemetic agents is recommended. In offered benefits, such as decreased overall infectious compli-
patients who experience PONV despite receiving prophylaxis, cations and reduced length of stay. Although the risk of
an antiemetic regimen acting at a different receptor should be vomiting is somewhat higher with early feeding, the risk of
used for rescue within the first 6 hours after surgery.150 After anastomotic dehiscence is not increased.160 One caveat is that
6 hours, PONV can be treated with any of the drugs used for most studies of early oral feeding involve patients undergoing
prophylaxis except dexamethasone and scopolamine. Other colorectal resection, which means that the results may not be
useful adjuvants to standard antiemetic drugs include beta applicable to patients with upper GI anastomoses.
blockers, alpha2 agonists, acupuncture, acupressure, and In fast track surgery, the protocol should be tailored in
transcutaneous electrical nerve stimulation (TENS).151,152 accordance with the procedure being done and by the patient’s
tolerance (e.g., as evidenced by PONV and abdominal dis-
ileus tention). After most types of abdominal surgery, patients are
Postoperative ileus is defined as a temporary paralysis of encouraged to take liquids on the night following the opera-
the gut after major surgical procedures. It occurs as a conse- tion, with light solids given on the morning of postoperative
quence of sympathetic reflexes resulting from surgery and day 1 and a normal diet initiated on postoperative day 2.
pain and of production of local and systemic inflammatory Protein-rich drinks are given between meals. This approach
mediators. The effect on bowel motility can last up to allows patients to resume recommended energy and protein
72 hours in the colon. Ileus causes discomfort and delays oral intake in just a few days and preserves lean body mass,
food intake, thereby prolonging recovery and the duration of particularly when combined with thoracic epidural analgesia
and early mobilization.161 Setting specific daily goals that are
hospitalization. The most effective technique for reducing
understood by the patients and formulating protocol-based
ileus is continuous thoracic epidural administration of local
orders for the nursing staff are important for achieving
anesthetics to block sympathetic visceral innervation and
adequate oral intake of calories and protein, given that simply
reestablish the balance between vagal and sympathetic
starting clear fluids on postoperative day 1 without a
neural influence on the gut. Other interventions, such as early
structured, written plan does not prevent negative nitrogen
feeding, prokinetics like metoclopromide and cisapride
balance.162
(currently unavailable because of a high incidence of cardiac
In patients for whom early oral feeding is not possible
dysrhthymias), prophylactic nasogastric intubation, have only
(e.g., those who have undergone major head and neck
minor effects on the occurrence of ileus. In the past few years,
surgery, esophageal or gastric anastomoses, or pancreatico-
there has been some interest in the mu-receptor antagonist
duodenectomy), especially in those who were undernourished
alvimopan, which may reduce the effect of opioids on the preoperatively, enteral tube feeding should be considered.
gut mucosa, favor the restoration of bowel function, and This is done via a tube placed distal to the anastomosis at
accelerate hospital discharge.153–155 the time of surgery; either a nasojejunal tube or a feeding
Within multimodal programs in GI surgery, the combina- jejunostomy may be employed. Enteral feedings are started at
tion of epidural analgesia using diluted concentrations of a low rate (10–20 mL/hr) within 24 hours after the procedure
local anesthetics and minimal amounts of opioids, aggressive and are slowly increased over the next few days as the patient’s
PONV prophylaxis, and early oral feeding and mobilization tolerance permits.10
has been found to shorten the duration of ileus.96 There is In undernourished patients, oral nutritional supplements
also evidence that reduced perioperative sodium administra- are continued for 10 weeks after discharge; this approach
tion and avoidance of fluid excess153 are associated with results in less weight loss, faster weight regain, better
earlier return of bowel function after abdominal surgery and preservation of muscle mass and grip strength, and improved
a shorter hospital stay.156 IV infusion of lidocaine during quality of life.163
surgery and the first 24 postoperative hours has been shown
to minimize ileus and facilitate dietary intake.85,157 mobilization
Postoperative bed rest should be discouraged. In addition
postoperative feeding
to impairing pulmonary function and predisposing to
GI motility is predictably decreased after major abdominal thrombotic complications,164 bed rest reduces exercise
surgery, with colonic motility requiring 3 to 5 days to recover. capacity in a linear fashion165 and decreases muscle mass166
On the assumption that bowel rest shortens the duration of and strength167 (a result that may be related to the develop-
ileus and protects anastomoses, patients have traditionally ment of postoperative fatigue168). Although the association of
been kept fasting until peristalsis has returned throughout the early postoperative mobilization with faster recovery and
entire GI tract, as evidenced by passage of flatus or stool158; lower pulmonary and thrombotic complications has been
a step-wise progression of oral intake is then allowed, result- acknowledged since the 1940s,169 modern surgical patients
ing in a planned minimum perioperative starvation period of actually spend very little time out of bed in conventional
several days. Yet after abdominal surgery, interruption of oral care plans. For example, patients in the control arm of a
intake is actually neither necessary nor beneficial in most trial comparing fast track care with conventional care after
08/08
colorectal resection spent a median of 8 minutes out of bed of afferent and efferent nervous impulses from and to the
on postoperative day 1, despite having been given thoracic bladder, it is customary to keep the bladder catheterized for
epidural analgesia.170 In an observational study of patients as long as epidural analgesia is in force. However, urinary
who had undergone upper abdominal surgery, the total catheters may cause discomfort and impede mobilization.
median upright mobilization time was only 34 minutes on In addition, the risk of urinary infection increases with the
postoperative day 4, and mobilization time predicted length duration of catheterization.185 Urinary infections prolong the
of stay.171 hospital stay, are expensive to treat, and cause unpleasant
Structured postoperative mobilization is an important symptoms. The incidence of urinary retention after epidural
component of fast track surgery protocols, and patients analgesia has been reported to be between 18 and 23%.186
should be given explicit written instructions preoperatively In one study, as part of an accelerated recovery program,
that outline the benefits of early mobilization. These instruc- bladder catheterization was discontinued 24 hours after colon
tions include specific goals for each day, which are also surgery in 102 patients receiving continuous postoperative
included in the postoperative nursing orders. The nursing epidural analgesia; the incidence of bladder recatheterization
culture and the ward environment should encourage and was low (only 9%).187 Accordingly, current practice, unless it
enable patient independence. Adequate pain control using is contraindicated by the type of surgery or by the need for
thoracic epidural analgesia with local anesthetics facilitates ongoing monitoring of urinary volumes, is to remove urinary
effective early mobilization.4 Asking patients to maintain a catheters 24 to 36 hours after the surgical procedure.
diary of the time spent out of bed and walking or suggesting discharge criteria
that they use a pedometer to self-monitor their ambulation
may help with compliance. Placing a wall chart at the bedside Patients can be discharged home when their oral intake is
that lists mobilization and diet goals for each day is also adequate, their pain is well controlled with oral analgesics,
helpful.172 they are voiding without difficulty, they are passing flatus or
Because patients in fast track protocols spend significantly stool, they ambulating independently or at baseline levels,
more time out of bed in the first postoperative week, the they feel ready for discharge, and they are able to care for
decrease in voluntary muscle strength traditionally seen after themselves at home.4 Yet even within an enhanced colorectal
major abdominal surgery is prevented.173,174 The importance recovery program, only 30% of patients are actually dis-
charged on the day of functional recovery; thus, it is clear that
of early mobilization may be independent of other elements
length of stay is not determined solely by medical factors but
of the protocol, in that compliance with “out-of-bed” day 0
is also greatly influenced by social and cultural factors.175
has been found to be a significant predictor of hospital stay,
even after other fast track elements, patient characteristics, postdischarge follow-up
presence of complications, and additional factors have been
Because of the earlier hospital discharge with fast track
adjusted for.175
programs, it is important that patients be able to contact a
use of drains and catheters team member easily should problems like fever, wound
redness or discharge, PONV, or worsening abdominal pain
Routine use of nasogastric tubes and abdominal drains
arise. A follow-up telephone call should routinely be made
after abdominal surgery is not supported by the evidence; 24 to 36 hours after patients go home. Patients should be
instead, selective use, based on clinical circumstances, is seen between postoperative day 7 and 10 so that the wound
indicated. Drains and catheters impede independent ambula- can be checked and their overall status assessed, then seen
tion,171 can be painful, and may pose a psychological barrier again at 1 month after the operation. Depending on the
to recovery.7 A meta-analysis of randomized trials concluded planned discharge day, the risk of readmission after fast track
that routine nasogastric decompression after abdominal colon surgery ranges from 10 to 20%.
surgery does not hasten recovery from ileus, increases Studies of the duration of convalescence after abdominal
pulmonary complications after upper abdominal surgery, is surgery report great discrepancies in the time away from
uncomfortable, and should be abandoned.176 With respect to regular activities; these discrepancies are partly attributable to
foregut surgery, anastomotic leaks were not increased in two variations in how patients are instructed.188 Very little infor-
randomized trials of routine versus selective nasoenteric mation is available about the recovery period after surgery,
decompression after partial or total gastrectomy.177,178 and a standardized approach to measurement of surgical
Similarly, reviews of randomized trials do not support the recovery is lacking. After discharge, patients are given specific
use of routine prophylactic drainage for colorectal anastomo- written instructions outlining the expected recovery course.
ses,179 thyroid surgery,180 cholecystectomy,181,182 uncompli- They are encouraged to continue the exercise program begun
cated liver resection,183 or pancreatic resection.184 Routine preoperatively, with a goal of 30 to 60 minutes of exercise per
drainage is associated with an increased SSI rate and a day. Undernourished patients continue to receive oral nutri-
longer hospital stay after laparoscopic cholecystectomy,181 an tional supplements. No specific restrictions are placed on the
increased hospital stay after thyroid surgery,180 and increased resumption of specific activities.
SSI and chest infection rates after open cholecystectomy182; it
does not lower the incidence or improve the diagnosis of other components
anastomotic leaks after colon surgery,181 nor does it decrease The preceding discussion outlines many of the more
abdominal sepsis after pancreatic resection.184 common components of multimodal perioperative rehabi-
It is common practice to catheterize the bladder just before litation. Specific programs may include a variety of other
major operations to monitor postoperative urine output and interventions, such as the administration of probiotics, the
prevent the development of postoperative urinary retention. avoidance of standard mechanical bowel preparation,189 and
Because epidural local anesthetics block the transmission the use of prokinetics and laxatives.4,6
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Implementation of Fast Track Surgery Program and expansion of the role played by the surgeon or peri-
operative caregiver in the preoperative phase. Certain surgical
organizational issues techniques (e.g., the use of transverse incisions or MIS)
Implementation of a multimodal rehabilitation requires may require surgeons to hone new skills; similarly, the sig-
substantial resources and effort. Success depends on the nificant role of thoracic epidural analgesia and pharmacologic
ability of the leader to interface with numerous stakeholders modulation of the stress response to surgery may require
over time in order to reach a multidisciplinary consensus. anesthesiologists to play a dramatically expanded role. Early
Several aspects of perioperative care (e.g., the use of drains, ambulation, goal-driven protocols for oral nutritional supple-
dietary and activity restrictions, and fluid management) that mentation, the presence of thoracic epidural analgesia, and
may have been passed down through generations of training early withdrawal of urinary catheters significantly change
are abandoned or significantly revised in fast track protocols. the way nursing care is provided on the postoperative ward.
In addition, the differences in patient preparation and Although guidance from published studies of successful
education necessitate revision of information given to patients fast track programs is available, especially in the colorectal
Table 1 Organization of Multimodal Perioperative Care Plan for Specific Procedure or Group of Procedures1
Step Personnel Involved Specific Task Time Line Comments

1. Develop protocol Everyone who interfaces Write pathway Meetings Requires committed leader and
with surgical patient: for 1–2 team members with ability to
surgery, anesthesia, hr/wk for reach consensus; requires
nursing (preop, postop, 1–2 mo significant time and energy
postdischarge), commitment
nutrition, psychology,
physiotherapy, pharmacy
2. Outline specifics of Surgeon Evaluate need for routine ~25 hr Emphasis on optimization of
preoperative Consulting internist tests; standardize cardiopulmonary disease,
preparation Nutrition strategy for prevention of glycemic control, prevention of
Physiotherapy complications; optimize infectious and thrombotic
nutrition and fitness complications, smoking cessation,
alcohol, weight loss
3. Develop anesthesia and Anesthesiology/pain service Optimize regional 1–2 mo May require special training for
analgesia programs Surgery techniques to reduce thoracic epidural analgesia and
Nursing stress response other neural blocks; requires post-
Pharmacy and optimize pain operative protocol for nursing
management unit
4. Minimize stress of Anesthesiology/pain service Optimize anesthetic Give short-acting opioids or short-
surgery Surgery technique; minimize acting muscle relaxants; use local
Nursing incision size; prevent anesthetics in thoracic epidural;
hypothermia preferably use vasopressor for
hypotension versus overhydration
5. Adjust postoperative Surgery Modify routine use of Create standard postoperative
care according to Nursing nasogastric tubes, drains, orders
evidence Pain service and bladder catheters;
protocolize feeding and
ambulation with specific
daily goals
6. Develop postoperative Nursing Enforce feeding, ambula- Staff may benefit from visiting an
nursing care programs Physiotherapy tion and sleeping established program
Nutrition protocols; determine
hospital discharge
criteria
7. Determine methods for Surgeon Arrange telephone Standardize discharge orders and
follow-up Nursing follow-up and office visit instructions, including nutrition
Surgical assistant and physical activity; develop
Pharmacy protocols for response to nausea,
vomiting, pain, fever, wound
problems
8. Develop patient All team members, possibly Develop standard oral,
information program headed by patient written, and electronic
educator material to educate
patient before operation
9. Document results and All team members, perhaps Choose outcome measures Identify methods for reassessment
tabulate problems and headed by data manager and method of follow-up and pathway failure
patient satisfaction;
revise and improve
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surgery literature, there are no off-the-shelf protocols, and 4. Write, circulate, and revise the protocol.
local differences in expertise, experience, and resources will 5. Implement the plan.
inevitably shape the development of the protocol for each 6. Measure the outcomes with timely feedback.
individual center. To further complicate implementation, 7. Revise the protocol in the light of the outcomes.
each surgical procedure or family of procedures requires an Once the protocol is introduced, there is an adjustment
individual protocol with specialized input from a team that and learning period for the medical and nursing personnel,
is experienced in caring for this subset of patients. Even which is estimated to last about 1 year.190
after the protocol is implemented, compliance remains an Examples of multimodal perioperative care plans for
important issue that necessitates ongoing monitoring and inpatient and outpatient surgical procedures are available
adjustment, particularly to ensure compliance with the post- [see Table 2, Table 3, Table 4, and Table 5].
operative components.175 Creating the protocol is necessary
for success but not sufficient to ensure it; even within a fast contraindications
track program, patients cared for by surgeons who are new Whether fast track surgery is applicable to a wide variety
adopters have longer hospital stays than those cared for by of patients and procedures has been questioned. Fast track
surgeons experienced with the protocol.172 protocols seem to be feasible for most patients undergoing
The implementation process has been well described1 and elective colon surgery, as demonstrated by a report from 24
includes the following major steps [see Table 1]: German centers of various sizes and affiliations that volun-
1. Assemble the relevant stakeholders (the multidisciplinary tarily adopted the same fast track protocol.191 Compliance
team). and outcomes were prospectively documented in more than
2. Examine the evidence for components of perioperative 1,000 patients with a median age of 66 years. More than 30%
care. of the patients had significant comorbid disease (American
3. Interpret the evidence in the light of local experience, Society of Anesthesiologists [ASA] class 3 or 4). Compliance
patient population, resources, and so forth. with the protocol was high, with more than 85% of the
Table 2 Sample Multimodal Perioperative Care Plan for Elective Colorectal Resection
Preoperative assessment and optimization

Evaluation of medication compliance and control of risk factors: hypertension, diabetes, COPD, smoking, alcohol, asthma, CAD,
malnutrition, anemia
Psychological preparation for surgery and postoperative recovery: explanation of preoperative bowel preparation, importance of generous
clear fluid intake up to 2 hr before surgery, intraoperative and postoperative trajectory and hospital stay (2–4 days for nonrectal
surgery, > 4 days for rectal surgery), immediate postoperative mobilization, early oral intake, presence of routine bladder catheter for
24 hr
Physical preparation with exercises at home: anaerobic and resistance 1–2 hr/day, gradual increase from 50% to 80% of maximum
capacity, breathing exercises
Surgical considerations: laparoscopic or laparotomy, risk of SSI, drains, bleeding risk, strategies for blood loss reduction.
Familiarization with epidural analgesia: occasional numbness in lower extremities, short spells of hypotension, pain assessment at rest and
on coughing and walking, care of the epidural catheter, explanation of possible risks (hematoma and paralysis, pain and abscess)
Nutritional preparation: oral nutritional supplements for patients with diminished oral intake or mild undernutrition
Intraoperative management
Anesthetic management
Allay anxiety with midazolam and good hydration. Insert epidural catheter at appropriate intervertebral level (T7–8 for right, transverse,
and left hemicolectomy; T9–10 for sigmoid and rectal resection). Use local anesthetics, and test epidural blockade for bilateral spread.
Infuse local anesthetics during surgery. Give minimal amount of IV opioids throughout surgery. Administer prophylactic antiemetics,
antibiotics, and DVT prophylaxis. Avoid overhydration. Avoid blood replacement in cancer resection. Maintain normothermia. Use
BIS to guide anesthesia titration. Avoid neostigmine to reverse muscle relaxants.
Surgical care
Minimize incision size, and use MIS if possible. Achieve accurate hemostasis and thorough removal of debris. Check integrity of
anastomosis. Do not routinely place nasogastric and abdominal drains.
Postoperative strategy
PACU
Discharge criteria: patient alert, cooperative, pain free, warm, normotensive, able to lift legs; urine output > 0.5 mL/kg
Surgical ward
Day of surgery (0–24 hr): Mobilize patient for 2 hr in chair and 2 hr walking, starting 6 hours after operation, and increase by 50% daily.
Have patient drink fluids, including nutritional supplements. Hold oral intake if abdomen distended. Place NG tube for persistent
PONV (repeated in subsequent days). Confirm working epidural block with VAS for pain at rest, cough, and mobilization. Check skin
site (repeated in subsequent days). Give oral acetaminophen, 1 g q. 4 hr, and NSAID (repeated in subsequent days).
Postoperative day 1 (24–48 hr): Remove urinary catheter in the morning. Mobilize patient for at least 6 hr. Institute light oral diet,
including nutritional supplement.
Postoperative day 2 and later (> 48 hr): Mobilize patient fully. Institute regular diet. Transition from epidural to oral medication
(oxycontin + oxycodone + acetaminophen + NSAIDs) if epidural stop test is successful (repeated in subsequent days if epidural stop
test is not successful). Enforce criteria for discharge: passing gas or stool, no fever, minimal pain, walking unattended, eating. If five
criteria are fulfilled, patient can go home.
Post discharge
Instructions while recovering at home or on chemotherapy/radiotherapy: normal diet (Psupplements), exercise every day for 1–2 hr, no
opioids for pain relief, psychological support
Clinic visit on postoperative day 14: check wound and overall recovery; discuss pathology and further treatment; plan further follow-up
BIS = bispectral index monitor; CAD = coronary artery disease; COPD = chronic obstructive pulmonary disease; DVT = deep vein thrombosis; MIS =
minimally invasive surgery; NG = nasogastric; NSAID = nonsteroidal antiinflammatory drug; PONV = postoperative nausea and vomiting; SSI = surgical site
infection; VAS = visual analog scale.
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Table 3 Sample Multimodal Perioperative Care Plan for Ambulatory Laparoscopic Cholecystectomy
Evaluation of medication compliance and control of risk factors: hypertension, diabetes, COPD, smoking, alcohol, asthma, CAD,
malnutrition, anemia
Psychological preparation for surgery and postoperative recovery: explanation of perioperative pathway, postoperative out-of-hospital
self-care, expectations about duration of recovery period
Day of surgery: drink clear fluids containing carbohydrate up to 2 hr before operation
Preinduction: give acetaminophen 1 gm and NSAID. Provide DVT prophylaxis.
Induce with propofol, give short-acting opiates for analgesia (e.g., fentanyl), consider adjuvants for analgesia (beta blockers [propanolol,
esmolol] or lidocaine), administer rocuronium or desflurane.
Prevent PONV with dexamethasone, ondansetron, or droperidol.
Give normal saline, 2 L IV, over intraoperative and postoperative time.
Keep patient warm.
Surgical care
Provide incisional anesthesia with local anesthetic at beginning and end of case. Keep abdominal insufflation pressure as low as possible
(12 mm Hg or less). Maximize use of small (5 mm) trocars.
PACU
Provide analgesia with strong short-acting opioid (e.g., fentanyl). Manage PONV with ondansetron. Encourage postoperative oral fluid
intake as soon as possible; do not wait for voiding to discharge from PACU.
> 6 hr after operation205
Provide nonopioid analgesia with NSAIDs (e.g., ketorolac, naproxen, COX-2 inhibitor) and acetaminophen. Add oxycodone, 5–10 mg
q. 4 hr, if pain persists.
Post discharge
Provide written instructions for postdischarge care; no specific activity limitations need be placed. Schedule follow-up visit at 2 wk after
surgery.
CAD = coronary artery disease; COPD = chronic obstructive pulmonary disease; DVT = deep-vein thrombosis; NSAID = nonsteroidal antiinflammatory drug;
PACU = postanesthesia care unit; PONV = postoperative nausea and vomiting;
patients undergoing epidural analgesia, oral nutrition, and col (also referred to as a critical pathway or clinical pathway)
mobilization on the day of the operation. The median length that multiple surgeons are willing to buy into may improve
of stay was 8 days, representing a 40% decrease from conven- efficiency and outcomes simply by removing variability
tional German data. Readmissions occurred in 4% of cases. and improving compliance with evidence-based care. This
A 2001 study enrolled 60 consecutive patients undergoing phenomenon has been demonstrated not only for colon
elective laparotomy and intestinal surgery over a 6-week surgery198 but also for more complex procedures such us pan-
period, including many reoperative and complex pelvic cases; creaticoduodenectomy199 and aortic surgery.200 By themselves,
only two of the 60 patients had to be excluded from the fast however, pathways often are not effective in decreasing the
track protocol on the basis of operative findings.192 Fast track length of stay.201
colorectal surgery has been successfully performed in older Fast track surgery represents an extension of the critical
patients,193 patients with significant comorbidities (ASA class pathway that integrates new modalities in anesthesia and
3 or 4),192,194,195 and patients requiring complex operations.195 nutrition, enforces early mobilization and feeding, and
Whether these results are applicable to more complex emphasizes reduction of the surgical stress response. It is
procedures in general is not known. In a study of fast track hoped that this approach will not only improve efficiency by
Ivor-Lewis esophagectomy, 75% of patients older than shortening the hospital stay and reducing variability, as any
70 years failed the protocol.196 standardized protocol might, but also decrease the physio-
logic impact of major surgery, thereby reducing organ dys-
Readmission is a concern after early discharge from hospi-
function and shortening the recovery time. Experience with
tal. The rate at which readmission occurs is related to the
fast track programs is accumulating in a number of different
planned day of hospital discharge, with readmission rates
areas. Most reports are single-center studies focusing on
after colon surgery decreasing from 20% to 11% as planned
colorectal surgery. A systematic review of three randomized
hospital stays increase from 2 days to 3. The difference is
trials and three additional prospective studies of enhanced
mainly attributable to a reduction in readmissions for
recovery programs for colon surgery found that fast track pro-
“social reasons” or observation; no significant differences in tocols were associated with decreased ileus, duration of hos-
complications have ben reported.197 A systematic review of pitalization, and morbidity, without any significant increase
fast track studies in colon surgery found no overall increase in the readmission rate.6 Fewer results are available for other
in readmission rates over those seen with conventional types of abdominal surgery. Preliminary reports, however,
care.6 suggest that it is possible to implement fast track protocols
even for debilitated patients undergoing complex procedures.
results
Some studies have reported dramatically low lengths of
There remains significant variability in perioperative care stay (e.g., a 3-day median length of stay after open aortic
among individual surgeons, institutions, and geographic aneurysm repair,202 a 2-day median length of stay after colon
areas, and overall adherence with evidence-based recommen- surgery,96 and an 88% discharge rate on postoperative day
dations and guidelines is still suboptimal.8 Consequently, it is 1 after laparoscopic donor nephrectomy203). Even if these
likely that creation of any standard perioperative care proto- results are not widely applicable, they might well stimulate us
08/08
Table 4 Sample Multimodal Perioperative Care Plan for Esophageal Resection206–208

Initial evaluation of medication compliance and control of risk factors: hypertension, diabetes, COPD, smoking, alcohol, asthma, CAD,
anemia
Psychological preparation for surgery and postoperative recovery: explanation of pathway, diet and mobilization plan, presence of drains,
expectations for length of hospital stay (7–8 days) and postdischarge recovery
Physical preparation with exercises at home: anaerobic and resistance 1–2 hr/day, gradual increase from 50% to 80% of maximum
capacity, breathing exercises
Surgical considerations: operative approach individualized on basis of tumor characteristics and location, patient comorbidity, previous
surgery
Familiarization with epidural analgesia: occasional numbness in lower extremities, short spells of hypotension, pain assessment at rest and
on coughing, walking, care of epidural catheter
Nutritional preparation: oral nutritional supplements for patients with diminished oral intake or mild undernutrition; formal nutritional
assessment if malnutrition is more severe
Insert thoracic epidural catheter. Use local anesthetics, and test epidural blockade for bilateral spread. Infuse local anesthetics during
surgery. Provide antibiotics and DVT prophylaxis. Give prophylactic antiemetics. Restrict fluids. Avoid blood transfusion. Maintain
normothermia. Perform early extubation (preferably in operating room).
Surgical care
Minimize blood loss. Place feeding jejunostomy. Routinely place NG tube and chest tubes.
Day of surgery (0–24 hr)
Admit to ICU or other unit with continuous monitoring of heart rate and pulse oximetry. Apply strict aspiration precautions; place head
of bed at 30°, and place NG tube to suction. Restrict fluids postoperatively as dictated by hemodynamics (~ 1–1.5 mL/kg/hr crystalloid
and 20–30 mL/hr urine output if renal function is normal). Place chest tube to suction. Have patient sitting in chair on evening of
surgery if possible and ambulating in hall on morning after surgery. Perform incentive spirometry. Monitor chest tube and urinary
output q. 4 hr. Obtain hemoglobin level q. 6 hr three times; measure electrolyte concentrations in morning.
Surgical ward
Postoperative day 1: Have patient ambulate 3–4 times daily; obtain physiotherapy consult. Perform incentive spirometry (repeated in
subsequent days). Apply strict aspiration precautions; place head of bed at 30°; place NG tube to suction (repeated in subsequent
days). Order complete blood count and electrolyte levels in morning (repeated in subsequent days). Obtain chest x-ray (repeated three
times in subsequent days). Confirm working epidural block with VAS for pain at rest, cough, and mobilization; check skin site
(repeated in subsequent days). Supply jejunal feedings at full concentration, starting at 20 mL/hr.
Postoperative day 2: Increase rate of jejunal feedings by 10 mL/4 hr until achieving target rate is achieved. Request nutritional therapy
consult. Remove anterior chest tube. Ambulate a minimum of four times daily until discharge.
Remove bladder catheter unless urinary output is poor.
Postoperative day 3: Remove NG tube if abdomen is not distended and gastric conduit is not dilated on chest x-ray.
Remove last chest tube if drainage < 450 mL/day (reassess in subsequent days if drainage is higher). Transition from epidural to
oral/J-tube analgesics (oxycontin + oxycodone + acetaminophen + NSAID) if epidural stop test is successful (repeated in subsequent
days if epidural stop test is not successful).
Postoperative day 4 or 5: Transition from epidural to oral/J-tube analgesics (oxycontin + oxycodone + acetaminophen + NSAID)
if epidural stop test is successful (repeated in subsequent days if epidural stop test is not successful). Perform sodium amidotrizoate–
meglumine amidotrizoate swallow. If there is no leak, advance to full liquid diet with oral supplements. Continue jejunal feedings.
Continue aspiration precautions: avoid eating if drowsy, and avoid recumbency within 3 hr of eating.
Postoperative day 5 or 6: Advance to soft diet. If patient is undernourished, start compressing jejunal feedings by increasing rate and
turning off for 4 hr/day. Arrange for home nighttime feedings (7 pm to 7 am). Remove central line. Continue physiotherapy and
aspiration precautions. Obtain nutritional education from dietitian.
Postoperative day 7: Discharge home on soft diet with aspiration precautions Pnighttime jejunal feedings.
Post discharge
Instructions while recovering at home and/or on chemotherapy/radiotherapy: eating normal diet (Psupplements), exercise every day for
1–2 hr, no opioids for pain relief, psychological support
Clinic visit on postoperative day 14 to check wound and overall recovery, discuss pathology and further treatment, and plan further
follow-up
CAD = coronary artery disease; COPD = chronic obstructive pulmonary disease; DVT = deep-vein thrombosis; ICU = intensive care unit; NG = nasogastric;
NSAID = nonsteroidal antiinflammatory drug.
to question our assumptions about what keeps patients in the use of probiotics, specific feeding protocols, preoperative
hospital after surgery. carbohydrate administration, bowel preparation, and specific
More research is required to understand which of the anesthesia protocols). Length of hospital stay is the most
multiple individual components of fast track surgery have the common outcome measure used, but this measure can be
greatest impact.6 In addition, it remains unclear whether confounded by nonphysiologic issues: even within fast track
certain patients are more likely than others to benefit from programs, only a minority of patients are discharged on the
fast track protocols. Several elements of this approach seem day of functional recovery.204 Yet little research has been
relatively consistent among fast track centers, at least with undertaken to achieve a better description of the recovery
respect to colorectal surgery (e.g., thoracic epidural analgesia process, and there is no currently accepted outcome measure
and the philosophy of encouraging early oral feeding and to define the length of clinical recovery. More research is also
ambulation), whereas several others are more variable (e.g., needed in the area of implementation.
08/08
Table 5 Sample Multimodal Perioperative Care Plan for Laparoscopic Foregut Surgery209

Initial evaluation of medication compliance and control of risk factors: hypertension, diabetes, COPD, smoking, alcohol, asthma, CAD,
anemia
Psychological preparation for surgery and postoperative recovery: explanation of pathway, diet and mobilization plan, expectations for
length of hospital stay (1–2 days) and postdischarge recovery
Nutritional preparation: oral nutritional supplements for patients with diminished oral intake or weight loss
Address aspiration risk. Give short-acting opioids. Use TIVA with propofol to minimize PONV. Provide good muscle relaxation to
facilitate surgical repair. Give prophylactic antiemetics to prevent postoperative retching (dexamethasone, 8 mg; droperidol, 0.625 mg;
ondansetron, 4 mg). Provide DVT prophylaxis. Initiate active warming.
Surgical care
Use small trocars. Administer preincisional and postoperative local anesthesia. Avoid lithotomy position (use split table and bean bag).
Apply pneumatic compression stockings. Do not routinely place Foley catheter or NG tube.
Give sips of water immediately after operation and fluids the morning after surgery. Request nutritional consult for education on
posthiatal surgery diet on postoperative day 1.
Have patient ambulate the night of the operation.
No routine postoperative investigations are required. Take stepwise approach to analgesia: start with NSAIDs and acetaminophen, avoid
opiates if possible, and do not use PCA. Assess for discharge criteria after lunch on postoperative day 1 (fluids tolerated, no fever, pain
controlled with oral analgesia).
CAD = coronary artery disease; COPD = chronic obstructive pulmonary disease; DVT = deep-vein thrombosis; NG = nasogastric; NSAID = nonsteroidal anti-
inflammatory drug; PCA = patient-controlled analgesia; PONV = postoperative nausea and vomiting; TIVA = total intravenous anesthesia.
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Acknowledgment
PS, Kehlet H. Readmission rates after a 204. Maessen JM, Dejong CH, Kessels AG, et al.
planned hospital stay of 2 versus 3 days in Length of stay: an inappropriate readout of Portions of this chapter are based on a previous
fast-track colonic surgery. Br J Surg 2007; the success of enhanced recovery programs. chapter “Fast Track Surgery” by Henrik Kehlet,
94:890–3. World J Surg 2008;[Epub ahead of print]. MD, PhD, FACS (Hon) and Douglas W.
198. Bradshaw BG, Liu SS, Thirlby RC. Stan- 205. Kehlet H, Gray AW, Bonnet F, et al. A Wilmore, MD, FACS. The authors wish to thank
dardized perioperative care protocols and procedure-specific systematic review and Drs. Kehlet and Wilmore.
08/08
© 2004 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice
ELEMENTS OF CONTEMPORARY PRACTICE 10 Fast Track Surgery — 1
10 FAST TRACK SURGERY

Henrik Kehlet, M.D., Ph.D., F.A.C.S. (Hon.), and Douglas W.Wilmore, M.D., F.A.C.S.
Over the past several decades, surgery has undergone revolution- surgery must be based on a process of multidisciplinary collabo-
ary changes that are leading to improved treatments (involving ration that embraces not only the surgeon, the anesthesiologist,
lower risk and better outcome) for an increasing number of dis- the physiotherapist, and the surgical nurse but also the patient.
eases. These salutary developments are the result of more ad- More specifically, fast track surgery depends on the inclusion and
vanced anesthetic techniques, new methods of reducing the peri- integration of a number of key constituent elements (see below).
operative stress response, wider application of minimally invasive
techniques, improved understanding of perioperative pathophysi-
ology, and more sophisticated approaches to the prevention of Constituent Elements
postoperative organ dysfunction. Currently, many operations that
EDUCATION OF THE PATIENT
once necessitated hospitalization can readily be performed in the
outpatient setting; in addition, many major procedures are now To obtain the full advantages of a fast track surgical program,
associated with a significantly reduced duration of hospitalization it is essential to provide patients with information about their peri-
and a shorter convalescence. operative care in advance of the procedure. Such educational
Although these anesthetic and surgical developments are the efforts often serve to reduce patients’ level of anxiety and need for
result of basic scientific and clinical research, they have also been pain relief, thereby providing a rational basis for collaboration
influenced by governmental and managed care policies aimed at with health care personnel, a process that is crucial for enhancing
encouraging more cost-effective treatments. Such extraclinical postoperative rehabilitation.1-3 Patients can supplement the infor-
influences, coupled with new clinical developments, have resulted mation they receive directly from health care providers by access-
in novel approaches designed to enhance the cost-effectiveness of ing reference sources such as www.facs.org/public_info/operation/
health care, such as so-called fast track surgery, critical pathways, aboutbroch.html, a collection of electronic brochures on specific
and various types of clinical guidelines. To understand the true clinical procedures that is provided by the American College of
potential value of such approaches, it is essential to recognize that Surgeons.
their aim is not merely to ensure that fewer health care dollars are
OPTIMIZATION OF ANESTHESIA
spent but, more important, to ensure that better and more effi-
cient health care is delivered. Although these novel approaches The introduction of rapid-onset, short-acting volatile anesthet-
may reduce cost, their primary purpose is to improve surgical ics (e.g., desflurane and sevoflurane), opioids (e.g., remifentanil),
management by reducing complications and providing better out- and muscle relaxants has enabled earlier recovery from anesthesia
comes. In what follows, we outline the basic concept, primary and thereby facilitated ambulatory and fast track surgery.4 Al-
components, and current results of fast track surgery, which is a though use of these newer general anesthetic agents has resulted
comprehensive approach to the elective surgical patient that is in quicker recovery of vital organ function after minor surgical
designed to accelerate recovery, reduce morbidity, and shorten procedures, it has not been shown to decrease stress responses or
convalescence. mitigate organ dysfunction after major procedures.
Regional anesthetic techniques (e.g., peripheral nerve blocks
and spinal or epidural analgesia), on the other hand, have several
Basic Concept advantages in addition to providing anesthesia. Such advantages
Fast track surgery involves a coordinated effort to combine (1) include improved pulmonary function, decreased cardiovascular
preoperative patient education; (2) newer anesthetic, analgesic, demands, reduced ileus, and more effective pain relief. Neural
and surgical techniques whose aim is to reduce surgical stress blockade is the most effective technique for providing postopera-
responses, pain, and discomfort; and (3) aggressive postoperative tive pain relief, and it has been shown to reduce endocrine and
rehabilitation, including early enteral nutrition and ambulation. It metabolic responses to surgery [see 1:6 Postoperative Pain]. For a
also includes an up-to-date approach to general principles of pronounced reduction in perioperative stress after a major opera-
postoperative care (e.g., use of tubes, drains, and catheters; mon- tion, continuous epidural analgesia for 24 to 72 hours is neces-
itoring; and general rehabilitation) that takes into account the sary.5,6 A meta-analysis of randomized trials evaluating regional
revisions to traditional practice mandated by current scientific anesthesia (primarily involving patients undergoing operations on
findings. It is believed that by these means, fast track surgery can the lower body) found that morbidity was 30% lower with region-
shorten the time required for full recovery, reduce the need for al anesthesia than with general anesthesia.7 However, the effect of
hospitalization and convalescence, and lower the incidence of continuous epidural analgesia on outcome after major abdominal
generalized morbidity related to pulmonary, cardiac, thromboem- or thoracic procedures has been questioned in the past several
bolic, and infectious complications.1-3 years. In three large randomized trials,8-10 no beneficial effect on
For an accelerated recovery program of this type to succeed, overall morbidity could be demonstrated, except for a slight
proper organization is essential. In general terms, fast track improvement in pulmonary outcome, and the duration of hospi-
talization was not reduced. It should be remembered, however, tions for hip fracture received either low-dose GH (20 mg/kg/day)
that in these studies, either an epidural opioid regimen or a pre- or placebo.28 Overall, those in the GH group were able to return
dominantly epidural opioid regimen was employed and that the to their prefracture living situation earlier than those in the place-
perioperative care regimens either were not described or were not bo group. A 1999 study reported increased mortality when GH
revised according to current scientific data regarding the use of was administered to ICU patients,29 but a 2001 meta-analysis
nasogastric tubes, early oral feeding, mobilization, and other care failed to confirm this observation.30 More work is necessary
parameters.3 We believe, therefore, that for further assessment of before definitive conclusions can be formed in this regard.
the role of continuous epidural local analgesic regimens that Postoperative insulin resistance is an important metabolic fac-
include local anesthetics in improving outcome, an integrated tor for catabolism. There is evidence to suggest that preoperative
approach within the context of fast track surgery is required.6 oral or intravenous carbohydrate feeding may reduce postopera-
Perioperative measures should also be taken to preserve intra- tive insulin resistance.31 Whether this approach yields clinical
operative normothermia. Hypothermia may lead to an augment- benefits in terms of improved recovery remains to be deter-
ed stress response during rewarming, impaired coagulation and mined,31,32 but its simplicity, its clear pathophysiologic rationale,
leukocyte function, and increased cardiovascular demands. and its low cost make it a potentially attractive option.
Preservation of intraoperative and early postoperative normother-
CONTROL OF NAUSEA, VOMITING, AND ILEUS
mia has been shown to decrease surgical site infection, intraoper-
ative blood loss, postoperative cardiac morbidity, and overall The ability to resume a normal diet after a surgical procedure
catabolism.11 (whether minor or major) is essential to the success of fast track
surgery. To this end, postoperative nausea, vomiting, and ileus
REDUCTION OF SURGICAL STRESS
must be controlled. Principles for rational prophylaxis of nausea
The neuroendocrine and inflammatory stress responses to and vomiting have been developed on the basis of systematic
surgery increase demands on various organs, and this increased reviews33: for example, 5-HT3 receptor antagonists, droperidol,
demand is thought to contribute to the development of postop- and dexamethasone have been shown to be effective in this
erative organ system complications. At present, the most impor- regard, whereas metoclopramide is ineffective.There is some rea-
tant of the techniques used to reduce the surgical stress response son to think that multimodal antiemetic combinations may be
are regional anesthesia, minimally invasive surgery, and pharma- superior to single antiemetic agents; unfortunately, the data cur-
cologic intervention (e.g., with steroids, beta blockers, or anabol- rently available on combination regimens are relatively sparse. In
ic agents).12 addition, analgesic regimens in which opioids are cut back or
Neural blockade with local anesthetics reduces endocrine and eliminated have been shown to decrease postoperative nausea
metabolic (specifically, catabolic) activation and sympathetic stim- and vomiting.
ulation, thereby decreasing the demands placed on organs and Paralytic ileus remains a significant cause of delayed recovery
reducing loss of muscle tissue; however, regional anesthetic tech- from surgery and contributes substantially to postoperative dis-
niques have no relevant effect on inflammatory responses.5,6 comfort and pain. Of the various techniques available for manag-
Minimally invasive surgical techniques clearly decrease pain ing ileus,34,35 continuous epidural analgesia with local anesthetics
and lessen inflammatory responses,13-15 but they appear to have is the most effective, besides providing excellent pain relief. Now
relatively little, if any, effect on endocrine and metabolic responses. that cisapride has been taken off the market, no effective anti-
Pharmacologic intervention with a single dose of a glucocorti- ileus drugs are available. In a 2001 study, however, a peripheral-
coid (usually dexamethasone, 8 mg) given before a minor proce- ly acting mu opioid receptor antagonist significantly reduced
dure has led to reduced nausea, vomiting, and pain, as well as to nausea, vomiting, and ileus after abdominal procedures, without
decreased inflammatory responses (interleukin-6), with no ob- reducing analgesia.36 If further studies confirm these findings, use
served side effects.16,17 This intervention may facilitate recovery of peripherally acting opioid antagonists may become a popular
from minor (i.e., ambulatory) procedures18; however, the data and effective way of improving postoperative recovery; this treat-
from major procedures are inconclusive.The use of perioperative ment is simple and apparently has no major side effects.
beta blockade to reduce sympathetic stimulation and thereby
ADEQUATE TREATMENT OF POSTOPERATIVE PAIN
attenuate cardiovascular demands has been shown to reduce car-
diac morbidity,19 as well as to reduce catabolism in burn patients Despite ongoing development and documentation of effective
[see Elements of Contemporary Practice:6 Risk Stratification, Pre- postoperative analgesic regimens—such as continuous epidural
operative Testing, and Operative Planning].20,21 Perioperative beta analgesia in major operations, patient-controlled analgesia
blockade may therefore become an important component of efforts (PCA), and multimodal (balanced) analgesia that includes non-
to facilitate recovery in fast track surgical programs. steroidal anti-inflammatory drugs as well as stronger agents37-39
For patients whose nutritional status is normal, oral feeding ad [see 1:6 Postoperative Pain]—postoperative pain still is too often
libitum is appropriate in the postoperative period. For patients inadequately treated. Improved pain relief, facilitated by an acute
who are elderly or nutritionally depleted, nutritional supplementa- pain service,40 is a central component of any fast track surgery
tion, administration of an anabolic agent (e.g., oxandrolone or an- program and is a prerequisite for optimal mobilization and oral
other anabolic steroid,22-24 insulin,25 or growth hormone [GH]26,27) nutrition, as well as a valuable aid in reducing surgical stress
to enhance deposition of lean tissue, or both may be beneficial. responses.37
Most of the studies addressing the use of anabolic agents have
APPROPRIATE USE OF TUBES, DRAINS, AND CATHETERS
focused on critically ill catabolic patients, in whom both indirect
effects (e.g., improved nitrogen balance26) and direct effects (e.g., There is substantial support in the literature for the idea that
improved wound healing and decreased length of stay with GH in nasogastric tubes should not be used routinely in patients undergo-
burned children27 and decreased mortality with insulin in critical- ing elective abdominal surgery.1,2 Randomized trials indicated that
ly ill patients25) on outcome have been demonstrated. In a study drains offered little benefit after cholecystectomy, joint replace-
published in 2000, a group of elderly patients undergoing opera- ments, colon resection, thyroidectomy, radical hysterectomy, or
pancreatic resection1,3,41 but that they might limit seroma forma- or a slightly modified fast track care program. On the whole, the
tion after mastectomy.1,3 Such postmastectomy drainage does not preliminary results from these studies are very positive: fast track
necessarily impede hospital discharge, and the patient generally surgery is associated with shorter hospital stays, reduced or at
may be treated on an outpatient basis. Urinary catheterization has least comparable morbidities, and low readmission rates, with no
been routinely performed after many operations, but scientific doc- apparent decrease in safety.
umentation of the requirement for this measure is often lacking. In Studies of fast track surgery in which organ function was
general, catheterization beyond 24 hours is not recommended with assessed postoperatively and compared with organ function after
colorectal procedures, except with the lowest rectal procedures, for traditional care found fast track surgery to be associated with ear-
which 3 to 4 days of catheterization may be indicated.3 lier ambulation,43,44 superior postoperative muscle function,44
Although tubes, drains, and catheters may lead to morbidity improved oral nutritional intake,45 better preservation of lean body
only when used for extended periods, they do tend to hinder mass,43,45 reduced postoperative impairment of pulmonary func-
mobilization, and they can raise a psychological barrier to the pa- tion,43 earlier recovery of GI motility,46 and mitigation of the de-
tient’s active participation in postoperative rehabilitation. There- crease in exercise capacity and impairment of cardiovascular
fore, such devices should be used not routinely but selectively, in response to exercise that are usually expected after an operation.43
accordance with the available scientific documentation. The few randomized trials performed to date (mostly involving
patients undergoing cholecystectomy, colonic resection, or mastec-
NURSING CARE, NUTRITION, AND MOBILIZATION
tomy) reported that fast track programs increased or at least main-
Postoperative nursing care should include psychological sup- tained patient satisfaction while achieving major cost reductions.
port for early rehabilitation, with a particular focus on encourag-
ing the patient to resume a normal diet and become ambulatory
as soon as possible. Early resumption of an oral diet is essential for Future Developments
self-care; furthermore, according to a 2001 meta-analysis of con- The initial promising results from the fast track surgical pro-
trolled trials, it may reduce infectious complications and shorten grams studied suggest that such programs can achieve major care
hospital stay after abdominal procedures, without increasing the improvements in terms of reducing postoperative stay. At present,
risk of anastomotic dehiscence.42 In addition, early resumption of however, sufficient scientific documentation is lacking for many
enteral feeding may reduce catabolism and may be facilitated by commonly performed major operations. Thus, there is a need for
the methods used to reduce postoperative nausea, vomiting, and additional data—in particular, data on the potential positive
ileus (see above). effects of fast track surgery on postoperative morbidity. The nec-
Postoperative bed rest is undesirable because it increases mus- essary data would probably be best obtained through multicenter
cle loss, decreases strength, impairs pulmonary function and tis- trials using identical protocols. Randomized trials within the same
sue oxygenation, and predisposes to venous stasis and throm- unit that allocate some patients to suboptimal care recommenda-
boembolism.3 Accordingly, every effort should be made to enforce tions for pain relief, mobilization, and nutrition would be difficult
postoperative mobilization; adequate pain relief is a key adjuvant to perform, if not unethical, though a few such reports have been
measure in this regard. published on colon surgery patients.44,47
Organization is essential for good postoperative nursing care: a As yet, it has not been conclusively demonstrated that reducing
prescheduled care map should be drawn up, with goals for reha- the duration of hospitalization necessarily reduces morbidity,48
bilitation listed for each day. though data from studies addressing colonic and vascular proce-
dures suggest that nonsurgical (i.e., cardiopulmonary and throm-
DISCHARGE PLANNING
boembolic) morbidity may be reduced and overall postoperative
Given that a primary result of fast track surgery is reduced recovery (assessed in terms of exercise performance and muscle
length of hospitalization, discharge planning must be a major con- power) enhanced. More study is required in this area. Future tri-
sideration in the preoperative patient information program, as als should also focus on identifying any factors that might be lim-
well as during hospitalization. Careful, detailed discharge plan- iting even more aggressive early recovery efforts, so that more
ning is essential for reducing readmissions and increasing patient effective fast track programs can be designed. Finally, studies are
safety and satisfaction. The discharge plan should include (1) needed to identify potential high-risk patient groups for whom fast
detailed information on the expected time course of recovery, (2) track surgery may not be appropriate or who may need to be hos-
recommendations for convalescence, and (3) encouragement of pitalized for slightly longer periods to optimize organ function.47
enteral intake and mobilization. For patients with a significant There has been considerable interest in whether the use of crit-
degree of postoperative disability, various acute care facilities are ical pathways improves postoperative care. Preliminary studies
available after hospital discharge. It should be kept in mind, how- involving coronary artery bypass grafting, total knee replacement,
ever, that the integrated care approach fundamental to fast track colectomy, thoracic procedures, and hysterectomy suggested that
surgery is specifically intended as a way of limiting or preventing critical pathways may reduce length of hospital stay, but the
such disability, thereby reducing patients’ need for and depen- reduction is no greater than can be observed in neighboring hos-
dence on postdischarge care facilities. pitals that do not use critical pathways.49 Thus, the initial enthusi-
asm for critical pathways notwithstanding, conclusive evidence
that they have a beneficial effect on postoperative care is still lack-
Reported Results ing.The continuously decreasing length of stay noted in hospitals
Ongoing efforts to formulate multimodal strategies aimed at without fast track programs may be partly attributable to the
improving postoperative outcome have led to the development of intense competition within the health care system, which can lead
a variety of fast track surgical programs [see Table 1]. Most of the to changes in care principles even without the formal adoption of
studies published to date have been descriptive ones reporting critical pathways or similar systems.49
consecutive patient series from single centers, the findings from All of the studies on the economic implications of fast track sur-
which have often been confirmed by other groups using the same gical programs and critical pathways have documented substantial
Table 1 Results from Selected Fast Track Surgical Programs
Type of Operation Postoperative Hospital Stay Comments and Other Findings
Abdominal procedures
Inguinal hernia repair59-61 1.5–6 hr Large consecutive series using local infiltration anesthesia in > 95%, with one
series59 using unmonitored anesthesia; documented low morbidity, with no urinary
retention; patient satisfaction ~90%, cost reduction > $250 with local anesthesia
Cholecystectomy (laparoscopic,62-67 > 80% discharge on same day Large consecutive series, with documented safety and patient satisfaction > 80%;
mini-incision68) cost reduction of $750/patient in randomized study64; recovery of organ functions
within 2–3 days, with <1 wk convalescence67; similar results with mini-incision in
consecutive series68
Fundoplication69,70 > 90% < 23 hr Large consecutive series with documented safety70
Open43,44,46,47,56,71-76 and laparo- 2–4 days Consecutive series including high-risk patients; reduced cardiopulmonary morbidity,
scopic72,77-79 colorectal procedures readmission rates 0%–15%; no documented advantages of laparoscopy-assisted
colonic resection, though costs may be reduced72; ileus reduced to < 48 hr in
> 90% of patients,46,56 with improved muscle and pulmonary function in fast track
patients and better preservation of postoperative body composition43; one random-
ized study showed similar morbidity, readmissions, and satisfaction with fast track
versus traditional care47
Complex pelvic-colorectal 3–6 days Short stay80 (~4–6 days) even with additional stoma; low readmission rate (7%)
procedures80,81
Rectal prolapse82 80% < 24 hr Consecutive series (N = 63) with Altemeier repair; 5% readmission rate (nonserious
indications)
Pancreaticoduodenectomy,83,84 — Hospital stay decreased by implementation of clinical pathway
complex biliary tract procedures85
Mastectomy86-90 90% < 1 day Large cumulative series; documented safety and major cost reduction with high
patient satisfaction; no increased morbidity with fast track, but less wound pain and
improved arm movement and no increase in risk of psychosocial complications
Vascular procedures
Carotid endarterectomy91-94 90% < 1 day Surgery done with local anesthesia; specialized nurses and wards
Lower-extremity arterial bypass95 2–3 days Large series (N = 130); documented safety
Abdominal aortic aneurysmectomy96,97 ~3 days Preliminary studies (N = 5096 and N = 7797); documented early recovery and safety;
one study with epidural analgesia,97 one without96
Urologic procedures
Radical prostatectomy98 ~75% 1 day Large consecutive series (N = 252); documented safety and patient satisfaction
Laparoscopic adrenalectomy99-101 < 1 day Small series; safety and low morbidity suggested
Cystectomy102,103 7 days Improved mobilization, bowel function, and sleep recovery with fast track surgery102;
low mortality; ileus a problem102,103
Laparoscopic donor nephrectomy104 < 1 day Preliminary study (N = 41); low readmission rate (2%)
Open donor nephrectomy105 2 days —
Pulmonary procedures106-110 ~1 day in some series,106,107 Shortest stay with fast track protocol including revision of drainage principles106,107;
~4–5 days in others safety with very early discharge suggested
Other procedures
Craniotomy111 ~40% < 24 hr Large consecutive series (N = 241) including tumor surgery; local anesthesia used;
low readmission rate; safety suggested
Parathyroid procedures112 ~90% ambulatory Selected consecutive series (N = 100); regional anesthesia and intraoperative
adenoma localization employed; documented safety
Vaginal procedures113 ~1 day Consecutive series (N = 108); surgery done with local anesthesia
cost savings. It should, however, be borne in mind that the last thereby achieving additional cost savings. As noted, the large-scale
portion of a hospital stay is much less expensive than the initial data with detailed patient description and stratification that are
portion; thus, the cost savings in this area may turn out to be needed to clarify the improvements achieved by fast track surgery
smaller than they would at first appear.50-52 This cavil should not are, unfortunately, lacking at present, but so far, all indications are
hinder further development and documentation of fast track that postoperative morbidity is comparable or reduced.
surgery, because inherent in the concept is the idea that revision A commonly expressed concern is that fast track surgery might
and optimization of perioperative care may also reduce morbidity, increase the burden on general practitioners and other parts of the
nonhospital care system. The evidence currently available clearly addressed patient functional status after fast track colonic surgery
indicates that increased use of ambulatory surgery is safe and is suggested that muscle function, exercise capacity, and body compo-
associated with a very low readmission rate.53,54 After major proce- sition are better preserved with this approach than with traditional
dures such as colorectal surgery, however, readmissions are often care, in which surgical stress, insufficient nutrition, and prolonged
unpredictable, and the readmission rate is not significantly reduced immobilization typically lead to significant deterioration of organ
by keeping patients in the hospital for an additional 2 to 3 days.55,56 function. Accordingly, an optimal fast track surgery regimen should
Moreover, in some studies of patients who have undergone coro- aim at early recovery of organ function, not just early discharge.
nary bypass57 and hip replacement,58 earlier discharge and hospital In summary, the basic concept of fast track surgery, which
cost savings have been offset by increased use of postacute rehabil- could be expressed as multimodal control of perioperative patho-
itation services. Thus, any assessment of the costs associated with physiology, seems to be a highly promising approach to improving
fast track surgery should include the total period during which care surgical outcome. We believe that the principles and techniques
(including both hospital care and rehabilitation care) is delivered. embodied in this approach will eventually be integrated into the
Again, however, it should be emphasized that the basic concept care of all surgical patients. To this end, resources should be allo-
of fast track surgery implies control of perioperative pathophysiolo- cated for evaluation and documentation of the effects of fast track
gy with the aim of enhancing recovery and thereby reducing the surgery and related systems on cost, postoperative morbidity, safe-
need for postdischarge care.The relatively few published studies that ty, and overall patient well-being.
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2 HEAD AND NECK 1 ORAL CAVITY LESIONS — 1
1 ORAL CAVITY LESIONS

Kiran Kakarala, MD, Sook-Bin Woo, DMD, MMSc, and Keith G. Saxon, MD, FACS
Approach to Oral Cavity Lesions

The oral cavity is a complex structure that plays a role in Hard
many important functions, including mastication, swallow- Upper Palate
Alveolus
ing, speech, and respiration. It extends from the vermilion
Retromolar
border of the lips to the oropharynx and is separated from the Trigone
oropharynx by the anterior tonsillar pillars, the junction of the
hard and soft palates, and the junction between the base of
the tongue and the oral tongue at the circumvallate papillae.
Subsites of the oral cavity include the lips, buccal mucosa,
alveolus, retromolar trigone, tongue, floor of the mouth, and
hard palate [see Figure 1].
In most cases, lesions of the oral cavity reflect locally
confined processes, but, on occasion, they are manifestations
of systemic disease. The cause of an oral cavity lesion can
usually be identified by the history and the physical examina-
tion; however, it is most often determined definitively by either
a response to a therapeutic trial or a biopsy. A systematic
classification of oral cavity lesions facilitates the development
of a differential diagnosis. One approach to classification
is based on the appearance of the lesion (e.g., white, red,
pigmented, ulcerative, vesiculobullous, raised, or cystic).
Another approach is first to categorize the lesion as either Buccal
Mucosa Oral
neoplastic or nonneoplastic and then to further divide the Tongue
nonneoplastic lesions into various subcategories (e.g., infec-
tious, inflammatory, vascular, traumatic, and tumorlike) [see
Table 1]. In the following discussion, we adopt the second Lower Floor of
approach. Alveolus Mouth
Clinical Evaluation Lip
history
The onset, duration, Figure 1 Depicted are the major anatomic subsites of the oral
cavity.
and growth rate of the
oral lesion should be
determined. Inflamma- A review of systems may uncover signs (e.g., rashes or
tory lesions usually have an acute onset and are self-limited, arthritis) that suggest a possible autoimmune disorder. The
and they may be recurrent. Neoplasms tend to exhibit medical history should always address previous or current
progressive enlargement; a rapid growth rate is suggestive connective tissue diseases, malignancies, radiation therapy,
of malignancy. It is often possible to identify specific events chemotherapy, and HIV infection. It is especially important
(e.g., upper respiratory tract infection, oral trauma, or medi- to elicit a medication history because many classes of medica-
cations) that precipitated the lesions. Both malignancies and tions cause drug eruptions that involve the oral mucosa: for
inflammatory conditions may be associated with various non- instance, well over 100 medications are associated with
specific symptoms, including pain and dysphagia. Symptoms lichenoid drug reaction, and even more are associated with
suggestive of malignancy include trismus, bleeding, a change xerostomia. Use of alcohol or tobacco is a notable risk factor
in denture fit or occlusion, facial sensory changes, and referred for the development of oral cavity carcinoma, as is a previous
otalgia. Fever, night sweats, and weight loss may occur in head and neck carcinoma. The quantity of alcohol or tobacco
various settings but are particularly associated with lympho- consumed should be determined because a dose-response
mas and systemic inflammatory conditions. Some oral lesions relationship exists between the level of use and the risk of
are identified without presenting signs or symptoms as inci- cancer. Other risk factors for oral cavity carcinoma include
dental findings noted during a general dental or medical sun exposure (lip cancer), human papillomavirus infection,
examination. and nutritional deficiencies. Radiation exposure is a risk
DOI 10.2310/7800.S02C01
02/10
Approach to Oral Cavity Lesions
Perform head and neck exam.

Patient presents with oral cavity lesion
•Visual assessment of mucosa of oral cavity
subsites
Obtain clinical history. •Color, depth, location, texture, and fixation
•Onset, duration, progression, precipitating of lesions
events, previous oral lesions •Ear exam, especially for otalgia
•Associated symptoms •Neck exam for adenopathy
•Review of systems •Nasal exam for palatal or upper alveolar
•Risk factors for malignancy lesions or systemic diseases
•Exam of oropharynx, larynx, and hypopharynx
if malignancy suspected
Diagnosis is probable
Estimate likelihood of malignancy.
Index of suspicion for malignancy is low Lesion is suspected of being premalignant

(leukoplakia or erythroplakia)
Further investigation with culture and sensitivity, lab tests,
or imaging may be warranted, depending on working diagnosis. •Small lesions: perform excisional biopsy.
Generally, these conditions can be managed with •Larger lesions: perform incisional biopsy.
observation, symptomatic treatment, or therapeutic trial. Treat specific lesion.
Inflammatory lesion Tumorlike lesion Benign neoplasm Hyperkeratosis
Infectious •Torus: intervention only if Treat with local Observe; repeat biopsy
•Viral: symptomatic treatment, antivirals if denture fit affected excision. if changes noted.
patient is immunocompromised •Cyst: observation or
•Bacterial: antibiotics excision
•Fungal: antifungals, usually topical (systemic •Fibroma: observation or
for persistent infection) excision
•Oral hairy leukoplakia or unusual infection: •Odontogenic cyst:
rule out HIV infection, refer patient to excision or debridement;
infectious disease specialist tooth extraction for
Noninfectious dentigerous cyst
•Aphthous ulcer: symptomatic treatment,
topical anti-inflammatories
•Traumatic ulcer: symptomatic treatment
•Autoimmune: symptomatic treatment, topical
or systemic steroids
•Necrotizing sialometaplasia: observation,
biopsy to rule out cancer
If lesion persists or therapeutic trial

fails, perform biopsy.
02/10
Formulate initial diagnostic impressions.
Diagnosis is uncertain
Investigate further with culture and sensitivity, imaging,

or lab tests.
Consult dermatologist or hematologist as appropriate.
Perform biopsy if malignancy is possible.
Treat identified condition as appropriate (see below).
Index of suspicion for malignancy

is high
Perform biopsy.
Treat specific malignancy.
Dysplasia or CIS Invasive cancer
Assess margins. If clear, Ensure adequate margins.

consider reexcision with wider Consider reexcision with
margins or observation; if close frozen-section control.
or positive, perform reexcision
with frozen-section control.
Minor salivary gland malignancy Mucosal melanoma Squamous cell carcinoma Kaposi sarcoma
Stage with CT, MRI, or PET. Stage with CT, MRI, PET, or Consider referral to medical
Assess with CT or MRI.
Perform wide local excision. panendoscopy. oncologist or infectious
Perform wide local excision.
•Clinically positive neck: •Stage 1 and 2: surgery disease specialist.
•Clinically positive neck: neck dissection.
•Clinically negative neck: consider neck dissection. or irradiation Rule out systemic disease.
selective neck dissection if tumor is •Clinically negative neck: •Stage 3 and 4: surgery with If asymptomatic, observe;
high grade. consider selective neck postoperative irradiation if symptomatic, consider
dissection. Perform neck dissection local or systemic treatment.
Consider postoperative irradiation for
Consider postoperative as indicated.
high-grade tumor or perineural spread.
irradiation.
02/10
Table 1 Differential Diagnosis of Oral Cavity Lesions The mucosa of the oral cavity is evaluated at each of the
Based on Etiology oral subsites. Any trismus should be noted, as should the
general health of the teeth and the gingiva. Percussion of
Inflammatory lesions
carious teeth with pulpitis often elicits pain, although this is
Infectious
Viral not always the case if caries is shallow or pulpal necrosis is
Herpes simplex present. Palpation of the tongue, the floor of the mouth, and
Herpes zoster the oral vestibule is an essential component of oral examina-
Cytomegalovirus tion. Palpation of the submandibular and submental regions
Herpangina is best performed bimanually.
Hand, foot, and mouth disease
Oral hairy leukoplakia (Epstein-Barr virus) Oral lesions should be characterized in terms of color,
Bacterial depth, location, texture, fixation, and other applicable attri-
Mycobacterial infection butes. When cancer is present, tenderness, induration, and
Syphilis fixation are common. Invasion of surrounding structures
Gingivostomatitis (e.g., the mandible, the parotid duct, or the teeth) by a malig-
Fungal
Candidiasis
nant lesion should be noted. Physical examination is not a
Coccidioidomycosis definitive means of detecting mandibular invasion, because
Noninfectious tumor fixation can be secondary to other factors and cortical
Recurrent aphthous stomatitis invasion can occur with minimal fixation.1,2 In addition,
Traumatic ulcer lesions in some areas of the oral cavity (e.g., the hard palate
Autoimmune disorders
and the attached gingiva) almost always appear to be fixed.
Behçet syndrome
Systemic lupus erythematosus A history of otalgia warrants otoscopic examination.
Wegener granulomatosis Otalgia in the absence of any identifiable pathologic condi-
Sarcoidosis tion of the ear often represents referred pain from a malig-
Amyloidosis nancy of the upper aerodigestive tract. The presence of
Pemphigus and pemphigoid otalgia in a middle-aged person should always trigger a search
Pyogenic granuloma
Necrotizing sialometaplasia for an underlying cause. The nasal cavity should be examined
Lichen planus with a speculum to rule out tumor extension in lesions of the
hard palate, and transnasal fiberoptic pharyngoscopy and
Tumorlike lesions
Mucocele
laryngoscopy should be done if a malignant neoplasm is a
Ranula possibility or if a systemic condition is suspected that may
Tori also affect the nasal or pharyngeal mucosa.
Fibroma Examination of the neck may reveal enlarged lymph nodes.
Odontogenic cysts Lymphadenopathy in an adult should be considered to
Neoplasms represent metastatic cancer until proved otherwise. A benign
Benign ulcer in the oral cavity may cause a reactive adenopathy as
Squamous papilloma a consequence of the associated inflammation, but in the
Minor salivary gland neoplasms setting of cervical lymphadenopathy, the initial diagnostic
Ameloblastoma
Hemangioma
assumptions should emphasize the strong possibility of a pri-
Granular cell tumor mary oral cancer with metastases to the neck. Asymmetrical
Brown tumor enlargement of the parotid or submandibular glands may
Neuroma, schwannoma, neurofibroma result either from obstruction of the ducts by an oral cavity
Osteoma, chondroma mass or from enlargement of nodes intimately associated with
Malignant
the glands. Symmetrical enlargement suggests a systemic pro-
Squamous cell carcinoma
Verrucous carcinoma cess (e.g., Sjögren syndrome or HIV infection). The cranial
Minor salivary gland malignancies nerves should be examined, with particular attention focused
Mucoepidermoid carcinoma on the trigeminal, facial, and hypoglossal nerves.
Adenoid cystic carcinoma
Polymorphous low-grade adenocarcinoma
Mucosal melanoma Investigative Studies
Kaposi sarcoma
Lymphoma The history and physi-
Osteosarcoma cal examination should
narrow down the differ-
factor for soft tissue sarcoma, lymphoma, and minor salivary ential diagnosis and lead
gland tumors, and HIV infection is a risk factor for Kaposi to a working diagnosis. If
sarcoma. a benign local process (e.g., aphthous stomatitis, traumatic
ulcer, or viral infection) is suspected, no further investigation,
physical examination other than reevaluation, may be needed. If the lesion persists
The head and neck should be examined in an organized or progresses, further investigation is warranted.
and systematic manner. Illumination with a headlight or a
reflecting mirror facilitates oral examination by freeing the laboratory tests
examiner’s hands for use in retracting the cheeks and the Laboratory studies are usually not beneficial in the initial
tongue. workup of oral cavity lesions. If a connective tissue disease
02/10
is suspected, serologic tests [see Table 2] and referral to a of technical experience available vary considerably among
rheumatologist or another appropriate specialist may be institutions. The role of PET imaging in the initial manage-
considered. ment and follow-up of head and neck cancer is still being
defined.
imaging
The value of advanced imaging with computed tomography biopsy
(CT), magnetic resonance imaging (MRI), or both in the For oral cavity lesions that are suggestive of malignancy or
management of oral cavity lesions has not been firmly estab- are probably of neoplastic origin, biopsy is usually required.
lished. Accordingly, judgment must be exercised. There is A brief observation period to allow reevaluation, with biopsy
evidence to suggest that early oral cavity malignancies can withheld, may be warranted if a response to therapy or
be managed without either CT or MRI. Nevertheless, many spontaneous resolution is possible. The potential morbidity
clinicians obtain these studies in all cases of malignancy and associated with a biopsy done in a previously irradiated region
in most cases of suspected malignancy. CT and MRI can should be considered in deciding whether biopsy is advisable.
help assess the size and location of the lesion and determine Specimens are usually sent to the pathologist in 10% buffered
the degree to which surrounding structures are involved. In
formalin, but there are notable exceptions. If a lymphoma is
patients with oral cavity carcinoma, imaging facilitates the
suspected, specimens should be sent without formalin for
staging of tumors and the planning of treatment. In patients
genetic testing and flow cytometry. If an autoimmune disease
with cervical metastases, physical examination augmented by
MRI and CT has a better diagnostic yield than physical is suspected, special tests requiring immunofluorescence
examination alone. Bone-window CT scans are particularly are indicated, and specimens should be sent either fresh or
helpful for assessing invasion of the mandible, the maxilla, in Michel solution. In addition, if fungal, mycobacterial,
the cervical spine, and the base of the skull. CT scans bacterial, or viral infection is suspected, a small portion of a
are highly sensitive and specific for detecting mandibular specimen may be sent separately for culture. If there is an
invasion.1–3 MRI provides better soft tissue delineation than associated neck mass, fine-needle aspiration (FNA) may be
CT, with fewer dental artifacts, and therefore is particularly performed to rule out metastatic disease.7 In general, FNA is
valuable for assessing malignancies of the tongue, the floor of not useful for biopsy of oral lesions: incisional biopsy is often
the mouth, and the salivary glands. Loss of the usual marrow technically easier and provides more tissue.
enhancement on T1-weighted MRI images suggests bone
invasion, although this is not a specific finding. Chest radio- examination under anesthesia and panendoscopy
graphy, CT, or both may be employed to search for lung In patients with oral carcinoma, examination under anes-
metastases or a second primary tumor. thesia (EUA) and panendoscopy should be performed before
Positron emission tomography (PET) is playing an increas- definitive resection to assess the extent of the primary tumor
ingly important role in the workup of patients with head and and identify any synchronous tumors. Both EUA and panen-
neck carcinoma or mucosal melanoma. PET is useful for con-
doscopy are commonly performed in the operating room
firming the presence of a malignancy, as well as for assessing
with the patient under general anesthesia. Panendoscopy
cervical and distant metastases; it is particularly valuable for
involves endoscopic examination of the larynx, the orophar-
detecting recurrent or persistent disease.4–6 The development
ynx, the hypopharynx, the esophagus, and, occasionally, the
of fused PET-CT images has allowed for greater accuracy in
nasopharynx. As a rule, assessment of the tumor and neck is
anatomically delineating tumors and planning treatment.
Drawbacks of PET include frequent false positive results more accurately performed when the patient is relaxed under
with active inflammation, high cost, and limited availability. a general anesthetic.
In addition, the quality of the images obtained and the level
Diagnosis and Management of Specific Oral Cavity
Lesions
Table 2 Serologic Tests for Diagnosing Connective inflammatory

Tissue Disease lesions
Connective Tissue Disease Serologic Tests Infectious
SLE CBC, antinuclear antibody, Viral stomatitis may
anti–double-stranded DNA
antibody, anti-Smith be caused by a number
antibody of different viruses, including herpes simplex virus (type 1 or
type 2), varicella-zoster virus, and coxsackievirus [see Figure 2,
Sjögren syndrome Antinuclear antibody,
rheumatoid factor, anti-Ro a and b].8 It is most common in children and immunocom-
(SS-A) and anti-La promised patients. The lesions of viral stomatitis are generally
(SS-B) antibodies vesicular, occur in the oral cavity and the oropharynx, and
Wegener granulomatosis cANCA, serum creatinine erupt over the course of several days to form painful ulcers.
level, urine microscopy Eruption may be preceded by local symptoms (e.g., burning,
Sarcoidosis Serum calcium and ACE levels itching, or tingling) or systemic symptoms (e.g., fever, rash,
malaise, or lymphadenopathy). The diagnosis is usually
ACE = angiotensin-converting enzyme; cANCA = cytoplasmic antineutrophil
cytoplasmic antibodies; CBC = complete blood count; SLE = systemic lupus established by the history and the physical examination and
erythematosus. may be confirmed by means of biopsy or viral culture.
02/10
a b
c d
Figure 2 Shown are infectious lesions of the oral cavity: (a) primary herpes stomatitis of the buccal mucosa and soft palate; (b)
primary herpes stomatitis of the tongue (in the same patient as in frame a); (c) oral candidiasis (pseudomembranous form); and
(d) oral candidiasis (erythematous form).
Treatment of viral stomatitis primarily involves managing Table 3 Clinical Presentation of Oral Candidiasis
symptoms with oral rinses, topical anesthetics, hydration,
Type of Oral Candidiasis Presentation
and antipyretics. Systemic antiviral medications may shorten
the course of herpetic stomatitis and are indicated in Pseudomembranous White, curdlike plaques on
immunocompromised patients.9 oral mucosa that when wiped
off (with difficulty) leave
Candidiasis is a common fungal infection of the oral cavity erythematous, painful base
[see Figure 2, c and d]. Candida albicans is the species most
Hyperplastic Thick white plaques on oral
commonly responsible; however, other Candida species can mucosa that cannot be
cause this condition as well, with Candida glabrata emerging rubbed off
as a growing problem in immunocompromised hosts. Factors
Erythematous Red, atrophic areas on palate
predisposing to oral candidal infection include immunosup- or dorsum of tongue
pression, use of broad-spectrum antibiotics, diabetes, pro-
longed use of local or systemic steroids, and xerostomia.10 Angular cheilitis Cracking and fissuring at oral
commissures
Oral candidiasis presents in several different forms [see
Table 3], of which pseudomembranous candidiasis (thrush)
is the most common. This form is characterized by white, possible. Treatment typically involves either topically admin-
curdlike plaques on the oral mucosa that may be wiped off istered antifungal agents or, if infection is severe or topical
(with difficulty) to leave an erythematous, painful base (the therapy fails, systemically administered antifungals. Patients
Auspitz sign). Widespread oral and pharyngeal involvement who are immunocompromised or have xerostomia may
is common. The diagnosis is based on the clinical appearance benefit from long-term prophylaxis.
of the lesion and on evaluation of scrapings with the potas-
sium hydroxide (KOH) test. Culture is generally not useful, Noninfectious
because Candida is a common commensal oral organism.11 Recurrent aphthous stomatitis Aphthous stomatitis is
Ideally, initial management of oral candidiasis is aimed at a common idiopathic ulcerative condition of the oral cavity
reversing the underlying condition, although this is not always [see Figure 3, a and b]. The ulcers are typically painful and
02/10
a b
c d
e f
g h
Figure 3 Shown are noninfectious inflammatory lesions of the oral cavity:

(a) minor aphthous ulcer of the lower lip; (b) minor aphthous ulcer of the
upper lip; (c) necrotizing sialometaplasia of the hard palate; (d) resolution
of necrotizing sialometaplasia without treatment (in the same patient as in
frame c); (e) pyogenic granuloma of the upper alveolus; (f) reticular lichen
planus involving the buccal mucosa; (g) lichen planus of the lateral tongue;
(h) pemphigus vulgaris of the oral cavity, with an erythematous base after
rupture of bullae (involving the left lateral tongue, the buccal mucosa, and
the lip); and (i) traumatic ulcer of the tongue secondary to dental trauma.
02/10
may occur anywhere in the oral cavity and the oropharynx by ill-fitting dentures.9 Biopsy is usually necessary to rule
but are rarely found on the hard palate, the dorsal tongue, out squamous cell carcinoma or a minor salivary gland
and the attached gingiva.9,12 Affected patients often have a malignancy. Review of the tissue by a pathologist well versed
history of lesions, beginning before adolescence. There are in head and neck pathology is essential. Characteristic histo-
three different clinical presentations of recurrent aphthous logic findings include coagulation necrosis of the salivary
stomatitis, of which minor aphthous ulcers are the most gland acini, ductal squamous metaplasia, preservation of
common [see Table 4].9 The diagnosis is made on the basis of the lobular architecture, and a nonmalignant appearance of
the history and the physical examination; biopsy is reserved squamous nests.13
for lesions that do not heal or that grow in size. Lesions resolve without treatment within 6 to 10 weeks
Numerous therapies have been tried for recurrent aphthous [see Figure 3d].
stomatitis, most with only minimal success. The majority of
aphthous ulcers heal within 10 to 14 days and require no Pyogenic granuloma A pyogenic granuloma is an
treatment; however, patients with severe symptoms may aggregation of proliferating endothelial tissue [see Figure 3e]
require medical intervention. Temporary pain relief can that occurs in response to chronic persistent irritation (e.g.,
be obtained with topical anesthetic agents (e.g., viscous from a calculus or a foreign body) or trauma.10 The lesion
lidocaine). Tetracycline oral suspension and antiseptic appears as a raised, soft, sessile or pedunculated mass with a
mouthwashes have also been used, with varying success.9,12 smooth, red surface that bleeds easily and can grow rapidly.14
Topical steroids are the mainstay of therapy and may shorten Surface ulceration may occur, but the ulcers are not invasive.
the duration of the ulcers if applied during the early phase.11,12 The gingiva is the most common location, but any of the oral
These agents may be applied either in a solution (e.g., dexa- tissues may be involved.
methasone oral suspension, 0.5 mg/5 mL) or in an ointment Conservative excision with management of the underlying
(e.g., fluocinolone or clobetasol). Ointments work much irritant is the recommended treatment. The classic presenta-
better in the oral cavity than creams or gels do. Systemic tion is in a pregnant woman, and hormonal influences may
steroids are indicated when the number of ulcers is large or have an additional influence on recurrence.
when the outbreak has persisted for a long time.
Lichen planus Lichen planus is a common immune-
Necrotizing sialometaplasia Necrotizing sialometapla- mediated inflammatory mucocutaneous disease [see Figure 3,
sia is a rare benign inflammatory lesion of the minor salivary f and g].15 Clinically, idiopathic lichen planus is indistinguish-
glands that resembles carcinoma clinically and histologically able from lichenoid drug reaction. The reticular form of
and is readily mistaken for it [see Figure 3c].8 This condition lichen planus is the most common one and presents as inter-
most commonly develops in white males in the form of lacing white keratotic striae on the buccal mucosa, the lateral
a deep, sudden ulcer of the hard palate. The presumed tongue, and the palate.15 Lichen planus is usually bilateral,
cause is ischemia of the minor salivary glands resulting from symmetrical, and asymptomatic.16 The symptomatic phases
infection, trauma, surgery, irradiation, or irritation caused may wax and wane, with erythematous and ulcerative changes
being the primary signs. Cutaneous lesions occur less fre-
quently and appear as small, violaceous, pruritic papules. The
Table 4 Clinical Presentation of Aphthous Stomatitis diagnosis is generally made on the basis of the history and the
physical examination; biopsy is not always necessary.
Type of Presentation Time to
Aphthous Resolution
For asymptomatic lesions, no treatment is required other
Ulcer than observation. For painful lesions, which are more common
with the erosive form of the disease, either topical or systemic
Minor Multiple painful, well- 7–10 days,
demarcated ulcers, < 1.0 cm without
steroids are appropriate.16 There is some controversy regard-
in diameter, are noted, with scarring ing the risk of malignant transformation; however, long-term
yellow fibrinoid base and follow-up is still recommended.16 The main risk posed by
surrounding erythema; lichen planus may be the masking effect that the white striae
typically involve mobile cause, which can prevent the clinician from observing the
mucosa, with tongue, palate,
and anterior tonsillar pillar the
early leukoplakic and erythroplakic changes associated with
most common sites epithelial dysplasia.
Major (Sutton Ulcers, often multiple, may 4–6 wk,
disease) range in size from a few with
Ulcer from autoimmune disease Oral ulcers may be
millimeters to 3 cm and may scarring the first manifestation of a systemic illness. The most common
penetrate deeply with elevated oral manifestation of systemic lupus erythematosus (SLE)
margins; typically involve is the appearance of painful oral ulcers in women of child-
mobile mucosa, with tongue, bearing age. Patients with Behçet disease present with the
palate, and anterior tonsillar
pillar the most common sites
characteristic triad of painful oral ulcers, genital ulcers, and
associated iritis or uveitis. Patients with Crohn disease or
Herpetiform Small (1–3 mm) ulcers occur in 1–2 wk Wegener granulomatosis frequently manifest oral ulceration
“crops” but are still limited to
movable mucosal surfaces; during the course of the illness. These disorders should be
gingival involvement, if managed in conjunction with a rheumatologist.
present, is caused by extension Mucous membrane pemphigoid and pemphigus vulgaris
from nonkeratinizing are chronic vesiculobullous autoimmune diseases that
crevicular epithelium frequently affect the oral mucosa [see Figure 3h]. In mucous
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membrane pemphigoid, the antibodies are directed at the as a consequence of obstruction of the sublingual duct,19
mucosal basement membrane, resulting in subepithelial secondary either to trauma or to sublingual gland sialoliths.
bullae.16 These bullae rupture after 1 to 2 days to form pain- If the ranula extends through the mylohyoid muscle into
ful ulcers, which may heal over a period of 1 to 2 weeks but the neck, it is referred to as a plunging ranula. A plunging
often do not display a predictable periodicity. Oral pain is ranula may present as a submental or submandibular neck
often the chief complaint, but there may be undetected ocular mass. Imaging helps delineate the extent of the mass and
involvement that can lead to entropion and blindness. may confirm the presence of a sialolith. The recommended
Pemphigus vulgaris is a more severe disease than mucous treatment is excision of the ranula with removal of the
membrane pemphigoid. In this condition, the antibodies are sublingual gland and often the adjacent submandibular
directed at intraepithelial adhesion molecules, leading to the gland. Marsupialization is an option but is associated with a
formation of intraepithelial bullae.9 The blisters are painful relatively high recurrence rate.19,20
and easily ruptured and tend to occur throughout the oral A mucous retention cyst (salivary duct cyst) is usually the
cavity and the pharynx.17 The Nikolsky sign (i.e., vesicle result of partial obstruction of a salivary gland duct accompa-
formation or sloughing when a lateral shearing force is applied nied by mucous accumulation and ductal dilatation [see Figure
to uninvolved oral mucosa or skin) is present in both pem- 4e].19 It is a soft, compressible mass that may occur at any
phigus and pemphigoid. In most cases, biopsy with patho- location in the oral cavity where minor salivary glands are
logic evaluation (including immunofluorescence studies) is present. Treatment involves surgical excision with removal of
helpful in establishing the diagnosis. Circulating antibodies the associated minor salivary gland.
may be present in either condition but are more common
fibroma
in pemphigus. Serologic tests may suffice to establish the
diagnosis, without any need for biopsy. Management involves A fibroma is a hyperplastic response to inflammation or
administration of immunosuppressive agents, often in trauma [see Figure 4, f and g].8 It is a pedunculated soft or firm
conjunction with a dermatologist. mass with a smooth mucosal surface that may be located any-
where in the mouth. Such lesions are managed with either
Traumatic ulcer Trauma (e.g., from tooth abrasion, observation or local excision.
tooth brushing, poor denture fit, or burns) is a common cause
odontogenic cyst
of oral mucosal ulceration [see Figure 3i]. The ulcers usually
are painful but typically are self-limited and resolve without A dentigerous cyst is an epithelium-lined cyst that, by
treatment. Topical anesthetic agents may be beneficial if pain definition, is associated with the crown of an unerupted
is severe enough to limit oral intake. tooth [see Figure 4h]. Such cysts cause painless expansion of
the mandible or the maxilla. Treatment involves enucleation
of the cyst and its lining and extraction of the associated
Tumorlike Lesions tooth.21
An odontogenic keratocyst is a squamous epithelium–lined
torus mandibularis and torus palatinus
cyst that produces keratin. Bone resorption occurs secondary
Palatal and mandibular tori are benign focal overgrowths to pressure resorption and to inflammation caused by retained
of cortical bone [see Figure 4, a and b].10 They appear as keratin. Management involves either excision or débridement
slow-growing, asymptomatic, firm, submucosal bony masses and creation of a well-ventilated and easily maintained
developing on the lingual surface of the mandible or the cavity.22
midline of the hard palate.14 When these lesions occur on the
labial or buccal aspect of the mandible and the maxilla, they
are termed exostosis.18 Torus mandibularis tends to occur Neoplastic Lesions
bilaterally, whereas torus palatinus arises as a singular, often benign
lobulated mass in the midline of the hard palate. Surgical
management is required only if the tori are interfering with Squamous Papilloma
denture fit. Squamous papilloma is one of the most common benign
neoplasms of the oral cavity [see Figure 5, a and b].13 It usually
mucocele and mucous retention cyst
presents as a solitary, slow-growing, asymptomatic lesion,
A mucocele is a pseudocyst that develops when injury to typically less than 1 cm in diameter. It is well circumscribed
a minor salivary gland duct causes extravasation of mucus, and pedunculated and has a warty appearance.16 The palate
surrounding inflammation, and formation of a pseudocapsule and tongue are the sites most frequently affected13; occasion-
[see Figure 4, c and d].14 Mucoceles are soft, compressible, ally, multiple sites are involved. The presumed cause is a viral
bluish or translucent masses that may fluctuate in size. infection, most likely human papillomavirus.23
They are most commonly seen on the lower lip but also Papillomas are managed with complete excision, including
may develop on the buccal mucosa, anterior ventral tongue, the base of the stalk.
and floor of the mouth. Only very rarely do they involve the
upper lip; masses in the upper lip, even if they are fluctuant, Giant Cell Lesions
should be assumed to be neoplastic, developmental, or infec- Central giant cell granulomas, brown tumors of hyperpara-
tious. Treatment involves excision of the mucocele and its thyroidism, aneurysmal bone cysts, and lesions associated
associated minor salivary gland. with genetic diseases (e.g., cherubism) may all be seen in the
A ranula (from a diminutive form of the Latin word for jaws. Of particular note is the aneurysmal bone cyst that may
frog) is a mucocele that develops in the floor of the mouth occur at sites of trauma, which, in theory, is the consequence
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a b c
d e f
g h
Figure 4 Shown are tumorlike lesions of the oral cavity: (a) torus mandibularis, with bilateral bony protuberances on the lingual
surface of the mandible; (b) mandibular exostosis, with a unilateral bony protuberance on the labial-buccal surface of the
mandible; (c) mucocele of the lip (note the bluish hue of the cystic lesion; cf. frame e); (d) mucocele of the floor of the mouth
associated with the sublingual gland (ranula); (e) mucous retention cyst of the lower lip (presenting much like mucocele but
appearing more transparent); (f) fibroma of the hard palate resulting from denture trauma; (g) fibroma of the lower lip; and
(h) dentigerous cyst (a unilocular radiolucency surrounding the crown of an unerupted tooth, with no bone destruction).
of an organizing hematoma that leads to bony expansion and Approximately 30% of minor salivary gland neoplasms
giant cell proliferation.24 Eventually, erosion of the buccal are benign. Of these benign lesions, the most common
cortex may occur with the development of facial swelling. is pleomorphic adenoma, which presents as a painless,
Management involves enucleation and curettage.24,25 The slow-growing submucosal mass [see Figure 5, c and d].13,26
surgeon should be prepared for bleeding during treatment. Pleomorphic adenoma is managed with complete surgical
The use of calcitonin or intralesional steroid injections is excision to clear margins. This tumor exhibits small, pseudo-
gaining popularity.25 podlike extensions that may persist and cause recurrence if
enucleation around an apparent capsule is attempted.
Minor Salivary Gland Neoplasms
The minor salivary glands are small, mucus-secreting Granular Cell Tumor
glands that are distributed throughout the upper aerodiges- A granular cell tumor is a benign neoplasm that is thought
tive tract, with the largest proportion concentrated in the oral to arise from Schwann cells.13 It usually presents as a small,
cavity. Minor salivary gland neoplasms are uncommon, but asymptomatic, solitary submucosal mass. The lateral border
when they do occur, they are most likely to develop in the and the dorsal surface of the tongue are the sites where this
oral cavity. Within the oral cavity, the hard palate and the soft tumor is most frequently found in the oral cavity.27 Pathologic
palate are the most common sites of minor salivary gland examination may reveal pseudoepitheliomatous hyperplasia,
neoplasms; however, tumors involving the tongue, the lips, which is similar in appearance to well-differentiated squa-
the buccal mucosa, and the gingivae have been described. mous cell carcinoma.28 This similarity has led to reports of
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a b c
d e
Figure 5 Shown are benign neoplasms of the oral cavity: (a) squamous papilloma of the
frenulum; (b) squamous papilloma of the ventral tongue; (c) pleomorphic adenoma of the
hard palate; (d) pleomorphic adenoma of the hard palate on coronal computed tomography
(CT) (note the soft tissue thickening along the left hard palate, with no bone erosion or
destruction); (e) ameloblastoma of the left angle and ramus of the mandible (a multilocular
radiolucency); and (f) ameloblastoma on CT, with a soft tissue mass in the left mandible
and erosion of the lingual plate of the mandible.
misdiagnosis on histopathologic evaluation. Accordingly, associated with an unerupted third molar tooth and, with
given the known rarity of squamous cell carcinoma of the the exception of the desmoplastic variant, rarely appear
dorsal surface of the anterior two thirds of the tongue, it may radiopaque. They may also appear unilocular on radiographic
be prudent to obtain a second histopathologic opinion when- imaging.31 Histologic examination shows proliferating odon-
ever a diagnosis of squamous cell carcinoma is rendered in togenic epithelium with palisading peripheral cells that
this location. Treatment consists of conservative excision.27 display reverse polarization of the nuclei.13
Appropriate management of ameloblastomas involves
Ameloblastoma resection to clear margins. For mandibular ameloblastomas,
Ameloblastoma is a neoplasm that arises from odontogenic either a marginal or a segmental mandibulectomy is done,
(dental) epithelium, most frequently in the third and fourth depending on the relation of the lesion to the inferior cortical
decades of life [see Figure 5, e and f].8,26 It often presents as border. Curettage is associated with a high recurrence rate.29
a painless swelling with bony enlargement. Approximately The prognosis for maxillary multicystic ameloblastoma is
80% of ameloblastomas involve the mandible and 20% the relatively poor because of the higher recurrence rate and the
maxilla29; the mandibular ramus is the most common site.29 greater frequency of invasion of local adjacent structures
Ameloblastomas are usually benign but are often locally (e.g., the skull base).32
aggressive and infiltrative. Malignant ameloblastomas are rare Most types of mesenchymal neoplasms may be found also
but are notable for being associated with pain, rapid growth, in the oral region. Benign mesenchymal neoplasms known
and metastases.11 to occur in the oral cavity include (but are not limited to)
On CT and panoramic jaw films, ameloblastomas typically hemangiomas, lipomas, schwannomas, neuromas, and neuro-
appear as multilocular radiolucent lesions with a honeycomb fibromas. These are relatively rare lesions but should none-
appearance and scalloped borders.30 These tumors are often theless be included in the differential diagnosis of intraoral
02/10
masses. The diagnosis is usually made on the basis of histo- leukoplakia, with biopsy performed to rule out a malignant or
pathologic examination of biopsy specimens. Benign bone premalignant lesion. Complete surgical excision is indicated
tumors, although uncommon, are not unknown. Chondro- if either a malignancy or a premalignancy is confirmed, and
mas, hemangiomas, ossifying fibromas, and osteomas may all frequent follow-up is nec-
present as intraoral masses with bony expansion and normal essary.
overlying mucosa.
malignant
premalignant
Minor Salivary Gland
Leukoplakia Malignancies
Leukoplakia is defined The majority (60 to
by the World Health 70%) of minor salivary
Organization as a whitish gland neoplasms are malignant, with adenoid cystic carci-
patch or plaque that noma, mucoepidermoid carcinoma, and adenocarcinoma [see
cannot be characterized clinically or pathologically as any Figure 6a] being the most commonly encountered cancers.26,34
other disease and that is not associated with any physical or As with benign minor salivary gland neoplasms, the hard and
chemical causative agent (except tobacco).33 It is therefore a soft palates are the most common sites.34
clinicopathologic entity of exclusion. It is often considered a A minor salivary gland malignancy usually appears as a
potentially premalignant lesion. Leukoplakic lesions vary in painless, slow-growing, intraoral mass.35 Nodal involvement
size, shape, and consistency; there is usually no relation at presentation is uncommon.26 Treatment usually involves
between morphologic appearance and histologic diagnosis. surgical excision; adequate margins should be obtained
Histologic examination may reveal hyperkeratosis, dysplasia, with frozen-section control. Because these malignancies—
carcinoma in situ (CIS), or invasive squamous cell carcinoma, particularly adenoid cystic carcinoma and polymorphous
or other pathologic processes.16 Dysplasia occurs in as many low-grade adenocarcinoma—have a propensity for perineural
as 30% of leukoplakic lesions.8 Whereas a small percentage of spread, frozen-section analysis of the nerves within the field
lesions show invasive squamous cell carcinoma on pathologic of resection is usually obtained at the time of operation.
examination,14 60% of oral mucosa carcinomas present as If perineural spread occurs, postoperative irradiation is
white, keratotic lesions.16 usually indicated, and distant metastases are likely to develop
Because leukoplakias are clinicopathologic entities, a biopsy despite surgery and locoregional radiotherapy. As a result, it
result of “hyperkeratosis, acanthosis with or without inflam- is usually best to limit the extent of the operation if major
mation” must be further interpreted by the clinician as to morbidity is anticipated from a radical resection.
whether the clinical lesion could represent a frictional injury Neck dissection is warranted in the treatment of minor
such as morsicatio mucossae oris, benign alveolar ridge salivary gland malignancies only if there is clinical or
keratosis, or some other less well-defined frictional keratosis. radiographic evidence of cervical metastases. Postoperative
This is because it is well known that some so-called “benign irradiation is indicated for most patients with high-grade
leukoplakias” will develop squamous cell carcinoma when malignancies, positive or close surgical margins, cervical
followed. Furthermore, the entity “proliferative verrucous metastases, or pathologic evidence of perineural spread
leukoplakia” almost always shows benign histology for many or bone invasion.35 Studies suggest that postoperative radio-
years and the majority if not all of such lesions become therapy allows improved local control and may lead to longer
invasive cancer when followed over time. disease-free survival.36,37
All leukoplakic lesions should undergo biopsy. For small Local recurrence and distant metastases are common, often
areas of leukoplakia, excisional biopsy is usually appropriate. developing many years later; regional recurrence is uncom-
For larger lesions, incisional biopsy is generally preferable: it mon.34 The survival rate for adenoid cystic carcinoma is
is important to obtain an adequate-size biopsy specimen in relatively high (approximately 80%) at 5 years but decreases
that varying degrees of hyperplasia and dysplasia may occur dramatically over the subsequent 10 to 15 years.34,38 Various
within the same specimen. There is no consensus regarding factors predictive of poor survival have been identified [see
the management of “nondysplastic” leukoplakias that in the Table 5].38
clinician’s opinion are not reactive or inflammatory in nature.
Some believe that such hyperkeratotic lesions should be Mucosal Melanoma
followed on a long-term basis, with rebiopsy performed if After the sinonasal region, the oral cavity is the site at
there are any changes in size or appearance. Others believe which mucosal melanoma most often occurs in the head and
that they should be narrowly excised and, if the lesion recurs, neck.39 Within the oral cavity, mucosal melanoma is most
more widely excised. Lesions characterized by dysplasia and frequently found involving the upper alveolus and the hard
CIS should be completely excised to clear margins when palate.40 It is most common in men, usually developing in the
possible. sixth decade of life.40 No specific risk factors or premalignant
lesions have been identified. There may, however, be an
Erythroplakia increased risk among certain subsets of East Asian patients.
Erythroplakia is defined as a red or erythematous patch of Oral mucosal melanoma typically appears as a flat or
the oral mucosa. It is associated with significantly higher rates nodular pigmented lesion, frequently associated with ulcer-
of dysplasia, CIS, and invasive carcinoma than leukoplakia ation. Amelanotic melanoma is, fortunately, rare.41 Patients
is.8 Erythroplakia is managed in much the same fashion as usually seek medical attention at an advanced stage of the
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a b c
d e f
Figure 6 Shown are malignant lesions of the oral cavity: (a) polymorphous
low-grade adenocarcinoma of the hard palate (raised, erythematous lesion);
(b) extensive squamous cell carcinoma of the tongue, the alveolar ridge, and the
floor of the mouth; (c) squamous cell carcinoma of the right floor of the mouth, with
mandibular invasion on computed tomography scan; (d) squamous cell carcinoma
of the lip (ulcerative lesion); (e) squamous cell carcinoma of the floor of the
mouth (exophytic lesion); (f) squamous cell carcinoma of the hard palate; and
(g) squamous cell carcinoma of the retromolar trigone.
disease, when pain develops or when they notice a change immunohistochemical staining (e.g., for HMB-45 antigen,
in the fit of their dentures. Early asymptomatic lesions Melan-A, or S-100 protein). Any suspicious pigmented
are usually identified incidentally by either a physician or lesion in the oral cavity should undergo biopsy to rule out
a dentist. Approximately 25% of patients have nodal melanoma. Amalgam tattoos are common in the oral cavity
metastases at presentation.40 Tumors thicker than 5 mm are and can often be diagnosed on the basis of the presence of
associated with an increased likelihood of nodal metastases metallic fragments on dental radiographs.
at presentation.42 Mucosal melanoma is managed primarily with surgical
No formal staging system has been developed for mucosal resection. The role of radiation therapy in this setting remains
melanoma. The diagnosis is made by means of biopsy and controversial.39 Some clinicians recommend postoperative
radiotherapy for all cases of mucosal melanoma; others rec-
ommend it only for patients with close or positive margins.
Table 5 Poor Prognostic Factors for Minor Salivary Gland The role of lymph node mapping has not been defined for
Malignancies
mucosal melanoma. Because of the high incidence of nodes
Advanced disease at time of diagnosis at presentation and the high regional recurrence rates reported
Positive nodes
in some studies, consideration should be given to treating
High-risk histologic type (i.e., high-grade malignancies such as
high-grade mucoepidermoid carcinoma, adenocarcinoma, the neck prophylactically by extending the postoperative
carcinoma ex pleomorphic adenoma, and adenoid cystic radiation fields to cover this region.39,40
carcinoma) The poor prognosis of mucosal melanoma with conven-
Positive margins tional treatment employing surgery and irradiation is a strong
Male sex
argument for referring patients to a medical oncologist for
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potential enrolment in postoperative systemic therapy trials. Table 7 Growth Patterns of Squamous Cell Carcinoma of
The survival rate for oral mucosal melanomas at 5 years Oral Cavity48
ranges from 15 to 45%,40,41,43 with most patients dying of Growth Pattern Characteristics
distant disease. Nodal involvement further reduces survival.41
Melanoma of the gingiva has a slightly better prognosis than Ulceroinfiltrative Most common pattern; appears as ulcerated
lesion that penetrates deep into underly-
melanoma of the palate.41 Several factors predictive of poor ing structures with surrounding indura-
survival have been identified [see Table 6].40 The relation tion
between lesion depth and prognosis is not as clearly defined
Exophytic Common on lip and buccal mucosa;
for oral mucosal melanoma as it is for cutaneous melanoma. appears as papillary mass that may
ulcerate when large
Squamous Cell Carcinoma
Endophytic Uncommon; extends deep into soft tissue,
The incidence of squamous cell carcinoma increases with with only small surface area involved
age, with the median age at diagnosis falling in the seventh
decade of life,44,45 and is higher in men than in women. This
Superficial Flat, superficial appearance; may be either
cancer may be found at any of a number of oral cavity sub- a white patch or a red/velvety patch
sites [see Figure 6, b through g]. Lip carcinoma is the most
common oral cavity cancer; 80 to 90% of these lesions occur
on the lower lip.13 After the lip, the most common sites for tongue and the mandible. Decreased tongue mobility as a
oral cavity carcinoma are the tongue and the floor of the result of fixation is an indicator of an advanced tumor.48,49
mouth. When the primary lesion is on the tongue, the lateral Mandibular invasion occurs frequently in carcinomas of the
border is the most common location, followed by the anterior floor of the mouth, the retromolar trigone, and the alveolar
tongue and the dorsum.8 Approximately 75% of cases of oral ridge as a consequence of the tight adherence of the mucosa
cavity squamous cell carcinoma arise from a specific 10% of to the periosteum in these regions. The risk of mandibular
the mucosal surface of the mouth,11 an area extending from invasion increases with higher tumor stages. The majority (70
the anterior floor of the mouth along the gingivobuccal sulcus to 80%) of alveolar ridge carcinomas occur on the lower
and the lateral border to the retromolar trigone and the ante- alveolus, often in areas of leukoplakia.50
rior tonsillar pillar.11 Verrucous carcinoma is a subtype of Oral cavity carcinoma is generally classified according to
squamous cell carcinoma and occurs most frequently on the the staging system developed by the American Joint Commit-
buccal mucosa, appearing as a papillary mass with keratiniza- tee on Cancer [see Table 8 and Table 9].51 Staging is based on
tion. clinical examination and diagnostic imaging. The diagnosis is
Between 80 and 90% of patients with oral cavity carcinoma made on the basis of biopsy and immunohistochemical stain-
have a history of either tobacco use (cigarette smoking or ing (e.g., for cytokeratin and epithelial membrane antigen).
tobacco chewing) or excessive alcohol intake.46 A synergistic Squamous cell carcinoma of the oral cavity is usually man-
effect is created when alcohol and tobacco are frequently aged with surgery, radiation therapy, or a combination of the
used together.46 In Asia, the practice of reverse smoking is two. Chemotherapy is increasingly used in combination with
associated with a high incidence of palatal carcinoma; betel radiotherapy for patients at high risk of local or regional
nut chewing is associated with a high incidence of buccal recurrence. For localized disease without bone invasion, the
carcinoma. The incidence of tumors in patients who have cure rate for radiation therapy is comparable to that of sur-
never smoked or drunk alcohol is rising, and the role of gery.46 The development of free tissue transfer has allowed for
human papillomavirus in the pathogenesis and prognosis of the successful cosmetic and functional reconstruction of large
this disease continues to be defined.47 surgical defects of the oral cavity, including the mandible.
Small lesions tend to be asymptomatic. Larger lesions are Advanced tumors of the oral cavity are best managed with
often associated with pain, bleeding, poor denture fit, facial both surgery and irradiation. Traditionally, in North Amer-
weakness or sensory changes, dysphagia, odynophagia, and ica, oral cavity cancer is treated primarily with surgery, and
trismus. Oral intake may worsen the pain, leading to malnu- postoperative radiotherapy is added if the disease is advanced
trition and dehydration. or if there are pathologic features indicative of a high risk of
Squamous cell carcinoma of the oral cavity has four differ- recurrence (i.e., positive margins on microscopy, extensive
ent possible growth patterns: ulceroinfiltrative, exophytic, perineural or intravascular invasion, two or more positive
endophytic, and superficial [see Table 7].48 Lip and buccal car- nodes or positive nodes at multiple levels, or nodal capsular
cinomas tend to appear as exophytic masses. Ulceration is extension). North American practice is reflected in the guide-
less common early in the course of cancers arising at these lines developed by the American Head and Neck Society
sites, but it may develop as the lesion enlarges. Cancers of the (www.headandneckcancer.org/clinicalresources/docs/oralcav-
floor of the mouth may be associated with invasion of the ity.php).
Radiation may be delivered to an oral cavity carcinoma via
either external beam radiotherapy or brachytherapy, with the
Table 6 Poor Prognostic Factors for Mucosal Melanoma former being more commonly employed. Postoperative radia-
Amelanotic melanoma
tion, if indicated, should be started 4 to 6 weeks after surgery.
Advanced stage at presentation The total radiation dose depends on the clinical and patho-
Tumor thickness > 5 mm logic findings; the usual range is between 50 and 70 Gy,
Presence of vascular invasion administered over 5 to 8 weeks. Primary radiation therapy is
Distant metastases indicated for patients with stage I and selected stage II oral
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Table 8 American Joint Committee on Cancer TNM Classification of Head and Neck Cancer
Primary tumor (T) TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor 2 cm or less in greatest dimension
T2 Tumor more than 2 cm but not more than 4 cm in greatest dimension
T3 Tumor more than 4 cm in greatest dimension
T4a Tumor invades adjacent structures, extending through cortical bone into deep (extrinsic) muscles of
tongue, maxillary sinus, or facial skin
T4b Tumor invades masticator space, pterygoid plates, or skull base or encases internal carotid artery
Regional lymph nodes (N) NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastases
N1 Metastases in a single ipsilateral lymph node f3 cm in greatest dimension
N2a Metastases in a single ipsilateral lymph node > 3 cm but f6 cm in greatest dimension
N2b Metastases in multiple ipsilateral lymph nodes, none > 6 cm in greatest dimension
N2c Metastases in bilateral or contralateral lymph nodes, none > 6 cm in greatest dimension
N3 Metastases in lymph node > 6 cm in greatest dimension
Distant metastases (M) MX Distant metastases cannot be assessed
M0 No distant metastases
M1 Distant metastases
cavity carcinomas, patients who refuse surgery or in whom Squamous cell carcinoma of the oral cavity tends to spread
surgery is contraindicated, and patients with incurable lesions to regional lymph nodes in a relatively predictable fashion.
who require palliative treatment. Radiation therapy is less The primary levels of metastatic spread from oral cavity car-
effective against large or deeply invasive tumors, especially cinoma include level I through III nodes and, less frequently,
those that are invading bone, and therefore generally is not level IV nodes53–55; metastases to level V are infrequent.53,55
used alone for curative management of T3 and T4 lesions. The likelihood that cervical node metastases will develop
For advanced-stage tumors of the oral cavity, surgery with varies depending on the location of the primary tumor in the
postoperative radiotherapy is performed to decrease recur- oral cavity and on the stage of the tumor. Cervical metastases
rence rates. Brachytherapy can be used as an adjunct when from carcinomas of the lip or the hard palate usually occur
close or positive margins are noted. Brachytherapy also has a only in advanced disease8; however, cervical metastases from
role in the management of recurrence or previously irradiated carcinomas of any of the other oral cavity subsites are common
patients.52 at presentation [see Table 10].8,11,48,50,51,53,56,57 Larger tumors
The decision regarding which treatment is presented to a carry a higher risk of cervical metastasis.
patient as the first option is often determined by factors other The clinically positive neck is usually managed with either
than the extent of the tumor. Patient factors to be considered a radical or a modified radical neck dissection, depending on
include desires and wishes, age, medical comorbidities, and the extent of the disease. Some studies have found that for
N1 and some N2a patients, a comparable control rate can be
performance status. Disease factors to be considered include
achieved with a selective neck dissection encompassing levels
tumor grade and stage, extent of invasion, primary site, the
I through IV, with postoperative radiation therapy added
presence and degree of nodal or distant metastasis, and previ-
when indicated.58,59
ous treatment. It is often helpful to discuss each case at a
The clinically negative neck can occasionally be managed
multidisciplinary treatment planning conference to develop a
with observation alone, with treatment initiated only when
ranked list of options. nodal metastases develop. Alternatively, the nodal basins at
risk can be managed prophylactically by means of either sur-
gery or radiation therapy (involving levels I through III and,
possibly, IV). The rationale for prophylactic neck manage-
Table 9 American Joint Committee on Cancer Staging ment is that treatment initiated while metastases are still
System for Head and Neck Cancer
Stage T N M
0 Tis N0 M0
Table 10 Incidence of Nodal Metastases* at Presentation in
I T1 N0 M0 Oral Cavity Subsites
II T2 N0 M0 Oral Cavity Subsite Incidence of Metastases (%)
III T3 N0 M0 Lip 10
T1, T2, T3 N1 M0
Tongue 30–40
IVA T4a N0, N1 M0
T1, T2, T3, T4a N2 M0 Floor of the mouth 50
IVB Any T N3 M0 Alveoli 28–32
T4b Any N M0
Buccal mucosa 40–52
IVC Any T Any N M1
*Clinically detectable or occult.
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occult is thought to be more effective than treatment initiated common oral infection seen almost exclusively in the HIV
after the disease has progressed to the point where it is clini- population. It presents as an asymptomatic, corrugated, whit-
cally detectable. For this reason, many clinicians advocate ish, nonremovable, slightly raised patch on the lateral borders
prophylactic neck dissection for patients with oral cavity car- of the tongue. The finding of such a lesion on clinical exam-
cinomas who are at moderate (15–20%) risk for occult metas- ination of an HIV patient is suggestive of the diagnosis, but
tases at presentation. The selective neck dissection not only confirmation of the diagnosis requires biopsy. Treatment
addresses any occult metastatic nodes but also functions as a usually is not necessary. High-dose acyclovir may be given if
staging procedure that helps in determining the prognosis the patient requests treatment.
and assessing the need for postoperative radiotherapy.60,61 In Several rare infections of the oral cavity are being seen
general, elective neck management is recommended for T2 with increasing frequency in the HIV population, including
and higher-stage carcinomas of the tongue, the floor of the tuberculosis, syphilis, Rochalimaea henselae infection (bacil-
mouth, the buccal mucosa, the alveolus, and the retromolar lary angiomatosis), Borrelia vincentii infection (acute necrotiz-
trigone, as well as for advanced (T3 or T4) carcinomas of the ing ulcerative gingivitis), cryptococcosis, histoplasmosis,
lip and the hard palate.8,11,48,56,57,62,63 Most surgeons now coccidioidomycosis [see Figure 7], and human papillomavirus
emphasize the depth of invasion of the primary tumor as a infection.
critical determinant of the risk of occult nodal metastases. It
has been suggested that elective treatment of the neck with neoplasms
surgery or radiation therapy should be considered on the The two most common intraoral neoplasms in the HIV
basis of the depth of tumor invasion rather than the surface population are Kaposi sarcoma and non-Hodgkin lymphoma.
diameter of the lesion. The tumor depth that is held to war- Kaposi sarcoma occurs most commonly in patients with HIV,
rant investigation varies among published studies, ranging although it is not exclusive to this population. It frequently
from 2 to 5 mm.64–66 Bilateral neck dissection may be indi- involves the oral cavity, showing a predilection for the attached
cated for midline oral cavity cancers. mucosa of the palate or the gingiva.68 The characteristic
The prognosis depends on the location of the tumor in the
lesions are blue, brown, purple, or red exophytic masses that
oral cavity. Overall, if all of the oral cavity subsites are con-
may be either confined to the oral mucosa or systemic. They
sidered together, the presence of cervical metastases decreases
are usually asymptomatic but may become painful or obstruc-
survival by approximately 50%. Varying 5-year survival rates
tive with growth or ulceration. Treatment is aimed at pallia-
have been reported for the different subsites of the oral cavity
tion of symptoms and may involve sclerotherapy, intralesional
[see Table 11].8,11,48,50,51,56,67
chemotherapy, laser ablation, cryotherapy, surgical excision,
or radiation therapy.69 Systemic chemotherapy may be
Oral Cavity Manifestations of HIV Infection provided if the disease is systemic.
Infectious and neoplastic oral cavity lesions are often the
first manifestation of HIV infection or the first indication of
the progression to AIDS.
infections
The same organisms that affect the general population
cause most of the oral infections seen in the HIV population;
however, oral infections in HIV patients tend to be recurrent,
comparatively severe, and relatively resistant to treatment.68
Oral hairy leukoplakia, caused by Epstein-Barr virus, is a
Table 11 Five-Year Carcinoma Survival Rates for Oral

Cavity Subsites
Oral Cavity Subsite Survival Rate
Lip 80%; > 90% for early-stage disease
Figure 7 Shown is coccidioidomycosis of the tongue in an
Tongue 30–35% (advanced-stage disease); HIV-positive patient.
> 80% (early-stage disease)
Floor of the mouth 85% for stages I and II (T1 lesions
The risk of non-Hodgkin lymphoma is much higher in the
> 95%); 20–52% for stages III and HIV population than in the general population.69 It should be
IV suspected in any HIV patient who presents with an intraoral
Alveoli 50–60% mass or an ulcerated lesion. Non-Hodgkin lymphoma appears
as painful lesions that show a predilection for the palate, the
Retromolar trigone 75% for T1 and T2 lesions;
retromolar trigone, and the tongue. Associated symptoms
approximately 20–50% for T3 and
T4 lesions include facial paresthesias, loose dentition, fever, night sweats,
and weight loss. Local disease is managed with radiation;
Buccal mucosa 49–68%
systemic disease is managed with chemotherapy.
Palate 85% for T1 lesions; 30% for T4
lesions
Financial Disclosures: None Reported.
02/10
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gingiva: a follow-up study of 83 cases. J Acknowledgments FACS, John W. Hellstein, DDS, and Gerry F.
Craniomaxillofac Surg 2000;28:331. Funk, MD, FACS, to the development and
68. Laskaris G. Oral manifestations of HIV writing of this chapter.
disease. Clin Dermatol 2000;18:447. The authors and editors gratefully acknowledge
69. Casiglia JW, Woo S. Oral manifestations of the contributions of the previous authors, David
HIV infection. Clin Dermatol 2000;18:541. P. Goldstein, MD, Henry T. Hoffman, MD, Figure 1 Tom Moore
02/10
2 HEAD AND NECK 2 PAROTID MASS — 1
2 PAROTID MASS
Harrison W. Lin, MD, and Neil Bhattacharyya, MD, FACS*
Demographics the masseter muscle, and then turns medially to pierce the
Major salivary gland tumors constitute 3 to 6% of all buccinator muscle at the level of the second maxillary molar
tooth and open into the mouth through the parotid papilla.
tumors of the head and neck in adults,1 and approximately
The expected course of the duct is approximated by a line
85% of these salivary gland tumors are found in the parotid
drawn between the tragus and philtrum of the upper lip,
gland. Roughly 16% of these neoplasms are malignant.2 The
midway between the angle of the mouth and the zygomatic
spectrum of histopathologic entities encompassed by the term
arch.
“parotid mass” is exceedingly broad and continues to evolve
as our understanding of the origin and clinical behavior of the
various tumors arising from the parotid gland expands. Etiology
Two predominant theories of the neoplastic pathogenesis
Anatomy of parotid masses have been proposed, including the bicell-
ular and multicellular theories. The former, also referred to
The parotid gland is an irregular, wedge-shaped, unilobu- as the reserve cell theory, suggests that tumors arise from
lar salivary gland residing in the parotid space, a compart- stem cell populations in both the excretory and intercalated
ment that additionally contains the facial nerve (cranial nerve ductal systems. Warthin tumor, mixed tumor, oncocytoma,
VII), sensory and autonomic nerves, branches of the external acinic cell carcinoma, adenoid cystic carcinoma, and onco-
carotid artery and external jugular vein, and lymphovascula- cytic carcinoma are proposed to arise from stem cells of the
ture [see Figure 1].3 The gland itself resides within the split intercalated duct, whereas squamous cell carcinoma (SCC)
layers of the superficial layer of the deep cervical fascia and and mucoepidermoid carcinoma are thought to derive from
overlies the upper one fourth of the sternocleidomastoid excretory duct stem cells. Alternatively, the multicellular
muscle, the ramus of the mandible, and the masseter muscle. theory suggests that the various parotid tumors arise from the
Approximately 20% of the gland extends medially through fully differentiated cells within the salivary gland unit. Based
the stylomandibular tunnel, which is formed by the posterior on this theory, mucoepidermoid and squamous cell carcino-
edge of the mandibular ramus, the anterior border of the mas derive from excretory duct cells, oncocytic tumors from
sternocleidomastoid muscle, and the posterior belly of the striated duct cells, acinous tumors from acinar cells, and
digastric muscle. At its lower pole, the parotid gland is sepa- mixed tumors from intercalated duct cells and myoepithelial
rated from the submandibular gland by the stylomandibular cells.4
ligament, which extends from the tip of the styloid process to Although the true nature of the neoplastic transformation
the angle and the posterior edge of the mandible. of parotid gland cells is yet to be fully elucidated, these and
The seventh cranial nerve artificially divides the parotid other classification systems are founded on the understanding
gland into two surgical zones: tissue lateral to the facial nerve that primary parotid tumors are of epithelial origin. The
is designated as the superficial lobe, whereas the medial parotid gland also hosts numerous lymph nodes that serve as
portion is referred to as the deep lobe. Moreover, each lobe a basin for metastatic spread of malignancies of the head.
has been described to have variable processes, including the Accordingly, parotid masses will not infrequently represent
the presenting sign of a cutaneous SCC or melanoma of the
condylar, meatal, and posterior processes of the superficial
temple or scalp, for example.
lobe and the glenoid and stylomandibular processes of
the deep lobe. Furthermore, a retromandibular portion of
the deep lobe resides in the prestyloid compartment of the Differential Diagnosis
parapharyngeal space, anterior to the styloid process and
associated musculature, the carotid sheath, and cranial nerves nonneoplastic conditions
IX through XII. Note that the separation of the parotid gland The causes of nonneoplastic parotid masses include
into superficial and deep lobes is not based on a fascial plane. congenital, infectious or inflammatory, and lymphoepithelial
The parotid isthmus, the portion of the gland between the conditions. Congenital lesions such as hemangiomas and
ramus of the mandible and the posterior belly of the digastric vascular malformations often present in childhood as a swell-
muscle, connects the superficial with the deep lobes of the ing in the preauricular region. First branchial cleft cysts can
parotid gland. also present in the pediatric population and can be manifest
The parotid (Stensen) duct originates from the superficial as a mass inferior to the cartilaginous external auditory canal
lobe of the gland, courses anteriorly on the lateral surface of and with a cyst tract that will have a variable relationship with
the branches of the facial nerve.
* The authors and editors gratefully acknowledge the contribu- Inflammatory disorders of the parotid gland can be catego-
tions of the previous author, Ashok R. Shaha, MD, FACS, to rized into acute and chronic processes. Moreover, acute
the development and writing of this chapter. infections of the salivary glands can be further subclassified
DOI 10.2310/7800.S02C02
09/10
Figure 1 Anatomy of the parotid region. Branches of the facial nerve: A = temporal; B = zygomatic; C = buccal; D = marginal;
E = cervical.
into viral and bacterial processes. Although viral parotid many of the antibacterial lysosomes, antibodies, and mucins
infections by the RNA virus paramyxovirus resulting in the found in the mucinous saliva produced by the other major
mumps syndrome are now exceedingly rare following the salivary glands. Accordingly, bacterial sialadenitis most
introduction of the mumps vaccine in 1967, acute viral commonly affects the parotid gland. Relatively sudden onset
parotitis from the influenza, parainfluenza, adenovirus, cyto- of pain, tenderness, and swelling of the parotid are the most
megalovirus, coxsackievirus, and enteric cytopathic human frequent presenting signs and symptoms, and treatment
orphan (ECHO) viruses have been reported in the literature.5 consists of hydration, sialagogues, and systemic antistaphylo-
Acute bacterial infections of the parotid gland, however, are coccal therapy. If a discrete abscess is suspected and identi-
by far more common and are believed to be the result of fied on cross-sectional imaging, surgical or radiologically
retrograde contamination of the salivary ducts and parenchy- guided needle drainage may be required.
mal tissues by oral flora combined with stasis of salivary flow, Chronic inflammatory disorders of the parotid gland are
often attributable to dehydration. Additionally, the serous frequently manifested by a mildly painful, recurrent, and
composition of the saliva produced by the parotid gland lacks gradual enlargement of the gland. Of these disorders, chronic
09/10
sialadenitis is the most frequently encountered and is believed rates. Benign salivary tumors tend to be more common in
to be the result of reduced rates of salivary production and younger persons, whereas malignant parotid lesions are more
flow, resulting in frequent subacute suppurative infections, common in the fifth and sixth decades of life.8 The classic
sialectasis, ductal ectasia, and progressive acinar cell loss. presentation of a benign parotid tumor is that of an asymp-
Initial treatment is similar to that of acute bacterial sialadeni- tomatic parotid mass that has been present for months to
tis, and failure to respond to conservative measures may years, often exhibiting slow growth.
prompt consideration for surgical interventions, including
ductal dilation, ductal ligation, and parotidectomy. In Benign Neoplasms
sarcoidosis, salivary gland involvement may cause duct Benign neoplasms of the parotid, which include pleomor-
obstruction, pain associated with the duct, xerostomia, or phic adenoma, basal cell adenoma, myoepithelioma, Warthin
enlargement of the gland. The diagnosis is supported by chest tumor, oncocytoma, and cystadenoma, are typically slow-
films that show bilateral hilar adenopathy and by elevated growing and rarely exhibit malignant transformation.
levels of angiotensin-converting enzyme. Uveoparotid fever However, the observation of rapid growth in a long-standing
(Heerfordt disease), a subtype of sarcoidosis manifested pleomorphic adenoma (often 10 to 15 years later) is sugges-
by the triad of uveitis, parotid enlargement, and facial weak- tive of malignant transformation. In a 2005 study of 94
ness, can persist for months to years and will often resolve patients with pleomorphic adenoma, malignant transforma-
spontaneously and without treatment.6 tion to carcinoma ex pleomorphic adenoma was documented
Lymphoepithelial lesions of the parotid gland may be in 8.5% of cases.9 Rapid tumor growth, metastasis to lymph
divided into lymphocytic infiltrative diseases and lymphomas. nodes, deep fixation, and facial nerve weakness are all strongly
In many cases, patients with lymphocytic infiltrative diseases suggestive of malignant disease and are indicators of a poor
such as Mikulicz disease, sicca complex, and Sjögren syn- prognosis.10 Although pain is more often experienced by
drome have had their conditions for long periods and simply patients with inflammatory or infectious conditions, it is
believe that their chronic enlargement of bilateral parotid also reported by some patients with infiltrative malignant
glands was normal facial soft tissue changes associated with tumors. In these patients, pain is another indicator of a poor
age. Eighty percent of patients with primary Sjögren syn- prognosis.11,12
drome will experience parotid gland swelling; moreover,
malignant transformation to high-grade lymphoma is known Malignant Neoplasms
to occur. Lymphoepithelial cysts are benign cystic lesions that Although considerable debate continues to surround the
may arise from lymph nodes or from lymphoid aggregates in histopathologic classification of malignant parotid tumors,
the salivary gland. These lesions may be associated with HIV most clinicians currently prefer the classification system of
infection. the Armed Forces Institute of Pathology13 or that of the
Primary lymphoma of the salivary gland is uncommon,
World Health Organization.14 Malignant parotid neoplasms
occurring in fewer than 5% of patients with parotid masses.
include primary SCC, mucoepidermoid carcinoma, acinic
Suggestive clinical features include (1) the development of a
cell carcinoma, adenocarcinoma, adenoid cystic carcinoma,
parotid mass in a patient with a known history of malignant
carcinoma ex pleomorphic adenoma, and malignant mixed
lymphoma, (2) the occurrence of a parotid mass in a patient
tumor. The presence of facial nerve palsy should raise the
with an immune disorder (e.g., Sjögren syndrome, rheuma-
index of suspicion for malignancy. Occasionally, patients
toid arthritis, or AIDS), (3) the presence of a parotid mass in
present with classic Bell palsy. This condition is usually of
a patient with a previous diagnosis of benign lymphoepithelial
lesion, (4) the finding of multiple masses in one parotid gland viral origin, and most patients recover over time. If Bell palsy
or of masses in both parotid glands, and (5) the association persists, however, further investigation is required, including
of a parotid mass with multiple enlarged cervical lymph nodes imaging or biopsy studies to rule out an associated parotid
unilaterally or bilaterally.7 lesion.15
As discussed, infectious or inflammatory diseases involving Mucoepidermoid carcinoma is the most common malig-
the parotid, unlike neoplasms, tend to give rise to pain in nant tumor of the parotid gland, comprising roughly one
their early stages. However, certain parotid malignancies may third of all parotid cancers, and is subclassified into low-,
also present with pain attributable to sensory nerve involve- intermediate-, and high-grade tumors. For high-grade tumors,
ment. Most such inflammatory conditions begin with diffuse selective cervical node dissection may be indicated and
enlargement of one or more salivary glands rather than with postoperative radiation therapy is often required. Combined
presentation with a discrete, palpable parotid mass. Although surgical and radiation therapies for such tumors results in a
parotitis is generally unilateral, it may be bilateral or affect 5-year survival rate of under 50%. In contrast, low-grade
other salivary glands if a systemic causative condition is tumors are more circumscribed and contain more mucinous
involved. The pain reported may be related to the presence cells. Surgical therapy without radiation yields a 5-year
of a stone in the salivary duct or to diffuse obstructive paroti- survival rate of 75%.
tis. Chronic parotitis may lead to recurrent infection and Adenoid cystic carcinoma is an aggressive salivary gland
inflammation. When recurrent swelling of the salivary gland tumor that exhibits a very high incidence of perineural spread
does occur, it may be directly related to eating and increased with skip metastasis along the facial nerve and its branches,
salivation. and the incidence rises with higher tumor stages.16 The inci-
dence of local recurrence is also very high; therefore, post-
neoplastic conditions operative radiation therapy should be provided to patients
Neoplastic masses may be present for years without caus- who are at high risk for relapse, such as those with close or
ing any symptoms and affect both men and women at similar positive margins and those with perineural invasion. Although
09/10
Approach to Evaluation
of a Parotid Mass
Patient presents with parotid mass
Obtain clinical history.

Perform physical examination of parotid region, focusing on
extent of parotid disease, localized effects of lesion, and any
motor or sensory deficits.
Diffuse enlargement is present Solitary mass is identified
Diagnosis is obvious Diagnosis is uncertain
Plan treatment (conservative or surgical, Initiate further workup:

as indicated). • Imaging (CT, MRI, ultrasonography, sialography,
?sialoendoscopy, ?PET)
• FNA biopsy (routine use is controversial)
Lesion is benign Lesion is malignant
Treat surgically with parotidectomy, preserving Treat surgically with superficial, total, or radical
facial nerve. parotidectomy, as necessary, preserving facial nerve if possible.
If cervical lymphadenopathy is present, consider elective neck
dissection (comprehensive or selective, as appropriate).
Provide postoperative radiotherapy for all patients except those
with T1 or T2 tumors of low-grade histology and clear margins.
09/10
the incidence of cervical lymph node metastasis in patients presentations of some nonneoplastic conditions resemble
with adenoid cystic carcinoma is relatively low, the incidence those of neoplasms, and distinguishing one type of condition
of distant metastasis (especially pulmonary metastasis) has from the other can be challenging. Accordingly, the history
been reported to be as high as 38%.17 Long-term follow-up should continue with further questions focusing on local or
in these patients is essential. systemic signs and symptoms, the presence of swelling or
Adenocarcinoma has been considered a shrinking category other masses in the salivary glands, and previous medical
as advances in electron microscopy and immunohisto- conditions, including cancers of the skin.
chemistry have reclassified many of these tumor variants into
other subtypes and histopathologies. Adenocarcinomas are physical examination
exceedingly aggressive tumors with high rates of facial nerve The physical examination begins with an assessment of the
involvement, regional disease, and distant metastases and, extent of the disease in the parotid region, the neck, and the
accordingly, should be managed as a high-grade parotid parapharynx. Extension of a tumor to regional compartments
tumor with surgical and radiation therapies. can be manifest as trismus or as motor or sensory deficits
Acinic cell carcinoma is a low-grade tumor with a female resulting from neural invasion. Palpation of the mass will
predominance and bilateral presentation approximately 3% reveal whether it is painless or painful; soft, firm, hard, or
of the time. Tumors are frequently well circumscribed, but a cystic; and mobile or fixed to deep tissue or skin. The skin of
small percentage of patients will present with cervical nodal the scalp, ear, and face should be carefully examined for sus-
metastases. Patients with acinic cell carcinoma are typically picious lesions, and the neck is palpated for adenopathy. In
managed with surgical therapy alone, although histopatho- the oral cavity, the Stensen ducts are examined for discharge
logic findings to suggest a more aggressive, high-grade tumor or saliva with parotid massage. The oropharynx is examined
have been proposed to serve as indicators for postoperative for asymmetries or lateral wall deviation.
radiation therapy.18 The most common presentation of a parotid mass, whether
Primary SCC of the parotid gland is quite rare, and most benign or malignant, is an asymptomatic swelling in the
diagnoses of parotid SCC represent skin cancer that has preauricular or retromandibular region. Of note, the location
metastasized to the periparotid lymph nodes. Primary SCC of the parotid mass is a very important diagnostic factor.
has a high malignant potential, and radical surgical extirpa- A benign tumor will classically present as a firm, mobile, and
tion (with preservation of the facial nerve when possible), marblelike mass in the superficial portion of the gland and
followed by planned postoperative radiotherapy, is the not fixed to the deeper structures or to the skin. Parotid
treatment of choice.19 tumors that originate in the deep lobe, however, may present
as a vague, diffuse swelling behind the angle of the mandible
Metastatic Neoplasms to the Parotid
or as a swelling of the parapharyngeal area, resulting in
The parotid gland represents the first or second nodal basin medial displacement of the tonsil, soft palate, or lateral
for metastatic scalp, temple, and auricular cutaneous malig- oropharyngeal wall.
nancies. Although the incidence of metastatic parotid disease Occasionally, patients will present with metastases to one
is comparatively low in the Northern Hemisphere, it has been or more of the 17 to 20 intraparotid or periparotid lymph
reported to be far more common than primary parotid disease nodes in the substance of the parotid and along its tail. These
in regions of the world with high rates of skin cancers, such lymph nodes may be directly affected by metastatic tumors
as Australia.20 Cutaneous SCC and melanoma are by far the originating from the anterior scalp or the temporal, periocu-
most frequently encountered metastatic parotid malignancies lar, or malar regions. It is critical to obtain a detailed history
and, despite treatment, will exhibit local or distant failure in of any previously excised skin lesions, some of which may
25 to 50% of cases. Other cancers that have been reported to have been an SCC or a melanoma primary tumor that metas-
metastasize to the parotid include basal cell, Merkel cell, and tasized to the periparotid nodes. Generally, such metastasis
small cell carcinomas. involves multiple superficial lymph nodes and presents as
diffuse enlargement of the parotid parenchyma. With massive
Presentation and involvement of the parotid gland, facial nerve palsy is not
Diagnostic Workup uncommon in this setting. Although the majority of metasta-
ses to the parotid gland derive from cutaneous SCC or mela-
history noma, metastatic spread from the lung, breast, and kidney
Evaluation of any has also been reported.
parotid mass should As with any patient with an otolaryngologic complaint, a
begin with a detailed thorough evaluation of the head and neck, including a detailed
clinical history. Com- visualization of the oral cavity and laryngopharynx, is required.
prehensive inquiries Occasionally, a tumor of the oropharynx presents as cervical
regarding the dura- lymphadenopathy or as metastatic disease in the tail of the
tion of signs and parotid. In such cases, it may be difficult to determine whether
symptoms are paramount as masses resulting in local pain the patient has a primary salivary gland tumor or a metastatic
and swelling of recent onset (i.e., within the past few days) lesion. The presence of any suspicious pathologic condition
are more likely to be infectious or obstructive in nature. If in the oropharynx or the base of the tongue is an indication
the mass has been present for a longer period (i.e., weeks for appropriate endoscopy and biopsy of the suspected
to months), a neoplasm is more likely. Unfortunately, the primary site.
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Physical findings suggestive of malignancy include a large Table 1 Salivary and Nonsalivary Pathologic Processes
and fixed mass, facial nerve weakness, lymph node metasta- Distinguished by Fine-Needle Aspiration Biopsy
sis, and skin involvement; patients with advanced parotid Salivary processes
malignancies may present with trismus. Although patients Benign
with benign parotid tumors rarely exhibit facial nerve Mixed tumor
weakness, approximately 12 to 15% of patients with parotid Warthin tumor
malignancies have facial nerve dysfunction at presentation. Oncocytoma
Malignant
The most common causes of facial nerve weakness in this Primary salivary gland cancer
setting are adenoid cystic carcinoma, poorly differentiated Adenoid cystic carcinoma
carcinoma, and SCC. Acinic cell carcinoma
The presence of cervical lymph node metastasis may direct Adenocarcinoma
SCC
the clinician’s attention to the parotid mass, although less Mucoepidermoid carcinoma
than 20% of persons with parotid malignancies actually Metastatic disease in salivary gland
have clinically apparent cervical lymph node metastases at the Melanoma
time of the initial presentation.11,21 The parotid tumors most SCC
commonly associated with metastatic disease to the lymph Nonsalivary processes
nodes at presentation are undifferentiated carcinoma (89%),22 Lipoma
high-grade mucoepidermoid carcinoma (42%),23 and SCC Sebaceous cyst
Lymph node pathology
(44%).24 Lymph node metastases may also derive from high-
Metastatic cancer
grade adenocarcinomas (22%) or malignant mixed tumors Lymphoma
(16%).25
SCC = squamous cell carcinoma.
Some patients will present without any symptoms, with the
only significant physical examination finding being an oro-
pharyngeal mass, which is suggestive of either a deep-lobe
parotid or parapharyngeal tumor. Given that between 80 and
therapies. Additionally, preoperative knowledge of a parotid
90% of the parotid tissue is superficial to the facial nerve, the
malignancy has been shown to significantly impact both sur-
majority of parotid tumors, not surprisingly, develop within
gical planning and surgical results. In one study, patients who
the superficial lobe of the parotid. However, approximately
underwent parotidectomy for an FNAC-diagnosed parotid
10% of parotid masses will be found within the deep lobe.
Most deep-lobe parotid tumors are benign, in which case, malignancy had significantly higher rates of both upfront
surgical treatment generally consists of a superficial paroti- cervical neck dissections and clear pathologic margins.26 In
dectomy with dissection and preservation of the facial nerve, addition, knowledge of the nature of a parotid mass may
followed by removal of the tumor. Occasionally, however, greatly influence patient counseling, which may have particu-
malignant deep-lobe parotid tumors do occur, and such lar utility in patients who are poor surgical candidates or
tumors frequently involve the facial nerve. Surgical treatment prefer a watchful-waiting strategy, when appropriate. Accord-
may require sacrifice of the facial nerve in select circum- ingly, the use of FNAC in the evaluation of a parotid mass
stances. Most patients who have undergone surgical should be strongly considered as it is generally felt to be an
treatment of a malignant deep-lobe tumor will require excellent investigational tool as long as it is employed in the
postoperative radiation therapy. appropriate clinical context.
fine-needle aspiration cytology imaging

Although fine-needle aspiration cytology (FNAC) has been Modern imaging of
shown to play a vital part in the management of head and salivary gland pathol-
neck SCC, the role of FNAC in parotid gland masses has yet ogy predominantly
to be fully resolved. This is attributable in large part to the consists of computed
perceived minimal impact of FNAC results on therapeutic tomography (CT) or
decision making as most parotid masses, both benign and magnetic resonance
malignant, will require surgical excision and thereby provide imaging (MRI) or
a definitive pathologic diagnosis. Moreover, the variability of both. As with their
histopathologic subtypes, intralesional cellular distribution, characteristics in the
and cytopathologist expertise has led some surgeons to imaging of other
question the utility of preoperative FNAC. regions of the body,
However, the ability of FNAC to distinguish masses of CT is considered superior to MRI for evaluation of the bony
benign nature from those of malignant nature, salivary gland structures, whereas MRI is typically more helpful in soft
origin from those of nonsalivary gland origin (e.g., sarcoid, tissue resolution and in distinguishing between inflammatory
lymphoma, metastatic melanoma), and, in some cases, conditions and neoplasms. Additionally, MRI may better dis-
low-grade malignancy from high-grade malignancy has been cern an inferior tail of a parotid mass from an upper cervical
suggested to provide useful guidance for medical and surgical mass and detect radiologic signs of malignancy, including
planning [see Table 1]. Preoperative discovery of a non– irregular, indistinct margins with parotid tissue, low signal
salivary gland neoplasm in a parotid mass may preclude intensities on all imaging sequences, and tumor infiltration
surgical excision in lieu of medical, radiation, or palliative into muscle, bone, or nerve [see Figure 2].
09/10
appropriate parotidectomy with identification and assessment

of the facial nerve for tumor involvement is considered the
current standard of care. Postoperative radiation therapy is
often indicated for more involved and advanced-stage tumors.
Moreover, benign parotid masses are frequently managed
surgically as well, with exploration of the parotid gland, iden-
tification and preservation of the facial nerve, and evaluation
of the neoplasm regarded as the customary surgical interven-
tions. Enucleation, once considered an acceptable alternative
to superficial parotidectomy for benign pathologies, is now
discouraged owing to the possibility of tumor spillage, incom-
plete removal of the tumor, inadvertent injury to the branches
of the facial nerve, and high rates of local recurrence. The
need for revision surgery for benign parotid processes is
considered unacceptable given the difficulty of surgery on a
Figure 2 Axial (a) T1 and (b) T2 magnetic resonance images
previously operated tissue bed and consequential increased
of a left superficial parotid pleomorphic adenoma demon-
strating the classic irregular, bosselated appearance. risk of injury to the facial nerve.
surgical therapy
Similar to FNAC, the utility of the various imaging modal- Surgery is the primary treatment modality for nonlymphoid
ities used in the evaluation of a parotid mass continues to be salivary gland neoplasms, both benign and malignant.
controversial. Many surgeons believe that preoperative ultra- Optimal surgery for the parotid gland should address both
sonography, CT, and MRI will provide little to no influence the primary tumor and cervical disease, if present, in a single
on therapy for a small, mobile, superficial parotid nodule, operation. The minimum surgical intervention for a parotid
which would be better assessed with FNAC, surgery, or both. mass is superficial parotidectomy with identification, dissec-
Conversely, management of the more advanced, fixed, aggres- tion, and preservation of the facial nerve, although a subtotal
sive, and deep parotid tumors can be considerably influenced or total parotidectomy and neck dissection may be required
by CT or MRI findings. Patients with diffuse parotid enlarge- for larger tumors that involve the deep lobe of the parotid
ment, tumor extension beyond the superficial lobe, facial gland or for patients with clinical or radiologic evidence of
nerve weakness, trismus, or deep tumors that are difficult regional disease, respectively. If the tumor involves and
to evaluate clinically should be initially assessed with CT. directly infiltrates the facial nerve, a diagnosis of malignancy,
Fixation to the deeper structures may prompt the need for if not previously established preoperatively, should be
MRI to evaluate the extent and for parapharyngeal extension explored. If a malignant diagnosis is confirmed, a low thresh-
or origin. Patients with tumors in close proximity to the facial old for nerve sacrifice should be maintained. However, facial
nerve, external auditory canal, mastoid, mandible, or regional nerve preservation despite tumor encroachment on the nerve
musculature may also benefit from a preoperative MRI, which can be considered as long as all gross disease is removed.
may influence surgical planning. With the availability of adjuvant radiation therapy, the sur-
Currently, the role of positron emission tomography (PET) geon can choose to leave behind microscopic disease, which
in the initial evaluation of a parotid mass remains undefined. can be addressed postoperatively. In addition to temporary or
This modality may, however, be of some value in the evalu- permanent facial weakness, patients should be counseled on
ation of suspected recurrent parotid cancers, lymph node and consented for other potential complications of parotid
metastases, or distant metastases. surgery, including permanent numbness of the auricle from
greater auricular nerve injury and Frey and first-bite
Management syndromes. Frey syndrome, also known as auriculotemporal
syndrome or gustatory sweating, is believed to result from
basic principles misdirected regeneration of cut parasympathetic fibers from
Treatment of a the otic ganglion to the parotid gland, leading to the innerva-
parotid mass depends tion of sweat glands and subcutaneous vasculature. Patients
on the nature and report discomfort, erythema, and perspiration over the parotid
extent of the lesion, bed or neck when eating. First-bite syndrome is a poorly
which, like most understood complication of surgery in the parapharyngeal
cancers of the body, space believed to result from injury to the cervical sympa-
is categorized and thetic chain. A denervation hypersensitivity of parotid myo-
described by a uni- epithelial cells to parasympathetic neurotransmitters results,
versal staging system. Staging for cancers of the parotid leading to supramaximal myoepithelial contraction and
gland is accomplished by means of the familiar tumor-node- consequent pain with the first bite of a meal. Intracutaneous
metastasis (TNM) system developed by the American Joint and intraglandular injections of botulinum toxin type A have
Committee on Cancer (AJCC) [see Table 2 and Table 3]. been shown to provide patients with long-term and effective
Malignant parotid masses are primarily treated surgically relief from the symptoms of Frey and first-bite syndromes,
according to established oncologic principles [see Table 4]. An respectively.
09/10
Table 2 American Joint Committee on Cancer TNM Clinical Classification of Major Salivary Gland Tumors
Primary tumor (T)
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
T1: Tumor ≤ 2 cm in greatest dimension without extraparenchymal extension
T2: Tumor > 2 cm but ≤ 4 cm in greatest dimension without extraparenchymal extension
T3: Tumor having extraparenchymal extension without seventh nerve involvement and/or > 4 cm but < 6 cm in greatest dimension
T4a: Tumor invades the skin, mandible, external auditory canal, seventh nerve, and/or > 6 cm in greatest dimension
T4b: Tumor invades the base of skull, pterygoid plates, carotid artery
Regional lymph nodes (N)
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in a single ipsilateral lymph node, ≤ 3 cm in greatest dimension
N2: Metastasis in a single ipsilateral lymph node, > 3 cm but ≤ 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none
> 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none > 6 cm in greatest dimension
N2a: Metastasis in a single ipsilateral lymph node > 3 cm but ≤ 6 cm in greatest dimension
N2b: Metastasis in multiple ipsilateral lymph nodes, none > 6 cm in greatest dimension
N2c: Metastasis in bilateral or contralateral lymph nodes, none > 6 cm in greatest dimension
N3: Metastasis in a lymph node > 6 cm in greatest dimension
Distant metastasis (M)
MX: Distant metastasis cannot be assessed
M0: No distant metastasis
M1: Distant metastasis
An incision in a preauricular skin crease gently curving identify the posterior belly of the digastric muscle. Identifica-
2 mm below the auricular lobule and continuing 2 to 3 cm tion of the tragal pointer is then accomplished with cautious
below the mandible is made down to the level of the parotid dissection along the tragal cartilage, and the main trunk of the
fascia to prevent lobular distortion and transection of the facial nerve is typically found roughly 1 cm anterior and deep
marginal mandibular branch of the facial nerve, respectively. to this important landmark at the level of the digastric muscle.
An anterior flap above the level of the parotid fascia is After the nerve is identified, the superficial lobe of the parotid
elevated with a blade or scissors, whereas a posterior flap is is removed with the mass with careful dissection along the
raised to expose the tail of the parotid, sternocleidomastoid nerve branches.27 In certain instances, a retrograde approach
muscle, and mastoid tip. Dissection then proceeds deeper to to facial nerve identification can be used and has been
shown to reduce operative time and blood loss and conserve
Table 3 American Joint Committee on Cancer Staging normal parotid tissue without compromising surgical margin
System for Major Salivary Gland Tumors
status.28
Stage T N M High-grade tumors involving the deep lobe or with exten-
I T1 N0 M0 sion to the parapharyngeal space may require a total paroti-
dectomy. Following removal of the superficial portion of the
II T2 N0 M0
gland, the facial nerve and its branches are carefully raised
III T3 N0 M0 off the deep parotid tissue or tumor, and this tissue is subse-
T1, T2, T3 N1 M0
quently elevated off the masseter muscle and removed. A
IVA T4a, T4b N0, N1 M0 cervical-parotid approach with exposure of the internal and
T1, T2, T3, T4a N2 M0 external carotid arteries, internal jugular vein, and vagus,
IVB T4b Any N M0 spinal accessory, and hypoglossal nerves may facilitate
Any T N3 M0 identification and excision of parapharyngeal space masses
IVC Any T Any N M1 posterior to the stylomandibular ligament. A midline man-
dibulotomy to provide additional exposure and control of
Table 4 Principles of Treatment of Parotid Tumors vessels can also be added for tumors extending to the skull
base or encasing the carotid artery. If the tumor extends
Adequate local excision of tumor, based on extent of primary
beyond the parotid gland and involves the skin, infratemporal
lesion
Preservation of facial nerve if possible fossa, ascending ramus of the mandible, or mastoid process,
Elective neck dissection reserved for selected patients more extensive surgical procedures (e.g., composite
Postoperative radiotherapy when indicated (in appropriate fields) resection, lateral temporal bone resection, or radical
Prognosis determined primarily by stage and grade of tumor parotidectomy) may become necessary.
09/10
Patients with preoperative facial weakness or paralysis will patient without evidence of cervical disease, selective neck
often require sacrifice of the main trunk of the facial nerve. If dissection may be considered for staging purposes. Moreover,
the tumor involves only an isolated branch of the facial nerve, if frozen-section examination provides a definitive diagnosis
the surgeon can elect to selectively sacrifice the involved of malignancy, further decisions about the extent of paroti-
branch alone. Following nerve sacrifice, nerve grafting should dectomy and possible selective neck dissection can be made
be considered in the same procedure. Reconstruction of the accordingly. If the pathology is unrevealing, the procedure
facial nerve can be performed with a nerve graft from the originally planned can be performed, and any further inter-
greater auricular nerve, medical or lateral antecubial cutane- ventions, if required, can be dictated by the final pathologic
ous nerve, sural nerve, and ansa hypoglossi, among others. diagnosis. Notably, significant caution should be exercised
The functional results of nerve grafting vary considerably, when deciding on facial nerve preservation or sacrifice based
depending on the age of the patient, the extent of the disease, solely on frozen-section results as frozen-section classification
and the identification of and appropriate anastomosis to of the wide variety of parotid tumors (both benign and
the peripheral branches of the facial nerve. If postoperative malignant) is often difficult and will often depend on the
radiation therapy is envisioned, its potential deleterious effects experience of the frozen-section pathologist.
on nerve regeneration should be considered. neck dissection
facial nerve monitoring Overall, about 10 to 20% of patients with malignant
Postoperative facial weakness is a frequent complication of parotid tumors present with clinically detectable cervical
parotid surgery and is the most feared complication for both lymphadenopathy, most frequently in levels II and III. Nodal
the patient and the surgeon. Transient facial dysfunction after metastasis reduces the survival rate by roughly 50%.11,21,34
parotidectomy ranges from 20 to 40%, whereas permanent Patients with clinically or radiologically positive cervical
paralysis has been reported to be as high as 5%. Continuous metastases are treated with either a comprehensive, modified
radical, or selective neck dissection, depending on the extent
visual observation of the patient’s ipsilateral face by the assis-
of the disease. However, the surgical management of patients
tant surgeon or nurse has historically been the traditional
with salivary malignancies who have no detectable cervical
method of facial nerve monitoring during a parotidectomy.
lymphadenopathy continues to be a matter of debate. Studies
More recently, however, facial nerve stimulators and continu-
have revealed that only 12 to 16% of patients without clinical
ous electromyographic neuromonitoring of the facial nerve
evidence of cervical disease demonstrated pathologically
have been employed by surgeons as a means to assist in nerve
positive nodes.25,35 In view of the low incidence of occult
identification, to provide additional indication for what is
metastases, these investigators do not recommend routine
“safe” to cut, and to reduce operative time.
elective treatment of the neck.
Although a few small retrospective case-control compari-
Other authors have investigated the patient and tumor
sons have noted a significant reduction in the rates of tempo- factors that may predict the presence of neck disease. Two
rary and/or permanent facial weakness with the use of these large population studies identified older age, facial nerve
electrophysiologic devices,29 the vast majority of studies have paralysis, extraparotid involvement, higher tumor grade, and
failed to demonstrate a significant improvement in post- perilymphatic invasion as variables predictive of occult cervi-
operative facial nerve function outcome.30,31 Given the exceed- cal disease.34,36 In addition, Bhattacharyya and Fried deter-
ingly low incidence of inadvertent permanent facial paralysis mined that tumor size and histopathologic type were also
in parotid surgery, however, Eisele and colleagues pointed predictors of regional disease and identified adenocarcinoma
out that a prospective, randomized study would need, at and SCC as histopathologies with the highest odds ratios for
minimum, 1,000 patients to demonstrate a reduction in nodal metastases.34 Similarlly, Regis De Brito Santos and
permanent facial nerve injury from 2% to 1%.32 Accordingly, colleagues found that the variables that showed the highest
the authors suggested that a large, multi-institutional study correlation with the incidence of lymph node metastasis were
will be needed to ascertain the benefits and drawbacks of the histopathologic type (i.e., adenocarcinoma, undifferenti-
electrophysiologic nerve monitoring technologies and that ated carcinoma, high-grade mucoepidermoid carcinoma,
surgeons who believe that patients will benefit from the SCC, or salivary duct carcinoma) and tumor stage.37
information provided should continue to use the devices. Accordingly, an elective neck dissection may be considered
in patients with advanced-stage primary tumors, those whose
intraoperative frozen-section analysis
tumors are of high histologic grades, and those whose tumors
The role of intraoperative frozen-section examination in are of certain specific histologic types. A selective neck dis-
the evaluation of a parotid mass, like that of fine-needle aspi- section may be performed to remove levels IB, II, III, and the
ration biopsy, is the subject of considerable debate. Neverthe- upper part of V for the purposes of staging.38 However, a
less, frozen-section examination has been found to be useful more comprehensive neck dissection that encompasses levels
for distinguishing salivary processes from nonsalivary pro- I through V may be necessary in patients who present with
cesses and benign disease from malignant disease. In 80 to clinically or radiologically apparent cervical metastases.
90% of cases, the findings from intraoperative frozen-section
examination correlate with the final pathologic diagnosis.33 If radiation therapy
frozen-section examination shows a benign tumor and con- Candidates for postoperative radiation therapy include
firms the presumed preoperative diagnosis, lateral superficial patients with advanced-stage disease, a large primary tumor,
parotidectomy should be sufficient. If frozen-section exami- close or positive margins, nodal disease, perineural spread,
nation shows high-grade mucoepidermoid carcinoma in a soft tissue extension, preoperative facial nerve dysfunction, or
09/10
Table 5 Indications for Postoperative Radiation Therapy Table 6 Prognostic Factors for Salivary Gland Tumors
for Parotid Cancer
Increasing age at diagnosis
Aggressive, highly malignant tumor Pain at presentation
Invasion of adjacent tissues outside parotid capsule Higher T stage
Regional lymph node metastases Higher N stage
Deep-lobe cancer Skin invasion
Gross residual tumor after resection Facial nerve dysfunction
Recurrent tumor after resection Perineural growth
Invasion of facial nerve by tumor Positive surgical margins
Soft tissue invasion
Treatment type
high-grade tumors [see Table 5].39,40 Accordingly, postopera- Survival

tive radiation therapy is suggested for all patients with parotid Survival of patients with parotid gland malignancies is
malignancy other than those with low-grade T1 or T2 tumors influenced by multiple factors [see Table 6]. The various
and clear surgical margins. Combined surgical and radiation histopathologies with variable aggressiveness will naturally
therapy has been shown to result in 5- and 10-year survivals exert different influences on mean survival durations and
of as high as 95% and 84%, respectively.41 rates; histopathologic distributions and survival estimates
A role for radiation therapy for the treatment of an N0 neck of parotid gland cancers extracted from a national cancer
in lieu of an elective neck dissection has been proposed, and database are provided in Table 7.44 In this study, acinar cell
there is some evidence to suggest that elective irradiation is carcinomas and mucoepidermoid carcinomas exhibited the
as effective as elective neck dissection.25 Some authors have best survival, whereas carcinoma ex pleomorphic adenoma,
proposed that postoperative patients who will already be adenocarcinomas, and SCCs displayed substantially poorer
requiring radiation therapy for additional primary-site survivals. Of note, separate survival analyses of the different
sterilization are excellent candidates for elective radiation of grades of mucoepidermoid carcinoma demonstrated statisti-
the neck.42 cally significant differences in overall survival according to
Additionally, there is substantial interest in the potential grade.
role of neutron radiotherapy as a primary treatment modality In addition to histopathology, increasing age, tumor size,
for certain parotid malignancies, including advanced inoper- tumor grade, extraglandular extension, and the presence of
able cancers, adenoid cystic carcinomas, and recurrent cervical disease all significantly and negatively impacted
pleomorphic adenomas, and for poor surgical candidates. survival, whereas the use of external-beam radiation therapy
Particle radiation may be of particular benefit in adenoid provided a statistically significant survival benefit.44,45 More-
cystic carcinoma to treat perineural extension. Although over, Lima and colleagues concluded in their institutional
additional work and further data on survival and related experience that the presence of facial nerve dysfunction also
complications await this treatment modality, neutron negatively influenced prognosis.21
radiotherapy may be the best option currently available for
patients with inoperable parotid cancer.43 Financial Disclosures: None Reported
Table 7 Histopathologic Distribution of Major Salivary Gland Malignancies of the Parotid

Mean Survival 5-Year Actuarial 10-Year Actuarial
Histopathology n % (mo) Survival (%) Survival (%)
Mucoepidermoid carcinoma 367 40.6 105 81.5 63.5
Primary SCC 191 21.2 60 46.1 27.2
Adenocarcinoma 189 20.9 70 65.9 49.7
Acinar cell carcinoma 95 10.5 108 80.0 77.7
Carcinoma ex pleomorphic adenoma 23 2.5 59 40.2 0.0
Malignant mixed tumor 20 2.2 95 73.3 55.0
Adenoid cystic carcinoma 18 2.0 95 70.7 NA
Total 903 100.0 88 66.6 49.7
NA = not available; SCC = squamous cell carcinoma.
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452. Cancer 1992;69:615. nodes in patients with malignant neoplasms
12. Spiro RH. Salivary neoplasms: overview of a 26. Lin AC, Bhattacharyya N. The utility of of the parotid gland. ORL J Otorhinolaryngol
35-year experience with 2,807 patients. Head fine needle aspiration in parotid malignancy. Relat Spec 2001;63:123.
Neck Surg 1986;8:177–84. Otolaryngol Head Neck Surg 2007;136: 39. Harrison LB, Armstrong JG, Spiro RH, et al.
13. Ellis GL, Auclair PL. Tumors of the salivary
793–8. Postoperative radiation therapy for major
glands. Atlas of tumor pathology, series 3,
27. Thompson DM, McCafferey TV. Surgical salivary gland malignancies. J Surg Oncol
fascicle 17. Washington (DC): Armed Forces
approaches for primary parotid malignancies. 1990;45:52.
Institute of Pathology; 1996.
Oper Techn Otolaryngol Head Neck Surg 40. Tullio A, Marchetti C, Sesenna E, et al.
14. Seifert G, Sobin LH. Histological classifica-
1996;7:358–64. Treatment of carcinoma of the parotid gland:
tion of salivary gland tumours. In: World
28. Bhattacharyya N, Richardson ME, Gugino the results of a multicenter study. J Oral
Health Organization. International histologi-
cal classification of tumours. Berlin: Springer- LD. An objective assessment of the advan- Maxillofac Surg 2001;59:263.
Verlag; 1991. tages of retrograde parotidectomy. Otolaryn- 41. Spiro IJ, Wang CC, Montgomery WW.
15. Quesnel AM, Lindsay RW, Hadlock TA. gol Head Neck Surg 2004;131:392–6. Carcinoma of the parotid gland. Analysis of
When the bell tolls on Bell’s palsy: finding 29. Terrell JE, Kileny PR, Yian C, et al. Clinical treatment results and patterns of failure after
occult malignancy in acute-onset facial outcome of continuous facial nerve monitor- combined surgery and radiation therapy.
paralysis. Am J Otolaryngol 2010. DOI: ing during primary parotidectomy. Arch Cancer 1993;71:2699–705.
10.1016/j.amjoto.2009.04.003. Otolaryngol Head Neck Surg 1997;123: 42. Gold DR, Annino DJ Jr. Management of the
16. Vrielinck LJ, Ostyn F, van Damme B, et al. 1081–7. neck in salivary gland carcinoma. Otolaryngol
The significance of perineural spread in ade- 30. Reilly J, Myssiorek D. Facial nerve stimula- Clin North Am 2005;38:99–105.
noid cystic carcinoma of the major and minor tion and postparotidectomy facial paresis. 43. Laramore GE, Krall JM, Griffin TW, et al.
salivary glands. Int J Oral Maxillofac Surg Otolaryngol Head Neck Surg 2003;128: Neutron versus photon irradiation for unre-
1988;17:190. 530–3. sectable salivary gland tumors: final report of
17. Spiro RH. Distant metastasis in adenoid 31. Grosheva M, Klussmann JP, Grimminger C, an RTOG-MRC randomized clinical trial.
cystic carcinoma of salivary origin. Am J Surg et al. Electromyographic facial nerve moni- Radiation Therapy Oncology Group. Medi-
1997;174:495. toring during parotidectomy for benign cal Research Council. Int J Radiat Oncol Biol
18. Gomez DR, Katabi N, Zhung J, et al. Clinical lesions does not improve the outcome of post- Phys 1993;27:235.
and pathologic prognostic features in acinic operative facial nerve function: a prospective 44. Bhattacharyya N, Fried MP. Determinants
cell carcinoma of the parotid gland. Cancer two-center trial. Laryngoscope 2009;119: of survival in parotid gland carcinoma: a
2009;115:2128–37. 2299–305. population-based study. Am J Otolaryngol
19. Lee S, Kim GE, Park CS, et al. Primary squa- 32. Eisele DW, Wang SJ, Orloff LA. Electrophys- 2005;26:39–44.
mous cell carcinoma of the parotid gland. Am iologic facial nerve monitoring during paroti- 45. Jeannon JP, Calman F, Gleeson M, et al.
J Otolaryngol 2001;22:400–6. dectomy. Head Neck 2010;32:399–405. Management of advanced parotid cancer. A
20. Bron LP, Traynor SJ, McNeil EB, O’Brien 33. Seethala RR, LiVolsi VA, Baloch ZW. Rela- systematic review. Eur J Surg Oncol 2009;35:
CJ. Primary and metastatic cancer of the tive accuracy of fine-needle aspiration and 908–15.
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2 head and neck
3 NECK MASS
Christopher Scally, MD, and Gerard M. Doherty, MD*
Assessment of a Neck Mass physical

examination
The head and neck
examination is chal-
Clinical Evaluation lenging because much
history of the area to be
examined is not easily
The evaluation of seen. Patience and
any neck mass practice are neces-
begins with a careful sary to master the
history taken with special instruments and techniques of examination. A head
the differential diag- and neck examination is usually performed with the patient
nosis in mind [see sitting in front of the physician. Constant repositioning of
Table 1] because directed questions can narrow down the the head is necessary to obtain adequate visualization of the
diagnostic possibilities and focus subsequent investigations. various areas. Gloves must be worn during the examination,
For example, in younger patients, one might suspect particularly if the mucous membranes are to be examined.
congenital or inflammatory lesions, whereas in older adults, Good illumination is essential. Fiberoptic endoscopy with a
the first concern is often neoplasia. flexible laryngoscope and a nasopharyngoscope is a com-
The duration and growth rate of the mass are important: mon component of the physical examination for evaluating
malignant lesions are more likely to grow rapidly than
benign ones, which may grow and shrink. The location of
the mass in the neck can also narrow the list of possibilities. Table 1 Etiology of Neck Mass
This is particularly important for differentiating congenital Inflammatory and infectious disorders
masses from neoplastic or inflammatory ones because each Acute lymphadenitis (bacterial or viral infection)
Subcutaneous abscess (carbuncle)
type usually occurs in particular locations. In addition, the
Infectious mononucleosis
location of a neoplasm has both diagnostic and prognostic Cat-scratch fever
significance. The possibility that the mass is an infectious or AIDS
inflammatory process should also be assessed. One should Tuberculous lymphadenitis (scrofula)
Fungal lymphadenitis (actinomycosis)
evaluate for evidence of infection or inflammation (e.g., Sarcoidosis
fever, pain, or tenderness); a recent history of tuberculosis, Congenital cystic lesions
sarcoidosis, or fungal infection; the presence of dental prob- Thyroglossal duct cyst
lems; and a history of trauma to the head and neck. Masses Branchial cleft cyst
Cystic hygroma (lymphangioma)
that appear inflamed or infected are far more likely to be Vascular malformation (hemangioma)
benign. Laryngocele
Finally, factors suggestive of cancer include a history of Benign neoplasms
malignancy elsewhere in the head and neck (e.g., a history Salivary gland tumor
Thyroid nodules or goiter
of skin cancer, melanoma, thyroid cancer, or head and neck Soft tissue tumor (lipoma, sebaceous cyst)
cancer); night sweats (suggestive of lymphoma); excessive Chemodectoma (carotid body tumor)
exposure to the sun (a risk factor for skin cancer); smoking Neurogenic tumor (neurofibroma, neurilemmoma)
Laryngeal tumor (chondroma)
or excessive alcohol consumption (risk factors for squamous
Malignant neoplasms
cell carcinoma of the head and neck); nasal obstruction or Primary
bleeding, otalgia, odynophagia, dysphagia, or hoarseness Salivary gland tumor
(suggestive of a malignancy in the upper aerodigestive Thyroid cancer
Upper aerodigestive tract cancer
tract); or exposure to low-dose therapeutic radiation (a risk Soft tissue sarcoma
factor for thyroid cancer). Skin cancer (melanoma, squamous cell carcinoma, basal cell
carcinoma)
Lymphoma
* The authors and editors gratefully acknowledge the contribu- Metastatic
Upper aerodigestive tract cancer
tions of the previous authors, Barry Roseman, MD, FACS, and
Skin cancer (melanoma, squamous cell carcinoma)
Orlo Clark, MD, FACS, to the development and writing of this Salivary gland tumor
chapter. Thyroid cancer
Adenocarcinoma (breast, gastrointestinal tract,
Financial disclosure information is located at the end of this chapter genitourinary tract, lung)
before the references. Unknown primary tumor

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2 head and neck 3 neck mass — 2
Assessment of a Neck Mass Patient presents with a neck mass
Obtain clinical history
Determine
• Duration and growth rate of mass
• Location of mass
Ask about
• Factors suggestive of infection or
inflammatory disorder
• Factors suggestive of cancer
Formulate initial diagnostic impressions Perform physical examination of

head and neck
Look for
• Asymmetry • Signs of trauma
• Skin changes • Movement of mass on
Diagnosis is probable, and Diagnosis is uncertain, or further deglutition • Bruit • Vocal changes
further diagnostic information is needed or desired
investigation is unnecessary Attempt to determine source of mass, and
Consider investigative studies: assess its physical characteristics. Examine the
Biopsy: Fine-needle aspiration following areas in detail:
(FNA) is preferred method. • Cervical lymph nodes • Skin • Thyroid
Imaging studies: Not routinely • Salivary glands • Oral cavity and
called for, but ultrasonography, oropharynx • Larynx and hypopharynx
CT, MRI, arteriography, angiography, • Nasal cavity and nasopharynx
and plain x-rays are sometimes
helpful. Consultation with a head
and neck radiologist is desirable.
FNA is diagnostic or confirmatory FNA yields negative or inconclusive results
Repeat FNA or perform open biopsy.
Inflammatory or Congenital cystic lesion Benign neoplasm Malignant neoplasm

infectious disorder
These include These include Determine whether cancer is
Treat medically. • Thyroglossal duct cysts • Salivary gland tumors primary or metastatic.
Drain abscesses. and branchial cleft cysts • Thyroid nodules and goiters
(treated surgically) • Soft tissue tumors
• Cystic hygromas and • Chemodectomas
hemangiomas (treated • Neurogenic tumors
expectantly) • Laryngeal tumors
Treat surgically. (Observation
is appropriate in some cases.)
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Primary neoplasm
These include
• Lymphoma • Thyroid cancer
• Upper aerodigestive tract cancer
• Soft tissue sarcoma • Skin cancer
Treat with surgery, radiation therapy, and/or
chemotherapy, as appropriate.
Metastatic tumor
Primary is known Primary is unknown
Metastatic squamous cell carcinoma: Evaluate nasopharynx, larynx,

Perform selective neck dissection and esophagus, hypopharynx, and
consider adjuvant radiation therapy. tracheobronchial tree
Metastatic adenocarcinoma: Perform endoscopically.
neck dissection (selective or other) Biopsy nasopharynx, tonsils,
and consider adjuvant radiation and hypopharynx.
therapy. Perform unilateral neck dissection
Metastatic melanoma: Perform full- followed by irradiation of neck,
thickness excision and SLN biopsy; entire pharynx, and nasopharynx.
if there are positive SLNs or lymph
nodes are palpable, perform modified
neck dissection.
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the larynx, the nasopharynx, and the paranasal sinuses, The tracheoesophageal groove nodes (level VI) are then
especially when these areas cannot be adequately inspected palpated.
with other techniques.
The examination should begin with inspection for asym- Skin
metry, signs of trauma, and skin changes. The examiner Careful examination of the scalp, the ears, the face, the
should ask the patient to swallow to observe whether the oral cavity, and the neck can identify potentially malignant
mass moves with deglutition and should palpate the neck skin lesions, which may give rise to lymph node metastases.
from both the front and behind. Auscultation can detect
audible bruits. One should also both listen to and ask about Thyroid Gland
the patient’s voice, changes in which may suggest either a The thyroid gland is first observed as the patient swal-
laryngeal tumor or recurrent nerve dysfunction from locally lows; it is then palpated and its size and consistency are
invasive thyroid cancer. assessed to determine whether it is smooth, diffusely
During the physical examination, one should be thinking enlarged, or nodular and whether one nodule or several are
about the following questions: What structure is the neck present. If it is unclear whether the mass arises from the
mass arising from? Is it a lymph node? Is the mass arising thyroid, one can clarify the point by asking the patient
from a normally occurring structure, such as the thyroid to swallow and watching to see whether the mass moves
gland, a salivary gland, a nerve, a blood vessel, or a muscle? upward with the larynx. Signs of superior mediastinal syn-
Or is it arising from an abnormal structure, such as a drome (e.g., cervical venous engorgement and facial edema)
laryngocele, a branchial cleft cyst, or a cystic hygroma? Is suggest retrosternal extension of a thyroid goiter. Elevation
the mass soft, fluctuant, easily mobile, well encapsulated, of the arms above the head can elicit this finding in a patient
and smooth? Or is it firm, poorly mobile, and fixed to with a substernal goiter (a positive Pemberton sign). The
surrounding structures? Does it pulsate? Is there a bruit? larynx and trachea are examined, with special attention to
Does it appear to be superficial, or is it deeper in the neck? the cricothyroid membrane, over which Delphian nodes can
Is it attached to the skin? Is it tender? be palpated. These nodes can be an indication of thyroid or
The following areas of the head and neck are examined in laryngeal cancer.
some detail.
Major Salivary Glands
Cervical Lymph Nodes Examination of the paired parotid and submandibular
The cervical lymphatic system consists of interconnected glands involves not only palpation of the neck but also an
groups or chains of nodes that parallel the major neurovas- intraoral examination to inspect the duct openings. The sub-
cular structures in the head and neck. The skin and mucosal mandibular glands are best assessed by bimanual palpation,
surfaces of the head and neck all have specific and predict- with one finger in the mouth and one in the neck. They are
able nodes associated with them. The classification of normally lower and more prominent in older patients. The
cervical lymph nodes has been standardized to comprise six parotid glands are often palpable in the neck, although the
levels [see Figure 1]. Accurate determination of lymph node deep lobe cannot always be assessed. A mass in the region
level on physical examination and in surgical specimens of the tail of the parotid must be distinguished from
not only helps establish a common language among clini- enlarged level II jugular nodes. The oropharynx is inspected
cians but also permits comparison of data among different for distortion of the lateral walls. The parotid (Stensen) duct
institutions. may be found opening into the buccal mucosa, opposite the
The location, size, and consistency of lymph nodes furnish second upper molar.
valuable clues to the nature of the primary disease. Other
physical characteristics of the adenopathy should be noted Oral Cavity and Oropharynx
as well, including the number of lymph nodes affected, The lips should be inspected and palpated. Dentures should
their mobility, their degree of fixation, and their relation to be removed before the mouth is examined. The buccal mucosa,
surrounding anatomic structures. One can often establish a the teeth, and the gingiva are then inspected. The patient
tentative diagnosis on the basis of these findings alone. For should be asked to elevate the tongue so that the floor of the
example, soft or tender nodes are more likely to derive from mouth can be examined and bimanual inspection performed.
an inflammatory or infectious condition, whereas hard, The tongue should be inspected both in its normal position in
fixed, painless nodes are more likely to represent metastatic the mouth and during protrusion.
cancer. Multiple regions of enlarged lymph nodes are usu- Most of the oropharyngeal contents are easily visualized
ally a sign of systemic disease (e.g., lymphoma, tuberculosis, if the tongue is depressed. Only the anterior two thirds of
or infectious mononucleosis), whereas solitary nodes are the tongue are clearly visible on examination, however. The
more often due to malignancy. Firm, rubbery nodes are base of the tongue is best inspected using a mirror. In most
typical of lymphoma. persons, the tongue base can be palpated, although with
The submental and submandibular nodes (level I) are some discomfort to the patient. The ventral surface of the
palpated bimanually. The three levels of internal jugular tongue must also be carefully inspected and palpated.
chain nodes (levels II, III, and IV) are best examined by The hard palate is examined by gently tilting the patient’s
gently rolling the sternocleidomastoid muscle between the head backward, and the soft palate is inspected by gently
thumb and the index finger. The posterior triangle nodes depressing the tongue with a tongue blade. The movement of
(level V) are palpated posterior to the sternocleidomastoid. the palate is assessed by having the patient say “ahh.”
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Superficial Parotid Nodes Mastoid Nodes

(Deep Parotid Nodes Deep to
Parotid Gland)
Occipital Nodes
Facial Nodes Sternocleidomastoid

(Buccal Nodes) Muscle
External Jugular Node
(Lateral Superficial
Subparotid Node Cervical Node)
Mandibular and
Submandibular Jugulodigastric Node
Nodes Deep Lateral Nodes
(Spinal Accessory Nodes)
Submental Node
Intercalated Node
Suprahyoid Node
Internal Jugular Chain of Nodes Jugulo-omohyoid Node

(Deep Lateral Cervical Nodes) Jugular Trunk
Superior Thyroid Nodes Inferior Deep Cervical

(Scalene) Node
Anterior Deep Cervical
(Pretracheal and Thyroid) Transverse Cervical
Nodes (Deep to Strap Chain of Nodes
Muscle)
Anterior Superficial
Cervical Nodes
(Anterior Jugular Nodes)
Supraclavicular Nodes
Subclavian Trunk and Node Thoracic Duct

of Subclavian Chain
Figure 1 Cervical lymph nodes. Inset: Classification of cervical lymph nodes by anatomic level.
The tonsils are then examined. They are usually symmetri- between the oropharyngeal structures. The mirror is
cal but may vary substantially in size. For example, in young carefully introduced into the oropharynx without touching
patients, hyperplastic tonsils may almost fill the oropharynx, the base of the tongue. The oropharynx, the larynx, and the
but in adult patients, this is an uncommon finding. Finally, the hypopharynx can be inspected by changing the angle of the
posterior pharyngeal wall is inspected. mirror.
The lingual and laryngeal surfaces of the epiglottis are
Larynx and Hypopharynx examined. Often the patient must be asked to phonate to
The larynx and the hypopharynx are best examined by bring the endolarynx into view. The aryepiglottic folds
indirect or direct laryngoscopy. A mirror is warmed, and the and the false and true vocal cords should be identified. The
patient’s tongue is gently held forward to increase the space mobility of the true vocal cords is then assessed: their resting
05/12
position is carefully noted, and their movement during A thyroid nodule with an adjacent abnormal lymph node in
inspiration is recorded. Normally, the vocal cords abduct a young patient probably represents thyroid cancer. In an
during breathing and move to the median position during elderly patient with a substantial history of smoking
phonation. The larynx is elevated when the patient attempts and alcohol use, a neck mass may be a metastasis from
to say “eeeee”; this allows one to observe vocal cord move- squamous cell carcinoma in the aerodigestive tract.
ment and to better visualize the piriform sinuses, the post- The initial diagnostic impressions and the degree of
cricoid hypopharynx, the laryngeal surface of the epiglottis, certainty attached to them determine the next steps in the
and the anterior commissure of the glottic larynx. Passage of workup and management of a neck mass; options include
a fiberoptic laryngoscope through the nose yields a clear empirical therapy, ultrasonographic scanning, computed
view of the hypopharynx and the larynx. This procedure is tomography (CT), fine-needle aspiration (FNA), and obser-
well tolerated by almost all patients, particularly if a topical vation alone. For example, in a patient with suspected bacte-
anesthetic is gently sprayed into the nose and swallowed, rial lymphadenitis from an oral source, empirical antibiotic
thereby anesthetizing both the nose and the pharynx. therapy with close follow-up is a reasonable approach. In a
patient with a suspected parotid tumor, the best first test is
Nasal Cavity and Nasopharynx a CT scan: the tumor probably must be removed, which
The nasopharynx is examined by depressing the tongue means that one will have to ascertain the relation of the mass
and inserting a small mirror behind the soft palate. The to adjacent structures. In a patient with suspected metastatic
patient is instructed to open the mouth widely and breathe cancer, FNA is a sensible choice: it will confirm the presence
through it to elevate the soft palate. With the patient relaxed, of malignancy and may suggest a source of the primary
a warmed nasopharyngeal mirror is carefully placed in cancer.
the oropharynx behind the soft palate without touching the
mucosa. Investigative
The nasal septum, the choanae, the turbinates, and the Studies
eustachian tube orifices are systematically assessed. The
Neck masses of
dorsum of the soft palate, the posterior nasopharyngeal
suspected infectious
wall, and the vault of the nasopharynx should also be
or inflammatory ori-
inspected. The exterior of the nose should be carefully
gin can be observed
examined, and the septum should be inspected with a nasal
for short periods.
speculum. Polyps or other neoplasms can be mistaken for
Most neck masses in
turbinates.
adults, however, are abnormal and are often manifestations
Careful evaluation of the cranial nerves is essential, as is of serious underlying conditions. In most cases, therefore,
examination of the eyes (including assessment of ocular further diagnostic evaluation should be rigorously pursued.
movement and visual activity), the external ear, and the
tympanic membrane. ultrasonography
Additional Areas Ultrasonography of the neck can be extremely useful in
clarifying physical examination findings and supplying
The remainder of the physical examination is also impor- additional definitive information. In many clinics, ultraso-
tant, particularly as regards the identification of a possible nography is considered an extension of the physical
source of metastases to the neck. Other sets of lymph examination and is applied for nearly all patients with neck
nodes—especially axillary and inguinal nodes—are exam- masses. Ultrasonography can also be useful to guide tissue
ined for enlargement or tenderness. Women should undergo sampling and is helpful for mapping of normal or abnormal
complete pelvic and rectal examination. Men should under- lymph nodes, for characterizing lesions as cystic or solid,
go rectal, testicular, and prostate examinations; tumors from and for defining the risk of some individual lesions (espe-
these organs may metastasize to the neck, albeit rarely. cially thyroid lesions) of being malignant. Ideally, point-of-
care ultrasound examination by the treating physician can
Developing a Dif- guide and clarify the subsequent evaluation.
ferential Diagnosis tissue sampling
Once a compre- Whether or not the history and the physical examination
hensive history and strongly suggest a specific diagnosis, the information
examination have obtained by sampling tissue from the neck mass is often
been performed, one highly useful. In many cases, biopsy establishes the diagno-
is likely to have a sis or, at least, reduces the diagnostic possibilities. At pres-
better idea of the ent, the preferred method of obtaining biopsy material from
etiology of the mass. a neck mass is FNA, which is generally well tolerated and
In some patients, the findings are clear enough to strongly can usually be performed without local anesthesia. Although
suggest a specific disease entity. For example, a rapidly FNA is, on the whole, both safe and accurate, it is an inva-
developing mass that is soft and tender to palpation is sive diagnostic procedure and carries a small but definable
most likely a reactive lymph node from an acute bacterial risk of potential problems (e.g., bleeding and sampling
or viral illness. A slow-growing facial mass associated with error). Accordingly, FNA should be done only when the
facial nerve deficits is probably a malignant parotid tumor. results are likely to influence management.
05/12
FNA can be used to sample cystic or solid lesions and can provides very little information about the physical charac-
often diagnose malignancy. It has become the standard for teristics of the mass. Plain radiographs of the neck are rarely
making treatment decisions in patients with thyroid nodules helpful in differentiating neck masses, but a chest x-ray can
and for assessing for suspicious adenopathy for treatment often confirm a diagnosis (e.g., in patients with lymphoma,
planning. Benign FNA results should not be considered the sarcoidosis, or metastatic lung cancer).
end point of any search and do not rule out cancer. It is important to communicate with the radiologist: an
Several studies have shown FNA to be approximately experienced head and neck radiologist may be able to offer
90% accurate in establishing a definitive diagnosis.1 Lateral the surgeon valuable guidance in choosing the best diagnos-
cystic neck masses that collapse on aspiration usually repre- tic test in a specific clinical scenario. Furthermore, providing
sent hygromas, branchial cleft cysts, or cystic degeneration the radiologist with a detailed clinical history facilitates
of a metastatic papillary thyroid cancer, although the cystic interpretation of the images.
nature of these lesions is best determined on ultrasonogra-
phy. Fluid from these masses is sent for cytologic examina-
Management of
tion. If both cystic and solid components are evident on a
Specific Disorders
sonogram, or if a palpable mass remains after cyst aspira-
tion, then tissue sampling should target the solid component cervical
as the morphology of the cells will be better preserved. adenopathy
If a complete physical examination including ultrasono-
graphy has been completed and the FNA is not diagnostic, Anatomy
then an open biopsy may be necessary to obtain a specimen The lymph nodes
for histologic sections and microbiologic studies. It is of the neck are typi-
estimated that open biopsy eventually proves necessary in cally divided into six levels [see Table 2 and Figure 1], based
about 10% of patients with a malignant mass. For an open on common patterns of metastatic spread.4 These six levels
biopsy, it is important to orient skin incisions within the correspond to the submandibular and submental nodes
boundaries of a neck dissection; the incisions can then, if (level I), the jugular nodes (levels II to IV), the posterior
necessary, be extended for definitive therapy or reexcised if triangle nodes (level V), and the anterior triangle nodes
reoperation subsequently proves necessary. (level VI). The boundaries of level I are the mandible supe-
imaging riorly, the anterior belly of the digastric muscle anteriorly,
and the stylohyoid muscle posteriorly. Malignant nodes in
Diagnostic imaging beyond ultrasound studies should be this level most commonly contain metastases from cancers
used selectively in the evaluation of a neck mass; imaging of the lips, the oral cavity, or the facial skin.
studies should be performed only if the results are likely to Level II contains nodes located near the upper third of the
affect subsequent therapy. Such studies often supply useful
internal jugular vein. The anterior boundary of level II is the
information about the location and characteristics of the
stylohyoid muscle; the posterior boundary is the posterior
mass and its relation to adjacent structures. Diagnostic
border of the sternocleidomastoid. Level II extends inferi-
imaging is particularly useful when a biopsy has been
orly to the level of the hyoid bone. Level III relates to the
performed and a malignant tumor identified. In such cases,
middle third of the jugular vein. The superior border is the
these studies can help establish the extent of local disease
hyoid bone, the inferior border is the level of the cricoid
and the presence or absence of metastases.
cartilage, and the anterior and posterior borders are the
CT is useful for differentiating cysts from solid neck
sternohyoid and sternocleidomastoid muscles, respectively.
lesions and for determining whether a mass is within or out-
side a gland or nodal chain.2 In addition, CT can delineate Level II and level III lymph nodes are common sites for
small tongue base or tonsillar tumors that have a minimal lymph node metastases from primary cancers of the
mucosal component. Magnetic resonance imaging (MRI) oropharynx, the larynx, and the hypopharynx.
provides much the same information as CT. T2-weighted Level IV contains nodes relating to the lower third of the
gadolinium-enhanced scans are particularly useful for internal jugular vein. Its anterior and posterior borders are
delineating the invasion of soft tissue by tumor: endocrine the same as those for level III; the superior border is the
tumors are often enhanced on such scans. Fluorodeoxyglu- cricoid cartilage, and the inferior border is the superior edge
cose (FDG) positron emission tomography (PET) is increas- of the clavicle. Metastases in level IV lymph nodes can arise
ingly employed in the diagnosis and staging of both from cancers of the upper aerodigestive tract, cancers of the
primary and metastatic head and neck malignancies, includ- thyroid gland, or cancers arising below the clavicle.
ing squamous cell carcinoma, thyroid cancer, lymphoma, Level V consists of the posterior triangle of the neck and
and melanoma.3 FDG-PET is generally reserved for specific contains several nodal groups: the spinal accessory, trans-
situations, however, rather than as a primary imaging verse cervical, and supraclavicular nodes. Nodal metastases
modality. FDG-PET-positive, radioiodine-negative, meta- in the posterior triangle can arise from nasopharyngeal and
static thyroid cancers are more aggressive than their thyroid cancers and from squamous cell carcinoma or mela-
radioiodine-avid counterparts, for example. noma of the posterior scalp and the pinna of the ear. The
Arteriography is useful mainly for evaluating vascular eponymous Virchow node in the left supraclavicular region
lesions and tumors fixed to the carotid artery. Angiography is a common site of distant metastasis. The anterior border
is helpful for evaluating the vascularity of a mass, its of level V is the sternocleidomastoid; the posterior border is
specific blood supply, or the status of the carotid artery but the anterior edge of the trapezius muscle. Level V extends
05/12
Table 2 Classification of Cervical Lymph Nodes

Level Nodes Common Sources of Metastatic Disease
I Submental nodes Oral cavity and lip, facial skin
Submandibular nodes
II Upper internal jugular chain nodes Oropharynx, larynx, hypopharynx
III Middle internal jugular chain nodes Oropharynx, larynx, hypopharynx
IV Lower internal jugular chain nodes Upper aerodigestive tract, thyroid
V Spinal accessory nodes Remote metastases (Virchow node); posterior scalp
Transverse cervical nodes
VI Tracheoesophageal groove nodes Thyroid, larynx
superiorly from the point at which the sternocleidomastoid staging and for planning therapy, as well as in patients
and trapezius converge to the clavicle inferiorly. with a primary tumor of the head and neck who are not
Level VI contains the lymph nodes of the anterior com- candidates for operation but in whom a tissue diagnosis is
partment of the neck. The borders are the hyoid superiorly necessary for appropriate nonsurgical therapy to be initiat-
and the sternal notch inferiorly, and this level extends later- ed. A wide variety of primary tumors may metastasize
ally to the carotid arteries on each side. Nodes in level VI to the cervical lymph nodes, and therapy depends on the
commonly contain metastases from thyroid cancer, as well primary site and the type and stage of the tumor.
as from laryngeal cancers. FNA of an enlarged cervical node does have limitations.
Sampling error or an inadequate sample may occur; in these
Investigative and Diagnostic Studies cases, a repeat aspiration or an excisional biopsy may be
Lymph node enlargement is a frequent finding with a useful.
wide differential diagnosis. Most commonly, lymph node When lymphoma and metastatic squamous cell carcinoma
enlargement occurs as a reaction to acute infection; however, are diagnostic possibilities, FNA alone is often incapable of
given the potential for alternate causes such as malignancy, determining the precise histologic subtype for lymphoma,
a benign diagnosis cannot be assumed. A careful history and but it is usually capable of distinguishing a lymphoprolif-
thorough examination, as well as consideration by the clini- erative disease from metastatic squamous cell carcinoma.
cian of all potential causes, are essential. Acute infection of This is a crucial distinction in that the two neoplasms are
the neck (cervical adenitis) is most often the result of dental treated in drastically different ways.
infection, tonsillitis, pharyngitis, viral upper respiratory If a lymphoma is suspected, FNA is typically followed by
tract infection, or skin infection. In this situation, the open biopsy, frozen-section confirmation, and submission
enlarged lymph nodes are usually just posterior and inferior of fresh tissue for further pathologic characterization. The
to the angle of the mandible. Signs of acute infection (e.g., intact node is placed in normal saline and sent directly to
fever, malaise, and a sore mouth or throat) are usually pres- the pathologist for analysis of cellular content and nodal
ent. A constitutional reaction, tenderness of the cervical architecture and identification of lymphocyte markers. If,
mass, and the presence of an obvious infectious source however, metastatic squamous cell carcinoma is suspected,
confirm the diagnosis. Treatment should be directed toward FNA usually suffices for establishing the diagnosis and
the primary disease and should include a monospot test for formulating a treatment plan, which is specific to the site
infectious mononucleosis. and size of the primary tumor but often includes chemo-
For patients with cervical adenopathy without an obvious therapy and radiation initially. In this setting, performing
acute infection, further investigation is indicated. Various an open biopsy can lead to significant wound healing
chronic infections (e.g., tuberculosis, fungal lymphadenitis, complications; there is no need to incur this risk when FNA
syphilis, cat-scratch fever, and AIDS) may also involve cer- is sufficient to initiate treatment.
vical lymph nodes. Certain chronic inflammatory disorders
(e.g., sarcoidosis) may present with cervical lymphadenopa- thyroid nodules: benign and malignant thyroid
thy as well. Because of the chronic lymph node involvement, disease
these conditions are easily confused with neoplasms, espe- Thyroid disease is a relatively common cause of neck
cially lymphomas. Biopsy is occasionally necessary; how- mass. Nearly 4% of the population have a palpable thyroid
ever, skin tests and serologic studies are often more useful nodule. The majority of thyroid nodules are benign; how-
for establishing a diagnosis. Treatment of these conditions is ever, approximately 5% of these lesions are malignant.5 The
primarily medical; surgery is reserved for complications. evaluation of a thyroid nodule begins with a careful history,
In adult patients with cervical adenopathy and no clear focusing on both local symptoms (dysphagia, hoarseness,
infectious etiology, there is a high risk of malignancy, and vocal changes, sleep apnea) and systemic symptoms, as well
FNA is recommended. FNA may provide a conclusive diag- as a family history of thyroid disease and past exposure to
nosis or further reduce the range of diagnostic possibilities. radiation [see Figure 2]. A past history of radiation exposure
FNA is also useful in patients with a known distant malig- in particular is associated with increased risk of malignancy.
nancy in whom confirmation of metastases is needed for After a thorough history and examination, including
05/12
History, physical examination
Low TSH Normal or Elevated
123
I or Ultrasonography
99
Nonfunctioning
Tc scan
Hyperfunctioning
Medically FNA
Nondiagnostic
treat and
observe
Benign Malignant Suspicious Indeterminate

for PTC
Follow Preoperative Hürthle Follicular

evaluation cell neoplasm
and surgery neoplasm
Consider
Not thyroid
hyperfunctioning scintigraphy
Hyperfunctioning
Figure 2 Management algorithm for thyroid nodules. FNA = fine-needle aspiration; PTC = papillary thyroid cancer; TSH = thyroid-stimulating
hormone.
ultrasonography, further investigation is usually warranted. performed. If the nodule is hyperfunctioning, then no fur-
This can include laboratory studies, further imaging, and ther evaluation is needed as the risk of malignancy is low.
cytologic assessment.6 Patients with a hyperfunctioning nodule, a depressed serum
A serum thyroid-stimulating hormone (TSH) level TSH, and clinical symptoms may then be evaluated and
should be obtained on any patient with a palpable thyroid medically treated for hyperthyroidism. Additionally, an
nodule or a nodule detected incidentally on imaging. If the elevated TSH is associated with a small increased risk of
serum TSH is low, then radionuclide scanning should be malignancy.
05/12
Ultrasonography should be performed for any patient repeatedly yield nondiagnostic samples, surgical excision
with a palpable thyroid nodule as part of the initial evalua- should be considered, particularly if the nodule is solid
tion. Sonography can indicate the size of the nodule and its rather than cystic. For nodules with FNA findings diagnostic
position within the gland; it can identify features that sug- of malignancy, surgical resection is recommended. For
gest a benign or malignant nodule. A thorough ultrasound benign nodules, no further investigation is required. How-
examination may also help the practitioner identify suspi- ever, if a benign nodule continues to grow, as demonstrated
cious cervical adenopathy, additional nodules not palpated on follow-up ultrasonography, repeated biopsy should
on examination, or other abnormalities. Findings of micro- be performed, and a diagnostic thyroid lobectomy may be
calcifications, irregular margins, and increased vascularity indicated.
are suggestive of papillary thyroid cancer. Follicular cancers Nodules with indeterminate cytology are typically
are often iso- or hyperechoic with a peripheral “halo” of reported as “cellular atypia,” “Hürthle cell neoplasm,” or
decreased echogenicity. “follicular neoplasm” and are an area of significant debate
FNA is recommended for the majority of thyroid nodules in terms of management. Many molecular markers and
detected either by palpation or imaging. Table 3 outlines the imaging studies have been evaluated for a possible role in
current recommendations for FNA based on clinical history, improving the diagnostic accuracy in patients with these
size of the nodule, and imaging characteristics. FNA is not lesions. Most recently, the role of 18FDG-PET has been
routinely recommended for nodules smaller than 1 cm; explored as a promising method of determining malignant
however, in patients with a higher risk of malignancy, potential; however, the findings of most studies of FDG-PET
including those with a family history of thyroid cancer or a utility show low specificity. Currently, for indeterminate
history of radiation exposure in childhood or adolescence, lesions interpreted as “suspicious for papillary carcinoma”
FNA of a smaller nodule may be indicated. FNA can be or “Hürthle cell neoplasm,” surgical resection is recom-
performed either by palpation or ultrasound guidance. mended.6 For the remainder of indeterminate lesions, a
The latter is recommended for most nodules as it decreases radionuclide study can be considered; if the nodule is
not hyperfunctioning, then surgical resection may be
the occurrence of nondiagnostic results but especially for
warranted.
those that are predominantly cystic, located posteriorly
in the thyroid lobe, or nonpalpable. FNA is useful in the Thyroid Cancer: Overview of Surgical and Medical
evaluation of thyroid nodules in children.7 Management
Interpretation of FNA Cytology The procedure of choice for a papillary thyroid cancer that
is small (< 1 cm in diameter) and confined to the gland, as
FNA results can be classified as nondiagnostic, benign,
well as for minimally invasive follicular thyroid cancer, is a
malignant, suspicious for malignancy, or indeterminate.8
thyroid lobectomy. For the remainder of papillary or follicu-
Nearly 20% of FNAs are nondiagnostic; repeated FNA lar cancers, as well as Hürthle cell and medullary thyroid
under ultrasound guidance can lead to a diagnostic cytology cancer, total or near-total thyroidectomy is preferable.
specimen in 50 to 75% of these nodules. For nodules that Patients with thyroid nodules and a history of radiation
exposure should also undergo a total thyroidectomy as
approximately 40% of these patients have at least one addi-
Table 3 Thyroid Nodule Assessment tional focus of papillary thyroid cancer. Total thyroidectomy
Recommended Size
also allows the use of 131I scanning to monitor for recurrence
Nodule Sonographic or Clinical Features Threshold for FNA and increases the sensitivity of thyroglobulin and calcitonin
assays in posttreatment surveillance. New information
High-risk history
regarding the molecular basis for thyroid neoplasia is
Nodule with suspicious sonographic > 5 mm gradually informing the individualized care for patients
features with these tumors.9
Nodule without suspicious sonographic > 5 mm Patients with medullary thyroid cancer should addition-
features ally undergo bilateral central neck dissection, screening for
Abnormal cervical lymph nodes All ret proto-oncogene mutations, and screening for pheochro-
mocytoma.10 Anaplastic thyroid cancer is best treated with
Microcalcifications present in nodule ≥ 1 cm
a combination of chemotherapy and radiation therapy, in
Solid nodule conjunction with removal of as much of the neoplasm as can
And hypoechoic > 1 cm be safely excised. Most patients with thyroid lymphomas
should receive chemotherapy, radiation therapy, or a
And iso- or hyperechoic ≥ 1.5 cm combination of the two.
Mixed cystic-solid nodule
neoplastic
With any suspicious sonographic ≥ 1.5–2.0 cm
features masses
Without any suspicious sonographic ≥ 2.0 cm Salivary Gland
features Tumor
Purely cystic nodule FNA not indicated Salivary gland neo-
Spongiform nodule ≥ 2.0 cm plasms usually pre-
Adapted from Cooper DS et al.6
sent as an enlarging
FNA = fine-needle aspiration. solid mass in front of
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and below the ear, at the angle of the mandible, or in the Neurogenic Tumor (Neurofibroma, Neurilemmoma)
submandibular triangle. Benign salivary gland lesions are The most common neurogenic tumors in the head and
often asymptomatic; malignant ones are often associated neck, neurilemmomas (schwannomas) and neurofibromas,
with seventh cranial nerve symptoms or skin fixation. arise from the neurilemma and usually present as painless,
Diagnostic imaging studies (CT or MRI) indicate whether slowly growing masses in the lateral neck. Neurilemmomas
the mass is salivary in origin but do not help classify it his- can be differentiated from neurofibromas only by means of
tologically. The diagnostic test of preference is open biopsy histologic examination.
in the form of complete submandibular gland removal or Given the potential these tumors possess for malignant
superficial parotidectomy. degeneration and slow but progressive growth, surgical
With any mass in or around the ear, one should be resection is indicated. This may include resection of the
prepared to remove the superficial lobes of the parotid, the involved nerves, particularly with neurofibromas, which
deep lobes, or both and to perform a careful facial nerve tend to be more invasive and less encapsulated than
dissection. Any less complete approach reduces the chances neurilemmomas.
of a cure: there is a high risk of implantation and seeding
of malignant tumors. Benign mixed tumors make up two Laryngeal Tumor
thirds of all salivary tumors; these must also be completely In rare cases, a chondroma may arise from the thyroid
removed because recurrence is common after incomplete cartilage or the cricoid cartilage. It is firmly fixed to the
resection. Malignant lesions may require additional therapy cartilage and may present as a mass in the neck or as the
with radiation or chemotherapy.11 cause of a progressively compromised airway. Surgical
Soft Tissue Tumor (Lipoma, Sebaceous Cyst) excision is indicated.
Superficial intracutaneous or subcutaneous masses may Lymphoma
be sebaceous (or epidermal inclusion) cysts or lipomas. Final Cervical adenopa-
diagnosis and treatment usually involve simple surgical
thy is one of the most
excision, often done as an office procedure with local
common presenting
anesthesia.
symptoms in patients
Chemodectoma (Carotid Body Tumor) with Hodgkin and
non-Hodgkin lym-
Carotid body tumors belong to a group of tumors known
phoma. The nodes
as chemodectomas (or, alternatively, as glomus tumors
tend to be softer,
or nonchromaffin paragangliomas), which derive from the
smoother, more elastic, and more mobile than nodes
chemoreceptive tissue of the head and neck. Chemodecto-
containing metastatic carcinoma. Rapid growth is common,
mas most often arise from the tympanic bodies in the middle
particularly in non-Hodgkin lymphoma. Involvement of
ear, the glomus jugulare at the skull base, the vagal body
extranodal sites, particularly Waldeyer tonsillar ring, often
near the skull base along the inferior ganglion of the vagus,
occurs in patients with non-Hodgkin lymphoma; enlarge-
and the carotid body at the carotid bifurcation. They are
sometimes familial and can occur bilaterally.12 ment of these sites may provide a clue to the diagnosis. The
A carotid body tumor presents as a firm, round, slowly diagnosis is usually suggested by FNA and then confirmed
growing mass at the carotid bifurcation. Occasionally, a via excisional biopsy of an intact lymph node. Lymphoma is
bruit is present. The tumor cannot be separated from the typically treated by radiation therapy, chemotherapy, or
carotid artery by palpation and can usually be moved both depending on the disease’s pathologic type and clinical
laterally and medially but not in a cephalocaudal plane. The stage.
differential diagnosis includes a carotid aneurysm, a bran- Upper Aerodigestive Tract Cancer
chial cleft cyst, a neurogenic tumor, and nodal metastases
fixed to the carotid sheath. The diagnosis is made by CT or Many localized tumors of the aerodigestive tract can be
arteriography, which demonstrate a characteristic highly cured with surgery alone. Treatment of locally advanced
vascular mass at the carotid bifurcation. Neurofibromas squamous cell cancers, however, often necessitates a multi-
tend to displace, encircle, or compress a portion of the modality approach.13 Such an approach has traditionally
carotid artery system, events that are readily demonstrated consisted of surgery followed by radiation therapy, but
by carotid angiography. recent data indicate that concurrent chemoradiotherapy has
Biopsy should be avoided. Chemodectomas are some- an additional beneficial effect as an adjuvant measure.14,15
times malignant and should therefore be removed in most Chemoradiotherapy is also employed for unresectable
cases to prevent subsequent growth and pressure symp- disease, and induction chemotherapy may be administered
toms. Fortunately, even malignant chemodectomas are usu- preoperatively to reduce operative morbidity. Among the
ally low grade; long-term results after removal are generally chemotherapeutic agents active against head and neck squa-
excellent. Vascular surgical experience is desirable in that mous cell cancers are the taxanes, cisplatin and fluorouracil,
the tumors are very vascular and intimately involve the and various newer targeted agents (e.g., epidermal growth
carotid artery, and clamping of the carotid artery may result factor receptor antagonists).
in a stroke. Expectant treatment may be indicated in older Treatment planning for such patients depends on the
or debilitated individuals. Radiotherapy may be helpful for tumor’s location and stage, the patient’s age, and the pres-
patients with unresectable tumors. ence and severity of associated medical conditions, among
05/12
other factors.16 Consultation with a specialist in this field is typical pigmented, irregularly shaped skin lesions, malig-
generally required. Therefore, cancers involving the nose, nant melanoma can also arise on the mucous membranes of
the paranasal sinuses, the nasopharynx, the floor of the the nose or the throat, on the hard palate, or on the buccal
mouth, the tongue, the palate, the tonsils, the piriform sinus, mucosa. The treatment of choice is wide surgical resection.
the hypopharynx, or the larynx are best managed by an Radiation therapy, chemotherapy, and immunotherapy may
experienced head and neck oncologic surgeon in conjunc- be useful in specific situations.
tion with a radiation therapist and a medical oncologist.
metastatic
Soft Tissue Sarcoma disease
Malignant sarcomas are not common in the head and Metastatic
neck. The sarcomas most frequently encountered include Squamous Cell
rhabdomyosarcoma in children, fibrosarcoma, liposarcoma, Carcinoma
osteogenic sarcoma (which usually arises in young adults),
The basic principle
and chondrosarcoma. The most common head and neck
in the management
sarcoma, however, is malignant fibrous histiocytoma (MFH).
of metastatic squa-
MFH occurs most frequently in the elderly and extremely mous cell carcinoma
rarely in children, but it can arise at any age. It is often dif- is wide excision of the primary tumor and treatment of all
ficult to differentiate from other entities (e.g., fibrosarcoma). regional lymph node groups at highest risk for metastases
MFH can occur in the soft tissues of the neck or involve the by means of surgery or radiation therapy, depending on the
bone of the maxilla or the mandible. The preferred treatment clinical circumstances. Selective lymph node dissection can
is wide surgical resection; adjuvant radiation therapy and be performed along with wide excision of the primary
chemotherapy are being studied in clinical trials. tumor at the time of the initial operation. Sentinel lymph
Rhabdomyosarcoma, usually of the embryonic form, is node (SLN) biopsy may provide a low morbidity staging
the most common form of sarcoma in children. It generally opportunity for this as in other diseases.17 For example, car-
occurs near the orbit, the nasopharynx, or the paranasal cinomas of the oral cavity are treated with supraomohyoid
sinuses. The diagnosis is confirmed by biopsy. A thorough neck dissection, and carcinomas of the oropharynx, the
search for distal metastases is important before treatment— hypopharynx, and the larynx are treated with lateral neck
consisting of a combination of surgical resection, radiation dissection. If extranodal extension or the presence of multi-
therapy, and chemotherapy—is begun. ple levels of positive nodes is confirmed by the pathologic
findings, the patient should receive adjuvant bilateral neck
Skin Cancer
radiation therapy for 4 to 6 weeks after operation.
Basal cell carcinomas are the most common of the skin
malignancies. These lesions arise most commonly in areas Metastatic Adenocarcinoma
that have been extensively exposed to sunlight (e.g., the Adenocarcinoma in a cervical node most frequently
nose, the forehead, the cheeks, and the ears). Treatment represents a metastasis from the thyroid gland, the salivary
consists of local resection with adequate clear margins. glands, or the gastrointestinal (GI) tract. The primary
Metastases are rare, and the prognosis is excellent. Inade- tumor must therefore be sought through endoscopic and
quately excised and neglected basal cell carcinomas may radiologic study of the bronchopulmonary tract, the GI tract,
ultimately spread to regional lymph nodes and can cause the genitourinary tract, the salivary glands, and the thyroid
extensive local destruction of soft tissue and bone. For gland. Other possible primary sites include breast and
example, basal cell carcinoma of the medial canthus may pelvic tumors in women and prostate cancer in men.
invade the orbit, the ethmoid sinus, and even the brain. If the primary site is controlled and the tumor is poten-
Periauricular basal cell carcinoma can spread across the tially curable, or if the primary site is not found and the
cartilage of the ear canal or into the parotid gland. In such neck disease is the only established site of malignancy,
cases of locally advanced basal cell cancer or nodal involve- neck dissection is the appropriate treatment. Postoperative
ment with tumor, patients may require more extensive adjuvant radiation may also be considered. If the patient
surgical treatment (i.e., modified neck dissection). Postop- has thyroid cancer and palpable nodes, lateral neck dissec-
erative radiation therapy is often administered to optimize tion (levels II to V) and central neck dissection (level VI) are
local control and reduce the risk of recurrence. recommended.
Squamous cell carcinoma also arises in areas associated Overall survival is low—about 20% at 2 years and 9% at
with extensive sunlight exposure; the lower lip and the pin- 5 years—except for patients with papillary or follicular
na are the most common sites. Unlike basal cell carcinoma, thyroid cancer, who have a good prognosis. Two factors
however, squamous cell carcinoma tends to metastasize associated with a better prognosis are unilateral neck
to both regional and distant sites. This tumor must also be involvement and limitation of disease to lymph nodes above
excised with an adequate margin. the cricoid cartilage.
Melanoma is primarily classified on the basis of depth of
invasion (as quantified by Clark level or Breslow thickness), Metastatic Melanoma
location, and histologic subtype, although the prognosis is If the patient has a thin melanoma (Breslow thickness
closely related to the thickness of the tumor [see Metastatic < 1 mm; Clark level I, II, or III), full-thickness excision with
Disease, Metastatic Melanoma, below]. In addition to the 1 cm margins is adequate treatment for the primary site.
05/12
Patients with intermediate-thickness melanomas (Breslow Metastatic Adenocarcinoma, above]. The most common pri-
thickness 1 to 4 mm; Clark level IV) should have a full- mary sites in the head and neck are the salivary glands and
thickness excision with at least a 1.5 cm margin. These the thyroid gland. The possibility of an isolated metastasis
patients also have a definable risk of lymph node spread and from the breast, the GI tract, or the genitourinary tract must
thus should be concurrently staged with lymphatic mapping also be rigorously investigated. If no primary site is identi-
and SLN biopsy. All patients with intermediate-thickness fied, the patient should be considered for protocol-based
melanomas and positive SLNs and all melanoma patients chemotherapy and radiation therapy, directed according to
with palpable lymph nodes should undergo complete what the primary site is most likely to be in that patient.
staging with full-body CT/PET scans. If no other disease
is found, modified neck dissection should be performed to congenital neck
obtain optimal local disease control. Because these tumors mass
may metastasize to nodes in the parotid region, superficial Thyroglossal Duct
parotidectomy is often included in the neck dissection, Cyst
particularly in the case of melanoma located on the upper
face or the anterior scalp. Consultation with a medical Thyroglossal duct
oncologist is indicated for all patients with intermediate- cysts are remnants
thickness or thick (Breslow thickness > 4 mm; Clark level V) of the tract along
melanomas; immunotherapy or chemotherapy may be con- which the thyroid
sidered. Radiation therapy is often considered in patients gland descended
with extensive local or nodal disease following adequate into the neck from the foramen cecum [see Figure 3]. They
surgical resection. account for about 70% of all congenital abnormalities of the
neck. Thyroglossal duct cysts may be found in patients of
Metastasis from an any age but are most common in the first decade of life.
Unknown Primary They may present as a lone cyst, a cyst with a sinus tract, or
Malignancy a solid core of thyroid tissue. They may be so small as to be
Management of barely perceptible, as large as a grapefruit, or anything in
patients with an between. Thyroglossal duct cysts are almost always found
unknown primary in the midline, at or below the level of the hyoid bone; how-
malignancy is chal- ever, they may be situated anywhere from the base of the
lenging for the sur-
geon. It is helpful to
know that when cervical lymph nodes are found to contain
metastatic squamous cell carcinoma, the primary tumor is in
the head and neck about 90% of the time. Typically, such
patients are found to have squamous cell carcinoma on the
basis of FNA of an abnormal cervical lymph node; this find-
ing calls for an exhaustive review of systems and a detailed
physical examination of the head and neck.
If no primary tumor is identified, the patient should
undergo endoscopic evaluation of the nasopharynx, the
hypopharynx, the esophagus, the larynx, and the tracheo-
bronchial tree under general anesthesia. Biopsies of the
nasopharynx, the tonsils, and the hypopharynx often
identify the site of origin (although there is some debate on
this point). If the biopsies do not reveal a primary source of
cancer, the preferred treatment is unilateral neck dissection,
followed by radiation therapy directed toward the neck, the
entire pharynx, and the nasopharynx. In 15 to 20% of cases,
the primary cancer is ultimately detected. Overall 5-year
survival in such cases ranges from 25 to 50%.
If a malignant melanoma is found in a cervical lymph
node but no primary tumor is evident, the patient should be
asked about previous skin lesions, and a thorough repeat
head and neck examination should be done, with particular
attention to the scalp, the nose, the oral cavities, and the
sinuses. An ophthalmologic examination is also required.
If physical examination and radiographic studies find no Figure 3 The course of the thyroglossal duct from the foramen
evidence of metastases, modified neck dissection should be cecum to the pyramidal lobe of the thyroid gland. The operative
performed on the involved side. treatment of thyroglossal duct abnormalities includes removal of the
Metastatic adenocarcinoma in a cervical lymph node central portion of the hyoid bone to ensure complete tract removal,
with no known primary tumor is discussed elsewhere [see thus limiting the risk of recurrence.
05/12
tongue to the suprasternal notch. They occasionally present (where it may involve the parotid gland), and in the midline
slightly lateral to the midline and are sometimes associated (where it may involve the tongue, the floor of the mouth, or
with an external fistula to the skin of the anterior neck. They the larynx).
are often ballotable and can usually be moved slightly from The typical clinical picture is of a diffuse, soft, doughy,
side to side but not up or down; however, they do move up irregular mass that is readily transilluminated. Cystic
and down when patients swallow or protrude the tongue. hygromas look and feel somewhat like lipomas but have less
Thyroglossal duct cysts must be differentiated from well-defined margins. Aspiration of a cystic hygroma yields
dermoid cysts, lymphadenopathy in the anterior jugular chain, straw-colored fluid. They may be confused with angiomas
and cutaneous lesions (e.g., lipomas and sebaceous cysts). (which are compressible), pneumatoceles from the apex
Operative treatment is almost always required, not only of the lung, or aneurysms. They can be distinguished from
because of cosmetic considerations but also because of the vascular lesions by arteriography. On occasion, a cystic
high incidence of recurrent infection, including abscess hygroma grows suddenly as a result of an upper respiratory
formation. About 1% of thyroglossal duct cysts contain cancer; tract infection, infection of the hygroma itself, or hemor-
papillary cancer is the neoplasm most commonly encountered, rhage into the tissues. If the mass becomes large enough, it
followed by squamous cell carcinoma. About 25% of patients can compress the trachea or hinder swallowing.
with papillary thyroid cancer in thyroglossal duct cysts have In the absence of pressure symptoms (i.e., obstruction
papillary thyroid cancer in other parts of the thyroid gland as of the airway or interference with swallowing) or gross
well. About 10% have nodal metastases, which in some cases deformity, cystic hygromas may be treated expectantly.
are bilateral. They tend to regress spontaneously; if they do not, complete
surgical excision is indicated. Excision can be difficult
Branchial Cleft Cyst because of the numerous satellite extensions that often
Branchial cleft cysts are vestigial remnants of the fetal surround the main mass and because of the association of
branchial apparatus from which all neck structures are the tumor with vital structures such as the cranial nerves.
derived. Early in embryonic development, there are five Recurrences are common; staged resections for complete
branchial arches and four grooves (or clefts) between them. excision are often necessary.
The internal tract or opening of a branchial cleft cyst is situ-
ated at the embryologic derivative of the corresponding Vascular Malformation (Hemangioma)
pharyngeal groove, such as the tonsil (second arch) or the Hemangiomas are usually considered congenital because
piriform sinus (third and fourth arches). The second arch is they either are present at birth or appear within the first year
the most common area of origin for such cysts. The position of life. A number of characteristic findings—bluish-purple
of the cyst tract is also determined by the embryologic coloration, increased warmth, compressibility followed by
relation of its arch to the derivatives of the arches on either refilling, bruit, and thrill—distinguish them from other head
side of it. and neck masses. Angiography is diagnostic but is rarely
The majority of branchial cleft cysts (those that develop indicated.
from the second, third, and fourth arches) tend to present as a Given that most of these congenital lesions resolve spon-
bulge along the anterior border of the sternocleidomastoid taneously, the treatment approach of choice is observation
muscle, with or without a sinus tract. Branchial cleft cysts alone unless there is rapid growth, thrombocytopenia, or
may become symptomatic at any age, but most are diagnosed involvement of vital structures.
in the first two decades of life. They often present as a smooth,
painless, slowly enlarging mass in the lateral neck. Frequently, Financial Disclosures: None Reported
there is a history of fluctuating size and intermittent tender-
ness. The diagnosis is more obvious when there is an
external fistulous tract and there is a history of intermittent References
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10. Wu LS, Roman SA, Sosa JA. Medullary thyroid cancer: an tumor staging in advanced laryngeal cancer: implications
update of new guidelines and recent developments. Curr for treatment selection. J Clin Oncol 2010;28:2315–7.
Opin Oncol 2011;23:22–7. 17. Paleri V, Rees G, Arullendran P, et al. Sentinel node biopsy
11. Rizk S, Robert A, Vandenhooft A, et al. Activity of chemo- in squamous cell cancer of the oral cavity and oral pharynx:
therapy in the palliative treatment of salivary gland tumors: a diagnostic meta-analysis. Head Neck 2005;27:739–47.
review of the literature. Eur Arch Otorhinolaryngol 2007;
264:587–94.
12. Dziegielewski PT, Knox A, Liu R, et al. Familial paragan- Acknowledgment
glioma syndrome: applying genetic screening in otolaryn-
gology. J Otolaryngol Head Neck Surg 2010;39:646–53. Figures 1 and 3 Tom Moore
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2 HEAD AND NECK 4 HEAD AND NECK DIAGNOSTIC PROCEDURES — 1
4 HEAD AND NECK DIAGNOSTIC

PROCEDURES
Donald J. Annino Jr, MD, DMD, and Laura A. Goguen, MD, FACS*
Head and neck diseases can be inflammatory, infectious, con- The inner ear is made up of a system of channels and
genital, neoplastic, or traumatic. An accurate diagnosis is chambers within the otic capsule. It has two parts anato-
mandatory and is based on a detailed history and physical mically and functionally: the vestibular labyrinth and the
examination, as well as ancillary tests. After a detailed history, cochlear. The vestibular system is responsible for balance and
including the chief complaint, history of present illness, past the cochlear system for hearing.
medical history, current medications, allergies, social history Tumors of the ear may present with pain, discharge,
including tobacco and ethanol use, and family history, is decreased hearing, facial nerve involvement, and dizziness.
obtained, a physical examination should be done. nose and paranasal sinuses
The physical examination of the head and neck is com-
The external nose is made of two fused nasal bones and
plicated by the close relationship of structures and the need
four alar cartilages. There are two nasal passages that are
to examine many of the structures through orifices. The
separated by a vertical septum composed of cartilage (antero-
entire mucosal surface of the head and neck needs be exam- inferiorly) and bone (the thin perpendicular plate of the
ined when evaluating for head and neck cancers. Once a ethmoid bone and the vomer). The nose is lined with ciliated
detailed history and physical examination have been done, a respiratory mucoperichondrium, which contains glands and
differential diagnosis list is created. The correct diagnosis and mucus-secreting cells. The cribriform plate forms the roof of
treatment plan are arrived at with the use of diagnostic the nose, with the hard palate forming its floor. The lateral
procedures including imaging and sampling of the tissue. wall is a partition between the paranasal sinuses and the nasal
passages. There are three turbinates on each lateral wall:
superior, middle, and inferior. The inferior turbinate is the
Anatomy
largest and most vascular. The turbinates divide the nasal
The regions of the head and neck are usually divided into passages vertically and create the superior, middle, and
the following areas: the ear, the nose and paranasal sinuses, inferior meatuses.
the oral cavity, the pharynx, the larynx, the salivary glands, There are four paranasal sinuses on each side. The frontal
and the neck, including the thyroid [see Figure 1]. and sphenoid sinuses are midline and frequently are asym-
metrical. The ethmoid and maxillary sinuses are placed later-
ear ally. The ethmoid sinus is considered the key sinus and can
The ear is divided into three parts: the external, middle, provide access to all the other sinuses [see Figure 2]. Its
and inner ear. The external ear is made of the pinna and roof is the fovea ethmoidales, which, in conjunction with the
external auditory canal. The pinna is the only part of the ear cribriform plate, separates the anterior cranial vault from the
that grows after birth. It is composed of an irregular plate of nose. The sphenoid sinus is the most posterior sinus and has
fibrocartilage tightly covered by skin and a thin layer of sub- the internal carotid artery, optic nerve, second division of the
cutaneous tissue. The external auditory canal is a tortuous trigeminal nerve, and vidian nerve all in close proximity.
passage with an average length of 3.7 cm in an adult male. The symptoms associated with nasal cavity tumors fre-
The canal has thicker skin overlying cartilage in the outer quently do not occur early in the diseases because much of
the nasal cavity and paranasal sinuses is air filled. This can
half. This skin also has hair and special glands that secrete
also be a hard area to examine, and the symptoms are usually
cerumen. The inner portion of the canal is thin skin over
first attributed to more mundane conditions, such as allergies
bone. The tympanic membrane is the common wall between
and sinusitis. The most common symptoms are facial pain,
the external ear and the middle ear. It is semitranslucent,
nasal obstruction, epistaxis, nasal discharge, decreased sense
cone shaped, and concave laterally. of smell, and changes to the orbit.
The middle ear is an air-filled chamber that has five bony
walls. The sixth wall is the tympanic membrane. Within the Oral Cavity
middle ear are ossicles. It is connected to the nasopharynx The limits of the oral cavity are the lips anteriorly and the
by the eustachian tube. It runs downward and forward and is anterior tonsil pillars and circumvallate papillae of the tongue
composed of a cartilaginous segment and a bony segment. posteriorly. The oral cavity is divided into the vestibules,
which is the space between the teeth and cheek; the alveolar
* The authors and editors gratefully acknowledge the con- ridges, which are the teeth-bearing areas of the maxilla and
tributions of the previous authors, Adam S. Jacobson, MD, mandible; the floor of the mouth; the retromolar trigone,
Mark L. Urken, MD, FACS, and Marita S. Teng, MD, to the which is the triangular area of gum and soft tissue immedi-
development and writing of this chapter. ately posterior to the lower molars; the buccal mucosa, which
DOI 10.2310/7800.2028
11/10
Sphenoidal Sinus Superior Sagittal Sinus

Concha Suprema
Frontal Sinus
Superior Concha
Falx Cerebri
Middle Concha
Pharyngeal Orifice
of Auditory Tube
Inferior Concha
Straight Sinus
Oral Part
of Tongue
Sublingual Fold
Pharyngeal Recess
Pharyngeal Part
of Tongue
Salpingopharyngeal Fold
Epiglottis Palatine Tonsil
Hyoid Bone
Oral Part of Pharynx
Laryngeal Part
of Pharynx
Vocal Fold
Thyroid Cartilage
Esophagus
Figure 1 The anatomic structures of the head and neck are shown.
is the mucous membrane lining of the cheek; and the oral The sublingual glands are located in the floor of the mouth
tongue, which is the anterior two thirds of the tongue. The and frequently have multiple ducts. The secretion is
posterior limit is the circumvallate papillae. mucous.
Thousands of minor salivary glands are present throughout
Salivary Glands the oral cavity, pharynx, and epiglottis. Minor salivary gland
Salivary glands are subdivided into major and minor sali- neoplasms are usually malignant, with quoted rates around
vary glands. The major salivary glands consist of the parotid 75%.
glands, submandibular glands, and sublingual glands. The
parotid gland is the largest salivary gland. It is incompletely Pharynx
split by the facial nerve into deep and superficial lobes. The The pharynx is an incomplete muscular tube from the base
main duct runs horizontal to the zygoma on the lateral of the skull to the inlet of the esophagus. The pharynx is
surface of the masseter and enters the oral cavity opposite the divided into three parts: the nasopharynx, oropharynx, and
second maxillary molar. It has serous secretions with low hypopharynx. The nasopharynx sits behind the nasal cavity,
mineral content. Approximately 80 to 85% of the neoplasms extending from the choanae to the inferior surface of the
in the parotid are benign. palate. Adenoid tissue and the eustachian tubes are present
The submandibular gland is below the body of the man- in the nasopharynx. Malignancies of the nasopharynx can
dible. It lies on the lateral surface of the mylohyoid muscle. present as nasal obstruction, epistaxis, tinnitus, headache,
The duct passes upward and medially to the anterior floor diminished hearing, and facial pain.
of the mouth. Its secretions are mixed serous and mucous, The oropharynx extends from the junction of the hard and
and it has a higher mineral content than the parotid gland. soft palates and the circumvallate papillae to the valleculae.
Neoplasms in the submandibular glands are more evenly split It includes the soft palate and uvula, base of the tongue,
between malignant and benign. pharyngoepiglottic and glossoepiglottic folds, palatine arch
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Figure 2 The paranasal sinuses are shown.
(which includes the tonsils and the tonsillar fossae and commissure, true vocal cords, and posterior commissure.
pillars), valleculae, and lateral and posterior oropharyngeal The most common symptom of carcinoma of the glottis is
walls. Carcinomas of the oropharynx can present as pain, sore hoarseness.
throat, dysphagia, and referred otalgia.
The hypopharynx extends from the superior border of the Subglottis
hyoid bone to the inferior border of the cricoid cartilage. The subglottis extends from the junction of squamous and
It includes the piriform sinuses, hypopharyngeal walls, and respiratory epithelium on the undersurface of the true vocal
postcricoid region (i.e., the area of the pharyngoesophageal cords (approximately 5 to 10 mm below the true vocal cords)
junction). Malignancies of the hypopharynx can present as to the inferior edge of the cricoid cartilage. The cricoid is the
odynophagia, dysphagia, hoarseness, referred otalgia, and only complete cartilaginous ring in the airway; therefore, it is
excessive salivation. the only rigid area in the respiratory tree. The most common
larynx symptom of carcinoma of the subglottis is hoarseness.
The larynx is subdivided into the supraglottis, glottis, neck
and subglottis. It consists of a framework of cartilages that are The neck is divided into different compartments by fascia.
held together by extrinsic and intrinsic musculature and lined
The visceral compartment is in the midline and contains the
with a mucous membrane that is topographically arranged
larynx, pharynx, trachea, thyroid, parathyroid glands, recur-
into two characteristic folds (the false and true vocal cords).
rent laryngeal nerves, and cervical esophagus. The neurovas-
The larynx has the following basic functions: (1) to protect
cular compartment runs the entire length of the neck from
the lower airway; (2) to conduct air to the lungs; and (3) to
the base of the skull to the esophageal inlet. It contains the
allow vocalization. Neoplasms of the larynx can present
carotid artery, internal jugular vein, vagus nerve, and jugular
as hoarseness, dyspnea, stridor, hemoptysis, odynophagia,
dysphagia, and otalgia. lymph nodes. There are two muscular compartments on each
side of the neck. Neoplasms in the neck usually present as
Supraglottis masses. Most commonly, they are painless. When malignant,
The supraglottis extends from the tip of the epiglottis to they are usually metastastic from primary malignancies in the
the junction between respiratory and squamous epithelium aerodigestive tract.
on the floor of the ventricle (the space between the false and The thyroid gland performs a vital role in regulating
true cords). Carcinomas of the supraglottis can present as metabolic function. It is susceptible to benign conditions
sore throat, odynophagia, dysphagia, and otalgia. (e.g., nodule, goiter, and cyst), inflammatory disease (e.g.,
thyroiditis), and malignancies. Additionally, congenital
Glottis anomalies of the thyroid, such as a thyroglossal duct cyst, can
The space between the free margin of the true vocal cords present later in life. Thyroid lesions can present as pain,
is the glottis. This structure is bounded by the anterior hoarseness, dyspnea, or dysphagia.
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On the posterior aspect of the thyroid gland reside the

four parathyroid glands. These glands play a vital role in
maintaining calcium balance. Parathyroid adenomas and,
rarely, carcinomas can develop.
Clinical Evaluation
The diagnostic approach to the upper aerodigestive tract
begins with a thorough history, starting with a detailed evalu-
ation of the chief complaint. Once a complete history of the
chief complaint has been obtained, the physician should elicit
a more comprehensive general medical history from the
patient, including pertinent past medical history, past surgical
history, medications, allergies, social history (tobacco,
ethanol, and intravenous drug use), and family history.
The next step is to perform a comprehensive physical
examination. This begins with a thorough inspection of the
entire surface of the head and neck. The examination should
proceed in an orderly fashion. The exact order is not impor-
tant, but examiners should determine the order with which
they are most comfortable and not deviate from that order.
This way, they are unlikely to skip an anatomic area. The
mucosal surfaces of the aerodigestive tract are inspected.
Endoscopic evaluation of the upper aerodigestive tract is
crucial in establishing a definitive diagnosis. The equipment
used consists of both rigid and flexible laryngoscopes, bron-
choscopes, and esophagoscopes. Many of these techniques
can be performed in the office setting, providing the surgeon
with an array of methods for gaining the information
necessary for a working diagnosis and, in some cases, for per-
forming a therapeutic intervention [see Figure 3]. Operative
endoscopy is performed to obtain a definitive diagnosis, to
stage tumors, and to rule out synchronous lesions. There is
no substitute for a thorough examination and biopsy of a
lesion with the patient under general anesthesia. Regardless Figure 3 Otolaryngology clinic office space with needed
equipment, including an examination chair, a headlight, and
of the endoscopic method used, an adequate biopsy specimen
a fiberoptic rhinolaryngoscope.
must be obtained for a histologic diagnosis.
An accurate history and a careful physical examination of
the head and neck, including the mucosal surfaces, are the a tissue specimen, and, in patients with cancer, assess the rest
most important steps in evaluating a lesion in this part of the of the upper aerodigestive tract for a synchronous primary
body; this clinical evaluation usually provides only a working tumor.
diagnosis. The head and neck surgeon must then proceed in After a histologic diagnosis has been made and correlated
a stepwise fashion to further clarify the diagnosis and, in the with imaging, the patient and the physician can have a
case of a neoplasm, to perform an accurate staging. comprehensive discussion of the pathology, the stage of the
Radiographic techniques allow the head and neck surgeon disease, and the selection of therapy.
to visualize the mass and determine its characteristics (i.e.,
nose
to differentiate between solid and cystic lesions), as well as
its anatomic associations. Ultrasonography, magnetic reso- Anterior Rhinoscopy
nance imaging (MRI), computed tomography (CT), and Anterior rhinoscopy is the examination of the nasal cavities
dual-modality positron emission tomography (PET)/CT each with the use of a nasal speculum [see Figure 4]. The speculum
provide a unique view of the pathology in question and is used to spread the ala. When done, the speculum should
thereby help narrow the differential diagnosis. Acquisition of touch only the parts that are covered with skin. Resting the
a tissue specimen for cytologic or histologic analysis, or both, speculum on the nasal mucosa is painful. Anterior rhinoscopy
is the next step. Fine-needle aspiration (FNA) is often used is best done before and after topical vasoconstriction of
at this stage in the workup provided that the location of the the nasal mucosa. A good coaxial light source is needed. The
mass lends itself to a safe procedure. If the lesion is located more anterior portions of the nasal cavity are most readily
deep in the neck near vital structures, image-guided FNA can examined.
be attempted before resorting to an open biopsy. If the lesion
is on a mucosal surface of the upper aerodigestive tract, Posterior Rhinoscopy
an endoscopic biopsy is performed. Often panendoscopy is Posterior rhinoscopy is used to examine the posterior
performed at this point to accurately map the lesion, obtain portion of the nasal cavity and, more importantly, the
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deeply and rhythmically, as if panting like a dog. The non-

dominant hand of the examiner grasps the patient’s tongue
with gauze. The mirror is warmed and placed gently against
the soft palate. To optimize the view, the examiner should ask
the patient to say “ee.” This technique can be performed
rapidly and is inexpensive.
Flexible Laryngoscopy
Flexible laryngoscopy is also referred to as flexible rhino-
laryngoscopy [see Figure 6]. It has become the most common
way to examine the nasopharynx, oropharynx, hypopharynx,
and larynx and is superior to indirect laryngoscopy. It allows
better visualization and assessment of the structures, and
since the tongue is not grasped, it allows better assessment
of how structures function. The procedure is better tolerated
by the patient, with less gagging. It has the disadvantage of
requiring more expensive equipment than indirect laryngos-
copy. Topical anesthesia is used. Most commonly, an anes-
thetic and a decongestant are sprayed into the nasal cavity
Figure 4 Shown is an assortment of nasal specula. prior to the procedure. The passage of the scope is best toler-
ated passing just inferior to the middle turbinate. If the patient
nasopharynx. It is done with a small-angled mirror placed has a deviated septum, the side with less obstruction is
posterior to the palate and uvula. The tongue should be used.
depressed using a tongue blade with the other hand. This Fiberoptic examinations in the clinic setting are not toler-
examination is limited at times by the patient’s gag reflex and ated by all patients. Even if this examination is tolerated, an
the presence of enlarged adenoids. exact diagnosis frequently is not reached or a lesion is seen
that cannot be biopsied in the clinic. It is recommended that
Rigid Nasal Endoscopy the patients undergo an examination under anesthesia. This
Rigid nasal endoscopy offers a superior view of the nasal is done to look for an occult synchronous tumor and to
cavity. Topical anesthesia and vasoconstriction are required more accurately examine and map the known tumor. The
for a good examination. The image is magnified, and deeper advantages of doing this under anesthesia are that it is better
structures are better visualized than with anterior rhinoscopy. tolerated by the patient (gagging is eliminated) and allows
The endoscopes come in a variety of lens angles (0, 30, and deeper digital palpation and biopsies as needed. The disad-
90 degrees). This allows inspection of structures that may be vantage is that it requires general anesthesia and its possible
blocked from direct line of site. A more complete examina- complications as well as the complications of the procedure.
tion of both the anterior and posterior nasal cavities and
Direct Laryngoscopy
nasopharynx is obtained than with anterior and posterior rhi-
noscopy. Rigid nasal endoscopy has become the examination Direct laryngoscopy requires general anesthesia and there-
of choice for a through nasal evaluation. fore is done in the operating room. It is done with hollow,
metal, rigid tubes [see Figure 7]. The laryngoscopes used by
larynx and pharynx otolaryngologists differ from those used by anesthesiologists.
They are straight and tubular and have distal lighting. There
Indirect Laryngoscopy
Indirect laryngoscopy is used to examine the larynx,
oropharynx, and hypopharynx. It is done in the clinic under
topical or no anesthesia. An angled mirror is used, and the
patient needs to be sitting upright with the neck straight and
the head thrust slightly forward [see Figure 5]. A bright coax-
ial light source is used. The patient should relax and breathe
Figure 5 Shown is a laryngeal mirror, which is used for Figure 6 A small-caliber flexible laryngoscope is used for
indirect laryngoscopy. rhinolaryngoscopy.
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a b
Figure 7 Shown are (a) normal vocal folds directly visualized via (b) a rigid laryngoscope.
are many different laryngoscopes. The sides of the laryngo- Rigid Esophagoscopy
scope hold surrounding soft tissue out of the way, allowing Rigid esophagoscopy has been used for more than a cen-
uninterrupted direct inspection of pharyngeal and laryngeal tury [see Figure 8]. It is used to diagnose cancer and remove
structures. The teeth are protected with a guard, and the foreign bodies. Unlike flexible esophagoscopy, it needs to be
structures in the oral cavity, pharynx, and larynx are all exam- done under general anesthesia. The esophagoscope is a
ined. It is best to become accustomed to doing this procedure hollow metal tube of varying lengths and widths. The patient
in a specific order so that it becomes routine and lesions will is placed supine and the maxillary teeth are protected with a
not be missed. With the use of general anesthesia, palpation mouth guard. The scope is passed transorally under direct
of the structures and a lesion can be done. The examination visualization down the right side of the oral cavity and phar-
can be improved with suspension of the laryngoscope from ynx. If resistance is met, the scope should never be forced.
a Mayo stand or the use of other suspension devices to There is a greater chance of perforation than with a flexible
allow the surgeon’s hands to be free to perform procedures. scope. As the scope is advanced, the lumen of the esophagus
Increased magnification is possible with the added use of is kept in the center of the field of vision. The lumen has the
a microscope. This is particularly useful when examining appearance of a rosette. When advancing the scope, the left
laryngeal lesions and is referred to as suspension microlaryn- thumb is used. The right hand helps direct the scope and is
goscopy. A laser can also be used if needed. used to pass instruments through its lumen. With rigid esoph-
agoscopy, the removal of the scope is as important, if not
esophagus more so, than inserting it. Removal allows better visualization
Esophagoscopy plays an important role in the evaluation of the mucosal surface as it slips over the tip of the instrument
as it is removed.
of patients with dysphagia, odynophagia, caustic ingestion,
trauma, ingested foreign bodies, suspected anomalies, and trachea and lungs
upper aerodigestive tract malignancies. This procedure may
Bronchoscopy is the technique of visualizing the trachea
be performed with either a flexible or a rigid scope.
and lungs for both diagnostic and therapeutic reasons. Two
Flexible Esophagoscopy basic forms of bronchoscopes are available: rigid and flexible.
Each has it own advantages and disadvantages.
Flexible esophagoscopy is a diagnostic tool used to exam-
ine the esophagus and stomach. It is not well suited to visual- Rigid Bronchoscopy
izing the pharynx and is usually used in an outpatient setting The use of rigid bronchoscopy began in the 19th century
with sedation and topical anesthesia. It is easier to perform with Killian. A rigid bronchoscope is a hollow, metal tube
than rigid esophagoscopy in patients who are elderly or have that is available in differing widths and lengths [see Figure 9].
limited neck mobility, short, thick necks, and/or a limited
mouth opening. The examination is usually done in the lat-
eral decubitus position with the neck flexed. Air insufflation
is important to completely visualize the mucosal surfaces.
Tissue sampling is performed with a cup forceps through a
working channel or by obtaining a brush biopsy. An endo-
scopic ultrasound probe can be passed to help define the
extent of cancer of the esophagus. It is particularly useful to
see the depth to which a tumor has invaded into the wall of
the esophagus. If a lesion is found within the esophagus, its
location is measured in centimeters from the teeth. Figure 8 Shown is a rigid esophagoscope.
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a FNA is possible for lesions that can be palpated. A

thin-gauge needle is passed into the lesion, allowing a small
number of cells to be sampled. It is a safe procedure that can
be done under local or no anesthesia. It has not been shown
to have an increased risk of seeding of the tumor spread along
b its tract. However, there is a risk of sampling error. This
occurs if the needle does not collect a representative sample
from the lesion. In reality, the test has a high sensitivity and
specificity. The benefits of FNA include the rapid availability
of results.
To optimize sampling, FNA can be done under guidance
with CT or ultrasonography. The use of imaging allows
Figure 9 (a) Rigid bronchoscopes incorporate stainless steel direct visualization of the biopsy and therefore increases the
tubes of varying lengths and diameters. The beveled distal likelihood of obtaining an accurate sample.
end of this Hopkins bronchoscope facilitates mobilization of The procedure is performed with a thin-gauge needle such
the epiglottis during intubation; the side ports permit as a 23-gauge needle. The needle is attached to a 20 mL
ventilation and use of suction catheters. (b) Illumination is syringe, which allows negative pressure to be generated [see
provided by fiberoptic rods that are inserted into the Figure 10]. Multiple passes are made through the lesion prior
bronchoscope. to removing the needle. Just before the needle is removed
from the skin, any negative pressure in the syringe is released
It is used to examine the trachea and lungs and requires and the needle is withdrawn. If a cyst is encountered, it
general anesthesia. It is used to remove foreign bodies and to should be completely evacuated and the fluid sent for cyto-
diagnose and biopsy tumors and is better than flexible bron- logic analysis. Ideally, for FNA, there should be minimal to
choscopes for evaluation of large-volume hemoptysis because no fluid or tissue in the syringe. The cells should be in the
it allows suctioning and instruments to be used together. needle. The sample is then placed on a glass slide. A smear
The patient is under general anesthesia with the neck is made by laying another glass slide on top of the drop of
hyperextended. fluid and pulling the slides apart to spread the fluid. Fixative
The bronchoscope is passed into the trachea either directly spray is then applied. Alternatively, wet smears are placed
or through a slotted laryngoscope. Once in the airway, venti- in 95% ethyl alcohol and treated with the Papanicolaou
lation is usually done through a port on the scope. Venturi technique and stains.
jet ventilation is also possible through a rigid bronchoscope. When the lesion is not easily palpated or is close to a deli-
The entire trachea and main bronchi of both lungs are easily cate structure, FNA may need to be done under imaging.
examined. Bronchial lavage is also possible. The most common imaging techniques used are ultrasono-
graphy and CT. When ultrasonography is used, it allows
Flexible Bronchoscopy
real-time imaging of the needle’s passage. This results in an
In the 1970s, Ikeda introduced flexible bronchoscopy. It is accurate trajectory and avoidance of vital structures. It also
usually performed under sedation and is more common than provides an image of the mass, allowing its characterization
rigid bronchoscopy. The instrument is thinner and longer as solid, cystic, or heterogeneous. With cystic or complex
than a rigid scope. There is a working channel that allows masses, the tip of the needle can be placed into the wall to
passage of biopsy forceps and brushes and lavage. increase specimen yield.
Panendoscopy CT guidance also provides visualization of the needle as
it is passed through the tissue and into the underlying mass.
When visualization of the entire mucosal surface of It has the disadvantage of requiring ionizing radiation.
the aerodigestive tract is needed, then panendoscopy is
performed. Panendoscopy is the term used when direct Core Biopsy
laryngoscopy (with or without microscopic assistance), esoph- A core biopsy is a percutaneous biopsy done with a large-
agoscopy, and bronchoscopy are done in the same setting. bore needle. The needle has a cutting tip and a hollow core.
Biopsy The area is infiltrated with local anesthesia prior to the
needle being passed. The procedure can be done with image
After a thorough physical examination and history, tissue
sampling should be considered if a lesion has been present for
more than 3 to 4 weeks. To make a diagnosis, an open biopsy
is not immediately indicated. Other methods are available to
help obtain tissue and make a diagnosis. However, a biopsy
is not recommended until after the history and physical
examination have been done and appropriate imaging has
been obtained. Imaging is important prior to a biopsy because
the biopsy may cause a distortion of the tissue, such as occurs
when a hematoma develops.
When a biopsy is indicated to establish a diagnosis for a
neck mass or lesion, the options include FNA, a core biopsy, Figure 10 A 20 mL syringe with a 23-gauge needle attached.
and an open biopsy. FNA offers the advantages of being The syringe is mounted in a handle to help allow creation of
simple and quick and can be done in the clinic. negative pressure.
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guidance if needed. It has the disadvantage of causing more evaluation of the primary tumor and regional metastasis. It is
bleeding and has an increased risk of seeding the tumor along usually used as part of the workup for head and neck
the needle tract. For most lesions in the neck, FNA is usually malignancies and for surveillance posttreatment.
the first choice.
Magnetic Resonance Imaging
Open Biopsy MRI results in superior evaluation of soft tissue compared
An open biopsy is indicated when a needle biopsy or core with CT and does so without ionizing radiation. Instead, its
biopsy is unable to give a diagnosis. This can be done in images are attributable to a strong magnetic field that aligns
either the clinic or, more commonly, in the operating room. the nuclear magnetization of hydrogen atoms in water. The
Whenever possible, open biopsy is usually done after other examination is more difficult for some patients to tolerate
techniques have not yielded a diagnosis. It has the greatest compared with CT. The machine can make patients feel
chance of seeding the tumor along the path of the biopsy. more claustrophobic and is noisier during the procedure. It
also has the disadvantage that patients with implanted ferro-
magnetic foreign material are not able to go into the magnetic
Imaging
field. MRI is not as accurate for calcium structures such as
Imaging studies are important in the workup of patients bone and teeth.
with head and neck complaints. This is true because direct
visualization of many structures is difficult because most Positron Emission Tomography/Computed Tomography
of the structures are examined through orifices. The most PET is a study that measures tissue metabolic activity by
common studies ordered are a barium swallow, CT, MRI, using a radioactive tracer. The tracer is fluorodeoxyglucose
ultrasonography, and dual-modality PET with CT. (FDG), an analogue of glucose. FDG is short acting with a
half-life of 110 minutes. The scan works because neoplastic
ultrasonography cells have a higher rate of glycolysis; therefore, the tracer is
Ultrasonography offers many advantages. It is inexpensive, localized in the tissue. Unfortunately, tracer localization is
offers real-time imaging, and is performed without radiation not specific for neoplastic disease and can occur with inflam-
exposure. Ultrasonography is particularly helpful in differen- matory processes as well. Muscle activity will also result in
tiating between solid and cystic masses. It allows evaluation increased uptake of the FDG. The scan is also limited by
of surrounding structures such as blood vessels. It is an excel- the inability to identify neoplasms that are smaller than 3 to
lent tool to follow masses to assess for changes in the size or 4 mm. In this situation, the amount of FDG concentrated is
character of the structure. It can also be used to help guide not large enough to stand out from the surrounding struc-
cytologic evaluation with FNA. tures. The dual-modality scan of PET/CT has, for the most
part, replaced the PET scan alone. Performing coregistered
Barium Swallow scans allows the metabolic activity from the PET scan to be
A barium swallow is used to examine the esophagus and, more accurately correlated with the anatomic detail of the
to a lesser extent, the stomach. Barium sulfate is swallowed CT. PET/CT is most useful in head and neck oncology to
and is used to identify tumors, ulcers, diverticula, and stric- look for unknown primary tumors, second primary tumors,
tures. It is done under fluoroscopy to be able to follow the and metastatic disease, both regional and distant. In the era
dynamic passage of the barium through the esophagus and of chemoradiotherapy, PET/CT has been used posttreatment
stomach. to assess for response to treatment. This is most accurately
done 2 to 3 months after treatment because the inflammation
Computed Tomography must resolve first.
CT of the neck with contrast is the most common test
performed to evaluate a mass in the head and neck. It allows Financial Disclosures: None Reported
Recommended Reading
Bailey B. Head and neck surgery—otolaryngology. Thawley SE, Panje WR, Batsakis JG, Lindberg,
3rd ed. Philadelphia: Lippincott Williams & RD. Comprehensive management of head
Wilkins; 2001. and neck tumors. 2nd ed. Philadelphia: W.B.
Saunders; 1999.
11/10
2 HEAD AND NECK 5 ORAL CAVITY PROCEDURES — 1
5 ORAL CAVITY PROCEDURES

Carol R. Bradford, MD, FACS, and Mark E.P. Prince, MD, FRCSC
Preoperative Evaluation using sensate tissue similar in form to the tissue that was
Oral cavity procedures are commonly performed to treat excised. With experience and careful judgment, the surgeon
malignancies. Tumors should be assessed preoperatively to can usually determine when a defect is too large for primary
allow accurate staging of the disease and to facilitate planning closure or when primary closure is likely to cause distortion
of definitive treatment. In most cases, an examination under and tethering of adjacent tissues and result in a significant
anesthesia with endoscopy and biopsy is required to stage functional disturbance. In such cases, a flap reconstruction
the primary tumor and to look for synchronous second pri- must be considered. In select cases, pedicled flaps may be
mary tumors. Except in the case of very superficial lesions, appropriate. Often, particularly with larger or more compli-
computed tomography (CT) plays an important role in pre- cated defects, free flaps provide the best reconstructive result.
operative planning. In selected cases, plain radiographs (e.g., Free tissue reconstruction has the advantage of allowing
Panorex views) may be useful in evaluating the mandible. the surgeon to reconstruct the defect with the exact tissue
When the lesion is located in the tongue, magnetic resonance components that were excised, including bone and skin. In
imaging (MRI) may provide additional information about the addition, free flaps can be reinnervated to achieve a sensate
extent of the primary tumor. reconstruction.
Wide surgical margins are necessary for adequate treat- If the planned surgical procedure involves resection of part
ment of primary squamous cell carcinoma of the head and of the maxilla or the mandible, appropriate dental consulta-
neck. A margin of 1 to 2 cm should be achieved whenever tion should be obtained. If a postoperative splint, obturator,
possible, ideally with frozen-section control. Current evidence or dental prosthesis is to be placed, it is critical that dental
clearly indicates that overall patient outcome improves when impressions be obtained before operation. Thyroid function
clear margins are obtained. should be tested in all patients who have a history of radiation
Nodal metastases are common with oral cavity tumors. therapy to the neck to confirm that they are euthyroid.
Accordingly, patients should be assessed for cervical adenop- In cooperative patients, small primary lesions of the oral
athy both clinically and radiographically. A chest x-ray should cavity can sometimes be excised with local anesthesia; how-
be obtained in all cases. CT or MRI can provide valuable ever, general anesthesia with adequate relaxation is required
information regarding the nodal status of the neck. In patients in the majority of cases. The route of intubation must be
with advanced disease, a more extensive search for distant carefully considered for each patient. When the planned
metastases should be conducted, including a CT scan of the resection is extensive and when significant postoperative
chest. In some circumstances, combining CT with positron edema is anticipated, a tracheostomy should be performed.
emission tomography (PET) may be useful. Patients with bulky lesions should undergo tracheostomy
under local anesthesia before general anesthesia is induced.
When a tracheostomy is not planned, nasotracheal intubation
Operative Planning is often desirable.
Surgical management of the neck is an evolving field. In When the excision is limited to the oral cavity, periopera-
general, if the risk of occult metastasis is greater than 20 to tive antibiotics are generally unnecessary. When a graft, a
25%, a selective neck dissection is recommended, particularly flap, or packing is employed, however, perioperative intrave-
if postoperative radiation therapy is not planned. Whenever nous administration of antibiotics is advisable. In all cases in
there is clinical evidence of nodal disease, treatment of the which the neck is entered, perioperative antibiotics are rec-
neck must be included in operative planning. ommended. The oral cavity can be prepared preoperatively
The oral cavity is a major component of a number of with chlorhexidine and a toothbrush.
important functions, including speech and swallowing. A nasogastric feeding tube should be inserted whenever it
Reconstruction of the anticipated surgical defect must be is believed that the patient may have a problem maintaining
carefully planned to achieve the best results. Several basic oral nutrition postoperatively. Patients who undergo primary
considerations must be kept in mind. Tongue mobility and closure or split-thickness skin grafting or whose surgical
sensation must be maintained to the extent possible. Mainte- wound is allowed to heal by secondary intention may be
nance of mandibular continuity (especially in the anterior allowed clear liquids in 24 to 48 hours and a pureed diet by
segment of the mandible) is vital for ensuring postoperative postoperative day 3; they can often tolerate a soft diet within
oral competence. Separation of the nasal cavity from the oral 1 week. Patients who undergo flap reconstruction will have
cavity is critical for the oral phase of swallowing and speech. to be fed via a nasogastric tube until they have healed to the
Maintenance of the gingivobuccal and gingivolabial sulcus is point where they can resume oral intake.
important for oral function and the fitting of dentures. Patients should be advised to maintain oral hygiene post-
As a rule, oral cavity defects should be closed primarily operatively by means of frequent irrigation and rinses with
whenever possible. Primary closure has the advantage of either normal saline or half-strength hydrogen peroxide.
DOI 10.2310/7800.S02C05
07/10
Teeth may be gently cleaned with a soft toothbrush until

healing has occurred.
Anterior Glossectomy
operative planning
Either orotracheal or nasotracheal intubation may be
appropriate, depending on the surgical approach and the
extent of the planned resection. A tracheostomy should be
performed whenever significant postoperative swelling or
airway compromise is anticipated.
The depth of the excision and the size of the anticipated
defect determine the optimal reconstructive approach. Defects
that connect to the neck, unless they are small and can easily be
closed primarily, usually necessitate creation of a flap for optimal
reconstruction. When the excision extends down to the underly-
ing musculature but there is no connection to the neck, a skin
graft may be used. If a postoperative dental splint is planned to
hold a skin graft in place, a dental consultation must be obtained
before operation.
The patient should be supine in a 20° reverse Trendelenburg
position. Turning the table 180° may facilitate access and Figure 1 Anterior glossectomy. A lip-splitting incision is
positioning for the surgeon. made that extends downward straight through the mentum.
operative technique
Step 1: Surgical Approach To create a visor flap, an incision is made from mastoid to
mastoid along a skin crease in the neck, with care taken to
Small anterior lesions up to 2 cm in diameter may be
remain below the marginal mandibular nerves. The skin
approached transorally, as may certain carefully selected
flap is elevated in the subplatysmal plane to the level of the
larger lesions. Exposure of the tongue is usually achieved with
mandible. The marginal mandibular nerves are preserved.
the help of an appropriately sized bite block; alternatively,
The flap is elevated from the lateral surface of the mandible,
a specialized retractor (e.g., a Molt retractor) may be used.
and the two mental nerves are divided. An incision is made
Retraction of the tongue is facilitated by the use of a piercing
in the oral cavity mucosa along the gingivolabial sulcus and
towel clip or a heavy silk suture placed through the tip of the
tongue.
Access to posterior lesions and most larger lesions is
obtained by performing a mandibulotomy through a lip-
splitting incision [see Figure 1]. A stair-step incision is made
in the lip and extended downward straight through the
mentum, and a Z-plasty is done at the mental crease.
Alternatively, the incision may be carried around the mental
subunit.
The mandibular periosteum is elevated and a plate
contoured to the mandible before the mandible is divided;
this measure ensures exact realignment of the cut ends of
the mandible. When possible, the mandibulotomy should be
made anterior to the mental foramen to preserve sensation
throughout the distribution of the mental nerve. Repair of the
mandibulotomy is greatly facilitated by making a stair-step
or chevron-type mandibulotomy [see Figure 2]. A paralingual
mucosal incision is made to allow retraction of the mandible
and exposure of the posterior oral cavity.
As an alternative, a visor flap may be created [see Figure 3].
Such a flap allows the surgeon to avoid making a lip-splitting
incision and provides adequate exposure of small lesions of
the anterior oral cavity; however, it is inadequate for exposure
of lesions posterior to the middle third of the tongue or in
the area of the retromolar trigone. Furthermore, creation of
a visor flap results in anesthesia of the lower lip because of Figure 2 Anterior glossectomy. A stair-step mandibulotomy
the necessity of dividing both mental nerves. is made.
07/10
Step 3: Reconstruction
After negative margins are confirmed by frozen-section
examination, repair of the surgical defect is initiated. Careful
preoperative assessment of the anticipated defect lays the
groundwork for optimal reconstruction. Many defects can be
either repaired primarily or allowed to heal by secondary
intention. Free tissue transfer is an excellent reconstructive
option in many cases, allowing the maintenance of tongue
mobility and the separation of the tongue from the mandible
and making sensate reconstruction possible.
In many patients with wedge-excised lateral tongue lesions,
primary closure of the defect yields good results. The deep
muscle is carefully reapproximated with long-lasting absorb-
able sutures. The mucosa is also closed with absorbable
sutures. Care should be taken not to strangulate tissues by
making the sutures too tight. When complete primary closure
is not possible or desirable, the tongue may be allowed to
granulate and heal by secondary intention. Split-thickness
skin grafts, although useful for relining the floor of the mouth,
generally do not take well on the tongue.
For large defects of the tongue and those involving the
floor of the mouth, flap reconstruction is appropriate. Defects
that connect to the neck, unless they are small and can be
closed primarily, should also be closed with a flap. Free tissue
transfer is frequently the optimal reconstructive approach.
Free fasciocutaneous flaps from the radial forearm, the ante-
rior lateral thigh, or the lateral arm are well suited to recon-
struction in this area. Pedicled flaps (e.g., myocutaneous flaps
from the pectoral muscle) are also used in this setting but are
bulkier and harder to contour to the defects.
If a mandibulotomy was made, it is repaired with the pre-
viously contoured plate. The lip-splitting incision is closed in
Figure 3 Anterior glossectomy. As an alternative to a three layers (mucosa, muscle, and skin). Great care must be
lip-splitting incision with mandibulotomy, a visor flap may be taken to ensure accurate realignment of the vermilion border
employed for exposure. and the orbicularis oris muscle.
Alternative Procedure: Laser Vaporization
continued so that it connects to the skin incision. The flap is Very superficial and premalignant lesions of the tongue
then retracted superiorly to expose the anterior mandible and may be vaporized by using a CO2 laser. The desired depth of
the oral cavity. tissue destruction for leukoplakia is approximately 1 to 2 mm.
Step 2: Resection troubleshooting

The excision should include a generous mucosal margin Larger excisions may lead to airway edema. Whenever this
around the visible lesion. A significant amount of the tongue possibility is a concern, a tracheostomy should be performed.
musculature surrounding the lesion should be resected as A single intraoperative dose of steroids may reduce postop-
well. Palpation of the lesion is critical for obtaining adequate erative tongue edema without adversely affecting wound heal-
deep surgical margins. ing. Using a stair-step incision for the lip-splitting incision
Resection may be performed with a monopolar electro- facilitates accurate reapproximation of the vermilion border.
cautery, with the cutting current used to incise the mucosa Excessive tongue movement may result in dehiscence of
and the coagulation current used to cut the muscle. Alterna- the closure. Voice rest for 3 to 5 days after operation may be
tively, resection may be performed with a scalpel and scissors. beneficial.
Hemostasis is achieved with a monopolar or bipolar electro-
cautery. Larger vessels are ligated with chromic catgut or postoperative care
Vicryl ties. Patients who undergo primary closure of the tongue may
Lesions of the lateral tongue should be wedge-excised in a begin a fluid diet on the day after operation; they should
transverse (rather than horizontal) fashion to facilitate closure remain on a liquid diet for 7 to 10 days. Patients who undergo
and enhance postoperative function. With larger lesions, for skin grafting may also begin a liquid diet on postoperative day
which either flap reconstruction or healing by secondary 1. If a flap was used to close the defect or if there is some
intention is typically indicated, the shape of the defect is question whether the patient will be capable of adequate oral
contoured so as to obtain wide margins around the lesion, intake, a nasogastric feeding tube should be inserted and
and the flap is designed to fill the contoured defect. maintained until the suture lines heal.
07/10
Bolster dressings may be removed and skin grafts inspected Step 3: Reconstruction
after 7 to 10 days. Patients with skin grafts should stay on a After clean surgical margins have been verified by frozen-
soft diet for 2 weeks. If a tracheotomy was performed, the section examination, repair of the surgical defect is initiated.
patient may be decannulated when postoperative edema has Small superficial defects of the floor of the mouth may be
settled. allowed to heal by secondary intention.
Meticulous and frequent oral hygiene is essential. Mouth For small defects that do not connect to the neck, recon-
rinses and irrigation with normal saline or half-strength struction with a 0.014 to 0.016 inch–thick split-thickness
hydrogen peroxide should be done at least four times a day skin graft is appropriate. The graft is cut to size and sutured
and after every meal. Teeth may be gently cleaned with a soft in place with 4-0 chromic sutures. Several perforations
toothbrush. should be made in the graft to allow the egress of blood
complications and serum. A Xeroform gauze bolster is fashioned to fit
over the skin graft and sutured in place with 2-0 silk tie-over
The main complications of anterior glossectomy are as
bolster stitches; alternatively, it may be held in place by a
follows:
prefabricated dental prosthesis.
1. Injury to the lingual nerve, which causes numbness and For larger defects, particularly those involving the tongue,
loss of the sense of taste in the ipsilateral tongue a flap reconstruction typically yields the best functional
2. Injury to the submandibular and sublingual gland ducts, results. In select cases, a platysma flap may be used for
which causes obstruction of the glands, pain and swelling, reconstruction of defects in the floor of the mouth. Other
and possibly ranula formation regional flaps tend to be bulky and difficult to shape to the
3. Injury to the hypoglossal nerve, portions of which are contours of the defect. Free tissue transfer frequently pro-
resected with the lesion. Injury to the main trunk of this vides the most suitable reconstructive tissue characteristics
nerve leads to paralysis and atrophy of the remaining and the most favorable postoperative results. A free fasciocu-
ipsilateral tongue. taneous radial forearm flap is usually the optimal choice
4. Tethering and scarring of the tongue, which can lead to for reconstruction of floor-of-mouth defects when a flap is
difficulties with speech and swallowing. This problem can required.
usually be avoided by careful preoperative planning of
reconstruction. troubleshooting
Special care should be taken to identify the lingual nerve
and artery so that these structures are not inadvertently
Excision of Floor-of-Mouth Lesions
divided. Meticulous hemostasis should be obtained in all
operative planning cases. Any skin grafts used should be adequately sized and
Planning for excision of a lesion from the floor of the mouth should not “tent up.” Generally, skin grafting and bolsters
is essentially the same as that for anterior glossectomy [see do not work well on mobile structures. Quilting grafts to
Anterior Glossectomy, Operative Planning, above]. If either the underlying tissues with multiple absorbable sutures can
or both of Wharton ducts are to be transected without eliminate the need for a bolster and result in acceptable graft
excision of the submandibular glands, consideration must be take.
given to the management of these glands. postoperative care
operative technique Postoperative care of patients undergoing excision of floor-
of-mouth lesions is virtually identical to that of patients
Step 1: Surgical Approach
undergoing anterior glossectomy [see Anterior Glossectomy,
The surgical approach is the same as that described for Postoperative Care, above].
glossectomy [see Anterior Glossectomy, Operative Technique,
Step 1, above]. complications
Excision of floor-of-mouth lesions is associated with the
Step 2: Resection
same complications as anterior glossectomy [see Anterior
The area to be excised, including adequate margins, is Glossectomy, Complications, above].
marked. The lesion is then excised with a monopolar electro-
cautery; as in a glossectomy, the cutting current is used to cut
the mucosa and the coagulation current to cut the deeper Excision of Superficial or Plunging Ranulas
tissues. Palpation is important for obtaining adequate deep
operative planning
surgical margins.
If the excision cuts across the Wharton duct, the duct Planning for excision of a superficial or plunging ranula
should be identified and transected obliquely to create a resembles that for glossectomy. A Ring-Adair-Elwyn (RAE)
wider opening. The transected stump is held with a 4-0 chro- tube is inserted orally and taped to the contralateral cheek.
mic catgut suture. Once the resection is complete, the duct is Cervical exploration is usually unnecessary because the cer-
transposed posteriorly to the cut edge of the mucosa of the vical component of the ranula resolves after removal of
floor of the mouth and sutured in place with two or three the ipsilateral sublingual gland. In select cases, especially
4-0 chromic sutures. During subsequent reconstruction, care those involving disease recurrence after a previous attempt at
should be taken not to obstruct the orifice of the duct. excision, a transcervical approach should be considered.
07/10
operative technique Meticulous hemostasis should be obtained in all cases. If the

submandibular gland duct is injured, it should be transected
Step 1: Surgical Approach and the cut end sutured to the adjacent floor-of-mouth
Ranulas are resected via the transoral approach. A bite mucosa (sialodochoplasty).
block or a Molt retractor is used to gain exposure.
complications
Step 2: Resection
The three main complications of the procedure for excising
A local anesthetic preparation with epinephrine is infil- a ranula are among those that are also associated with
trated into the area of the mucosal incisions. A small super- anterior glossectomy and excision of floor-of-mouth lesions:
ficial ranula may be marsupialized and packed with gauze. injury to the lingual nerve, injury to the submandibular
The ranula is widely unroofed and the contents removed with gland duct, and injury to the hypoglossal nerve [see Anterior
suction. The margins of the cyst are sutured to the mucosa Glossectomy, Complications, above].
with 4-0 chromic sutures, and the cavity is packed with
iodoform strip gauze. The gauze may be removed in 5 to
7 days. Removal of Submandibular Gland Duct Stones
A plunging ranula is treated with complete surgical exci-
operative planning
sion of the cyst and the sublingual gland [see Figure 4]. A
mucosal incision is made directly over the cyst. Careful dis- When a submandibular gland duct stone is readily palpable
section is carried out around the cyst and the associated in the floor of the mouth, a transoral approach is appropriate.
gland. Hemostasis is achieved with a bipolar electrocautery, When the stone is within the hilum of the gland, however,
with care taken not to injure the adjacent lingual nerve. The it generally cannot be removed transorally and often must be
submandibular gland duct is cannulated with a lacrimal probe treated by excising the submandibular gland.
to help guard against inadvertent injury to this structure.
operative technique
The incision is closed with 4-0 chromic suture.
troubleshooting
The procedure is easily accomplished with local anesthesia
Efforts should be made to identify the lingual nerve and
in a cooperative patient. The patient is seated upright in the
artery to prevent inadvertent division of these structures.
examining chair, and a topical anesthetic is applied to the oral
cavity.
Step 2: Resection
A local anesthetic preparation with epinephrine is infil-
trated into the floor of the mouth and around the duct in
which the stone is palpated. A 2-0 silk suture may be placed
around the duct behind the stone to prevent it from migrating
back into the hilum of the gland.
A lacrimal probe is inserted into the duct and advanced to
the stone in a retrograde manner. A mucosal incision is then
made directly over the stone and extended downward to the
duct, with the stone and the lacrimal probe serving as guides.
The duct is incised and the stone delivered. As a rule, repair
of the duct is not required.
troubleshooting
Careful dissection directly onto the duct and stone usually
serves to prevent inadvertent injury to the lingual nerve.
complications
The main complications of the procedure are as follows:
1. Injury to the lingual nerve, resulting in numbness and loss
of the sense of taste to the ipsilateral tongue
2. Stricture of the submandibular gland duct. This is an
unusual complication that can be corrected by transecting
the duct posterior to the stricture and suturing it to the
mucosa of the floor of the mouth.
Resection of Hard Palate

Figure 4 Excision of plunging ranula. A mucosal incision is operative planning
made over the cyst, dissection is done around the cyst and the
associated sublingual gland, and the cyst and gland are Careful evaluation is required to determine whether resec-
completely excised. tion of part of the hard palate will suffice or whether a more
07/10
extensive dissection (e.g., maxillectomy) will be required. Step 3: Reconstruction

If it is anticipated that a dental prosthesis will be required, a After surgical margins have been verified by frozen-section
dental consultation should be obtained before operation. review, repair of the surgical defect is initiated. Small mucosal
When the lesion to be resected is superficial or only a limited defects may be allowed to heal by secondary intention. Small
amount of the bony hard palate must be resected, the through-and-through resections may be closed by placing
procedure may be performed via the transoral approach. relaxing incisions laterally and advancing the mucosa to
operative technique permit primary closure. Larger defects may be closed with
palatal mucosal flaps. Many through-and-through defects can
Step 1: Surgical Approach be closed quite satisfactorily with a dental obturator.
The patient is supine, with the bed turned 180° to facilitate
postoperative care
the surgeons’ access to the operative site. An oral RAE tube
is inserted and taped in the midline. The lesion is approached The patient should be maintained on a soft diet postopera-
transorally, and a Dingman or Crowe-Davis retractor is used tively. Meticulous oral hygiene is important. Oral rinses and
to obtain exposure. flushes with normal saline or half-strength hydrogen peroxide
should be performed at least four times daily and after
Step 2: Resection meals.
An incision is made around the periphery of the lesion
in such a way to maintain adequate margins; a monopolar complications
electrocautery with a needle tip is ideal for this purpose. The The most significant potential complication of hard
periosteum is elevated away from the underlying bone, and palate resection is oral antral or oronasal fistula; careful tissue
the lesion is removed [see Figure 5]. reconstruction and the use of an obturator can prevent this
When bone must be resected, the periosteum is elevated complication.
away from the incision site. A high-speed oscillating saw or
an osteotome is used to make the cuts in the bone, after
Maxillectomy
which the specimen is rocked free and removed.
operative planning
General anesthesia with muscle relaxation is essential for
all types of maxillectomy. Either orotracheal or nasotracheal
intubation may be appropriate, depending on the surgical
approach. Skin incisions should be marked before the endo-
tracheal tube is taped in place to avoid distortion of facial
structures and skin lines. The patient should be supine in
a 20° reverse Trendelenburg position. The eyes should be
protected carefully (e.g., with a corneal shield or a temporary
nylon tarsorrhaphy suture).
Radiographic evaluation plays a vital role in planning the
surgical approach and determining the extent of resection
required [see Figure 6]. Lesions of the infrastructure of the
maxilla can be excised by means of partial maxillectomy via
the transoral route. More extensive lesions usually must be
accessed via facial incisions in conjunction with the transoral
approach.
In all cases, a dental consultation should be obtained
preoperatively so that a dental impression can be taken and
an obturator fashioned for intraoperative use. Antibiotics
should be given perioperatively and continued until nasal
packing is removed.
operative technique

In addition to the transoral approach, maxillectomy usually
requires exposure of the anterior face of the maxilla. There
are several options for achieving such exposure, including a
Weber-Ferguson incision and midface degloving. Midface
degloving has the advantage of eliminating the need for visi-
ble facial incisions but yields limited exposure in the ethmoid
Figure 5 Resection of hard palate. An incision is made around region. The choice of surgical approach is determined by the
the lesion, with adequate margins maintained, the periosteum extent of the planned resection and by the preferences of the
is lifted off the bone, and the lesion is removed. patient and the surgeon.
07/10
b c
Figure 6 Maxillectomy. Radiographic assessment helps determine the required extent of resection. Depicted are (a) medial
maxillectomy, (b) subtotal maxillectomy without orbital exenteration, and (c) total maxillectomy with orbital exenteration.
In the Weber-Ferguson approach, the first step is to mark are elevated from the anterior wall of the maxillary sinus;
the path of the incision, which begins in the midline of the if access to the pterygomaxillary fissure is desired, elevation
upper lip; extends through the philtrum; curves around should be continued up to the zygoma.
the nasal vestibule and the ala; continues upward along the In a midface degloving, the skin of the lower face and nose
lateral nasal wall, just medial to the junction of the nasal is mobilized and retracted superiorly. A standard transfixion
sidewall and the cheek; and ends near the medial canthus. incision is made, transecting the membranous septum.
For added exposure in the ethmoid region, a Lynch exten- Intercartilaginous incisions are then made bilaterally and
sion, in which the incision is continued superiorly up to the connected to the transfixion incision. The incision is then
medial eyebrow, may be performed. Alternatively, the Weber-
continued laterally along the cephalic border of the lower
Ferguson incision may be continued laterally in the subciliary
lateral cartilage and across the floor of the nose. To prevent
crease along the inferior eyelid to the lateral canthus of the
eye; this extension yields added exposure of the posterolateral stenosis, a small Z-plasty or triangle is incised medially just
aspect of the maxilla. before the transfixion incision is joined. The soft tissues are
The skin incisions should initially be made with a scalpel elevated over the nasal dorsum and the nasal tip with Joseph
and then continued with an electrocautery. The upper lip is scissors. An incision is made in the gingivolabial sulcus with
divided through its full thickness, and the incision is con- the monopolar cautery, and this incision is connected to the
tinued in the gingivolabial sulcus laterally until the postero- floor-of-nose incisions by means of gentle dissection. The soft
lateral aspect of the sinus is exposed. When possible, the tissues are then elevated from the anterior maxilla as far as
infraorbital nerve is identified and preserved. The soft tissues the infraorbital rims and laterally as far as the zygoma.
07/10
Step 2: Resection A split-thickness skin graft, 0.014 to 0.016 inches thick, is

A Molt retractor is placed on the side opposite the side of harvested and used to line the raw undersurface of the cheek
the planned excision and opened as wide as possible to expose flap. The skin graft is sutured to the mucosal edge of the
the hard palate and the alveolus. cheek flap with 3-0 chromic sutures. Superiorly, the graft is
The infraorbital rim should be preserved if it is possible to not sutured but draped into position and retained by a layer
do so safely. Often a thin strip of the rim can be preserved of Xeroform packing and strip gauze coated with antibiotic
even when the rest of the bone must be resected. If the orbital ointment. Gentle pressure is applied to the packing so that it
floor must be resected but the orbital contents can be conforms to the defect. The previously fabricated dental
preserved, the periorbita can be dissected away from the bone obturator is placed to support the packing and to close the
of the orbital floor and preserved. If the orbital contents oral cavity from the nasal cavity. In a dentulous patient, the
are involved, an orbital exenteration must be performed in obturator may be wired to the remaining teeth; in an edentu-
conjunction with the maxillectomy. lous patient, it may be temporarily fixed in place with two
The cut along the infraorbital rim and superior anterior screws placed in the remaining hard palate.
maxillary wall is made with a high-speed oscillating saw with The skin incisions are closed in two layers, with interrupted
a fine blade. The level at which this superior cut is made is absorbable sutures used for the deep layers and nonabsorb-
determined by the extent of the resection. Lesions that are able monofilament sutures for the skin. If a lip-splitting
confined to the alveolus or the palate and do not invade the incision was made, care must be taken to ensure exact
maxilla typically can be removed by excising the infrastruc- reapproximation of the orbicularis oris and the vermilion
ture of the maxilla. The line of transection is continued border.
through the nasal process of the maxilla medially and down- If the infraorbital rim was resected, it should be recon-
ward through the piriform aperture. Laterally, the cut extends structed to yield good aesthetic results. A split calvarial bone
to the zygomatic process of the maxilla and around the graft may be used for this purpose when there is adequate soft
posterolateral aspect of the sinus. tissue coverage for the bone grafts available. When soft tissue
If the pterygoid plates are to be preserved, they are cut free coverage is inadequate or the orbital floor must be recon-
by placing a curved osteotome along the posterior wall of structed, an osteocutaneous radial forearm or scapular flap
the sinus and sharply dividing the plates from the sinus wall. may be employed, with excellent results.
If the pterygoid plates, part of the pterygoid musculature,
Alternative Procedure: Peroral Partial Maxillectomy
or both are to be resected, the soft tissue attachments are cut
sharply with curved Mayo scissors once the entire maxillary The oral cavity is exposed with cheek retractors. An
specimen has been mobilized. incision is made in the gingivobuccal sulcus and the mucosa
The line of transection in the maxillary alveolus can run of the hard palate, with care taken to maintain adequate
between two teeth if a suitable gap is evident. In the majority margins; a monopolar electrocautery, set to use the cutting
of cases, however, it is advisable to extract a tooth and make current, is suitable for this purpose. Incisions are made cir-
the cut through the extraction site. A power saw is used, and cumferentially through all the soft tissues up to the anterior
the cut is connected to the transection line through the nasal wall of the maxilla and the hard palate. The infraorbital
process of the maxilla and the piriform aperture. The hard nerve should be preserved if it is not involved with the disease
palate mucosa is then incised lateral to the proposed cut in process.
the hard palate bone to preserve a flap of mucosa that can be The cut in the hard palate mucosa should be made lateral
used to cover the raw cut bony edge of the palate. This inci- to the planned cuts in the hard palate bone to create a muco-
sion is made with a needle-tip electrocautery and carried sal flap, which will be used to cover the cut bony edge of
down to the bone of the hard palate. It should extend from the hard palate. If necessary, teeth may be extracted to allow
the maxillary tuberosity posteriorly to the cut bone in the the surgeon to make bone cuts through tooth sockets while
maxillary alveolus anteriorly, with care taken to obtain ade- preserving adjacent teeth. The bone is cut with a high-speed
quate mucosal margins. The mucosa is elevated for a short power saw, and an osteotome is used to divide any remaining
distance over the hard palate bone to create a short mucosal bony attachments and deliver the specimen. If the mucosa
flap that is wrapped over the cut bony edge of the palate. The remaining in the maxillary antrum is not diseased, it need not
mucosal cut is connected around the maxillary tuberosity to be removed.
the gingivolabial sulcus incision that was made earlier. A split-thickness skin graft, 0.014 to 0.016 inches thick, is
The hard palate is then cut with a power saw. Once all the harvested from the anterolateral thigh and used to reline the
bone cuts are complete, an osteotome may be used to con- raw buccal mucosa area. The graft is sutured to the cut edge
nect them if necessary. The remaining soft tissue attachments of the buccal mucosa with 4-0 chromic catgut. Xeroform and
are divided along the posterior hard palate with curved Mayo strip gauze coated with antibiotic ointment are gently packed
scissors. The surgical defect is packed to control bleeding. into the defect to secure the skin graft. The previously fabri-
Bleeding from the internal maxillary artery is controlled by cated dental obturator is wired to the remaining teeth to hold
ligatures or ligating clips. the packing in place.
Step 3: Reconstruction troubleshooting

All sharp spicules of bone are débrided. The flap of hard If a lip-splitting incision is planned, lip contraction can
palate mucosa is brought up over the cut bony edge of be reduced and vermilion border realignment improved by
the palate and held in place with several Vicryl sutures. The employing a stair-step lip incision and a Z-plasty. A single
anterior and posterior cut edges of the soft palate are intraoperative steroid dose reduces facial edema without
reapproximated with absorbable sutures. compromising wound healing. Retention of the obturator is
07/10
aided by the band of scar tissue that forms at the junction The patient should be supine in a 20° reverse Trende-
of the mucosa and the skin graft. Covering the cut edge of lenburg position. Perioperative antibiotics should be
the hard palate bone with mucosa eliminates pain caused by administered.
pressure from the obturator on thinly covered bone.
If more than a small area of the floor of the orbit is resected, operative technique
it should be repaired to prevent enophthalmos. Epiphoria is Step 1: Exposure
uncommon; when it occurs, it is related to scarring of the
nasolacrimal duct. Identifying the duct and transecting it Wide exposure for access to primary tumors of the oral
obliquely should reduce the incidence of this complication. cavity and the mandible may be achieved by means of either
a lower-cheek flap or a visor flap. The former is often prefer-
postoperative care able in that it allows resection of the primary and ipsilateral
A nasogastric tube is placed at the end of the procedure. lymph nodes.
Many patients are able to begin a liquid diet and advance to To create a lower-cheek flap, a lip-splitting incision is made
a soft diet within a few days after operation. A soft diet should through the full thickness of the lower lip and carried down
be continued for at least 2 weeks. Oral rinses and flushes with through the chin tissues to the periosteum of the anterior
normal saline or half-strength hydrogen peroxide should be mandible [see Figure 7]. This incision may be made straight
performed at least four times daily and after meals. through the mental subunit with a Z-plasty placed at the
The obturator and the packing may be removed from the mental crease; alternatively, it may be made around the
cavity in 7 to 10 days. The obturator should be replaced to mental subunit. The incision is continued vertically to
maintain oral competence. The prosthodontist makes a final approximately the level of the thyrohyoid membrane and then
obturator once healing is complete and the cavity has stabi- extended laterally to the mastoid along a skin crease. The
lized. Facial incisions are cleaned twice daily and coated with transverse component of the incision should be made at least
antibiotic ointment. Facial sutures are removed 5 to 7 days two fingerbreadths below the mandible to prevent injury to
after operation. the marginal mandibular nerve. The cheek flap is fully devel-
oped by incising the oral mucosa along the gingivolabial
complications sulcus while maintaining adequate surgical margins around
The main complications of maxillectomy are as follows: the lesion. The periosteum of the mandible is then elevated
and the cheek flap retracted to expose the mandible.
1. Enophthalmos and hypophthalmos, which create a cos-
A visor flap [see Figure 3] has the advantage of not requiring
metic deformity
a lip-splitting incision and provides adequate exposure for
2. Infraorbital nerve injury, which results in anesthesia or
lesions of the anterior oral cavity. However, it is inadequate
paresthesia of the ipsilateral cheek and upper lip. On occa-
for exposing lesions posterior to the middle third of the
sion, the infraorbital nerve may have to be sacrificed as
part of the planned resection. tongue or in the area of the retromolar trigone and may lead
3. Epiphoria, caused by scarring of the nasolacrimal duct to anesthesia of the lower lip as a consequence of the need
4. Difficult retention of the dental prosthesis, which can usually to divide both mental nerves. The technical aspects of
be prevented by careful preoperative evaluation and appro-
priate choice of reconstructive method. In select cases,
free tissue reconstruction without a dental prosthesis may be
optimal.
Mandibulectomy
operative planning
General anesthesia with muscle relaxation is essential for
all types of mandibulectomy. Either orotracheal or nasotra-
cheal intubation is appropriate, depending on the surgical
approach and the extent of the planned resection. A trache-
ostomy should be performed whenever significant post-
operative swelling or airway compromise is anticipated. Skin
incisions should be marked before the endotracheal tube is
taped in place.
Preoperative radiographic evaluation is essential for plan-
ning the surgical approach and determining the extent of the
proposed resection. For lesions without radiographic or clin-
ical evidence of bone invasion, a marginal mandibulectomy is
often appropriate. This procedure may also be performed to
obtain adequate surgical margins for lesions that are in close
proximity to the mandible. When the lesion is small, it is
occasionally possible to perform marginal mandibulectomy Figure 7 Mandibulectomy. A cheek flap is created by making
via the transoral route. For more extensive lesions and a lip-splitting incision and extending it down to the level of
those that show evidence of bone invasion, a segmental the thyrohyoid membrane and then laterally to the mastoid
mandibulectomy is required. along a skin crease.
07/10
visor flap creation are summarized elsewhere [see Anterior bone is cut with a high-speed saw in such a way that the cuts
Glossectomy, Operative Technique, Step 1, above]. are rounded off and lack sharp angles, which are prone to
fracturing. Once the bone cuts are made, an osteotome may
Step 2: Resection be used to free the specimen.
If a plate is to be used in the reconstruction of the man-
dible, a template and a reconstruction plate are shaped and Step 3: Reconstruction
conformed to the mandible before resection. The segment of When a marginal mandibulectomy has been performed, a
mandible to be resected is marked. The plate is applied to the plate is sometimes needed to support the mandible. This is espe-
buccal cortex of the mandible, and screw holes are predrilled cially likely to be the case for a patient with a thin edentulous
in the mandible for gauging of depth. The plate is then set mandible, in which the remaining bone cannot withstand the
aside until needed for reconstruction. forces of mastication.
Mucosal incisions are made around the lesion with the When the anterior mandible has been resected, it must be
electrocautery, with care taken to maintain adequate surgical reconstructed with vascularized bone. Any of several free flaps
margins. The mandibular segment to be removed is cut with may be employed, depending on the tissue requirements for
a high-speed sagittal saw. The lingual nerve and the hypo- the planned reconstruction. Free tissue flaps from the fibula, the
glossal nerve are preserved if possible. Muscle attachments scapula, or the iliac crest can provide bone that is suitable for
mandibular reconstruction, as well as soft tissue that is suitable
to the resected mandibular segment are sharply divided,
for reconstruction of accompanying mucosal and cutaneous
allowing the surgical specimen to be delivered [see Figure 8].
defects.
In some cases, only a marginal mandibulectomy of the
After lateral mandibular resections, good results can be
lingual or alveolar cortex of the mandible is necessary. The
achieved by using mandibular reconstruction plates with suit-
able soft tissue reconstruction. There is a significant risk of plate
failure, however, especially in dentulous patients. In many cases,
replacing the resected portion of the mandible with vascularized
bone—especially if the defect is longer than a few centimeters—
yields better long-term results than using a reconstruction plate
alone.
postoperative care
A nasogastric tube is placed at the end of the surgical
procedure; most patients will need to be fed through this tube
until their incisions are healed. A soft diet should be contin-
ued for 6 weeks. Oral rinses and flushes with normal saline
or half-strength hydrogen peroxide should be performed at
least four times a day and after meals.
Facial incisions are cleaned twice a day and coated with
antibiotic ointment. Facial sutures are removed 5 to 7 days
after operation.
troubleshooting
Contouring the reconstruction plate to the mandible before
resecting the mandibular segment will prevent malocclusion
and enhance cosmetic results. Preserving the lingual nerve
and the hypoglossal nerve, when possible, will improve
postoperative swallowing and speech. The marginal mandib-
ular nerve should be identified and protected as well. If a
lip-splitting incision is used, performing a stair-step lip inci-
sion and a Z-plasty reduces lip contraction and improves
vermilion border realignment.
complications
The main complications of mandibulectomy are as
follows:
1. Malocclusion, caused by inaccurate repair of the resected
mandibular segment
2. Plate failure or fracture, which can be reduced by recon-
structing bony defects larger than 1 to 2 cm with revascu-
Figure 8 Mandibulectomy. The segment to be removed is cut larized bone
with a high-speed saw, with care taken to preserve the lingual 3. Oral incompetence, caused by inadequate reconstruction
and hypoglossal nerves if possible, and the muscle attach- of anterior mandibular defects.
ments to the segment are sharply divided to free the surgical
specimen. Financial Disclosures: None Reported
07/10
Additional Readings
Baurmash H. Submandibular salivary stones: improved cosmetic outcome. J Laryngol Otol segmental resection. J Surg Oncol 2006;94:
current management modalities. J Oral 2002;116:703. 538.
Maxillofac Surg 2004;62:369. Johnson JT, Leipzig B, Cummings CW. Manage- Schramm VL, Myers EN, Sigler BA. Surgical
Brown JD. The midface degloving procedure ment of T1 carcinoma of the anterior aspect management of early epidermoid carcinoma
for nasal, sinus and nasopharyngeal tumors. of the tongue. Arch Otolaryngol 1980; of the anterior floor of the mouth. Laryngo-
Otolaryngol Clin North Am 2001;34:1095. 106:249. scope 1980;90:207.
Brown JS, Kalavrezos N, D’Sousa J, et al. Factors Katz P, Fritsch MH. Salivary stones: innovative Spiro RH, Gerold FP, Strong EW. Mandibular
that influence the method of mandibular techniques in diagnosis and treatment. Curr “swing” approach for oral and oropharyngeal
resection in the management of oral squa- Opin Otol Head Neck Surg 2003;11:173. tumors. Head Neck 1981;3:371.
Lanier DM. Carcinoma of the hard palate. In: Stern SJ, Geopfert H, Clayman G, et al. Squa-
mous cell carcinoma. Br J Oral Maxillofac
Bailey BJ, editor. Surgery of the oral cavity. mous cell carcinoma of the maxillary sinus.
Surg 2002;40:275.
Chicago: Year Book Medical Publishers; Arch Otolaryngol Head Neck Surg 1993;
Campana JP, Meyers AD. The surgical manage- 1989. p. 163. 119:964.
ment of oral cancer. Otolaryngol Clin North Leipzig B, Cummings CW, Chung CT, et al. Wald RM, Calcaterra TC. Lower alveolar carci-
Am 2006;39:331. Carcinoma of the anterior tongue. Ann Otol noma: segmental v. marginal resection. Arch
Galloway RH, Gross PD, Thompson SH, et al. Rhinol Laryngol 1982;91:94. Otolaryngol 1983;109:578.
Pathogenesis and treatment of ranula: report Osguthorpe JD, Weisman RA. “Medial max-
of three cases. J Oral Maxillofac Surg 1989; illectomy” for lateral nasal neoplasms. Arch
47:299. Otolaryngol Head Neck Surg 1991;117:751. Acknowledgment
Hussain A, Hilmi OJ, Murray DP. Lateral Schrag C, Chang YM, Tsai CY, Wei FC. Com-
rhinotomy through nasal aesthetic subunits: plete rehabilitation of the mandible following Figures 1 through 8 Alice Y. Chen
07/10
2 HEAD AND NECK 6 PAROTIDECTOMY — 1
6 PAROTIDECTOMY
Leonard R. Henry, MD, and John A. Ridge, MD, PhD, FACS
Anatomic Considerations the surgical anatomy are essential in parotid surgery. The
The parotid (“near the ear”) gland, the largest of the salivary use of magnifying loupes and headlights is recommended.
glands, occupies the space immediately anterior to the ear, General anesthesia without muscle relaxation should be
overlying the angle of the mandible. It drains into the oral employed.
cavity via Stensen’s duct, which enters the oral vestibule The patient is placed in the supine position, with the head
opposite the upper molars. The gland is invested by a strong elevated and turned away from the side undergoing operation
fascia and is bounded superiorly by the zygomatic arch, ante- and with the neck slightly extended. The table is positioned
riorly by the masseter muscle, posteriorly by the external to allow the first assistant to stand directly above the patient’s
auditory canal and the mastoid process, and inferiorly by the head, while the surgeon faces the operative field. A small
sternocleidomastoid muscle. The masseter muscle, the styloid cottonoid sponge is placed in the external auditory canal,
muscles, the posterior belly of the digastric muscle, and a where it remains for the duration of the procedure to prevent
portion of the sternocleidomastoid muscle lie deep to the otitis externa from blood clots in the external auditory
parotid. Terminal branches of the external carotid artery, the canal. The skin is painted with an antiseptic agent. A single
facial vein, and the facial nerve are found within the gland. perioperative dose of an antibiotic is administered.
Parasympathetic innervation to the parotid is via the otic The patient is draped in a fashion that permits the operat-
ganglion, which gives fibers to the auriculotemporal branch of ing team to see all of the muscle groups innervated by
the trigeminal nerve. Sympathetic innervation to the gland the facial nerve. To this end, we employ a head drape that
originates in the sympathetic ganglia and reaches the auricu- incorporates the endotracheal tube and hose. This drape
lotemporal nerve by way of the plexus around the middle secures the airway, keeps the tube from interfering with the
meningeal artery.1 surgeon, and permits rotation of the head without tension
The facial nerve trunk exits the stylomastoid foramen and on the endotracheal tube. The skin of the upper chest and
courses toward the parotid. Once inside the gland, it com- neck is widely painted and draped with a split sheet to allow
monly bifurcates into superior (temporal-frontal) and inferior additional exposure in the unlikely event that a neck dissec-
(cervicomarginal) divisions before giving rise to its terminal tion or a tracheostomy becomes necessary. The nose, the lips,
branches. The nerve branching within the parotid can be and the eyes are covered with a sterile transparent drape that
quite complex, but the common patterns are well known and allows observation of movement during the procedure and
their relative frequencies well established.2,3 The portion of permits access to the oral cavity (if desired) [see Figure 1].
the parotid gland lateral to the facial nerve (about 80% of the
gland) is designated as the superficial lobe; the portion medial
to the facial nerve (the remaining 20%) is designated as the Operative Technique
deep lobe. Deep-lobe tumors often present clinically as retro- step 1: incision and skin flaps
mandibular or parapharyngeal masses, with displacement of
the tonsil or the soft palate appreciated in the throat. The incision is planned so as to permit excellent exposure
with good cosmetic results. It begins immediately anterior to
the ear, continues downward past the tragus, curves back
Operative Planning under the ear (staying close to the earlobe), and finally turns
Obtaining informed consent for parotidectomy entails downward to descend along the sternocleidomastoid muscle
discussing both the features and the potential complications [see Figure 1]. Either all or part of this incision may be used,
of the procedure. It is appropriate to address the possibility depending on circumstances. The incision is marked before
of facial nerve injury, but in doing so, the surgeon should not draping. Skin creases typically help conceal the resulting
neglect other, far more common sequelae, such as cosmetic scar.
deformity, earlobe numbness, and Frey syndrome. Even con- Skin flaps are then created to expose the parotid gland. A
ditions that are expected beforehand may prove distressing tacking suture is placed within the dermis of the earlobe so
or debilitating for the patient. The risk of complications that it can be retracted posteriorly. Skin hooks are used to
such as nerve injury is greater in cases involving reoperation apply vertical traction. The anterior flap is created superficial
or resection of malignant or deep-lobe tumors. The over- to the parotid fascia to afford access to the appropriate dis-
whelming majority of parotid tumors, however, are benign section plane. Vertically oriented blunt dissection minimizes
and lateral to the facial nerve. Accordingly, in what follows, the risk of injury to the distal branches of the facial nerve [see
we focus primarily on superficial parotidectomy, referring to Figure 2]. The face is observed for muscle motion. The flap
variants of the procedure where relevant. is raised until the anterior border of the gland is identified.
Excellent lighting, correctly applied traction and The facial nerve branches are rarely encountered during flap
countertraction, adequate exposure, and clear definition of elevation until they emerge from the parenchyma of the
DOI 10.2310/7800.S02C06
07/08
Figure 1 Parotidectomy. (a) Shown are the recommended head position and incision. A transparent drape is placed over the
eyes, the lip and oral cavity. (b) The head drape incorporates the hose from the endotracheal tube.
parotid. If muscle movement occurs, the flap has been more branches of this nerve should be preserved if possible to pre-
than adequately developed. The anterior flap is retracted with vent postoperative numbness of the earlobe.4,5 The parotid
a suture through the dermis. tail is dissected away from the sternocleidomastoid muscle.
The posterior-inferior skin flap is then elevated in a similar Vertical traction is applied to the gland surface with clamps
manner. Careful dissection is performed to define the rela- to facilitate exposure.
tionship of the parotid tail to the anterior border of the ster-
nocleidomastoid. During this portion of the procedure, the Troubleshooting
great auricular nerve is identified coursing cephalad and A favorable skin crease, if available, may be used for
superficial to the sternocleidomastoid muscle. Uninvolved the incision to improve the postoperative cosmetic result;
a b
Figure 2 Parotidectomy. (a) Shown is the creation of the anterior skin flap superficial to the parotid gland. (b) Vertically
oriented blunt dissection minimizes the risk of injury to facial nerve branches as they exit the gland.
07/08
however, it is important to keep the incision a few millimeters deep-lobe tumors may displace the nerve from its normal
from the earlobe itself. A wound at the junction of the earlobe location. For appropriate and safe exposure of the nerve
with the facial skin will distort the earlobe and create a visible trunk, it is necessary to mobilize several centimeters of the
contour change. An incision behind the tragus may lead to parotid, thereby creating a trough rather than a deep hole.
similar problems. Small arteries run superficial and parallel to the facial nerve;
these must be divided. Use of the electrocautery this close to
step 2: identification of facial nerve
the nerve is potentially hazardous. Bleeding is typically minor
Once the skin flaps have been developed and retracted, the but nonetheless must be controlled.
next step is to identify the facial nerve. Usually, the nerve may
be identified either at its main trunk (the antegrade approach) Retrograde Approach
or at one of the distal branches, with subsequent dissection As noted, when the main trunk cannot be exposed, the
back toward the main trunk (the retrograde approach). For a most common alternative method of identifying the facial
lateral parotidectomy, our preference is to identify the main nerve is to find a peripheral branch and then dissect proxi-
trunk first (unless it is thoroughly obscured by tumor or mally toward the main trunk. Which branch is sought may
scar). depend on factors such as the surgeon’s comfort with the
anatomy and the known consistency of the nerve branch’s
Antegrade Approach
location. In this setting, tumor bulk is often the deciding
The dissection plane is immediately anterior to the factor.
cartilage of the external auditory canal. The gland is mobi- The anatomic relationships between the nerve branches
lized anteriorly by means of blunt dissection. To reduce the and various landmarks can be exploited for more efficient
risk of a traction injury, tissue is spread in a direction that is identification. For example, the marginal mandibular branch
perpendicular to the incision and thus parallel to the direction of the facial nerve characteristically lies below the horizontal
of the main trunk of the nerve [see Figure 3]. The nerve trunk ramus of the mandible.7 Often, the facial vein can be traced
can usually be located underlying a point about halfway toward the parotid on the submandibular gland; the nerve
between the tip of the mastoid process and the ear canal. In branch can then be found coursing perpendicular and super-
addition, there are several anatomic landmarks that facilitate
ficial to the vein. The buccal branch of the facial nerve has a
identification of the nerve, including the tragal pointer, the
typical location in the so-called buccal pocket—the area infe-
posterior belly of the digastric muscle, and the tympanomas-
rior to the zygoma and deep to the superficial musculoapo-
toid suture. Of these, the tympanomastoid suture is closest to
neurotic layer, which contains the buccal fat pad and Stensen’s
the main trunk of the facial nerve.6 The clinical utility of this
duct in addition to the buccal branch.7 The zygomatic branch
landmark is limited, however, because the tympanomastoid
of the facial nerve lies roughly 3 cm anterior to the tragus,
suture is not easily appreciated in every case. In addition,
and the temporal-frontal branch lies at the midpoint between
the outer canthus of the eye and the junction of the ear’s helix
with the preauricular skin.7 Nerve branches to the eye should
be dissected with particular care: even transient weakness of
these branches may have a significant impact on morbidity.
Troubleshooting
Special efforts should be made to ensure that the cartilage
of the ear canal is not injured during exposure of the facial
nerve trunk. Any injury to this cartilage must be repaired, or
else an intense whistling will be heard from the closed suction
drain after operation.
The anxiety associated within isolation of the nerve trunk
may be alleviated somewhat by keeping in mind that the
nerve typically lies deeper than one might expect. In a study
of 46 cadaver dissections, the facial nerve was found to lie at
a median depth of 22.4 mm from the skin at the stylomastoid
foramen (range, 16 to 27 mm). The diameter of the nerve
trunk was found to range from 1.1 to 3.4 mm.8 In our expe-
rience, the facial nerve trunk is slightly larger than the nearby
deep vessels.
Some surgeons advocate the use of a nerve stimulator to
aid in identifying the facial nerve trunk or its branches; how-
ever, we have substantial reservations about whether this
Figure 3 Parotidectomy. Depicted is identification of the
facial nerve at its trunk. A wide trough is created anterior to
measure should be employed on a regular basis [see Compli-
the external auditory canal and deepened by spreading a blunt cations, Facial Nerve Palsy, below]. Knowledge of the ana-
curved instrument in a direction perpendicular to the incision tomy and sound surgical technique are the keys to a safe
and parallel to the nerve trunk. Anatomic landmarks assist in parotidectomy; it may be hazardous to rely too much on
identification of the nerve. practices that may diminish them.
07/08
step 3: parenchymal dissection The vertical portion of the dissection seldom poses a threat
Once identified, the plane of the facial nerve remains uni- to the integrity of the facial nerve, but care must be taken to
form throughout the gland (unless the nerve is displaced by maintain appropriate margins. If division of Stensen’s duct is
a tumor) and serves to guide the parenchymal dissection. required, the distal remnant may be either left open12 or
Although some surgeons advocate the use of hemostatic ligated.
devices for parenchymal division,9,10 our practice is to divide Caution is appropriate in the resection of deep-lobe tumors.
the substance of the parotid gland sharply and use ligatures Tumors medial to the facial nerve may displace this structure
as appropriate when bleeding is encountered. Usually, there laterally. Thus, after establishing the plane of the facial nerve,
is no significant hemorrhage: loss of more than 30 mL of the surgeon must remain careful when dissecting near the
blood is rare. tumor to keep from injuring the nerve. Once the substance of
The parenchymal dissection proceeds directly over the the gland obscuring the tumor has been removed, the nerve
facial nerve. We favor using fine curved clamps for this branches in the area of the tumor are retracted to allow expo-
portion of the procedure. To prevent trauma to the nerve, sure of the deep portion of the gland and facilitate resection.
care must be taken to resist the tendency to rest the blades of Traction injury to the nerve may still result in transient facial
the clamp on the nerve during dissection. Each division of the weakness.
gland should reveal more of the facial nerve [see Figure 4].
Troubleshooting
When this is the case, the surgeon can continue the paren-
chymal dissection with confidence that the nerve will not Complete superficial parotidectomy with full dissection of
be injured. As a rule, if a parenchymal division does not all facial nerve branches is seldom necessary, though in some
immediately show more of the facial nerve, it is in an improper cases it is mandated by tumor size or histologic findings.
plane. Removal of the entire superficial lobe with the intention of
We do not regularly resect the entire lateral lobe of the obtaining a larger lateral margin is rarely useful, because the
parotid unless the tumor is large and such resection is required closest margin is usually where the tumor is nearest the facial
on oncologic grounds. The goal in resecting the substance of nerve. Even temporary paresis of the temporal-frontal branch
the parotid is to obtain sound margins while preserving the of the facial nerve may have devastating consequences, and
remainder of the gland. This so-called partial superficial dissection near this branch is usually unnecessary in treating
parotidectomy has been shown to reduce the incidence of a benign tumor in the parotid tail. Any close margins remain-
Frey syndrome without increasing the rate of recurrence of ing after nerve-preserving cancer treatment can be addressed
pleomorphic adenoma.11 The plane of dissection is developed by means of postoperative radiation therapy, usually with
along facial nerve branches until the lateral margins have excellent results.13
been secured. This is the portion of the procedure during The question of whether to sacrifice the facial nerve almost
which the risk of nerve injury is highest. Once the lateral invariably arises in the setting of malignancy. In our view, this
margins have been secured, the parenchymal dissection can measure is seldom necessary. Benign tumors tend to displace
proceed from deep to superficial for the excision of the tumor. the nerve, not invade it. Sacrifice of the nerve probably does
not enhance survival.14,15 Although this issue remains a sub-
ject of debate, our practice, like that of others,16 is to sacrifice
only those branches intimately involved with tumor. Repair,
if feasible, should be performed [see Complications, Facial
Nerve Injury, below].
step 4: drainage and closure

Before closure, absolute hemostasis is confirmed (including
hemostasis during the Valsalva maneuver, which is approxi-
mated by transiently increasing airway pressure to 30 cm
H2O1). We may then assess the integrity of the facial nerve
with a nerve stimulator. A 5 mm closed suction drain is
placed through a stab incision posterior to the inferior aspect
of the ear in a hair-bearing area. The tip of the drain is loosely
tacked to the sternocleidomastoid muscle, with care taken to
avoid direct contact with the facial nerve). The wound is
closed with the drain placed on continuous suction. The skin
is closed with interrupted 5-0 nylon sutures. Bacitracin is
applied to the wound. No additional dressing is necessary or
desirable [see Figure 5].
Troubleshooting
Figure 4 Parotidectomy. Dissection of the gland
The use of interrupted skin sutures instead of a continuous
parenchyma is carried out over the branches of the facial
nerve to minimize the risk of nerve injury. Each division of suture allows the surgeon to perform directed suture removal
the substance of the gland should reveal more of the facial to drain the rare postoperative hematoma or fluid collection
nerve. instead of reopening the entire wound.
07/08
Figure 5 Parotidectomy. Shown is drainage and closure after parotidectomy. (a) A closed suction drain is placed in the
operative bed and loosely tacked to the sternocleidomastoid muscle. (b) Interrupted monofilament sutures are used for the skin.
Bacitracin is applied. No additional dressings are used.
Postoperative Care Complications

Facial nerve function is evaluated in the recovery room, facial nerve injury
with particular attention paid to whether the patient is able
to close the eyelid. The patient resumes eating when nausea Studies have found that transient paralysis of all or part of
(if any) abates. Pain is generally well controlled by means of the facial nerve occurs in 17 to 100% of patients undergoing
oral agents. At discharge, the patient should be warned to parotidectomy,17–20 depending on the extent of the resection
protect the numb earlobe against cold injury. The closed and the location of the tumor. Fortunately, permanent paral-
suction drain is kept in place for 5 to 7 days (until the ysis is uncommon, occurring in fewer than 5% of cases.19,21
first postoperative visit) to minimize the risk of salivary Nerve monitoring has been advocated to reduce the
fistula. incidence or severity of facial nerve injury, particularly in the
07/08
setting of surgery for a recurrent parotid tumor.22 To date, iodine test is employed, the incidence of Frey syndrome
however, no randomized trial has demonstrated that intra- may reach 95% at 1 year after operation.25 Fortunately, the
operative facial nerve monitoring or nerve stimulators yield majority of patients have only subclinical findings, and only a
any significant reduction in the incidence of facial nerve small fraction complain of debilitating symptoms.25 Most
paralysis after either primary parotidectomy or recurrence symptomatic patients are adequately treated with topical
surgery. Indeed, indiscriminate use of nerve monitoring and antiperspirants; eventually, however, they tend to become
nerve stimulators may imbue the surgeon with a false sense noncompliant with such measures, preferring simply to dab
of security and cause him or her to pay insufficient attention the face with a napkin while eating.25 Despite the relatively
to the appearance of nerve tissue. Transient nerve dysfunc- low incidence of clinically significant Frey syndrome, there is
tion may follow inappropriate (or even appropriate and an extensive literature addressing prevention and additional
unavoidable) trauma to or traction and pressure on nerve treatment of this condition.11,21,26–34
trunks. Nerve monitoring does not prevent such problems;
sialocele (salivary fistula)
moreover, it adds to the cost of the procedure and lengthens
the operating time.23 Some, in fact, have suggested that Sialocele, or salivary fistula, has been reported to occur
nerve stimulators may actually increase transient dysfunction. after 1 to 15% of parotidectomies.11,35 Although this condi-
Accordingly, our use of nerve stimulators is selective. tion is generally minor and self-limited, it may nonetheless be
The management of facial nerve injury depends on when embarrassing for the patient. We believe that the incidence of
the injury is discovered and on how sure the surgeon is of the sialocele can be reduced by maintaining closed suction drain-
anatomic integrity of the nerve. If the injury is discovered age for 5 to 7 days (to facilitate adhesion of the skin flaps to
intraoperatively, it should be repaired if posssible. Primary the underlying parotid parenchyma). Postparotidectomy sali-
repair—performed with interrupted fine permanent monofila- vary fistula is usually attributable to gland disruption rather
ment sutures under magnification24—is preferred if sufficient than to duct transection and therefore tends to resolve with-
nerve is available for a tension-free anastomosis. If both tran- out difficulty.36 Compression dressings are generally effec-
sected nerve ends are identified but tension-free repair is not tive.35 Anticholinergic agents have been used in this setting as
feasible, interposition nerve grafts may be used. A sensory well.37–40 Low-dose radiation,41 completion parotidectomy,
nerve harvested from the neck (e.g., the great auricular nerve) and tympanic neurectomy42 have all been employed in
is often employed for this purpose. If the nerve is injured refractory cases.
(or deliberately sacrificed) in conjunction with treatment
cosmetic changes
of malignancy, use of nerve grafts from distant sites may be
indicated.24 Parotidectomy creates a hollow anterior and inferior to the
If unexpected facial nerve dysfunction is identified in the ear, which may extend behind the mandible and may reach a
postanesthesia care unit and if the surgeon is unsure of the significant size in patients with large or recurrent tumors.
anatomic integrity of the nerve (ideally, a rare occurrence), This cosmetic change is a necessary feature of the procedure,
the patient should be returned to the operating room for not a complication; nonetheless, it should be discussed with
wound exploration so that either the continuity of the nerve the patient before operation. Many augmentation methods,
can be confirmed or the injury to the nerve can be identified using a wide variety of techniques, have been devised for
and, if possible, repaired. When the surgeon is certain that improving postoperative appearance (as well as alleviating
the nerve is intact, facial nerve dysfunction can be managed Frey syndrome).27–31,43,44 All of these methods have limitations
without reoperation, in anticipation of recovery24; however, or drawbacks that have kept them from being widely applied
this may take many months. and accepted.
Management of enduring facial nerve paralysis (from any
cause) is beyond the scope of our discussion and constitutes Outcome Evaluation
a surgical subspecialty in itself.24 With proper surgical technique, superficial or partial super-
ficial parotidectomy can be performed safely and within a
gustatory sweating (frey syndrome)
reasonable operating time. The requirement for blood trans-
Gustatory sweating, or Frey syndrome, occurs in most fusions should be vanishingly rare. Given adequate exposure,
patients after parotidectomy; it has been seen after good knowledge of the relevant anatomy, limited trauma to
submandibular gland resection as well. The symptom com- the nerve, and appropriate use of closed suction drains (see
plex includes sweating, skin warmth, and flushing after above), complications should be uncommon. Although
chewing food and is caused by cross-innervation of the para- patients may tolerate parotidectomy on an outpatient basis,
sympathetic and sympathetic fibers supplying the parotid we prefer to keep them in the hospital overnight. Patients
gland and the overlying skin. The reported incidence of should be able to leave the hospital with minimal pain, com-
Frey syndrome varies greatly, apparently depending on the fortable with their drain care, by the morning of postoperative
sensitivity of the test used to elicit it. When Minor’s starch day 1.
References
1. Berkovitz BKG, Moxham BJ. A textbook of cervicofacial halves. Surg Gynecol Obstet 4. Hui Y, Wong DS, Wong LY, et al. A pro-
head and neck anatomy. Chicago: Year Book 1956;102:385–412. spective controlled double-blind trial of
Medical Publishers, Inc; 1988. 3. Bernstein L, Nelson RH. Surgical anatomy great auricular nerve preservation at paroti-
2. Davis BA, Anson BJ, Budinger JM, Kurth of the extraparotid distribution of the dectomy. Am J Surg 2003;185:574–9.
LR. Surgical anatomy of the facial nerve and facial nerve. Arch Otolaryngol 1984;110:177– 5. Christensen NR, Jacobsen SD. Parotidecto-
the parotid gland based upon a study of 350 83. my: preserving the posterior branch of the
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great auricular nerve. J Laryngol Otol 1997; possible etiologic factors and results with 33. Beerens AJ, Snow GB. Botulinum toxin A in
111:556–9. routine facial nerve monitoring. Laryngo- the treatment of patients with Frey syndrome.
6. de Ru JA, van Benthem PP, Bleys RL, et al. scope 1999;109:754–62. Br J Surg 2002;89:116–9.
Landmarks for parotid gland surgery. 20. Bron LP, O’Brien CJ. Facial nerve function 34. Marchese-Ragona R, De Filippis C, Marioni
J Laryngol Otol 2001;115:122–5. after parotidectomy. Arch Otolaryngol Head G, Staffieri A. Treatment of complications of
7. Peterson RA, Johnston DL. Facile identifica- Neck Surg 1997;123:1091–6. parotid gland surgery. Acta Otorhinolaryngol
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Surg 1987;14:785–8. for parotid tumours: 19-year experience 35. Wax M, Tarshis L. Post-parotidectomy
8. Salame K, Ouaknine GER, Arensburg B, from The Netherlands. Br J Surg 1992;79: fistula. J Otolaryngol 1991;20:10–3.
et al. Microsurgical anatomy of the facial 1159–61. 36. Ananthakrishnan N, Parkash S. Parotid
nerve trunk. Clin Anat 2002;15:93–9. 22. Makeieff M, Venail F, Cartier C, et al. fistulas: a review. Br J Surg 1982;69:641–3.
9. Colella G, Giudice A, Vicidomini A, Sperlon- Continuous facial nerve monitoring during 37. Cavanaugh K, Park A. Postparotidectomy
gano P. Usefulness of the LigaSure Vessel pleomorphic adenoma recurrence surgery.
fistulas: a different treatment for an old prob-
Sealing System during superficial lobectomy Laryngoscope 2005;115:1310–4.
lem. Int J Pediatr Otorhinolaryngol 1999;
of the parotid gland. Arch Otolaryngol Head 23. Terrell JE, Kileny PR, Yian C, et al. Clinical
47:265–8.
Neck Surg 2005;131:413–6. outcome of continuous facial nerve monitor-
10. Jackson LL, Gourin CG, Thomas DS, et al. ing during primary parotidectomy. Arch 38. Vargas H, Galati LT, Parnes SM. A
Use of the harmonic scalpel in superficial Otolaryngol Head Neck Surg 1997;123: pilot study evaluating the treatment of
and total parotidectomy for benign and 1081–7. postparotidectomy sialoceles with botulinum
malignant disease. Laryngoscope 2005;115: 24. Shindo M. Management of facial nerve toxin type A. Arch Otolaryngol Head Neck
1070–3. paralysis. Otolaryngol Clin North Am 1999; Surg 2000;126:421–4.
11. Leverstein H, van der Wal JE, Tiwari RM, 32:945–64. 39. Guntinas-Lichius O, Sittel C. Treatment
et al. Surgical management of 246 previously 25. Linder TE, Huber A, Schmid S. Frey’s of postparotidectomy salivary fistula with
untreated pleomorphic adenomas of the syndrome after parotidectomy: a retrospec- botulinum toxin. Ann Otol Rhinol Laryngol
parotid gland. Br J Surg 1997;84:399–403. tive and prospective analysis. Laryngoscope 2001;110:1162–4.
12. Woods JE. Parotidectomy: points of tech- 1997;107:1496–501. 40. Chow TL, Kwok SP. Use of botulinum toxin
nique for brief and safe operation. Am J Surg 26. Bonanno PC, Palaia D, Rosenberg M, type A in a case of persistent parotid sialocele.
1983;145:678–83. Casson P. Prophylaxis against Frey’s syn- Hong Kong Med J 2003;9:293–4.
13. Garden AS, el-Naggar AK, Morrison WH, drome in parotid surgery. Ann Plast Surg 41. Shimms DS, Berk FK, Tilsner TJ, Coulthard
et al. Postoperative radiotherapy for malig- 2000;44:498–501. SW. Low-dose radiation therapy for benign
nant tumors of the parotid gland. Int J Radiat 27. Ahmed OA, Kolhe PS. Prevention of Frey’s salivary disorders. Am J Clin Oncol 1992;
Oncol Biol Phys 1997;37:79–85. syndrome and volume deficit after parotidec- 15:76–8.
14. Renehan AG, Gleave EN, Slevin NJ, tomy using the superficial temporal artery 42. Davis WE, Holt GR, Templer JW. Parotid
McGurk M. Clinico-pathological and treat- fascial flap. Br J Plast Surg 1999;52:256–60. fistula and tympanic neurectomy. Am J Surg
ment-related factors influencing survival 28. Bugis SP, Young JE, Archibald SD. Sterno- 1977;133:587–9.
in parotid cancer. Br J Cancer 1999;80: cleidomastoid flap following parotidectomy. 43. Kerawala CJ, McAloney N, Stassen LF. Pro-
1296–300. Head Neck 1990;12:430–5. spective randomized trial of the benefits of
15. Magnano M, Gervasio CF, Cravero L, et al. 29. Jeng SF, Chien CS. Adipofascial turnover a sternocleidomastoid flap after superficial
Treatment of malignant neoplasms of the flap for facial contour deformity during parotidectomy. Br J Oral Maxillofac Surg
parotid gland. Otolaryngol Head Neck Surg parotidectomy. Ann Plast Surg. 1994;33: 2002;40:468–72.
1999;121:627–32. 439–41.
44. Chao C, Friedman DC, Alford EL, et al.
16. Spiro JD, Spiro RH. Cancer of the parotid 30. Govindaraj S, Cohen M, Genden EM, et al.
Acellular dermal allograft prevents post-
gland: role of 7th nerve preservation. World J The use of acellular dermis in the prevention
parotidectomy soft tissue defects: a prelimi-
Surg, 2003;27:863–7. of Frey’s syndrome. Laryngoscope 2001;111:
17. Witt RL. Facial nerve monitoring in parotid 1993–8. nary experience. Int Online J Otorhinolaryn-
surgery: the standard of care? Otolaryngol 31. Nosan DK, Ochi JW, Davidson TM. Preser- gol Head Neck Surg 2000;2(5).
Head Neck Surg 1998;119:468–70. vation of facial contour during parotidectomy.
18. Reilly J, Myssiorek D. Facial nerve stimula- Otolaryngol Head Neck Surg 1991;104:
tion and postparotidectomy facial paresis. 293–8. Acknowledgment
Otolaryngol Head Neck Surg 2003;128: 32. Sinha UK, Saadat D, Doherty CM, Rice DH.
530–3. Use of AlloDerm implant to prevent Frey The authors wish to thank Veronica Levin for her
19. Dulguerov P, Marchal F, Lehmann W. syndrome after parotidectomy. Arch Facial assistance in the preparation of this chapter.
Postparotidectomy facial nerve paralysis: Plast Surg 2003;5:109–12. Figures 1a, 2b, 3, 4 Tom Moore.
07/08
2 HEAD AND NECK 7 NECK DISSECTION — 1
7 NECK DISSECTION
Miriam N. Lango, MD, Bert W. O’Malley Jr, MD, FACS, and Ara A. Chalian, MD, FACS
Preoperative Evaluation tomography (PET) detects lesions with increased metabolic

In the majority of cases, cancer in the neck is a metastasis activity but has the limitation of being unable to detect lesions
from a primary lesion in the upper aerodigestive tract, smaller than 1 cm in diameter. Primary lesions greater than
although metastases from skin, thyroid, and salivary gland 1 cm in diameter usually are easily identified on physical
neoplasms are also encountered. Lymphomas often present examination and other imaging studies; thus, PET scans add
as cervical lymphadenopathy. little in this setting. In 5 to 10% of patients who present with
When a patient presents with a suspicious lesion in the a metastatic node, the primary lesion is never found despite
neck, a careful history and physical examination should be extensive workup.
performed, along with a thorough evaluation of the aerodiges-
incidence and imp act of neck metastases
tive tract aimed at locating the source of possible metastatic
disease. Fine-needle aspiration (FNA) of the neck mass should Cutaneous Squamous Cell Carcinoma
then be done to determine whether the mass is malignant. The incidence of cervical metastases is governed by many
FNA can often differentiate between epithelial and lymphoid factors. Cervical metastases from cutaneous squamous cell
malignancies, and this differentiation will guide subsequent carcinomas are rare, occurring in 2 to 10% of cases. How-
workup. The reported sensitivity of FNA ranges from 92 to ever, certain lesions—those that are greater than 2 cm in
98% and the reported specificity from 94 to 100%.1,2 diameter; are recurrent; are deeper than 6 mm; involve the
If FNA reveals the presence of atypical lymphoid cells, an ear, the temple, or the classic H zone; occur in an immuno-
excisional lymph node biopsy may be performed if additional compromised patient; or are poorly differentiated—have a
tissue is required for adequate tumor typing. An excisional significant occult metastatic rate, ranging from 20 to 60%.
biopsy may also be performed if the FNA is negative or inde- The presence of cervical metastases reduces 5-year survival to
terminate, the surgeon suspects a malignancy, and the rest of about 32%,3 which suggests that early intervention for high-
the physical examination yields negative results. Routine exci- risk cutaneous lesions, involving regional lymphadenectomy,
sional biopsy of neck masses for diagnostic purposes is not sentinel lymph node (SLN) biopsy, or irradiation of at-risk
recommended, however, because it may result in tumor spill- lymph node basins, may be warranted.
age into the wound and complicate subsequent definitive
resection. Salivary Gland Neoplasms
Once the presence of an epithelial malignancy is estab- With salivary gland neoplasms [see 2:1 Oral Cavity Lesions],
lished, the primary site of the lesion must be determined. The the incidence of cervical metastases is related to the histopa-
clinical setting provides clues regarding the source of the thology and the size of the tumor. The most aggressive sali-
cancer. For example, in an elderly patient with a previous vary gland lesions are squamous cell carcinoma, carcinoma ex
history of skin cancer, with abnormal cutaneous lesions over pleomorphic adenoma, adenocarcinoma, and salivary ductal
the scalp or face and a nontender, enlarging posterior triangle carcinoma. Patients with these lesions often have cervical
neck mass, a metastasis from a cutaneous cancer is suspected. metastases at presentation that warrant a therapeutic neck
Alternatively, in a 50-year-old alcohol abuser with an enlarg- dissection [see Table 1]. How best to manage occult cervical
ing level II lymph node also complaining of a several-month salivary gland metastatic disease is controversial. The occult
history of sore throat and otalgia, a metastasis from a pharyn- metastatic rate for aggressive lesions ranges from 25 to 45%.
geal primary cancer should be entertained. In any patient For such lesions, a selective neck dissection is typically incor-
with metastatic cervical adenopathy thought to originate in porated into the surgical approach.4
the upper aerodigestive tract, panendoscopy and biopsy
with general anesthesia are mandatory for locating and char- Metastatic Well-Differentiated Thyroid Cancer
acterizing the primary source of the tumor and ruling out the Cervical lymph node metastases are present in 10 to 15%
presence of synchronous lesions. The most common occult of patients with well-differentiated thyroid carcinoma. The
primary sites are the base of the tongue, the tonsils, and the impact of nodal metastases on local recurrence and survival
nasopharynx. Imaging studies (e.g., computed tomography has not been established. Other factors (e.g., age, sex, tumor
[CT] and magnetic resonance imaging) may be helpful in extent, and distant metastases) appear to have a greater effect
locating the source of a cervical metastasis. Positron emission on prognosis. Nevertheless, in the presence of clinically
DOI 10.2310/7800.S02C07
01/09
Table 1 Incidence of Cervical Metastases in Selected associated with a high risk of regional recurrence and distant
Head and Neck Cancers metastases.7–9 The presence of ECS in lymph node metastases
Tumor Incidence of may, in fact, be the single most important prognostic factor in
Cervical patients with head and neck cancer. Identification of this
Adenopathy (%) patient subset may be the most important benefit of elective
Cutaneous squamous cell carcinoma 2–10 neck dissection in that it allows these patients to be offered
adjuvant therapy. The presence of extracapsular extension is
Salivary gland malignancies 30–70
Mucoepidermoid carcinoma (high grade)
an indication for adjuvant concurrent chemoradiation, which
has been shown to decrease the risk of recurrence and improve
Adenoid cystic carcinoma 8 survival in randomized clinical trials.10,11
Malignant mixed tumor 25 Whereas anatomic and pathologic factors (e.g., ECS) have
Squamous cell carcinoma 46 long been known to predict tumor behavior, it is only com-
paratively recently that the impact of comorbidity has been
Salivary duct carcinoma 50
well characterized. When patients are stratified by tumor
Acinic cell carcinoma 40 stage, those with comorbidities fare worse. In fact, the impact
Metastatic well-differentiated 10–15 of comorbidity on overall survival is greater than that of
thyroid cancer tumor stage or treatment type.12,13 In addition, comorbidity is
Squamous cell carcinoma of upper associated with both increased frequency and increased sever-
aerodigestive tract ity of surgical complications. These factors may be important
in treatment selection and patient counseling. To date,
Alveolar ridge 30
comorbidity has not been incorporated into clinical staging of
Hard palate 10 head and neck cancer patients.
Oral tongue 30
staging of neck cancer
Anterior pillar/retromolar trigone 45
Staging of the neck for metastatic squamous cell carcinomas
Floor of mouth 30
of the head and neck is based on the TNM classification
Soft palate 44 formulated by the American Joint Committee on Cancer
Tonsillar fossa 76 (AJCC) [see 2:1 Oral Cavity Lesions]. The N classification
applies to cervical metastases from all upper aerodigestive
Tongue base 78
tract mucosal sites except the nasopharynx; nodal metastases
Bilateral 20 from cutaneous, sinonasal, and thyroid malignancies have
their own staging systems.
The purpose of staging is to characterize the tumor burden
apparent nodal disease, a formal neck dissection is advised: of an individual patient. Precise characterization and differ-
so-called cherry-picking operations or limited lymph node entiation of tumors facilitate identification of those patients
excisions result in higher rates of recurrence.5 who are most likely to benefit from treatment. However, the
TNM staging system does not include a number of factors
Squamous Cell Carcinoma of the Upper Aerodigestive Tract that are known to have an impact on prognosis, such as the
With upper aerodigestive tract squamous cell carcinomas, the presence or absence of ECS and the pattern of lymphatic
incidence of cervical metastases is related to the site of the pri- spread. Nonanatomic factors (e.g., comorbidity, immune
mary lesion, the size of the tumor, the degree of differentiation, status, and nutritional status) have a strong impact on sur-
the depth of invasion, and other biologic factors. A significant vival as well but are also not incorporated in the current stag-
proportion of head and neck cancer patients who harbor clini- ing system. In general, TNM staging may be inadequate for
cally silent primary tumors of the base of the tongue, the tonsils, use in clinical trials.14
or the nasopharynx initially present with cervical adenopathy The limitations of clinical staging of the neck are well
[see Table 1]. These sites lack anatomic barriers that limit tumor described. In particular, patients with short, thick necks are
spread and are supplied by rich lymphatic networks that facili- challenging to stage accurately on physical examination alone.
tate metastasis. In contrast, patients with glottic and lip cancers The addition of imaging to clinical examination improves diag-
rarely present with clinical adenopathy. nostic sensitivity but not specificity. Pathologic review of neck
The presence of cervical metastases negatively affects prog- specimens remains the gold standard for anatomic staging.
nosis and has been associated with increased recurrence rates The addition of ultrasound-guided FNA of neck nodes yields
and reduced disease-free and overall survival. The presence of enhanced diagnostic accuracy in cases in which the neck is
clinical adenopathy decreases survival by 50%. Metastatic clinically negative, but the radiologic findings are positive. This
tumors that rupture the lymph node capsule—a process known approach is employed to select patients for neck dissection in
as extracapsular spread (ECS)—are biologically more aggres- a number of centers, particularly in Europe; whether it pro-
sive. Patients who have palpable cervical lymphadenopathy vides more accurate staging than alternative methods, such as
with ECS manifest a 50% decrease in survival compared with SLN biopsy, remains to be determined. The results from the
those who have palpable cervical lymphadenopathy without First International Conference on Sentinel Node Biopsy in
ECS.6 In addition, about 50% of clinically negative, patho- Mucosal Head and Neck Cancer revealed that SLN biopsy of
logically positive neck specimens exhibit ECS. Clinically neg- the clinically negative neck has a sensitivity comparable to that
ative, pathologically positive, and ECS-positive specimens are of a staging neck dissection.15 In general, imaging modalities
01/09
appear to be neither sufficiently sensitive nor sufficiently

specific in the evaluation of the clinically negative neck.
Uptake of 2-deoxy-3 [18F] fluoro-D-glucose, as measured by
PET scans, is undetectable in small foci of cancer in the clin-
ically negative neck.16
Proper staging is important for stratification of patients into
risk categories on the basis of tumor biology so that high-risk
patients may be appropriately selected for clinical trials or
offered adjuvant therapy and other patients may be spared
unnecessary treatment. Until accurate methods of assessing
the clinically negative neck are developed, selective neck dis- II
section will be performed to treat the neck when the occult
metastatic rate is expected to be higher than 20%. I
indications for neck dissection

Neck dissections are considered either therapeutic (per-
III VI
formed to remove clinically identifiable cancer in the neck)
or elective (performed when the expected incidence of occult
V
metastases from a lesion exceeds 20%). In patients with
head and neck cancer, neck dissection may be performed as
part of initial definitive treatment, often combined with IV
resection of the primary cancer. Alternatively, neck dissec-
tion may be performed in an adjuvant setting to remove
residual cancer in the neck following treatment with radia-
tion or chemoradiation. Technically, neck dissections are
classified as comprehensive dissections, which incorporate Figure 1 Cervical lymph nodes are divided into six levels on
five levels of the neck, or selective dissections, in which only the basis of their location in the neck.
selected lymph node levels are removed according to pre-
dicted drainage patterns from specific primary sites. There
is also a third technical classification, extended neck dissec-
tions, which can be combined with selective or comprehen- Operative Planning
sive neck dissections for removal of additional nodal basins choice of procedure
[see Operative Planning, Choice of Procedure, below]. Six
lymph node drainage basins in the neck are recognized [see Comprehensive Dissection: Radical and
Figure 1]. The extent of neck dissection is determined by the Modified Radical Neck Dissection
clinical setting. The radical neck dissection was first described in 1906 by
George Crile, who based his approach on the Halstedian
contraindications to neck dissection principle of en bloc resection. The procedure was subse-
The only absolute contraindication to neck dissection is quently standardized by Hayes Martin at Memorial Hospital
surgical unresectability. The determination of unresectability in New York in the 1930s and 1940s. In this latter version of
is made by the operating surgeon either preoperatively, on the procedure, lymphatic structures from the strap muscles
the basis of imaging studies, or in the operating room. Typ- anteriorly, the trapezius posteriorly, the mandible superiorly,
ically, the presence of Horner syndrome, paralysis of the and the clavicle inferiorly are removed. Nonlymphatic struc-
vagus nerve or the phrenic nerve, or invasion of the brachial tures in this space are also sacrificed, including the spinal
plexus or the prevertebral muscles indicates that the tumor accessory nerve, the sternocleidomastoid muscle, the internal
is unresectable. The involvement of the carotid artery may and external jugular veins, the submandibular gland, and sen-
be predicted on the basis of imaging studies. Encasement of sory nerve roots. The routine sacrifice of the spinal accessory
the carotid artery by tumor suggests direct invasion of the nerve, the internal jugular vein, and the sternocleidomastoid
vessel; however, studies correlating imaging characteristics muscle contributes to the significant morbidity associated
and pathologic invasion of the carotid have shown that with radical neck dissection.
tumors surrounding 180˚ or more of the carotid’s circumfer- Since the 1970s, the necessity of en bloc resection for onco-
ence have a higher incidence of carotid invasion than tumors logic cure has been reexamined. Structures once routinely sac-
surrounding less than 180˚ (75% versus 50%). In the absence rificed are now routinely preserved unless they are grossly
of direct invasion of the vessel wall, tumor may be peeled off involved with cancer. The various functional, or modified, rad-
by means of subadventitial surgical dissection. Tumors sur- ical neck dissections are classified according to which structures
rounding 270˚ of the vessel have an 83% incidence of carotid are preserved. Type I dissections preserve the spinal accessory
invasion, necessitating sacrifice of the artery.17 However, sac- nerve; type II, the spinal accessory nerve and the internal jugu-
rifice of the carotid artery, with or without reconstruction lar vein; and type III, both of these structures, along with the
with a vein graft, has been associated with significant mor- sternocleidomastoid muscle. Modified radical neck dissections
bidity. The survival of patients with such extensive neck dis- have proved to be as effective in controlling metastatic disease
ease is uniformly poor.18 to the neck as the classic radical neck dissection.19
01/09
Selective Neck Dissection [see 2:6 Parotidectomy]. Retropharyngeal nodes may be removed
In a selective neck dissection, at-risk lymph node drainage in the treatment of selected cancers originating in the posterior
basins are selectively removed on the basis of the location of pharynx, the soft palate, or the nasopharynx. A mediastinal
the primary tumor in a patient with no clinical evidence of lymph node dissection may be combined with a neck dissec-
cervical lymphadenopathy. Cancers in the oral cavity, for tion in the treatment of metastatic thyroid carcinomas.
example, typically metastasize to levels I through III and, Bilateral Neck Dissection
occasionally, IV; laryngeal cancers typically metastasize to
levels II through IV. The rationale for selective neck dissec- With primary lesions located in the midline in the base of
tion is based on retrospective pathologic reviews of radical the tongue, the supraglottic larynx, or the medial wall of the
neck dissection specimens from patients without palpable piriform sinus, bilateral regional metastases are common, and
lymphadenopathy. These reviews revealed that lymph node bilateral neck dissections are therefore indicated. Provided
micrometastases were confined to specific neck levels for a that at least one internal jugular vein is preserved, bilateral
given aerodigestive tract site.20 neck dissection is well tolerated. In contrast, sacrifice of both
The advantages of selective neck dissection over radical internal jugular veins is associated with significant morbidity,
and modified radical neck dissection are both cosmetic and including increased intracranial pressure, syndrome of inap-
functional. A selective neck dissection involves less manipula- propriate antidiuretic hormone secretion, airway edema, and
tion (and thus less risk of devascularization) of the spinal death. Bilateral internal jugular sacrifice is managed by stag-
accessory nerve, thereby decreasing the incidence of postop- ing the neck dissections or by carrying out vascular repair.
erative shoulder dysfunction. Preservation of the sterno- neck dissection after chemoradiation
cleidomastoid muscle alleviates the cosmetic deformity seen
with a radical neck dissection and provides some protection The indications for neck dissection have been significantly
for the carotid artery. Preservation of the internal jugular vein affected by the increasing use of organ preservation protocols
decreases venous congestion of the head and neck and is nec- for the treatment of head and neck cancer. Nasopharyngeal
essary if the contralateral internal jugular vein is sacrificed. carcinomas, which are uniquely radiosensitive, are generally
In the presence of multiple pathologically positive lymph treated with irradiation, with or without chemotherapy. Fol-
nodes or evidence of ECS, adjuvant therapy is indicated.21 lowing chemoradiation, neck dissection is reserved for patients
Accordingly, selective neck dissection may be viewed as a with an incomplete clinical response to treatment who are at
diagnostic and a therapeutic procedure. To date, however, no high risk of cancer recurrence in the neck. Most patients with
randomized clinical trials have demonstrated that selective early nodal disease (N0 or N1) treated according to organ
neck dissection with adjuvant treatment as needed is better preservation protocols do not require neck dissection. Patients
than so-called watchful waiting with regard to prolonging sur- who have advanced neck disease (N2 or N3) are less likely to
vival in patients who present without evidence of cervical respond completely to nonsurgical treatment and require a
metastatic disease. Therefore, it is not yet possible to justify neck dissection. Early surgery (within 8 to 10 weeks) is recom-
the added cost and morbidity of elective neck dissection in mended for a number of reasons. After this period, progressive
patients without evidence of metastatic disease. SLN map- soft tissue fibrosis develops, resulting in difficult surgical dis-
ping may facilitate pathologic staging in this setting and spare section and increased postoperative morbidity. Over time,
low-risk patients from unnecessary interventions; however, its surgery is also less effective in clearing disease from the neck,
sensitivity and specificity for this purpose are still under and surgical treatment of such so-called neck failures is rarely
investigation. curative.23 Observation of necks suspected of harboring resid-
The growing focus on preservation of function and limita- ual cancer after chemoradiation is therefore not recommended.
tion of morbidity has led some surgeons to promote the use Since observation may lead to nonsalvageable regional recur-
of selective neck dissection to treat node-positive neck tumors. rences, some surgeons recommend that all patients presenting
Although retrospective studies have suggested that a selective with N2 or N3 cervical lymphadenopathy undergo planned
neck dissection may be adequate in carefully selected node- neck dissection, regardless of clinical response to chemoradia-
positive patients,22 the effectiveness of this approach is still tion therapy.24 Others recommend that imaging with CT of
unproven, and its application remains subject to individual the neck be used to evaluate clinical response following
surgical judgment. chemoradiation to determine the need for neck dissection.25
The presence of nodes on CT scan measuring greater than
1.5 cm or any nodes with focal lucency, enhancement, or cal-
Extended Neck Dissection cification suggest the presence of residual disease. In their
Extended neck dissections can be combined with selective study, only 2 of 34 patients (6%) with a complete radiographic
or comprehensive neck dissections to remove additional nodal response were found to have residual cancer in the neck dis-
basins, such as the suboccipital and retroauricular nodes. section specimen, suggesting that this imaging modality is a
These groups of nodes, which are located in the upper pos- sensitive means by which to identify patients at high risk for
terior neck, are the first-echelon nodal basins for posterior harboring residual disease after chemoradiation.
scalp skin cancers. The retroauricular nodes lie just posterior The required extent of planned neck dissection after
to the mastoid process, and the suboccipital nodes lie near chemoradiation is still under investigation. Pathologic reviews
the insertion of the trapezius muscle into the inferior nuchal of comprehensive neck specimens after chemoradiation reveal
line. Cancers of the anterior scalp, the temple, and the pre- that in patients with oropharyngeal cancer, levels I and V are
auricular skin drain to periparotid lymph nodes; these lymph rarely involved in the absence of radiographic abnormalities,26
nodes are removed in conjunction with a parotidectomy which suggests that a planned selective dissection involving
01/09
levels II through IV may be sufficient for oropharyngeal may facilitate the reconstructive process. Typically, several
cancer patients treated with chemoradiation. This more lim- vessels, including an artery and one or two veins, are required
ited approach undoubtedly causes less morbidity, but addi- for inflow and outflow into a free flap. The facial artery, the
tional data are required to assess its oncologic efficacy. retromandibular vein, and the external jugular vein, which
For patients in whom no primary site can be identified, are preserved during level I and level II dissection, are the
neck dissection followed by radiation is usually recommended. vessels that are most frequently used for flap revasculariza-
This approach has also been used selectively to treat bulky tion. If these vessels are unavailable as a consequence of high-
nodal disease in patients with small primary cancers, although volume neck disease, the superior thyroid artery and the
this practice is controversial.27 Bulky cervical adenopathy is transverse artery, with companion veins, are suitable substi-
unlikely to exhibit a complete pathologic response to nonsur- tutes. To date, there is no evidence in the literature that pres-
gical treatment, and postradiotherapy neck dissections are ervation of vascular structures in the neck predisposes patients
generally associated with higher rates of surgical complica- to regional recurrence. Caution must, however, be exercised
tions. A patient who requires dental extractions before radia- in the setting of pathologic lymphadenopathy.
tion therapy may undergo a neck dissection at the same time,
proceeding to radiation therapy 10 to 14 days after operation.
Early neck dissection decreases the tumor burden, thereby Operative Technique
allowing lower adjunctive doses of radiation to be delivered radical neck dissection
to the neck. Significant delays in initiating treatment to the
primary site should be avoided. Step 1: Incision and Flap Elevation
When a radical or modified radical neck dissection is indi-
reconstruction and recurrence cated, appropriate neck incisions must be designed so as to
after neck dissection facilitate exposure while preserving blood flow to the skin flaps
The use of microvascular free tissue transfer to reconstruct [see Figure 2]. The incision provides access to the relevant
surgical defects in the head has allowed surgeons to resect levels of the neck, affects cosmesis, and determines the extent
large tumors with large margins while simultaneously achiev- of lymphedema and postoperative fibrosis (“woody” neck),
ing improved functional results. Preservation of vascular— especially in previously irradiated areas. If a biopsy was previ-
and, occasionally, neural—structures during neck dissection ously performed, the tract should be excised and incorporated
a b c
d e f
Figure 2 Illustrated are incisions used for neck dissections. Incision design is a critical element of operative planning. Incisions
are chosen with the aims of optimizing exposure of relevant neck levels and minimizing morbidity. The incisions depicted in
(a) and (b) are useful for selective neck dissections. For the more extensive exposure required in a radical or modified radical
neck dissection, a deeper half-apron–style incision (c) may be used, or a vertical limb may be dropped from a mastoid-
submental incision (d ); the latter incision is less reliable and may break down, exposing vital structures such as the carotid. The
incision depicted in (e) is also useful for selective neck dissections. The Macfee incision ( f ) provides limited exposure and results
in persisent lymphedema in the bipedicled skin flap.
01/09
into the new incision. When a total laryngectomy is done, the of the submental triangle. The omohyoid muscle is identified
stoma may be fashioned separately from the neck incision; in inferior to the digastric tendon and followed inferiorly to the
the event of a pharyngocutaneous fistula, the salivary flow will sternocleidomastoid muscle. The omohyoid muscle forms the
be diverted away from the stoma. anteroinferior limit of the dissection.
Once the incision is made, subplatysmal flaps are raised. Fat and lymphatic structures are dissected away from the
If there is extensive lymphadenopathy or extension of tumor digastric muscle and the mylohyoid muscle. The hypoglossal
into the soft tissues of the neck, skin flaps may be raised in and lingual nerves lie just deep to the mylohyoid muscle and
a supraplatysmal plane to ensure negative surgical margins. are protected by it [see Figure 3]. In this region, the distal end
Such flaps, however, are not as reliably vascularized as sub- of the facial artery can be identified and preserved as needed
platysmal flaps. Clinical judgment must be exercised in for reconstructive purposes. Once the posterior edge of the
these situations. The flaps are raised to the mandible supe- mylohyoid muscle is visualized, an Army-Navy retractor is
riorly, the clavicle inferiorly, the omohyoid muscle and the inserted beneath the muscle to expose the submandibular
submental region anteriorly, and the trapezius posteriorly. duct, the lingual nerve with its attachment to the subman-
Radical neck dissection for bulky cervical adenopathy typi- dibular gland, and the hypoglossal nerve. The submandibular
cally necessitates wide exposure of levels I through V. If a duct and the submandibular ganglion, with its contributions
vertical limb is used [see Figure 2d], it must not be centered to the gland, are ligated, and the submandibular gland is
over the carotid artery, because of the risk of potentially retracted out of the submandibular triangle.
catastrophic dehiscence. Deep utility-type incisions yield The posterior belly of the digastric muscle is then identified
more limited exposure of level I but provide reliable vascular inferior to the submandibular gland and skeletonized to the
inflow to skin flaps. sternocleidomastoid muscle posteriorly, where it inserts on
the mastoid tip. The specimen must be mobilized off struc-
Step 2: Dissection of Anterior Compartment tures just inferior to the digastric muscle. To prevent inadver-
Embedded within the fascia overlying the submandibular tent injury, it is essential to understand the relationships
gland is the marginal mandibular branch of the facial nerve, among these structures [see Figure 3]. The hypoglossal nerve
which must be elevated and retracted to prevent lower-lip emerges from beneath the mylohyoid muscle and passes into
weakness. The submental fat pad is then grasped, retracted the neck under the digastric muscle. It then loops around the
posteriorly and laterally, and mobilized away from the floor external carotid artery at the origin of the occipital artery and
Internal Carotid
Artery
External
Carotid
Artery
Facial
Artery
Digastric
Muscle
Spinal Lingual
Accessory Artery
Nerve
Hypoglossal
Nerve
Occipital Artery
Mylohyoid
Internal Jugular Muscle
Vein
Hyoid Bone
Ansa Hypoglossi
Superior
Thyroid Hyoglossal
Artery Muscle
Carotid Sheath
Common Carotid
Artery
Vagus Nerve
Figure 3 Depicted are the key anatomic relationships in levels I and II that must be kept in mind in
performing a neck dissection. View is of the right neck.
01/09
ascends to the skull base between the external carotid artery modified radical neck dissection
and the internal jugular vein. Often the hypoglossal nerve is The incision is made and flaps are elevated as in a radical
surrounded by a plexus of small veins, branching off the neck dissection. Care must be exercised in elevating the pos-
common facial vein. Bleeding in this region places the hypo- terior skin flap. Typically, the platysma is deficient in this
glossal nerve at risk. The jugular vein, located just posterior area, and often no natural plane exists. Dissection deep in the
to the external carotid artery and the hypoglossal nerve, may posterior triangle may result in inadvertent injury to the spinal
be isolated and doubly suture-ligated at this point. Fre- accessory nerve, which travels inferiorly and posteriorly across
quently, the spinal accessory nerve is identified just lateral the posterior triangle in a relatively superficial plane to inner-
and posterior to the internal jugular vein, proceeding posteri- vate the trapezius.
orly into the sternocleidomastoid muscle. A type I modified radical neck dissection begins with dis-
In a radical neck dissection, the sternocleidomastoid muscle sections of levels I and II, as described for a radical neck
and the spinal accessory nerve are transected at this point and dissection (see above). The spinal accessory nerve is identi-
elevated off the splenius capitis and the levator scapulae to fied just superficial or posterior to the internal jugular vein
the trapezius posteriorly. The anterior edge of the trapezius is and preserved; the distal spinal accessory nerve is then identi-
skeletonized from the occiput to the clavicle. In a radical neck fied in the posterior triangle. Typically, the spinal accessory
dissection, the accessory nerve is again transected where it nerve can be identified 1 cm superior to the cervical plexus
penetrates the trapezius. along the posterior border of the sternocleidomastoid muscle.
Step 3: Control of Internal Jugular Vein Inferiorly; Provided that the patient is not fully paralyzed, the surgeon
Ligation of Lymphatic Pedicle can distinguish this nerve from adjacent sensory branches by
using a nerve stimulator.
The sternal and clavicular heads of the sternocleidomastoid Once the spinal accessory nerve is identified, it is dissected
muscle are transected and elevated to expose the anterior and mobilized distally. Proximally, the nerve is dissected
belly of the omohyoid muscle. The soft tissue overlying the through the sternocleidomastoid muscle, which is transected
posterior belly of the omohyoid muscle is clamped and ligated over the nerve. The branch to the sternocleidomastoid muscle
as necessary. The omohyoid muscle is then transected, and is divided with Metz scissors, and the nerve is fully mobilized
the jugular vein, the carotid artery, and the vagus nerve are from the trapezius posteroinferiorly to the posterior belly of the
exposed. The jugular vein is isolated and doubly suture- digastric muscle anterosuperiorly and then gently retracted out
ligated. Care is taken not to transect the adjacent vagus nerve of the way.
and carotid artery. The lymphatic tissues in the base of the The rest of the neck dissection proceeds as described for a
neck adjacent to the internal jugular vein are clamped and radical neck dissection. If the tumor does not involve the
suture-ligated 1 cm superior to the clavicle. If a chyle leak is internal jugular vein, it may also be preserved; this constitutes
encountered, a figure-eight stitch is placed along the lym- a type II modified radical neck dissection. If the spinal acces-
phatic pedicle until there is no evidence of clear or turbid sory nerve, the internal jugular vein, and the sternocleidomas-
fluid on the Valsalva maneuver. Care is taken to avoid inad- toid muscle are all preserved, the procedure is a type III
vertent injury to the vagus nerve or the phrenic nerve, which modified radical neck dissection. In a type III dissection, the
course through this region. sternocleidomastoid muscle is fully mobilized and retracted
Step 4: Mobilization of Supraclavicular with two broad Penrose drains, and the contents of the neck
Fat Pad (“Bloody Gulch”) are exposed. The spinal accessory nerve is preserved though-
out its entire course, including the branch to the sternocleido-
The fascia overlying the supraclavicular fat pad is incised, mastoid muscle. The remainder of the neck dissection
and the supraclavicular fat pad is bluntly retracted superiorly proceeds as previously described (see above).
so as to free the tissues from the supraclavicular fossa. If
transverse cervical vessels are encountered, they are clamped selective neck dissection
and ligated as necessary. Fascia is left on the deep muscles of
the neck, which also envelop the brachial plexus and the Levels I to IV
phrenic nerve. In a selective neck dissection, the posterior triangle is not
removed; thus, there is no need to elevate skin flaps posterior
Step 5: Dissection and Removal of Specimen to the sternocleidomastoid muscle. Limited elevation of skin
Attention is then turned to the posterior aspect of the neck. flaps is beneficial, particularly for patients who have previously
Fat and lymphatic tissues are retracted anteriorly with Allis undergone chemoradiation therapy, in whom extensive flap
clamps, and the specimen is dissected off the deep muscles of elevation may contribute to significant persistent lymphedema
the neck with a blade. Again, a layer of fascia is left on the after operation. Subplatysmal skin flaps are raised sufficiently
deep cervical musculature: stripping fascia off the deep cervi- to expose the neck levels to be dissected, with the central com-
cal musculature results in denervation of these muscles, which partment left undisturbed. If level I dissection is planned, the
adds to the morbidity associated with accessory nerve sacri- fascia overlying the submandibular gland is raised and retracted
fice. Once the specimen is mobilized beyond the phrenic so as to preserve the marginal nerve. The submental fat pad
nerve, the cervical nerves (C1–C4) may be divided. The spec- is grasped and mobilized away from the floor of the submental
imen is peeled off the carotid artery and removed. triangle (composed of the anterior belly of the digastric muscle
and the mylohyoid muscle). Inferiorly, the lymphatic tissues
Step 6: Closure are mobilized off the posterior aspect of the omohyoid muscle,
The neck incision is closed in layers over suction drains. which forms the anteroinferior limit of the neck dissection.
01/09
Once the digastric tendon and the posterior edge of the where it inserts on the mastoid tip. The specimen is then
mylohyoid muscle are visualized, the mylohyoid is retracted mobilized away from structures just inferior to the digastric
with an Army-Navy retractor so that the submandibular duct, muscle. The hypoglossal nerve emerges from beneath the
the lingual nerve with its attachment to the submandibular mylohyoid muscle and passes into the neck just below the
gland, and the hypoglossal nerve are visualized. The subman- digastric muscle, looping around the external carotid artery
dibular duct and ganglion are ligated, and the submandibular at the origin of the occipital artery and ascending to the skull
gland is retracted out of the submandibular triangle. base between the external carotid artery and the internal
At this point, the facial artery is encountered and suture- jugular vein. Bleeding from small branches of the common
ligated. Because the artery curves around the submandibular facial vein that envelop the hypoglossal nerve places this
gland, the facial artery, if not preserved, must be ligated twice structure at risk for injury. The spinal accessory nerve is often
(proximally and distally). If the neck dissection is part of a large visualized just superficial or posterior to the internal jugular
extirpative procedure involving free-flap reconstruction, the vein, extending posteriorly to innervate the sternocleidomas-
facial artery is preserved for use in microvascular anastomosis. toid muscle.
The posterior belly of the digastric muscle is then identified Next, the fascia overlying the sternocleidomastoid muscle
inferior to the submandibular gland. This muscle has been is grasped and unrolled medially throughout its length, start-
referred to as one of several “resident’s friends” in the neck ing at the anterior edge of the muscle. The fascia is removed
because it serves to protect several critical structures that lie until the spinal accessory nerve is identified at the point where
just deep to it, including the hypoglossal nerve, the external it penetrates the muscle. This nerve is dissected and mobi-
carotid artery, the internal jugular vein, and the spinal acces- lized superiorly through fat and lymphatic tissues to the
sory nerve [see Figure 4]. The posterior belly of the digastric digastric muscle. Care must be taken not to inadvertently
muscle is skeletonized to the sternocleidomastoid muscle, injure the internal jugular vein, which lies in close proximity
External
Digastric Muscle Mylohyoid Carotid Occipital
(Posterior Belly) Muscle 12th Nerve Artery Artery
Omohyoid Common Internal Sternocleido- 11th Nerve

Muscle Carotid Jugular mastoid
Artery Vein Muscle
Figure 4 Selective neck dissection. The posterior belly of the digastric muscle is identified
inferior to the submandibular gland. This muscle protects several critical structures just deep to
it (the hypoglossal nerve, the carotid artery, the internal jugular vein, and the spinal accessory
nerve). View is of a left neck dissection.
01/09
to the nerve superiorly. Tissue posterior to the accessory and ligation. In these cases, it is acceptable to pack the jugu-
nerve is grasped and freed from the deep muscles of the neck, lar foramen for hemostasis.
the digastric muscle superiorly, and the sternocleidomastoid It is important to gain distal control of the internal jugu-
muscle posteriorly. The tissue included in so-called level IIb lar vein before repair to prevent air embolism. Harbingers
is passed beneath the spinal accessory nerve and incorporated of air embolism include the presence of a sucking sound in
into the main specimen. the neck, a mill-wheel murmur over the precordium, elec-
The sternocleidomastoid muscle is retracted, and the trocardiographic changes, and hypotension. Predisposing
fascia posterior to the internal jugular vein is incised. Dissec- factors include elevation of the head of the bed and spon-
tion is carried down to the deep cervical musculature and taneous breathing, which increase negative intrathoracic
cervical nerves, which form the floor of the dissection. The pressure and thus promote entry of air into the venous
specimen is retracted anteriorly. A layer of fascia is left on system. Injury to the internal jugular vein is more difficult
the deep cervical musculature and the cervical nerves to pre- to control when it occurs distally in the neck or chest at the
serve innervation of the deep muscles of the neck and protect junction with the subclavian vein. For this reason, ligation
the phrenic nerve as it courses over the anterior scalene of the internal jugular vein in radical and modified radical
muscle. neck dissection is typically performed 1 cm superior to the
The specimen is peeled off the internal jugular vein and clavicle.
removed. Dissection too far posteriorly behind the vein may Opalescent or clear fluid in the inferior neck suggests the
result in injury to the vagus nerve or the sympathetic trunk presence of a chyle fistula. Chyle fistulae generally can be
and predisposes to postoperative thrombosis of the vein. prevented by clamping and ligating the lymphatic pedicle at
Ligation of internal jugular vein branches should be done the base of the neck. Those fistulae that occur are repaired
without affecting the caliber of the vein or giving the vessel at the time of the neck dissection. There is no benefit in
a “sausage link” appearance, which would create turbulent isolating individual lymphatic vessels, because these struc-
flow patterns predisposing to thrombosis. Overall, gentle dis- tures are fragile, do not hold stitches, and are prone to tear-
section around all vessels, with care taken to avoid pulling- ing. A figure-eight stitch is placed along the lymphatic
related trauma, minimizes the risk of endothelial injury. pedicle until there is no evidence of clear or turbid fluid on
A level IV dissection may be facilitated by retracting the omo- the Valsalva maneuver. Care must be taken not to inadver-
hyoid muscle inferiorly or by dividing it for additional exposure. tently injure the vagus nerve or the phrenic nerve during
The tissue inferior to the omohyoid is mobilized and delivered repair of a chyle leak.
with the main specimen. The lymphatic pedicle is clamped and
ligated. Care is taken to look for leakage of chyle, particularly postoperative
when a level IV dissection is performed on the left. The best treatment of postoperative complications such as
hematoma and chyle leak is prevention. Hematomas, once
Levels II to IV present, are best managed by promptly returning the patient to
When level I is spared, a smaller incision suffices for exposure. the operating room for evacuation. Management of postopera-
Subplatysmal flaps are raised superiorly to the level of the tive leakage of chyle depends on the volume of the leak. Low-
submandibular gland. The inferior flap is raised, exposing the volume leaks may be managed with packing, wound care, and
anterior edge of the sternocleidomastoid muscle. Dissection nutritional supplementation with medium-chain triglycerides.
proceeds just inferior to the submandibular gland until the Wound complications (e.g., infection, flap necrosis, and
posterior belly of the digastric muscle is identified. The digas- carotid artery exposure or rupture) share certain interrelated
tric muscle is skeletonized posteriorly to the sternocleidomas- causative factors. Poor nutritional status, advanced tumor
toid muscle and anteriorly to the omohyoid muscle, which stage at presentation, hypothyroidism, and preoperative radi-
forms the anterior limit of the dissection. The rest of the neck ation therapy have all been associated with wound complica-
dissection proceeds as described for a selective neck dissections. After chemoradiation therapy, the use of smaller
tion involving levels I through IV. incisions and more limited dissection of soft tissues may lower
the incidence of postoperative wound problems, including
persistent lymphedema and soft tissue fibrosis. Conversely,
Complications poor planning of skin incisions may increase the likelihood of
wound complications such as wound breakdown, skin flap
intraoperative loss, and exposure of vital structures. Wound complications
Most intraoperative complications may be prevented by predispose to carotid artery rupture, the most catastrophic
means of careful surgical technique, coupled with a thorough complication of neck dissection.
understanding of head and neck anatomy. Injury to the inter- In some cases, severe edema after planned neck dissections
nal jugular vein may occur either proximally or distally. in patients previously treated with chemoradiation may cause
Uncontrolled proximal bleeding endangers adjacent critical respiratory decompensation that necessitates tracheotomy.
structures, such as the carotid artery and the hypoglossal Postoperative internal jugular vein thrombosis is not uncom-
nerve. The bleeding may be initially controlled with pressure, mon despite preservation at the time of surgery,28 and it may
followed by a methodical search for the bleeding source. exacerbate facial and upper airway edema. Impaired venous
Internal jugular vein lacerations can often be repaired with outflow predisposes to increased intracranial pressure.29 This
5-0 nylon sutures; if a laceration cannot be repaired, the vein may be a greater concern in patients who require bilateral
must be ligated. Occasionally, a laceration extends up to the neck dissections. If a radical neck dissection is performed on
skull base, and the vessel cannot be controlled with clamping one side, the internal jugular vein must be preserved on the
01/09
other, or else the neck dissections must be staged. These Shoulder dysfunction and pain are exacerbated when nerves
problems are further exacerbated when the patient has under- supplying the deep muscles of the neck are also sacrificed.
gone chemoradiation therapy before operation. All patients benefit from physical therapy, which preserves
Most neck dissections result in some degree of temporary full range of motion in the shoulder while function
shoulder dysfunction. Patients in whom nerve-sparing pro- returns.
cedures are performed can expect function to return within
3 weeks to 1 year, depending on the procedure performed. Financial Disclosures: None Reported
References
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Acknowledgment
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2004;350:1945. Head Neck Surg 2002;128:1180. Figures 1 through 3 Tom Moore.
01/09
2 HEAD AND NECK 8 TRACHEOSTOMY — 1
8 TRACHEOSTOMY
H. David Reines, MD, FACS, and Elizabeth Franco, MD, MPH&TM
History oral intubation is unsuccessful. When an attempt at oral

The word tracheotomy first appeared in Libri Chirgurae 12, intubation fails and ventilation is a problem, immediate cri-
published in 1649, but it was not until Laurence Heruter, cothyroidotomy should be performed. A semielective surgical
a German surgeon, reintroduced it that it became part of airway should be undertaken in a patient whose injuries may
modern medicine. It was initially performed as a lifesaving result in progressive laryngeal and cervical soft tissue edema
procedure to establish an airway. Alexander the Great is prior to decompensation from respiratory distress. Patients
reported to have used his sword to open the trachea of a with a Glasgow Coma Scale (GCS) less than or equal to
8 cannot protect their airway, and intubation should be
suffocating soldier. The term tracheotomy is defined as a surgi-
performed immediately. If this is not possible, then a surgical
cal creation of an opening in the anterior trachea that can be
airway should be considered prior to transporting the
reversible and temporary, whereas, technically, tracheostomy is
patient.
the formation of an opening into the trachea by suturing the
edges of the opening to the skin of the neck. However, over
the years, the two terms have been used interchangeably. For Early Tracheostomy
this document, we use the term tracheostomy to describe the
If the patient is ventilator dependent or has severe head
procedure.
injury and will need prolonged airway protection, early
tracheostomy should be considered when intracranial pres-
Indications sure is not elevated. Early tracheostomy is defined as occur-
ring at or before 7 days, whereas late tracheostomy occurs
The indication for a tracheostomy has changed over the
after 7 days. Early tracheostomy has been associated with
years. Originally, it was conceived as a method to obtain an
decreased incidence of ventilator-associated pneumonia,
airway for obstruction from infections, neoplasm, or trauma.
decreased days of mechanical ventilation, decreased hospital
The most common indications for modern tracheostomy
stay, decreased intensive care unit (ICU) length of stay,
are prolonged ventilation for respiratory failure and airway
and increased patient comfort. Although no study has dem-
protection following traumatic brain injury with neurologic
onstrated a decrease in overall mortality with early tracheos-
dysfunction.
tomy, tracheostomy does provide easier access for suctioning
Patients requiring tracheostomy or cricothyroidotomy fall
and allows patients to be liberated from the ventilator without
into four categories:
the loss of an airway.
1. Emergency for airway control, that is, airway obstruction
from the epiglottis, foreign-body aspiration, laryngeal
trauma, or maxillofacial trauma Pertinent Anatomy
2. Semielective for patients requiring prolonged intubation or The trachea lies relatively superficially in the anterior
mechanical ventilation for respiratory failure or high spinal neck covered by the strap muscles midline and the platysma.
cord injury The first tracheal ring is just below the cricothyroid, whereas
3. Elective for airway protection, that is, traumatic brain the next three rings may lie beneath the thyroid isthmus. The
injury, stroke, sleep apnea, or vocal cord problems sixth through seventh rings lie low in the neck and into
4. Elective for long-term airway access. Permanent tracheos- the sternal notch [see Figure 1]. When performing a tracheos-
tomies are used to maintain airway access when patients tomy, knowledge of the normal and potentially abnormal
undergo major head or neck dissection for tumors of the vasculature is imperative. Care must be taken with a horizon-
larynx and the base of the tongue. tal incision to avoid bleeding from injury to the anterior
jugular vein. Other potential causes of hemorrhage may arise
Patients who arrive with either acute airway compromise from injury to a high-riding innominate artery, a medially
from neck trauma or facial burns should first undergo an placed carotid artery, and the thyroid ima vessels in the
attempt at oral intubation, and if this fails, an emergent surgi- midline. Tumors, hematoma, and edema can cause tracheal
cal airway is required. deviation from midline. Other anatomic variants should
Laryngoscopy should be attempted prior to performing also be considered. An obese patient may require deeper
surgical airway. If a patient arrives talking, but there is dissection, longer instruments, and the use of an extra-long
evidence of hoarseness with increasing airway compromise, tracheostomy tube. The length of the neck and the distance
the surgeon should be prepared for a surgical airway if from the jaw to the thyroid cartilage should also be examined.
Patients with a known or potential neck injury or with kypho-
* The authors and editors gratefully acknowledge the contribu- sis must be positioned without extension. Access to the
tions of the previous author, Ara A. Chalian, MD, FACS, to trachea may be compromised, and plans for dissecting the
the development and writing of this chapter. thyroid isthmus should be considered.
Indicates the text is tied to a SCORE learning objective. Please see the
HTML version online at www.acssurgery.com. DOI 10.2310/7800.S02C08
04/10
more ergonomically difficult than in the operating room

(OR) because the patient is on a hospital bed; however,
finding OR time and transporting the patient may be incon-
venient. Several studies comparing bedside open to percuta-
neous tracheostomies find the techniques to be essentially
equivalent in outcome with the open technique and possibly
lower in cost. Percutaneous tracheostomy is most commonly
performed at the bedside, in the ICU, and does not require
the same lighting or instrumentation and nursing availability
that an open tracheostomy does. A cricothyroidotomy is
frequently performed in the trauma bay, although it may be
executed anywhere and requires the least amount of instru-
mentation. Emergency tracheostomy and cricothyroidotomy
are frequently not performed in the OR.
Anesthesia
Anesthesia can frequently be given as conscious sedation
and/or local anesthesia with epinephrine. Paralysis should be
avoided when possible in a patient with any spontaneous
breathing.
Patient Positioning
Extension of the neck is desirable; however, if the patient
has a known or potential cervical spine injury, operation in
Figure 1 Surgical tracheostomy. A transverse cutaneous the neutral position is necessary. When possible, the patient
incision is made that is approximately 2 to 3 cm long (or as should be placed on an operating table with a shoulder roll
long as is necessary for adequate exposure). The extent of flap and a foam pad (donut) under the head. When the neck can
elevation may be 1 cm or less.
be extended, the head rest of the surgical bed can be lowered
and the patient placed in a 30° head elevation position to
decrease venous pressure. Extending the head allows better
palpation of the landmarks. If cervical spine precautions are
Physiology
necessary, the posterior portion of the cervical collar should
When undergoing a tracheostomy, ideally, the patient remain in place and the head stabilized by a team member.
should be adequately ventilated and hyperoxygenated in Another alternative is to stabilize the neck with bilateral head
anticipation of a period of apnea during tracheostomy tube rolls with tape over the forehead and chin extending across
placement. An oxygen saturation of 100% and a normal the bed.
pH and carbon dioxide tension (PCO2) are desirable at the
start of an elective tracheostomy. Use of 100% oxygen during
the procedure will help maintain adequate oxygenation Operative Techniques
throughout the procedure. When an emergency cricothyroid- emergent surgical airway
otomy or tracheostomy is necessary, an attempt should be
made to preoxygenate and ventilate. Cricothyroidotomy
Cricothyroidotomy is generally performed for emergent
control of the airway. Inability to secure an airway, especially
Counseling and Informed Consent
with severe facial trauma, requires immediate access to the
The patient, the family, or both should be advised of the trachea. A cricothyroidotomy can be performed rapidly and
risks and benefits of a tracheostomy. Commonly discussed does not risk the anatomic problems of a tracheostomy
issues, including pain, mortality, and the range of possibilities because the cricothyroid membrane is thin and closest to
of early and late complications (see below), should be on the skin directly under the thyroid membrane If a #5 or #6
the consent form. A tracheostomy should be proposed as the tracheostomy tube is not available, an endotracheal tube can
best option for the patient requiring prolonged mechanical be introduced for immediate airway access.
ventilation or airway protection. Tracheostomy contributes to
patient comfort, allowing improved oral care, oral alimenta- Transtracheal Needle Ventilation and Oxygenation
tion, and speaking as well as the potential for earlier liberation Transtracheal needle access also can be used in emergency
from the ventilator. situations. A large-bore 12- or 14 gauge angiocatheter or a
pulmonary artery catheter introducer sheath is placed through
the cricoid membrane and attached to oxygen tubing with
Site of the Procedure the capability of providing oxygen at 50 psi. A hole in the
Elective open tracheostomy requires good lighting and tubing is finger-occluded and intermittently opened to allow
electrocautery. Some may find open tracheostomy in the ICU for ventilation. Adequate ventilation can be provided for
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20 to 30 minutes. This method is best used as a bridge dissecting caudally are helpful. Care must be taken, espe-
while awaiting the proper equipment and support for an cially in women, to palpate the thyroid and not the hyoid
orotracheal or surgical airway. cartilage [see Figure 3].
3. Dissection of the thyroid gland. The thyroid isthmus fre-
open tracheostomy
quently lies in the field of dissection. Because its size and
Steps thickness vary greatly and can vary from 5 to 10 mm in
1. Incision of the skin. The patient should be assessed for a vertical dimension, dissection of this can be undertaken,
high-riding innominate artery, abnormally placed vessels, and, in many cases, immobilizing the trachea and retract-
and tracheal deviation. Incision can be made either verti- ing the isthmus either superiorly or inferiorly to place the
cally or horizontally. The horizontal scar heals better tracheal incision in the second or third tracheal interspace
than the vertical scar. However, visualization, especially can be accomplished [see Figure 4]. However, if the isth-
if the neck cannot be extended, is frequently easier in a mus is a problem, especially in cases where the neck cannot
vertical incision. Damage to the anterior jugular veins like- be extended, it can be divided and the edges ligated either
wise is less likely with a vertical incision. In an emergency, with ties or with a Harmonic scalpel. When there is an
a longer vertical incision can facilitate exposure while isthmus nodule, the isthmus should be removed for diag-
avoiding the subplatysmal anterior jugular veins [see nostic and therapeutic purposes. Recurrent laryngeal
Figure 2]. In general, the incision should be made midway nerves should not be directly in the operative field and are
between the cricoid cartilage and the sternal notch. rarely at risk as long as one stays in the midline anterior on
The size of the incision is up to the individual surgeon.
the trachea. If significant deviation of the trachea is noted,
However, a minimum of 2 to 2.5 cm is desirable.
the nerves may be injured. Because the blood supply to the
Subsequent dissection must be performed perpendicular
trachea is laterally based, one should not encounter them.
to the trachea. A common mistake when dividing the sub-
cutaneous tissue is to deflect in a slightly oblique fashion, However, a thyroid ima vessel is frequently noted in the
arriving lower in the trachea than anticipated. lower portion of the isthmus, and this may need to be
2. Retracting the strap muscles. The midline raphe is divided ligated prior to dissection.
and an assistant with Senn or Army-Navy retractors 4. Incision of the trachea. Tracheostomy should be performed
or with a self-retraining retractor then retracts the strap with a sharp blade. The pretracheal tissues may be
muscles laterally. Undermining should be minimized to coagulated with a bipolar electrocautery. The opening of
decrease the potential creation of dead-space areas. In the airway may bring volatile gasses into the operative
the case of a malignant neoplasm overlying the thyroid field; therefore, monopolar electrocautery should be
compartment, the anatomic landmarks may be less clear. avoided if volatile gasses are in use. Several types of
In such a case, palpation of the thyroid cartilage and incisions are possible:
Figure 3 Surgical tracheostomy. With the strap muscles

retracted, the thyroid isthmus is visualized, and the inferior
Figure 2 Surgical tracheostomy. Retractors are placed, the (or superior) edge of the isthmus is dissected down to the
skin is retracted, and the strap muscles are visualized in the trachea. The isthmus is then retracted superiorly (or inferi-
midline. The muscles are divided along the raphe and then orly) or divided to permit visualization of the trachea before
retracted laterally. the tracheal incision is made.
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b. T-type incision. This incision is a combination of a

vertical incision that crosses the second ring and forms
a “T” with a transverse incision below the third
tracheal ring. Stay sutures are placed laterally and
allow for controlled opening of the trachea with a
tracheostomy spreader.
c. Tracheal window. Although a tracheal window with
removal of a portion of the third tracheal ring has been
performed, this is more difficult and may not heal as
rapidly as a ring-preserving incision.
d. Björk flap. A Björk flap is an inferiorly based U-shaped
flap that incorporates the ring below and the tracheal
incision [see Figure 4]. A U-type incision is made from
the third tracheal ring through the second tracheal ring,
and the second tracheal ring is then retracted inferiorly
and sutured with a dissolvable suture as high in the
neck as possible to the skin. The theoretical justifica-
tion for this is to keep the tracheal incision close to
the skin edges in the instance of tracheostomy tube
displacement, to ensure ease of airway access. This
flap suture can be released 3 to 5 days after creation
once the tract has been established or after the first
Figure 4 Surgical tracheostomy. A tracheotomy is made tracheostomy change.
either between the second and third tracheal rings or between 5. Stay sutures. Stay sutures using a 2-0 nonabsorbable suture
the third and fourth rings. A Björk flap (inset) may be created on a UR6 needle can be placed either laterally or inferiorly
by extending the ends of the tracheostomy downward through and superiorly. These help stabilize the tracheostomy
the next lower tracheal ring in an inverted U shape. during the procedure. The sutures are then taped to the
chest and labeled so that they will not be inadvertently
removed. Stay sutures may provide access to a fresh
a. Linear incision. This transverse incision is made either tracheostomy if the tracheostomy tube becomes dislodged
between the second and third rings or the third and in the immediate postoperative period. These sutures are
fourth rings. Stay sutures are then placed superiorly left in place until the first tube change.
and inferiorly around the tracheal rings [see Figure 5].
In adults, a number 8(outside diameter [OD]) or 6(OD)
tube is preferable. If there is significant edema or obesity, the
use of an extra-long tube is desirable. If a tracheostomy tube
is not available, a standard endotracheal tube can be used to
intubate the neck. Remember when trimming the tube to
spare the pilot balloon.
percutaneous tracheostomy
Percutaneous tracheostomy was first described over 50
years ago, but the availability of a dilational percutaneous
tracheostomy kit prompted widespread use in the 1990s.
In many centers, this has become the method of choice
for tracheostomy. Although initial contraindications included
morbid obesity, inability to extend the neck as in potential
cervical spine injuries, short neck, enlarged thyroid isthmus,
and previous tracheostomy, these have been disproven with
increasing experience. A benefit of the percutaneous approach
is the ability to perform the procedure at bedside in the
ICU, reducing OR costs and scheduling conflicts. The
percutaneous approach has been championed for its ease
of performance at the bedside in the ICU; however, several
studies comparing cost and personnel use demonstrate
open bedside tracheostomy to be more cost-effective with
equivalent complications and safety outcomes. The long-term
Figure 5 Surgical tracheostomy. The tracheostomy tube is cosmetic effects of percutaneous tracheostomy appear to be
inserted into the tracheal opening from the side, with the better than those of the open technique.
faceplate rotated 90° so that the tube’s entry into the airway The choice between percutaneous and open tracheostomy
can be well visualized. remains a decision best left to individual centers.
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Operative Technique tracheostomy collar or tracheostomy tube. A tracheostomy

Equipment and personnel The personnel necessary collar allows more patient freedom and less torque than a T
for the procedure are a respiratory therapist, a critical care tube when frequent suctioning is not required. Speech
nurse, a surgeon, and a bronchoscopist to safely perform a pathology consultation should be obtained for swallowing
percutaneous tracheostomy. The equipment required is a evaluation and speaking valve placement versus capping the
bronchoscope and a percutaneous dilation tracheostomy kit. tracheostomy tube. The approach depends on the patient’s
Surgical instruments for an open tracheostomy should be mental status and suctioning requirements. Once the patient
is tolerating either tracheostomy tube occlusion or a speaking
readily available. Maximum sterile barriers are employed,
valve for greater than 24 hours and managing his or her
including sterile gown, gloves, and drapes. All participating
own secretions, the tracheostomy is removed. In preparation
personnel must wear mask and head covers.
for decannulation, the patient should be suctioned and a
replacement tracheostomy with a stylet should be available
Procedure
in case of sudden respiratory decompensation. An occlusive
1. Incision. Once conscious sedation is initiated, the sub-
dressing is left in place for 24 hours. Generally, no further
cutaneous tissue is infiltrated with local anesthetic 1 cm dressing is required afterward.
caudal to the cricoid cartilage. A 1 to 1.5 cm incision is
made either in a horizontal or a vertical fashion. The sub-
cutaneous tissue is then bluntly dissected using a hemostat Complications
to spread the tissue down to the level of the trachea. Reported complication rates from tracheostomy range
2. Bronchoscopy. The bronchoscope is advanced to the tip from 5 to 31%, with an average of nearly 12%. Major com-
of the endotracheal tube. With the surgeon providing plications range from 2 to 6%. Mortality is extremely low
one-finger ballottement at the level of the first or second (0.5%).
tracheal ring, the endotracheal tube is slowly withdrawn
while maintaining the bronchoscope at the tip of the tube early complications
until one-to-one ballottement is appreciated. Every step Displacement
of the procedure involving instrumentation of the trachea
The most dangerous complication is early accidental
is preferably performed under direct bronchoscopic
displacement or decannulation. This can occur when moving
visualization.
the patient to the ICU or recovery room and when patients
3. Transcutaneous tracheostomy. The introducer needle is
are turned for care or x-rays in the ICU in the first 5 to 7 days
advanced through the incision at the level where one- after placement. A loosely tied tracheostomy or one placed
to-one ballottement was appreciated. Constant aspiration in a precarious position can be dislodged, resulting in the
of the syringe and direct bronchoscopic visualization inability to ventilate and oxygenate. If this is suspected, the
immediately identify the entrance into the trachea. Once patient should immediately be placed supine and an attempt
the needle is noted to be in a good position, the guide at ventilation should commence. If the patient cannot be
wire is introduced again under direct bronchoscopic ventilated, an attempt to replace the tube should be tried
visualization. if stay sutures or a Björk flap is present. Emergency oral intu-
4. Dilation. Using a modified Seldinger technique, the needle bation should be performed if the attempt fails. Multiple
is removed and a stiff conical dilator is introduced and attempts to replace the tube can result in a false passage. The
removed. The tract is then dilated with the largest conical tracheostomy can then later be replaced via the same incision
dilator to the level marked for the skin. The dilator is with the proper light and proper retraction. A new tracheos-
removed and fully introduced three times. The tracheostomy tube should be available in the room or above the bed
tomy tube is then introduced over the snuggest fitting for all patients who have had a fresh tracheostomy.
dilator. Once the tracheostomy tube is in place, the guide
wire and dilator are removed. Often the endotracheal Pneumomediastinum/Pneumothorax
tube must be withdrawn a short distance to allow for serial Pneumomediastinum can occur, especially with a low
dilation and introduction of the tracheostomy tube. tracheostomy or if a false passage is created. Pneumothorax
5. Confirmation of placement. Once the tracheostomy tube is is a rare (< 2%) complication that can occur especially in
in place, the bronchoscope is withdrawn from the endotra- children, in whom the cupola of the lung may ride high.
cheal tube and introduced through the tracheostomy tube Pneumothorax can also occur in patients who require high
to confirm placement within the trachea. The endotracheal ventilatory pressures or who cough vigorously during the pro-
tube is kept in place until confirmation is complete. The cedure. A low tracheostomy and deep dissection potentially
tracheostomy tube is then secured with sutures from the increase the risk of pneumothorax.
faceplate to the skin and tied in place.
Bleeding
A small amount of blood via the wound or tracheostomy
Tracheostomy Management
immediately following the procedure is not alarming. How-
Tracheal sutures are removed on postoperative day 7. If ever, the persistence of blood around the trachea implies
the patient is on minimal ventilator settings or liberated from venous bleeding from either the skin, subcutaneous tissues,
the ventilator, the tracheostomy tube is downsized. Once or thyroid gland. In general, this can be controlled with gentle
the patient is liberated from the ventilator, the tracheostomy packing and the use of a bioabsorbable hemostatic agent.
tube cuff is deflated and the patient is placed on humidified If bleeding continues, the patient should be taken to the OR
air or oxygen. The humidified air can be delivered via a if possible and reintubated under ideal light and retraction;
04/10
the tracheostomy should be removed and the bleeding con- Tracheal Granulation
trolled with cautery or sutures if necessary. If hemorrhage Tracheal granulation may cause bleeding or occlusion
is demonstrated via the tracheostomy tube, early careful of the tracheostomy tube if a flap of granulation tissue is
bronchoscopy should be performed to ascertain the site of
elevated on exhalation. Granulation tissue may mimic tra-
bleeding. Significant bleeding from the tracheostomy is
cheal stenosis. This complication is often easily treatable with
usually a late complication and may be related to a
removal of the tracheostomy tube. Occasionally, resection of
tracheoinnominate fistula (see below).
the granulation tissue is necessary.
Infection
Vocal Cord Dysfunction
Tracheostomy infections requiring treatment are much
less common than one would imagine, considering the con- Vocal cord dysfunction occurs in less than 2%, whereas
tamination of the bronchial/tracheal tree in many patients voice changes, including hoarseness and weakness, occur in
who have been intubated for a period of time. The majority 10 to 20% of patients. In cases of bilateral vocal cord paraly-
of infections can be treated with local wound care, although sis, a tracheostomy is necessary until the paralysis resolves.
deep infections from Staphylococcus aureus and Pseudomonas Most complaints of vocal changes are considered minor by
aerigunosa may require antibiotics and removal of sutures. patients.
Placing tracheostomies through burn eschar presents a
separate problem. Tracheoesophageal Fistula
Tracheoesophageal fistula occurs in less than 0.3% of
Acute Obstruction patients following tracheostomy. It can occur if a puncture
The most common cause for acute obstruction of a trache- is made into the posterior trachea or a cuff erodes into
ostomy is dislodgment. If that is not the case, the tracheos- the esophagus. The combination of a a tracheostomy tube
tomy may have accumulated blood or mucus, which can clog and a stiff nasogastric tube in the esophagus increases the risk
the airways. To avoid this, humidified oxygen should always of this complication. Symptoms include aspiration and
be administered, and gentle careful suctioning should be persistent cuff leak around the tracheostomy. Persistent tra-
initiated by experienced personnel. The inner cannula should cheobronchitis or pneumonia may also be present. A swallow
be removed and examined. Occasionally, bronchoscopy will
study with the cuff deflated or CT and panendoscopy
be necessary to remove and irrigate mucus plugs.
will demonstrate the defect. Definitive therapy is usually
Negative Pressure Pulmonary Edema necessary.
A rare complication of upper airway obstruction may occur Tracheoinnominate Fistula
after a tracheostomy is performed for airway obstruction.
Patients generating large negative pressure against resistance, Tracheoinnominate fistula has a reported incidence of
which is suddenly released, can experience a noncardiogenic 0.4 to 4.5% and presents initially as “sentinel bleeding” that
pulmonary edema. The patient becomes hypoxic, develops usually develops within the first month following the proce-
rales in the lungs, and can demonstrate pink frothy pulmo- dure. Mortality between 50 and 75% has been reported. Risk
nary edema via the tube. A chest x-ray may demonstrate factors include a low (below the third ring) tracheostomy,
bilateral pulmonary edema. This process is usually self- caudal migration from leverage on the tube, and the presence
limited and responds to positive end-expiratory pressure of a more cephalad-coursing innominate artery. An attempt
(PEEP) and positive pressure ventilation. to visualize the site of bleeding should be undertaken. If
hemorrhage is significant, hyperinflate the cuff and try to
late complications
compress the vessel against the posterior sternum. If this
Late complications of tracheostomy are often attributable is unsuccessful, oral intubation should be performed. The
to the cuff, either from the tracheostomy tube or from the tracheostomy tube must be removed and replaced with
endotracheal tube in place prior to tracheostomy. Complica- digital pressure through the tracheostomy to tamponade the
tions attributable to cuff injuries are less common now than bleeding en route to the OR. Often the upper extremity of
previously as a result of improvement in technology allowing the person responsible for maintaining digital pressure is
for lower-pressure cuffs, but they still occur in patients who prepared into the operative field in preparation for median
undergo prolonged endotracheal intubation.
sternotomy
Tracheostomy cuff pressures should be measured daily
or more often to prevent tracheal necrosis. X-rays demon- Tracheocutaneous Fistula
strating a dilated cuff in the trachea require assessment of the
Rarely, the tracheostomy wound does not completely close
tube, cuff, and trachea.
in 24 to 48 hours. Granulation tissue may be treated topically
Subglottic Tracheal Stenosis with silver nitrate with good success. Occasionally, the
Tracheal stenosis has a reported incidence of 4 to 18%. tracheostomy site must be surgically closed in layers for a
Stenosis is associated with a longer hospital stay and pro- nonhealing tracheocutaneous fistula.
longed time to tracheostomy. Dyspnea and stridor result
Scar
when tracheal stenosis is greater than 50% of tracheal diam-
eter. In suspected tracheal stenosis, referral to a specialist for Cosmetic results vary following tracheostomy. Ten to 15%
evaluation either by computed tomography (CT) or rigid of patients consider scar revision of the tracheostomy site.
laryngoscopy is essential for diagnosis. Once the diagnosis is
confirmed, treatment may require tracheal reconstruction. Financial Disclosures: None Reported.
04/10
Additional Reading
American College of Surgeons Committee on Grover A, Robbins J, Bendick P, et al. Open ver- patients. Cochrane Database and Systematic
Trauma. Airway and ventilatory manage- sus percutaneous dilatational tracheostomy: Reviews 2009;(4).
ment. In: Advanced trauma life support for efficacy and cost analysis. Am Surg 2001;67: Silvester W, Goldsmith D, Uchino S, et al.
doctors, student edition. Chicago, IL: Ameri- 297–302. Percutaneous versus surgical tracheostomy:
can College of Surgeons; 2008. p. 25–53. Marx WH, Ciaglia P, Graniero KD. Some a randomized controlled study with long
Clec’h C, Albert C, Vincent F, et al. Tracheosto- important details in the technique of percuta- term follow up. Crit Care Med 2006;34:
my does not improve the outcome of patients,
neous dilatational tracheostomy via the 2145–52.
requiring prolonged mechanical ventilation: a
propensity analysis. Crit Care Med 2007;35: modified Sledinger technique. Chest 1996;
135–8. 110:762–6.
Griffiths J, Barber VS, Morgan L, Young JD. Pratt LW, Ferlito A, Rinaldo A. Tracheostomy.
Systematic review and meta-analysis of Historical review. Laryngoscope 2008;1188:
1597–606.
Acknowledgments
studies of the timing of tracheostomy in adult
patients undergoing artificial ventilation. Silva B, Andriolo R, Saconato H, Atalla A. Early
BMJ 2005;330(7500):1243–50. versus late tracheostomy for critically ill Figures 1 through 5 Thom Graves
04/10
2 HEAD AND NECK 9 THYROID DISEASES — 1
9 THYROID DISEASES
Karen R. Borman, MD, FACS, and Jennifer L. Rabaglia, MD*
Approach to the Patient with Thyroid Disease Table 1 Etiologies of Hyperthyroidism

The thyroid plays a central role in normal metabolic and Disease Predominant Treatment
homeostatic processes, including thermomodulation, protein
synthesis, carbohydrate and lipid metabolism, and modula- Iodine induced (jodbasedow) Medical
tion of adrenergic activity. A normal thyroid weighs 15 to Subacute thyroiditis Medical
25 g and is firm, mobile, and smooth to palpation. The (de Quervain)
thyroid contains two distinct, physiologically active cell types. Chronic lymphocytic thyroiditis Medical (surgical for
Follicular cells are responsible for thyroid hormone synthesis, (Hashimoto thyroiditis) compressive symptoms)
whereas parafollicular or C cells produce calcitonin. Patients Postpartum thyroiditis Medical
are most often referred to the surgeon for control of hyper-
Drug induced (e.g., Medical (rarely surgical)
thyroidism or for treatment of euthyroid nodular disease. amiodarone)
approach to the Struma ovarii Surgical (resect ovarian
patient with teratoma)
hyperthyroidism Graves disease Medical or surgical
The symptoms of thy- Toxic nodular goiter (Plummer Surgical or medical
roid hormone overpro- disease)
duction are numerous Solitary hyperfunctioning Surgical; rarely medical
and often nonspecific, nodule
including palpitations,
heat intolerance, weight changes (gain or loss), increased clinical evaluation
appetite, poor concentration, decreased libido, and irregular
menses. The diagnosis of hyperthyroidism is definitively History and Physical Examination
established by thyroid function testing (TFT); thyroid-stimu- A thorough history may raise considerations of thyroiditis
lating hormone measurement (TSH, thyrotropin) is the single (e.g., amiodarone, pregnancy, iodinated contrast agents) and
most useful test. TSH normally ranges between 0.3 and 3.0 lead to reconsideration of nonsurgical management. Previous
mU/L; values less than 0.3 indicate hyperthyroidism (excess or ongoing treatment with thyroxine or antithyroid medica-
thyroid hormone causing decreased TSH secretion), and tions (ATMs) is noteworthy, along with review of recent
values > 3.0 suggest hypofunction (low levels of circulating TFT results. Factors that could influence treatment choices
thyroid hormone stimulating increased TSH secretion). Free (e.g., iodine allergy, comorbid diseases) should be identified.
thyroxine (T4) and triiodothyronine (T3) levels can provide Adrenergic symptoms (e.g., palpitations, tremor) are valuable
further confirmation. Total T4 and T3 levels are influenced by in assessing antithyroid treatment response and readiness for
serum protein derangements and must be interpreted with operation. Compression symptoms (dysphagia, nocturnal
caution. Thyroglobulin (Tg) and calcitonin determinations dyspnea) are more likely with TNG than Graves disease or
are not useful for diagnosing hyperthyroidism. solitary toxic nodule (STN). Dysphonia is extremely rare
with benign disease and should be definitively evaluated
differential diagnosis before thyroidectomy is recommended.
Potential etiologies for hyperthyroidism are numerous, Examination of the thyroid begins with observation of the
but relatively few lead to surgical referrals. Thyroidectomy as neck for goiter, including size and symmetry. Palpation may
a treatment option is largely confined to three entities: diffuse discriminate the smooth, soft, diffuse Graves gland from the
toxic goiter (Graves disease), toxic nodular goiter (TNG; firm, multinodular toxic goiter or the STN. Tenderness to
Plummer disease), and solitary hyperfunctioning nodule. palpation is most consistent with thyroiditis, as is bilateral
Other forms of hyperthyroidism most often respond to med- lymphadenopathy. Unilateral, hard, or fixed cervical or supra-
ical management and/or withdrawal of the inciting agent clavicular adenopathy should prompt evaluation as outlined
(e.g., amiodarone) while the underlying thyroiditis resolves below for euthyroid nodular disease. Substernal extension of
[see Table 1]. the goiter and cervical tracheal deviation should be noted
when present. A solitary or dominant nodule should be
characterized as to its location, size, and mobility. Physical
* The authors and editors gratefully acknowledge the contribu- examination should also focus on other signs of hyperthyroid-
tions of the previous authors of “Thyroid and Parathyroid ism, including Graves ophthalmopathy (lid lag, lid retraction,
Operations,” Wen T. Shen, MD, Gregg H. Jossart, MD, proptosis, exophthalmos) and adrenergic excess (tachycardia,
FACS, and Orlo H. Clark, MD, FACS, to the development bilateral fine tremor of the hands). General medical status
and writing of this chapter. should be assessed as for any potential preoperative patient.
01/11
I. Patient referred with thyroid disease

Clinical evaluation includes history, physical examination,
clinical and laboratory assessment of thyroid function
I.A Patient is hyperthyroid (TSH < 0.002) II.A. Patient is euthyroid (Go to page 3)
I.A.1 Patient is postpartum

Consider postpartum thyroiditis
Begin antithyroid medications
I.A.2 Patient takes amiodarone
Work with cardiologist to revise

medications
I.A.3 Patient has smooth goiter

without nodules I.B.1 Graves Disease
Consider Graves disease Diffuse homogeneous uptake
Measure antibodies
I.B.2 Solitary
I.A.4 Patient has thyroid nodule(s) I.B Radionuclide scan 123
I Hyperfunctioning nodule
I.B.3 Toxic multinodular goiter

Multiple nodules with heterogenous
uptake
I.B.1.a Radioactive iodine
131
I treatment preferred
I.B.1.b Thyroidectomy preferred

I. B.1 Graves Disease Iodine allergy
Pregnancy
Diffuse homogeneous uptake Contraception averse
Exophthalmos
Patient preference
I.B.1.c Long-term antithyroid

medications I.B.2.a.i Nodule > 4 cm
Limited life expectancy Thyroidectomy preferred

I.B.2 Solitary
I.B.2.a.ii Radioactive iodine or
Hyperfunctioning nodule I.B.2.a Measure nodule thyroidectomy
Nodule < 4 cm
Examination ± ultrasonography
Patient preference
I.B.2.a.iii Long-term antithyroid

I.B.3.a. Thyroidectomy preferred medications
Limited life expectancy
I.B.3.b Radioactive iodine 131I
Patient preference
I.B.3 Toxic multinodular goiter
Multiple nodules with heterogenous uptake I.B.3.c. Long-term antithyroid medications
Limited life expectancy
01/11
II.A
Patient is euthyroid
Ultrasonography
II.A.1 Cystic
II.A.2 II.A.3
Multiple nodules Solitary nodule (solid
Aspiration (multinodular goiter) or heterogeneous)
cytology
-
+ FNA
Compressive
symptoms, dominant
Repeat nodule > 4 cm
evaluation
at 6 wks Dominant
+
nodule(s) (> 1 cm and
Recurrence < 4 cm)
Surgery Treat as for solitary nodule
Re-aspiration
× 1, if recurs
again, then
surgery
II.A.3 FNA
II.A.3.g
compatible with Medullary thyroid
II.A.3.a
carcinoma
FNA insufficient for diagnosis
Staging
Repeat FNA Baseline calcitonin measurement
If remains insufficient, treat as indeterminate Screening for MEN 2
(surgery) Thyroidectomy (total) + MRLND
II.A.3.b
FNA is sufficient but indeterminate II.A.3.f
Repeat FNA × 1 Suspicious for follicular neoplasm
If still indeterminate, proceed to
thyroidectomy Thyroidectomy (lobe for diagnosis)
II.A.3.c
FNA is benign
II.A.3.e
Clinical and ultrasound surveillance FNA suspicious for (or compatible with)
Repeat FNA or thyroidectomy for growth or change papillary thyroid carcinoma
Staging
II.A.3.d Thyroidectomy (total)
compatible with Lymphoma
Staging with medical oncologist
Thyroidectomy if localized or if compression symptoms
01/11
Imaging Graves Disease

Thyroid scintigraphy reliably characterizes the hyperthy- Graves disease is the
roid processes most often referred to surgeons and should leading cause of hyper-
precede any other form of imaging. Technetium pertechne- thyroidism in the United
tate (Tc-99m) scanning is rapid and produces sharper images States, comprising about
at lower cost than iodine-123 (123I). 123I scintigraphy is supe- 70% of cases. Women
rior when precise uptake quantification is required (before between the ages of 20
radioactive 131I treatment) or when better bone penetration and 50 years are most
is necessary (substernal goiter).1 Graves disease appears as commonly affected.3 There are three effective, long-term
homogeneous radionuclide uptake. An enlarged, heteroge- treatments for Graves disease: prolonged ATM administra-
neous gland with two or more areas of increased uptake sur- tion, radioactive iodine (RAI), and thyroidectomy. Factors
rounded by areas of normal or decreased uptake is typical of influencing treatment choice include overall patient status
TNG. An STN is confirmed when a single, high-uptake (age, gender, comorbidities, life expectancy); thyroid findings
(“hot”) focus is seen against a suppressed background. Com- (goiter size, dominant nodule, compression symptoms);
puted tomography (CT) and magnetic resonance imaging health care system characteristics (access to physicians,
(MRI) have limited utility in hyperthyroidism other than for medications, and laboratory testing); and patient preference.
assessment of substernal goiters, and iodinated contrast
administration will interfere with any subsequent 131I treat- Prolonged ATM administration Although common in
ment. Once the etiology of the hyperthyroidism is established, Europe and Asia, this treatment is not often chosen in the
treatment options may then be considered. TNG and STN United States, perhaps linked to the rare but potentially life-
are preferentially treated operatively, whereas the algorithm threatening side effect profile of thionamides. This approach
for Graves is a bit more complex; ultrasonography (US) and also requires a prolonged medication trial (12 to 24 months),
fine-needle aspiration (FNA) may be indicated to exclude and patients often find this less palatable when more rapidly
malignancy if nonoperative treatment is chosen. acting treatments with higher success rates are available.
treatment considerations Remission (euthyroidism for at least 1 year posttreatment) is
achieved initially in approximately 50% of cases, but this suc-
Initial Therapy cess rate declines to 30% at 10 years.2,3,5 Negative predictors
Medical management for control of symptoms and signs of remission include large goiter, severe biochemical disease,
of hyperthyroidism precedes surgical treatment. ATMs and high serum ratio of T3 to T4, male gender, multiple relapses,
beta blockers are the most commonly used agents. The and very high TSH receptor antibody titers.2,5 Remissions are
thionamides propylthiouracil (PTU) and methimazole limit more common in adults than in children. Prolonged ATM
thyroid hormone synthesis by disrupting organification of administration should be considered when life expectancy is
iodine. PTU also inhibits peripheral conversion of T4 to the limited. Here methimazole has the advantage of twice-daily
metabolically more active T3. Minor side effects (pruritis, dosing versus PTU, which is given three to four times per
fever, gastrointestinal disturbances, and arthralgia) occur in 5 day. Patients who fail to achieve remission or who relapse can
to 25% of patients receiving thionamides, and agranulocyto- be salvaged with RAI or surgery.
sis affects 0.2 to 0.5% of patients receiving either medica-
tion.2 Rare cases of fulminant hepatic failure and autoimmune Radioactive iodine RAI is the definitive management of
vasculitis have been associated with PTU alone.2–4 Beta block- choice for Graves disease in the United States. Approximately
ers (atenolol, propranolol) may be added to ATM for more 60% of patients are euthyroid within 6 to 8 weeks after a
rapid control of severe adrenergic symptoms when present. single oral dose of 5 to 15 mCi, and nearly all the remaining
Treatment efficacy is monitored by TFTs and clinical evalu- patients become euthyroid within several months.4 Hyperthy-
ation (resolution of tachycardia and tremor). Most patients roidism persists or recurs in 5 to 25% of cases and is dose
are rendered euthyroid within 6 weeks of treatment initiation; dependent. Posttreatment hypofunction is also dose depen-
virtually all are euthyroid at 3 months. PTU is often chosen dent. The risk of hypothyroidism is 20% within the first year
over methimazole during pregnancy as methimazole is more and 3 to 5% per year thereafter. Thus, TFTs must be fol-
apt to cross the placenta and has been linked to fetal scalp lowed lifelong in all patients treated with RAI. Acute adverse
aplasia cutis. reactions are uncommon after RAI administration. Pain
secondary to radiation thyroiditis and nausea are reported
Preoperative Therapy most often. Because RAI treatment can trigger thyrotoxicosis,
Achieving euthyroidism markedly reduces the chance of pretreatment with ATM before RAI administration may be
thyrotoxicosis and thyroid storm intra- or postoperatively. appropriate for patients who are elderly or have concurrent
Preoperative treatment goals include normalization of TFTs, heart disease. An exceedingly rare but more serious complica-
a resting heart rate of 60 to 70 beats per minute, and resolution is hypoparathyroidism, which can be detected promptly
tion of tremor. In Graves disease patients, inorganic iodine by monitoring serum calcium.
administration in the form of Lugol solution (3 to 5 drops RAI may not be the preferred treatment for some sub-
t.i.d.) or saturated solution of potassium iodide (SSKI; 2 to groups of patients with Graves disease. Although little cred-
3 drops t.i.d.) may decrease the size and vascularity of the ible evidence supports a generalized oncogenic effect of RAI,
gland when given for 7 to 10 days immediately preopera- parental concerns about future cancers may prompt a choice
tively. Beta blockade alone supplemented by inorganic iodine for prolonged ATM administration or surgery in Graves
is somewhat less effective but is rarely used in urgent clinical disease in children and adolescents. RAI may exacerbate
circumstances or for patients intolerant of thionamides. eye manifestations in patients with Graves ophthalmopathy,
01/11
particularly in smokers or when hyperthyroidism is severe.6,7 remission. Definitive management of TNG by ATM there-
Concurrent glucocorticoid administration minimizes this fore requires lifelong ATM administration. Because of
risk,6,7 although moderate to severe ophthalmopathy remains rare but sometimes life-threatening adverse reactions to the
a relative contraindication to RAI therapy, and surgery may thionamides, only TNG patients with limited life expectan-
be preferred in cases where eye findings of Graves disease are cies are suitable for primary ATM treatment.
clinically overt. Pregnancy and lactation are absolute contra-
indications to RAI because 131I crosses the placenta and is Radioactive iodine Iodine uptake is lower and less
secreted into breast milk. Women should defer pregnancy for uniform in TNG than in Graves disease, making effective
6 to 12 months after receiving RAI to allow for stabilization RAI dosing less predictable. Substantially higher initial doses
of maternal thyroid function and to prevent transplacental are necessary, and up to 20% of patients require at least one
passage of residual radioisotope and subsequent fetal hypo- additional RAI treatment.2 Thus, patients may experience
thyroidism. RAI therapy is also contraindicated in patients more side effects, including prolonged xerostomia and
who are allergic to iodine. xerophthalmia, oral ulcers, and sialadenitis.13 As with Graves
disease, the time to euthyroidism is prolonged, and the risk
Surgery Surgical intervention provides rapid normaliza- of posttreatment hypothyroidism remains substantial. RAI
tion of thyroid function with the lowest rate of recurrent shrinks the gland in less than half of patients, and radiation
hyperthyroidism while avoiding both the potential risks of thyroiditis may cause serious, symptomatic thyroid edema. As
prolonged ATM administration and the theoretical risk of a result, RAI is particularly unsuited for TNG patients with
ionizing radiation. Surgical treatment is preferred for Graves large or substernal goiters or with pretreatment compression
disease patients with relative or absolute contraindications to symptoms. RAI for treatment of TNG is typically reserved for
RAI, as outlined above, as well as in patients with compres- patients who are poor surgical candidates or those with small,
sive symptoms and those with concurrent suspicious or inde- asymptomatic goiters who refuse surgery.
terminate nodules. Operation also is favored in patients for
whom RAI is less likely to be effective, including patients with Surgery Thyroidectomy is the treatment of choice for
large goiters, severe biochemical disease, a high serum ratio TNG. Surgery allows for rapid control of hyperthyroidism,
of T3 to T4, male gender, or very high TSH receptor antibody relief of compressive symptoms, and histologic examination
titers. Graves ophthalmopathy frequently stabilizes and some- of any dominant or suspicious nodules and avoids any long-
times regresses after operation.8,9 In some cases, patients may term side effects of ionizing radiation. Total thyroidectomy is
choose surgery to avoid ionizing radiation, to simplify family favored when performed by surgeons with acceptable com-
planning, or to minimize the duration of thyrotoxicosis. plication rates and confers the advantages of easy titration
Recommendations about the optimal extent of thyroidec- of thyroid replacement and a nonexistent recurrence rate.
tomy for Graves disease have evolved over time. Bilateral Inorganic iodine (Lugol, SSKI) generally is not given pre-
subtotal resection was historically advocated for its safety operatively in this setting as the variable and unpredictable
profile and control of hyperthyroidism with the potential for iodine uptake by TNG raises the risk of triggering acute
euthyroidism without medication. However, estimation of thyrotoxicosis.
tissue remnant size that will avoid hypothyroidism while min-
imizing recurrent hyperthyroidism may be difficult. Recent Solitary Toxic Nodule
studies suggest similar complication rates following subtotal STN causes less than
and total resections, whereas cure rates are substantially 5% of all cases of hyper-
higher after total thyroidectomy.8,10,11 When performed by thyroidism in the United
surgeons with appropriately low morbidity (recurrent laryn- States. The frequency of
geal nerve injury less than 1% and permanent hypoparathy- STN is higher in women
roidism less than 3%8,10), total thyroidectomy is now favored and increases with age. STNs are usually palpable on physi-
over lesser resections. cal examination as thyrotoxicosis is rare when nodules are
under 3 cm in diameter.2 Like TNG, STN can be associated
Toxic Nodular Goiter with T3 toxicosis and normal T4 levels. Treatment choices
Much less prevalent include ATM, RAI, and surgery.
than Graves disease,
TNG accounts for about Prolonged ATM administration Excess thyroid hor-
25% of all cases of hyper- mone secretion by the autonomously functioning STN will
thyroidism in the United recur after ATM withdrawal. Definitive management of STN
States. TNG is uncom- by lifelong ATM treatment is an option of last resort because
mon in patients under 50 years of age but is the most common of the rare but sometimes life-threatening adverse reactions
cause of hyperthyroidism in the elderly.12 TFT abnormalities to the thionamides, and this is indicated only for patients with
are similar to those in Graves disease, although a higher pro- limited life expectancy.
portion of patients with TNG will have T3 thyrotoxicosis.
Treatment options include ATM, RAI, and surgery. Radioactive iodine RAI can be effective definitive
treatment for STN but usually is reserved for very-high-risk
Prolonged ATM administration TNG results from surgical candidates and for patients who refuse operation.
thyroid hormone production by multiple autonomously The differential RAI uptake of the surrounding suppressed
functioning nodules without the potential for spontaneous gland compared with the STN can confound RAI dosing.
01/11
Intense RAI concentration by the STN itself exposes the symptomatic relief in bulky benign disease, definitive diagno-
adjacent normal thyroid to potentially oncogenic levels of sis for indeterminate lesions, and definitive therapy for malig-
ionizing radiation, with subsequent risk of thyroid neoplasia. nancy. Although the incidence of thyroid cancer has doubled
since 1973,14 85 to 96% of palpable and subclinical nodules
Surgery Thyroidectomy is the treatment of choice for are benign. The rate of malignancy varies with factors includ-
STN. Resection of the affected thyroid lobe promptly ing age, gender, family history, and radiation exposure.
controls hyperthyroidism in patients with STN and relieves Screening for thyroid cancer is not cost-effective in the gen-
any symptoms associated with these relatively large nodules. eral population but is appropriate for some high-risk groups
The risks of operation are quite low because lobectomy (e.g., multiple endocrine neoplasia [MEN] kindreds, after
plus isthmusectomy is sufficient in most cases. When the substantial radiation exposure). When considering treatment
contralateral remaining lobe is normal, long-term T4 supple- options, near-total (residual tissue < 1 g) and total (removal
mentation is usually unnecessary. all visible thyroid) thyroidectomy will be used interchange-
ably. Subtotal resection refers to residual tissue more than 1
and less than 5 g.
Approach to the
Patient with differential diagnosis
Euthyroid Nodular The clinical challenge of euthyroid nodular disease is to
Disease reliably identify the small subset of patients with substantial
Thyroid nodules are likelihood of malignancy while avoiding the risks of surgery
very common and repre- for the vast majority of patients with benign disease. Most
sent a wide spectrum of thyroid disease, both benign and thyroid nodular disease is more common in women and
malignant [see Table 2 and Table 3]. Palpable disease is pres- occurs in middle age, although anaplastic thyroid cancer
ent in 5 to 7% of women and 1 to 2% of men, whereas cervi- (ATC), lymphoma, and sporadic medullary thyroid cancer
cal US reveals subclinical nodular disease in up to 67% of (MTC) peak somewhat later.15 Papillary (PTC) and follicular
patients.14 Most patients with nodules are clinically and bio- (FTC) thyroid cancers are often grouped together as well-
chemically euthyroid. Surgical referral is usually targeted at differentiated thyroid cancer (WDTC).
clinical evaluation
Table 2 Benign Etiologies of Euthyroid Nodular Disease
History and Physical Examination
Predominant
Disease Nodularity Treatment A palpable solitary or dominant nodule should lead to
documentation of duration, changes in size, associated symp-
Colloid nodule Solitary or Observation
multiple toms, exposure to ionizing radiation, prior thyroid disease, or
prior therapy with T4. Recent TFT results should be reviewed.
Simple cyst Solitary or Observation or aspiration
Bearing in mind that most WDTCs are slow-growing and
multiple if > 4 cm or growing
asymptomatic, rapid growth with associated symptoms sug-
Follicular Solitary or Resection (thyroid gests an aggressive process, such as ATC or lymphoma.16
adenoma (FA) multiple lobectomy) to exclude
Dysphagia and dyspnea are more common with multinodular
malignancy
goiter (MNG), whereas pain and hoarseness should heighten
Multinodular Often with Resection for compressive concerns for malignancy. Hashimoto disease raises the chance
goiter (MNG) dominant symptoms, dominant
nodule in nodule > 4 cm, or
of lymphoma, and exposure to ionizing radiation, especially
multinodular suspicious dominant in childhood or adolescence, increases the likelihood of PTC.
gland nodule Family history should target a history of familial endocrinop-
Chronic Heterogeneous Resection for compressive athy or other hereditary tumor syndromes linked to thyroid
lymphocytic gland; may symptoms or if disease, especially in the setting of suspected MTC17 [see
thyroiditis have suspicious dominant Table 4]. A history of prior neck surgery or irradiation should
(Hashimoto dominant nodule be carefully documented.
disease) nodule On examination, the neck is observed for visible nodule
or goiter. Voice quality and volume are noted. Palpation
Table 3 Malignant Etiologies of Euthyroid Nodular defines thyroid size, symmetry, and consistency, as well as the
Disease number, size, location, consistency, tenderness, and mobility
of nodules; the number, size, location, and mobility of cer-
Disease Percentage
vical lymph nodes; and the presence of tracheal deviation or
Papillary thyroid cancer (PTC) 80 substernal extension. A firm, mobile, solitary nodule is most
Follicular thyroid cancer (FTC) 10 often a colloid nodule or simple cyst but also may represent
Hürthle cell cancer (HCC) 1
follicular adenoma; a hard, fixed mass suggests cancer but
may represent Hashimoto disease. Central or unilateral
Anaplastic thyroid cancer (ATC) 2 adenopathy favors PTC or MTC. Thyromegaly of variable
Medullary thyroid cancer (MTC) 5 texture and multiple nodules are most common with MNG;
Lymphoma 1 substernal extension may produce cervical tracheal deviation
or venous engorgement. General medical status should be
Metastases <1
assessed as for any potential preoperative patient.
01/11
Table 4 Familial Syndromes of Thyroid Disease Table 5 Bethesda Classification of FNA Cytology and
Associated Malignancy Risk
Gene/Tumor
Syndrome Thyroid Disease Marker Bethesda FNA Cytology Class Risk of Malignancy (%)
MEN type IIA Medullary thyroid ret proto-oncogene/ Nondiagnostic/unsatisfactory 1–4
cancer calcitonin
Benign 0–3
MEN type IIB Medullary thyroid ret proto-oncogene/
cancer calcitonin AUS/FLUS 5–15
FMTC Medullary thyroid ret proto-oncogene/ Suspicious for follicular neoplasm 15–30
cancer calcitonin
Suspicious for malignancy 60–75
Familial Papillary thyroid APC
adenomatous cancer Malignant 97–99
polyposes
AUS = atypia of undetermined significance; FLUS = follicular lesion of
Carney complex Well-differentiated PRKAR1A undetermined significance; FNA = fine-needle aspiration.
thyroid cancer
Cowden disease Follicular adenoma/ PTEN
(PTEN multiple follicular
unrelated fluorodeoxyglucose–positron emission tomographic
hamartoma carcinoma (FDG-PET) scan.14,23 When US confirms MNG and com-
syndrome) pression symptoms are absent, FNA is indicated for the
Peutz-Jeghers Well-differentiated STK 11 or LKB 1 dominant nodule.
syndrome thyroid cancer
Sequencing of Investigations
FMTC = familial medullary thyroid carcinoma; MEN = multiple endocrine
neoplasia. US typically precedes FNA as US findings may change the
FNA target (e.g., an unsuspected suspicious nodule). “Pure”
cystic lesions are rare, are overwhelmingly benign, and can be
Ultrasonography
observed without FNA for diagnosis when asymptomatic.
Further assessment is accomplished with US, a safe, non- When a mixed nodule has a substantial cystic component,
invasive, cost-effective means of imaging thyroid parenchyma US-guided FNA allows fluid aspiration for cytology and
and the cervical nodal basins. Patients are categorized as FNA of the residual solid component. For solid nodules, US-
having solitary or multiple nodules, and lesions are subdi-
guided FNA can reduce the rates of nondiagnostic and false
vided into cystic, solid, or mixed cystic-solid. In a multinodu-
negative results when the likelihood of inadequate material
lar thyroid, a particularly large or irregular nodule is termed
or sampling error is high (difficult to palpate, posteriorly
dominant. Benign nodules typically are round, homogeneous,
located).14 Operation without FNA is indicated for a solitary
slightly hypoechoic, and easily separable from surrounding
or dominant nodule exceeding 4 cm given the substantial
tissue. Malignant nodules are more often irregular in shape,
heterogeneous, markedly hypoechoic, and poorly demar- chance of malignancy and the possibility of nonrepresentative
cated. Tiny, hyperechoic, “comet tail”–shaped lucencies in sampling by FNA (although many clinicians obtain a biopsy
a nodule favor benignity, whereas fine internal calcifications for the purpose of operative planning). FNA is also unneces-
or hypervascularity suggests malignancy.18 Thin-walled cysts sary when US confirms MNG in a patient with compression
without internal echoes are overwhelmingly benign; mixed symptoms.
cystic-solid nodules are indeterminate and grouped with solid morphology-based treatment considerations
lesions for further evaluation.
Cystic Lesions
Fine-Needle Aspiration
Incidentally discovered
FNA provides the most accurate, cost-effective assessment
simple cysts do not
of thyroid nodules. Benign lesions comprise 70% of FNA
require investigation or
results, whereas roughly 5% of FNA are read as definitively
malignant. Most of the remaining lesions are “follicular treatment. Clinically evi-
aspirates,” ranging from hyperplastic nodules to follicular dent cysts are aspirated
cancer. A benign FNA diagnosis is credible19,20 and requires dry and the fluid sent for
no further intervention other than periodic screening. The cytology. Benign cysts commonly recur and are reaspirated;
sensitivity and specificity of FNA for the diagnosis of malig- thyroid lobectomy is indicated after two failed aspirations or
nancy approach 94% and 99%, respectively.21 A standardized for cysts greater than 4 cm. Percutaneous ethanol injection
thyroid FNA reporting system (Bethesda criteria) has recently carries a 20% recurrence rate and is an alternative treatment
been advocated.22 There are six general diagnostic categories: for smaller cysts.14 Mixed cystic-solid nodules are managed
nondiagnostic or unsatisfactory, benign, atypia of undeter- like solid lesions based on cytology and FNA results.
mined significance (AUS) or follicular lesion of undetermined
Multinodular Goiter
significance (FLUS), suspicious for follicular neoplasm, sus-
picious for malignancy, and malignant. Risk of malignancy Most MNG patients
varies by category [see Table 5]. FNA of solid solitary or dom- are managed medically
inant nodules greater than 1 cm is appropriate in most cases. with serial clinical eval-
Solid lesions 5 to 10 mm may warrant FNA if the nodule is uations (examination,
hypoechoic and microcalcifications are present, if the history TFT, and US) unless
discloses a high risk for cancer, or if they are found on an compressive symptoms
01/11
or dominant nodules develop. Thyroidectomy is indicated adenoma and follicular carcinoma cannot be made by FNA
for patients with US findings of MNG and compressive cytology. Assessment for malignancy is based on capsular or
symptoms. Compressive symptoms are typically associated vascular invasion, and lobectomy is indicated for tissue diag-
with markedly asymmetrical goiters or those with substernal nosis. Completion thyroidectomy is performed for final diag-
extension. When examination or US findings are inconsistent noses of follicular cancer or follicular variant of papillary
with symptomatology, CT or MRI can help exclude other cancer. Some patients opt for total thyroidectomy initially
etiologies. These cross-sectional modalities are also useful to to avoid the need for reoperation; this strategy is reasonable
delineate the extent of the mediastinal component if present. when complication rates are kept low.
Indications for surgery include compressive symptoms, severe
or bothersome cosmetic deformity, any dominant nodule FNA suspicious for malignancy A small number of
greater than 4 cm, or any nodule greater than 1 cm with FNA abnormal cells within a sparsely cellular or more benign-
results that meet the criteria for removal. Total thyroidec- looking background characterizes lesions in this category.
tomy is preferred over lesser resections to minimize recurrent Malignancy rates are 60 to 75%.22 Thyroid lobectomy is the
disease from remnant hypertrophy and is appropriate for minimum adequate treatment, and total thyroidectomy is
these patients when done by surgeons with low complication preferable when complication rates are low.
rates. Nearly all substernal goiters can be safely removed
through a generous collar incision, and the remaining few FNA malignant Roughly 5% of cytologic diagnoses are
are reached via partial sternotomy. Patients with tracheal conclusively malignant, and the positive predictive value of
deviation or substernal goiters may present endotracheal FNA for cancer is 97 to 99%.22 Comments about the cell type
intubation challenges; airway management is optimized by are usually provided. Total thyroidectomy is the preferred
preoperative dialogue between the surgeon and the anesthe- treatment for WDTC and MTC, whereas lobectomy suffices
siologist. Frozen section adds little value except when pre- for unilateral metastases from other primary sites. Resections
operative FNA was nondiagnostic or not performed or when for primary thyroid lymphoma and ATC are tailored to the
intraoperative findings suggest unexpected malignancy. extent of disease, although resection for ATC is usually aimed
at palliation only.
Solitary or Dominant Nodule
High-Risk Patients
The management of a
Patients exposed to ionizing radiation, especially in child-
solitary nodule is highly
hood or adolescence, have a lifetime increased risk of PTC.
dependent on cytologic
Whereas FNA is credible for assessing their nodules, total
diagnosis and can be
thyroidectomy should be considered once nodules develop.
broken down into six
Patients who retain irradiated thyroids require extremely
categories based on the
close surveillance, so noncompliant individuals are better
Bethesda criteria.22
served by operation. A contralateral nodule developing after
a lobectomy for cancer most often warrants completion thy-
FNA nondiagnostic About 10 to 15% of aspirates are
roidectomy. Close surveillance is acceptable for compliant
nondiagnostic, most often attributable to technical error, patients when FNA is clearly benign. Large (> 4 cm) solitary
inadequate sampling, or a substantial cystic component. Less or dominant nodules should be resected to allow complete
than 5% of these are malignant. Repeat FNA often yields histopathologic examination; lobectomy is the minimum
adequate and definitive material24; US guidance may enhance acceptable procedure. When intraoperative findings suggest
yields. Persistently insufficient results should prompt malignancy (e.g., adherence to strap muscles), total thyroid-
lobectomy. ectomy is appropriate for surgeons with low complication
rates. For less experienced surgeons or when findings are
FNA benign A benign diagnosis is rendered in nearly benign, lobectomy suffices, and further resection decisions
70% of all specimens, and no intervention is required. The are based on the final pathology. Frozen section cannot
risk of malignancy is 0.5 to 3%.22 Surveillance by serial clini- exclude malignancy in these cases because of the potential
cal evaluations (examination, TFT, and US) is done annually sampling error.
and then less often for stable nodules. Enlarging lesions
(50% or more increased volume) warrant repeat FNA. Additional Studies
Additional laboratory tests are seldom indicated preopera-
FNA AUS/FLUS Atypia or follicular lesion of undeter- tively. When the history raises the potential for MTC, the
mined significance is a heterogeneous subset of cytologically cytopathologist should be alerted and special cytologic stains
indeterminate nodules; roughly 5 to 15% prove to be malig- performed. Any suspicion of MTC on FNA should trigger
nant.22 AUS/FLUS is managed like FNA nondiagnostic: exclusion of pheochromocytoma and assessment for primary
repeat FNA and then lobectomy if a definitive diagnosis hyperparathyroidism prior to thyroidectomy (plasma or urine
remains elusive. Molecular markers (e.g., braf, ras) hold metanephrine assays, serum parathyroid hormone and cal-
promise for future use in this patient subset; FDG-PET cium levels). Additional imaging is warranted for palpable
specificity is too low to add clinically relevant value. cervical adenopathy in the setting of any thyroid malignancy;
the modality is selected based on local expertise. US avoids
FNA suspicious for follicular neoplasm Cancer is iodinated contrast administration (which confounds post-
present in 15 to 30% of suspicious for follicular neoplasm operative 131I scanning or therapy), but accuracy is more
(SFN),22 but the distinction between benign follicular operator dependent than for CT or MRI. FNA is appropriate
01/11
when other etiologies for adenopathy are present or when even though nodal disease is absent. Proven lateral nodal
documented nodal metastases would change management disease is best treated by level II–IV en bloc functional
(e.g., lobectomy only is planned, tertiary care referral). For resection when appropriate surgical expertise is available [see
nodes detected only on preoperative imaging, image-guided Figure 1].
FNA is used similarly. Preoperative laryngoscopy to docu-
ment vocal cord function is indicated for patients with vocal disease-specific treatment considerations
complaints, audible vocal abnormalities, and prior neck Papillary Thyroid Cancer
operation or radiotherapy, although some surgeons perform
laryngoscopy routinely. Vocal cord paralysis or other con- PTC is the most common thyroid cancer and carries
cerns for tracheal or esophageal invasion should be investi- an excellent prognosis when treated appropriately (> 90%
gated by endoscopy and imaging. Vocal cord paralysis should 10-year survival overall). Poor prognostic factors include age
also trigger preoperative dialogue about airway management less than 20 or more than 60 years, tumor greater than 4 cm,
with both the patient and the anesthesiologist. Radionuclide extrathyroidal extension, and the presence of distant
scanning is not useful, and the role of FDG-PET in metastases.25,26 Lymphatic spread worsens the prognosis and
preoperative staging remains ill-defined. increases local recurrence risk for patients over 45 years and
Intraoperative observations may lead to revision of the those with clinically apparent nodal involvement.14 The tall
operative plan. Strap muscle adherence, adjacent soft tissue cell, columnar, diffuse sclerosing, trabecular, and insular
invasion, and extracapsular tumor extension are consistent variants are more aggressive but uncommon. The follicular
with malignancy and favor total thyroidectomy. Contralateral variant is more common but behaves more like classical PTC.
disease palpable through the strap muscles warrants at least One quarter of PTCs are multicentric, and lymph nodes are
FNA (through the muscles) and consideration of total involved at the initial presentation in about one third.27 Dis-
thyroidectomy. To lessen the morbidity of reoperation, the tant metastases, usually pulmonary, are present initially in
contralateral strap muscles should not be elevated unless 5% of cases. PTC rates are sharply increased by ionizing
resection is planned at the same operative session. Suspicious radiation, with a lag time of 15 to 25 years. The high long-
nodes may be evaluated by FNA or frozen section. Multiple term survival rates of PTC patients and paucity of large ran-
suspicious central nodes or a positive biopsy result merit domized controlled trials have contributed to inconsistent
central lymphadenectomy [see Figure 1, Level VI]. Central treatment guidelines and to multiple prognostic scoring
neck dissection also should be considered by surgeons systems [see Table 6]. Staging should follow the TNM classi-
with low complication rates for T3 or T4 WDTC tumors fication [see Table 7]. Most scoring systems correlate with
recurrent disease, whereas the TNM system links best to
mortality. Recent consensus evaluation and treatment recom-
mendations from the American Thyroid Association are
achieving widespread recognition.14
Total thyroidectomy should be performed for most PTCs
exceeding 1 cm28; this procedure addresses multicentricity,
maximizes the therapeutic impact of postoperative RAI, and
facilitates surveillance for recurrences. Lobectomy suffices for
small, intrathyroidal PTC discovered incidentally in glands
resected for other diagnoses when radiation exposure, nodal
disease, and poor prognostic variants are absent. Central neck
dissection is added based on FNA or operative findings
suggesting lymphatic spread [see Figure 1, Level VI]. Judicious
addition of prophylactic dissection by surgeons with low
complication rates is reasonable, particularly for patients over
45 years, larger tumors (T3–T4), and more aggressive
histologies.14,27 The favorable natural history of PTC and the
morbidity of lateral cervical lymphadenectomy suggest that
this procedure be added only for pathologically proven lateral
nodal disease. An aggressive operative approach should be
considered in good operative candidates with PTC invading
the trachea or esophagus. A functioning recurrent laryngeal
nerve (normal vocal cord function) should seldom, if ever,
be sacrificed.
Postoperative administration of RAI for thyroid remnant
ablation may also have an adjuvant therapeutic effect on
residual microscopic disease in the central neck. RAI ablation
is indicated when nodal or distant metastases are known to
be present and for T3–T4 tumors.14 Ablation may also reduce
recurrence rates for N1 disease or T2 tumors. Lifelong
levothyroxine is given postoperatively at doses sufficient to
Figure 1 Cervical lymph nodes can be classified into six suppress TSH secretion without causing overt hyperthyroid-
levels (inset) on the basis of their location in the neck. ism. Dose reduction may be required if the osteoporosis risk
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Table 6 Elements of Common Prognostic Schemes for Well-Differentiated Thyroid Cancer

Prognostic Patient Operative
Scheme Characteristics Tumor Characteristics Factors
Histologic Histologic Extrathyroidal Nodal Distant Completeness of
Age Gender Size Grade Subtype Extension Metastasis Metastasis Resection
AGES + − + + * + − + −
AMES + + + − + + − + −
MACIS + − + − * + − + +
MSKCC + − + + + + + + −
+ = variable used in defining risk group; − = variable not used; * = only for papillary thyroid carcinoma; AGES = patient age, tumor grade, extent, and tumor
size; AMES = patient age, presence of distant metastases, extent, and tumor size; MACIS = metastatic lesions, patient age, completeness of resection, invasion,
and size of tumor; MSKCC = Memorial Sloan-Kettering Cancer Center scheme.
Table 7 Staging of Differentiated Thyroid Cancer

Tumor Type Stage Patient Age (yr) Tumor Node Metastasis
PTC/FTC I < 45 Any T Any N M0
I 45 or older T1 N0 M0
II < 45 Any T Any N M1
II 45 or older T2 N0 M0
III 45 or older T3 N0 M0
III 45 or older T1–3 N1a M0
IVA 45 or older T4a N0-1a M0
IVB 45 or older T4b Any N M0
IVC 45 or older Any T Any N M1
Adapted from Greene FL, editor. AJCC Cancer Staging Manual, Sixth Edition. New York: Springer-Verlag; 2002.
FTC = follicular thyroid cancer; PTC = papillary thyroid cancer.
is high or atrial fibrillation develops. Postoperative surveil- contain at least 75% oncocytes and demonstrate capsular or
lance can include RAI whole body scan, serum Tg levels, and vascular invasion. Oncocytic cancers are considered more
cervical US; test combinations and frequencies are individu- aggressive than classical FTC because extrathyroidal exten-
alized based on tumor staging, estimated recurrence risks, sion and metastases (nodal and distant) are more common
and patient compliance. Anti-Tg antibodies should be and RAI uptake is often minimal.15,29 Total thyroidectomy is
measured simultaneously with each Tg assay. indicated for nearly all HCCs, although this is often done in
a two-stage fashion because FNA cannot provide a definitive
Follicular Thyroid Cancer diagnosis. Central or lateral lymphadenectomy is performed
FTC comprises 10 to 15% of thyroid malignancies. In con- when nodes are clinically positive. Staging should follow the
trast to PTC, FTC is typically solitary, and metastasis is more TNM classification. RAI ablation is indicated for all HCCs,
often hematogenous than lymphatic, favoring lung and bone. and levothyroxine suppression is given as for FTC. Sur-
Poor prognostic factors include age over 50 years and tumors veillance includes US and Tg; FDG-PET may be useful
over 3.5 cm. An FTC with a limited area of microscopic cap- when Tg is elevated and a radioiodine whole body scan is
sular invasion and no vascular invasion is termed “minimally negative.
invasive” and carries no excess mortality when treated by
thyroid lobectomy. Total thyroidectomy is indicated for more Anaplastic Thyroid Cancer
extensive capsular invasion or for vascular invasion. Central ATC is rare in the United States, representing less than 2%
[see Figure 1, Level VI] or lateral lymphadenectomy [see of thyroid malignancies.29,30 The median survival for patients
Figure 1, Level II–IV] is performed for clinically evident or with ATC is approximately 6 months.15,30 ATC is suspected
palpable nodal disease. Staging follows the TNM classifica- when older patients present with rapidly progressive, bulky,
tion. RAI ablation is indicated for all FTCs except minimally fixed tumors. Diagnosis may require core-needle or incisional
invasive lesions. Levothyroxine suppression is given, and biopsy when FNA is inadequate. The vast majority of tumors
surveillance is performed as for PTC. Stage for stage, FTC are unresectable at diagnosis because of locoregional spread.
and PTC have equivalent prognoses. Over 40% of patients have extensive nodal involvement, and
nearly 50% present with distant metastases (lung, bone,
Oncocytic (Hürthle Cell) Carcinoma brain, adrenal).30 Surgery has little utility other than for estab-
Hürthle cell carcinomas (HCCs) comprise less than 5% lishing an airway for palliation. External beam radiotherapy
of WDTCs and are a subset of follicular neoplasms. They plus chemotherapy may transiently shrink the tumor;
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palliative debulking is occasionally feasible for the few patients thyroid carcinoma (FMTC). MTC associated with MEN
with significant and sustained responses. type IIB is the most aggressive, followed by MEN type IIA
and then FMTC. Hereditary lesions usually are bilateral
Medullary Thyroid Carcinoma and are associated with a precursor lesion termed C-cell
Unlike WDTC, MTC is a neuroendocrine tumor that hyperplasia. MEN type IIA accounts for two thirds of hered-
arises from the calcitonin-secreting parafollicular cells. MTC itary MTCs. Ret proto-oncogene testing is recommended
constitutes about 5% of thyroid cancers; most (75%) cases before age 6 within known kindreds. Prophylactic total thy-
are sporadic, whereas the remainder are hereditary. Sporadic roidectomy and central neck dissection are performed when
disease presents as a solitary nodule, often with palpable ade- a ret mutation is confirmed, after excluding pheochromocy-
nopathy. Cytologic features are characteristic and confirmed toma.31,32 MTC has an earlier age at onset in MEN type IIB,
by immunostaining for calcitonin. Distant metastases to lung, and genetic screening is conducted shortly after birth. Posi-
liver, and bone are frequent. Staging follows the TNM clas- tive ret testing is followed by total thyroidectomy and central
sification [see Table 8]. Preoperative staging includes neck, neck dissection in the first year of life.31 FMTC is defined by
chest, and abdominal CT or MRI for all but those with small the presence of four or more MTC cases within a family in
primary tumors and no adenopathy. Liver and lung lesions the absence of associated endocrinopathy. The age at onset
are often multiple but sometimes small enough to escape of FMTC is delayed compared with that of MEN type II,
detection via CT. A baseline calcitonin should be measured but FMTC survival is optimized by childhood genetic screen-
preoperatively. Testing to exclude pheochromocytoma also is ing and operation (total thyroidectomy and central neck
essential because the patient may represent the index case of dissection).
an unsuspected kindred with MEN. If present, pheochromo-
cytoma must be resected prior to thyroidectomy for MTC. Primary Thyroid Lymphoma
Overall survival in MTC is considerably lower when com- Primary thyroid lymphoma (PTL) accounts for approxi-
pared with WDTC. Poor prognostic features include large mately 1% of thyroid malignancies and 1% of extranodal
tumor size, high preoperative calcitonin, advanced age, and lymphomas.27,28 The risk of PTL is increased by Hashimoto
mediastinal adenopathy.28 Surgery is the only effective treat- thyroiditis. FNA is diagnostic in most cases (80%); core-
ment modality and should consist of total thyroidectomy plus needle or incisional biopsy may be required for diagnosis or
central neck dissection [see Figure 1, Level 6] and ipsilateral for tumor markers. About 75% of PTL are diffuse large B cell
modified radical neck dissection [see Figure 1, Levels I–V]. lesions and 25% are mucosa-associated lymphoid tissue
Contralateral lymphadenectomy is added when bilateral (MALT) lymphomas, with MALT lesions carrying a better
thyroid masses or clinically positive nodes are identified. prognosis.16 Poor prognostic features include size greater than
Extrathyroidal or extranodal tumor extension worsens the 10 cm, advanced stage, compressive symptoms, mediastinal
prognosis. Calcitonin is followed serially as a tumor marker involvement, and rapid tumor growth. Constitutional symp-
postoperatively. A subset of patients with persistent or recur- toms are rare. PTLs are chemo- and radiosensitive, so mul-
rent hypercalcitonemia follow a prolonged course, and reop- tiagent chemotherapy is usually combined with external-beam
eration may be indicated when tumor masses are detected by radiation as definitive treatment. Surgery alone may be appro-
imaging and confirmed by FNA. Aggressive cervical reopera- priate for early-stage MALT tumors.16,30 If PTL is diagnosed
tion for persistent hypercalcitonemia alone is controversial. intraoperatively, total thyroidectomy is appropriate.
Symptomatic hypercalcitonemia is unusual. RAI has no
therapeutic role for MTC. Metastases
MTC occurs as a component of three familial syndromes: Metastases to the thyroid are rare. Renal cell and breast
MEN type IIA, MEN type IIB, and familial medullary tumors are common tumors of origin. FNA will suggest
metastatic tumor, although perhaps not identify a specific
tumor of origin. When the thyroid is the sole site of
Table 8 Staging of Medullary and Anaplastic Cancer metastatic disease, thyroidectomy (lobe versus total) may be
Tumor Type Stage Tumor Node Metastasis curative. Palliative resection is seldom, if ever, appropriate.
Preoperative evaluation is tailored to the tumor of origin.
MTC I T1 N1 M0
II T2–3 N0 M0
Thyroidectomy: Technique, Tips, and Troubleshooting
III T1–3 N1a M0
IVA T4a N0–1a M0
operative technique
IVA T1–4a N1b M0 Proper Positioning

IVB T4b Any N M0 The first step to a safe thyroidectomy is positioning the
IVC Any T Any N M1 patient to optimize operative exposure. A shoulder roll or a
sandbag placed between the scapulas allows the neck to be
Anaplastic IVA T4a Any N M0
extended and shifted anteriorly. Proper positioning is particu-
IVB T4b Any N M0 larly important in facilitating access to substernal goiters
IVC Any T Any N M1 through the cervical approach. Neck extension must be gentle
in all patients and should be limited in patients with known
Adapted from Greene FL, editor. AJCC Cancer Staging Manual, Sixth
Edition. New York: Springer-Verlag; 2002. cervical disk disease, rheumatoid arthritis, or osteoporosis.
MTC = medullary thyroid cancer. The occiput should be stabilized by support with a foam
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pillow. Neck hyperextension or poor occipital support can

result in significant postoperative muscle spasm and
associated headache.
General Technical Principles

The thyroidectomy incision is located in a cosmetically
sensitive area, but exposure should not be compromised by
an inadequate incision. A larger operative field is generally
needed for resections for Graves disease and toxic mul-
tinodular goiters, for large nontoxic multinodular goiters
producing compression symptoms (particularly those with
substernal components), when preoperative evaluation sug-
gests extrathyroidal extension of tumor, and when there is a
high likelihood of performing a lymphadenectomy.
Operative complications are best avoided by unhurried
dissection in a bloodless field.33,34 If encountered, bleeding Figure 2 The initial incision in a thyroidectomy is made
can and should be controlled first by pressure so that the 1 cm below the cricoid cartilage and follows normal skin lines.
relationship of the source vessel to the recurrent laryngeal A sterile marking pen is used to mark the midline of the neck,
nerve can be clarified. Early identification of the nerve the level of the incision, and the lateral borders of the
incision. A 2-0 silk tie is pressed against the neck to mark the
facilitates safe control of vessels. Suture ligatures should be
incision site itself.
considered for controlling vessel ends that are likely to retract
away from the operative field (e.g., cephalad end of the supe-
rior thyroid artery at the superior pole, mediastinal end of a Step 2: Mobilization of Strap Muscles
thyroidea ima artery). Operating telescopes (2.5 to 3.5 power
The thyroid gland is exposed by dividing the investing and
magnification) are a useful adjunct during delicate dissection
pretracheal layers of the cervical fascia in the midline. The
around the recurrent nerve and vascular branches supplying
sternohyoid and sternothyroid muscles can then be elevated
parathyroid glands.
as a single unit on each side off the thyroid lobe in what is
When bilateral resection is planned, dissection should
usually a bloodless plane [see Figure 3]. The dissection is car-
nearly always be done first on the side of the suspected tumor
ried laterally until the lateral border of the sternothyroid
or larger goiter. Should a problem be encountered (e.g., para- muscle is easily seen. Partial or complete division of the ster-
thyroid involvement by tumor or recurrent nerve operative nothyroid muscle at its insertion into the thyroid cartilage can
injury), the operative plan can be revised to a subtotal resec- significantly improve exposure of the superior pole while
tion on the contralateral side to enhance protection of the avoiding denervation of the muscle. Routine division of both
parathyroid glands and recurrent nerve on that side. Rarely, strap muscles is unnecessary in most cases. Once the strap
when tumors are known or suspected preoperatively to be muscle unit is elevated fully, side-arm blades can be inserted
very extensive, beginning on the “easy” (less abnormal) side and fixed to the self-retraining retractor for lateral retraction
may facilitate identification of and access to the trachea and of the strap muscles.
esophagus. In patients operated on to exclude or to treat malignancy,
Step 1: Skin Incision and Subplatysmal Flaps a deliberate pause prior to further dissection is appropriate
after the strap muscle unit is fully elevated from the thyroid
A collar incision paralleling the normal cervical skin lines lobe. The size, location, color, and consistency of the solitary
offers extensile exposure. Typically, the incision is sited about or dominant nodule should be noted, along with the integrity
1 cm caudad to the cricoid cartilage and extends between the of the overlying thyroid capsule and the presence of fibrosis
sternocleidomastoid muscles [see Figure 2]. Shifting the inci- in or adherence of adjacent soft tissues to the lobe. The char-
sion cephalad should be considered when the superior poles acteristics of visible central neck lymph nodes should be
are likely to extend significantly upward (e.g., Graves disease) assessed.
or caudad when a substernal goiter is present. After dividing
the platysma, subplatysmal flaps are raised widely in all direc- Tips and troubleshooting The midline fascia should be
tions in this bloodless plane, avoiding the anterior jugular opened down to the inferior aspect of the sternal notch, where
veins that may be particularly prominent in patients with the interclavicular ligament can be palpated, facilitating later
Graves disease or substernal goiters. mobilization of substernal goiter, identification of inferior
parathyroid glands, and central lymphadenectomy.
Tips and troubleshooting Developing the superior flap Tissue attachments or vessels crossing the plane between
to 1 to 2 cm above the thyroid cartilage notch will facilitate the thyroid and the midline strap muscles are concerning for
later access to the superior poles and the pyramidal lobe. malignancy, and any densely adherent portion of strap muscle
Taking the inferior flap until the flat surface of the manu- should be sacrificed and left attached to the underlying
brium is palpable will aid exposure of substernal goiters. thyroid for en bloc resection. This maneuver will also aid the
A retractor with attachable side-arm blades (e.g., the pathologist later in determining extrathyroidal extension of
Mahorner-Hamburger-Brennan) is particularly useful for tumor, a finding that is an important predictor of recurrence.
operations on larger glands but requires a slightly longer skin Tissue reaction to a preoperative FNA biopsy can simulate
incision for atraumatic placement into the neck. tumor adherence. Benign central lymph nodes should be
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Figure 3 To expose the thyroid, a midline incision is made through the superficial layer of deep cervical fascia between the
strap muscles. The incision is begun at the suprasternal notch and extended to the thyroid cartilage.
small, firm but not hard, and mobile and have well-defined
capsules; nodes appearing otherwise should be regarded as
suspicious, and intraoperative FNA should be considered.
Benign lymphadenopathy is most often associated with
Graves disease and Hashimoto thyroiditis.
Step 3: Initial Mobilization of the Thyroid Lobe and Superior
Parathyroid Gland Identification
A 2-0 suture is placed deeply through the thyroid lobe for
retraction to facilitate exposure. The stitch should not tra-
verse a thyroid nodule as it is more likely to pull loose and
may create artifacts that confound later histopathologic
interpretation. The lobe is retracted medially while the filmy
soft tissue lateral to the lobe is divided close to the gland.
Dissection parallel to the usual course of the recurrent laryn-
geal nerve is safest. The addition of inferior traction facilitates
carrying the dissection up to the superior pole. Vessels are
controlled and divided near or on the surface of the lobe
whenever feasible, limiting risk to the nerve and minimizing
the chance of parathyroid devascularization. The superior
thyroid artery is best managed by dividing it at the branch
level, controlling the individual branches low on the thyroid Figure 4 The superior pole vessels should be individually
gland, which minimizes the risk of injury to the external identified and ligated low on the thyroid gland to minimize
branch of the superior laryngeal nerve [see Figure 4]. the chances of injury to the external branch of the superior
laryngeal nerve.
Tips and troubleshooting A small sponge applied to
the gland surface further facilitates lobar retraction and less- cricothyroid muscle through the Berry ligament [see Figure 6].
ens trauma to the thyroid surface, particularly when the With the thyroid lobe retracted medially and anteriorly, the
gland is hypervascular (e.g., Graves disease). Palpation of the nerve is put on stretch and can be palpated as a taut, linear
inferior cornu of the hyoid bone is advisable as the lobe is
structure (“guitar string”) slightly inferior to the inferior
retracted medially and caudally as a guide to the location of
thyroid artery. The filmy soft tissue overlying the nerve can
the recurrent nerve, which enters the cricothyroid muscle in
be lifted anteriorly away from the nerve and divided under
close proximity to the cornu. As the lobe is rotated medially
and the superior pole branches are divided, the superior direct vision, allowing the nerve to be followed to its crico-
parathyroid gland usually is easily seen and should be gently thyroid entry. Sharp, fine-bladed scissors (e.g., tenotomy,
freed from the perithyroidal soft tissue [see Figure 5]. The Jameson) and fine-tipped hemostats (“mosquito”) are essen-
parathyroid with its adjacent soft tissue and fat is gently swept tial instruments for this step. Having looped around the right
away from the thyroid. subclavian artery, the right recurrent nerve follows a more
oblique lateral-to-medial course than the left nerve, which
Step 4: Recurrent Laryngeal Nerve Identification follows a straight vertical course somewhat more deeply in the
It is usually safest to identify the recurrent laryngeal nerve tracheoesophageal groove, having looped around the ductus
low in the neck and then to follow it to where it enters the arteriosus in the mediastinum.
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Figure 5 The upper parathyroid glands are usually situated on either side of the thyroid at the level where the recurrent
laryngeal nerve enters the cricothyroid muscle. The lower parathyroid glands are usually anterior to the recurrent laryngeal
nerve and inferior to where the inferior thyroid artery crosses this nerve.
Figure 6 The recurrent laryngeal nerve enters the cricothyroid muscle at the level of the cricoid cartilage, first passing through
the Berry ligament.
Tips and troubleshooting In about 0.5% of persons, superiorly will usually allow identification of any nerve
the right recurrent laryngeal nerve is, in fact, “nonrecurrent,” branches. Some surgeons find intraoperative nerve monitor-
arising as a direct branch from the vagus in the midneck and ing to be helpful, but its use is not uniform among endocrine
coursing toward the thyroid from either laterally or superi- surgeons.35
orly.1 Rarely, both a recurrent and a nonrecurrent nerve are
present on the right. Branching of the nerve is common on Step 5: Thyroid Mobilization and Identification of Inferior
both sides, and all branches must be preserved because all Parathyroid Glands
of the motor fibers of the recurrent laryngeal nerve are Once the course of the recurrent laryngeal nerve has been
usually in the most medial branch. Initial identification of the identified, the lobe can be further rotated medially along its
nerve near the level of the inferior thyroid pole rather than length and around the inferior pole, again controlling vessels
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close to the lobar surface. During this dissection, the inferior Tips and troubleshooting The pyramidal lobe may
parathyroid gland is typically seen. Located in a plane ante- extend to the base of the tongue as a thyroglossal duct
rior to the recurrent nerve, the parathyroid gland often remnant, but it is often just a fibrotic strand, particularly
appears attached to the capsule of the inferolateral thyroid superior to the hyoid bone. Complete resection of the pyra-
pole. The attachment is filmy and easily separated, but midal lobe up to the tongue and removal of the middle third
care must be taken to avoid injuring the small vessels to the of the hyoid bone are important components of the Sistrunk
parathyroid. operation for thyroglossal duct cyst. Resection of the
pyramidal lobe within the usual thyroidectomy operative field
Tips and troubleshooting Parathyroid glands should be without hyoid excision is sufficient during thyroid resection
swept from the thyroid gland on as broad a vascular pedicle for other diseases.
as possible to prevent devascularization. If the pedicle is
injured or if the parathyroid changes from its normal dark Step 7: Completing the Thyroid Resection
mustard color to a dusky purple, a tiny piece of the gland Once the lobe has been mobilized superiorly, inferiorly,
should be sent for frozen section to confirm its identity as and laterally, it must be freed from its attachments to the
parathyroid. Once confirmed, the gland is resected and trachea. As the lobe is rolled from lateral to medial, the most
put on sterile iced slush for autotransplantation into the challenging part of the dissection involves the thyrotracheal
sternocleidomastoid muscle just prior to closure. ligament (Berry ligament), connecting the posterior aspect
In patients who have invasive tumors or who require of the lobe to the trachea just caudal to the cricoid cartilage
reoperation, extensive scarring is often present. It may be [see Figure 6]. A small branch of the inferior thyroid artery
preferable to identify the recurrent laryngeal nerve from a traverses the ligament, as do one or more thyroid veins; con-
superior and medial approach by dividing the isthmus and trolling bleeding from these vessels risks recurrent nerve
the superior thyroid vessels. Careful medial to lateral rotation injury as the nerve passes through or under the ligament.
of the thyroid lobe from the trachea allows visualization of the Should bleeding occur, it should be controlled by applying
nerve at its most consistent location (i.e., at its entrance into
pressure with a gauze pad, avoiding clamps and ligatures until
the larynx immediately posterior to the cricothyroid muscle).
the course of the nerve through the ligament has been clearly
Alternatively, the nerve can be approached from laterally by
delineated. Irrigating the field to limit blood staining of
identifying the lateral border of the sternothyroid muscle at
tissues is helpful. In some patients, a lateral projection of the
the level of the inferior thyroid pole and working medially
thyroid (the tubercle of Zuckerkandl) overlies the nerve and
toward the inferior thyroid artery. The approach is modified
ligament. Once the thyrotracheal ligament has been divided,
to maximize dissection through the least scarred plane.
the remaining thyroid attachments to the trachea can be
Step 6: Mobilization of the Pyramidal Lobe divided through what is usually an avascular plane on the
A pyramidal lobe is found in about 80% of patients. This tracheal surface.
embryologic remnant usually arises from the left thyroid lobe Division of the isthmus should be done between clamps
near the midline and extends for a variable distance cranially. and the ends suture ligated. When lobectomy is performed,
Inferior traction on the left lobe will bring most if not all of the point of division should be at the junction of the isthmus
the pyramidal lobe into the operative field. The pyramidal with the contralateral lobe that will remain in situ. Division
lobe is dissected free medially and laterally from adjacent soft of the isthmus may be done earlier in the dissection when
tissue and is transected at its cephalad termination. It is left doing so will facilitate thyroid retraction or mobilization.
attached to the main thyroid mass caudally and resected en
bloc. As the pyramidal lobe is mobilized, one or more central Tips and troubleshooting If bilateral resection will be
neck nodes may be encountered overlying the cricothyroid performed, the isthmus may be left intact until the contralat-
membrane (so-called Delphian nodes) [see Figure 7]. eral lobe is dissected free and the entire gland delivered as a
Figure 7 Delphian lymph nodes may be found just cephalad to the isthmus over the cricothyroid membrane.
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single specimen The thyroid lobe should be carefully exam- early postoperative care
ined after removal. If a parathyroid gland is identified with
the specimen, a frozen section biopsy is sent for confirmation Unilateral Resection (Lobectomy)
and the gland is autotransplanted back into the neck unless Thyroid lobectomy is often accomplished successfully on
the parathyroid appears to be involved by thyroid tumor an outpatient or ambulatory basis, particularly when regional
extension (see above). The resected thyroid should be anesthesia is used. Patients with multiple comorbidities or
oriented for the pathologist; marking sutures or clips are those living in remote areas may be candidates for overnight
helpful for this purpose. observation, along with those failing to meet ambulatory
surgical unit discharge criteria. The patient is maintained in
Step 8: Closure a gentle head-up position (10° to 20°) for the first 24 hours
The best strategy to avoid a postoperative neck hematoma when nonambulatory to enhance venous drainage and minimize
is taking time to ensure meticulous hemostasis prior to edema formation. After regaining consciousness at a level suffi-
closure. Thorough irrigation of the field followed by precise cient to protect the airway, the patient is allowed liquid intake
identification and control of bleeders should be repeated as and can be advanced to a regular diet by the following morning.
necessary until the field is hemostatic and dry throughout. Liberal use of antiemetics during the early postoperative period
The recurrent nerve should always be reidentified prior to will minimize retching and emesis. Initial patient-controlled
placement of clamps or ligatures. The sternothyroid and ster- analgesia should be transitioned to oral analgesics as soon as
nohyoid muscles are reapproximated as separate layers in the smooth swallowing is observed. Unless there has been neck
midline. The platysma is closed as a separate layer once the surgery previously, there is no risk of clinically important
subplatysmal flaps have been released from the self-retaining hypocalcemia after thyroid lobectomy. It is unnecessary to
retractor and verified to be hemostatic. The skin can be measure serum calcium levels or to prescribe prophylactic
closed in several ways, including subcuticular suture, butter- calcium supplementation. The quality of the voice and the
adequacy of the airway should be assessed in the postanesthe-
fly clips, or tissue adhesive; the key factor in cosmesis is gentle
sia care unit and prior to discharge to home. If there is any
tissue handling, not the closure method.
concern about the integrity of recurrent laryngeal nerve
Smooth emergence from anesthesia with avoidance of
function, flexible fiberoptic laryngoscopy should be per-
coughing and retching can reduce the chance of high pres-
formed. Finally, if there is any question of a developing neck
sures being transmitted to the neck veins, and administration
hematoma, the patient should be kept hospitalized for airway
of an antiemetic during closure can be helpful, along
monitoring. A tray with sufficient instruments to reopen the
with spraying the oral cavity with a topical local anesthetic.
neck incision urgently is kept at the bedside (e.g., tracheos-
Endotracheal extubation with the patient still in a relatively
tomy tray).
“deep” plane of anesthesia is also helpful if not otherwise
contraindicated. If postoperative laryngoscopy is contem- Bilateral Resection
plated, insertion of a nasal pack containing cocaine or another Patients undergoing bilateral thyroid resections are typically
local anesthetic and decongestant during wound closure will observed overnight or admitted for a brief inpatient stay. Patients
facilitate early flexible fiberoptic endoscopy in the operating undergoing removal of extensive tumors, tracheal or esophageal
room or postanesthesia care unit. resections, or lymphadenectomies have longer lengths of stay.
Positioning, antiemetics, diet, and patient-controlled analgesia
Tips and troubleshooting It is not necessary to reattach are given as for lobectomy. Severe sore throat may be improved
a divided sternothyroid muscle to its thyroid cartilage inser- by topical anesthetic spray or solution. Voice quality and airway
tion. However, the distal sternothyroid segment should be adequacy should be assessed in the postanesthesia care unit
stretched to full length during closure to allow accurate and periodically thereafter; any concern about the integrity
approximation to the contralateral sternothyroid muscle. of recurrent laryngeal nerve function should be evaluated
When both sternothyroid muscles have been divided superi- promptly with flexible fiberoptic laryngoscopy. Patients
orly, they can be anchored by including bites of both sterno- with known coagulation abnormalities or evidence of neck
hyoid muscles at the cephalad end of the sternothyroid layer hematoma merit close monitoring in a special care unit for
closure. 24 to 48 hours. A tray with sufficient instruments to
Drainage of the thyroid bed is no substitute for adequate reopen the neck incision urgently is kept at the bedside (e.g.,
hemostasis. A drain does not prevent wound hematoma, nor tracheostomy tray).
does it provide “early warning” of significant wound hemor- Patients undergoing bilateral resections (or completion
rhage. A suction drain placed beneath the midline strap thyroidectomy after prior lobectomy) are at risk for transient
muscle closure may be useful when there is a large dead space or permanent hypoparathyroidism; the risk is increased with
in the resected thyroid bed (e.g., after excision of very large malignancy and by lymphadenectomy. Strategies for detect-
goiters). The drain is generally removed on postoperative ing and treating hypocalcemia vary among surgeons.36 Total
day 1. calcium is more often available and less expensive compared
When a subcuticular closure is performed, a patient-friendly with ionized calcium. In some series, postoperative parathy-
wound dressing can be created using a clothlike strip (e.g., roid hormone levels are early predictors of hypocalcemia, but
roller gauze, Cover Strip II) placed directly over the incision parathyroid hormone may not always be available. In the
and painted with collodion to render it waterproof. The absence of symptoms (perioral tingling, digital paresthesias),
patient is allowed to shower or wash over the wound begin- there is little reason to measure serum calcium until the
ning on the first postoperative day. The dressing separates morning of postoperative day 1. An exception might be when
from the skin at 7 to 10 days and is easily removed by the multiple parathyroid glands have been autotransplanted or
patient at that time. when parathyroid tissue is excised deliberately en bloc with
01/11
tumor. A simultaneous albumin level allows correction of the Replacement, achieving a TSH level within the normal range,
total calcium level for hemodilution by perioperative fluids; is the treatment goal for patients with benign diagnoses.
otherwise, ionized calcium alone is the optimal single mea- For patients with WDTC, suppression such that TSH is
surement. An elevated serum phosphate level (> 4.5 mg/dL) undetectable is the therapeutic target. Lower T4 doses (less
denotes an increased risk of parathyroid hypofunction. Mag- suppression) should be considered for older patients, those
nesium assay is performed when patients are symptomatic with cardiac disease, when osteoporosis risks are increased, or
because hypomagnesemia can mimic or worsen hypocalce- when clinically important hyperthyroid symptoms develop on
mia. An abnormal calcium value (unexplained by hemodilu- full suppression. Some clinicians favor full suppression for the
tion) when symptoms are absent merits reassessment in 6 to first few years postoperatively and then T4 dose reduction to
8 hours and again on postoperative day 2. Symptomatic replacement levels if there is no evidence of recurrent WDTC.
patients and those with total calcium values less than A steady-state TSH level is reached at 4 to 6 weeks after
7.5 mg/dL warrant treatment. When symptoms are minimal, starting T4 or after a dose adjustment.
oral calcium suffices; calcium citrate is the best absorbed of Patients with MTC, ATC, or lymphoma are started on
the calcium salts. Severe symptoms (e.g., dark vision, feelings
replacement doses of T4 postoperatively because there is no
of doom) or neuromuscular findings (e.g., Trousseau sign or
proven benefit to TSH suppression in these diseases.
claw hand) merit intravenous calcium; calcium gluconate is
the least problematic if extravasated. Calcium is remeasured complications
if treatment is required and reaches a steady state 5 to 6 hours
after oral dosing. Vitamin D supplementation is seldom Thyroidectomy is well tolerated by most patients. General
necessary but is useful for patients who have required intra- postoperative complications such as atelectasis and deep vein
venous calcium or who are marginally controlled by 3 to 4 g thrombosis or pulmonary embolism are possible but less
calcium citrate total daily doses. 1,25-Dihydroxycholecalcif- common than after intracavitary operations. Thyroidectomy is a
erol is the maximally effective vitamin D agent and is given clean operation, and wound infection should be rare. If wound
in one to two doses daily (0.5 to 1.0 µg total daily dose). infection occurs, however, it is potentially quite serious.
Some surgeons use a strategy of routine postoperative oral Infection-related soft tissue edema can lead to airway compro-
calcium (1.5 to 3 g daily, with or without vitamin D) for all mise, and local infection can progress to mediastinitis since
patients after bilateral resections to facilitate early discharge the soft tissues of the thoracic inlet are usually opened during
to home. Serum calcium is measured at the first postoperative thyroidectomy. Thyroidectomy should be postponed if a patient
visit and weaned as tolerated thereafter. arrives for operation with a recent history or current symptoms
of acute pharyngitis.
postoperative thyroid hormone management Complications specific to thyroidectomy include neck hema-
The half-life of T4 is long enough that thyroid hormone toma or seroma, recurrent or external laryngeal nerve injury, and
replacement can be withheld safely until the final surgical transient or permanent hypoparathyroidism. Postoperative
pathology results are available. Awaiting the final diagnosis bleeding into the neck can produce life-threatening airway
allows efficient, individualized treatment. Previously euthy- compromise, and any postoperative respiratory distress should
roid patients seldom become hypothyroid after lobectomy raise concern for neck hematoma. Urgent bedside decompres-
alone. TFT measurement by the patient’s primary care physi- sion by reopening the wound down through the strap muscles
cian at 6 months (sooner if hypothyroid symptoms develop) is lifesaving when symptoms are sudden and severe. The patient
will detect most patients who need T4 supplementation. is then returned to the operating room for wound exploration
Older patients and those with Hashimoto disease are at and reclosure under anesthesia. Neck hematoma development
greatest risk. with few or no symptoms merits intensive care unit observation
Patients will require T4 therapy after bilateral resections. for at least 24 hours. Most bleeding occurs within 4 hours of
For patients with benign disease, levothyroxine can be started operation, and virtually all occurs within 24 hours. Neck seroma
as soon as the pathology results are known. For patients with is particularly likely after resection of very large goiters because
cancer, a decision for or against RAI will guide next steps.
of the residual dead space, and subplatysmal fluid is ballotable
When RAI will be given, efficient preparation with minimal
early postoperatively. In the absence of airway symptoms or
hypothyroid symptoms is accomplished by giving low-dose T3
persistent dysphagia, reassurance of the patient is the only inter-
(50 µg b.i.d.) for 3 weeks. One week thereafter, most patients
vention necessary. Percutaneous aspiration is performed for
will have a TSH level suitable for RAI administration. Alter-
airway or swallowing symptoms or when preferred by the patient
natively, patients may be given no thyroid hormone for the
4 weeks prior to RAI administration, but this approach for cosmetic or comfort reasons.
more often results in bothersome symptoms. Patients can Symptoms or signs of airway compromise not attributable
also reach appropriately high TSH levels by administration of to neck hematoma may indicate injury to the recurrent
recombinant human TSH for a brief period prior to giving laryngeal nerves. Prompt performance of flexible fiberoptic
RAI; this option, however, is very expensive, and the efficacy laryngoscopy allows assessment of vocal cord position and
of RAI using this approach is not conclusively known. A base- function along with evaluation for other etiologies of respira-
line Tg level is most sensitive for the detection of residual tory distress (laryngeal edema, laryngospasm). Diagnostic
thyroid tissue and/or residual WDTC when measured while laryngoscopy should not delay securing the airway of a patient
the patient is thyroprival (TSH is elevated). Anti-Tg antibody with true stridor. Laryngoscopy may, however, be a useful
assay should be measured along with each Tg level; Tg is adjunct to rapid, safe reintubation. Paretic or paralyzed vocal
unreliable when antibodies are present. cords warrant reintubation. Symptomatic patients who are
Regardless of the RAI preparation approach chosen, T4 maintaining their oxygenation without tachypnea may benefit
is started after RAI treatment and/or whole body scan. from inhaling a helium-oxygen admixture. The clinical
01/11
response is rapid, and the admixture should be continued clearly stabilized. Nerve dysfunction at 1 year is likely to be
for several hours before attempting weaning to supplemental permanent.
oxygen alone. Superior laryngeal nerve external branch dysfunction typi-
The reintubated patient should be kept in a head-up cally is more subtle than recurrent nerve injury, and injury
position for 36 to 48 hours. A parenteral dexamethasone rates are not as well established. Referral for comprehensive
bolus may be useful at the time of reintubation and carries evaluation of vocal function is appropriate for persistent voice
little risk. Once the patient has mobilized his perioperative symptoms despite good vocal cord movement or for patients
fluids and has minimal neck edema (usually by 48 hours whose livelihoods require normal voices (e.g., a professional
postoperatively), airway reassessment can be undertaken. singer or storyteller). The impact of routine intraoperative
The patient who can vocalize and move air through the larynx nerve monitoring on recurrent and external branch nerve
with the endotracheal tube in place but with the cuff deflated injury rates is unclear.
is likely to tolerate extubation. Flexible laryngoscopy should Permanent hypoparathyroidism (requirement for calcium
be done immediately postextubation to document vocal cord supplementation more than 1 year postoperatively) should be
function and adequate airway lumen. Close observation for uncommon (< 2%) after bilateral thyroid resections. Up to
an additional 24 to 48 hours is appropriate after successful 10% of patients may have transient hypocalcemia that requires
extubation. For the patient failing extubation, laryngoscopic treatment, especially with Graves disease or synchronous
findings should drive the decision for early tracheostomy lymphadenectomy. Resolution is usually fairly rapid (< 6
or for a second extubation attempt. Vocal cord function weeks). Autotransplanted parathyroid tissue is usually
sufficient to maintain the airway must be documented before functional within 12 weeks postoperatively. Diagnosis and
tracheal decannulation. management of hypocalcemia have already been discussed
Some hoarseness or other vocal change is fairly common [see Early Postoperative Care, Bilateral Resections, above].
early postoperatively and can represent intubation trauma
rather than recurrent nerve injury. Intubation-related vocal outcome evaluation
changes improve rapidly postoperatively. Hoarseness that Surgeons performing thyroidectomies should track their
persists at the first outpatient office visit deserves diagnostic individual rates of nerve and parathyroid injuries along with
laryngoscopy. If vocal cord motion is impaired, consideration wound infections and neck hematomas. Participation in a
should be given to confirmation by a second, independent registry system such as the National Surgical Quality Improve-
observer. Voice rest and aspiration precautions should be ment Program (NSQIP) facilitates recognition of nonspecific
instituted, and the patient is followed carefully. When symp- complications (e.g., urinary tract infection) and system
toms resolve or plateau, laryngoscopy is repeated to docu- parameters (e.g., length of stay).
ment the level of functional return. Interventions such as
vocal cord injection are not undertaken until function has Financial Disclosures: None Reported
References
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2006;191:400–5. lymphoma. World J Surg 2007;31:978–86. 747–56.
9. Jarhult J, Rudberg C, Larsson E, et al. Graves’ 17. Dotto J, Nosé V. Familial thyroid carcinoma. 25. Kinder BK. Well differentiated thyroid
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ophthalmopathy—long term results of a 18. Kim TB Orloff LA. Thyroid ultrasonogra- 26. Ito Y, Miyauchi A. Prognostic factors and
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total thyroid resection. Thyroid 2005;15: ultrasonography. 1st ed. San Diego: Plural nomas of the thyroid. Endocr J 2009;56:
1157–64. Publishing; 2008. p. 69–114. 177–92.
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27. Mazzaferri EL, Doherty GM, et al. The pros 31. Richards ML. Thyroid cancer genetics: 35. Sturgeon C, Sturgeon T, Angelos P. Neuro-
and cons of prophylactic central compart- multiple endocrine neoplasia type 2, non- monitoring in thyroid surgery: attitudes,
ment lymph node dissection for papillary medullary familial thyroid cancer and familial usage patterns, and predictors of use among
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Ann Surg 2007;246:375–84. thyroid cancer: early detection and novel parathyroidism after total thyroidectomy.
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2 HEAD AND NECK 10 PARATHYROID DISEASES AND OPERATIONS — 1
10 PARATHYROID DISEASES AND

OPERATIONS
Patrick B. O’Neal, MD, Atul Gawande, MD, MPH, Francis D. Moore Jr, MD, and Daniel T. Ruan, MD
Anatomy/Embryology Function
The parathyroid glands arise during the fourth and fifth The primary function of the parathyroid glands is to
weeks of gestation from branchial pouches III and IV. The maintain calcium homeostasis within the body. Calcium
superior glands descend into the neck from branchial pouch concentrations in the serum are directly regulated by a sensi-
IV, whereas the inferior glands descend into the neck from tive calcium-sensing receptor that is highly expressed on
branchial pouch III. In general, the superior glands settle the surface of the parathyroid cells. When ionized calcium is
1 cm superior to the inferior thyroid artery in a posterior posi- bound within this receptor, release of parathyroid hormone
tion to the thyroid gland, and the inferior glands settle at the (PTH) is inhibited. In contrast, when ionized calcium levels
lower pole of the thyroid gland in a posterolateral position. are low, fewer receptors are bound, and production of PTH
The superior and inferior parathyroids are consistently is stimulated. PTH is an 84–amino acid protein with multiple
located posterior and anterior to the recurrent laryngeal effects on calcium homeostasis. PTH increases osteoclast and
nerve, respectively. osteoblast activity, leading to the net release of calcium from
The parathyroid glands can be found in ectopic locations. bone stores as clastic activity is more affected than blastic
Approximately 60% of parathyroids on reoperation are not activity. Furthermore, PTH increases gastrointestinal absorp-
located in the typical locations. The inferior glands have a tion and renal calcium retention, primarily in the proximal
higher propensity for this in comparison with the upper tubule and the loop of Henle. Lastly, PTH increases renal
glands. Common ectopic locations of the inferior glands at hydroxylation of 25-hydroxyvitamin D. In addition to increas-
reoperation include the thymus (46%), within the thyroid ing serum calcium, PTH also decreases serum phosphate and
itself (7%), undescended (4%), and the carotid sheath (1%). increases renal bicarbonate excretion.
Common ectopic locations of the superior glands include the
posterior superior mediastinum (40%), the tracheoesopha- Dysfunction
geal groove (17%), within the thyroid (1.5%), and the carotid
Primary hyperparathyroidism (PHPT) results from the
sheath (1.5%). Of note, the posterior and anterior relation to
inappropriately high secretion of PTH causing hypercalce-
the recurrent laryngeal nerve is typically preserved in superior
mia. This is thought to be caused by the spontaneous loss of
and inferior ectopic glands, respectively.
calcium-sensing receptors in parathyroid tissue. This may be
Most commonly, there are four parathyroid glands;
caused by dysfunction in one or multiple parathyroid glands.
however, the incidence of supernumerary glands is around
Approximately 90% of PHPT is caused by adenomas, which
13%. All four glands derive their blood supply from the infe- can be multiple in approximately 3 to 8% of cases. In con-
rior thyroid artery. Venous drainage is by the venous network trast, 9% of PHPT is attributable to four-gland hyperplasia
of the thyroid capsule and/or venous pedicles of the thyroid and approximately 1% is the result of parathyroid carcinoma.
body. The glands are often found embedded in fat. When As much as 3% of PHPT is associated with the multiple
dissected, normal parathyroid glands have a flat triangular endocrine neoplasia (MEN) syndromes. PHPT is not caused
shape with a mustard hue whereas pathologic parathyroids by renal disease, a history of lithium use, or gastrointestinal
are plump with a reddish-brown hue resembling a grape. malabsorptive syndromes.
The recurrent laryngeal nerves innervate all intrinsic Although PHPT has traditionally been considered to
muscles of the larynx except the cricothyroid muscles. These manifest itself by hypercalcemia in the setting of excessive
nerves arise from the vagus nerves in the chest and travel PTH secretion, a less common manifestation of PHPT that
upward on either side of the trachea through the tracheo- has only minimal, intermittent, or even the absence of hyper-
esophageal groove. They usually cross posterior to the infe- calcemia is now being recognized. As many at 15% of patients
rior thyroid arteries but can pass anteriorly. They will then with PHPT will have “normocalcemic hyperparathyroidism.”
cross posterior to or through the Berry ligament to insert As noted, these patients will have elevated PTH levels but
into the cricothyroid muscles. Caution should be taken when will not have persistently elevated calcium levels. In fact,
dissecting this area as the nerve may branch into an anterior some may have calcium levels that are consistently within a
motor branch and a posterior sensory branch. One can normal range. They will still exhibit, however, the destructive
easily mistake a posterior sensory branch as the only branch complications of PHPT. Because one cannot use hypercalce-
and ligate the motor branch causing ipsilateral vocal cord mia as a diagnostic tool for this entity, diagnosis is difficult.
paralysis. Typically, PTH levels are inappropriately elevated in the
10/11
presence of PHPT complications. Vitamin D deficiency and this includes studies showing increased blood pressure, arte-
benign familial hypocalciuric hypercalcemia should be rial stiffness, and intima/media thickness in patients with
excluded prior to the diagnosis. Additionally, evidence sug- PHPT as well as derangements in a number of metabolic
gests that calcium-loading challenges may assist in identifying processes leading to the development of cardiovascular dis-
these patients. In most normal patients, an oral calcium load ease, including dyslipidemia and impaired glucose metabo-
has been shown to suppress serum PTH levels by 70% or lism. In fact, cardiovascular complications are the most
more, whereas in patients with normocalcemic PHPT, this is common cause of death in both treated and untreated patients
usually not the case. Nonetheless, this is not a perfect test and with PHPT. Estimates of mortality resulting from cardiovas-
cannot be used alone to identify these patients. cular disease in patients with PHPT range from 53 to 68%.
Secondary hyperparathyroidism (SHPT) occurs from the This includes death from myocardial infarction, stroke, and
physiologic response to low serum calcium levels of nonpara- heart failure. Epidemiologic studies suggest that the life
thyroid origin. Although the pathophysiology of SHPT is
expectancy in patients with PHPT is lower than that in
complex, it is most commonly caused by chronic renal fail-
matched controls.
ure, which interferes with vitamin D metabolism, which in
turn leads to decreased calcium absorption from nutritional
sources. Other causes include “hungry bone syndrome,” Evaluation of Primary Hyperparathyroidism
sprue, chronic vitamin D deficiency, and aluminum
Although often unrevealing, a thorough history and physi-
toxicity from hemodialysis. Generally, hypercalcemia is not a
cal examination should be performed. This may reveal symp-
characteristic of this disease.
toms or complications of hyperparathyroidism that may need
Tertiary hyperparathyroidism (THPT) is the long-term
consequence of prolonged SHPT after the cause is corrected. to be addressed. Additionally, the information obtained may
It results in autonomously elevated PTH concentrations as a reveal the need to evaluate patients for familial causes of
result of the loss of calcium-sensing receptors in parathyroid hyperparathyroidism, particularly the MEN syndromes.
tissue. The net result of THPT is elevated serum calcium. Physical examination may reveal a palpable neck mass that
The typical scenario is the patient with SHPT attributable to may alert the surgeon to the possibility of malignancy. Phys-
end-stage renal disease who undergoes renal transplantation. ical examination findings in chronic PHPT include band
In this condition, all four glands are treated as hyperplastic keratopathy and intraoral tumors.
glands. Laboratory workup should include serum calcium and
Parathyroid carcinoma is a very rare cause of hyperparathy- PTH levels and 24-hour urinary calcium levels to rule out
roidism. It often results in markedly elevated levels of both familial hypocalciuric hypercalcemia. As noted earlier, patients
PTH and calcium. Complications of hyperparathyroidism are with PHPT typically have elevated serum PTH and serum
more common with parathyroid carcinoma. The incidence of calcium levels but PTH may fluctuate and near normocalce-
kidney stones is over 50%, whereas severe bone disease is mic variants have been reported. In these patients, one will
observed in as many as 90% of patients. These lesions are see a persistently elevated (as opposed to suppressed) PTH
more likely palpable than benign hypersecreting glands, and level despite near normal serum calcium or high normal
on gross inspection, they exhibit invasive features. Histologi- serum calcium levels. Patients with PHPT may have normal
cally, parathyroid carcinoma shows features of capsular and but often have high 24-hour urinary calcium levels as the
vascular invasion, cellular mitoses, thick fibrous bands sepa- kidneys surpass their threshold for calcium resorption.
rating tumor lobules, and a trabecular pattern. Of course, the Patients with benign familial hypocalciuric hypercalcemia will
hallmark of parathyroid carcinoma is its invasive nature. have low 24-hour urinary calcium levels. Additionally, patients
Thirty percent of patients will have nodal metastases on pre- with familial hypocalciuric hypercalcemia generally have
sentation, and the 5-year survival rate approximates 60% mildly elevated serum calcium levels. Benign familial hypo-
with treatment. Posttreatment, recurrent hypercalcemia is a
calciuric hypercalcemia can be excluded in patients with a
good marker for local recurrence or new metastases.
history of normal serum calcium levels in the distant past.
Hyperparathyroid patients are typically hypophosphatemic,
Complications of Hypercalcemia and alkaline phosphatase may predict high-turnover bone
The normal serum calcium level is 9 to 10.5 mg/dL. Dys- disease. 25-Hydroxyvitamin D should be checked to exclude
regulation of calcium homeostasis has profound effects on vitamin D deficiency.
patient well-being. On questioning, patients often complain Localization studies have improved dramatically over
of a general sense of poor physical performance. This includes recent years, allowing for progressively fewer invasive surgical
symptoms of depression, fatigue, muscle weakness, cognitive options. Because 80% of patients with PHPT have a single
deficits, and forgetfulness. In addition, patients may present adenoma, preoperative localization studies allow far less
with gastrointestinal complaints, particularly constipation extensive neck dissection. The mainstays of localization
and gastroesophageal reflux. studies are ultrasonography and sestamibi scanning. Ultraso-
More seriously, 30% of patients with PHPT will develop nography has a sensitivity of 79%. Sestamibi scanning has a
nephrolithiasis and 15% of patients will develop osteoporosis. sensitivity of 88%. When these two modalities are combined,
Occasionally, patients can develop severe osteodystrophy, sensitivity increases to greater than 90%. Sestamibi scanning
resulting in bone pain, osteomalacia, pathologic fractures, works on the premise that both thyroid and parathyroid
and osteitis fibrosa cystica (brown tumors of bone). absorb tracer but that, as a result of increased blood flow in
Interestingly, there is now a growing literature implicating the thyroid, thyroid tracer washes out more quickly (minutes
hyperparathyroidism in atherosclerotic disease. Evidence for to 2 hours), allowing for visualization of enlarged parathyroid
10/11
glands. When comparing early and delayed sestamibi images minimal efficacy and are considered palliative interventions in
persistent uptake may be seen in the delayed images at this context.
the location of pathologic parathyroid glands. Occasionally,
these imaging modalities are insufficient. The advent of
Surgical Technique
four-dimensional computed tomographic (CT) scanning has
allowed for the localization of many allusive parathyroid  
glands. Other options include venous PTH sampling.
Patients with profound hypercalcemia (serum calcium
Although localization studies are useful for surgical planning,
≥ 12.5 mg/dL) or mild to moderate renal failure should be
they should not be used to establish the biochemical
hydrated and given furosemide before operation. On rare
diagnosis.
occasions, such patients require additional treatment—for
example, administration of bisphosphonates, mithramycin, or
Treatment calcitonin. Bisphosphonates should be used with caution as
they can exacerbate postoperative hypocalcemia. Electrolyte
Treatment algorithms depend on the pathology causing
abnormalities, such as hypokalemia, should also be corrected
hyperparathyroidism. In general, PHPT is treated surgically
prior to this elective surgery. Optimally, patients should
with removal of all hyperfunctioning parathyroid tissue. There
have any anticoagulation held perioperatively and should
is agreement that all symptomatic disease should be treated be deemed safe from a cardiopulmonary standpoint for
surgically. However, the indications for the treatment of anesthesia.
asymptomatic disease are less clear-cut. These indications We recommend either bilateral exploration or focused
receive a great deal of scrutiny and are periodically revised exploration with intraoperative PTH assay for most patients
by National Institutes of Health consensus conferences undergoing initial operations for primary sporadic hyperpara-
in response to evolving data. Currently, surgery is recom- thyroidism. The latter approach can be taken only when the
mended for asymptomatic patients with serum calcium levels abnormal gland has been identified by sestamibi scanning
1.0 mg/dL above the upper limit of normal, a glomerular and/or ultrasonography. For patients with familial primary
filtration rate less than 60 mL/min, T scores less than −2.5 or secondary hyperparathyroidism, bilateral exploration is
at any site and/or previous fracture fragility, or age less than recommended because most of these patients have multiple
50 years. T score refers to the number of standard deviations abnormal parathyroid glands.
above or below the normal bone mineral density a person’s Other preoperative localization studies (e.g., magnetic
own bone mineral density is. Normal is defined by a T score resonance imaging [MRI] and CT scanning) are generally
above −1. Osteopenia is defined by a T score between −1 and unnecessary: they provide useful information in about 75% of
−2.5. Osteoporosis is defined by a T score less than −2.5. It patients but are often not considered cost-effective, because
is expected that these criteria for surgery in the asymptomatic an experienced surgeon can treat hyperparathyroidism suc-
patient may be further revised as new data elucidate cessfully without imaging 95 to 98% of the time. Such studies
other complications of hyperparathyroidism, particularly are, however, essential when reoperation for persistent or
atherosclerotic disease. recurrent hyperparathyroidism is indicated. High-resolution,
For individuals who cannot undergo surgery, patients with four-dimensional CT scanning is particularly useful for
persistent hyperparathyroidism in which hyperfunctioning patients in this setting. Patients requiring reoperation should
tissue cannot be found, and patients with hypercalcemic be considered for direct or indirect laryngoscopy before
crisis, a number of medical therapies may improve hypercal- operation to evaluate vocal cord function.
cemia. These include hydration with normal saline, loop Optimum exposure of the parathyroid glands is facilitated
diuretics, bisphosphonates, calcitonin, mithramycin, and cal- by placing a soft roll transversely across the scapula and a
cium receptor agonists. SHPT generally is not considered a support under the occiput; in this way, the neck is gently
surgical disease. Instead, these patients are treated with cal- extended and the thyroid or parathyroids can assume a more
cimimetics, calcium, and vitamin D replacement. Rarely, anterior position. This positioning also facilitates identifica-
with failure of medical management, surgery may be consid- tion of the recurrent laryngeal nerve by placing it under slight
ered. In this case, indications for surgery may include severe tension. The head must be supported to prevent postopera-
pruritis, musculoskeletal pain, renal osteodystrophy, and tive posterior neck pain. Care also is taken to ensure that
calciphylaxis. no body parts are exposed to undue pressure. The skin is
Tertiary hyperthyroidism is primarily a surgical disease. prepared with betadine or chlorhexidine.
Because all parathyroid tissue is hyperfunctioning in these  
patients, the preferred operation is four-gland parathyroidec-
tomy with autotransplantation of half of a single gland or General Troubleshooting
subtotal parathyroidectomy. In the latter case, a parathyroid Safe parathyroid operations require good visualization
remnant roughly the size of a normal parathyroid gland is left of central neck structures. Therefore, the field should be
in situ. bloodless and well illuminated, preferably with the use of a
Parathyroid carcinoma absolutely requires surgery if cure is headlamp. Operating telescopes (×2.5 or ×3.5 magnification)
to be achieved. In this case, the operation of choice is en bloc are also recommended because the recurrent laryngeal nerve
resection of the malignant parathyroid tumor with the overly- can be difficult for some to visualize without magnification.
ing musculature and ipsilateral thyroid lobe. Additionally, If bleeding occurs, surgeons should avoid grasping or
local recurrences and localized distant metastases should be clamping a poorly visualized vessel. A bleeding vessel should
treated surgically. Systemic chemotherapy and radiation have be clamped only after it is precisely identified and inclusion
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of the recurrent laryngeal nerve is excluded. Preoperative muscles. Because the strap muscles are farthest apart low in
localization studies should be available in the operating room the neck, the incision is begun at the sternal notch and
to guide the dissection. extended upward to the thyroid cartilage [see Figure 2].
On the side where the suspected parathyroid adenoma is
Step 1: Incision and Mobilization of Skin Layers
located, the more superficial sternohyoid muscle is separated
A transverse incision paralleling the normal skin lines of the from the underlying sternothyroid muscle by blunt dissection
neck is made approximately 1 cm caudad to the cricoid car- using a Kitner sponge. This typically does not cause bleeding
tilage [see Figure 1]. Preferably, this incision can be placed and should extend posterolaterally until the ansa cervicalis
completely within a skin crease. Such creases can be marked becomes visible on the lateral edge of the sternothyroid
in the preoperative setting with the patient sitting upright muscle and on the medial side of the internal jugular vein.
with a neutral neck position. As a rule, the incision should be The sternothyroid muscle is then dissected free from the
about 4 to 6 cm long and should extend from the anterior thyroid and the prethyroidal fascia with electrocautery until
border of one sternocleidomastoid muscle to the anterior the middle thyroid vein or veins are encountered laterally.
border of the other. Either sharp dissection or electrocautery The thyroid is retracted anteriorly and medially and the
can be used to dissect through the subcutaneous layer and carotid sheath laterally; this retraction places tension on the
platysma muscle. Straight Kelly or small Kocher clamps middle thyroid veins and helps expose the area posterolateral
are placed on the dermis for retraction, which facilitates the to the thyroid, where the parathyroid glands and the
creation of flaps in the avascular plane located just deep to recurrent laryngeal nerves are situated. The middle thyroid
the platysmal muscle and anterior to the anterior jugular veins are ligated with sutures or with a hemostatic device
veins and their branches. These subplatysmal flaps are made
to mobilize the thyroid and provide exposure behind the
in the cephalad direction up to the level of the thyroid carti-
superior portion of the thyroid lobe [see Figure 3].
lage notch and caudally down to the suprasternal notch.
Self-retaining retractors are then applied.
Troubleshooting Separation of the sternohyoid muscle
from the sternothyroid muscle improves exposure of the
Troubleshooting Placing the incision approximately
operative field and does not worsen postoperative morbidity.
1 cm below the cricoid locates it precisely over the thyroid
The middle thyroid veins should be dissected free to prevent
isthmus. The course of the incision should conform to or
injury to the recurrent laryngeal nerve prior to their ligation.
overlay the natural skin creases. The length of the incision
It is always safest to mobilize tissues parallel to the recurrent
should be modified as necessary for good exposure. Patients
laryngeal nerve rather than transversely across its anticipated
with short, thick necks or large, low-lying tumors require
course. If the exposure is so limited that the strap muscles
longer incisions. The lateral margins of the incision should be
have to be divided, this should be done horizontally and
at equal distances from the midline, and the overall shape
high enough in the neck to preserve innervation to the bulk of
of the incision should be symmetrical. Flaps must be created
the muscles. These muscles can be closed with interrupted
using anterior traction and taking care not to perforate the
figure-of-eight 2-0 absorbable sutures, holding the muscle
skin.
apposed as the sutures are taken to prevent shredding. The
Step 2: Midline Dissection and Mobilization of Strap Muscles neck can be gently flexed or held in a neutral position at this
and Thyroid late stage of the operation to facilitate muscle approximation.
The thyroid gland is exposed via a longitudinal midline Step 3: Identification of Upper Parathyroid Glands
incision through the deep cervical fascia between the strap
Dissection is continued superiorly, laterally, and posteri-
orly with a small Kitner sponge on a clamp. This maneuver
can be performed with minimal bleeding when done gently.
The superior thyroid artery and veins are identified by retract-
ing the thyroid inferiorly and medially. The tissues postero-
lateral to the upper lobe of the thyroid and medial to the
carotid sheath can be mobilized caudally to the cricothyroid
muscle; the recurrent laryngeal nerve enters the larynx
just posterior to the Berry ligament at this craniocaudal level
[see Figure 4]. Berry ligament refers to the lateral ligament
suspending the thyroid to the trachea. It is attached to the
inferior margin of the cricoid cartilage cornu and extends
inferomedially onto the trachea. At the level of the cricoid
cartilage, the mean distance between the attachment of the
ligament to the cricoid cartilage and the recurrent laryngeal
nerve is 1.9 mm. This is the most common location of recur-
rent laryngeal nerve injury. Caution should be taken when
Figure 1 The initial incision is made 1 cm below the cricoid
dissecting caudal to the cricoid cartilage in this region, where
cartilage and follows normal skin lines. A sterile marking pen the recurrent nerve can be encountered.
is used to mark the midline of the neck, the level of the The tissues posterior and lateral to the superior pole can be
incision, and the lateral borders of the incision. A 2-0 silk tie easily swept by blunt dissection away from the thyroid gland
is pressed against the neck to mark the incision site itself. medially and anteriorly and away from the carotid sheath
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Figure 2 To expose the thyroid, a midline incision is made through the superficial layer of deep cervical fascia between the
strap muscles. The incision is begun at the suprasternal notch and extended to the thyroid cartilage.
laterally. The upper parathyroid gland is often identified the tracheoesophageal groove and more obliquely on the
at this time near the level of the cricoid cartilage situated right. As such, it can be more susceptible to accidental injury
posterior to the recurrent laryngeal nerve. on the right side. Dissection should proceed cephalad along
the lateral edge of the thyroid. Fatty and lymphatic tissues
Step 4: Identification of Recurrent Laryngeal Nerves and loosely attached to the thyroid capsule are swept from it with
Lower Parathyroid Glands a Kitner sponge on a clamp, and small vessels are ligated.
When the thyroid lobe is further mobilized and retracted No tissue should be transected until one is sure that it is not
anteromedially, the lower parathyroid gland is often found the recurrent laryngeal nerve. Some find it helpful to use a
anterior to the recurrent laryngeal nerve and inferior to where nerve monitoring device for this portion of the dissection.
the inferior thyroid artery crosses the recurrent laryngeal
nerve [see Figure 5]. The carotid sheath is gently retracted Troubleshooting The upper parathyroid glands are
laterally, and the thyroid gland is retracted anteriorly and usually situated on each side of the thyroid gland just postero-
medially. This retraction puts tension on the inferior thyroid lateral to where the recurrent laryngeal nerves enter the
artery and consequently on the recurrent laryngeal nerve, cricothyroid muscle [see Figure 4 and Figure 5]. Because the
thereby facilitating the identification of the nerve. The recur- recurrent laryngeal nerve enters the larynx posterior to the cri-
rent laryngeal nerve is situated more medially on the left in cothyroid muscle at the level of the cricoid cartilage, caution
should be taken when dissecting caudal to this area.
The right and left recurrent laryngeal nerves should be
preserved during every parathyroid operation. Although both
nerves enter at the posterior medial position of the larynx in
the cricothyroid muscle, their courses vary considerably. The
right recurrent laryngeal nerve takes a more oblique course
than the left recurrent laryngeal nerve and may pass either
anterior or posterior to the inferior thyroid artery. In about
0.5% of persons, the right recurrent laryngeal nerve is non-
recurrent and may enter the thyroid from a superior or lateral
direction. On rare occasions, both a recurrent and a nonre-
current laryngeal nerve may be present on the right. The left
recurrent laryngeal nerve almost always runs in the tracheo-
esophageal groove because of its deeper origin within the
thorax as it loops around the ductus arteriosus. Recurrent
laryngeal nerves often branch before entering the larynx; the
left nerve is more likely to do this. Although all nerve branches
should be preserved, the motor fibers of the recurrent
laryngeal nerve are usually in the most medial branch.
It is helpful to remember that the recurrent laryngeal nerves
are supplied by a small vascular plexus and that a tiny vessel
runs parallel to and directly on each nerve, which contrasts
with the white color of the nerve [see Figure 4]. In young
Figure 3 The middle thyroid veins are divided to give better persons, the artery usually is readily distinguished from the
exposure behind the superior portion of the thyroid lobe. recurrent laryngeal nerve. However, in older persons with
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Figure 4 The recurrent laryngeal nerve enters the cricothyroid muscle at the level of the cricoid cartilage, first passing through
the Berry ligament.
arteriosclerosis, the white-appearing artery may be mistaken the surrounding tissue in the neck; they feel like a taut
for the nerve, and caution should be taken. Lateral traction ligature of approximately 2-0 gauge.
on the carotid sheath and medial and anterior traction on the About 85% of people have four parathyroid glands, and in
thyroid gland place tension on the inferior thyroid artery; this about 85% of these persons, the parathyroids are situated on
maneuver often helps identify the recurrent laryngeal nerve the posterior lateral capsule of the thyroid. Normal parathy-
where it courses lateral to the midportion of the thyroid roid glands measure about 3 × 3 × 4 mm and are light brown
gland. It is usually safest to identify the recurrent laryngeal in color. The upper parathyroid glands are more posterior
nerve low in the neck and then to follow it to where it enters and more constant in position (at the level of the cricoid
the cricothyroid muscle through the Berry ligament. Some- cartilage) than the lower parathyroid glands, which typically
times the recurrent laryngeal nerves can be palpated through are more anterior (on the posterolateral surface of the thyroid
Figure 5 The upper parathyroid glands are usually situated on either side of the thyroid at the level where the recurrent
laryngeal nerve enters the cricothyroid muscle. The lower parathyroid glands are usually anterior to the recurrent laryngeal
nerve and inferior to where the inferior thyroid artery crosses this nerve.
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gland). Both the upper and the lower parathyroid glands is often in the mediastinum. To minimize the risk of recurrent
are supplied by small branches of the inferior and superior nerve injury during removal of identified parathyroids, dis-
thyroid arteries in most patients. About 15% of parathyroid section should be directly on the surface of the capsule with-
glands are intrathymic, and about 1% are intrathyroidal. out disruption. The risk of permanent hypoparathyroidism or
Other abnormal sites for the parathyroid glands are (1) the injury to the recurrent nerve should be less than 2%.
carotid sheath, (2) the anterior and posterior mediastinum,
and (3) anterior to the carotid bulb or along the pharynx Step 6: Closure
(undescended parathyroids). The strap muscles are approximated with interrupted 3-0
The upper parathyroid glands are usually posterolateral to Vicryl sutures, and an opening is left in the midline at the
the recurrent laryngeal nerve at the level of the Berry liga- suprasternal notch to make any bleeding that occurs more
ment. When the upper parathyroids are not found at this site, evident and to allow the blood to exit the central neck. The
they often can be found in the tracheoesophageal groove or platysma is reapproximated with interrupted absorbable
in the posterior mediastinum along the esophagus. The lower sutures. The skin is then closed using a deep dermal absorb-
parathyroid glands are almost always situated anterior to the able stitch, and either a skin adhesive or sterile tape is applied
recurrent laryngeal nerves and caudal to where the recurrent on the epidermis.
laryngeal nerve crosses the inferior thyroid artery; they may
be surrounded by lymph nodes. When the lower parathyroids  
are not found at this site, they usually can be found in Four-Gland Parathyroidectomy for Hyperplasia
the anterior mediastinum (typically in the thymus or the
perithymic fat). This procedure will render a patient permanently
hypocalcemic. We prefer to leave a remnant of the most
Step 5: Parathyroid Resection normal-appearing parathyroid gland in situ. Alternatively,
Abnormal parathyroid glands are then removed. In about autotransplantation can be done by mincing the most normal
80% of patients with PHPT, one parathyroid gland is abnor- parathyroid into 1 mm cubes and placing it in a pocket inside
mal; in about 15%, all glands are abnormal (diffuse hyperpla- the sternocleidomastoid muscle, subcutaneous tissue, or
sia); and in about 5%, two or three glands are abnormal and forearm muscle. Clips can be placed in this location to aid in
one or two are normal. Parathyroid cancer occurs in about localization should a second resection become required.
1% of patients with PHPT.
Parathyroid Cancer
Troubleshooting In some patients, parathyroid tumors Parathyroid lesions that grossly extend into neighboring
and hyperplastic parathyroid glands are difficult to find. If this structures should prompt suspicion of malignancy. Such
is the case, the first step is to explore the sites where the para- lesions should be removed en bloc with the ipsilateral thyroid
thyroids are usually located, near the posterolateral surface of lobe by hemithyroidectomy. On rare occasions, parathyroid
the thyroid gland within 1 cm of the point where the inferior cancers may invade the trachea or the esophagus. As much as
thyroid artery crosses the recurrent laryngeal nerve. Typically, 5 cm of the trachea can be resected safely, without impair-
the upper and lower parathyroid glands are located posterolat- ment of the patient’s voice. If the invasion is not extensive
eral and anteromedial to the recurrent nerve, respectively. and is confined to the anterior portion of the trachea, a small
When a lower gland is missing from the usual location, it is section of the trachea that contains the tumor should be
often intrathymic in the upper mediastinum or lower neck. excised, and a tracheostomy may be placed at the site of
Approximately 15% of parathyroids are found within the resection. If the invasion is more extensive or occurs in the
thymus. If an upper parathyroid gland cannot be located, one lateral or posterior portion of the trachea, a segment of the
should look not only far behind the thyroid gland superiorly trachea measuring several centimeters long is resected, and
but also in a paraesophageal position down into the posterior the remaining segments are reanastomosed. To prevent
mediastinum. A thyroid lobectomy should be done on the side tension on the anastomosis, the trachea should be mobilized
where fewer than two parathyroid glands have been located before resection, the recurrent laryngeal nerves should be pre-
and no abnormal parathyroid tissue has been identified, served and mobilized from the trachea, and the mylohyoid
and the preoperative consent should prepare patients for this fascia and muscles should be divided above the thyroid carti-
possibility. The carotid sheath and the area posterior to the lage to drop the cartilage. Care must be taken not to injure
carotid, as well as the retroesophageal area, should also be the internal laryngeal nerves during this dissection, given that
explored for unidentified upper parathyroids. In rare cases, these nerves course from lateral to medial just above the
there may be an undescended parathyroid tumor anterior to lateral aspects of the thyroid cartilage. After resection, the
the carotid bulb. trachea is reapproximated with 3-0 Maxon sutures. One or
Although we do not recommend routine biopsy of more two Penrose drains should be left near the resection site to
than one normal-appearing parathyroid gland, we do recom- allow air to exit. The drains are removed after several days,
mend taking a small biopsy of all normal parathyroid glands when there is no more evidence of air leakage.
when no abnormal parathyroid tissue can be found. This can If the esophagus is invaded by tumor, the muscular wall of
be done by placing a small clip across the apex of the gland the esophagus can be resected along with the tumor, with the
followed by sharp dissection; this achieves good hemostasis inner esophageal layer left in place. If the recurrent nerve is
without devascularizing the gland and permanently marks it surrounded or invaded by tumor, it is known that it can be
for future reference. When four normal parathyroid glands dissected free, even with a slight coating of tumor, without
are found in the neck, the fifth (abnormal) parathyroid gland adversely affecting the patient’s cancer prognosis. However,
10/11
preoperative direct laryngoscopy or the use of nerve monitor- muscular contractions with hyperextension of the fingers
ing can allow the surgeon to determine whether the nerve is in some hypocalcemic patients.
still functional prior to this dissection by testing proximal to Hypoparathyroidism may arise as the result of removal,
the point of invasion. Knowledge that the nerve is not func- bruising, ischemic injury, or devascularization of the
tioning can then be used to more aggressively resect the tissue parathyroid glands. These injuries can be avoided by
in the ipsilateral paratracheal space, including the nerve. In restricting any dissection to the plane nearest the thyroid
the absence of nerve testing, careful observation can reveal a capsule and then gently teasing tissue away in a postero-
full, white nerve proximal to the tumor but a collapsed, gray lateral direction. As noted, hypocalcemia from hypopara-
nerve distal to the tumor, in which case, a complete interrup- thyroidism may be transient or permanent if all four glands
tion by the tumor can be inferred. In general, a recurrent are permanently damaged. If one is concerned about the
laryngeal nerve that is functioning normally preoperatively inadvertent devascularization of normal parathyroid tissue
also should be functioning postoperatively. intraoperatively, biopsy should be performed on the gland
  to confirm its identity and then minced pieces should be
autotransplanted into a pocket in the sternocleidomastoid
Patients with hyperparathyroidism should have values for
muscle. This tissue should not be expected to function
serum calcium, phosphorus, and PTH checked in follow-up
immediately; rather, it will begin to function in a matter of
to evaluate for the possibility of persistent or recurrent hyper-
weeks. Only about 50% of autotransplanted parathyroid
parathyroidism. Persistent hyperparathyroidism is considered
glands survive.
when hypercalcemia in the setting of elevated PTH levels
occurs within 6 months of surgery, whereas recurrent Laboratory values in postoperative patients with hypo-
hyperparathyroidism is considered when corrected calcium parathyroidism are likely to show low serum calcium, high
and PTH levels rise again 6 months or more after surgery. phosphorus, and low or even undetectable PTH levels.
As many as 10% of patients will develop recurrent hyperpara- It is also important to note magnesium levels as calcium
thyroidism in their lifetime. replacement can be dependent on maintaining normal
In the immediate postoperative days, patients should magnesium levels as well.
receive oral calcium and vitamin D as prophylaxis against Hungry bone syndrome is a phenomenon that occurs
hypocalcemia that can occur in the early days after parathy- after the PTH stimulus for bone resorption has been taken
roidectomy. Such temporary calcium supplementation allows away and the bones suddenly begin to sequester calcium.
the remaining, normal, potentially suppressed parathyroid The consequence of this sequestration is hypocalcemia.
tissue time to upregulate. Serum calcium level checks during Additionally, phosphorus will be absorbed as well, giving
this period of supplementation can be used to guide with- low serum phosphorus levels. PTH levels may be slightly
drawal. A typical starting dose for calcium supplementation elevated here as they begin to respond to the declining
is 5 days’ worth of two calcium citrate tablets four times serum calcium concentration. This phenomenon may last
daily. days or, sometimes, even weeks. A severe manifestation
of this condition occurs in patients with osteitis fibrosa
 cystica. In addition to the profound hypocalcemia that
The following are the most significant complications of may occur after parathyroidectomy, these patients may
parathyroidectomy: have very high alkaline phosphatase levels.
Patients treated for a single adenoma are more likely to
1. Hypocalcemia. Hypocalcemia after parathyroidectomy has
have hypocalcemia secondary to hungry bone syndrome.
a number of causes, including permanent hypoparathy-
This generally presents 2 to 3 days postoperatively. Patients
roidism, transient hypoparathyroidism, and a condition
being treated with four-gland exploration with multiple
referred to as hungry bone syndrome. Whereas the normal
serum calcium is 9.0 to 10.5 mg/dL, anything below that resections are more likely to experience permanent hypo-
would be considered hypocalcemic. Few people, however, calcemia. This can present within 2 hours of surgery.
will have symptomatic hypocalcemia with only mildly low Treatment and prophylaxis for hypocalcemia associated
serum calcium. Symptoms generally do not occur unless with both problems are similar; in particular, treatment
serum calcium is less than 8.0 mg/dL. Additionally, it is consists of oral calcium, calcitriol, and magnesium when
important to note that symptomatic hypocalcemia may be it is also low. It is our practice to give every patient for
related to both the actual serum calcium level as well as its 5 days after surgery, calcium citrate four times per day and
rate of fall. It is important to acknowledge how high a 0.5 mg calcitriol daily. If patients complain of symptoms,
patient’s serum calcium level was preoperatively when we ask them to take double doses. We recommend cal-
faced with an individual complaining of hypocalcemic cium citrate over calcium carbonate because calcium
symptoms. citrate is better absorbed. Rarely does anyone require
Hypocalcemia can have a wide range of severity. Mild intravenous calcium replacement as oral calcium is readily
hypocalcemia may present with perioral numbness and absorbed.
tingling in the fingertips, whereas severe hypocalcemia 2. Injury to the recurrent laryngeal nerve. Unilateral recurrent
may present with muscle cramping, spasm, and tetany. nerve dysfunction usually results in a hoarse voice and
Signs of hypocalcemia include Chvostek sign, a twitching sometimes aspiration when swallowing liquids of thin con-
of the facial muscles when the cheek is tapped over the sistency. If a recurrent nerve is transected during surgery,
facial nerve. Trousseau sign is elicited by inflating a sphyg- the ends should be débrided and anastomosed with
momanometer above systolic blood pressure, which causes 6-0 permanent interrupted sutures. This does not restore
10/11
vocal cord function but medializes the cord and prevents somewhat controversial whether or not it adds much when
atrophy. Bilateral injury to the recurrent laryngeal nerve there is concordance between operative findings and preop-
may result in airway obstruction, which often requires erative imaging. Based on our experience, it does not add
tracheostomy. significantly when preoperative localization studies are con-
3. Bleeding. Postoperative bleeding can be life threatening in cordant. When ultrasonography, sestamibi scanning, and
that it can compress the trachea and result in airway intraoperative PTH testing are combined, patients have an
obstruction. Any postoperative respiratory distress should approximately 98% chance of cure. This is equal in success
be attributed to a neck hematoma until proven otherwise. to the results from bilateral neck surgery and four-gland
Most bleeding occurs within 4 hours of operation, and exploration.
virtually all occurs within 24 hours. Acute airway compro-
mise from hematoma requires that the incision be opened
Multiple Endocrine Neoplasia Syndromes
emergently without waiting for reintubation.
4. Infection. This complication is exceedingly rare after The MEN syndromes are an inherited group of disorders
parathyroidectomy. Any patient with acute pharyngitis or characterized by the propensity for patients to develop tumors
neck cellulitis should not undergo this procedure until the and diffuse hyperplasia of endocrine tissues. They are
infection resolves. inherited in an autosomal dominant fashion. Because these
5. Seroma. Most seromas are small and reabsorb spontane- syndromes can present with simultaneous, different endo-
ously. Symptomatic seromas can be aspirated. Compres- crine tumors, treatment algorithms will be influenced by the
sion bandages after aspiration are helpful in some cases. consequences of the various presenting tumors. Additionally,
6. Keloid. Hypertrophic and keloid scar formation after thy- prophylactic operations in these patient populations may
roidectomy is most common in African-American patients be recommended by the high penetrance of endocrine
and in patients with a history of this problem. malignancies.
MEN I is characterized by hyperparathyroidism and pitu-
  itary and pancreatic neuroendocrine tumors. Ninety percent
The patient should have a normal voice and be normocal- of patients with this syndrome will have a mutation in the
cemic. The overall complication rate should be less than 2%. MENIN tumor suppressor gene located on chromosome
Most patients can return to work or full activity in 1 to 11q13. All MEN I cases will present with hyperparathyroid-
2 weeks. ism, two thirds of which will be the initial manifestation of
this syndrome. Most cases will occur before age 40 and will
  exhibit multiglandular disease. About 70% of MEN I patients
Much has been written and discussed about limiting will have neuroendocrine tumors of the pancreas. In this
parathyroid surgery to the exposure and removal of a single population, the tumors are usually multiple and are generally
parathyroid, with consequent reduced morbidity and benign. Gastrinomas are the most common for MEN I
improved cosmesis. As experience has been gained with these patients as opposed to the general population, which has a
techniques, we have come to realize that virtually all parathy- higher incidence of insulinomas. The most common pituitary
roid surgery can be performed on an outpatient basis and tumor is prolactinoma. The workup for these patients should
that the morbidity is independent of the size of the incision routinely include serum calcium and gastrin levels, pancreatic
or the extent of the exploration. Thus, the advantage of polypeptide levels, fasting blood glucose, serum prolactin,
the “limited,” “concise,” “focused,” or “mini” parathyroid visual field testing, and head imaging. Because hypercalcemia
exploration may be only to those with cosmetic concerns. often exacerbates the symptoms of pancreatic neuroendo-
Nonetheless, “mini” parathyroidectomy remains a popular crine tumors, it is preferable to treat the hyperparathyroidism
operative method, limiting the necessity for a full four-gland in MEN I patients first. All patients should undergo four-
exploration. This uses preoperative ultrasonography and gland parathyroidectomy with autotransplantation of a single
sestamibi scanning to direct a more focused exploration. remnant to prevent permanent hypocalcemia. Supernumer-
When both modalities have concordant results suggesting a ary parathyroids are common in this group.
single abnormal gland, one has a greater than 97% success MEN IIa is characterized by hyperparathyroidism,
with a focused parathyroidectomy that avoids bilateral neck medullary thyroid cancer, and pheochromocytomas. These
dissection. In our experience, we have found it useful to take patients generally have a mutation in the ret proto-oncogene
the time to explore the ipsilateral presumed “normal” para- on chromosome 10. This gene codes for a cell membrane
thyroid under these circumstances. On rare occasions, this receptor tyrosine kinase. Only about half of these patients will
ipsilateral gland will be abnormal and prompt the appropriate have hyperparathyroidism, again involving multiple glands.
bilateral neck exploration. Around 70% will have pheochromocytomas, and in this
Also of utility with this method is intraoperative PTH patient population, they are often bilateral, multiple, and
testing. Because PTH has a half-life of less than 5 minutes, extra-adrenal. Only rarely are they malignant. Most patients
comparison of a predissection PTH level to one obtained will present with pheochromocytomas in the third or fourth
10 minutes after excision of the adenoma should show a 50% decade of life. All of these patients will develop medullary
or greater drop if all the abnormal parathyroid tissue has been thyroid carcinoma. Because these tumors present at a younger
removed. If this does not happen, the surgeon is generally age than sporadic medullary thyroid carcinoma, it is recom-
directed to continue exploring the neck. At its inception, mended that patients have prophylactic total thyroidectomies
this assay received great attention; however, it has become at 2 years of age. All of these patients should undergo ret
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proto-oncogene mutation screening as it is 95% sensitive for MEN IIb is characterized by medullary thyroid carcinomas
this syndrome. Additionally, serum calcium levels should be (95%), pheochromocytomas (50%), neuromas (100%), and
monitored, pentagastrin-stimulated plasma calcitonin can be marfanoid habitus (70%). This syndrome is also associated
used to follow patients for recurrence, and urinary catechol- with the ret proto-oncogene mutation. In these patients,
amines and their metabolites, as well as metaiodobenzylgua- medullary thyroid carcinoma presents 15 years earlier than in
nidine (MIBG) testing, should be considered in patients. In patients with MEN IIa and is more severe, and metastases are
patients with concurrent tumors, pheochromocytomas should almost always found on presentation. The workup is the same
be treated first as operative management of other tumors may as that for patients with MEN IIa. Again, pheochromocyto-
precipitate hypertensive crisis. Patients with hyperparathy- mas should be treated first. Prophylactic total thyroidectomy
roidism should undergo four-gland parathyroidectomy with should be performed as soon as the diagnosis of MEN IIb is
single-gland remnant autotransplantation. Some kindreds made.
have uniglandular disease and do not require such extensive
surgery. Financial Disclosures: None Reported
Recommended Reading
Chen H, Sokol LJ, Udelsman R. Outpatient Clark OH: Endocrine surgery of the thyroid and Henry JF, Audiffret J, Denizot A, et al. The
minimally invasive parathyroidectomy: a parathyroid glands. Philadelphia (PA): WB nonrecurrent inferior laryngeal nerve: review
combination of sestamibi-SPECT localiza- Saunders; 2003. of 33 cases, including two on the left side.
tion, cervical block anesthesia, and intraop- Gawande AA, Monchik JM, Abbruzzese TA, et al. Surgery 1988;104:977.
erative parathyroid hormone assay. Surgery Reassessment of PTH monitoring during Tezelman S, Shen W, Shaver JK, et al.
1999;126:1016. parathyroidectomy for primary hyperparathy-
Double parathyroid adenomas: clinical and
Chertok-Shacham, E: Biomarkers of hypercoagu- roidism after two preoperative localization
studies. Arch Surg 2006;141:381. biochemical characteristics before and after
lability and inflammation in primary hyper- parathyroidectomy. Ann Surg 1993;218:300.
parathyroidism. Med Sci Monit, 2008;14: Gerlach C, et al. Increased plasma N-terminal
pro-B-type natriuretic peptide and markers of Thompson NW, Olsen WR, Hoffman GL. The
CR628–632. continuing development of the technique of
inflammation related to atherosclerosis in
Clark OH. Total thyroidectomy and lymph node thyroidectomy. Surgery 1973;73:913.
patients with primary hyperparathyroidism.
dissection for cancer of the thyroid. In: Hyhus Clin Endo 2005;63:493–498. Wang H. Reporting thyroid fine-needle aspiration:
LM, Baker RJ, editors. Mastery of surgery. Gordon LL, Snyder WH, Wians JR, et al. The literature review and a proposal. Diagnostic
2nd ed. Boston: Little, Brown and Co; 1992. validity of quick intraoperative hormone Cytopathology 2005;34:67–76.
p. 204. assay: an evaluation of seventy-two patients
Clark OH. Total thyroid lobectomy. In: Daly JM, based on gross morphology criteria. Surgery
Cady B, Low DW, editors. Atlas of surgical 1999;126:1030.
oncology. St. Louis: CV Mosby; 1993. p. 41. Irvin GL, Molinari AS, Figuero C, et al. Improved
Clark O, Duh QY, Kebebew El. Textbook of success rate in reoperative parathyroidectomy
Acknowledgment
endocrine surgery. 2nd ed. Philadelphia (PA): with intraoperative PTH assay. Ann Surg
Elsevier Saunders; 2005. 1999;229:874. Figures 1 through 5 Tom Moore
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3 BREAST, SKIN, AND SOFT TISSUE 1 BREAST CANCER — 1
1 BREAST CANCER
Stephen B. Edge, MD, FACS*
Breast cancer is the most common malignancy in women in a genetic specialist for genetic counseling and possible genetic
the Western world. It is increasingly prevalent in developing testing. Finally, a thorough history of medication use should
countries and leads to the death of hundreds of thousands be recorded. In addition to common prescription medication,
of women worldwide annually. In the United States, general the patient should be queried regarding the use of supple-
surgeons treat most breast cancers. It is the responsibility of ments and other alternative medicine because of the potential
surgeons to have a thorough understanding of the principles effect on hormone metabolism and bleeding.
and current practices of breast cancer surgery and care beyond Examination of the breast and chest wall begins maneuvers
surgery, including the use of imaging and other diagnostic to accentuate skin puckering or retraction, including extend-
modalities, pathology, radiation, and systemic therapy, so ing the arms over the head and/or flexing the pectoral muscles
that surgical care is coordinated as a component of compre- with the hands on the patient’s hips. Examination of the axilla
hensive breast cancer care. is best performed in the sitting position. The key to successful
Breast cancer refers primarily to a malignancy of the examination of the axilla is relaxation of the muscles of the
epithelium of the ductal and lobular epithelial components of shoulder girdle. This is best accomplished with the examiner
the breast. Nonepithelial malignancies of the breast are much supporting the full weight of the arm abducted from the body
less common and include tumors of mesenchymal origin at about an angle of 60{198} while palpating the axilla with
(phylloides tumors, soft tissue sarcomas) and lymphoma.1,2 the other hand. Care should be taken to examine the axilla
The breast is only rarely the site of metastases from other fully underneath the pectoral muscles and along the chest
primary malignancies. This chapter addresses only the wall toward the latissimus muscle. It is important to examine
treatment of epithelial malignancies. both axillae. The supraclavicular region should be carefully
examined for the presence of enlarged lymph nodes.
Investigative Studies The most common technique for examining the breast
includes accentuating the skin of the breast by placing the
history and physical examination patient’s hand behind her head. The surgeon should develop
Most women with breast cancer are asymptomatic at the a standard manner of examining the breast so that the entirety
time of presentation, but a complete history of breast-related of both breasts is fully examined. It is generally best to begin
symptoms and evaluation for symptoms related to metastatic the examination with the breast opposite the breast of con-
disease should be performed. Particular attention should be cern so that this examination is not forgotten. Most examin-
paid to skeletal symptoms and their extent or degree and ers use a process of pushing the breast tissue back against
duration. A prior history of imaging findings and biopsies is the underlying rib cage starting at the areola and working
important. The history should include the presence of masses out in a circular motion extending through the entire breast,
or lumps in the breast, any apparent swelling, edema or thick- recognizing that the breast tissues goes into the axilla. The
ening in the breast tissue or skin, and the presence or absence character and size of any masses identified should be noted.
of discharge from the nipple (character, color, consistency, The density and glandularity of the breast should be identi-
frequency, and mode of expression—spontaneous or elicited). fied. It is important to compare areas of dense glandular
The patient should be queried regarding any changes in tissue with the contralateral side to identify subtle differences
the appearance of the nipple and the areola, the presence in the size and density of breast tissue. Although the primary
of scaling, eczematous changes, or peeling of the skin. The examination is performed in the supine position, the patient
physician should also document factors related to breast should be queried as to whether she perceives a palpable
cancer risk: age at onset of menarche and menopause, age at lesion and should be asked to reproduce the position where
first-term pregnancy and hormone use, and a detailed family the lesion is best examined. Frequently, patients will identify
history, including the type of cancer and age at onset of all a lesion in a position other than the supine position, and
first-degree and second-degree relatives with breast cancer subtle findings may be identified in this way. After examina-
and ovarian cancer, on both the maternal and paternal sides tion of the breast, the skin of the nipple and areola should
of the family. If there is evidence of a syndrome of inherited also be carefully examined, and after warning the patient, the
susceptibility to breast and ovarian cancer or to other inher- nipple may be compressed to elicit a discharge.
ited syndromes, consideration should be made for referral to Ultrasonography is an excellent adjunct to physical exami-
nation to allow the characterization of palpable lesions as
* The author and editors gratefully acknowledge the contribu- solid or cystic and to help define whether there is a specific
tions of the previous authors, Doreen M. Agnese, MD, FACS, lesion identified in areas of dense breast. Surgeons who
Stephen P. Povoski, MD, FACS, and Wiley W. Souba, MD, perform ultrasonography in the office need to be fully familiar
ScD, FACS, to the development and writing of the original with its value and limitations and should undergo appropriate
chapter. training and certification of their skill. Surgeon-performed
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ultrasonography may or may not replace ultrasonography the known cancer. MRI detects mammographically occult
performed as part of the diagnostic breast imaging. breast cancer in the contralateral breast in as many as 3% of
women.9
IMAGING
MRI may assist in surgical planning. It is critical to reco-
Mammography gnize that surgical planning for cancer treatment cannot be
based on the MRI finding alone and requires biopsy confir-
The majority of breast cancers are detected by screening
mation of any suspicious findings. Retrospective studies show
mammography. Controversy continues over the exact popu- that the surgical treatment planning is changed by MRI find-
lations that benefit from screening mammography, but most ings in as many as 20% of cases—most commonly, alteration
organizations recommend mammography annually beginning from planned breast conservation to mastectomy. However,
at age 40 and at a younger age for women at substantial risk every study to date that has examined the question has failed
for increased risk of cancer.3–5 to show any difference in outcomes, including local recur-
Concerning findings include new masses, asymmetry, rence in women having presurgical MRI.10 Use of MRI may,
distortion in the architecture of the breast tissue, and the paradoxically, unnecessarily increase the use of mastectomy.
presence of calcifications grouped (“clustered”) in an area of Therefore, the use of MRI in treatment planning remains
breast tissue. When an abnormality is identified, the mam- controversial.
mogram becomes a “diagnostic mammogram,” and supple- MRI may be useful in women with locally advanced breast
mental views are obtained in addition to the standard cancer for whom neoadjuvant chemotherapy is being con-
bilateral craniocaudad and mediolateral oblique screening sidered to downsize the tumor to allow breast conservation.
views. These include accentuated positions, localized “spot” In addition, MRI clinical response quantified by changes
compression, and magnified settings. Any finding should be in enhancement and in reduction in tumor volume may be
compared with previous mammograms to determine if it is prognostic of ultimate cancer outcome.
new. Mammogram findings are assigned a score of 0 to 6
using the Breast Imaging Reporting and Data System (BI- Other Imaging Modalities
RADS), with BI-RADS 4 and 5 findings requiring biopsy.6 Other imaging modalities include sestamibi imaging and
Mammography detects only 80 to 90% of breast cancers and positron emission tomography (PET).11–13 Sestamibi imaging
is less sensitive in women with dense glandular tissue (more remains investigational. PET scanning is of minimal value in
common in younger women) and for lobular cancer. Suspi- evaluating the primary tumor. Other whole-body imaging
cious physical findings (e.g., a lump or discharge) should be of the asymptomatic patient with breast cancer is not useful
evaluated and biopsied even if breast imaging is normal. in stage I and II breast cancer unless there are symptoms
Mammography also has a relatively low specificity, with about suggestive of metastatic disease but may be used in those with
60 to 70% of all lesions requiring biopsy proving benign. advanced disease.
Ultrasonography
Ultrasonography is an adjunctive imaging tool to define Evaluation of Suspicious Findings
the characteristics of a lesion identified by other imaging A breast lesion suspicious for malignancy requires tissue
modalities. Ultrasonography itself is not a useful screening biopsy. Percutaneous needle biopsy is preferred over surgical
tool. It primarily defines whether a lesion is cystic or solid. excision in all circumstances. Surgical excision as a diagnostic
Malignant lesions are solid and tend to have irregular borders procedure is not a justifiable alternative simply because of
and inhomogeneous acoustic shadowing. However, ultra- “patient choice” and should be performed only when needle
sound features alone are insufficient to define if the lesion is biopsy cannot be performed for specific technical reasons,
malignant. Ultrasonography may also be used to direct needle when a needle biopsy is either nondiagnostic, the result is not
biopsy by fine-needle aspiration (FNA), core biopsy, or concordant with the imaging findings (i.e., the needle biopsy
vacuum-assisted needle biopsy. is benign, but the lesion is of high suspicion), or in highly
select other cases. Technical reasons that may preclude needle
Magnetic Resonance Imaging biopsy include anatomic location of the lesion on mammog-
Magnetic resonance imaging (MRI) may be used in breast raphy directly opposed to the chest wall or in the far periph-
cancer screening and evaluation of breast cancers.7 MRI visu- ery of the breast so that it cannot be visualized on stereotactic
alization of breast cancers requires contrast enhancement imaging devices.
using intravenous gadolinium. Indications for breast MRI FNA that provides cytology only, used extensively in the
continue to evolve. MRI may detect cancers that are occult past, has largely been supplanted by core biopsy or vacuum-
on mammography but suffers from a substantial rate of false assisted needle biopsy that provides tissue for histologic
positive findings, which leads to otherwise unnecessary biop- examination. The specimens also allow performance of tumor
sies and significant patient concern. MRI screening is useful marker studies.
in women at defined increased risk of developing breast Needle biopsy may be directed by direct palpation or image
cancer. Standard criteria in 2009 are to consider MRI screen- guidance. Lesions that are clearly palpable may be accurately
ing for women with a lifetime breast cancer risk of at least 20 localized for biopsy by palpation in the office without using
to 25%.8 imaging equipment. However, it is best to use image guid-
The use of MRI in women with a known breast cancer ance if there is any question or if the lesion is not palpable.
has the dual purpose of screening the remainder of breast The choice between ultrasound, stereotactic mammographic,
tissue and providing additional information on the extent of or MRI guidance is based on the character of the lesion
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(i.e., calcifications require mammographic guidance) and the Noninvasive Cancer

expertise and preference of the provider. In a few cases, surgi- Cancer that is confined to the lumen of the duct or lobule
cal excision is required for lesions defined as benign by needle of the breast and has not penetrated the basement membrane
biopsy. is termed in situ cancer. This generally refers to ductal carci-
In addition to the “nonconcordant” finding, this includes noma in situ (DCIS) but also encompasses a benign entity
cases where the biopsy shows the benign lesions atypical
called lobular carcinoma in situ (LCIS).
hyperplasia (ductal or lobular) or lobular carcinoma in situ.
Excision is necessary in these cases because there is a small lobular carcinoma in situ
chance that there is cancer in the tissue immediately
Small uniform cells confined to the lobule of the breast
surrounding the biopsy-sampled tissue.14
characterize LCIS. It is generally a clinically and mammo-
graphically occult lesion that is identified only incidentally
Breast Cancer Management when a biopsy is performed for calcifications or a mass that
proves to be some other benign lesion. LCIS is actually not
The treatment of breast cancer requires coordination
cancer but rather is a benign lesion and does not require
between multiple disciplines.
Surgical care cannot be done in a vacuum and must be cancer treatment per se. The primary issue with LCIS is that
integrated with adjuvant therapies, including radiation and it conveys an increased lifelong risk of subsequent invasive
systemic therapy. Although it is not mandatory that every cancer quantified at 0.5 to 0.75% per year.17 In addition,
breast cancer patient consult with specialists in each relevant when LCIS is identified on a core-needle biopsy, there is a
discipline prior to surgery, it is incumbent upon the surgeon 10 to 20% chance of DCIS or invasive cancer in the sur-
to ensure that the surgical care is appropriately coordinated rounding tissue; therefore, surgical excision is warranted.18
in overall breast cancer care. Long-term follow-up shows that the large majority of
Breast cancer management addresses two major issues. women with LCIS never develop invasive breast cancer.
The first is the treatment of the local disease in the breast Therefore, ablative surgical therapy and radiation for LCIS
itself. This is generally accomplished through surgical resec- are not necessary. Previously, LCIS was considered in and of
tion with or without radiation. The second is the adjuvant itself an indication to consider bilateral mastectomy. How-
systemic therapy (chemotherapy and endocrine therapy) ever, mastectomy is generally not indicated in women with
because any woman with invasive cancer has the risk of LCIS and should be performed only in the context of risk
harboring occult microscopic metastatic disease that will reduction for those at very high risk related to factors such as
ultimately lead to clinically apparent metastatic disease and inherited susceptibility.19
death. Because women with a diagnosis of LCIS are at increased
Decisions about treatment require accurate information on risk for subsequent invasive cancer, they should be counseled
the extent of the cancer at the time of diagnosis codified using regarding that risk and may benefit from consultation with
staging systems. The clinically used staging system is the genetics professionals if they have a family history of breast
TNM system of the American Joint Committee on Cancer or ovarian cancer. Women with a biopsy showing LCIS may
(AJCC).15 This classifies the size and extent of the primary also consider risk-reducing chemoprevention with one of the
tumor (T), the involvement of regional lymph nodes (N), the selective estrogen receptor modulators (SERM’s), tamoxifen
presence or absence of distant metastases (M), and a “stage or raloxifene. These reduce the risk of subsequent invasive
group” derived from the T, N, and M. The AJCC TNM cancer by about 50%, with an acceptable toxicity profile.20,21
system was recently revised for cases diagnosed beginning in Raloxifene is the preferred agent in postmenopausal women.
2010.
ductal carcinoma in situ
Stage should be documented in the medical record at two
distinct points in treatment. The histologic hallmark of DCIS is the presence of
Clinical stage is the initial cancer stage used in treatment malignant-appearing cells confined to the lumen of the ductal
planning and includes information gleaned from the history system in the breast. DCIS is most often diagnosed because
and physical examination and any available imaging studies of the presence of calcifications clustered in one area of the
prior to surgery or the start of systemic or radiation therapy. breast. The calcifications suspicious for DCIS are often linear
Pathologic stage is the clinical stage supplemented with the (not round), growing in a ductal distribution. The DCIS
findings from surgical resection. When neoadjuvant therapy may not be confined to the extent of calcifications, and not
is used, the extent of disease after treatment is the posttreat- all DCIS is manifested by calcification. Therefore, the size or
ment stage. The degree of response to neoadjuvant therapy extent of DCIS may not be defined by the mammographic
may be prognostic. The rules and specifics of the TNM stag- appearance. Although DCIS occasionally presents as a mass,
ing system are presented in detail in the AJCC Cancer Staging the presence of the mass even in the setting of a biopsy show-
Manual (seventh edition).15 ing DCIS most often signifies that the cancer is primarily
Breast cancer management continues to evolve, and no invasive.
book chapter can remain up to date. Surgeons are urged DCIS is generally considered a precursor to invasive
to remain current with the relevant literature and refer to cancer.22 The purpose of treatment of DCIS is to prevent
guidelines in making treatment decisions. The most com- progression to invasive cancer with the sequelae of metastatic
prehensive guidelines that are updated at least annually are disease and death. However, indirect evidence suggests
supplied by the National Comprehensive Cancer Network that not all DCIS lesions will progress to invasive cancer.
(NCCN) and are available at www.nccn.org.16 Unfortunately, despite extensive research, there is insufficient
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evidence to identify which DCIS lesions will progress to inva- extend beyond the area of calcifications seen on mammogra-
sive cancer and which will remain clinically occult for the phy, the rate of positive margins on the initial excision for
duration of a woman’s life.23 Therefore, all women diagnosed DCIS ranges as high as 20 to 25%. Women who have a posi-
with DCIS should undergo appropriate treatment. tive margin on the initial excision for DCIS must undergo
DCIS encompasses a spectrum of histologic subtypes. repeat surgery to obtain a negative margin. On occasion, even
Malignant-appearing cells confined to the breast duct charac- with such “reexcision,” the DCIS extends to the new margin,
terize all of these. However, the appearance ranges from and some of these women ultimately require mastectomy.
bland, uniform cells growing from the wall of the duct or The definition of a “negative margin” is an area of
bridging the duct (papillary; cribriform) to cells filling the controversy.29,30
entire duct (solid). These cells also vary in nuclear morphol- The NSABP studies used the definition of a negative
ogy, ranging from low-grade, uniform-appearing nuclei to margin as the absence of the ink used to paint the surgical
varying size and shape and large nuclei (high grade) and in margin on any cancer cells. However, the margin width,
the presence or absence of central necrosis within the duct. measured as the distance from the closest surgical margin to
The combination of high nuclear grade and central necrosis the DCIS, affects the risk of local recurrence, with the
is termed “comedo-DCIS” or “comedocarcinoma.” It is pos- lowest rates among women with a full 1 cm margin.31 The
sible that these subtypes of DCIS are different disease entities best current evidence is that a margin of at least 2 mm is
with different potential for progression to invasive cancer, but required to obtain optimal rates of local recurrence.32
this is poorly understood. The clinical relevance of the DCIS Substantial research has focused on identification of those
subtypes is that they may have different potential for local women with DCIS who may not require radiation. Some
recurrence after breast-conserving surgery, which may impact evidence from nonrandomized series suggests that the size of
on the utility of radiation as an adjunct to wide excision. the area of DCIS coupled with the nuclear grade and the
The presence of high-grade cells or comedonecrosis is not an width of the resection margin may identify subsets of women
indication of metastatic potential and does not itself warrant with DCIS for whom the risk of local recurrence is so low
systemic therapy or lymph node staging.
that radiation is not warranted.33,34 However, in randomized
Treatment trials, there are no subsets that can be identified for whom
radiation does not reduce the risk of local recurrence. There-
The overall cancer-specific survival for women with DCIS
fore, the decision to omit radiation therapy with DCIS
approaches 100% almost irrespective of the subtype of DCIS
requires careful counseling of the patient coupled with
and the type of treatment [see Figure 1].22 Mastectomy is
effective in DCIS, but in most cases, a breast-conserving multidisciplinary input.
approach is possible. Recurrence in the skin of the mastec- The standard radiation treatment is whole-breast radiation
tomy site or on the chest wall muscle (“local recurrence”) therapy to a dose of about 50 Gy potentially coupled with a
may occur, but the frequency after mastectomy for DCIS is 15 Gy boost to the site of the surgical excision. Because most
extremely low (1 to 3%).24 Most women with DCIS may be local recurrences occur in the breast tissue close to the origi-
treated by surgical excision (“lumpectomy” or “wide exci- nal DCIS, it is possible that radiation administered only to
sion”) of the DCIS with some surrounding normal breast the affected region of the breast may be as effective as whole-
tissue to achieve a “negative margin.” The choice between breast radiation therapy. Techniques for administering
breast-conserving surgery (BCS) and mastectomy may be so-called accelerated partial-breast irradiation therapy allow
influenced by the size of the area of involvement, the size of treatment to be delivered over a much shorter period of time
the breast, and the location of the DCIS. (as short as 5 days), making it an attractive alternative.35
There is no specific size above which mastectomy is However, as of 2009, there are no long-term data demon-
mandatory. Wide excision (“lumpectomy”) with a generous strating the effectiveness of accelerated partial-breast
margin of normal breast tissue can be accomplished in most irradiation in DCIS, and it remains investigational.
women. The choice between mastectomy and breast conservation
Large-scale randomized clinical trials in North America may be difficult. It is different for women with DCIS than for
and Europe have demonstrated the effectiveness of BCT those with invasive cancer primarily because those with DCIS
and the role of radiation in DCIS. The National Surgical do not face the threat of death from metastatic disease. For
Adjuvant Breast and Bowel Project (NSABP), the European women with disease treatable by breast conservation, mastec-
Organization for Research and Treatment of Cancer tomy remains a reasonable option if selected by the patient.
(EORTC), and others conducted trials comparing wide exci- The choice may also be influenced by the risk of developing
sion alone versus wide excision plus radiation therapy.25–28 a subsequent second breast cancer related to family history
Every study demonstrated long-term overall survival approa- and biologically defined inherited susceptibility. An initial
ching 100% irrespective of treatment. However, women reaction of “just remove it” is insufficient justification for
treated with BCT had a substantial risk of recurrence in the mastectomy and should be followed by careful counseling
same breast, and radiation reduced this risk. The rate of local and reassurances regarding the long-term outlook for women
recurrence in the NSABP study was 30% without radiation with DCIS.
and about 12% with radiation. The size and histologic char- Reconstruction of the breast mound is available to most
acteristics of the DCIS as well as the extent of the margin of women who require or choose mastectomy for DCIS. Breast
resection also affect the risk of local recurrence. reconstruction may be performed at the same time as the
A key factor in breast-conserving surgery for DCIS is mastectomy using implant techniques or tissue transfer using
obtaining a negative surgical margin. Because the DCIS may a variety of tissue flaps (see below).
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Patient has suspicious breast lesion

Biopsy required
Needle biopsy preferred over surgical excision
Patient has breast cancer

Management based on clinical stage
Stage III Stage IV

Stage I–II (tumor < 5 cm) tumor > 5 cm or T4 distant metastases
or N2/N3 nodes
Stage 0 – ductal carcinoma

in situ (DCIS)
Define extent of DCIS DCIS NOT amenable

from imaging to wide excision
DCIS amenable Mastectomy with SNB

to wide excision (consider immediate reconstruction)
Follow-up
Treatment Choice
• Wide excision; no SNS
or
• Mastectomy
Positive margin:
reexcision to negative margin;
or mastectomy
Wide excision:
assess margins Negative margin: Consider endocrine therapy
breast irradiation follow-up
(omit radiation in select cases)
Figure 1 Guidelines for treatment of ductal carcinoma in situ (DCIS). SNB = sentinel node biopsy.
An important issue with DCIS is that there is a risk that be performed. Exceptions are the presence of a suspicious
invasive cancer is identified in the final surgical specimen in mass—indicative of invasive cancer—or when the DCIS is in
5 to 20% of women for whom needle biopsy showed DCIS. the axillary tail of the breast, and excision may preclude sub-
Invasive cancer is more likely in cases where a mass is present sequent SNB because of interruption of lymphatic flow to the
on imaging or physical examination. This leads some sur- axilla. SNB is appropriate when mastectomy is used for DCIS
geons to recommend lymph node surgery in all women with because of the chance that the breast harbors an invasive
DCIS. However, lymph node surgery is unnecessary in the cancer. Mastectomy may preclude subsequent SNB; there-
management of DCIS because it has no metastatic potential. fore, mastectomy without SNB for women with DCIS may
For women undergoing breast-conserving treatment, if an commit those women to undergoing a full axillary lymph
invasive cancer is identified in the final surgical specimen, node dissection if invasive cancer is present.
lymph node staging with sentinel node biopsy (SNB) may be Women who undergo radiation with DCIS may also ben-
performed at a subsequent surgical procedure with the same efit from adjuvant endocrine therapy. The NSABP conducted
level of accuracy as if done at the time of excision. Some a clinical trial of wide excision plus radiation with or without
surgeons advocate SNB in all women with DCIS, making the tamoxifen.38 Tamoxifen reduced the risk of local recurrence
argument that it is cost-effective compared with a separate by 40%. A subsequent clinical trial not as yet reported in
SNB procedure for those with invasive cancer, but there are 2010 addresses whether an aromatase inhibitor is effective
no high-level data to support this statement. In addition, and comparable or superior to tamoxifen in reducing the rate
SNB carries some risk of long-term morbidity; careful evalu- of local recurrence in DCIS. The use of endocrine treatment
ation on prospective studies demonstrates that women with in DCIS must be balanced against the toxicity of the selected
SNB have about a 6% risk of at least mild lymphedema.36,37 drug, recognizing that endocrine therapy is not lifesaving
Therefore, with breast-conserving surgery, SNB should not in this situation. There are no data supporting the use of
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endocrine therapy in women treated for DCIS with mastec- mucinous carcinoma, medullary carcinoma, and metaplastic
tomy. carcinoma. Tubular and mucinous carcinomas may have a
lower propensity for lymphatic metastases and a generally
paget disease of the breast
better prognosis than typical ductal cancers.41,42
An uncommon presentation of breast cancer is with ecze- Medullary cancer was historically considered a cancer with
matoid changes directly in the nipple, often with beet red and a better prognosis, but the term is overused, and most tumors
ulcerated skin in the nipple. This is due to malignant cells classified this way are high-grade cancers with a poor progno-
with a characteristic “fried egg” appearance occurring in sis. Standard guidelines do not assign medullary cancer to a
the nipple skin or “Paget cells.” This is Paget disease of the good prognosis subgroup.16 Because of the potential overuse
nipple. In most cases of Paget disease, there is a cancer in the of these subgroup terms, great care should be taken in making
underlying breast, and the cells in the nipple may represent treatment decisions based on these subgroups without ensur-
intraductal spread of the cancer to the nipple, although this ing with the pathologist that the tumor truly is the special
process is poorly understood. In most cases, the underlying histology.
cancer is relatively close to the nipple and in most cases is Inflammatory breast cancer is an infiltrating cancer charac-
DCIS. terized by skin edema and erythema encompassing over half
Women with these changes in the nipple are often misdi- the breast and associated with an especially high likelihood
agnosed as having benign skin conditions and are treated with of subsequent metastases and death. It often correlates with
topical agents, including steroids. If such treatments are used the histologic finding of dermal lymphatics clogged by tumor
and the lesion does not resolve, or if there is any clinical sus- cells, but the diagnosis of inflammatory cancer is only a clin-
picion, a biopsy of the affected skin is needed. If the biopsy ical diagnosis. Skin biopsy showing dermal lymphatic involve-
shows Paget disease, then the breast should be carefully ment is not necessary to classify a cancer as inflammatory.15
imaged by mammography supplemented by MRI if the breast Breast cancers may be better classified by biologic charac-
is dense to search for primary tumor in the breast. If a breast teristics rather than histologic appearance. At the very least,
lesion is found, it, too, should be biopsied.
all breast cancers should be analyzed for expression of the
Treatment is generally based on the type (in situ or inva-
hormone receptors for estrogen and progesterone and the
sive) of primary tumor in the breast and treatment of the
level of expression or amplification of the HER-2/neu gene.16
nipple. This may be accomplished in many cases with removal
These provide key prognostic information and “predictive”
of the nipple in continuity with the breast cancer, followed by
information about sensitivity to specific drugs to treat breast
radiation.39 Mastectomy is still often used but may be reserved
cancer. It is expected that biologic classification of breast
for cases with more extensive involvement.40 Lymph node
cancers beyond these three receptors will ultimately allow a
surgery is warranted only with invasive cancer. Adjuvant
higher degree of personalization of both local and systemic
systemic therapy is administered by standard guidelines.
treatment.43,44
The accuracy of testing for estrogen, progesterone, and
Invasive Breast Cancer HER-2 varies, and this variation impacts significantly on
The majority of breast cancers are classified as invasive patient outcome. To improve this situation, national organi-
or infiltrating, characterized by the cancer invading through zations have established practice standards for laboratories
the basement membrane of the duct or lobule. The same performing this testing.45,46 Pathology should be reported
properties allow basement membrane invasion may allow the using structured documentation according to the templates
malignant cells to invade surrounding blood vessels or lym- provided by the College of American Pathologists (www.cap.
phatic channels and raise a possibility of spread to distant org). Surgeons should be sure that testing for their patients is
sites. Although most have probably not spread as assessed by performed and reported in accordance with these standards.
long-term survival without distant metastases, the treatment
local therapy of t1 and t2 invasive breast cancer
issues for invasive breast cancer include not only the local
treatment of the breast but also the potential for distant The primary goal of local therapy of breast cancer is
spread and the role for adjuvant systemic drug therapy. eradication of the primary tumor to prevent progression and
further dissemination of the disease [see Figure 2]. In addition,
classification staging of the regional lymph nodes is performed to provide
The majority of breast cancers arise from the ductal com- prognostic information and to guide systemic treatment as
ponent of the terminal ductal lobular unit and are termed well as provide regional control in the common regional nodal
invasive ductal cancer. An additional 10 to 15% arise within basins.
the lobule and have a characteristic appearance of small cells
infiltrating in a linear fashion through the breast stroma, Mastectomy versus Breast-Conserving Surgery
termed invasive lobular cancer. Invasive lobular carcinoma Historically, local treatment of breast cancer meant
carries the same risk of distant metastases as ductal carci- mastectomy. One can argue that the development of the
noma. However, lobular carcinoma may be more insidious operation of radical mastectomy was the single most impor-
because of the infiltrative nature of the disease, which results tant advance in the treatment of breast cancer. At the time it
in a lesion more difficult to detect by mammographic or was developed in the late 1800s, most women presented with
clinical means. breast cancers that were locally advanced and were likely to
Certain subtypes may have a different prognosis than typi- progress to difficult painful and infected local problems.
cal invasive ductal cancer. These include tubular carcinoma, However, the ability to treat breast cancer effectively led to
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Clinical Stage I / II (Tumor < 5 cm)
Treatment choice:
• Initial surgery before adjuvant systemic therapy
- Wide excision with axillary surgery
- Mastectomy with axillary surgery
or
• Neoadjuvant chemotherapy or endocrine therapy
Initial surgery: both breast and axillary Neoadjuvant therapy:

consider with larger tumors
Breast surgery
Axillary surgery
Patient has Patient has Neoadjuvant therapy
wide excision mastectomy [see next page] as per stage III algorithm
Margins Margins
negative positive Consider immediate
reconstruction
Reexcision to
negative margins
Plan adjuvant or Margins Margins
therapy: mastectomy negative positive
(a) Systemic and negative nodes or positive nodes
(b) Radiation
Plan adjuvant therapy: Plan adjuvant therapy:
Radiation to Systemic only (a) Systemic
whole breast No radiation (b) Radiation to chest wall
Radiation to nodes and nodal basins
for multiple positive nodes
Figure 2 Overview schema for local therapy for stage 1/II breast cancer.
women presenting with smaller cancers. However, it was not the tumor. As with DCIS, major clinical trials testing BCT
until the 1970s that the so-called “halstedian” thesis, that defined a negative margin as no ink on the tumor. However,
breast cancers progressed in a stepwise fashion from the in general, a minimum 2 mm margin is optimal. A specific
breast (local) to lymph nodes (regional) to distant disease exception may be at the chest wall, where the pectoralis
(metastases), was proven incorrect. In the 1970s and 1980s, fascia has been taken, and anteriorly at the skin. If a negative
landmark clinical trials demonstrated that breast cancer is a margin cannot be obtained with lumpectomy, including with
systemic disease with the possibility of disseminated disease a second or occasionally a third operation for “reexcision,”
even at the smallest primary tumor and that removal of the mastectomy is necessary.
tumor without mastectomy provided long-term outcome Indications for mastectomy include the presence of multi-
equivalent to mastectomy. The most significant study was the centric disease in the breast—separate cancers in distinct
NSABP B-06 trial comparing mastectomy with lumpectomy parts of the breast separated by at least 5 cm of normal breast
alone and with lumpectomy plus radiation therapy.47 Long- tissue, occurring in 2 to 5% of cases; a very large tumor
term follow-up on this trial demonstrated no difference in in relation to the size of the breast that is not amenable to
overall survival between the three groups. However, with lumpectomy or does not respond sufficiently to neoadjuvant
lumpectomy alone, the cancer recurred in the same breast systemic therapy; and previous radiation treatments to the
in as many as 40% of women. Radiation reduced this rate breast, such as with a prior breast cancer or for treatment
of local recurrence to approximately 12%. On the basis of of other cancers, such as lymphoma. Radiation may not be
this finding, lumpectomy plus radiation therapy became an administered during pregnancy, but with standard sequenc-
accepted standard in the late 1980s and became widely used ing of systemic and radiation after BCT, radiation is usually
through the 1990s. timed such that it is administered after delivery of the baby;
Breast-conserving surgery may be performed in a majority therefore, BCT is possible for women presenting with
of women with invasive breast cancer. Successful BCT breast cancer during pregnancy. In addition, mastectomy is
requires obtaining negative margins of resection around indicated after completion of systemic chemotherapy for
11/10
inflammatory breast cancer because of the likelihood of the 70%, and this may improve survival.55 Subset analysis of large
microscopic extent of disease both in the skin and within the clinical trials and limited clinical trials in women with small
breast beyond the area of known cancer. cancers failed to identify cancers of sufficiently small size that
An unusual presentation of breast cancer is with axillary radiation does not reduce the risk of local recurrence.
lymph node involvement without the presence of a detectable One group in whom the omission of radiation is reasonable
primary cancer in the breast (occult breast primary tumor). is women over age 70 with cancers that are hormone receptor
If a woman has suspicious lymph nodes in the axilla, biopsy positive, 2 cm or smaller, with clinically negative nodes.
is warranted. If the histology shows an adenocarcinoma A clinical trial conducted by Cancer and Leukemia Group B
(as opposed to lymphoma or melanoma), the primary source (CALGB) randomized such women to lumpectomy and
of this metastatic deposit is almost invariably the breast, even tamoxifen with or without radiation.56 There was no differ-
if the hormone receptors are negative. Mammography usually ence in long-term survival. Local recurrence occurred in 1%
shows the primary tumor, but MRI may find some of these with and 6% without radiation. However, the same number
cancers not seen on mammography.48 However, in a few of women in both groups ultimately underwent mastectomy
cases, even MRI will be negative, yet the source is invariably as those who had not received radiation or were most often
the breast. A whole-body search for another source of treated with lumpectomy and radiation. Therefore, omission
adenocarcinoma is not indicated. The woman should receive of radiation is reasonable in this group. A similar trial con-
therapy assuming that this is a breast cancer. ducted in Canada for women age 50 and over demonstrated
In the past, mastectomy was used for all women with an local recurrence rates of about 15% among women between
occult breast primary tumor with a positive axillary node. age 50 and 70, lending caution to omitting radiation for
However, recent data show that mastectomy is not younger women.57
necessary. The standard radiation treatment after breast-conserving
They should undergo axillary lymph node dissection and surgery is treatment of the entire breast to a dose of about
then receive adjuvant systemic therapy (chemotherapy and 50 Gy, with an additional boost of radiation to the primary
endocrine therapy) as appropriate based on stage and biologic tumor site of about 15 Gy. Radiation treatment takes about
features and then radiation to the breast.49,50 6 weeks of therapy and is well tolerated. Long-term serious
Women who have inherited susceptibility with a mutation sequelae of whole-breast radiation are uncommon.
known in BRCA1 or BRCA2 also often choose mastectomy Recent clinical research has focused on the potential for
or bilateral mastectomy. The overall survival for women limiting the extent and time required to deliver radiation to
treated with BCT in this situation is the same as for women the breast. This research is based on the finding that most
without inherited susceptibility.51 However, they are at recurrences occur within a short distance from the primary
increased risk for developing a second primary cancer in the tumor site. Only about 15% of new events in the treated
same breast, a chance that approaches 50%, especially in breast occur outside the area of the original tumor area and
women under age 50 at the initial diagnosis.52 are most likely a new second primary cancer. It is hypothe-
sized that limitation of radiation treatment only to the site of
Radiation in Local Therapy the primary cancer can provide local control equivalent to
Mastectomy should be supplemented with radiation when whole-breast radiation therapy. So-called accelerated partial-
the cancer is over 5 cm in size, when surgical resection breast irradiation (APBI) has one major advantage: because
margins are close or positive, or when multiple lymph nodes of the technical issues in radiation dosimetry and tissue
are involved.53 The “textbook” standard is that radiation is tolerance, APBI may be delivered in a much shorter time
indicated with four or more positive nodes. However, radia- frame—generally two fractions a day over only 5 days. Another
tion should be considered even when only one to three nodes purported advantage is that if there is a second disease event
are involved based on the findings of randomized clinical in the affected breast, this may be treated by a repeat lumpec-
trials demonstrating improved survival. Unfortunately, a tomy rather than mastectomy. However, there are no data to
major American clinical trial addressing the use of radiation support this thesis.
after mastectomy for women with one to three positive nodes There are a number of techniques to deliver APBI.58 The
failed to accrue sufficient numbers of patients to provide an technique with the longest-term follow-up, albeit in a limited
answer to this critical question. number of patients, is multicatheter brachytherapy. This
The possible need for radiation after mastectomy may technique is cumbersome, unsightly, and seldom used. More
affect decisions regarding the cosmetic outcome of immediate recent alternative techniques for delivery of APBI include
breast reconstruction.54 Immediate reconstruction may com- three-dimensional computed tomography (CT)–directed
plicate radiation dosimetry and uniform dose delivery over external beam radiation, brachytherapy using a radiation seed
the entire field and increase the volume of tissue outside the in a balloon catheter placed in the lumpectomy site, and a
field, including the lung and heart. In addition, radiation may single intraoperative dose of radiation. These are promising
compromise the cosmetic result of immediate reconstruction technologies, but there are no long-term data from controlled
through contracture of the scar capsule around an implant clinical trials demonstrating the safety and effectiveness of
and/or contracture of tissues within an autologous tissue flap. these techniques.58 Data from noncontrolled series are scant
The potential need for radiation after mastectomy should be and have very short-term follow-up in a setting where, at the
discussed with all women having mastectomy for invasive very least, 5-year follow-up is required. Large clinical trials
breast cancer. are ongoing, including a study by the NSABP. Therefore,
Radiation is generally administered in all cases with BCT. as of 2010, APBI remains investigational and whole-breast
Radiation reduces the risk of local recurrence by as much as radiation therapy remains the standard.16,59
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Local Recurrence with Mastectomy or Breast-Conserving their patient’s concerns or to their styles of decision making.63
Surgery This has led to the development of decision assistance and
Local recurrence after surgical treatment of breast cancer support tools and to the recognition of the need for multidis-
occurs with both mastectomy and BCT. The risk of local ciplinary counseling, especially in more complex situations
recurrence after lumpectomy is somewhat lower than reported or those associated with questions surrounding inherited
in the NSABP B-06 trial. When performed by experienced susceptibility and genetics.64
surgeons with careful pathologic control, appropriate radia- One of the key factors in this process is the recognition that
tion, and stage-appropriate adjuvant systemic therapy, the breast cancer treatment is not an immediate emergency.
rate of local recurrence with BCT is as low as 1 to 5%. Local There are no data to support the contention that treatment
recurrences are also a significant issue among women treated initiated within a few days of diagnosis improves outcome
with mastectomy. This risk is about 2 to 5% for women with compared with that delayed a reasonable period of time,
negative lymph nodes and ranges as high as 25% for women measured in a number of weeks or even months. Women
with multiple positive lymph nodes.60,61 should be given the opportunity to seek additional counsel-
Local recurrence is a serious event whether it occurs after ing, research information on their own, and obtain second
BCT or mastectomy. These women have a higher risk of opinions if they so desire. Inclusion of professionals of other
developing distant metastases compared with women with disciplines, including radiation oncology, plastic surgery,
similar-stage cancer who do not suffer local recurrence. It has medical oncology, radiology, psychology and social support,
previously been generally cited that radiation impacts only nursing, and genetics, may be warranted.
the risk of local recurrence and not overall survival. However, management of the contralateral breast
a meta-analysis of all available data for women treated with
BCT and mastectomy demonstrated that radiation therapy Women with breast cancer have a risk of second malignan-
not only reduces the risk of local failure but also improves cies and especially the risk of developing a contralateral
survival.55 The best estimate is that radiation saves one life for primary breast cancer. Outside the setting of inherited sus-
every four local recurrences prevented. Radiation is therefore ceptibility, the chance of developing a contralateral primary
recommended for women who have a risk of local failure over breast cancer is about 10% over 20 to 30 years.47 Given that
10% regardless of the type of primary surgery. the average woman is in her 50s or 60s and that most of
The accepted treatment for local recurrence after BCT is these contralateral breast cancers will be effectively treated,
mastectomy. This is because the recurrence may be multifo- the risk that a woman with a breast cancer will succumb to
cal and because full-dose radiation cannot be administered a new contralateral breast cancer is far outweighed by both
safely a second time because of tissue toxicity. Local recur- the risk of death from the current breast cancer and the
rence after mastectomy is more difficult to treat and carries a long-term risk of death from other causes during the very
more serious prognosis. Treatment usually includes resection long-term follow-up in which second cancers occur. There-
of a local recurrence in the skin, muscle, or regional nodes if fore, treatment addressing the other breast is generally not
possible, followed by radiation to the chest wall and regional necessary.
nodes. The role for additional adjuvant systemic therapy Previously, it was believed that women with invasive
after local recurrence is uncertain, and there are no clinical lobular cancer had a much higher risk of a contralateral
trial data supporting its use. However, many oncologists will breast cancer compared with ductal cancer. The added risk
deliver additional systemic treatment based on the type of of contralateral cancer with lobular cancer is relatively small
previous treatment and the nature and extent of the local and should have little bearing on treatment decisions.
recurrence. The issues are different for women with inherited sus-
ceptibility, most notably those with mutations in BRCA1
Selection of Breast-Conserving Surgery versus Mastectomy and BRCA2. They are generally younger at breast cancer
The decision between BCT and mastectomy is a complex diagnosis and have a higher risk of developing a second
and difficult one for women with breast cancer. From a tech- cancer. This risk appears dependent on the age at which they
nical standpoint, BCT is possible in the large majority of are diagnosed with their first breast cancer: 25 to 50% for
women with breast cancer. More than 90% of women with those under age 50 at the initial diagnosis and 15 to 20% for
tumors under 2 cm in size (T1) may undergo BCT given the those over age 50.52
absolute and relative contraindications to BCT discussed Careful counseling can largely allay a woman’s fears of the
above. However, many other factors in addition to the techni- impact of the risk of a second cancer. However, some women,
cal ability to perform BCT affect the decision. Ultimately, especially those undergoing mastectomy for the index cancer,
the individual patient is the determinant of whether or not may request contralateral mastectomy. Recent observational
she will have mastectomy. Her choice may be influenced by studies demonstrate that the number of women undergoing
perceptions or values based on personal or family experi- prophylactic contralateral mastectomy increased significantly
ences, real or perceived increased risks of recurrent cancer over the last decade. In New York State, about 4% of
based on family history, and other factors. women treated with mastectomy in 1995 had a contralateral
Counseling women regarding the choice of surgery is one mastectomy compared with 15% in 2005.65
of the most important tasks for the treating surgeon.62 Sur-
geons need to learn the skills of nondirective counseling and lymph node staging in breast cancer
must incorporate other professionals and resources into their The presence of metastases in regional lymph nodes is a
practice. Careful study of the decision-making process has key prognostic factor used in making treatment decisions, as
shown that physicians are not necessarily fully sensitive to discussed below [see Figure 3]. In addition, removing lymph
11/10

(Continued)
Axillary surgery
Nodes clinically negative Nodes clinically positive
Axillary sentinel node biopsy Consider ultrasound-guided

FNA or core biopsy
Sentinel node(s) negative: Sentinel node(s) positive Not done or Needle biopsy negative:
no further node surgery needle biopsy positive: consider sentinel node biopsy
level I / II or or axillary dissection.
level I / II / III
axillary dissection Axillary dissection
Single node with isolated Macrometastases or if SNB positive
tumor cells or micrometastases multiple positive nodes:
level I / II lymph node dissection level I / II or
or level I / II / III
Consider omission of lymph node dissection
lymph node dissection
Figure 3 Axillary surgery management schema. FNA = fine-needle aspiration; SNB = sentinel node biopsy.
nodes prevents recurrence risk in the regional lymph node During the 1990s, the hypothesis that lymphatic drainage
basin. However, treatment of lymph nodes does not itself to the axilla could be mapped using radioactive or large
affect survival. Defining the involvement of regional lymph colloidal particle tracers and that the first few lymph nodes
nodes requires surgical resection. No noninvasive test of the identified by these mappings would define the status of the
regional lymph nodes has proven insufficient sensitivity and lymph nodes was tested and proven accurate.73 Termed the
specificity to replace surgical resection. Therefore, surgical sentinel lymph node, the first few lymph nodes can be identi-
evaluation of regional nodes remains a key component of fied and full axillary lymph node dissection limited only to
breast cancer treatment.66 those women with proven nodal metastases. Morbidity,
Lymph fluid from the breast drains primarily through the including the risk of lymphedema, is lower with SNB than
axillary lymph nodes.67 A small fraction of lymph drainage with axillary dissection, but lymphedema still may occur.36
from the breast is through other pathways, including direct SNB is appropriate for women with clinically negative
drainage through the supraclavicular nodes and via the nodes. Those with clinically positive nodes are not candidates
internal mammary chain.68 Because the majority of drainage for SNB and should have full axillary lymph node dissection.
is through the axilla, and because of potential morbidity of If there is a question about nodes, involvement of nodes may
internal mammary lymph node dissection, most surgeons be confirmed before surgery using ultrasound-guided needle
limit surgical evaluation of lymph nodes to the axilla. biopsy (core biopsy or FNA).
The axilla contains an average of 15 to 20 lymph nodes SNB is performed by injecting radiolabeled tracer and/or
extending under the axillary vein medially toward the vital dyes that drain to and are trapped in the initial lymph
thoracic inlet. Until the last decade, evaluating these nodes nodes in the chain. The injection is generally in the periareo-
required dissection of the entire axillary contents. A safe lar skin and under the nipple-areola complex. This identifies
operation, it carries substantial risk of long-term morbidity an average of three lymph nodes, which are then removed
related to disruption of the lymphatic flow from the arm and and examined for metastases. SNB is appropriate in virtually
permanent swelling, termed lymphedema.69–71 Lymphedema all women with invasive breast cancer clinically negative
is a chronic lifelong condition that ranges from minimal nodes. SNB may be performed in women with local recur-
effects to disabling swelling. The risk of lymphedema is about rence after previous breast-conserving surgery and radiation,
10% with axillary dissection alone and substantially higher although the accuracy of SNB in this setting has never been
when radiation is also required after node dissection.37,72 tested.
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breast reconstruction
Women treated with mastectomy may consider recon-
Adjuvant systemic therapy:
struction of the breast mound performed either at the time of
mastectomy (immediate reconstruction) or at a later time
(delayed reconstruction).74 Immediate reconstruction is rea- Consider in all cases:
sonable in women with early-stage breast cancer. However, Based on
the potential need for postmastectomy radiation must be con- • Primary tumor characteristics
sidered in reconstruction planning.54 Although satisfactory
• Hormone receptor status
cosmetic outcomes may be obtained even with radiation
to the implant, radiation increases the rate of painful scar • HER-2/neu status
contracture. Decisions regarding immediate breast recon- • Genomic profiling
struction should be made in collaboration with the entire
multidisciplinary treatment team. Conversely, delayed Principles of Systemic Therapy
reconstruction requires that the woman live without the • ER positive: endocrine therapy and
reconstructed breast for a period of 1 to 2 years and may be
consider adding chemotherapy even with negative nodes
more difficult to perform because there is less skin remaining
from the original mastectomy to be used in reconstruction. • ER negative: consider chemotherapy even with negative nodes
Options for breast reconstruction include prosthetic recon- • HER-2/neu positive: add trastuzumab to chemotherapy
struction with an implant or “tissue expander implant” gener-
ally placed beneath the pectoralis major muscle or transfer of Figure 4 Principles of adjuvant systemic therapy.
autologous tissue from another region in the body.74 Implant ER = estrogen receptor.
reconstruction is generally simpler and quicker to perform
but may not leave as attractive an aesthetic result. Complica-
tions of implant reconstruction include contracture around
of features about the cancer, including the size of the invasive
the implant (which may be exacerbated if radiation is
component of the cancer, the presence or absence of regional
necessary) and infection, resulting in loss of the implant.
lymph node metastases, the grade of the cancer, and the
Autologous tissue reconstruction often leaves a superior cos-
presence or absence of specific biomarkers associated with
metic result but at the cost of more complex surgery, longer
prognosis and response to treatment. The three clinically
recovery, and the potential for complications at the site of the
used markers are the estrogen receptor, the progesterone
donor tissue. The most common donor sites are the rectus
receptor, and HER-2/neu protein expression or gene amplifi-
abdominus muscle (so-called transverse rectus abdominus
cation. In making these assessments, it must be recognized
myocutaneous [TRAM] flap), the more superficial fat and
that a substantial fraction of women with negative lymph
skin from the abdominal wall (deep inferior epigastric per-
nodes still develop metastatic disease.15
forator [DIEP] flap), and the latissimus dorsi muscle flap.
Treatment entails two major classes of drugs: endocrine
These flaps may be used in conjunction with complete spar-
drugs, which block the effect of circulating estrogen on breast
ing of all the skin of the breast that provides for an even better
cosmetic result. In general, the nipple and areola are resected cancers that express estrogen and progesterone receptors, and
with mastectomy, but in select circumstances, such as small systemic cytotoxic chemotherapy. The best available treat-
tumors located in the periphery of the breast, some surgeons ments are codified in widely accepted practice guidelines
have been experimenting with mastectomy that preserves the developed and updated annually by the NCCN.16
nipple.75–77 Endocrine therapy is effective only for women whose
tumors express hormone receptors. This includes pre-
adjuvant systemic therapy menopausal women and postmenopausal women as they
Women with invasive cancer also face the risk of have low levels of circulating estrogens from non-ovarian
developing distant metastases. These metastases develop sources. There are two primary classes of endocrine drugs:
from microscopic dissemination of cancer cells prior to SERMs, of which the primary agent used in breast cancer is
diagnosis. Staging studies including CT, PET, and MRI are tamoxifen, and aromatase inhibitors, which block peripheral
not insensitive at detecting this microscopic disease. In stage synthesis of estrogen and are effective only in postmenopausal
I and stage II cancer, these studies are unnecessary unless women.78 Recent clinical trials demonstrated that aromatase
there are symptoms such as new skeletal pain or other con- inhibitors are superior to tamoxifen in preventing the recur-
stitutional symptoms. The chance of identifying metastatic rence of breast cancer, with a slightly improved safety profile
disease is very low, and there is a substantial chance of false in postmenopausal women. Aromatase inhibitors are not
positive scans, requiring extensive evaluation and invasive effective in premenopausal women, for whom tamoxifen
studies. remains the drug of choice. These drugs are remarkably safe
Therefore, every woman with invasive cancer must con- and effective, with only rare serious side effects.
sider whether to receive systemic adjuvant therapy to prevent With only a few exceptions, all women with hormone
the growth of this microscopic metastatic disease [see receptor–positive breast cancers should receive prolonged
Figure 4]. The decision depends on both the estimated risk of endocrine therapy. At least 5 years of therapy is warranted.
developing metastatic disease and the degree of benefit that Ongoing clinical trials are addressing whether prolonged
treatment may provide. These risks are estimated by analysis therapy with aromatase inhibitors may be of value.
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Women with hormone receptor–positive breast cancers neoadjuvant systemic therapy and locally
should consider whether to also receive systemic chemother- advanced breast cancer
apy. A large body of evidence from clinical trials shows that Locally advanced breast cancer is generally defined as any
survival may be improved by the addition of chemother- tumor over 5 cm, involving the skin, or with extensive lymph
apy.79,80 However, the magnitude of benefit over the benefit node involvement [see Figure 5]. In these cases, surgery may
of endocrine therapy alone may be small. For otherwise be difficult and even standard mastectomy may not be pos-
healthy women who have positive lymph nodes, additional sible. With the advent of chemotherapy in the 1970s, clinical
chemotherapy may be strongly considered. For those with trials investigated the value of systemic treatments, most
negative nodes, the benefit varies according to the character- notably chemotherapy, prior to surgery. These demonstrated
istics of the cancer. Until recently, many women received that such “neoadjuvant” presurgical therapy with locally
chemotherapy for a survival advantage as low as 1%. Recently, advanced breast cancer often reduced the size and extent
genomic profiling of cancers through characterization of of the cancer more than 50%, which often allowed standard
the expression of multiple genes has allowed identification of surgery. Equally interesting was that 15 to 25% had complete
women in this situation with a very high and with a very low disappearance of cancer clinically and half of these women
risk of distant disease and also has to find which patients had no viable tumor identified pathologically (pathologic
benefit from chemotherapy.81,82 The most widely used complete response). Neoadjuvant chemotherapy became
genomic profiling system in breast cancer in 2009 is Onco- the accepted standard treatment for locally advanced and
typeDx. This profiling is validated for use in women with inflammatory breast cancer (stage III).
hormone receptor–positive, lymph node–negative invasive This finding with locally advanced breast cancer led to
studies of presurgical chemotherapy with lower-stage cancer.88
breast cancer.
Large-scale studies, most notably the NSABP B-18 study,
Endocrine therapy is not effective in women with hormone
demonstrated similar cancer responses with presurgical
receptor–negative breast cancer. For these women, the only
chemotherapy.89 Neoadjuvant therapy did not convey any
treatment to reduce the risk of distant metastases is cytotoxic
survival advantage over chemotherapy administered post-
chemotherapy.79,80 Unless otherwise contraindicated by operatively. However, women treated with presurgical che-
serious comorbidities, women with cancers over 1 cm and motherapy were more likely to have BCT, and the rate of
negative hormone receptors should receive chemotherapy.16 local recurrence after this treatment was equivalent to that of
Those with tumors under 1 cm have a lower risk of distant others receiving BCT. The degree of response to neoadjuvant
metastases and may derive substantially less benefit from therapy is itself of significant prognostic importance.89–91
chemotherapy. Those women who achieve a major response, especially those
Breast cancers that express the HER-2/neu protein have who achieve a complete pathologic response in the tumor,
a higher risk of developing distant metastases. However, are more likely to have long-term survival compared with
the monoclonal antibody trastuzumab (Herceptin) directed those who do not.88 These and other factors have led to an
against HER-2 has proven to be safe and effective when given increasing use of neoadjuvant therapy.
in combination with chemotherapy. The risk of distance Presurgical endocrine therapy may also be of value in
metastatic disease is cut by about half over the benefit of select cases.92,93 A response to neoadjuvant chemotherapy is
chemotherapy alone when combined with trastuzumab.83 most likely among women with high-grade and hormone
The most difficult situation is when estrogen, progesterone, receptor–negative cancers. Those with endocrine receptor–
and HER-2/neu are negative. So-called “triple negative positive cancers may be somewhat less likely to respond.
cancers” are more common in younger women, those of However, these tumors may also respond to presurgical
African American ancestry, and those with inherited suscep- endocrine therapy, with similar benefits in terms of surgical
tibility. There is active ongoing clinical research to define treatment. With endocrine therapy, the time to maximal
improved approaches in this setting. tumor response is longer than with chemotherapy; it may
Clinical trials over the last three decades have defined the take 6 months to achieve maximum tumor response prior to
surgery.
most effective drugs in breast cancer. Chemotherapy drugs
It is therefore reasonable to administer neoadjuvant ther-
are most effective when used in combination with other
apy to any woman who would otherwise receive chemother-
drugs. The most effective drugs in breast cancer are the
apy for treatment for breast cancer. In general, neoadjuvant
anthracyclines, of which the most widely used agent is doxo-
therapy is administered to those with larger T2 cancers (those
rubicin (Adriamycin), cyclophosphamide (Cytoxan), and the over three or 4 cm in size) and T3 cancers in an effort to
taxanes (paclitaxel and docetaxil). Readers are referred to allow breast conservation. In addition, neoadjuvant therapy is
a large-scale meta-analysis of the value of adjuvant chemo- the treatment of choice for those with cancer that involves the
therapy and endocrine therapy and to recent reviews on the skin or chest wall (T4), with extensive lymph node involve-
subject.79,80,84 ment clinically, or those who have inflammatory cancer.
Decisions regarding adjuvant systemic therapy are complex Regardless of the final surgery type and the degree of tumor
for both patients and their physicians. To aid these decisions, response, women with locally advanced breast cancer should
there are mathematical models that incorporate relevant receive surgery and radiation.94
prognostic factors and provide individualized risk of distant
recurrence and benefit from treatment. The most widely used stage iv breast cancer
models are Adjuvant! (www.adjuvantonline.com) and A small fraction of breast cancers have distant metastases
CancerMath.net (http://cancer.lifemath.net/).85–87 (stage IV) at the time of the initial cancer presentation [see
11/10
Clinical Stage III

Tumor > 5 cm
or
T4 Tumor or N2 / N3 Cancer
or
Stage II Cancer Desiring BCS
Operable
Inoperable
Not candidate for Neoadjuvant therapy:

Candidate for BCS if tumor responsive chemotherapy or
BCS if tumor responsive to therapy to therapy consider endocrine therapy
if ER positive
Mastectomy Neoadjuvant therapy: Mastectomy Responsive and Inoperable

Delayed reconstruction chemotherapy or Delayed reconstruction operable
Postoperative consider endocrine Postoperative
Adjuvant therapy: therapy if ER positive Adjuvant therapy:
(a) Systemic (a) Systemic Mastectomy +
(b) Radiation Lymph node staging: (b) Radiation axillary dissection
Chest wall + nodes Clinically positive: FNA Chest wall + nodes Delayed reconstruction
Clinically negative: Radiation
SNB before or after Chest wall + nodes
neoadjuvant therapy
Consider preoperative
radiation
Major response : Minor or no response: Individualize therapy
BCS if possible mastectomy
SNB if node negative SNB if node negative
Node dissection if node positive Node dissection if node positive
Delayed reconstruction
Radiation:
whole breast + nodes Radiation:
chest wall + nodes
Figure 5 Schema for treatment of locally advanced breast cancer. BCS = breast-conserving surgery; ER = estrogen receptor;
FNA = fine-needle aspiration; SNB = sentinel node biopsy.
Figure 6]. This disease is generally incurable, and treatment tumor does progress, surgery and/or radiation may be used
is targeted at preventing disease progression for the longest for local control and preserving quality of life.
time possible while maintaining high quality of life. It is There is an interesting literature from population cancer
generally necessary to obtain tissue from the primary tumor registries suggesting that those women who present with met-
to obtain hormone receptor and HER-2/neu information, astatic disease who undergo surgery at the time of diagnosis
as well as to biopsy a metastatic site if there is any doubt have longer survival than those who do not have surgery.95–97
regarding whether the metastatic deposit is truly a However, this finding is most likely a selection bias in
metastasis. that women with a lower burden of disease are more likely to
First-line treatment is generally systemic therapy.16 In the have undergone surgery before the discovery of the metastatic
absence of symptomatic or aggressive visceral disease, those cancer and are therefore more likely to survive longer.
with endocrine-sensitive tumors are best treated with oral There are no controlled clinical trial data to support either
endocrine therapy. Many may achieve a major response and argument.
have long, progression-free intervals with high quality of life
without significant treatment-related toxicity. Those with
hormone receptor–negative cancers may begin with systemic Breast Cancer in Pregnancy
chemotherapy. Breast cancer is uncommon in young women but may
For those diagnosed with metastases before the primary occur during the childbearing years. Therefore, breast cancer
tumor in the breast is removed, there is generally no reason may occur during pregnancy and, in fact, is the second most
to do surgery. Systemic treatment often provides a major common cancer associated with pregnancy. Women in this
response in the breast and achieves sufficient local control for age group are generally not undergoing routine breast cancer
the duration of the woman’s life. For those women fortunate screening, and changes in the breast associated with pre-
enough to have prolonged survival but in whom the primary gnancy can mask the presence of a mass. Therefore, breast
11/10
therefore is timed to occur after delivery of the child. There-

Patient Has Distant Metastases fore, breast conservation can be used safely during pregnancy.
(Stage IV) Similarly, chemotherapy may be used safely during preg-
nancy. There are extensive data demonstrating the safety of
chemotherapy for both the mother and the fetus. SNB may
also be performed during pregnancy using the radioactive
tracers. The estimated radiation dose to the fetus is exceed-
Systemic Therapy: ingly low and is considered safe.99 The vital dyes isosulfan
Selection based on blue and methylene blue have potential teratogenic effects
• Presence/absence symptoms and are contraindicated during pregnancy.
• Visceral vs bone disease Women who have breast cancer at a young age or during
• ER, PR, and HER-2/neu pregnancy may wish to have additional children. Decades
ago, they were advised against this because of concern that
hormonal changes associated with pregnancy could promote
recurrence. This has been proven incorrect. Women may
Endocrine therapy primary choice with ER choose to have children after breast cancer treatment with no
positive/asymptomatic additional risk of breast cancer recurrence and death.
Radiation for symptomatic or weight-bearing Breast Cancer in Men

bone metastases Breast cancer occurs in men with an incidence less than
1% of that of women. No screening for men is warranted, but
a mass in the breast should be fully evaluated. Most masses
proved to be gynecomastia. Breast cancer in a younger man
may be indicative of inherited susceptibility within that family
particularly related to BRCA2. Careful family history and
counseling regarding this risk should be provided.
Follow Local Disease and Distant Metastases: The treatment of breast cancer in men follows the same
principles as in women.100,101
Surgery is generally mastectomy because of the tumor is
Change systemic therapy based on
directly under the nipple complex. Wide margins should be
response and symptoms
obtained. Radiation may be administered if the tumor is
larger or involves the skin and/or chest wall. SNB and axillary
Local therapy for local disease lymph node dissection should be performed using the same
Progression and control indications as in women. Men should also receive adjuvant
Especially with stable distant metastases systemic therapy using the same criteria as women. Most
are hormone receptor positive, and endocrine therapy is
effective.
Figure 6 Schema for treatment of women with cancer with
distant metastases at presentation (stage IV). ER = estrogen
receptor; PR = progesterone receptor. Follow-up after Breast Cancer Treatment
Patients who have been treated for invasive breast cancer
cancer diagnosis is often delayed in this situation. Women are at risk for developing distant metastases, local recurrence,
with a suspicious breast mass detected during pregnancy and a contralateral or ipsilateral new breast cancer. Most
should be evaluated aggressively. Imaging can generally be recurrences occur within the first 5 to 10 years, with the
done with judicious use of mammography, ultrasonography, peak at 4 to 6 years. Occasionally, women develop distant
and biopsy performed as in any woman with a suspicious metastases many years later.
breast lesion. Women with breast cancer often assume that careful
The principles of treatment are the same as in any woman screening is warranted to allow early detection of metastases
with breast cancer.98 The only limitations are that chemo- on the assumption that early detection will provide a better
therapy cannot be administered during the first trimester chance of a successful outcome. Unfortunately, there is no
and radiation cannot be administered until after delivery. such entity as early metastatic cancer. Once breast cancer
However, neither of these issues limits aggressive treatment metastases are established to the extent that they are detect-
of women with breast cancer during pregnancy. Termination able, there is no therapy that is curative, and treatment is
of the pregnancy is not necessary, although some women largely palliative, as discussed above related to stage IV breast
diagnosed early in pregnancy may choose to do so. cancer. Because of this, extensive testing for metastatic dis-
Older texts suggested that mastectomy is the preferred ease on a periodic basis does not provide any advantage to a
treatment in women with breast cancer during pregnancy. woman with breast cancer.102 This question has actually been
However, the same choices are available to women with tested in randomized clinical trials of extensive testing versus
cancer during pregnancy because the radiation that is admin- simple follow-up for local recurrence only combined with
istered is generally delayed until after chemotherapy and evaluation of any symptoms suggestive of metastatic disease.
11/10
These studies showed no survival advantage despite detection cancer survivorship

of metastatic disease, and those recurred an average of In addition to covering medical issues in cancer follow-up,
3 months earlier in the screened group. surgeons should provide ongoing resources to help women
Screening women for evidence of local recurrence with adjust to the cancer diagnosis, deal with psychological issues,
both invasive and in situ cancer may be of value. This should address cancer genetic and family concerns, and identify
include mammography of the ipsilateral breast in women other long-term sequelae of cancer.103 Patients should be
treated with breast conservation, contralateral mammography provided with a written “care plan” for their ongoing care
for all women, and a careful history and physical examina- and should be encouraged to seek individual counseling and
tion. Mammography should be done annually, with the his- participate in support groups as they see the need and to gain
tory and physical examination done every 6 to 12 months. the value of engagement in the vast array of support and
The role of breast MRI in breast cancer follow-up is unclear. advocacy activities available in most communities.104
Women should maintain a primary care provider to be sure
that other regular medical care is provided.
Financial Disclosures: None Reported
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3 BREAST, SKIN, AND SOFT TISSUE 2 Soft Tissue Infection — 1
2 SOFT TISSUE INFECTION

Mark A. Malangoni, M.D., F.A.C.S., and Christopher R. McHenry, M.D., F.A.C.S.
Approach to the Patient with Soft Tissue Infection

Soft tissue infections are a diverse group of diseases that involve factors that may have disrupted the normal skin barrier [see Table
the skin and underlying subcutaneous tissue, fascia, or muscle. 2], as well as about any host factors that may increase their sus-
Such infections may be localized to a small area or may involve a ceptibility to infection and limit their ability to contain it. It is par-
large portion of the body. They may affect any part of the body, ticularly important that they be questioned about specific clinical
though the lower extremities, the perineum, and the abdominal scenarios associated with unusual pathogens, such as an animal
wall are the most common sites of involvement. Some soft tissue bite (associated with Pasteurella multocida), a human bite (Eikenella
infections are relatively harmless if treated promptly and ade- corrodens), chronic skin diseases (Staphylococcus aureus), saltwater
quately; others can be life-threatening even when appropriately exposure or ingestion of raw seafood (Vibrio vulnificus), and brack-
treated. The symptoms and signs range from subtle or nonspecif- ish or freshwater exposure (Aeromonas hydrophila).
ic indicators (e.g., pain, localized tenderness, and edema without Physical examination usually reveals erythema, tenderness, and
fever) to obvious features (e.g., necrosis, blistering, and crepitus induration. Vesicular lesions and honey-colored crusted plaques
associated with systemic toxicity). are seen in patients with impetigo. Intense, sharply demarcated
Soft tissue infections were first defined as such more than a cen- erythema is characteristic of erysipelas. A tender, swollen erythe-
tury ago. In 1883, Fournier described a gangrenous infection of matous papule, often containing a visible hair shaft, is indicative of
the scrotum that continues to be associated with his name.1 In folliculitis. A single painful, tender, indurated, erythematous skin
1924, Meleney documented the pathogenic role of streptococci in nodule suggests a furuncle, and the presence of multiple inflam-
soft tissue infection.2 Shortly thereafter, Brewer and Meleney matory nodules with sinus tracts is consistent with a carbuncle.
described progressive polymicrobial postoperative infection of the Cellulitis in association with a decubitus ulcer or an ischemic leg
muscular fascia with necrosis3 (though the term necrotizing fasci- ulcer frequently signals a polymicrobial infection with gram-nega-
itis was not introduced until more than 25 years later4).The asso- tive organisms. An erythematous linear streak, characteristic of
ciation between toxic-shock syndrome and streptococcal soft tis- lymphangitis, usually indicates a superficial infection secondary to
sue infection was delineated as this disease reemerged in the Streptococcus pyogenes; associated lymphadenopathy may be pre-
1980s.5 sent as well.
Various classification systems and eponyms are used to describe Patients with necrotizing soft tissue infections often complain of
specific forms of soft tissue infection [see Discussion, Etiology and severe pain that is out of proportion to their physical findings.
Classification of Soft Tissue Infection, below]. In our view, howev- Compared with patients who have nonnecrotizing infections, they
er, it is more important to develop a common approach to the are more likely to have fever, bullae, or blebs [see Figure 1]; signs of
diagnosis and treatment of these conditions than to refine the systemic toxicity; hyponatremia; and leukocytosis with a shift in
minor details of classification. For therapeutic purposes, the pri- immature forms. Physical findings characteristic of a necrotizing
mary consideration is to distinguish between necrotizing soft tissue infection include tenderness beyond the area of erythema, crepi-
infections and nonnecrotizing infections. Nonnecrotizing soft tis- tus, cutaneous anesthesia, and cellulitis that is refractory to antibi-
sue infections involve one or both of the superficial layers of the otic therapy.6 Tenderness beyond the borders of the erythematous
skin (epidermis and dermis) and the subcutaneous tissue, and they
usually respond to antibiotic therapy alone. Necrotizing soft tissue
infections may involve not only the skin, the subcutaneous tissue,
and the superficial fascia but also the deep fascia and muscle, and Table 1 Common Soft Tissue Infections
they must be treated with urgent surgical debridement. At times,
it is difficult to distinguish between these two categories of infec-
Pyoderma
tion, especially when obvious clinical signs of necrotizing soft tis- Impetigo
sue infection are absent. Erysipelas
In this chapter, we review diagnosis and management of the Folliculitis
main soft tissue infections seen by surgeons, including both super- Furuncles and carbuncles
ficial infections (e.g., pyoderma, animal and human bites, and cel- Superficial infections Infections developing in damaged skin
lulitis) and necrotizing infections involving superficial and deep tis- Animal bites
sues [see Table 1]. Human bites
Cellulitis
Nonnecrotizing
Clinical Evaluation Necrotizing
The diagnosis of soft tissue infection is usually made on the Necrotizing fasciitis
basis of the history and the physical examination. Patients typical- Deep necrotizing Myonecrosis
cutaneous infections Gas gangrene
ly seek medical attention because of pain, tenderness, and erythe-
Metastatic gas gangrene
ma of recent onset. They should be asked about environmental
value of these findings was only 26%.10 The absence of these find-
Table 2 Environmental Factors That Disrupt ings in a patient without obvious clinical signs of a necrotizing soft
Skin and Alter Normal Barrier Function tissue infection had a negative predictive value of 99%. A normal
serum creatine kinase (CK) level rules out muscle necrosis.
Cuts, lacerations, or contusions In a 2004 report, one group of investigators described the devel-
Injections from contaminated needles opment and application of the Laboratory Risk Indicator for
Animal, human, or insect bites
NECrotizing fasciitis (LRINEC) score.11 This scoring system
assigns points for abnormalities in six independent variables:
Burns
serum C-reactive protein level (> 150 mg/L), WBC count (>
Skin diseases (e.g., atopic dermatitis, tinea pedis, eczema, scabies,
15,000/mm3), hemoglobin level (< 13.5 g/dl), serum sodium level
varicella infection, or angular cheilitis)
(< 135 mmol/L), serum creatinine level (> 1.6 mg/dl), and serum
Decubitus, venous stasis, or ischemic ulcers
glucose level (> 180 mg/dl).With a score of 8 or higher, there is a
Contaminated surgical incisions 75% risk of a necrotizing soft tissue infection. The authors of the
report recommended that the LRINEC score be used to deter-
mine which patients require further diagnostic testing, given that
area is an especially important clinical clue that develops as the the negative predictive value of this screening tool was 96%.
infection in the deeper cutaneous layers undermines the skin. A plain x-ray of the involved area demonstrates soft tissue gas in
Early in the course of a necrotizing soft tissue infection, skin only 15% to 30% of patients with necrotizing infections [see Figure
changes may be minimal despite extensive necrosis of the deeper 3].6 Computed tomography is more sensitive in identifying soft tis-
cutaneous layers. Bullae, blebs, cutaneous anesthesia, and skin sue gas, but other CT findings are seldom diagnostic.
necrosis occur as a result of thrombosis of the nutrient vessels and Magnetic resonance imaging is currently the preferred imaging
destruction of the cutaneous nerves of the skin, which typically study for documenting deep necrotizing infections [see Figure 4].
occur late in the course of infection. The presence of soft tissue gas on MRI is diagnostic of a necrotiz-
Clinicians should be mindful of certain diagnostic barriers that ing soft tissue infection.T2-weighted images demonstrate thicken-
may delay recognition and treatment of necrotizing soft tissue ing and increased signal intensity of the deep fascial planes.12,13
infections.7 In particular, these infections have a variable clinical Increased signal intensity in the subcutaneous tissue and edema of
presentation. Although most patients present with an acute, rapid- the adjacent muscle are also frequently present. High signal inten-
ly progressive illness and signs of systemic toxicity, a subset of sity on T2-weighted images and tissue enhancement after gadolin-
patients may present with a more indolent, slowly progressive ium administration are indicative of inflamed tissue and may also
infection. Patients with postoperative necrotizing infections often occur with certain nonnecrotizing soft tissue conditions (e.g., exer-
have a more indolent course. Moreover, in the early stages, under- tional muscle injury, lymphedema, dermatomyositis, polymyositis,
lying necrosis may be masked by normal-appearing overlying skin. eosinophilic fasciitis, and neoplastic disease).13-17 Low or absent
As many as 20% of necrotizing soft tissue infections are primary signal intensity on gadolinium-enhanced T1-weighted images is
(idiopathic) and occur in previously healthy patients who have no indicative of necrosis, a finding that is more specific for a necro-
predisposing factors and no known portal of entry for bacterial tizing soft tissue infection.18-20 The reported sensitivity of MRI for
inoculation. Finally, crepitus is noted in only 30% of patients with diagnosis of necrotizing soft tissue infection ranges from 89% to
necrotizing soft tissue infections. Overall, fewer than 40% of 100%, and its specificity ranges from 46% to 86%.18,20
patients exhibit the classic symptoms and signs described.8,9 A prospective study from 2000 evaluated the use of MRI to dif-
Accordingly, it is imperative to maintain a high index of suspicion ferentiate necrotizing from nonnecrotizing soft tissue infection in
for this disease in the appropriate setting. nine patients.20 The absence of gadolinium enhancement on T1-
weighted images was indicative of fascial necrosis in all six patients
Investigative Studies
Diagnostic studies have a low yield in patients with superficial
soft tissue infections. They are rarely necessary and are used only
in specific clinical circumstances. Either needle aspiration at the
advancing edge of erythema with Gram staining and culture or
full-thickness skin biopsy and culture may be helpful when celluli-
tis is refractory to antibiotic therapy or when an unusual causative
organism is suspected. Because of their low yield, blood cultures
are obtained only in patients with signs of systemic toxicity, those
with buccal or periorbital cellulitis, and those with infection sus-
pected of being secondary to saltwater or freshwater exposure;
these clinical situations are associated with a higher likelihood of a
positive culture.
When the characteristic clinical features of necrotizing soft tis-
sue infection are absent, diagnosis may be difficult. In this setting,
laboratory and imaging studies become important [see Figure 2].
In one study, logistic regression analysis showed that an elevated
white blood cell (WBC) count (≥ 15,400/mm3) and hyponatre-
mia (serum sodium level lower than 135 mmol/L) at the time of
hospital admission were highly sensitive for the presence of a Figure 1 Lower-extremity necrotizing fasciitis is characterized
necrotizing soft tissue infection; however, the positive predictive by bullae, blebs, and discolored skin.
Necrotizing soft tissue infection is suspected
Patient has one or more obvious clinical Patient has no obvious signs of
signs of necrotizing soft tissue infection necrotizing soft tissue infection
Initiate operative exploration.
Patient has WBC count > 15,000/mm3, Patient has WBC count ≤ 15,000/mm3
disproportionate pain, bullae or blebs, and does not have disproportionate pain,
or refractory cellulitis bullae or blebs, or refractory cellulitis
Perform MRI.
Initiate antibiotic therapy.
Soft tissue gas is seen on MRI No soft tissue gas is seen

on MRI
Initiate operative exploration. Antibiotic therapy is Antibiotic therapy fails
successful
Perform full-thickness
No further action is biopsy and frozen-
necessary. section examination, and
Edema, inflammation, or Edema, inflammation, and obtain cultures.
gadolinium enhancement gadolinium enhancement
of deep soft tissues is of deep soft tissues are
present absent
Perform biopsy and frozen-

section examination. Diagnostic studies Diagnostic studies
yield positive results yield negative results
Perform operative Reassess antibiotic

debridement. therapy.
Biopsy and frozen-section Biopsy and frozen-section
examination are positive examination are negative
Figure 2 Algorithm outlines diagnostic evaluation of
Perform operative
debridement. patients with soft tissue infection.6
who underwent operative debridement.20 Operation was avoided nose or rule out soft tissue infection [see Figure 2]. This procedure
in two patients who showed no evidence of necrosis on MRI. A may be performed at the bedside with local anesthesia.The obser-
third patient without MRI evidence of necrosis underwent opera- vation of necrotic or infected tissue through the biopsy incision
tive exploration because of a high degree of clinical suspicion and indicates that immediate debridement is needed.
was diagnosed as having nonnecrotizing cellulitis. In a prospective
study from 1998, the investigators successfully employed MRI to
differentiate necrotizing from nonnecrotizing infections in 16 of 17 General Management of Nonnecrotizing and Necrotizing
patients (11 of 11 patients with necrotizing fasciitis and five of six Soft Tissue Infection
patients with nonnecrotizing cellulites).19
NONNECROTIZING INFECTION
The finding of soft tissue gas on diagnostic imaging warrants
immediate operative exploration and debridement. Because of the Antibiotic therapy is the cornerstone of treatment for patients
high sensitivity of MRI, necrotizing infection can be excluded with nonnecrotizing infections. Such patients usually require
when no involvement of the superficial fascia, subcutaneous tissue, antibiotics that are effective against group A streptococci or S.
or the deeper cutaneous layers is demonstrated. However, the aureus. The prevalence of community-acquired methicillin-resis-
inflammatory changes seen on MRI when necrotizing soft tissue tant S. aureus (MRSA) strains has increased significantly. These
infection is present may also be seen in patients with nonnecrotiz- strains now outnumber methicillin-sensitive strains by a two-to-
ing infections, as well as in those with other inflammatory condi- one margin.21 This development has necessitated a change in the
tions affecting the deep soft tissues. Because of the relatively low empirical treatment of these infections. Topical, oral, or intra-
specificity of this study, biopsy of the deeper cutaneous layers, with venous preparations may be employed, depending on the nature
frozen-section examination and culture, may be needed to diag- and severity of the disease process [see Management of Specific
Nonoperative Measures
Patients with necrotizing soft tissue infections frequently present

with tachycardia and hypotension, reflecting depleted intravascular
volume and possible septic shock. Such patients often exhibit
extensive extracellular fluid sequestration within the affected area,
as well as more generalized sequestration resulting from sepsis. A
balanced isotonic electrolyte solution, such as lactated Ringer solu-
tion (or 0.9% normal saline, for patients with renal dysfunction),
is administered to replace these fluid deficits. The adequacy of
intravascular volume repletion is often assessed by monitoring vital
signs and urinary output; however, it sometimes proves necessary
to use a central venous catheter to monitor central venous or pul-
monary arterial pressure in patients with associated myocardial
dysfunction, septic shock, chronic pulmonary disease, renal insuf-
ficiency, or other severe chronic illnesses.
Hyponatremia is usually corrected by infusing isotonic fluids.
Hypocalcemia, which can result from calcium precipitation in
Figure 3 Upper-extremity x-ray of a patient with necrotizing patients with extensive fat necrosis, is usually corrected by admin-
soft tissue infection demonstrates soft tissue gas outlining the istering I.V. calcium gluconate. Hyperglycemia is corrected with
muscles. insulin, given either via subcutaneous injection or, for patients with
more severe abnormalities, via I.V. infusion. Lactic acidosis gener-
ally responds to fluid administration. Renal function is assessed by
measuring blood urea nitrogen (BUN) and serum creatinine con-
centrations. CK levels should be monitored and a qualitative eval-
uation of urine myoglobin done if muscle necrosis is suspected or
renal failure is present. Myoglobinuria and elevated CK levels are
Patient requires treatment for necrotizing

soft tissue infection
Replace fluid deficits with lactated Ringer

solution or 0.9% NS.
If patient is anemic, give RBCs.
Initiate broad-spectrum antibiotic therapy.
Figure 4 Lower-extremity MRI of a patient with necrotizing

fasciitis of the left leg demonstrates inflammatory changes typical
of necrosis.
Hypotension persists Hypotension resolves
Insert central venous or

Soft Tissue Infections, below]. If polymicrobial infection is suspect- pulmonary arterial catheter.
ed, broad-spectrum antimicrobial agents should be given, either
alone or in combination.
NECROTIZING INFECTION
Management of necrotizing soft tissue infections is predicated Patient shows evidence Patient shows no
on early recognition of symptoms and signs and on emergency of septic shock evidence of septic
shock
operative debridement. Once the diagnosis of necrotizing soft tis-
sue infection is established, patient survival and limb salvage are Administer vasoactive agents:
• Dopamine, 5–10 μg/kg/min, or
best achieved by means of prompt operation; precise identification
• Norepinephrine, 0.02–0.08
of the causative bacteria and correct assignment of the patient to a μg/kg/min, or
specific clinical syndrome are unnecessary.The delay between hos- • Vasopressin, 0.1–0.4 IU/min
pital admission and initial debridement is the most critical factor
influencing morbidity and mortality: a number of reports have
demonstrated a strong correlation between survival and the inter-
val between onset of symptoms and initial operation.9,22-24
The components of treatment of necrotizing soft tissue infection Perform operative debridement.
are (1) resuscitation and correction of fluid and electrolyte disor-
ders, (2) physiologic support, (3) broad-spectrum antimicrobial
therapy, (4) urgent and thorough debridement of necrotic tissue, Figure 5 Algorithm outlines treatment of necrotizing soft tissue
and (5) supportive care [see Figure 5]. infection.
Table 3 I.V. Antibiotic Dosages for Adult Pathogenesis of Soft Tissue Infections, below], improved leukocyte
Patients with Necrotizing Soft Tissue Infection function, and attainment of tissue oxygen levels that are bacterici-
dal for Clostridium perfringens and bacteriostatic for other anaerobic
and Normal Renal Function bacteria. Hyperbaric oxygen does not, however, neutralize exotox-
in that has already been released.25 At present, except for some
Ampicillin-sulbactam 3 g q. 6 hr data from retrospective studies, there is little evidence supporting
Imipenem-cilastatin 500–750 mg q. 6 hr the benefits of hyperbaric oxygen therapy. Such therapy has not
Single agents Meropenem 1–2 g q. 8 hr been demonstrated to improve survival or to bring about earlier
Piperacillin-tazobactam 3.375 g q. 6 hr resolution of necrotizing soft tissue infection, and it has been asso-
Ticarcillin-clavulanate 3.1 g q. 6 hr
ciated with barotrauma, pneumothorax, and oxygen toxicity.
Aerobic/facultative coverage Accordingly, we believe that operative debridement should not be
Ampicillin 2 g q. 6 hr delayed to accommodate hyperbaric oxygen therapy and that such
Cefotaxime 1–2 g q. 8 hr therapy should not be considered a substitute for complete
Ceftazidime 1 g q. 8 hr
Cefuroxime 1.5 g q. 8 hr debridement of infected nonviable tissues.
Ciprofloxacin 400 mg q. 12 hr I.V. antimicrobial therapy is indicated in all patients with necro-
Agents used in
Daptomycin 4 mg/kg q. 24 hr tizing soft tissue infections [see Table 3]. Such therapy is important,
combination Gentamicin 1.7 mg/kg q. 8 hr or but it is not a substitute for prompt and adequate operative
regimens 5.1 mg/kg q. 24 hr
Linezolid 600 mg q. 12 hr debridement. Necrotizing soft tissue infections are most often
Moxifloxacin 400 mg q. 24 hr caused by a mixed polymicrobial bacterial flora [see Table 4].
Tigecycline 100 mg initially; then Approximately 25% to 30% of necrotizing soft tissue infections are
50 mg q. 12 hr monomicrobial. Although S. pyogenes is the bacterium most fre-
Vancomycin 1 g q. 12 hr
Anaerobic coverage quently involved, the microbiology of the infections often cannot
Clindamycin 600–900 mg q. 8 hr be accurately predicted before final identification of organisms on
Metronidazole 500 mg q. 6 hr culture. Thus, the empirical antibiotic regimen chosen should be
effective against a diverse group of potential pathogens.26 In addi-
tion, because these patients have a high incidence of associated
suggestive of myonecrosis. Anemia is treated with packed red nosocomial infections and even of metastatic infections, it is
blood cell transfusions. important to ensure that the dosage is high enough to achieve ade-
Patients whose hypotension does not resolve with appropriate quate serum concentrations.9,23 Once the results of intraoperative
intravascular fluid resuscitation often experience septic shock. In culture and antimicrobial sensitivity testing become available,
these circumstances, low dosages of I.V. dopamine (5 to 10 antibiotic therapy is adjusted accordingly. This adjustment can be
μg/kg/min), vasopressin (0.1 to 0.4 IU/min), or norepinephrine challenging, in that all of the pathogens identified must be treated.
(0.02 to 0.08 μg/kg/min) are useful for raising blood pressure and I.V. antimicrobial therapy is continued until operative debride-
improving myocardial function. ment is complete, there is no further evidence of infection in the
Patients with traumatic wounds or other contaminated sites involved tissues, and signs of systemic toxicity have resolved.
should receive tetanus toxoid or human tetanus immunoglobulin, Topical antiseptic agents (e.g., Dakin solution and Burrow solu-
depending on their immunization status. tion) may help control infection that progresses despite adequate
Hyperbaric oxygen has been advocated as adjunctive therapy for debridement and I.V. antibiotics.Topical application of mycostatin
extensive necrotizing infections, particularly those caused by powder may help control progressive fungal infection. When
clostridia.25 The beneficial properties of hyperbaric oxygen include patients are able to resume oral intake, they can often be switched
inhibition of bacterial exotoxin production [see Discussion, from I.V. to oral antimicrobial therapy. Antimicrobial therapy
should not, however, be prolonged merely because oral agents are
available.
Table 4 Organisms Causing Necrotizing
Soft Tissue Infection Operative Treatment
The most critical factors for reducing mortality from necrotiz-
Gram-positive ing soft tissue infections are early recognition and urgent operative
Group A Streptococcus debridement.9,22,24,27 The extent of debridement depends on intra-
Enterococcus species operative findings and cannot be accurately predicted before oper-
Staphylococcus aureus ation. Operative intervention helps limit tissue damage by remov-
Group B Streptococcus ing necrotic tissue, which serves as a nidus for infection.
Bacillus species Thorough exploration is necessary to confirm the diagnosis of
Gram-negative necrotizing soft tissue infection and determine the degree of
Aerobes
Escherichia coli involvement. Aggressive, widespread debridement of all apparent
Pseudomonas aeruginosa
necrotic, infected tissue is essential; antibiotics will not penetrate
Enterobacter cloacae
Klebsiella species
dead tissues.The underlying necrosis of subcutaneous tissues, fas-
Serratia species cia, and muscle typically extends beyond the obvious limits of cuta-
Acinetobacter calcoaceticus neous involvement. Operative debridement should therefore be
Vibrio vulnificus continued until viable tissue is reached. In most instances, the
involved tissues are easily separated from their surrounding struc-
Bacteroides species
tures.The presence of “dishwater pus” and noncontracting muscle
Anaerobes Clostridium species
Peptostreptococcus species
are additional indicators of necrotizing infection. The presence of
arterial bleeding generally indicates that tissues are viable; in the
absence of arterial bleeding, tissues are nonviable even if venous cera. Some have advocated using biologic materials or absorbable
bleeding is present.With deep necrotizing infections, debridement mesh for restoration of abdominal wall continuity; however, we
of the necrotic fascia and muscle may create large skin flaps that prefer to use permanent mesh in most circumstances, especially
are poorly perfused. It is best to preserve as much viable skin and when omentum is available for interposition between the mesh and
subcutaneous tissue as possible because these tissues can be essen- the small intestine.9
tial for later coverage of the wound. Nonviable skin, however, Mortality from necrotizing soft tissue infection ranges from 21%
should be resected. to 29%.9,22,24,27,28 Risk factors for mortality include age greater
Wound drainage or exudate should be submitted for Gram than 60 years, the presence of associated chronic illnesses, a rela-
staining, as well as for aerobic, anaerobic, and fungal cultures and tively high percentage of total body surface area involved, and,
antimicrobial sensitivity testing. Fasciotomy is rarely required.The most important, delays in recognition and treatment.9,22,24 Patients
presence of subcutaneous gas extending beyond areas of nonviable with truncal involvement or positive blood cultures also have a
tissue does not necessitate debridement if the surrounding tissues higher mortality.22,28
are viable. It is sometimes helpful to perform an exploratory inci-
sion over an area beyond the limits of debridement when it is
uncertain whether necrosis is undermining viable skin. If no necro- Management of Specific Soft Tissue Infections
tizing infection is found, the incision may be closed primarily. Normal skin functions as a protective barrier that prevents
Reexploration should be routinely performed within 24 to 48 microorganisms from causing soft tissue infection.The skin is made
hours to ensure that all necrotic tissue has been debrided. up of two layers, the epidermis and the dermis [see Figure 6]. The
Debridement is repeated as necessary until the infection is con- epidermis, the outer avascular epithelial layer, functions as a per-
trolled. If repeated debridement does not control infection, if there meability barrier for the rest of the body. The dermis, the inner
are persistent, fulminant infections of the extremities, or if an layer, contains blood vessels, lymphatic vessels, sweat and seba-
extremity remains nonfunctional after debridement has been com- ceous glands, and hair follicles. The subcutaneous tissue separates
pleted, amputation can be lifesaving. Amputation is most often the skin from the deep fascia, muscle, and bone.Typically, soft tis-
required for patients with clostridial myonecrosis and for diabetic sue infections result from disruption of the skin by some exogenous
patients with necrotizing infections.24 In two large series of patients factor; less commonly, they result from extension of a subjacent
with necrotizing soft tissue infections, the incidence of amputation infection or hematogenous spread from a distant site of infection.
was approximately 15% to 25%.9,22
SUPERFICIAL INFECTIONS
Patients with necrotizing soft tissue infections involving the per-
ineum and perirectal areas may need a diverting colostomy to pre- Superficial infections constitute the majority of soft tissue infec-
vent tissue contamination resulting from defecation and to control tions. They primarily involve the epidermis or dermis (pyoderma)
local infection. Overall, this measure is required in fewer than 25%
of cases.9
After debridement, the exposed areas should be treated with
0.9% normal saline wet-to-dry dressings. Once the initial infection
has been controlled and debridement is no longer necessary, dress-
ing changes can often be performed at the bedside after sufficient
analgesics have been given to achieve adequate pain management.
Patient-controlled analgesia is frequently useful early in the course
of treatment. Propofol or ketamine can be given in the intensive
care unit to facilitate pain control during dressing changes. Epidermis
Early enteral or parenteral nutritional support should be insti-
tuted to optimize recovery. Nutritional support should begin once
resuscitation is complete, the infection is adequately controlled, Papillary
and the signs of sepsis have resolved. Because it frequently proves Dermis
necessary to return the patient to the operating room, enteral feed-
ing tubes should be placed beyond the pylorus so that enteral Dermis
nutrition can be provided without interruption. Alternatively, par-
enteral nutrition may be employed.
Reticular
Once the localized infection is under control and the patient is Dermis
recovering, the exposed soft tissues should be covered.This is most
commonly done with split-thickness skin grafting, though other
reconstructive procedures (e.g., rotational flaps) [see 3:7 Surface Superficial
Fascia
Reconstruction Procedures] can be effective in this setting as well.
Subcutaneous
Vacuum-assisted closure devices can reduce the exposed surface
Tissue
area and lessen the need for skin graft coverage. Exposed tendons, Deep
nerves, or bone often should be covered with full-thickness skin to Fascia
prevent desiccation and preserve limb function. Premature closure Muscle
of highly contaminated or persistently infected sites usually fails and
leads to recurrence of infection and a greater likelihood of death.
When the abdominal or chest wall has been excised to control
infection, reconstruction is necessary. Prosthetic mesh is useful for
restoring continuity of the abdomen or the chest wall, and overly- Figure 6 Depicted is the normal anatomy of the skin and the
ing moist dressings can help prevent desiccation of underlying vis- deeper cutaneous layers.6
The diagnosis is established by Gram stain and culture of the

Table 5 Topical and Oral Antibiotic Agents vesicular fluid or the crusted plaque. The skin lesions usually
Used for Superficial Soft Tissue Infections* resolve spontaneously within 2 to 3 weeks.31 Antibiotic therapy
accelerates the resolution of these lesions. Mupirocin ointment
Mupirocin ointment (2%), applied to affected area t.i.d.† (2%) is applied topically three times a day until the lesions clear.
Erythromycin ointment (2%), applied to affected area b.i.d.† This agent possesses excellent in vitro activity against both staphy-
Clindamycin gel or lotion (1%), applied to affected area b.i.d.† lococci and streptococci and achieves high rates of cure in patients
Gentamicin cream or ointment (0.1%), applied to affected area t.i.d. with localized disease. Erythromycin and clindamycin ointments
or q.i.d. are acceptable alternatives [see Table 5]. For patients who have dis-
Penicillin V, 250–500 mg q.i.d. (pediatric: 25–50 mg/kg in divided
doses q.i.d.) seminated impetigo or impetigo of the scalp or mouth and those in
Amoxicillin, 250–500 mg t.i.d. (pediatric: 20–30 mg/kg/day p.o. in whom topical therapy fails, an oral antibiotic (e.g., dicloxacillin,
divided doses t.i.d.) cephalexin, cefadroxil, erythromycin, or clindamycin) may be used
Dicloxacillin, 250–500 mg q.i.d. (pediatric: 12.5–25.0 mg/kg/day in [see Table 5]. A 7-day course of oral antibiotic therapy is usually
divided doses q.i.d.)
sufficient.31
Cephalexin, 250–500 mg q.i.d. (pediatric: 25–100 mg/kg/day in
divided doses q.i.d.)
Cefadroxil, 500–1,000 mg b.i.d. (pediatric: 30 mg/kg/day in divided Erysipelas Erysipelas is an acute bacterial infection that prin-
doses b.i.d.) cipally involves the dermis. It is almost invariably caused by S. pyo-
Erythromycin, 250–500 mg q. 6 hr (pediatric: erythromycin ethyl genes. Most cases are preceded by influenzalike symptoms.
succinate, 40 mg/kg in divided doses q.i.d.)
Clindamycin, 150–450 mg q.i.d. (pediatric: 20 mg/kg/day in divided
Infection extends through the dermal lymphatic vessels and is typ-
doses t.i.d. or q.i.d.) ically manifested by a tender, pruritic, intensely erythematous,
Trimethoprim-sulfamethoxazole, 160/800 mg b.i.d. sharply demarcated, and raised plaque. Patients complain of pain,
Amoxicillin-clavulanate, 500 mg t.i.d. (pediatric: 40 mg/kg/day in often in conjunction with high fever, increased skin warmth, and
divided doses t.i.d.) leukocytosis. Lymphangitis and lymphadenopathy are sometimes
Ciprofloxacin, 500 mg p.o., b.i.d.
present as well. The leg is the most common site of involvement,
*All dosages are for patients with normal renal function.
but erysipelas may also occur on the face, the arms, and the upper
†Adult dosage and pediatric dosage are the same. thighs.
The factors predisposing to the development of erysipelas of the
extremity include local conditions such as tinea pedis (athlete’s
foot), leg ulcers, and venous stasis dermatitis.32 Erysipelas tends to
or the subcutaneous tissue (cellulitis) and secondarily occur in skin be more common in the presence of associated conditions such as
damaged by animal or human bites. Nonnecrotizing superficial lymphedema, diabetes mellitus, alcoholism, immunocompromise,
soft tissue infections are principally treated with antibiotics. and obesity,30,32 and it is more likely to recur in patients with these
Necrosis is rare but may develop in superficial infections that are associated diseases and in those whose underlying skin conditions
inadequately treated or neglected. are inadequately treated. Erysipelas recurs in 10% of patients with-
in 6 months of their first episode and in 30% within 3 years.32
Pyoderma The standard antibiotic treatment for uncomplicated erysipelas
Pyoderma is a general term referring to a bacterial infection of is penicillin, which is effective in at least 80% of cases. Oral and
the skin. It may be divided into several subcategories, including intravenous antibiotic regimens are equally efficacious. Amoxicillin
impetigo, erysipelas, folliculitis, and furuncles and carbuncles. appears to work as well as penicillin. Patients with erysipelas of the
lower extremity should be placed on bed rest, and the involved leg
Impetigo Impetigo is a highly contagious bacterial infection should be elevated to reduce edema and pain. Once the patient is
that is confined to the epidermis and that usually involves the face able to resume normal activities, he or she should be fitted with
or the extremities. It is most common in infants and preschool chil- elastic stockings, which help reduce the occurrence of edema and
dren and is seen more frequently in patients with preexisting skin lower the risk of lymphedema. For patients with tinea pedis, a top-
conditions (e.g., eczema, atopic dermatitis, varicella infection, ical antifungal agent is used to treat the infection and prevent
angular cheilitis, and scabies).Warm and humid weather, crowded recurrence.
living conditions, and poor hygiene can all contribute to the devel-
opment of impetigo.29 The dominant pathogen is S. aureus, which Folliculitis Folliculitis is an infection of the hair follicle that is
causes either a bullous or a nonbullous form of the disease; a less typically caused by S. aureus. It is characterized by a painful, ten-
common pathogen is S. pyogenes, which causes a nonbullous der, erythematous papule with a central pustule. A shaft of hair is
form.30 often seen in the center of the pustule. Shaving, plucking, waxing,
Impetigo usually occurs in areas of skin breakdown, though S. heat and humidity, the use of corticosteroids or antibiotics,
aureus may give rise to de novo infection in normal skin. Bullous immunosuppression, and occlusion of the skin by clothing, adhe-
impetigo is manifested by numerous blisters or bullae that rapidly sives, or plastics may predispose to folliculitis.29 Single or multiple
become pustules, then rupture within 1 to 2 days to form a thick, lesions may occur in the skin of any hair-bearing area. If the pus-
honey-colored, crusted plaque that remains for days to weeks. tule ruptures, superficial erosion often ensues. Infection that prin-
Nonbullous impetigo is characterized by erythema and tiny, less cipally involves the deeper part of the hair follicle is characterized
prominent vesicles that progress to crusted erosions in the skin. by a tender, swollen papule without an associated pustule at the
The skin lesions are intensely pruritic, and local spread may occur skin surface.
as a result of scratching and release of infected fluid from the blis- In rare cases, folliculitis is caused by pathogens other than S.
ters, bullae, or vesicles. Associated regional lymphadenopathy is aureus, such as Pseudomonas aeruginosa, Klebsiella species,
common. Glomerulonephritis may complicate streptococcal- Enterobacter species, Proteus species, yeasts, and fungi. Pseudomonas
induced impetigo.30,31 folliculitis usually results from exposure to inadequately chlorinat-
ed water in swimming pools, hot tubs, or whirlpools. Patients with

this infection have multiple papular or pustular lesions on the back, Table 6 Risk Factors for Soft Tissue Infection
the buttocks, and the extremities, along with fever and malaise
Complicating Animal or Human Bite
appearing 6 hours to 3 days after exposure.31,33 Organisms may be
cultured either from the pustules or from the infected water.
Location on the hand or the foot Immunosuppression
Klebsiella, Enterobacter, and Proteus species can cause folliculitis in or over a major joint Chronic alcoholism
patients receiving long-term antibiotic therapy for acne vulgaris.30 Location on the scalp or the face Diabetes mellitus
Yeast folliculitis and fungal folliculitis tend to occur in immuno- of an infant
Corticosteroid use
compromised patients.30 Puncture wound
Preexisting edema in an
In most patients, folliculitis resolves spontaneously within 7 to Delay in treatment lasting longer affected extremity
than 12 hr
10 days.31 Topical therapy with clindamycin, erythromycin, or
mupirocin ointments or benzoyl peroxide in combination with
warm soaks may accelerate resolution [see Table 5]. Isotretinoin can
be used to treat gram-negative folliculitis. Gentamicin cream may An incision-and-drainage procedure is recommended when a
be helpful in drying out the pustular lesions in patients with fluctuant carbuncle is present. A thorough search for loculated
Pseudomonas folliculitis. areas should be undertaken to facilitate drainage of deeper accu-
In patients with refractory or disseminated follicular infections, mulations of pus and to ensure adequate treatment. Wide local
oral antibiotic therapy is indicated.When S.aureus is considered the excision of the involved skin and subcutaneous fat is often neces-
most likely pathogen, trimethoprim-sulfamethoxazole, a tetracy- sary to prevent recurrent disease. An oral antistaphylococcal agent
cline, or clindamycin should be given, in view of the high preva- should be given. All patients with hair follicle infections should
lence of MRSA21,34; an oral quinolone is indicated for the treatment cleanse the site with chlorhexidine or an iodine-containing solution.
of gram-negative folliculitis [see Table 5]. Elimination of predispos-
ing factors is important for reducing the likelihood of recurrence. Infections Developing in Damaged Skin
Damage to skin as a result of animal or human bites predispos-
Furuncles and carbuncles Furuncles and carbuncles are es patients to soft tissue infection. An estimated 50% of all
deeper infections of the hair follicle that extend beyond the follicle Americans will be bitten by an animal or by another human being
to involve the subcutaneous tissue. For both, S. aureus is the usual during their lifetime.35 Animal and human bites account for
causative organism. approximately 1% of all emergency department visits.35 Soft tissue
A furuncle, or boil, is a small abscess, manifested as a firm, ten- infection is the most common complication of such bites.The risk
der, erythematous nodule that tends to occur in skin areas exposed of infection depends on the type of bite, the site of injury, the time
to friction (e.g., the inner thighs and the axilla). Furuncles also may elapsed from the bite until presentation, host factors, and the man-
occur on the face, the neck, the upper back, and the buttocks. agement of the wound [see Table 6].
Possible predisposing factors include increased friction and perspi- Most animal and human bites produce minor injuries for which
ration (as seen in obese individuals or athletes), corticosteroid use, patients do not seek medical attention.The overall risk of infection
diabetes mellitus, and inherited or acquired defects in neutrophil after a bite is estimated to be 5% to 15%36; however, among the
function.29,31 subset of patients who seek medical attention, estimated infection
Initial treatment consists of applying warm compresses to help rates range from 2% to 20% for dog bites, from 30% to more than
promote drainage and administering an oral antimicrobial agent 50% for cat bites, and from 10% to 50% for human bites.37 Most
that is effective against S. aureus (e.g., dicloxacillin, cephalexin, patients with an infected bite can be managed on an outpatient
cefadroxil, erythromycin, or clindamycin for infections presumed basis with oral antibiotic therapy and elevation of the involved site.
to be caused by methicillin-sensitive strains; trimethoprim-sul-
famethoxazole, a tetracycline, or clindamycin for suspected MRSA Animal bites In the United States, dog bites account for
infections) [see Table 5].With time, the furuncle becomes fluctuant, 80% to 90% of all animal bites, cat bites for 3% to 15%.37,38
and the pus coalesces at the skin surface. An incision-and-drainage Nondomestic animals are responsible for only 1% to 2% of all ani-
procedure is necessary when these lesions do not drain sponta- mal bites. Patients with infections resulting from animal bites typ-
neously. This procedure should be performed with local anesthe- ically present with significant pain, soft tissue swelling, and tender-
sia, and care should be taken to open the abscess cavity completeness; they may also have associated injuries to nerves, tendons,
ly. Lesions that have drained spontaneously should be examined to bones, joints, or blood vessels. Bites involving the hand are associ-
confirm that the cavity has been opened sufficiently. Failure to ated with an increased risk of tenosynovitis, septic arthritis, and
drain these lesions adequately may result in recurrence, as well as abscess formation.37
in progression to a more serious infection. Infections that occur after a dog or cat bite are usually polymi-
A carbuncle is a deep cutaneous infection involving multiple crobial, involving a mixture of aerobes and anaerobes [see Table 7].
hair follicles that is characterized by destruction of fibrous tissue P. multocida is the major pathogen, isolated from 50% to 80% of
septa and consequent formation of a series of interconnected infections related to cat bites and from 25% of those related to dog
abscesses. It is typically manifested by a painful, red, tender, bites.35,37 Infection with P. multocida is characterized by the acute
indurated area of skin with multiple sinus tracts. Systemic mani- onset of severe pain, tenderness, and swelling, usually within 12 to
festations (e.g., fever and malaise) are common. Carbuncles occur 18 hours of the bite. In rare cases (usually involving immunocom-
most frequently on the nape of the neck, the upper part of the promised patients), Capnocytophaga canimorsus causes soft tissue
back, or the posterior thigh. The thickness of the overlying skin in infection after a dog or cat bite. C. canimorsus infection can be quite
these areas leads to lateral extension of the infection and locula- serious, leading to overwhelming sepsis; the associated mortality is
tion. Patients commonly present with relatively large skin lesions 25% to 30%.37-39
that represent a confluence of inflammatory nodules.These lesions Wounds resulting from animal bites should immediately be
are associated with chronic drainage, sinus tracts, and scarring. washed with soap and water.When seen early, dog bites should be
copiously irrigated, debrided, and, in most circumstances, closed. species are more common [see Table 7]. Unlike the anaerobic
Infected wounds, wounds older than 12 hours, cat bites, and bites pathogens in dog and cat bites, however, those involved in human-
on the hand should be left open. In all cases of infection related to bite infections often produce β-lactamases.37 The predominant
an animal bite, aerobic and anaerobic cultures should be obtained aerobic organisms in human-bite infections are S. aureus,
from the site of infection.Tetanus immune status should be deter- Staphylococcus epidermidis, α- and β-hemolytic streptococci,
mined, and immunization against tetanus should be provided Corynebacterium species, and E.corrodens.E.corrodens is a fastidious
when appropriate. In cases of bites from nondomestic carnivores facultative aerobic gram-negative rod that is cultured from approx-
(e.g., bats, skunks, raccoons, foxes, or coyotes), wounds should be imately 25% of clenched-fist injuries and frequently causes a
irrigated with povidone-iodine to reduce the transmission of chronic indolent infection.37 It typically is susceptible to amoxi-
rabies, and immunization against rabies should be provided. cillin-clavulanate, trimethoprim-sulfamethoxazole, doxycycline,
Patients with established soft tissue infection and patients with and ciprofloxacin but resistant to dicloxacillin, nafcillin, first-gen-
noninfected bites who have risk factors for infection should receive eration cephalosporins, clindamycin, and erythromycin. Other
antibiotic therapy [see Table 6]. A broad-spectrum antibiotic effec- pathogens may also be transmitted as a result of contact with blood
tive against aerobic and anaerobic organisms should be chosen [see or saliva, including hepatitis B and C viruses, Mycobacterium tuber-
Table 5]. Amoxicillin-clavulanate is the antibiotic of choice because culosis, and, possibly, HIV.
of its broad spectrum of activity against common pathogens; Management of human-bite wounds is similar to that of animal-
trimethoprim-sulfamethoxazole, doxycycline, and ciprofloxacin bite wounds. The wound must be thoroughly irrigated, preferably
are also used [see Table 5]. Infections secondary to P. multocida with 1% povidone-iodine, which is both bactericidal and viricidal.
respond to oral treatment with penicillin V, amoxicillin, cefurox- Puncture bite wounds should be irrigated with a small catheter to
ime, or ciprofloxacin.37 Infections secondary to C. canimorsus achieve high-pressure irrigation. If the wound appears infected,
respond to penicillin, ampicillin, ciprofloxacin, erythromycin, or aerobic and anaerobic cultures are obtained. Devitalized tissue
doxycycline. Whether antibiotics are indicated for a fresh animal should be debrided, and the wound should be left open, whether
bite in a patient with a low risk of infection is controversial. infected or not. The injured extremity should be immobilized and
Because it is difficult to predict which bite wounds will become elevated.
infected, some experts advocate routine antibiotic treatment of all Because of the high degree of contamination and local tissue
dog bites for at least 3 to 5 days.35 damage associated with human-bite wounds to the hand, antimi-
crobial therapy is indicated for all such injuries. A prospective, ran-
Human bites Human bites may be classified as either occlu- domized study of 45 patients with human bites to the hand seen
sional bites (in which teeth puncture the skin) or clenched-fist within 24 hours after injury and without evidence of infection, ten-
injuries (in which the hand is injured after contact with teeth).37,39 don injury, or joint capsule penetration demonstrated that infec-
Occlusional bites carry roughly the same risk of infection as animal tion developed in 47% of the patients who did not receive antibi-
bites, except when they occur on the hand. Clenched-fist injuries otics but in none of those who did.40 Patients with an uncompli-
and all hand injuries are associated with a higher risk of infection. cated human bite to the hand should receive a broad-spectrum
Clenched-fist injuries typically occur at the third metacarpopha- oral antimicrobial agent, such as amoxicillin-clavulanate (or doxy-
langeal joint. Penetration of the metacarpophalangeal joint capsule cycline if they are allergic to penicillins).
may occur, with subsequent development of septic arthritis and Patients with human-bite wounds at sites other than the hand
osteomyelitis.35 who have risk factors for infection [see Table 6] should also receive
Soft tissue infections resulting from human bites are polymicro- antimicrobial therapy. However, minor bite wounds in patients
bial, involving a mixture of aerobes and anaerobes. On average, five who have no risk factors for infection do not call for antibiotic ther-
different microorganisms are isolated from a human-bite apy. As with animal-bite wounds, tetanus immunization status
wound37—significantly more than are usually isolated from an ani- should be determined, and tetanus toxoid, tetanus immunoglobin,
mal-bite wound. In addition, the concentration of bacteria in the or both should be administered as indicated.
oral cavity is higher in humans than in animals.The anaerobic bac- Patients with systemic manifestations of infection (e.g., fever or
teria isolated from human-bite wounds are similar to those that chills); severe cellulitis; compromised immune status; diabetes
cause infection after dog and cat bites, except that Bacteroides mellitus; significant bites to the hand; associated joint, nerve, bone,
or tendon involvement; or infection refractory to oral antibiotic
therapy should be admitted to the hospital for I.V. antibiotic ther-
Table 7 Organisms Most Frequently Isolated apy.37 Appropriate choices for I.V. treatment include cefoxitin,
cefotetan, and piperacillin-tazobactam. Tenosynovitis, joint infec-
from Dog- and Cat-Bite Wounds tions, and associated injuries to deep structures must also be treat-
ed if present.
Pasteurella multocida
Corynebacterium species Cellulitis
Aerobes Staphylococcus species Cellulitis is an acute bacterial infection of the dermis and the
Streptococcus species
subcutaneous tissue that primarily affects the lower extremities,
Capnocytophaga canimorsus (rare)
though it can affect other areas as well (e.g., the periorbital, buccal,
Bacteroides species and perianal regions; the areas around incisions; and sites of body
Prevotella species piercing).41 The most common causes of cellulitis are (1) soft tis-
Porphyromonas species sue trauma from injection of illicit drugs, puncture wounds from
Anaerobes Peptostreptococci foreign bodies or bites (animal, human, or insect), or burns; (2)
Fusobacterium species
surgical site infection; and (3) secondary infection of preexisting
Bacteroides fragilis
skin lesions (e.g., eczema; tinea pedis; and decubitus, venous sta-
Veillonella parvula
sis, or ischemic ulcers). Less common causes include extension of
a subjacent infection (e.g., osteomyelitis) and bacteremia from a Table 8 Suggested Parenteral Antibiotic Regimens
remote site of infection. Predisposing factors for the development for Treatment of Cellulitis in Adults
of cellulitis include lymphatic disruption or lymphedema, intersti-
tial edema, previous irradiation of soft tissue, diabetes mellitus,
immunocompromise, and peripheral vascular disease. Agent I.V. Dosage
Nafcillin 2 g q. 4 hr
Nonnecrotizing The overwhelming majority of patients with
cellulitis have a nonnecrotizing form of the disease. Patients typi- Cefazolin 1–2 g q. 8 hr
cally present for medical attention because of pain and soft tissue Clindamycin 600–900 mg q. 8 hr
erythema, and they often have constitutional symptoms (e.g.,
fever, chills, or malaise). Physical examination reveals erythema Vancomycin 1 g q. 8 hr
with advancing borders, increased skin warmth, tenderness, and Ampicillin-sulbactam 3 g q. 6 hr
edema. Lymphangitis may also be present, manifested as an ery-
thematous linear streak that often extends to a draining lymph
node basin; associated lymphadenopathy, fever, and leukocytosis Patients who are diabetic or immunocompromised and those
with a shift to immature forms may be apparent. who have high fever and chills, rapidly spreading cellulitis, or cel-
Cellulitis is usually caused by a single aerobic pathogen. The lulitis that is refractory to oral antibiotic therapy should be admit-
organisms most frequently responsible for cellulitis in otherwise ted to the hospital for I.V. antibiotic therapy [see Table 8]. Nafcillin
healthy adults are S. pyogenes and S. aureus. Of the two, S. pyogenes is the preferred I.V. agent. Cefazolin or piperacillin-tazobactam
is the more common and is the usual pathogen in patients with should be added if gram-negative organisms are suspected
associated lymphangitis. S.aureus is usually present in patients with pathogens, as when cellulitis complicates a decubitus or a diabetic
underlying chronic skin disease. Other microorganisms may cause foot ulcer.Vancomycin, tigecycline, linezolid, or gentamicin should
cellulitis on rare occasions but usually only in specific clinical cir- be given to patients with MRSA infections and those with serious
cumstances. Haemophilus influenzae sometimes causes cellulitis in penicillin allergies.
children or adults infected with HIV.42 Streptococcus pneumoniae
may cause this condition in patients with diabetes mellitus, alco- Necrotizing Necrotizing cellulitis is similar to nonnecrotizing
holism, nephrotic syndrome, systemic lupus erythematosus, or cellulitis in etiology and pathogenesis but is more serious and pro-
hematologic malignancies.43 P. multocida may cause cellulitis as a gressive. Necrosis generally occurs when the infection is neglected
complication of dog or cat bites. S. epidermidis is a recognized cause or inadequately treated. The microbiology of necrotizing cellulitis
of cellulitis among immunocompromised patients, including those is also similar to that of nonnecrotizing cellulitis, except that C. per-
with HIV infection and those receiving organ transplants.44 V. vul- fringens and other clostridial species may be involved when necro-
nificus occasionally causes cellulitis in patients who have ingested sis is present. In addition to antimicrobial therapy [see Table 8],
raw seafood or who have experienced minor soft tissue trauma and urgent operative debridement is indicated. In other respects,
are exposed to sea water.41 A. hydrophila may cause cellulitis in necrotizing cellulitis is treated in much the same way as deep
patients with soft tissue trauma who are exposed to brackish or necrotizing infections are (see below). In some patients with necro-
fresh water, soil, or wood.41 Cellulitis that complicates decubitus or tizing fasciitis, the skin is involved secondarily.
other nonhealing ulcers is usually a mixed infection that includes
DEEP NECROTIZING INFECTIONS
gram-negative organisms.
In most situations, cellulitis is treated with empirical antibiotic Infections that involve the soft tissues deep to the skin tend to
regimens that include agents effective against S. pyogenes and S. become apparent after necrosis has developed. It is possible that
aureus. Attempts to isolate a causative pathogen are usually unsuc- deep necrotizing infections begin without necrosis but progress
cessful; needle aspiration and skin biopsy at an advancing margin rapidly as a result of intrinsic factors. Alternatively, such infections
of erythema are positive in only 15% and 40% of cases, respective- may develop as a result of delayed recognition attributable to the
ly.45 Bacteremia is uncommon, and as a result, blood cultures are tissue depth at which the process takes place and the lack of spe-
positive in only 2% to 4% of patients with cellulitis.41,46 Blood cul- cific early signs and symptoms.The relatively poor blood supply to
tures are obtained selectively when the patient has high fever and subcutaneous fat makes this tissue more susceptible to microbial
chills, preexisting lymphedema, or buccal or periorbital cellulitis or invasion. Contamination of the deep soft tissues occurs either
when a saltwater or freshwater source of infection is suspected. In through neglect or inadequate treatment of cutaneous or subcuta-
all of these clinical situations, the prevalence of bacteremia is high- neous infections or through hematogenous seeding of microorgan-
er.46 Radiologic examination should be reserved for patients in isms in an area of injury.
whom it is difficult to exclude a deep necrotizing infection. Most deep necrotizing soft tissue infections are polymicrobial
In an otherwise healthy adult, uncomplicated cellulitis without and occur on the extremities, the abdomen, and the per-
systemic manifestations can be treated with an oral antibiotic on an ineum.9,22,24 Necrotizing infections that involve only muscle are
outpatient basis. Because the vast majority of cellulitides are uncommon; therefore, necrotizing fasciitis can be considered the
caused either by S. pyogenes or by a penicillinase-producing S. paradigm for these infectious processes.
aureus, one of the following agents is usually given: dicloxacillin, The early signs and symptoms of deep necrotizing soft tissue
cephalexin, cefadroxil, erythromycin, or clindamycin. When infection are localized pain, tenderness, mild edema, and erythema
MRSA infection is suspected, trimethoprim-sulfamethoxazole, a of the overlying skin. These characteristics may be subtle, and this
tetracycline, or clindamycin should be administered [see Table 5]. diagnosis may not readily come to mind. Sometimes, there is a his-
The margins of the erythema should be marked with ink to facili- tory of previous injury to the area of suspected infection, which can
tate assessment of the response to treatment. For lower-extremity lead to confusion about the diagnosis. The more classic findings
cellulitis, reduced activity and elevation are important ancillary associated with these infections—skin discoloration, the formation
measures. Appropriate analgesic agents should be given. of bullae, and intense erythema—occur much later in the process.
It is important to understand this point so that an early diagnosis fect environment for clostridial proliferation. A rare form of this dis-
can be made and appropriate treatment promptly instituted. ease occurs in patients with colon cancer in whom myonecrosis
caused by Clostridium septicum develops in the absence of tissue
Necrotizing Fasciitis damage. Myonecrosis may also result from the spread of contigu-
Necrotizing fasciitis is characterized by angiothrombotic micro- ous fascial infections.
bial invasion and liquefactive necrosis.6 Progressive necrosis of the Clostridial myonecrosis has a notably short incubation period:
superficial fascia develops, and the deep dermis and fascia are infil- severe progressive disease can develop within 24 hours of contam-
trated by polymorphonuclear leukocytes, with thrombosis of nutri- ination. This condition is characterized by acute catastrophic pain
ent vessels and occasional suppuration of the veins and arteries in the area of infection, with minimal associated physical findings.
coursing through the fascia; bacteria then proliferate within the Systemic signs of toxicity (e.g., confusion, incontinence, and delir-
destroyed fascia. Initially, tissue invasion proceeds horizontally, but ium) often precede the physical signs of localized infection. The
as the condition progresses, ischemic necrosis of the skin develops, skin initially is pale, then gradually becomes yellowish or bronze.
along with gangrene of the subcutaneous fat and dermis (charac- Blebs, bullae, and skin necrosis do not appear until late in the
terized by progressive skin necrosis, the formation of bullae and course of the disease. Edema and tenderness occur early, and the
vesicles, and occasional ulceration [see Figure 1]). absence of erythema distinguishes clostridial infections from strep-
tococcal infection. A thin serosanguineous discharge is present in
Myonecrosis involved areas and may emanate from an involved incision. Gram
Myonecrosis is a rapidly progressive life-threatening infection of stain reveals gram-positive coccobacilli with few leukocytes.
skeletal muscle that is primarily caused by Clostridium species.The When clostridial myonecrosis is suspected or confirmed, peni-
classic example of myonecrosis is clostridial gas gangrene, a disease cillin G, 2 to 4 million U every 4 hours, should be given immedi-
that was common in World War I soldiers who sustained extremity ately; clindamycin, 900 mg every 8 hours, should be added.When
injuries that were contaminated with soil. Delays in definitive treat- C. septicum is identified on culture, a search for an occult GI tract
ment and the use of primary closure for these contaminated malignancy should be made. Clostridial myonecrosis is the one soft
wounds contributed to the severity and mortality of these infec- tissue infection for which hyperbaric oxygen is recommended,
tions.47 Clostridial myonecrosis may also occur as a deep surgical though as yet, there is little evidence that this modality improves
site infection after contaminated operations, particularly those outcomes. If hyperbaric oxygen therapy is to be used, it should not
involving the GI tract or the biliary tract. Devitalized tissue is a per- be given before operative debridement.
Discussion
Etiology and Classification of Soft Tissue Infection Primary (idiopathic) soft tissue infections occur in the absence
Soft tissue infection commonly results from inoculation of bac- of a known causative factor or portal of entry for bacteria. Such
teria through a defect in the epidermal layer of the skin, such as may infections are uncommon and are believed to result from
occur with injury, preexisting skin disease, or vascular compromise. hematogenous spread or bacterial invasion through small unrecog-
Less commonly, soft tissue infection may be a consequence of nized breaks in the epidermis.48,49 Soft tissue infection caused by V.
extension from a subjacent site of infection (e.g., osteomyelitis) or vulnificus is an example of a primary soft tissue infection: it is attrib-
of hematogenous spread from a distant site (e.g., diverticulitis or C. uted to bacteremia developing after the ingestion of contaminated
septicum infection in patients with colonic carcinoma). It may also raw seafood. Only 10% to 15% of all necrotizing soft tissue infec-
occur de novo in healthy patients with normal-appearing skin, often tions are idiopathic; the remaining 85% to 90% are secondary
as a result of virulent pathogenic organisms.48 infections, developing as a consequence of some insult to the skin
Conditions that disrupt the skin and alter its normal barrier that predisposes to infection. Secondary soft tissue infections may
function [see Table 2] predispose patients to bacterial contamina- be further categorized as posttraumatic, postoperative, or compli-
tion. Host factors may increase susceptibility to infection and limit cations of preexisting skin conditions.
the patient’s ability to contain the bacterial inoculum. Clinically Soft tissue infections are classified as monomicrobial when they
occult infection or inadequate treatment of other conditions may are caused by a single organism and as polymicrobial when they are
also lead to secondary development of soft tissue infection (as is caused by multiple organisms. Most superficial soft tissue infec-
sometimes seen in patients with diverticulitis; perirectal, pilonidal, tions are caused by a single aerobe, usually S. pyogenes or S. aureus.
or Bartholin’s cyst abscesses; strangulated hernias; or panniculitis). Exceptions to this general rule include infections caused by animal
Delayed or inadequate treatment of superficial infections (e.g., fol- or human bites, cellulitis associated with decubitus or other non-
liculitis, furuncles, carbuncles, cellulitis, and surgical site infections) healing ulcers, and infections in immunocompromised patients.
may lead to more severe necrotizing infections. These infections are typically polymicrobial, often involving aero-
Soft tissue infections may be classified as superficial or deep, as bic or facultative gram-negative organisms and anaerobes in addi-
nonnecrotizing or necrotizing, as primary (idiopathic) or section to aerobic gram-positive bacteria.
ondary, and as monomicrobial or polymicrobial. Superficial infec- Deep necrotizing soft tissue infections are polymicrobial 70% to
tions involve the epidermis, dermis, superficial fascia, or subcuta- 75% of the time.They are caused by the synergistic activity of fac-
neous tissue, whereas deep infections involve the deep fascia or ultative aerobes and anaerobes [see Figure 7].50,51 S. aureus, S. pyo-
muscle [see Figure 6]. Necrotizing soft tissue infections are distin- genes, and enterococci are the most common gram-positive aer-
guished by the presence of extensive, rapidly progressing necrosis obes. Escherichia coli is the most common gram-negative enteric
and high mortality. Such infections are termed necrotizing celluli- organism. Bacteroides species and peptostreptococci are the most
tis, necrotizing fasciitis, or myonecrosis according to whether the common anaerobes.9,27,51 The remaining 25% to 30% of deep
deepest tissue layer affected by necrosis is subcutaneous tissue, necrotizing infections are monomicrobial. Most primary necrotiz-
deep fascia, or muscle, respectively. ing soft tissue infections are monomicrobial.48 These infections are
patient factors predispose susceptible individuals to these infec-

tions. Chronic illnesses can contribute to a diminished immuno-
logic response. Peripheral vascular disease impairs the local blood
and oxygen supply. Diabetes mellitus inhibits WBC function.
Chronic pulmonary disease can result in systemic hypoxemia.
Patients with congestive heart failure or significant coronary artery
disease may be unable to increase their cardiac output in response
to infection. Malnutrition can result in a lack of nutrients and crit-
ical enzymatic cofactors involved in the normal cellular response to
infection. Each of these patient factors impairs the host response
and thereby increases the likelihood that infection will develop.
In the 1920s, Meleney demonstrated that injection of animals
with pathogens isolated from patients with infectious gangrene
reproduced the characteristics of infection.2 Decades later, the
importance of bacterial synergy and exotoxins was demonstrated
in experiments performed by Seal and Kingston,52 who showed
that a spreading infection developed in 12% of animals that
received an intradermal injection of group A β-hemolytic strepto-
Figure 7 Meleney’s ulcer is characterized by central necrosis, cocci.When S. aureus was coinjected with β-hemolytic streptococ-
erythema, and edema. ci, spreading infections developed in 50% of animals, and when the
α-lysin of S. aureus was coinjected with streptococci, spreading
infections developed in 75%.
more fulminant and are notable for their acute onset, rapid pro-
gression, and systemic toxicity. Their characteristic clinical mani-
festations are related to exotoxin production by the pathogen Streptococcal Toxic-Shock Syndrome
involved [see Table 9 and Pathogenesis of Soft Tissue Infections, Hemolytic streptococci were originally described by Meleney as
below]. S. pyogenes is the pathogen in more than half of monomi- the cause of a “synergistic gangrene.”2 The current resurgence of
crobial infections; S. aureus, C. perfringens,V. vulnificus, and P. aerug- necrotizing soft tissue infections attributed to so-called flesh-eating
inosa are less common. bacteria probably represents an adaptation of group A streptococ-
ci to the contemporary environment.53 Streptococcal toxic-shock
syndrome (STSS) is defined as the isolation of group A strepto-
Pathogenesis of Soft Tissue Infections
cocci from a normally sterile body site in conjunction with
Soft tissue infections generally induce localized inflammatory hypotension and either renal impairment, acute respiratory distress
changes in the involved tissues, regardless of the species of bacte- syndrome, abnormal hepatic function, coagulopathy, extensive tis-
ria involved. As the infection progresses, tissue necrosis occurs as a sue necrosis, or an erythematous rash.45 STSS is considered the
result of (1) direct cellular injury from bacterial toxins, (2) signifi- probable diagnosis when these abnormalities occur in conjunction
cant inflammatory edema within a closed tissue compartment, (3) with isolation of group A streptococci from nonsterile body sites.
thrombosis of nutrient blood vessels, and (4) tissue ischemia. More than 60% of patients with STSS have bacteremia. STSS has
The exotoxins produced by gram-positive cocci and some been shown to be a major risk factor for mortality among patients
gram-negative bacteria are powerful proteolytic enzymes. S. pyo- with necrotizing soft tissue infections.54
genes produces hemolysins, fibrinolysins, hyaluronidases, and Population-based studies in North America and Europe docu-
streptolysins. S. aureus and P. aeruginosa produce coagulases that mented a nearly fivefold increase in group A streptococcal infec-
result in local tissue damage and necrosis. C. perfringens produces tions between the late 1980s and 1995.55 The current incidence of
numerous exotoxins. The α-toxin, a lecithinase enzyme, is highly group A streptococcal infections in the population of Ontario,
lethal: it destroys cell membranes, causes hemolysis, and alters cap- Canada, is estimated to be 1.5 per 100,000.55 STSS develops in
illary permeability. Other clostridial toxins lyse red blood cells and
have direct cardiotoxic effects. These toxins also cause platelet
aggregation and fibrin deposition, with resultant vascular throm- Table 9 Major Exotoxins Associated with
bosis and necrosis. Production of the θ-toxin leads to intravascular
Organisms Causing Monomicrobial Necrotizing
leukostasis and inhibits diapedesis of white blood cells into infect-
ed tissue.This unique collection of bacterial toxins accounts for the Soft Tissue Infection
rapid progression of C. perfringens infection in a setting of minimal
inflammatory changes. Bacterium Exotoxins
That most necrotizing soft tissue infections involve multiple bac- Pyrogenic exotoxins A and B, hemolysin,
terial species strongly suggests that bacterial synergy plays an Streptococcus pyogenes
fibrinolysin, hyaluronidase, streptokinase
important role in their pathogenesis.Toxin-induced cellular necro-
Hemolysins (intravascular hemolysis and
sis establishes an anaerobic environment that facilitates the growth Staphylococcus aureus
local tumor necrosis), coagulase
of both facultative and anaerobic bacteria.These anaerobes elabo-
rate additional enzymes and other by-products that facilitate tissue Collagenase (local tissue damage and
Pseudomonas aeruginosa
necrosis)
invasion and destruction.
Preexisting local tissue damage frequently serves as a nidus for α-Toxin (lecithinase causing tissue necrosis,
soft tissue infection.The reduced oxygen tension of this abnormal Clostridium perfringens intravascular hemolysis, hemoglobinemia,
and acute renal failure)
environment allows pathogens to proliferate. In addition, various
processes. The M proteins M1 and M3 are associated with the

majority of streptococcal necrotizing soft tissue infections.53
Streptococcal pyrogenic exotoxins (SPEs) are produced by most
streptococci that cause severe soft tissue infection and can be
transmitted by bacteriophages to different M types. They are the
cause of the fever, shock, and tissue injury associated with these
infections. SPE-A and SPE-B induce the synthesis of tumor
necrosis factor–α (TNF-α), interleukin-1β (IL-1β), and IL-6.
Peptidoglycan, lipoteichoic acid, and killed organisms also are
capable of inducing TNF-α production.
It has been proposed that M proteins or SPEs act as superanti-
gens. These exotoxins, along with certain staphylococcal toxins
(e.g., toxic-shock syndrome toxin–1 [TSST-1] and staphylococcal
enterotoxins), can stimulate T cell responses through convention-
al antigen-presenting cells, as well as through direct binding to the
Vβ region of the T cell receptor. Conventional T cell activation
Figure 8 Shown is the superficial appearance of streptococcal through antigen-presenting cells is a multistage process that stim-
gangrene of the posterior thigh. ulates a relatively small percentage of T cells and limits the mag-
nitude of the resultant cytokine response. In contrast, superanti-
gens bypass the normal antigen presentation pathway and do not
approximately 10% to 15% of these patients, necrotizing fasciitis undergo phagocytosis. The superantigen processing pathway can
in about 6%.56 It is likely that the rise in serious group A strepto- stimulate more than a thousand times more T cells than the con-
coccal infections reflects an antigenic shift that has increased the ventional antigen pathway and thus can trigger a massive release of
virulence of these organisms. cytokines. The idea that T cell stimulation by superantigens can
Soft tissue infections associated with STSS typically involve an explain the severe degree of illness and exaggerated response seen
extremity. Approximately 70% of patients will progress to necro- in these patients is attractive, but at present, there is no definitive
tizing fasciitis or myositis and will require operative treatment. proof that this process occurs in humans.
Only about 50% of patients with streptococcal soft tissue infec- Although S. pyogenes is susceptible to penicillin and other β-lac-
tions have a demonstrable portal of entry for bacteria.48,57 tam antibiotics in vitro, clinical treatment failure sometimes occurs
Severe pain is the most common initial symptom of STSS. It is when penicillin is used alone against S. pyogenes infections.53 Such
of sudden onset and generally precedes tenderness or other physi- failure is a particular problem with more aggressive group A strep-
cal findings. Fever is another common early sign. About 80% of tococcal infections and may be attributable to the large inoculum
STSS patients show clinical signs of soft tissue infection (e.g., local- size (the so-called Eagle effect). These large inocula reach the sta-
ized swelling, erythema, and tenderness) [see Figure 8]. In approx- tionary growth phase very quickly. Penicillin and other β-lactam
imately 50%, blood pressure is initially normal, but hypotension antibiotics are ineffective in the stationary growth phase because of
invariably develops within 4 to 8 hours after presentation. the reduced expression of penicillin-binding proteins in this phase.
Hemoglobinuria and an elevated serum creatinine concentra- Moreover, toxin production is not inhibited by β-lactam antibi-
tion are hallmarks of renal involvement. Even when adequate otics during the stationary growth phase. In contrast, antibiotics
resuscitation is provided and antibiotics and vasopressors are that inhibit protein synthesis have been associated with improved
given, hypotension persists in the overwhelming majority of survival after serious group A streptococcal infections.
patients. Renal dysfunction can persist or progress for 48 to 72 Clindamycin is more effective than β-lactam agents in manag-
hours despite treatment. Hypoalbuminemia and hypocalcemia are ing experimental and clinical infections caused by group A strep-
common. Mild leukocytosis is present initially; however, the per- tococci, particularly when necrosis is present.59 Clindamycin
centage of immature neutrophils is generally 40% or higher. inhibits protein synthesis, and its efficacy is unaffected by inocu-
S. pyogenes can be classified into more than 80 different strains, lum size or the stage of bacterial growth. In particular, it suppress-
or M types, on the basis of the M proteins expressed. M proteins es bacterial toxin synthesis and inhibits M-protein synthesis, thus
impede phagocytosis of streptococci and induce vascular leakage facilitating phagocytosis of S. pyogenes. Clindamycin also suppress-
by forming complexes with fibrinogen.58 They also cleave nicotinic es synthesis of penicillin-binding proteins, and it can act synergis-
acid dinucleotide (NAD), thereby interrupting elemental cellular tically with penicillin.
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J 139:30, 1998 Bacteriology of necrotizing fasciitis. Am J Surg
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Differentiation of necrotizing fasciitis and cellulitis 53. Stevens DL: Streptococcal toxic-shock syndrome:
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24. Elliott DC, Kufera JA, Myers RAM: Necrotizing 42. Ginsberg CM, Hurwitz RM: Haemophilus tein, a classical bacterial virulence determinant,
soft tissue infections: risk factors for mortality and influenzae type B is an unusual organism causing forms, complexes with fibrinogen that induce vas-
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25. Brown DR, Davis NL, Lepawsky M, et al: A mul- 43. Parada JP, Maslow JN: Clinical syndromes associ- group A streptococcal infections in Florida. South
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26. Elliott D, Kufera JA, Myers RAM: The microbiol- Current Therapy. Rakel RE, Ed.WB Saunders Co,
ogy of necrotizing soft tissue infections. Am J Surg Philadelphia, 1997, p 823 Acknowledgment
179:361, 2000 45. Stevens DL: Streptococcal infections. Cecil
27. Childers BJ, Potyondy LD, Nachreiner R, et al: Textbook of Medicine, 20th ed. Bennet JC, Plum Figure 6 Tom Moore.
3 BREAST, SKIN, AND SOFT TISSUE 3 PRINCIPLES OF WOUND MANAGEMENT
AND SOFT TISSUE REPAIR — 1
3 PRINCIPLES OF WOUND
MANAGEMENT AND SOFT
TISSUE REPAIR
Eric G. Halvorson, MD, and Joseph J. Disa, MD, FACS
Difficult Wounds soft tissue coverage. Surgically created wounds, which gener-
Problem wounds are ally pose less of a problem from a bacteriologic standpoint
characterized by one of than traumatic wounds, are best managed by an immediate
the following: large size coverage procedure when direct closure is impossible.
that precludes direct Traumatic wounds are more difficult to evaluate than surgi-
primary closure, gross cal wounds for several reasons. First, the potential for infection
infection or uncertain is high because of the environment in which the wound is cre-
bacteriologic status, or ated, the mechanism of injury, and the time that elapses before
threatened loss of critical operative intervention. Second, the mechanism of injury (e.g.,
structures exposed as crush, avulsion, or gunshot) may extend the zone of injury
a result of insufficient beyond what is immediately apparent [see Figure 1]. Serious
a b
Figure 1 (a) A so-called bumper injury of the leg is shown

after initial débridement and bony stabilization (2 days after
injury). (b) After the second débridement, the true extent of
devitalization of bone and soft tissue is apparent (4 days after
injury). (c) A latissimus dorsi free flap has been used to
reconstruct the soft tissue defect (5 days after injury).
DOI 10.2310/7800.S03C03
07/09
Acute reconstruction is indicated
Evaluate and treat open wound. Use wet-to-dry dressings or negative-pressure

wound therapy until infection is cleared and wound is healing.
Select coverage procedure to achieve healed wound and avoid infection.
Defer treatment of functional problems for secondary reconstruction.
Wound does not contain exposed bone, cartilage, nerve, or tendon but cannot be closed directly
Apply a skin graft.
Wound is a small defect but Wound has a large surface Wound is clean but in an
is in an area where graft area or is a small wound in area prone to contamination
contracture is not desirable a noncritical area
(e.g., face, hand, or flexion Apply meshed split-thickness
crease) Apply split-thickness skin graft. skin graft. Reinstitute early
dressing changes if infection
Apply full-thickness skin graft; develops.
donor sites include the ear,
upper eyelid, neck, and groin.
Secondary reconstruction of chronic defect is indicated
Defect is a small localized There is a shortage of skin One or more of the following
scar or a focal scar and subcutaneous tissue conditions is present:
contracture only, but skin graft coverage • Composite defect
is not desirable • Functional defect of muscle
Revise with Z-plasty or other or bone
local tissue rearrangement Use tissue expanders (except • Contour deformity
procedure. on hand or foot). • Unstable soft tissue
coverage of vital structure
• Inadequate soft tissue
coverage for bone or nerve
grafting
Repair with free or local flap.
07/09
Approach to Surgical Reconstruction

Approach to Surgical Reconstruction
Bone, cartilage, nerve, or tendon is exposed and cannot be covered by direct wound closure
Perform flap coverage procedure.
Local donor site meets needs and is not involved in the primary process Local flap is not possible or would not
provide appropriate tissue
Use local flap.
• Small or clean wound: use local skin flap if possible. Use free flap.
• Large or contaminated wound: use regional myocutaneous flap. • If wound is clean and thin flap is desired, apply skin or
fascial free flap.
• If wound is large or contaminated, apply muscle or
Head or neck defect Abdominal defect myocutaneous free flap.
Muscle flaps require coverage with a meshed split-thickness
• Small facial defect with no Use regional flap (e.g., tensor skin graft.
facial features involved: use fasciae latae, rectus femoris, or
Z-plasty, Limberg flap, or rectus abdominis), or employ
other advancement flap of component separation technique.
cheek or forehead. Head or neck defect Knee or leg defect
• Large defect of neck or lower • Large defect of scalp or • Major wound of the
head: use regional Gluteal or perineal defect upper face: cover with popliteal fossa: use free
myocutaneous flap of latissimus dorsi, scapular, flap if blood supply to
trapezius, latissimus Use regional myocutaneous or rectus abdominis gastrocnemius is
dorsi, or pectoralis major, flap (e.g., gluteus maximus, free flap, or use compromised.
or use anterolateral thigh flap. gracilis, tensor fasciae latae, or anterolateral thigh flap. • Defect of the lower third
biceps femoris).
• Floor of the mouth: replace of the leg: use latissimus
with forearm free flap. dorsi, rectus abdominis,
Chest or back defect scapular, or gracilis
• Mandible: reconstruct with
Thigh, knee, or leg defect free flap.
In most cases, use regional various composite free
myocutaneous flap (e.g., • Thigh defect: use regional flaps of bone and skin.
pectoralis major, rectus muscle flap (e.g., tensor • Oropharynx or cervical
abdominis, latissimus dorsi, or fasciae latae, rectus femoris, esophagus: use jejunum Foot defect
trapezius). vastus lateralis, or vastus free flap or forearm flap, or
medialis). use anterolateral thigh flap. • Plantar: repair very
large defect with muscle
• Defect of knee or proximal leg:
free flap covered with
Arm defect use gastrocnemius muscle flap.
a skin graft.
Forearm defect
Cover large wounds above the • Proximal or midleg defect: use
• Dorsum: use fascial free
elbow with latissimus dorsi soleus muscle flap. Cover large forearm wound flap and overlying skin
muscle transposed as a with free flap of rectus graft, or use thin skin
pedicled flap. abdominis, scapular, or free flap.
Foot defect latissimus dorsi muscle.
• Plantar: close defect of

Hand defect weight-bearing heel or midsole
with medially based skin Hand defect
Free flaps are preferred, but
rotation flap raised superficial • Exposed tendons on the
pedicled distant skin flaps from
to plantar fascia or with dorsum: cover with
the chest or abdomen are also
other myocutaneous or temporalis fascia free flap.
acceptable. Defects of the digits
fasciocutaneous plantar flap.
can be covered with cross- • Defect of the web space:
Cover limited defect of distal
finger flaps or, for tip injuries, correct with lateral arm
plantar surface with toe flap.
with thenar flaps. free flap.
• Posterior heel, Achilles tendon,
malleoli: use either extensor
digitorum brevis muscle as
pedicled flap or lateral
calcaneal artery flap.
07/09
postoperative infection may develop in these cases if definitive lished gross infection to a much lower level of bacterial
wound coverage is provided in the absence of adequate contamination, which is then compatible with successful sec-
débridement. Third, whereas accurate assessment of the ondary wound closure. For example, advances in the use of
chances for recovery of specific structures within the wound is NPWT [see Initial Treatment, Negative-Pressure Wound
vital for selecting the optimal method of treatment, such Therapy, below] have simplified the management of complex
assessment is often difficult immediately after injury. lower extremity traumatic wounds, reducing the use of free
tissue transfer.1
e v a luat ion
The initial step in the management of problem wounds is initial treatment
to decide whether the wound is suitable for immediate soft Débridement
tissue coverage. Wounds that are surgically created during the Devitalized tissue provides an ideal culture medium
course of an elective procedure are almost always best treated for bacteria and isolates them from host defense mecha-
with primary definitive coverage. Traumatic wounds that nisms. Surgical débridement must be performed aggres-
present within 1 or 2 hours of injury and have a minimal sively—and on a serial basis if necessary—to remove all
crush component are also best treated with a primary defini- necrotic tissue.
tive coverage procedure after thorough débridement (if the
patient’s hemodynamic status permits). High-Pressure Irrigation
Injuries with a significant crush component and exposure A useful adjunct to débridement is high-pressure irrigation,
of critical structures (e.g., nerves, vessels, tendons, or bone) which has been shown experimentally to reduce wound infec-
are best treated more aggressively. In these cases, thorough tion rates significantly.2,3 Some argue that small particulate
débridement requires considerable surgical experience materials may get pushed deeper into a wound bed; therefore,
because the tendency is to débride inadequately. The accu- this technique should not be used indiscriminately. It is rec-
racy with which tissue viability can be assessed varies from ommended as an adjunct once thorough débridement has
one type of tissue to another. For example, skin can be eval- been performed manually.
uated by its color, the nature of its capillary refill, the quality
of its dermal bleeding, or its bleeding response to pinprick. Quantitative Bacteriology
After intravenous fluorescein injection, skin viability can also The degree of bacterial wound contamination can be accu-
be assessed qualitatively, with a Wood light, or quantitatively, rately quantified. The standard technique of quantitative bac-
with a dermofluorometer. Muscle is the most difficult tissue teriology requires several days to complete and is therefore of
to evaluate. Color, capillary bleeding, and contractile response somewhat limited utility in the management of acute wounds.
to stimulation are not always reliable indicators of muscle In addition to a count, it provides identification and antibi-
viability. In severe injuries, they can be misleading. Inade- otic sensitivities of the organism. As an alternative, quantita-
quate débridement may lead to severe consequences resulting tive bacteriology can be performed by using the rapid slide
from infection. Therefore, serial débridement at 24- to 48-hour technique, which provides valuable information about the
intervals is essential for accurately establishing the limits of wound within 20 minutes.4,5 The level of bacterial contami-
muscle injury. Efforts should be made during débridement to nation has been shown to be a significant predictor of outcome
preserve tissues such as major nerves and blood vessels unless in wound closure by either skin graft or flap coverage tech-
they are severely injured. These structures are vital for func- niques. According to the golden period principle of wound
tion and are of small mass compared with other tissues (e.g., closure, a minimum time interval is necessary for bacteria to
skin, fat, and muscle) at risk for necrosis and subsequent proliferate to a certain threshold level. Contaminated wounds
infection. take a mean time of about 5 hours to reach a bacterial count
Wound débridement, therefore, should involve careful of 105/g of tissue. Attempts to close wounds that have counts
analysis of the injury from an anatomic point of view; débride- higher than 105/g of tissue will fail 75 to 100% of the time,
ment should not consist of indiscriminate excision of blocks whereas attempts to close wounds with lower counts are suc-
of tissue. Between débridement procedures, the wound cessful more than 90% of the time.6 b-Hemolytic streptococci
should be treated with sterile dressing changes or negative- are an exception in that much lower concentrations of these
pressure wound therapy (NPWT) if conditions permit. A organisms consistently result in failure of wound closure.
definitive soft tissue coverage procedure should then be per- When a b-hemolytic streptococcus is the dominant isolate,
formed as soon after the initial injury as wound conditions the wound should generally be treated openly until cultures
permit. When thorough débridement and definitive coverage become negative. Good clinical judgment often makes quan-
can be completed within less than 1 week, the wound will titative bacteriology unnecessary, and it is not used frequently.
generally heal uneventfully. Inadequate débridement fre- In many modern microbiology laboratories, it is no longer
quently results in the loss of any additional tissue invested to available.
achieve acute soft tissue coverage. The wound becomes
grossly infected, and important functional structures within Systemic and Topical Antibiotics
the wound are reexposed. The role of systemic antibiotics in wound management
Infected surgical wounds, neglected wounds, or other is not clearly defined. Broad-spectrum antibiotics should
complex wounds in which initial wound management fails be given in cases of severe trauma as a prophylactic dose
should be débrided and then treated by open methods. prior to surgery. Certain antibiotics provide broad-spectrum
Proper care of these wounds is aimed at converting estab- activity when applied topically. Neomycin, 10 mg/mL, or a
07/09
combination of bacitracin, 50 U/mL, and polymyxin B, s election of coverage p rocedu re

0.05 mg/mL, kills most common wound pathogens. These The main goals of
solutions can be used when wet dressings are indicated, or as coverage procedures in
described in the chapter “Management of the Burn Wound” the management of
[see 7:15]. In the past few years, numerous antibacterial dress- both acute and chronic
ings have been developed, including an antibacterial NPWT wounds are (1) to
sponge. Such dressings may prove useful in the treatment of achieve a healed wound
open, contaminated wounds; however, discussion of these and (2) to avoid infec-
products is outside the scope of this chapter. tion. The treatment of
Topical Antiseptics functional problems is
generally deferred for
A variety of topical antiseptics have been used empiri- secondary reconstruction.
cally in wound care. In the concentrations usually recom- The method of coverage depends on whether vital struc-
mended, however, these solutions are detrimental to wound tures (e.g., vessels, tendons, nerves, and bone) are exposed in
healing. Povidone-iodine (1%), hydrogen peroxide (3%), the wound. If no vital structures are exposed, skin graft cover-
acetic acid (0.25%), and sodium hypochlorite (0.5%) all age is indicated. Skin grafts can also be used over tendon if
have been shown to be lethal to fibroblasts, as well as to the paratenon is intact, over nerve if the epineurium is intact,
bacteria. More dilute concentrations of povidone-iodine and over bone if the periosteum is intact. Skin grafts are the
(0.001%) and sodium hypochlorite (0.005%) are effective most expendable type of soft tissue available for the coverage
against bacteria while being safe for fibroblasts.7 A number of open wounds. They allow the wound to heal completely
of these agents also inhibit normal white blood cell func- and set the stage for secondary reconstruction, during which
tion in the wound. more valuable tissue can be used to achieve other goals at
Damp Dressings minimal risk. When vital structures are exposed in the wound,
a flap is preferred because it provides more substantial soft
Open wounds can be treated with damp dressings, generally tissue coverage of the structure. The choice of flap depends
consisting of gauze soaked in saline or an acceptable topical on the location of the wound and on its overall size, depth,
antiseptic, and then wrung out until just damp. Damp-to- damp and topographic configuration (see below).
dressings prevent desiccation of exposed vital structures or
freshly placed skin grafts. Damp-to-dry dressings are useful for
assisting in daily wound débridement. These dressings are Skin Grafts
allowed to dry on the wound; when they are removed, adher- Skin grafts may be
ent fibrinous debris is removed with the dressing. Damp dress- either partial thickness
ings of either type should be changed at least twice a day. (i.e., split thickness) or
Small wounds can be expected to close by contraction and full thickness. Split-
secondary epithelialization after appropriate open management thickness grafts are
with the techniques described. Large wounds will improve with preferred for wounds
aggressive open care but will then stabilize into a chronic state with a large surface area.
of wound colonization of varying degrees. A soft tissue coverage Full-thickness grafts are
procedure may then be necessary to complete closure in these suitable only for small
cases. defects because their
donor sites must be closed primarily; the most common donor
Negative-Pressure Wound Therapy sites for full-thickness grafts are the ears, upper eyelids, neck,
In the past 10 years, the vacuum-assisted closure (VAC) and groin. Full-thickness grafts contract less with time than
device (VAC Dressing System, Kinetic Concepts Inc., San split-thickness grafts and are therefore particularly suitable for
Antonio, TX) has gained widespread acceptance for the treat- wounds of the hands, extremity flexion creases, nose, eyelids,
ment of open wounds. Because this device does not accomplish and other areas of the face.
débridement to any significant degree, it should be applied only Successful healing of skin grafts requires immobilization of
to a clean wound that has no necrotic debris or infection pre- the recipient site to prevent shearing in the plane between the
sent. If any significant necrotic tissue remains after sharp débride- graft and the wound bed. Although complete immobilization is
ment, wet-to-dry dressings may be employed until the wound desirable, the required dressings may preclude observation of a
is clean and granulating. Dressing changes are typically carried wound that is known to be significantly contaminated. In such
out every 2 or 3 days; this is a significant advantage, given that cases, a meshed split-thickness graft is indicated, and the wound
conventional dressing changes are generally done at least twice should be treated in an open fashion. A meshed graft can be
daily. Exudate is removed and quantified by the suction device, placed directly over the muscle of a flap and secured over its
and more robust wound granulation and contraction can be irregular contour with staples [see Figure 2]. Because the graft
observed. After treatment with a VAC device, wound closure is meshed, serum can escape between the interstices and there
can be accomplished secondarily with a skin graft, local flaps, is little risk of separation from the underlying tissue. A meshed
or free tissue transfer, depending on the clinical situation. The graft is also less vulnerable to disruption by shear forces. An
disadvantages of NPWT include the need for specialized equip- additional advantage of a meshed graft is that it permits the
ment and training and the increased cost. wound to be treated with wet dressings if there is still risk for
07/09
possible after the empirical discovery that a more vigorous

circulation develops in flaps raised in stages (the delay
phenomenon).9 The next flaps to come into common use
had an axial-pattern type of circulation, in which a sizable
artery coursed directly to a specific cutaneous territory [see
Figure 3b]. The groin was the first region where this arrange-
ment was carefully described, and it remains a useful source
of flaps for selected applications. Because longer flaps can
be made in areas where the blood supply has an axial pat-
tern, the length to width ratio and the delay phenomenon
became less important issues.10 Identification of an axial-
pattern blood supply to a given graft allows so-called island-
ing of the graft from the donor site except for the vascular
connection, which is preserved. Such island flaps have
greater mobility than flaps with a less attenuated attachment
to the donor site.
Figure 2 A meshed (1.5:1 ratio) skin graft has been secured A third type of flap was based on the myocutaneous blood
to the irregular contour of a muscle free flap with staples. No supply, a network of vessels that perforate muscles vertically
additional immobilization of the graft is needed. The inter-
and supply the overlying skin [see Figure 3c and Figure 3d].
stices of the graft allow free drainage of serous exudate from
These vessels are not necessarily the exclusive supply to the
the muscle.
skin in a specific region, but they are able to support the skin
entirely when other sources of blood supply are eliminated.
infection. A mesh expansion ratio of 1.5:1 is generally preferred, Investigation of the body musculature showed that there were
except when the surface area of the wound is very large and the at least five basic patterns of blood supply to muscle, distin-
availability of donor sites is limited. guished by the existence of and balance between primary
pedicles and secondary sources of blood supply [see Figure 4].
Flaps
Some muscles can be rotated or transposed as myocutaneous
Flaps consist of tis- flaps on the basis of either their dominant or their secondary
sues that have a self- blood supply (e.g., the pectoralis major and the latissimus
contained vascular dorsi). Some muscles have two dominant supplies and can be
system. They permit a transposed on either one (e.g., the rectus abdominis). Other
more substantial trans- muscles do not reliably support skin territories supplied by
fer of tissue bulk than minor pedicles (e.g., the gracilis).
do skin grafts and may Other patterns of cutaneous blood supply are now well
consist of skin and sub- recognized. Fasciocutaneous flaps with high length to width
cutaneous tissue, fascia, ratios can be reliably raised on the trunk, arms, and legs.
muscle, bone, or a com- The blood supply of deep fascia appears to consist of both
bination of several tissue types. Local flaps consist of tissue a deep and a superficial fascial plexus. These vessels con-
that is mostly detached from surrounding tissue but retains nect both to perforating vessels from the underlying muscles
enough connection to preserve an adequate blood supply to and to the subcutaneous tissue vessels above them.11 At
the entire flap. Local flaps are either transposed, rotated, or least three types of fasciocutaneous flaps may be distin-
advanced into adjacent defects for purposes of reconstruction. guished on the basis of the fascial blood supply to the skin
Island flaps are local flaps that are based only on their skele- [see Figure 5].12
tonized axial blood supply. Once created, an island flap is In some areas, fascia supplies overlying subcutaneous tissue
transferred through a subcutaneous tunnel into the defect. and skin more directly. Such a blood supply is most evident
The skeletonized pedicle remains in the subcutaneous space in the extremities, where direct branches from major vessels
while the cutaneous portion of the flap fills the defect. Free course through intermuscular septa to reach the deep fascia
flaps, in contrast, are totally detached; their blood supply is and supply the overlying skin and subcutaneous tissue. The
reconnected at the recipient site by means of surgically per- forearm is a clinically important donor site because thin sep-
formed microvascular anastomoses between recipient-site tocutaneous flaps fed by the radial artery can be raised as
blood vessels and the major vessels that supply the flap. either pedicled or free flaps. Other examples of fasciocuta-
neous flaps include the lateral arm septocutaneous flap, fed by
Blood Supply the profunda brachii artery; the scapular flap, fed by the circum-
The earliest flaps in common use were skin flaps that had flex scapular artery [see Figure 3d]; the fibular osteofascio-
what is known as a random-pattern type of circulation [see cutaneous flap, fed by the peroneal artery; and the anterolateral
Figure 3a], in which blood is supplied by the subdermal thigh flap, fed by the descending branch of the lateral cir-
capillary plexus rather than by a named vessel.8 The pre- cumflex femoral artery.
carious nature of the blood supply of such flaps severely lim- The 21st century has seen the popularization of “perfora-
ited flap design and resulted in a preoccupation with suitable tor” flaps, which are based on musculocutaneous branches
length to width ratios. Greater length to width ratios became (or perforators) of named, axial vessels. In the early years of
07/09
a b
d
c
Figure 3 (a) The blood supply of random-pattern skin flaps is limited; only small flaps (e.g., thenar flaps, shown here) are
consistently reliable. (b) Shown is an axial-pattern skin flap. (c) The skin and subcutaneous tissue of a myocutaneous flap can
exist as a complete island because the blood supply is derived from vertical muscular perforators. (d) Shown are a large free flap
of scapular area skin and the entire latissimus dorsi. The subscapular vessels that connect the two will supply both components
of the flap after microvascular anastomoses.
microsurgery, success was defined by a lack of microvascu- typ es of local flap s

lar thrombosis. As experience was gained and rates of Transposition Flaps
microvascular anastomotic failure decreased, focus was then
turned on limiting donor-site morbidity. Several myocuta- A flap that is moved laterally into the primary defect is
neous flaps used primarily for their skin and subcutaneous called a transposition flap. The essential concept in the design
components were modified such that musculocutaneous of such a flap is to ensure that the flap is long enough to cover
perforators supplying the overlying fat and skin were dis- the entire defect, so that the transfer can be done without
sected through the muscle down to the pedicle origin, thus tension [see Figure 6].
preserving muscle and function. Common perforator flaps The skin is marked and incised with a scalpel, and dissec-
include the deep inferior epigastric perforator flap, or DIEP tion is carried through the subcutaneous fat. The flap is
flap, and the superior and inferior gluteal artery perforator retracted with a skin hook, and dissection is performed with
flaps, or SGAP and IGAP flaps. These flaps are commonly blunt scissors until the flap is elevated sufficiently to allow it
performed for breast reconstruction. The anterolateral thigh to be transposed into the defect without tension. The second-
flap, or ALT flap, is supplied by a musculocutaneous perfo- ary defect is closed primarily; alternatively, depending on the
rator of the descending branch of the lateral circumflex location of the donor area and the degree of skin tension pre-
femoral artery roughly two thirds of the time and by a sep- sent there, a skin graft may be indicated. As with any local
tocutaneous branch one third of the time. flap, wide undermining of the surrounding tissues may be
07/09
TYPE I TYPE II TYPE III TYPE IV TYPE V
Tensor Fasciae Latae Gracilis Rectus Abdominis External Oblique Latissimus Dorsi
Figure 4 Schematized are the five basic patterns of blood supply to muscle. Individual muscles are classified on the basis of the
dominance, number, and size of the vessels that supply them. Type I is supplied by a single dominant pedicle. Type II is supplied
by one dominant vessel and several much smaller vessels. Type III is supplied by two dominant pedicles. Type IV is supplied by
multiple vessels of similar size. Type V is supplied by one dominant pedicle and several smaller segmental vascular pedicles.
TYPE A TYPE B TYPE C
Figure 5 At least three types of fasciocutaneous flaps exist, categorized by blood supply configuration. Type A
is supplied by multiple small, longitudinal vessels coursing with the deep fascia. These flaps must retain a base
of a certain width and cannot be raised as islands (e.g., longitudinally oriented flaps of skin and fascia on the
lower leg). Type B is supplied by a single major vessel within the fascia (e.g., scapular flap). Type C is
supplied by multiple perforating segments from a major vessel coursing through intermuscular septa
(e.g., forearm flaps).
necessary for closure of the defect and the donor site. Closure nasal defects involving the lateral aspect, the ala, or the tip.
is then performed in two layers. The keys to a successful bilobed flap are (1) accurate design
Bilobed flap A bilobed flap is a transposition flap con- and (2) wide undermining of the surrounding tissue in the
sisting of two lobes of skin and subcutaneous tissue based on submuscular plane to allow a smooth transposition. The
a common pedicle [see Figure 7]. It is often used to correct primary lobe is usually at an angle of 45° or less to the defect;
07/09
Figure 6 After excision of the defect, a transposition flap of adequate length is designed and elevated in the subcutaneous
plane. The flap is moved laterally into the defect and inset. It may be necessary to excise a dog-ear of excess skin at the tip of
the flap harvest site.
Figure 7 A flap with two lobes is created, with the first lobe the same size as the defect and the second lobe substantially
( 50%) smaller than the first. The flap is elevated in the submuscular plane. Wide undermining at this level is necessary for
tension-free transposition. The first lobe covers the initial defect, and the second covers the defect from the first. The
second lobe is placed in an area of loose skin, and its area of origin is closed primarily.
the secondary lobe is designed to achieve closure of the donor This extension should be oriented along relaxed skin tension
defect and is substantially smaller than the primary lobe. The lines, perpendicular to the line of maximum extensibility; it
angle between the two is 90° to 100°. Both flaps are raised constitutes the second side of the flap (XY). Next, a line
simultaneously in the submuscular plane. Wide undermining parallel and equal in length to YZ is drawn from X to outline
of the area (also in the submuscular plane) minimizes ten- the third side of the flap. Correct orientation of the rhomboid
sion. The primary lobe of the bilobed flap is transposed into is vital for achieving flap repair with minimal tension, par-
the initial defect, the secondary lobe is transposed into the ticularly with respect to the line of maximum extensibility: it
donor defect left by the primary lobe, and the defect left by is along this base line that maximum tension results when the
the secondary lobe is closed primarily. Closure is accom- donor defect is closed. Once the flap has been correctly
plished with 5-0 or 6-0 nylon. designed and elevated, it is transposed into the defect. Clo-
Rhomboid flap (Limberg flap) A rhomboid flap is a sure is done in two layers.
transposition flap that is designed in a specific geometric fash- Rhomboid flaps work best on flat surfaces (e.g., the upper
ion [see Figure 8]. The initial defect is converted to a rhom- cheek, the temporal region, and the trunk). Extra attention to flap
boid, with care taken to plan the flap in an area with minimal design is necessary when an attempt is made to close a defect over
skin tension. The rhomboid must be an equilateral parallelo- a convex surface with a rhomboid flap; improper flap design leads
gram with angles of 60° and 120°; this design allows the sur- to excessive tension and potential flap necrosis.
geon to excise less tissue than would be needed for an
elliptical flap. One face of the rhomboid constitutes the first Rotation Flaps
side of the flap (YZ). The short diagonal of the rhomboid is A flap that is rotated into the defect is called a rotation
then extended outward for a distance equal to its own length. flap.13,14 This type of flap is commonly used to repair a defect
07/09
a X b RSTL c
LME
Y Z Z
Z
X Y
608 1208
X Y
Figure 8 (a) The defect is converted to a rhomboid, with all four sides of equal length and angles of 60
and 120 . An extension XY is made that is the same length as the short diagonal of the rhomboid, and a
line of equal length is drawn from X paralleling YZ. (b) The flap is oriented so that XY follows the
relaxed skin tension lines (RSTL) and YZ the line of maximum extensibility (LME). (c) The flap is
inset.
on the scalp, where large flaps must be designed to overcome a

the inelasticity of scalp tissue. A rotation flap takes the form
of a semicircle, of which the defect occupies a wedge-shaped
segment [see Figure 9]. The original defect is converted to a
triangular shape (ABC). One side of the triangular defect
(AC) is extended to a point (D) that will serve as the pivot A C
D
point for the flap. The distance between A and D should be
at least 50% greater than that between A and C. A semicir-
cular line extending from C to D is then defined. b
The flap is incised with a scalpel, elevated, and rotated. As
with all local skin flaps, wide undermining of the surround-
ing tissue may be necessary to allow tension-free rotation
and wound closure. The flap is secured with a two-layer clo-
sure; the secondary defect may be closed primarily. Some-
times a so-called back cut is required to gain adequate
rotation. The most common technical error with rotation
flaps is improper design: a flap that is too small will not cover c
the defect adequately.
Advancement Flaps
Advancement flaps are moved directly forward into a defect
without either rotation or lateral movement. The single-
pedicle advancement flap is a rectangular or square flap of
skin and subcutaneous tissue that is stretched forward. The
flap is oriented with respect to the local skin tension, with
care taken to plan the advancement in an area where the skin d
is extensible. A rectangular defect is created, and the flap is
elevated in an area of loose skin and advanced to cover the
defect [see Figure 10]. When closure is performed, some
excess skin (dog-ears) at the base of the flap (Burow trian-
gles) may have to be excised.
V-Y advancement flap The V-Y advancement flap is a
modification of a basic advancement flap [see Figure 11]. The
use of a V-Y advancement flap eliminates the need to revise
Figure 9 (a) The defect is converted into a wedge. One side
the dog-ears that sometimes result with rotation flaps. When
(AC) is extended to a pivot point D, so that AD is at least 50%
possible, the flap should be oriented in accordance with the longer than AC. A semicircle from C to D is defined. (b) The
line of maximum extensibility. Its length should be 1.5 to flap is elevated, rotated, and inset. (c, d) If there is too much
2 times that of the defect in the direction of the closure. tension, a back cut may be necessary to release the flap and
Incisions are made completely through skin. As with other allow rotation. Care is taken not to make the back cut
flaps, skin hooks are used to retract the skin flap, and blunt excessively long; to do so could devascularize the flap.
07/09
a b a b c
A B A
B
A
Central
Limb 60⬚
B
Figure 12 (a) The central limb of the Z is placed along the

line of contracture. Incisions diverging from the scar at a 60
Figure 10 (a) A flap whose shape corresponds to that of the
angle will yield an increase of approximately 75% in the
defect is elevated in the subcutaneous plane and advanced
direction of the central limb. (b) The flaps are transposed.
into the defect. (b) Excision of Burow triangles (excess skin
(c) The length has been increased in the desired direc-
at the flap base) may be necessary to permit advancement.
tion, and the original Z design has been rotated 90 and
reversed.
a b The Z-plasty [see Figure 12] is an example of such tissue

rearrangement.15 Two triangular flaps are designed so that
they have in common a central limb aligned in the direction
along which additional length is desired. For example, the
limb may be placed along the line of a contracture. Two lines,
approximately equal in length to the central limb, are drawn
from either end of the limb, diverging from it at equal angles
varying from 30° to 90°. The degree of lengthening obtained
is determined by the size of this angle [see Table 1]. In theory,
maximal length gain is achieved by using the largest angle
possible, but in practice, the maximum usable angle is deter-
mined by the limits of skin elasticity. A 60° angle, which is
commonly used, will result in a 75% gain in length along the
central limb. Triangular flaps are elevated, and the fibrous
Figure 11 (a) A V-shaped flap is created whose length is 1.5 tissue band responsible for the contracture is divided. The
to 2 times that of the defect. With subcutaneous connections to triangular flaps are transposed and inset, yielding increased
the skin preserved (because these constitute the blood supply length in the desired direction, with the original Z rotated 90°
to the flap), the flap is advanced into the defect. (b) The V and reversed.
incision is converted to a Y as the base is closed primarily. Although Z-plasty is conceptually simple, it is not necessar-
ily easy: experience is necessary for the surgeon to realize the
scissors dissection is then performed. The point of the V on limitations of technique and appreciate the subtleties of
the flap is the area where tightness is most frequently encoun- proper design. Important considerations in the use of Z-plasty
tered; this area may have to be released to facilitate advance- include appropriate determination of the length of the central
ment. Care must be taken not to undermine the advancing limb and correct orientation of the limbs so that the new
flap excessively: doing so may impair or interrupt the blood central limb formed after transposition is parallel to skin ten-
supply to the flap and result in necrosis. Once adequately sion lines. Multiple Z-plasties may be useful for some local-
advanced, the flap is sutured at the advancing edge and at the ized scars.
base of the Y.
Table 1 Z-Plasty: Incision Angle and Degree of
Z-Plasty Lengthening Theoretically Possible
When reconstruction is indicated for small, localized scars, Incision Angle Theoretical Amount of
soft tissue coverage is generally sufficient. With such coverage, (degrees) Lengthening (%)
there is no threat of breakdown leading to exposure of impor-
30 25
tant structures; instead, the reconstructive problem is gener-
ally functional. An example is a flexion crease contracture, 45 50
which is commonly seen after a burn injury. A local procedure 60 75
that rearranges the existing tissue can relieve the tension by 75 100
making more tissue available in one direction, even though
the amount of tissue in the area is not actually increased. 90 120
07/09
regional alternatives in flap s election

Head and neck
Facial defects of small
to moderate size are
best treated with local
skin flaps. A variety
of flaps are available
for reconstruction of
limited defects of the
eyelids, cheeks, nose,
and mouth.16–18 Small
facial defects that do not directly involve the facial features can
often be closed with any of several types of flaps that rearrange
the existing tissue in the area—for example, a Z-plasty or a
Limberg flap. Tissues that are difficult to match (e.g., those of
the eyelids or lips) can often be reconstructed with flaps that
borrow tissue from their opposite, intact counterparts (e.g.,
LOCAL FLAPS MYOCUTANEOUS FLAPS FREE FLAPS the Abbe lip flap).
For coverage of some large defects in the head and neck
Figure 13 Defects in the central portion of the body are region, the trapezius, the latissimus dorsi, and the pectoralis
treated with myocutaneous flaps primarily; defects of the major can be used. Each muscle can be raised with an optional
peripheral areas are treated with either local flaps or free skin island. These flaps are generally too bulky to be used on
flaps. In some areas, several options exist, and the choice is
the face, and their reach is limited when used as pedicled
influenced by the size of the defect and the specific tissue
requirements.
flaps. None of them can cover major portions of the scalp or
comfortably reach the upper face.
Latissimus dorsi, scapular, and rectus abdominis free flaps
Local flaps versus free flaps The choice between a are useful for very large defects of the scalp or upper face.
local flap and a free flap is determined by the amount and the Smaller defects of the scalp are best treated with local
type of tissue needed, as well as by the availability of flaps in scalp flaps.
the immediate area of the wound [see Figure 13]. The avail- Other free flaps of a specialized nature are superior for
ability of local flaps, in turn, is determined by the nature of reconstruction of the floor of the mouth and mandible,
the regional blood supply. The vascular anatomy of a par- even though local myocutaneous flaps will reach this area.
ticular area determines the availability of arterialized skin For example, the forearm free flap based on the radial
flaps, fasciocutaneous flaps, myocutaneous flaps, and other artery is quite thin and pliable and therefore provides an
forms of composite flaps. Local flaps can be grouped region- ideal replacement for the floor of the mouth. Composite
ally by the types of tissue that they provide. free flaps that contain both bone and skin (e.g., those taken
A local flap is generally preferred over a free flap if the from the scapula, the ilium, the radius, and the fibula) pro-
two provide similar tissue, primarily because of the addi- vide tissue of the appropriate type and proper configuration
tional effort required to transfer a free flap. A free flap for defects of the lower face in which the mandible must be
procedure commonly takes twice as long as a local flap reconstructed along with the intraoral lining, the external
procedure. skin, or both.
Free flaps are indicated in areas where local flaps are
unavailable (e.g., the distal third of the leg) or when an Chest and back
extremely large flap is needed but cannot be obtained locally. Most clean defects
When regional donor sites are affected by the primary proof the chest and back
cess, free tissue transfer allows healthy, well-vascularized are amenable to
tissue to be brought into the compromised area. Moreover, if treatment with local
free tissue is transferred, the size of the wound is not extended, myocutaneous flaps
because the donor site is not contiguous but instead is located because of the wide
at a distance from the wound. arc of rotation of mus-
If expertise in microvascular surgery is available, free flaps cles located in these
are frequently a first-line choice. Free flaps allow selection of areas.19 In the pres-
the appropriate type of tissue in the most suitable size and ence of contamination,
configuration for the specific reconstructive problem. Com- open wound management is indicated. Traditionally, this
pared with free flaps, local flaps are inefficient ways of moving has been accomplished with wet-to-dry dressing changes,
tissue because only a small portion of a local flap actually which are especially effective for superficial débridement.
reaches the defect itself. The choice of donor site is greater Currently, these wounds are increasingly being managed
with free flaps because the limitations imposed by local avail- with NPWT after all necrotic tissue is débrided. A com-
ability are avoided. mon example is the wound resulting from the treatment
07/09
of poststernotomy mediastinitis. After sepsis is eliminated flap provides an ideal pulp replacement, as well as better sen-
and the wound is granulating, definitive flap closure can sory recovery than skin grafts. Fingertip injuries can also be
be performed.20,21 Midline sternal wounds can be covered closed with several types of V-Y advancement flaps that can
with pectoralis major, rectus abdominis, or omental flaps; be raised from either the volar surface or the lateral surfaces
lateral chest defects with latissimus dorsi or pectoralis of the end of the finger.
major flaps; and midline back defects with latissimus dorsi
or trapezius flaps. To cover midline defects, the pectora- Abdomen
lis major, the latissimus dorsi, and the trapezius can be Clean defects of the
divided from their primary vascular supply and folded over abdominal wall that
as local flaps based on their medial segmental intercostal require flap closure are
secondary blood supply. best treated with local
muscle flaps such as the
Arm and forearm tensor fasciae latae and
Large wounds above the rectus femoris from
the elbow can be cov- the thigh. The rectus
ered with a latissimus abdominis also can
dorsi myocutaneous flap occasionally be trans-
transposed as a pedicled posed to cover an abdominal defect. Each of these flaps is
flap, provided that the harvested along with skin, although a large tensor fasciae latae
vascular pedicle of the flap will probably necessitate skin-graft closure of the donor
muscle has not been site. The tensor fasciae latae flap has the advantage of includ-
affected by the injury. ing the thickened deep fascia (iliotibial band) of the thigh,
Forearm wounds that require flap closure are best treated with which can provide additional strength for abdominal wall
free flaps. A rectus abdominis, scapular, anterolateral thigh, or closure. Midline defects resulting from previous operation or
latissimus dorsi muscle flap can be used for large defects of the trauma can often be closed by means of the component sepa-
arm or forearm. Although soft tissue coverage with simultane- ration method. The external oblique fascia is divided lateral to
ous functional forearm muscle replacement can be achieved the lateral edge of the rectus sheath, and the bloodless plane
with a single flap (e.g., a gracilis muscle flap), this is generally between the external and internal oblique muscles is devel-
reserved as a secondary operation. A skin flap (e.g., a scapular oped. This maneuver mobilizes the recti toward the midline,
free flap) is preferred as a first stage of reconstruction to achieve usually allowing primary closure. Adding a prosthetic mesh
wound healing. reduces the recurrent rate of hernias but is more difficult to
manage when exposed or infected.
Hand As a consequence of the growing realization of the benefits
Both free flaps and of the open abdomen, increasing numbers of patients treated
pedicled skin flaps are for abdominal trauma, sepsis, and compartment syndrome
useful for soft tissue cov- are presenting for management and closure. With contami-
erage of hand wounds. nated wounds, the use of permanent meshes for reconstruc-
A temporalis fascia free tion is contraindicated, and definitive flap closure is best
flap is particularly thin delayed. In these difficult situations, the wound must be
and is ideal for coverage treated in an open manner, with close attention paid to the
of exposed tendons on unique vulnerability of the intestines to fistula formation.
the dorsum of the hand. Many treatment options are currently available for the open
A lateral arm free flap is abdomen [see 7:6 Operative Exposure of Abdominal Injuries and
ideal for reconstruction of a large defect of the first web space; Closure of the Abdomen]. Important considerations for any
it has sensory potential because it contains a large sensory treatment modality include whether the method controls
nerve. Both of these free flaps are small. Pedicled distant skin abdominal contents, whether it avoids promoting fistula for-
flaps from the chest or abdomen are available as an alternative mation, whether it achieves skin and fascial closure, whether
form of coverage for sizable hand defects. However, pedicled it removes and quantifies exudate, whether it controls infec-
skin flaps have major disadvantages: wound care is difficult, tion, and whether it promotes wound healing. The VAC
edema persists because elevation and movement of the hand device performs well with respect to all of these consider-
are seldom possible while it is attached to the trunk, and a ations, perhaps because of reverse tissue expansion and full-
second procedure is needed to divide these flaps. thickness wound contraction.22,23 Once all acute problems
Digital injuries with exposed tendons can be closed with a have been addressed and recovery is well under way, an
variety of cross-finger flaps of skin and subcutaneous tissue absorbable mesh is commonly applied, followed by dressing
raised from either the volar or extensor aspect of an adjacent changes or NPWT. To protect the underlying bowel, a layer
digit. Because these flaps do not contain a great deal of sub- of nonstick gauze should be applied before dressings or
cutaneous tissue, they are preferred for coverage of digits NPWT sponges. Once granulation is achieved, a skin graft
proximally, where a thick subcutaneous pad is not essential. can be placed. Chronic hernia formation is the rule and can
A thenar flap is useful for fingertip injuries in which the soft generally be treated as a stable chronic ventral hernia pro-
tissue pad of the fingertip is lost and bone is exposed. This vided that the wound is closed and free of infection.
07/09
Gluteal area and perineum into the area. Therefore, free flaps are a first choice, for exam-
Local muscle flaps ple, for coverage of major wounds of the popliteal fossa, knee,
with or without skin and proximal leg that involve the sural artery blood supply
are indicated for defects to the gastrocnemius; they are also highly useful for coverage
in the gluteal area or of defects in the distal third of the leg. Traumatic wounds of
the perineum. Such the distal lower extremity can also be managed with NPWT.
flaps are preferable to Increased use of this modality has been associated with the
large, random-pattern performance of fewer free tissue transfers and more delayed
advancement skin flaps local flap procedures for definitive closure.1
from the posterior thigh Skin flaps fed by the fascial blood supply can also be raised
and thoracolumbar over the leg.24 A number of fasciocutaneous flaps have been
rotation skin flaps. The gluteus maximus, for example, can be described in this area, but they tend to be smaller than muscle
used as a rotation flap, a V-Y advancement flap, or a turnover flaps and generally less reliable. These flaps are longitudinally
flap in the treatment of pressure sores. As a turnover flap, it oriented over the course of the anterior tibial artery or the
can be proximally or distally based, or it can be split along its peroneal artery. The maximum length at which such fascio-
longitudinal axis so that only a portion of it is used. Also useful cutaneous flaps are safe and their specific applications have
for covering defects in the gluteal area and the perineum is the not been well established.
myofasciocutaneous gluteal thigh flap, which is a combination
of a gluteus muscle flap and a fasciocutaneous flap from the Foot
posterior thigh that is supplied by an extension of the infe- The foot is as complex
rior gluteal artery. Because of its size and location, the gracilis as the hand and the face
muscle is well suited for coverage of defects of the perineum. in that it is composed of
The gracilis and the biceps femoris are generally secondary separate regions, each
choices for the treatment of pressure sores over the ischium. of which has a unique
The tensor fasciae latae is frequently used for treating open set of alternatives for
wounds over the greater trochanter. The entire quadriceps reconstruction. These
can be used to close defects resulting from hemipelvectomy. regions include the
plantar surface; the dor-
Thigh
sum; and the posterior
Flaps are rarely required for soft tissue coverage in the thigh (non–weight-bearing) heel, Achilles tendon, and malleoli.
area because critical vital structures are located deep within Superficial defects that lie completely within the non–
the thigh and are rarely exposed by injury or by surgical pro- weight-bearing portion of the midsole do not need flap cover-
cedures. A number of regional muscle flaps are available for age. Defects of the weight-bearing heel and midsole area that
coverage in this region, however, including the tensor fasciae are less than 6 cm in diameter can be closed with a medially
latae, the rectus femoris, the vastus lateralis, and the vastus based skin rotation flap that is raised superficial to the plantar
medialis. An anterior defect that involves exposure of the fem- fascia.25 This flap maintains plantar sensation. Limited defects
oral vessels can be covered with a rectus abdominis myocuta- of the distal plantar surface can be treated with local toe flaps
neous flap, a rectus femoris flap divided distally and turned that also maintain sensation. Very large plantar defects are
over, or a sartorius flap. The sartorius muscle has a segmental best resurfaced with a muscle free flap (e.g., latissimus dorsi,
blood supply and will not be reliable if more than one to two gracilis, or rectus abdominis) covered with a skin graft or thin
segmental pedicles are ligated, which limits its utility for larger fasciocutaneous flaps. Although this type of flap lacks sensa-
defects. A number of smaller local skin flaps that are supplied tion, it appears to provide the most durable form of coverage
with blood from the deep fascia can be raised over portions of because it resists shear forces well.26
the thigh. The anterolateral thigh flap is the most commonly Defects of the dorsum that require flap coverage are best cov-
employed thigh flap for free tissue transfer. ered either with a fascial free flap (e.g., temporalis fascia) and an
overlying skin graft or with a skin free flap that is thin (e.g., from
Knee, proximal leg, and midleg the forearm or the anterolateral thigh). The extensor digitorum
The two heads of the brevis can be raised from the dorsum as a pedicled flap fed by
gastrocnemius can be the dorsalis pedis artery. This flap, which measures approxi-
used either together or mately 5 × 6 cm, has an arc of rotation that makes it useful for
independently to cover the coverage of defects of the malleolus or the Achilles tendon
defects of the knee and area. A narrow transposition skin flap fed by the lateral calcaneal
the proximal third of artery is useful for coverage of defects approximately 3 cm in
the leg. The soleus is diameter that lie over the Achilles tendon or the non–weight-
useful for coverage of bearing posterior heel. A distally based reverse sural artery flap
defects of the proximal transfers skin, subcutaneous fat, and fascia from the proximal
and middle thirds of the posterior calf based on the vasa nervorum of the sural nerve,
leg. Local flaps should not be used for major leg wounds if the supplied by a distal branch of the peroneal at the level of the
extent of the injury suggests involvement of the muscle donor maleolus. This flap can also be used for defects of the ankle;
site. Instead, a free flap should be used to bring healthy tissue however, it can be prone to venous congestion.
07/09
Secondary Reconstruction infection, extrusion, deflation, flipped ports (remote type),

Selection of the and hematoma formation.27
proper method for sec- Tissue expanders are used in secondary reconstruction
ondary reconstruction only; they play no role in acute wound management. They
requires analysis of the are not indicated for contour defects (see below), because the
type and extent of tissue tissue they provide is two-dimensional and lacking in bulk.
deficiency that is pres- Expanded tissue may not be adequate for coverage of chron-
ent and consideration ically exposed structures (e.g., bone).
of the functional goals The scalp is an ideal location for the use of tissue expand-
that are involved. ers because no equivalent substitute for this type of hair-
Superficial defects may bearing tissue exists. Expanders work effectively when
require replacement or supplementation of only skin and sub- implanted over the hard calvarium and are useful in cases of
cutaneous tissue, whereas more complex defects may require burn alopecia and large nevi involving the scalp. Expanders
replacement of several types of tissue. Specialized tissue, such are also useful for breast reconstruction, for carefully selected
as vascularized nerve or intestine, may be necessary to provide large lesions of the face, and for certain scars of the limbs.
a functional reconstruction in some cases (see below). They are generally not indicated for use in the hands or feet.
Although some local flap donor sites (e.g., the forehead) can
be expanded before flap transfer, there is a loss of tissue pli-
s ma l l l oca l i ze d sc a r
ability that appears to limit the usefulness of this particular
When reconstruction is indicated for a small localized scar, application.
soft tissue coverage is generally sufficient and poses no threat
of breakdown leading to exposure of important structures. comp lex defects
Instead, the reconstructive problem is generally functional in Certain reconstruc-
nature. An example is a tight scar band across a flexion crease, tive problems require
which is commonly seen after a burn injury. A local proce- substantial amounts of
dure that rearranges the existing tissue can relieve the tension tissue of one or more
by making more tissue available in one direction, although types or of a very spe-
the amount of tissue in the area is not actually increased. cialized type. Either
The Z-plasty is an example of such tissue rearrangement. local or free flaps are
Multiple Z-plasties or other procedures, such as W-plasty, used to meet these
may be useful for some localized scars. tissue requirements.
s hor t a ge o f sk i n a n d sub c ut a n e o us tis s u e Composite Defect

A shortage of skin A composite defect may result from resection of an intraoral
and subcutaneous carcinoma with loss of the mandible and either the lining of
tissue may result from the mouth or external skin. Another example is a crush injury
excision of a large scar of the leg with loss of soft tissue and a segment of weight-
or a large congenital bearing bone. These defects require that a composite flap be
defect (e.g., a nevus). brought to the area to meet more than one type of tissue
Mastectomy commonly deficiency. Local flaps generally do not provide the necessary
leaves a shortage of skin types of tissue or permit the freedom of design possible with
that prevents creation free flaps. The wide variety of free flap donor sites that exists
of a breast mound. In allows selection of tissue in the appropriate quantity and con-
these cases, extra tissue can be created locally with the use of figuration for a particular defect [see Figure 14].
tissue expanders. These devices are inflatable plastic reser-
voirs of various shapes and volumes that are implanted under Functional Defect
the skin. The skin over the expander is stretched during a Functional defects require repair with specialized flaps.
period of several weeks as the expander is gradually filled by Free flaps are frequently used because the specific tissue
percutaneously injecting saline into an incorporated or remote requirements usually cannot be satisfied by a local flap.
fill port. The expander is then removed as a second proce- A functional defect may result, for example, in the cervical
dure, and the expanded area of skin is advanced to cover the esophagus from tumor resection or in the forearm from the
defect. The process of tissue expansion results in thinning of Volkmann contracture. A segment of small intestine can repair
all layers of tissue overlying the expander—except for the epi- the esophageal defect; transfer of a vascularized and inner-
dermis, which actually thickens. vated muscle (e.g., the gracilis) can replace forearm muscle.28
A number of important principles govern the use of tissue
expanders. The expanders must be placed so as to allow Contour Defect
expansion only in normal skin adjacent to the defect, not in Contour defects, such as those that result from mastectomy
the defect itself. To ensure adequate expansion, a sufficiently or from trauma to the lower extremity, can be reconstructed
large expander or multiple expanders must be used. Compli- with either local or free flaps. A mastectomy defect, because
cations associated with the use of tissue expanders include of its location on the chest, is suitable for reconstruction with
07/09
a b
c d
Figure 14 (a) A chronic draining sinus of the ulna with poor

overlying soft tissue coverage is shown. Simultaneous replace-
ment of both bone and overlying soft tissue with a composite
tissue flap is needed. (b) A radiograph shows nonunion of the
ulna with orthopedic hardware. (c) A fibular free flap
provides bone and skin in the appropriate amount and
configuration for replacement of the affected tissues in a
single stage. (d) The segment of ulna and overlying skin has
been replaced. (e) A radiograph shows the vascularized fibula
in place.
one of several myocutaneous flaps from either the back or the dorsi free flap, which provides a large volume of thin, pliable
abdomen [see 3:5 Breast Procedures]. A free flap from the muscle, which can be wrapped around orthopedic hardware.
abdomen or the gluteal area is another alternative. The best
reconstructive solution for a particular person is determined Unstable Soft Tissue Coverage
by variables such as body habitus and the size and configura- Marginal soft tissue coverage (e.g., skin grafts) may break
tion of the contralateral breast. down after repeated minor trauma. Bones may become
A contour defect of the lower extremity is best reconstructed exposed and are then at risk for osteomyelitis. This situation
with a large myocutaneous free flap that provides tissue of can be avoided by elective replacement of the tissue at risk
sufficient quantity and flexibility to allow sculpting into the with a more substantial soft tissue covering. As in acute
appropriate shape. An excellent example is the latissimus reconstruction, local flaps are the first choice for lesions of the
07/09
trunk or the proximal extremities, whereas free flaps are often recommended that transfusion be reserved for when indi-
more appropriate for lesions of the distal extremities. cated by other patient factors.
Soft tissue coverage is sometimes inadequate even in a Free flaps exhibit venous engorgement when placed in a
healed wound. For example, certain procedures (e.g., nerve dependent position up to several weeks postoperatively. Such
or bone grafting) require an ideal soft tissue bed to promote engorgement is generally not dangerous, although patients with
adequate graft revascularization. In some cases, it may ini- free flaps below the knee should be gradually mobilized in the
tially be necessary to replace the existing soft tissue coverage same fashion as patients with skin grafts in this location by
as a first-stage procedure before grafting a bone or nerve gap. keeping the lower extremity elevated for at least 10 to 14 days.
A skin or muscle flap is most commonly used in such cases. Free flaps in the head and neck area require that the
Muscle flaps tend to provide superior vascularity (e.g., for patient’s head motion be restricted somewhat for the first
bone grafts) but are considered inferior for coverage of ten- few days to prevent kinking of the vascular pedicle. It is
dons that need to glide. This problem is most common in important that electrocardiographic leads and tracheostomy
areas such as the distal extremities, where native soft tissue tube ties not compress the external jugular vein if it was used
coverage is not overly abundant and is easily lost as a conse- as a recipient vessel for anastomosis. If central lines are used
quence of trauma or tumor resection. Free flaps are usually after operation, they should be placed on the contralateral
chosen to provide a healthy, well-vascularized soft tissue bed side of the neck to prevent thrombosis near the microvascu-
before further functional reconstruction is undertaken. lar anastomosis.
Free flaps should be monitored on an hourly basis during
the early postoperative period. Most free flaps include an
pos t ope ra ti v e c a r e a n d f l a p m o n i toring
exposed skin island, which facilitates evaluation of the flap
Local Flaps circulation. The flap is observed for color and for capillary
The postoperative care of local flaps is not complex. Flap refill—the most important indicators of flap viability. A pale
healing is supported by adequate nutrition and maintenance flap generally indicates arterial insufficiency; however, this is
of a normal hemodynamic state, including normal blood not always the case, because certain donor sites, such as the
volume. Tension must not be placed on the flap. Tension can abdomen, are relatively light in color under normal circum-
develop in flaps on the trunk as a result of changes in patient stances, which means that a flap from one of these sites may
position or in flaps on the limbs as a result of loss of immo- appear pale while still having an adequate arterial supply.
bilization. Generally, the tip of any local flap is not only its Mottling is an indicator of arterial insufficiency in these cir-
most valuable portion but also its most vulnerable area. At cumstances. Flaps with venous insufficiency are characteristi-
the tip, the blood supply is the most precarious, and the det- cally blue in color and exhibit rapid capillary refill. In such
rimental effects of tension are magnified. Unfortunately, no flaps, an increase in the pink/red color of the skin with brisk
pharmacologic agents are of proven benefit in preventing capillary refill often precedes the blue discoloration, and it is
necrosis of a flap with failing circulation. Any flap necrosis cause for concern when observed. Bleeding from the edges of
that might develop should be minimized by preventing infec- a flap and swelling are common in the presence of venous
tion of the necrotic tissue. Necrotic tissue must therefore be hypertension.
débrided after the extent of tissue loss becomes clear. Por- If a skin island is exposed, Doppler ultrasonography should
tions of the flap that are undergoing demarcation but do not reveal the presence of a triphasic arterial pulse. The site of this
appear actively infected can be protected by the application pulse should be marked with a suture, staple, or permanent
of a topical antibiotic (e.g., silver sulfadiazine cream). ink to facilitate monitoring by nursing staff. A trained ear can
Extremities that are recipient sites for flaps, such as those distinguish between triphasic, biphasic, and monophasic
that are recipient sites for skin grafts, should be immobilized pulses, which (in that order) indicate increasing degrees of
and elevated after the operation until satisfactory wound heal- arterial compromise from arterial thrombosis or increasing
ing has occurred. venous hypertension. Sometimes a cutaneous venous signal
can be found. The venous signal is a multiphasic “whoosh-
Free Flaps ing” sound that augments with flap compression and then
Survival of free flaps, unlike that of local flaps, tends to be reduces as the flap fills with blood again. It then returns to its
an all-or-none phenomenon. Careful postoperative monitor- baseline. The signal will also get cut off when the pedicle is
ing of flap circulation is essential because flap failure is likely compressed. The nontrained ear will not distinguish between
to be the result of a problem at the vascular anastomoses. static and a normal venous signal, so it is important to train
Flaps are usually monitored for 7 days. However, the most the monitoring staff to assess the venous signal while perform-
critical time for free flap monitoring is the first 48 hours ing flap or pedicle compressing maneuvers. When the flap is
because the majority of vascular crises usually occur within buried, monitoring becomes more difficult. Alternative meth-
this period. Early detection and aggressive investigation of ods of monitoring buried free flaps are being developed and
such crises generally allow a flap to be salvaged. Mainte- are being used with increasing frequency. One example is the
nance of normal blood volume, treatment of hypothermia, implantable Doppler monitor. This device is placed in direct
and avoidance of pressors are particularly important in the contact with the artery or vein distal to the anastomosis to
early postoperative period to prevent vascular spasm. Spasm obtain a continuous Doppler signal.29 These devices are useful
causes flaps to appear pale and to exhibit a significant tem- for buried flaps, when cutaneous signals are not found, when
perature drop. There is no cutoff for hemoglobin or transfu- a complicated microanastomosis has been performed, and for
sion that has proven beneficial for flap survival. It is monitoring the flap during insetting. Too tight of a closure
07/09
will change the venous signal from a multiphasic signal with spasm are difficult to assess because their bleeding response to
augmentation on flap compression to a more monophasic needle puncture is poor despite intact anastomoses.
signal that does not augment. Tissue oximetry has also been As a rule, clinical judgment of flap viability on the basis of all
developed to monitor flaps with an external skin island.30 of these methods of flap monitoring will be highly predictive.
Using this device, a probe is placed on the skin island and If, however, some uncertainty exists, surgical exploration should
attached to a monitor that measures overall tissue oximetry be undertaken because the entire flap may be in jeopardy.
(arterial and venous). A baseline level is reached, and any Free flaps without skin islands are more difficult to monitor
significant fall below the baseline indicates vascular compro- accurately. Muscle flaps can be followed in much the same
mise. The flap can be monitored remotely via the Internet, way as skin free flaps by inserting needle temperature probes
and when the level falls below a preset point, the machine can directly into the muscle belly. A healthy muscle free flap is
notify personnel via a pager. red in color and typically has a serous ooze between the inter-
Surface temperature probes can also be used to monitor stices of the overlying meshed skin graft. A flap with an
free flaps that have a skin island. One probe is placed on the arterial problem quickly becomes dry and dark in appearance.
flap and another on a nearby area to serve as a control. The A muscle flap with a venous problem becomes dark and
flap surface temperature is generally about 1.0° to 2.5°C engorged with blood and exhibits bleeding from its surface
lower than the control temperature. A progressive widening and perimeter. A muscle free flap can be punctured with a
of this temperature difference is ominous and calls for critical needle to assess the quality of the bleeding if its circulatory
assessment of the flap circulation. The absolute temperature status is unclear.
of the flap probe is also significant: a flap temperature higher Fascial free flaps covered with skin grafts are also difficult
than 32°C indicates healthy circulation, whereas a tempera- to assess. They tend to transmit body core temperature read-
ture between 30° and 32°C indicates marginal circulation and ily because they are quite thin; therefore, needle temperature
a temperature lower than 30°C often indicates a vascular probes are generally unreliable. It is often possible in these
problem. In a healthy flap, temperature fluctuations may be cases either to observe the arterial pulsations in the flap
caused by a dislodged probe, an exogenous heat source (e.g., directly or to monitor them with a conventional or implant-
a lamp), cooling of one of the probes from an oxygen mist able Doppler device.
mask, or cleaning of the flap skin with alcohol (which results Some free flaps are completely buried beneath the skin.
in a precipitous drop in skin temperature). Others, such as intraoral skin free flaps, are equally difficult
To confirm the presence of an anastomotic problem, flap to monitor postoperatively. Specialized transplants (e.g., jeju-
circulation is assessed directly by a full-thickness puncture of nal transplants) are particularly vulnerable to short periods of
the flap skin with a 20-, 22-, or 25-gauge needle. If flap circu- anoxia and are not likely to be salvageable by the time a prob-
lation is healthy, a drop of bright red blood should appear at lem is recognized.
the puncture site within a few seconds, and another drop
should appear each time the previous drop is wiped away by
an alcohol swab. The failure of blood to appear or the delayed
appearance of a clear, serous ooze instead of blood is an indica-
tion of arterial insufficiency. Vigorous, dark bleeding confirms
a venous problem. Flaps that are pale as a result of vascular Financial Disclosures: None Reported.
References
1. Parrett BM, Matros E, Pribaz JJ, et al. Lower 8. Daniel RK, Kerrigan CL. Skin flaps: an ana- 16. Jackson IT. Local flaps in head and neck
extremity trauma: trends in the management of tomical and hemodynamic approach. Clin reconstruction. St. Louis: CV Mosby; 1985.
soft-tissue reconstruction of open tibia-fibula Plast Surg 1979;6:181. 17. Spinelli HM, Forman DL. Current treatment
fractures. Plast Reconstr Surg 2006;117:1315. 9. Cederna PS, Chang P, Pittet-Cuenod BM, of post-traumatic deformities: residual orb-
2. Edlich RF, Jones KC Jr, Buchanan L, et al. et al. The effect of the delay phenomenon on ital, adnexal, and soft-tissue abnormalities.
A disposable emergency wound treatment kit. the vascularity of rabbit abdominal cutaneous Clin Plast Surg 1997;24:519.
J Emerg Med 1992;10:463. island flaps. Plast Reconstr Surg 1997;99: 18. Luce EA. Reconstruction of the lower lip.
3. Stevenson TR, Thacker JG, Rodeheaver GT, 183. Clin Plast Surg 1995;22:109.
et al. Cleansing the traumatic wound by high 10. Milton SH. Pedicled skin-flaps: the fallacy of 19. Mathes SJ, Nahai F. Reconstructive surgery:
pressure syringe irrigation. J Am Coll Emerg the length:width ratio. Br J Surg 1970;57: principles, anatomy, technique. Vol 1. New
Phys 1976;5:17. 502. York: Churchill Livingstone; 1997.
4. Hollander JE, Singer AJ, Valentine SM, et al. 11. Lamberty BG. Cormack GC. Fasciocutane- 20. Orgill DP, Austen WG, Butler CE, et al.
Risk factors for infection in patients with trau- ous flaps. Clin Plast Surg 1990;17:713. Guidelines for treatment of complex chest
matic lacerations. Acad Emerg Med 2001; 12. Cormack GC, Lamberty BG. Arterial anatomy wounds with negative pressure wound therapy.
8:716. of skin flaps. Edinburgh: Churchill Livingstone; Wounds 2004; 16(12 Suppl B):1.
5. Edlich RF, Rodeheaver GT, Thacker JG. 1987. 21. Domkowski PW, Smith ML, Gonyon DL Jr,
Technical factors in the prevention of wound 13. Jackson IT. Local rotational flaps. In: Evans et al. Evaluation of vacuum-assisted closure
infection. In: Simmons R, Howard R, editors. GRD, editor. Operative plastic surgery. New in the treatment of post-sternotomy medias-
surgical infectious diseases. Norwalk (CT): York: McGraw-Hill; 2000. tinitis. J Thorac Cardiovasc Surg 2003;
Appleton-Century-Croft; 1981. 14. Worthen EF. Scalp flaps and the rotation 126:386.
6. Robson MC, Heggers JP. Delayed wound forehead flap. In: Strauch B, Vasconez LO, 22. Kaplan M, Banwell P, Orgill DP, et al.
closures based on bacterial counts. J Surg Hall-Findlay EJ, editors. Grabb’s encyclope- Guidelines for the management of the open
Oncol 1970;2:379. dia of flaps. Vol 1. Philadelphia: Lippincott- abdomen: recommendations from a multidis-
7. Teepe RG, Koebrugge EJ, Lowik CW, et al. Raven Publishers; 1998. ciplinary expert advisory panel. Wounds
Cytotoxic effects of topical antimicrobial and 15. McGregor IA, McGregor AD. The Z-plasty. 2005;17(10 Suppl):1.
antiseptic agents on human keratinocytes in In: Fundamental techniques of plastic surgery. 23. Miller PR, Thompson JT, Faler B, et al. Late
vitro. J Trauma 1993;35:8. Edinburgh: Churchill Livingstone; 1995. fascial closure in lieu of ventral hernia: the
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next step in open abdomen management. 27. Bennett RG. Hirt M. A history of tissue 30. Keller A. Noninvasive tissue oximetry for flap
J Trauma 2002;53:843. expansion: concepts, controversies, and com- monitoring: an initial study. J Reconstr Mic-
24. Taylor GI, Giantoutsos MP, Morris SF. The plications. J Dermatol Surg Oncol 1993; rosurg 2007;23:189–97.
neurovascular territories of the skin and 19:1066.
muscles: anatomic study and clinical implica- 28. Hidalgo DA, Disa JJ, Cordeiro PG. A review
tions. Plast Reconstr Surg 1994;94:1. of 716 consecutive free flaps for oncologic
25. Hidalgo DA, Shaw WW. Reconstruction of surgical defects: refinement in donor site
foot injuries. Clin Plast Surg 1986;13:663. selection and technique. Plast Reconstr Surg
26. May JW Jr, Halls MJ, Simon SR. Free micro- 1998;102:722.
vascular muscle flaps with skin graft recon- 29. Kind GM, Buntic RF, Buncke GM, et al.
Acknowledgment
struction of extensive defects of the foot: a The effect of an implantable Doppler probe
clinical and gait analysis study. Plast Reconstr on the salvage of microvascular tissue trans- Figures 4, 5, 7, 12, 13 Carol Donner.
Surg 1985;75:627. plants. Plast Reconstr Surg 1998;101:1268. Figures 6, 8, 9, 10, 11 Tom Moore.
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3 BREAST, SKIN, AND SOFT TISSUE 4 SURGICAL MANAGEMENT OF MELANOMA
AND OTHER SKIN CANCERS — 1
4 SURGICAL MANAGEMENT
OF MELANOMA AND OTHER SKIN
CANCERS
Jennifer A.Wargo, MD, and Kenneth Tanabe, MD
The clinical assessment and management of skin lesions can are considered to be suspicious. Careful attention should also
be challenging as the natural history and prognosis of these be paid to constitutional symptoms as patients may present
lesions are widely variable. Surgeons play a pivotal role in the with advanced disease with metastases and systemic or focal
treatment of these lesions, although the initial evaluation of complaints, such as headaches or visual changes in the case
these lesions is often performed by other clinicians. The man- of melanoma metastatic to the brain.
agement of various benign skin lesions is beyond the scope of Physical examination should include a complete skin exam-
this review. Evaluation and management of malignant skin ination and examination of mucous membranes. Specific
conditions are addressed in detail. attention should be paid to the presence of ulceration in a
The prevalence of malignant skin lesions has increased sig- skin lesion as this significantly affects the prognosis depend-
nificantly over the past several years. Approximately 1.2 million ing on the histology of the lesion. Consideration should be
cases of nonmelanoma skin cancer are diagnosed per year.1 paid to the potential draining nodal basins as lymph node
More alarming, up to 80,000 cases of melanoma are diagnosed metastases are known to occur in squamous cell cancer and
per year,2 an incidence that has been rapidly increasing,3 with melanoma.
a lifetime risk of 1 in 75 for the development of melanoma.2 Nonsuspicious lesions may be safely monitored conserva-
The disturbing increase in the incidence of both nonmelanoma tively with regular self-examination by patients and regular
skin cancer and melanoma can largely be attributed to the follow-up with their health care provider. Any change in a
social attitude toward sun exposure.4 lesion constitutes a criterion for biopsy.
biopsy
Assessment of Skin Lesions
Any suspicious lesion should be biopsied. This can be per-
history and physical examination formed by excisional biopsy if the lesion is small or incisional
Obtaining a careful history is critical to the evaluation of biopsy if the lesion is large. Excisional biopsy should be per-
skin lesions. Particular attention should be paid to a history formed incorporating a 1 to 4 mm margin of normal skin
of sun exposure. Blistering sunburn in childhood or adoles- surrounding the lesion depending on the clinical characteris-
cence is a significant risk factor and is present in virtually all tics. This may eliminate the need for subsequent reexcision
Caucasians who develop melanoma.5 Patients should also be for some types of lesions (e.g., dysplastic nevus). However,
questioned about any personal or family history of skin cancer no attempt should be made to perform a definitive radical
as those who report a history of melanoma in a first-degree excision until a diagnosis is established by biopsy. Full-
relative have an 8- to 12-fold risk for the development of thickness excision into the subcutaneous fat should be per-
melanoma.6 In addition, patients should be questioned regard- formed, and margins on the specimen should be marked for
ing immunosuppression and a history of transplantation as orientation. This allows the pathologist to comment on the
these put them at a higher risk of developing skin cancer. level of invasion and on margins for possible microscopic
A detailed history regarding when the lesion was first noted involvement with tumor cells. Electrocautery should generally
and changes in the size or the appearance of the lesion is not be used during excisional or incisional biopsy as margins
important to elucidate. Generally speaking, lesions are non- can be distorted significantly by the artifact created by this
suspicious if they remain stable and uniform in their physical technique. Shave biopsy for evaluation of pigmented lesions
characteristics (e.g., size, shape, color, profile, and texture). is discouraged as it runs the risk of a positive deep margin,
An example of a nonsuspicious lesion is a simple nevus, which which compromises the ability to determine the true depth of
typically becomes apparent at 4 to 5 years of age, darkens penetration of a melanoma or other malignant skin lesion.
with puberty, and fades in the seventh to eighth decades of The long axis of an elliptically shaped excisional biopsy
life. However, pigmented lesions that demonstrate an irregu- should be oriented along the long axis of the extremity, which
lar border or demonstrate a change in size, color, or texture facilitates subsequent reexcision if necessary. If the lesion is
DOI 10.2310/7800.S03C04
03/09
benign, no further treatment is warranted. If it proves to be represents the minority of these lesions but has clinical fea-
malignant, further excision with an appropriate margin is tures that are particularly pertinent to the surgeon. These
usually necessary, and staging of the tumor becomes impor- lesions are often larger than they appear clinically and have a
tant. Adequacy of margins is discussed under each particular
tumor type.
a
e xc isio n
If a lesion proves to be malignant, complete excision should
be performed with adequate margins as dictated by the type
of tumor. An elliptical-shaped excision, with a length approx-
imately 3.5 to 4 times the width, allows for a cosmetic closure
without “dog ears.” If an area cannot be closed without sig-
nificant tension, skin grafting may be necessary to achieve a
technically acceptable result. Tissue transfer may also be
required for very large lesions or for special areas, such as on
the face.
Specific Types of Skin Cancer

basal cell carcinoma
Incidence and Epidemiology
Basal cell carcinoma is the most common malignancy in
Caucasians7 and the most prevalent type of skin cancer. The
incidence is widely variable across the globe, with an inci-
dence of 146 per 100,000 in the United States and 726 per
100,000 in Australia.8 The lifetime risk for a Caucasian in the
United States for developing a basal cell carcinoma is approx-
imately 30%.1 Although the metastatic potential of these
lesions is very low, the economic and social burden remains
b
quite high.
In general, the vast majority of basal cell carcinomas occur
on the head and neck. Basal cell carcinoma develops without
a known precursor lesion, although it seems to be most closely
related to exposure to ultraviolet radiation. Significant sun
exposure during childhood and adolescence confers significant
risk for the development of these lesions, although studies have
failed to demonstrate a significant correlation between the
development of basal cell carcinoma and cumulative exposure
to ultraviolet light in adulthood.9 Several heritable conditions
are associated with an increased risk of basal cell carcinoma,
including albinism, xeroderma pigmentosum, and Gorlin syn-
drome. Patients with Gorlin syndrome develop multiple basal
cell carcinomas, as well as anomalies of the spine and ribs, jaw
cysts, pitting of the palms and soles, and calcification of the
falx cerebri. Inheritance is autosomal dominant.10
Histologic Subtyes of Basal Cell Carcinoma

Several subtypes of basal cell carcinoma exist. Typical pat-
terns seen in more mature lesions include nodular or cystic,
superficial, morpheaform, and pigmented. Nodular or cystic
basal cell carcinomas typically present as solitary lesions, often
on the face, and are usually shiny and red, with central telan-
giectasias [see Figure 1a]. The classic basal cell carcinoma is
the nodular type, which is also known as a “rodent ulcer.”
Figure 1 (a) Typical basal cell carcinoma. A pearly luster
These lesions are characterized by an indurated edge and an
and telangiectasias are evident in this typical basal cell
ulcerated center. Superficial basal cell carcinomas are typi- carcinoma on the cheek of a 43-year-old man. (b) Morphea-
cally found on the trunk and appear as an erythematous patch form basal cell carcinoma. This sclerosing (morpheaform)
that is often mistaken for eczema or psoriasis and are typically basal cell carcinoma on the nose of a 55-year-old man was
slow-growing.10 Perhaps the most pertinent of these lesions is found to be deeply invasive and exhibited multidirectional
the morpheaform basal cell carcinoma [see Figure 1b], which growth.
03/09
more aggressive natural history, which can make complete found in elderly patients, likely representing the result of
excision quite challenging. cumulative doses of sun exposure over the course of their
lifetime.
Treatment
Surgical excision remains the mainstay of treatment for pri- Precursor Lesions
mary basal cell carcinomas. Typically, a surgical margin of Unlike basal cell carcinomas, squamous cell skin cancers
4 mm is recommended when possible.11 Primary closure is gen- often arise in precursor lesions, such as actinic keratosis.18
erally possible for small defects, and rotation flaps or skin graft- Actinic keratoses, sometimes referred to as solar keratoses,
ing may be necessary for larger defects. Although present only develop in chronically sun-damaged areas of the body. They
extraordinarily rarely, lymphatic spread identified in the pri- are generally ill-defined and irregular and may range signifi-
mary tumor may be an indication for lymphatic mapping.12 cantly in size, from only a millimeter to a few centimeters.
Other surgical techniques include cryosurgery, curettage They have a scaly appearance, are often multiple, and can
and cautery, and Mohs micrographic surgery. Cryosurgery range in color from dark brown to flesh colored. Biopsy may
and curettage should generally be avoided in large or mor- be necessary to rule out the presence of a squamous cell car-
pheaform tumors or in those in high-risk areas (such as the cinoma. The rate of malignant transformation of actinic ker-
central face) as surgical margins cannot be assessed. Mohs atosis to squamous cell carcinoma is less than 0.1% per year,19
micrographic surgery is a technique involving excision of although lesions should be treated to decrease the chance of
serial sections with intraoperative histologic examination of progression. Treatment options include cryotherapy, curet-
frozen sections to control surgical margins. It is particu- tage, and topical agents. Surgical excision of actinic keratoses
larly useful in morpheaform or recurrent basal cell carcino- is rarely necessary but may be indicated if there is a high
mas or those in high-risk sites, with 5-year cure rates suspicion for a concurrent squamous cell carcinoma.
approaching 95%.13 Intraepithelial squamous cell carcinoma, carcinoma in situ,
Nonsurgical modalities available for treatment of basal cell is thought to be the next step in the progression from actinic
carcinoma include radiotherapy, photodynamic therapy, and keratosis to invasive squamous cell carcinoma. Another term
topical agents such as 5-fluorouracil, imiquimod, or intrale- for this lesion is Bowen disease, and lesions are typically
sional interferon alfa. Radiation therapy is generally reserved located on sun-exposed areas of the head, neck, trunk, or
for elderly patients with extensive lesions that preclude exci- legs. This lesion is referred to as “erythroplasia of Queyrat”
sion, with 5-year cure rates approaching 90%.14 Photody- when located on the genitalia. When it occurs on non–sun-
namic therapy involves the use of -aminolevulinic acid in a exposed areas, it may be associated with internal malig-
20% emulsion that is applied to the lesion followed by expo- nancy.20 These lesions typically appear as erythematous,
sure to light in the wavelength range of 620 to 640 nm. This slightly keratotic plaques and are usually larger than lesions
treatment is based on the uptake of the porphyrin metabolite of actinic keratosis. These lesions should be excised with a
by the tumor with subsequent conversion to protoporphyrin 5 mm to 1 cm margin.
IX, which is subject to destruction in the presence of light.10
Responses to treatment are somewhat lower, with an overall Diagnosis
clearance rate of 87% and a lower clearance rate of 53% in Squamous cell carcinomas occur on the head and neck in
nodular basal cell carcinoma.15 Fluorouracil 5% cream may approximately 50% of cases. Caucasians have nearly a 10%
also be used in the management of multiple basal cell carci- lifetime risk of developing a squamous cell carcinoma. Inter-
nomas of the trunk and limbs. Imiquimod is an immuno- estingly, in one series, nearly half of fatal cases of squamous
modulatory agent that is used in a 5% cream for basal cell cell carcinoma occurred in patients in whom the lesion arose
carcinomas, with a clearance rate of 70 to 100%.16 Intrale- from the ear.21 The mortality rate associated with squamous
sional interferon alfa has also been used experimentally, with cell carcinoma is estimated at 1:100,000.22
a 67% cure rate in a series of 140 patients treated in this As noted, squamous cell carcinomas are most often asso-
manner.17 ciated with sun exposure, although they may also be seen in
Patients who have been treated for any skin cancer, includ- a background of old scars, radiation-damaged skin [see
ing basal cell carcinoma, should perform frequent self- Figure 2a], or chronic open wounds.23 Chronic inflammation
examination to look for suspicious lesions as they are at a and irritation appear to be the common denominators. Mar-
greater risk for developing additional skin cancers. Counsel- jolin ulcer is a term for squamous cell carcinoma arising in
ing to reduce sun exposure should be undertaken to limit a burn scar or open wounds such as osteomyelitis draining
further damage from ultraviolet irradiation. High-risk indi- sites.
viduals, such as those with Gorlin syndrome or those who are These lesions typically appear as keratotic papules, which
on immunosuppressive therapy after renal transplantation, may ulcerate, and may be reddish-brown, pink, or flesh col-
are offered oral retinoid treatment in the hope of preventing ored [see Figure 2b]. A cutaneous “horn” may be evident if
the development of other nonmelanoma skin cancers.17 there is extensive hyperkeratosis.21 Symptoms that may sug-
squamous cell carcinoma gest malignant transformation of actinic keratosis include
pain, erythema, ulceration, or induration. Histologically, these
Incidence and Epidemiology lesions are characterized by nests of atypical keratinocytes that
Squamous cell carcinoma of the skin is the second most have invaded into the dermis, which may be well or poorly
common form of nonmelanoma skin cancer, with the major- differentiated.
ity (50 to 60%) of these lesions occurring on the head and Once a diagnosis of squamous cell carcinoma is suspected,
neck. Squamous cell carcinoma is the most common tumor careful attention should be paid to the draining nodal basins
03/09
a aspiration of palpable nodal masses should be performed to

diagnose metastatic squamous cell cancer, a condition that
should be treated by aggressive lymphadenectomy. Adjuvant
radiation therapy to the nodal basin is often indicated, based
on the extent of nodal metastases.
Other therapies for squamous cell carcinoma are similar to
those used to treat basal cell carcinoma and incude cryosur-
gery, curettage and cautery, Mohs micrographic surgery,
radiotherapy, photodynamic therapy, and topical agents such
as 5-fluorouracil, imiquimod, or intralesional interferon alfa.
Squamous cell carcinomas that develop from Marjolin ulcer
are characterized by aggressive growth after surgical excision.
Patients who have been treated for squamous cell carci-
noma should perform frequent self-examination to look for
suspicious lesions as they are at risk for developing other non-
melanoma skin cancers. Counselling to reduce sun exposure
b should be undertaken to limit further damage from ultraviolet
irradiation. High-risk individuals, such as those who are on
immunosuppressive therapy after renal transplantation, may
be offered oral retinoid treatment in the hope of preventing
the development of other nonmelanoma skin cancers.17
melanoma
Incidence and Epidemiology
Although it is less common than basal cell or squamous cell
carcinoma, melanoma is clearly the most deadly of these can-
cers. Up to 80,000 cases of melanoma are diagnosed per
year,2 and it is the sixth leading cause of cancer death in the
United States. The lifetime risk is estimated to be 1 in 75
individuals for the development of melanoma.2 The incidence
of melanoma is increasing significantly at a rate of 4.1% per
year, faster than any other malignancy. The incidence is
Figure 2 (a) Squamous cell carcinoma related to radiation slightly higher in men than in women, and the median age at
exposure. This squamous cell carcinoma involving the thumb diagnosis is 57 years.24 An average of 18.8 life-years are lost
and index finger of a 72-year-old man, a retired dentist, was per melanoma death,25 and it is estimated that one American
related to exposure to occupational hazards; he had subjected will die from melanoma every hour.26
these digits to repeated radiation exposures by holding dental Melanoma results from the malignant transformation of
x-rays against his patients’ teeth. (b) Squamous cell melanocytes, which are responsible for pigment production.
carcinoma related to sun exposure. This squamous cell
Both genetic and environmental factors are implicated in the
carcinoma on the lip of a 70-year-old man was related to sun
exposure; the patient was a nonsmoker.
development of melanoma. Genetic susceptibility is important,
and patients with melanoma often report a family history. Those
who report a history of melanoma in a first-degree relative have
as lymph node metastases are possible. Overall, the risk of
an 8- to 12-fold risk for the development of melanoma.6 Somatic
metastasis is between 2 and 4% and is higher in larger, poorly
mutations in the p16 tumor suppressor gene have been identi-
differentiated lesions and lesions located on the scalp, nose,
fied in both familial and sporadic cases of melanoma.27 Environ-
ear, lip, and extremities. The most common sites of metasta-
mental exposure to ultraviolet radiation also is implicated in the
sis are regional lymph nodes, the lungs, and the liver. Recur-
transformation of melanocytes. Risk for the development of
rence or metastases typically occur within 3 years after
melanoma is associated with intermittent, intense sun exposure
treatment of the index lesion.
rather than with a cumulative effect, although the exact mecha-
Treatment nism behind the pathogenesis remains unknown.
Surgical excision remains the mainstay of treatment for pri- In one study, six risk factors were identified by multivari-
mary squamous cell carcinomas as well, although the recom- ate analysis to be important in the development of malignant
mended margin of excision is generally larger than that for melanoma and include the following: a family history of
basal cell carcinoma, ranging from 0.5 to 2 cm. Primary clo- melanoma, a history of three or more blistering sunburns
sure is often possible for smaller lesions, although larger before age 20 years, the presence of blonde or red hair, the
lesions may require rotation flaps or skin grafting. Sentinel presence of actinic keratosis, a history of 3 or more years of
lymph node mapping should be considered for patients with an outdoor summer job as a teenager, and the presence of
large squamous cell carcinomas (e.g., > 2 cm) or those with marked freckling on the upper part of the back.28 Individuals
histologic evidence of lymphovascular invasion. Fine-needle with one or two of these factors have a 3.5-fold increased risk
03/09
Table 1 ABCD Guidelines for Pigmented Lesions a
Asymmetry Most early lesions grow at an uneven rate,

resulting in an asymmetrical pattern
Border irregularity The uneven growth rate also results in an
irregular border
Color variegation Irregular growth also causes new shades of
black and light and dark brown
Diameter Lesions with ABC freatures and diameters
of > 6 mm should be considered suspi-
cious for melanoma
of developing melanoma, whereas if they have three or more,

they have a 20-fold increase in risk.
Screening and Diagnosis

The frequency of screening of patients for melanoma
should be based on the above risk factors. Routine screening
of low-risk patients using a total body skin examination by
health care providers is not supported. Self-screening, how-
ever, is clearly recommended, with excellent educational
materials provided by the American Academy of Dermatol-
ogy and the American Cancer Society. Nevertheless,
physicians should take every opportunity to screen opportu-
nistically as lesions found by physicians are significantly
thinner than those detected by patients or their spouse.29
Early recognition of melanoma is paramount to its effective
treatment. The “ABCD” guidelines may be used in the evalua-
tion of pigmented lesions [see Table 1].30 These lesions often
occur on sun-exposed areas of the upper trunk and extremities
and are typically asymmetrical, with irregular borders and varie-
gated pigmentation [see Figure 3a]. Occasionally, they lack pig-
mentation or are associated with significant ulceration. Any
lesion suspicious for melanoma should be biopsied. Histologi-
cally, these lesions are characterized by atypical melanocytes b
with mitotic figures. Special staining may also be performed,
and the most commonly used markers are HMB-45 and S100.
Histologic Subtypes
Melanoma may be further classified into histologic subtypes
based on patterns of growth and anatomic location. The sig-
nificance of these subtypes is generally less important than the
pattern of growth (radial versus vertical growth) and depth of
penetration.31 The most common subtypes include lentigo
maligna melanoma, superficial spreading melanoma, acral
lentiginous melanoma, and nodular melanoma. Superficial
spreading accounts for over 70% of melanomas. These lesions
are most common in white adults and typically occur on the
back or legs. Nodular melanomas are the second most
common, accounting for between 15 and 30% of all melano-
mas. These lesions often appear dome shaped and may occur
anywhere on the body. They typically invade the dermis early
in their natural history owing to an early vertical growth phase.
Figure 3 (a) Typical melanoma. A halo effect caused by loss
Lentigo maligna melanoma accounts for approximately 5% of
of pigmentation is visible along the left margin of this
all melanomas and is thought to arise in a focus of lentigo melanoma on the upper back of a 33-year-old white woman;
maligna, or Hutchinson freckle. These lesions demonstrate a irregularities in shape, contour, and pigmentation are also
prolonged radial growth phase before developing an invasive evident. (b) Acral lentiginous melanoma. This melanoma, on
component. Acral lentiginous melanomas occur on the hands the sole of the foot of a 47-year-old black woman, shows
or feet [see Figure 3b], often under the nail bed, where the irregularities in shape, contour, and pigmentation.
03/09
dermis is thinner (e.g., subungal melanoma). A more rare his-

Table 2 Clark’s Levels for Staging of Malignant
tologic variant is desmoplastic melanoma, which typically Melanoma
occurs in areas of sun damage and tends more often to recur
Level 5 yr Survival
locally. Rate (%)
Prognostic Factors in Melanoma I Malignant melanocytes are confined 99
to the epidermis
An important variable in the prognosis of melanoma is the
thickness of the primary tumor as assessed using the Clark or II Malignant melanocytes infiltrate the 95
the Breslow system. The Clark system remains of primarily papillary dermis by single cells or
small nests of cells
historical interest. In this staging system, levels I to V are
defined by the presence of malignant melanocytes in each of III Malignant melanocytes fill and expand 82
the papillary dermis with extension
the following layers: epidermis, papillary dermis, reticular
of the tumor to the papillary-
dermis, and subcutaneous fat [see Figure 4 and Table 2].32 But reticular dermal interface (usually
the Breslow microstaging system has been demonstrated to signifies vertical growth phase)
have more prognostic information than the Clark system. IV Malignant melanocytes infiltrate the 71
Tumor thickness in the Breslow system is measured in milli- reticular dermis in a significant
meters from the epidermal surface to the deepest point of the fashion
tumor with a calibrated ocular micrometer [see Table 3].33 V Malignant melanocytes infiltrate the 49
Extensive research has been done over the past several subcutaneous fat
years regarding prognostic factors in both early and late
stage melanoma. Overall, clinical factors shown to have sig-
nificant prognostic value include patient age, sex, location Table 3 Breslow’s Microstages for Malignant Melanoma
of the melanoma, number of involved lymph nodes, pres- Stage 5 yr Survival (%)
ence of distant metastasis, and serum lactate dehydroge-
1: < 0.76 mm > 98
nase (LDH) level.34 Prognosis is generally better for patients
< 65 years of age, women, tumor location on the extremi- 2: 0.76–1.49 mm 87–94
ties, absence of lymph node involvement, absence of distant 3: 1.50–3.99 mm 66–83
metastasis, and a normal serum LDH level. The American
4: > 4.0 mm < 50
Joint Committee of Cancer (AJCC) approved the latest
version of the melanoma staging system in 2002, with
changes that were validated via analysis of over 17,000 Stage I and II melanoma Those with localized melanoma
patients with melanoma [see Table 4].34 Five-year survival represent the vast majority of patients, and several prognostic
rates correlate with stage [see Table 5].34 A new version of factors have been identified for risk stratification and prognosis
staging will be released in 2009, incorporating additional in this heterogeneous group. The most important prognostic
factors such as mitotic rate35 that influence prognosis and factors in early-stage melanoma are tumor thickness (T1 to T4)
survival. and the presence or absence of ulceration. These have significant
I II III IV V
Epidermis
Papillary Dermis
Reticular Dermis
Subcutaneous Fat
Figure 4 Clark categorized skin tumors according to their level of invasion. Tumors
of level I involve the epidermis and are essentially carcinoma in situ. In level II, the
tumor has extended into the papillary dermis. Tumor cells at level III are spread
along the papillary-reticular dermal interface. Invasion into the reticular dermis
occurs at level IV. Level V tumors extend into the subcutaneous tissue. In general,
survival decreases as the depth of invasion increases.
03/09
Table 4 AJCC Staging of Malignant Melanoma

T classification
T1 ≤ 1.0 mm A: without ulceration and Clark’s level II or III
T1 B: with ulceration or Clark’s level IV or V
T2 1.01–2.0 mm A: without ulceration
T2 B: with ulceration
T3 2.01–4.0 mm A: without ulceration
T4 > 4.0 mm A: without ulceration
N classification
N1 1 lymph node A: micrometastases
B: macrometastases
N2 2–3 lymph nodes A: micrometastases
B: macrometastases
C: in-transit metastases, satellite(s) without metastatic nodes
N3 4 or more metastatic lymph nodes,
matted lymph nodes, or
combinations of in-transit
metastases, satellites, or
ulcerated melanoma and
metastatic lymph node(s)
M classification
M1 Distant skin, subcutaneous or Normal LDH
lymph node metastases
M2 Lung metastases Normal LDH
M3 All other visceral or any distant Normal LDH
metastases Elevated LDH with any M
AJCC = American Joint Committee on Cancer; LDH = lactate dehydrogenase.
Stage 0: Tis, N0, M0; stage IA: T1a, N0, M0; stage IB: T1b, N0, M0; T2a, N0, M0; stage IIA: T2b, N0, M0; T3a, N0, M0; stage IIB:
T3b, N0, M0; T4a, N0, M0; stage IIC: T4b, N0, M0; stage IIIA: any T1–4a, N1b, M0; stage IIIB: any T1–4a, N2b, M0; stage IIIC: any T,
N2c, M0; any T, N3, M0; stage IV: any T, any N, M1–3.
implications in prognosis as 5-year survival in stage I to II mel- a predicted 5-year survival of 78.7% for nonulcerated lesions
anomas falls significantly with increasing thickness and dropped and 63% for ulcerated lesions. Thick (> 4 mm) lesions in
from 80% to 55% in the presence of ulceration in a 2006 anal- node-negative patients have an associated 5-year survival of
ysis.31 Mitotic rate in the primary tumor has been identified as 67.4%, which drops to 45.1% if the lesion is ulcerated.34
an important prognostic factor, possibly even surpassing ulcer- Stage III melanoma Stage III melanoma is character-
ation in importance in early-stage melanoma.34,36 The mitotic ized by the presence of nodal metastases (micro- or macro-
rate will be incorporated into the new version of the AJCC stag- metastases) with or without in-transit or satellite lesions. The
ing system, which will be released in 2009. presence of lymph node metastases confers a significantly
Thin (< 1 mm thick) melanomas in particular have also been worse prognosis, with less than half of node-positive patients
studied with great interest because they represent the largest surviving 5 years.34 The number of involved nodes is also of
group of patients. A recent publication from the University of prognostic significance and is reflected in the recent revisions
Pennsylvania describes a prognostic model using four factors to the AJCC staging system.
based on multivariate analysis: mitotic rate (0 versus 1), In patients with stage III disease, four prognostic factors for
growth phase (radial or vertical), gender, and tumor-infiltrating survival were identified: number of metastatic lymph nodes,
lymphocytes.37 Investigators developed an algorithm for risk microscopic versus macroscopic tumor deposits in lymph
stratification based on these factors, with minimal- and low-risk nodes, the presence of in-transit or satellite metastases, and
patients having a predicted risk for metastasis of less than 4%, the presence of ulceration in the primary lesion.34 In earlier
whereas those who were considered moderate or high risk had staging systems, the size of the involved lymph node was
a predicted risk for metastasis of 12 and 30%, respectively.37 thought to be of significance, although this has been dis-
Intermediate-thickness (1.0 to 4 mm) melanomas clearly proven.38 However, macroscopic disease (that which is identi-
have a worse prognosis, with 5-year survival rates of 89% for fied clinically and confirmed histologically) does have a
nonulcerated T2 lesions (1 to 2 mm) and 77.4% for ulcerated significant impact, with a much poorer survival in those with
lesions. Patients with ulcerated T3 lesions (2 to 4 mm) have macroscopic as opposed to microscopic disease.34
03/09
Table 5 5-Year Survival Rates Based on AJCC Stage history and physical examination, as well as a comprehensive
dermatologic examination. For patients with thin melanomas
Stage T, N, M 5 yr Survival (%)
(< 1.0 mm) or intermediate-thickness melanomas, no routine
IA T1a, N0, M0 95.3 laboratory or radiologic tests are recommended. Chest radiog-
IB T1b, N0, M0 90.9 raphy is considered optional in patients with stage IB or stage
II melanoma as this is unlikely to pick up occult metastatic
T2a, N0, M0 89.0
disease. For patients with stage III disease who present with
IIA T2b, N0, M0 77.4 clinically positive nodes, computed tomography (CT) of the
T3a, N0, M0 78.7 chest, abdomen, and pelvis may be performed to confirm the
IIB T3b, N0, M0 63.0
presence of regional disease and to exclude the possibility of
metastatic disease. In a patient with stage III disease defined
T4a, N0, M0 67.4 by a microscopically positive sentinel node, the yield of CT
IIC T4b, N0, M0 45.1 scans is much lower, although current guidelines leave it to the
IIIA Any T, N1a, M0 (no ulceration, 69.5 discretion of the treating physician. If inguinal lymphadenopa-
1 node, micrometastases) thy is apparent, pelvic CT should be obtained to assess iliac
N2a, M0 (no ulceration, 2–3 63.3
lymph nodes.39 For patients with stage IV disease, a chest
nodes, micrometastases) radiograph and serum LDH should be obtained. Brain mag-
netic resonance imaging and CT of the chest, abdomen, and
IIIB N1a, M0 (+ ulceration, 1 node, 52.8
micrometastases) pelvis should be performed before embarking on any surgery.
Other imaging will be guided by protocol if the patient is
N2a, M0 (+ ulceration, 2–3 49.6
enrolled in a clinical trial.39
nodes, micrometastases)
N1b, M0 (no ulceration, 1 node, 59.0 Surgical Treatment of Stage I and II Melanoma
macrometastases)
Margins of excision Surgical excision remains the main-
N2b, M0 (no ulceration, 2–3 46.3 stay of treatment for melanoma. The width of the recom-
nodes, macrometastases) mended surgical margins depends on the thickness of the
IIIC N1b, M0 ( + ulceration, 1 node, 29.0 lesion and has been well defined by a series of prospective
macrometastases) randomized clinical trials. The most recent recommendations
N2b, M0 (+ ulceration, 2–3 24.0 suggest that a 0.5 cm margin is adequate for in situ mela-
nodes, macrometastases) noma, whereas margins of 1 cm are suggested for melanomas
N3, M0 (+ ulceration, > 4 nodes, 26.7 less than 1.0 mm in thickness. Two-centimeter margins
micro- or macrometastases) should be obtained for lesions measuring 1 to 2 mm in depth.
IV Any T, any N, M1a (skin or 18.8 Although a reduction in surgical margin width to 1 cm for
subcutaneous metastases) melanomas 1 to 2 mm in thickness may slightly increase the
risk for local recurrence, it would not reduce overall survival
Any T, any N, M1b (lung 6.7
metastases) statistics. Two-centimeter margins should be obtained for
melanomas greater than 2 mm in thickness.40
Any T, any N, M1c (other 9.5
visceral metastases + LDH) Sentinel lymph node biopsy Another important issue
in the surgical management of melanoma is the use of senti-
AJCC = American Joint Committee on Cancer; LDH = lactate dehydrogenase.
nel lymph node biopsy (SLNB), which has essentially replaced
elective lymph node dissection. Sentinel lymph node status is
In-transit and satellite metastases represent dissemination the single most important predictor of survival in patients
of tumor via lymphatic channels, and the 5-year survival rate with melanoma41 and is considered a standard approach in
in patients with these findings is similar to that of those with this country. SLNB is recommended for intermediate-
lymph node metastases. If these findings are present in asso- thickness (1 to 4 mm) and thick (> 4 mm) melanomas. It is
ciation with lymph node metastases (N3), the survival rate generally not recommended for thin melanomas (< 1 mm)
drops significantly.34 unless the lesion is of high risk (presence of ulceration, exten-
Stage IV melanoma For stage IV melanoma, the site of sive regression, high mitotic rate, Clark level IV, or positive
distant metastasis and serum LDH seem to have the most value deep margin) or depending on the patient’s age (SLNB may
in prognosis, with a far more favorable prognosis in those with be performed in young patients). A positive result is defined
cutaneous metastases and a normal serum LDH. On analysis, as the presence of identifiable melanoma cells on either rou-
there is a significant difference in 1-year survival rates between tine hematoxylin-eosin stains and/or by immunohistochemi-
those with cutaneous, subcutaneous, or distant nodal metastases cal staining with S100 or HMB-45. Preoperative lymphatic
(M1) versus those with lung metastases (M2) versus those with mapping via lymphoscintigraphy is very helpful in these
any other visceral metastases, or any metastasis with an elevated patients as many lesions have variable drainage basins that
serum LDH (M3). Predicted 1-year survival rates for patients cannot be predicted clinically and may even drain to contra-
in these groups are 59%, 57%, and 41%, respectively.34 lateral nodes.42 The greatest accuracy is achieved when both
radioactive colloid and blue dye are used during SLNB.43
Initial Evaluation SLNB should not be performed in the setting of clinically
Recommendations for initial evaluation of patients with positive nodes or in patients who would otherwise not be
melanoma are as follows: all patients should receive a complete considered for lymphadenectomy.
03/09
The impact of SLNB for melanoma has been impressive. metastases in the remaining nonsentinel nodes. This was
The results are critical to accurate staging and are also addressed in a recent series of 658 patients, in which 90 (14%)
important in deciding whether to perform completion lymph- were found to have a positive sentinel node, with 18 (20%) of
adenectomy or offer adjuvant therapy. Several studies have that group having evidence of metastases in additional nonsen-
demonstrated increased survival and disease-free interval tinel nodes.54 The number of positive nodes clearly has an
between sentinel lymph node–negative and –positive impact on prognosis and is included in the AJCC staging
patients.44,45 One of these studies demonstrated a 3-year system.34 This adds credence to the argument for therapeutic
disease-free survival of 88.5% versus 55.8% in sentinel lymph lymph node dissection following a positive SLNB.
node–negative versus –positive patients, with a 58.6% increase Another aspect of this topic that is debated is the extent of
in disease-free survival if the SLNB was negative.44 lymph node dissection required. Investigators at the John
Wayne Cancer Institute recently reviewed their experience
Surgical Treatment of Stage III Melanoma with therapeutic lymph node dissection prior to the use of
Therapeutic lymph node dissection Therapeutic lymph sentinel node biopsy, and concluded that the extent of lymph
node dissection is currently recommended for management of node dissection is more important with higher tumor burden
the regional lymph node drainage basin in the presence of a and less important with a lower tumor burden.55 Those with
positive sentinel node and in clinical stage III disease. Some micrometastatic disease in a sentinel node and those with
challenge this recommendation as four randomized trials of bulky nodal disease are clearly different, and the potential ben-
elective lymph node dissection failed to demonstrate an overall efits of therapeutic lymph node dissection must be carefully
survival benefit.46–49 Yet the majority of patients in these studies weighed against the morbidity of the procedure.56 The role of
did not have nodal disease; thus, the trials were not sufficiently lymphadenectomy and adjuvant alpha 2B and its impact on
powered to detect a small survival benefit.50 Other trials have survival was addressed in the Sunbelt Melanoma trial,57 the
supported this practice, including the World Health Organiza- results of which were updated at the annual meeting of the
tion 14 trial, which on subgroup analysis demonstrated a sig- American Society of Clinical Oncology in May 2008 (pub-
nificantly improved 5-year survival rate in patients with occult lished in abstract form only). In essence, there was no signifi-
nodal metastases detected at elective lymph node dissection cant difference in disease-free or overall survival among
compared with patients who had delayed lymphadenectomy at patients randomized to completion lymphadenectomy versus
the time when they developed palpable nodal metastases (48% completion lymphadenectomy with adjuvant high dose inter-
versus 27%, respectively; p .04).48 feron. There is, however, clearly a role for therapeutic lymph
Nonetheless, the impact of completion lymphadenectomy on node dissection in patients with bulky nodal disease, and it can
overall survival is still a matter of debate. This has been further be performed with minimal morbidity and good palliation.58
addressed since the advent of the use of SLNB in melanoma. Isolated limb perfusion Patients with in-transit metas-
The results of the first Multicenter Selective Lymphadenectomy tases have an unfavorable prognosis. This reflects a dissemi-
Trial (MSLT-I) suggest that SLNB with immediate completion nated stage of disease, with a 5-year survival rate of 25 to
lymphadenectomy if the sentinel node is positive improves 30%. Surgical excision is the mainstay of therapy when the
disease-free survival but not overall survival for these patients.51 size and the number of lesions permit, although there is no
In this trial, 1,973 patients were randomized in a 4:6 ratio to formal recommendation regarding the extent of surgical
wide excision followed by nodal observation (WEO) or to wide margin. Amputation is rarely necessary.
excision plus lymphatic mapping and sentinel lymph node biopsy Another therapeutic option for patients with extensive
(LM/SLNB) with immediate completion lymphadenectomy if in-transit metastases in an extremity involves the use of iso-
the sentinel node was positive for metastasis. The groups were lated limb perfusion (ILP). This technique was introduced in
comparable in regard to age, gender distribution, and location, 1958 and holds the advantage of achieving high regional con-
thickness, and ulceration status of the lesion. Sentinel nodes were centrations of therapeutic agents while minimizing systemic
analyzed using hematoxylin-eosin stain and immunohistochem- side effects.59 The arterial supply and venous drainage are
istry. Wound complications at the primary site were comparable, isolated, and an oxygenated extracorporeal circuit is used to
although surgical morbidity was significantly greater when the circulate chemotherapeutic agents for 1 to 1.5 hours. A tour-
SLNB was followed by completion lymphadenectomy.51 A niquet is also often used. Melphalan is typically used as a
follow-up analysis presented at the American Society of Clinical chemotherapeutic agent, and the limb temperature is typi-
Oncology in 2005 demonstrated a significant difference in 5-year cally elevated to 39 to 40ºC.60 In patients who have clinically
disease-free survival (73% in WEO versus 78% in LM/SLNB); positive nodes, therapeutic lymph node dissection is per-
however, there was no difference in 5-year overall survival (86% formed at the same setting just prior to limb perfusion. The
in WEO versus 87% in LM/SLNB).52 Although there were sug- response to isolated limb perfusion can be dramatic. Com-
gestions based on the data that a survival benefit might be gained plete response with melphalan alone is 54%,61 which is
by LM/SLNB followed by completion lymph node dissection in increased to 91% with the addition of tumor necrosis factor.62
the event of a positive node, their statistical analysis has been However, these responses are often short-lived, with recur-
criticized.53 The role of lymphadenectomy will be addressed fur- rence rates of 50% within 1 to 1.5 years after limb perfu-
ther in the second Multicenter Selective Lymphadenectomy sion.63 Overall 5-year survival after ILP was 32% in a recent
Trial (MSLT-II), which is designed to evaluate the therapeutic series.63 Recurrences following ILP may be treated with
value of completion lymph node dissection versus SLNB alone excision, although repeat ILP has also been used with success
in patients who have metastasis in the sentinel node.52 in patients with extensive disease.64
An important factor in considering a therapeutic lymph node ILP can be very effective for in-transit metastases; however,
dissection following a positive SLNB is the likelihood of finding it is time and resource consuming and can be quite toxic. One
03/09
alternative to this approach involves the use of normothermic rate of 29% following pulmonary metastasectomy and a median
isolated limb infusion (ILI),65,66 a technique in which the artery survival of 40 months compared with 13 months in those who
and vein are isolated percutaneously and the limb is isolated were not eligible for resection.76 Similar results have been dem-
using a tourniquet. Melphalan is typically used as a chemo- onstrated in metastasectomy for metastatic lesions to the gas-
therapeutic agent. One major difference between the two (ILP trointestinal tract, with a series reporting a median survival of
versus ILI) is that in ILI, blood is circulated at a much lower 47.5 months in patients in whom a complete resection was
rate in the isolated extremity and only for 30 minutes. In addi- achieved.77 This was in sharp contrast to the median survival
tion, a pump oxygenator is not used in ILI; thus, the isolated of 4 weeks in those patients in whom complete resection could
extremity becomes hypoxic, leading to acidosis. The largest not be achieved.77 The aforementioned factors are of critical
series of ILI reports the use of this approach with melphalan importance in deciding whether to perform metastasectomy,
and dactinomycin chemotherapy in 135 patients.65 In this and patient selection is key. To enhance patient selection for
series, there was an overall response rate of 85%, with 41% curative procedures, some recommend treating patients with a
achieving a complete response and 42% achieving a partial single-site asymptomatic metastasis with 2 to 3 months of che-
response.65 No randomized controlled trials compare ILP with motherapy prior to resection to assess for disease stabilization
ILI, although the results from a single-institution prospective or the development of additional metastases.58 If there is a
database were recently published, yielding a higher overall and response to treatment or disease stabilization with no evidence
complete response rate for ILP versus ILI (88% versus 44% of further metastases, these authors proceed with resection.
and 57% versus 30%, respectively).66 Preoperative imaging is a critical part of the evaluation of a
potential metastasectomy patient and may include the use of
Adjuvant Therapy 18-fluorodeoxyglucose positron emission tomography (FDG-
Radiotherapy Radiotherapy has been used with some PET) to more accurately detect occult metastatic disease.
success in high-risk lesions following therapeutic lymph node A recent comparison of FDG-PET with conventional imaging
dissection, demonstrating a decrease in local recurrence67 and in patients with stage IV melanoma demonstrated a sensitivity
a modest survival benefit68 compared with historical controls. and a specificity of 76% and 87%, respectively, for conventional
This modality is typically employed in stage III disease in the imaging compared with 79% and 87%, respectively, for FDG-
setting of poor prognostic pathologic factors, including posi- PET.78 Sensitivity and specificity for combined conventional
tive surgical margins, multiple positive nodes, extracapsular imaging with FDG-PET were 88% and 91%, respectively.78 As
spread, or vascular or perineural involvement.69 with any other modality, it is important to understand the limits
Chemotherapy Adjuvant therapy with interferon alfa 2b is of the technology to apply its use properly.
associated with improvement in disease-free survival but is also Another important indication for metastasectomy is pallia-
associated with significant toxicity. In addition, it is unclear tion as the vast majority of patients with stage IV melanoma
whether adjuvant therapy with interferon alfa 2b enhances will not be candidates for metastasectomy for curative intent.
overall survival. Although initial studies (Eastern Cooperative The goal of a palliative procedure is to control identifiable
Oncology Group trial 1684) demonstrated prolongation of symptoms caused by an advanced malignancy while minimiz-
relapse-free interval and overall survival with 1 year of high- ing morbidity.58 Classic examples of palliative metastasec-
dose interferon alfa 2b,70 a subsequent meta-analysis showed no tomy include resection of bleeding small bowel metastases,
overall survival benefit.71 Furthermore, nearly all patients expe- resection of ulcerated subcutaneous metastases, and resection
rience adverse effects with interferon therapy, including fatigue, of symptomatic brain metastases. A thorough discussion
neutropenia, headache, fever, and chills.68 Interferon alfa 2b is should be held between the surgeon, the patient, and the
currently approved by the Food and Drug Administration for family to address the goals and expected outcomes and the
adjuvant treatment of stage IIB and stage III melanoma. potential morbidity of the procedure.
Melanoma vaccines Several experimental melanoma Chemotherapy Response rates following adjuvant che-
vaccines are currently being investigated for use in advanced- motherapy in the treatment of malignant melanoma have been
stage melanoma and use a variety of strategies to present mel- somewhat disappointing. Dacarbazine (DTIC) is the agent
anoma antigens to host immune cells in an immunostimulatory with the longest track record in the treatment of melanoma and
context.72–74 Despite initial optimism, a recent review of the offers marginal therapeutic benefit with moderate side effects.79
experience at the National Cancer Institute demonstrated a Various combination regimens have been used and include
response rate of only 2.6% for cancer vaccines,75 which was BOLD (bleomycin, Oncovin [vincristine], lomustine [CCNU],
comparable to the results obtained by others. The authors con- and DTIC), CVT (cisplatin, vincristine, and DTIC), and
cluded that this approach may still be viable but will require CBDT (cisplatin, BCNU [carmustine], DTIC, and tamoxi-
profound changes to improve the efficacy of these vaccines. fen) with response rates ranging from 9 to 55%.79 However,
the responses are not durable. More recently, temozolamide
Treatment of Stage IV Melanoma (an oral alkylating agent) was studied in stage IV melanoma
Metastasectomy A large body of literature supports patients, with a modest prolongation of survival compared with
resection of metastases from melanoma, with the following fac- DTIC and an acceptable side-effect profile.80
tors cited as predictive of improved survival: stage of the initial Melanoma vaccines Several experimental melanoma
disease, disease-free interval after treatment of the primary vaccines have been used in patients with stage IV melanoma
melanoma, initial site of metastasis (e.g., visceral versus subcu- in the context of clinical trials,72–74 although the results have
taneous), extent of metastatic disease (single versus multiple not been very encouraging. An extensive review of the use of
sites), and ability to achieve complete resection.58 This approach vaccines in advanced cancer suggests that significant improve-
can be successful as a recent series reported a 5-year survival ments must be made to increase vaccine efficacy.75
03/09
Immunotherapy Perhaps the most promising area of pillow and with the hip and knee slightly flexed. A Foley
investigation for the treatment of advanced melanoma is immu- catheter is inserted, and the patient is prepared and draped.
notherapy. Immunotherapy has a wide range of definitions but The femoral artery, anterior superior iliac spine, pubic
is generally considered a form of treatment based on the con- tubercle, and femoral triangle apex are marked, and a diago-
cept of modulating the immune system to achieve a therapeutic nally oriented skin incision is planned. The incision courses
goal.81 Multiple modalities can be considered immunotherapy, from medial to the anterosuperior iliac spine down to the apex
including the use of monoclonal antibodies and interferon- of the femoral triangle. An “S”-shaped incision is used to avoid
based therapy, although the focus of this review highlights the crossing the thigh flexion crease at a right angle. This incision
use of interleukin-2 (IL-2) and adoptive cell transfer. interferes least with the musculocutaneous and cutaneous vas-
High-dose IL-2 has been used to treat melanoma, with response cular territories of the skin, minimizes ischemia to the skin
rates in early series ranging from 15 to 20%, with complete flaps, and avoids a flexion contracture. Flaps are raised to iden-
regression in about half of these patients.82 Moreover, in those tify the medial border of the sartorius muscle, the lateral border
who achieve a complete response, the result is often durable.83 of the adductor longus muscle, and the external oblique fascia
However, this regimen is noted to be quite toxic. on the lower abdominal wall. Fat and nodal tissue are dissected
Another modality under active investigation involves the use off the external oblique aponeurosis, spermatic cord, and
of adoptive immunotherapy. Adoptive immunotherapy involves inguinal ligament and are reflected inferiorly [see Figure 5]. The
the use of activated cytotoxic T lymphocytes (CTLs) that are fat and lymph nodes are then dissected from the femoral tri-
generated against particular tumor types. This approach can angle starting medially at the lateral edge of the adductor
help break immunologic tolerance by allowing the selection of longus and proceeding laterally [see Figure 6 and Figure 7 ]. The
tumor-specific T lymphocytes that are capable of generating a femoral vessels are left undisturbed. At the fossa ovalis, the
strong immunologic response. These can be generated using saphenous vein is ligated and divided [see Figure 8]. It is also
specific tumor-associated antigens or by culture with tumor ligated and divided as it exits the femoral triangle distally. The
cells. The addition of nonmyeloablative lymphodepleting che- specimen is then dissected free from the femoral nerve, usually
motherapy prior to autologous transfer of tumor-specific CTLs sacrificing branches of the lateral femoral cutaneous nerve,
in conjunction with IL-2 administration results in rapid clonal thereby resulting in numbness of the anterolateral thigh. The
expansion of tumor-specific T lymphocytes in vivo, which is Cloquet lymph nodes are located medial to the femoral vein
associated with a significant clinical response.84 More recently,
transfer of a T cell receptor gene from a patient with a significant
antitumor response conferred impressive T cell responses.85
Despite some advances in therapy, the overall survival for MEDIAL DISSECTION Spermatic
patients with stage IV melanoma has not improved over the Inguinal Cord
past 20 years. Overall 5-year survival is dismal at less than Ligament
5%, with a median survival of only 7.5 months. Hope likely
lies in treatment of micrometastatic disease via targeted che- Pectineal Muscle
motherapy and immunotherapy.
Long Adductor
Lymphatics Muscle
Conclusions
Skin Fascia
The clinical assessment and management of skin lesions Specimen
are challenging, and surgeons play a pivotal role in treatment
of these lesions. Furthermore, the prevalence of malignant
lesions of the skin has increased dramatically over the past
several years, with nearly 1.2 million cases of nonmelanoma
skin cancer diagnosed per year1 and close to 80,000 cases of
melanoma diagnosed per year.2 Thus, it is critical for sur-
geons to have an astute awareness of these lesions, their
workup, and their management.
Specific Procedures
superficial and deep groin dissections
The inguinal nodes drain the anterior and inferior abdom-
inal wall, perineum, genitalia, hips, buttocks, and thighs. Distal Portion of
A superficial groin dissection removes the inguinal nodes, Great Saphenous
whereas a deep groin dissection additionally incorporates the Vein Ligated
iliac and obturator nodes. Palpable nodes can be marked on
the patient before operation.
Superficial Groin Dissection

The patient is placed in a supine position on the operating Figure 5 In a superficial groin dissection, the incision is
table, with the hip slightly abducted and supported by a deepened to include the deep muscular fascia.
03/09
Inguinal under the inguinal ligament and resected. Following removal

Ligament Lymphatics Continue under of the specimen, these nodes are dissected out and submitted
Inguinal Ligament Medial to
as a separate specimen. If the Cloquet nodes contain mela-
Specimen Femoral Vein
noma, the risk for iliac nodes with melanoma is high, and a
Retracted
deep groin dissection should be performed.
Great Saphenous
Vein Stump Deep Groin Dissection
Pectineal The iliac region is easily approached through a separate inci-
Muscle sion in the external oblique fascia, parallel to and above the
inguinal ligament. The retroperitoneal space is further exposed
by separating the internal oblique abdominal muscle fibers and
incising the transversus abdominis and fascia transversalis. The
deep circumflex iliac vessels are ligated, and blunt finger dis-
section separates the peritoneum from the retroperitoneal fat
and nodes. Alternatively, the inguinal ligament may be divided
to allow access to the retroperitoneal space, although recon-
struction of the inguinal ligament can be challenging.
Retractors are inserted to widen the retroperitoneal space,
and the peritoneum and the abdominal viscera are retracted
superomedially. The chain of lymph nodes, areolar tissue,
Femoral Sheath and adventitial tissues along the external iliac vessels is dis-
Being Entered sected; the dissection proceeds proximally to the origins of
the internal iliac vessels (avoiding the ureter) and incorpo-
Fascia rates the nodes overlying the obturator foramen by removing
the internal obturator fascia but carefully avoiding injury to
the obturator nerve. The lymph node–bearing specimen is
then removed as a unit, oriented, and labeled appropriately
with sutures. The space medial to the femoral vein under the
inguinal ligament is obliterated to prevent a hernia. The sar-
Figure 6 As the superficial groin dissection proceeds, the torius muscle is detached from the anterior superior iliac
investing fascia overlying the femoral nerve and vessels is spine and the midportion of the inguinal ligament to cover
removed. the femoral vessels. The skin and the subcutaneous tissues
are then closed in layers over a soft suction drain.
Specific details regarding SLNB are described in a separate
ACS chapter [see III:6 Lymphatic Mapping and Sentinel
LATERAL DISSECTION Lymph Node Biopsy].
Nodal Tissue Financial Disclosures: None Reported.
Fascia
Fat and
Lymphatics
Great
Saphenous
Vein Femoral
Sheath
Femoral
Branch of Vein
Femoral Femoral
Nerve Artery
Sartorius Muscle
Figure 7 The superficial groin dissection is continued at the

same level on the lateral side. Figure 8 The great saphenous vein is ligated and divided.
03/09
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66. Beasley GM, Petersen RP, Yoo J, et al. Iso- tion with irradiated, autologous melanoma with metastatic melanoma: long-term survival
lated limb infustion for in-transit malignant cells engineered to secrete granulocyte- update. Cancer J Sci Am 2000;6 Suppl 1:11–4.
melanoma of the extremity: a well-tolerated macrophage colony-stimulating factor by ade- 83. Dudley ME, Wunderlich J, Nishimura MI,
but less effective alternative to hyperthermic noviral-mediated gene transfer augments et al. Adoptive transfer of cloned melanoma-
isolated limb perfusion. Ann Surg Oncol 2008; antitumor immunity in patients with metastatic reactive T lymphocytes for the treatment of
15:2195. melanoma. J Clin Oncol 2003;21:3343–50. patients with metastatic melanoma. J Immu-
67. Stevens G, Thompson JF, Firth I, et al. 75. Rosenberg SA, Yang JC, Restifo NP. Cancer nother 2001;24:363.
Locally advanced melanoma: results of post- immunotherapy: moving beyond current vac- 84. Dudley ME, Wunderlich JR, Robbins PF,
operative hypofractionated radiation therapy. cines. Nat Med 2004;10:909–15. et al. Cancer regression and autoimmunity
Cancer 2000;88:88–94. 76. Neuman HB, Patel A, Hanlon C, et al. Stage in patients after clonal repopulation with
68. Ang KK, Byers RM, Peters LJ, et al. Regional IV melanoma and pulmonary metastases: fac- antitumor lymphocytes. Science 2002;
radiotherapy as adjuvant treatment for head tors predictive of survivial. Ann Surg Oncol 298:850–4.
and neck malignant melanoma. Arch Otolar- 2007;14:2847–53. 85. Hughes MS, Lu YYL, Dudley ME, et al.
yngol Head Neck Surg 1990;116:169–72. 77. Panagiotou I, Brountzos EN, Bafaloukos D, Transfer of a TCR gene derived from a
69. Morris KT, Marquez CM, Holland JM, Vetto et al. Malignant melanoma metastatic to the patient with marked antitumor response con-
JT. Prevention of local recurrence after surgi- gastrointestinal tract. Melanoma Res 2002; veys highly active T cell effector functions.
cal debulking of nodal and subcutaneous 12:169–73. Hum Gene Ther 2005;16:457–72.
03/09
3 BREAST, SKIN, AND SOFT TISSUE 5 BREAST PROCEDURES — 1
5 BREAST PROCEDURES
Angela Gucwa, MD, J. Garrett Harper, MD, and D. Scott Lind, MD
The procedures used to diagnose, stage, and treat breast dis- thus can potentially reduce the number of unnecessary biop-
ease are rapidly becoming less invasive and more cosmetically sies done for simple cysts or fibroglandular tissue presenting
satisfying while remaining oncologically sound. In particular, as a palpable nodularity. Whole-breast ultrasonography is not
percutaneous core biopsy has largely replaced excisional an effective screening tool and therefore should not be a
breast biopsy for both palpable and nonpalpable breast lesions substitute for annual mammography. The American College
and has proved to be an equally accurate, less invasive, and of Surgeons (ACS) and various surgical subspecialty organi-
less costly means of pathologic diagnosis.1 Moreover, in clin- zations offer a multitude of courses, at varying skill levels,
ically appropriate patients, sentinel lymph node biopsy geared toward training general surgeons in the use of breast
(SLNB) has proved to be an accurate method of staging the ultrasonography.
axilla that reduces the incidence of many of the complications
associated with traditional axillary node dissection.2 Further- techniqu e
more, breast conservation has largely supplanted mastectomy Most real-time ultrasound imaging is performed with hand-
for definitive surgical treatment of breast cancer; randomized held probes generating frequencies between 7.5 and 12 MHz.
trials continue to demonstrate equivalent survival rates for the The procedure is conducted with the patient supine, a pillow
two therapies.3 Even in those cases where mastectomy is behind the shoulder, and the ipsilateral arm extended over the
either required or preferred, advances in reconstructive tech- head for maximal spreading of the breast. Sonographic trans-
niques have been made that yield significantly improved out- mission gel is applied between the transducer and the skin to
comes after breast reconstruction.4 Finally, in an effort to reduce air artifacts, and the transducer is pressed slightly
eliminate the need for open surgical treatment of breast against the skin to improve image quality. The selected breast
cancer, various percutaneous extirpative and ablative local area is imaged from the nipple outward in a radial pattern.
therapies have been developed and are being evaluated for All lesions should be sonographically characterized with
potential use in managing breast cancer in carefully selected respect to margins, effect on adjacent tissue, internal echo
patients.5 pattern, compressibility, height to width ratio, and presence
A more minimally invasive approach to breast disease will of shadowing versus posterior enhancement. Classically, sim-
depend to a substantial extent on the availability of accurate ple cysts tend to be oval or lobulated, anechoic, and sharply
and efficient imaging modalities. Adeptness with such modal- demarginated; they typically demonstrate posterior enhance-
ities is rapidly becoming an essential part of the general sur- ment. Benign solid lesions tend to be well circumscribed,
geon’s skill set. In this chapter, we describe selected standard, hypoechoic, and wider than they are tall; they show homoge-
novel, and investigational procedures employed in the diagno- neous internal echoes and edge shadowing. Carcinomas are
sis and management of breast disease. The application of these also hypoechoic masses, but they cross tissue planes and there-
procedures is a dynamic process that is shaped both by tech- fore tend to be taller than they are wide, with irregular bor-
nological advances and by physicians’ evolving understanding ders; in addition, they can demonstrate heterogeneous interior
of the biology of breast diseases. patterns and broad acoustic shadowing [see Figure 1]. A lesion
that has a single indeterminate characteristic on ultrasonogra-
phy or that is clinically suspicious despite appearing benign on
Breast Ultrasonography
ultrasonography is an indication for core or open biopsy.
Breast ultrasonography can be useful for evaluating palpable Lesions should be characterized in at least two orthogonal
breast masses or mammographically indeterminate lesions; for planes, and the image should be saved for future reference.
carrying out postoperative and oncologic follow-up; for guid-
ing aspiration and biopsy of lesions; and for facilitating intra-
operative tumor localization, margin assessment, placement of Ductal Lavage
catheters for partial-breast irradiation, and investigational The majority of breast cancers originate from the epithe-
tumor-ablating techniques. lium of the mammary ducts. Originally developed to increase
In the office, breast ultrasonography has become a useful the cellular yield after nipple aspiration failed to obtain ade-
adjunct to the clinical breast examination, particularly in quate sampling, ductal lavage is a method of recovering breast
patients with radiographically dense mammograms. It defines duct epithelial cells for cytologic analysis via a microcatheter
breast lesions more clearly than physical examination does and that is inserted into the duct.6 Potential applications include
DOI 10.2310/7800.S03C05
12/09
a b c
Figure 1 Breast ultrasonography. Shown are (a) a simple cyst that has smooth margins, is anechoic, and shows posterior
enhancement; (b) a fibroadenoma that has smooth margins, is hypoechoic, and shows posterior shadowing; and (c) a mam-
mary carcinoma that has irregular borders, is hypoechoic, and shows irregular posterior shadowing.
identifying high-risk women, predicting risk with molecular techniqu e

markers, monitoring the effectiveness of chemopreventive Ductoscopy can be performed either in the office or in the
agents, and delivering drugs directly into the ducts. At pres- operating room with minimal discomfort. Before the proce-
ent, however, ductal lavage remains investigational, and its dure, a nipple block is usually performed with topical lido-
predictive value and clinical utility await further definition.7 caine cream, supplemented (if necessary) by intradermal
t e chn i q u e injection of 1% lidocaine around the nipple-areola complex
or intraductal instillation of lidocaine (or both). The breast is
The breast duct epithelium may be sampled by means of massaged to promote expression of nipple aspirate fluid,
either nipple fluid aspiration or ductal lavage. For the aspira- which facilitates identification of a ductal orifice. The duct is
tion of nipple fluid, a topical anesthetic is first applied to the then gently dilated, and the ductoscope is advanced with the
nipple, followed by a mild scrub with a dekeratinizing gel. Suc- help of insufflation under direct visualization. Most ducts
tion is then applied to the nipple while the breast is gently with pathologic discharge can readily be identified and dilated
massaged. Aspirated fluid is sent for analysis. In ductal lavage, sufficiently to allow passage of the ductoscope.12 Under direct
the breast and nipple are similarly prepared. The nipple duct visualization, the ductoscope is advanced using saline insuf-
orifice that yields fluid spontaneously or as a result of suction flation. An outer air channel on the fiberscope permits instil-
is cannulated, the duct is irrigated with saline, and the effluent lation and collection of saline solution so that cells can be
is collected for cytologic analysis. Cannulation of the duct is retrieved for ductal lavage.13 Intraductal lesions can be percu-
possible in the majority of women. Both nipple fluid aspiration taneously localized under direct endoscopic visualization for
and ductal lavage are generally well tolerated. The former is subsequent biopsy; alternatively, they may be amenable to
simpler and less expensive, but the latter retrieves more cells.8 endoscopic cytologic brushing or to the newly described tech-
nique of intraductal breast biopsy.12
Ductoscopy The procedure is usually well tolerated. It should be noted
that duct excision is still regarded as standard practice for
Advances in endoscopic technology have allowed for visu-
pathologic discharge, regardless of endoscopic findings.
alization and biopsy of the mammary ducts, including those in
more peripheral locations.9 Mammary ductoscopy is a proce-
dure in which a 0.9 mm microendoscope is employed to visu-
alize the lining of the ductal system directly. Previous studies Breast Biopsy
have revealed ductoscopy to be safe for use in three main Cytologic or tissue diagnosis of a palpable breast mass may
areas: (1) evaluation of patients with pathologic nipple be obtained by means of fine-needle aspiration (FNA) biopsy,
discharge,10 (2) evaluation of high-risk patients, and (3) evalu- core-needle biopsy (CNB), or open incisional or excisional
ation of breast cancer patients to determine the extent of biopsy. Currently, most solid lesions are initially diagnosed by
intraductal disease and perhaps reduce the rate of positive means of CNB, which is less invasive, less costly, and more
margins. This is especially important in those patients with in expeditious than open biopsy while achieving comparable
situ disease and benign radiographic findings.11 Current accuracy. In select circumstances, however, FNA biopsy and
research is aimed at the use of ductoscopy-directed biopsy and open biopsy may remain suitable options. All minimally inva-
ablation techniques. Perforation of the mammary duct is the sive biopsy techniques are facilitated when guided by imaging
most commonly reported complication; however, this appears modalities; such guidance enables the physician to perform a
to have minimal sequela. At present, this investigational tech- more directed biopsy that targets the lesion precisely while
nology is available at only a few centers, and further study will avoiding benign-appearing tissue, necrotic tissue, and adjacent
be required to determine its precise role in the evaluation and structures (e.g., the chest wall, skin, and axillary vessels).
management of breast disease. Therefore, even when a lesion is palpable, ultrasound-directed
12/09
biopsy is preferable to blind biopsy (although not absolutely Interpretation of Results

necessary) and is recommended if the surgeon has a suitable Accurate interpretation of FNA requires substantial experi-
ultrasound device in the office. ence on the part of both the operator and the cytopathologist;
The choice of a specific biopsy technique should be indi- only in a few select centers with expert breast cytopathologists
vidualized on the basis of the clinical and radiographic features has it remained the diagnostic procedure of choice for solid
of the lesion, the experience of the clinician, and the patient’s breast masses. Consequently, one must exercise considerable
condition and preference. caution about using FNA biopsy rather than CNB as the sole
fin e - n e e dl e a sp i r a t i o n b i o p sy means of confirming a cancer diagnosis before the initiation of
definitive operative management or neoadjuvant therapy. FNA
FNA biopsy permits the sampling of cells from the breast biopsy is unable to discriminate carcinoma in situ from inva-
or the axillary region for cytologic analysis. It is particularly sive carcinoma and therefore is incapable of establishing
useful for sampling a clinically or sonographically suspicious whether axillary node staging is needed. Furthermore, because
axillary node and for evaluating cyst fluid that is bloody or of the smaller quantity of tissue extracted, FNA biopsy is a
that comes from an incompletely collapsed or recurrent cyst. less reliable means of assessing receptor status than CNB is.
In patients receiving anticoagulants, FNA biopsy is a reason- Finally, in 1 to 2% of cases, FNA biopsy may yield false
able alternative to CNB for evaluation of a solid lesion in that positive results,14 potentially leading to an unnecessary cancer
there is less potential for hemorrhage if anticoagulation cannot operation. For these reasons, it is recommended that malig-
be discontinued. Discrete masses discovered on physical exam- nancies identified by FNA biopsy be confirmed by means of
ination may be either cystic or solid. A lesion that is shown CNB or open biopsy (preferably the former) before definitive
by ultrasonography to be a simple cyst need not undergo FNA therapy is provided.
biopsy unless it is symptomatic. Cytologic analysis that is diagnostic of a specific benign
lesion (e.g., a fibroadenoma) may generally be relied on if it
Technique
is in concordance with the clinical features of the lesion. How-
The skin of the breast or axilla is prepared, and a local ever, a negative result from FNA biopsy does not exclude
anesthetic is injected superficially via a 25-gauge needle. cancer: this procedure fails to diagnose as many as 40% of
Although smaller needles may be used, a 21-gauge needle is breast malignancies.14 Cellular atypia, pathologic discordance,
optimal for FNA biopsy because it can be effectively used or a nondiagnostic FNA is an indication for tissue diagnosis.
both for aspiration of potentially viscous fluid and for procure-
ment of sufficient cellular material from solid masses. To gen-
erate adequate suction, a 10 mL or larger syringe should be core-needle biop s y
used. As noted (see above), FNA biopsy ideally is performed As noted (see above), CNB is the diagnostic procedure of
under ultrasonographic guidance. If such guidance is unavail- choice for breast lesions. Like FNA biopsy, it is easily per-
able, the lesion is held steady between the thumb and the formed in an outpatient setting. Unlike FNA biopsy, CNB
index finger of the nondominant hand. Before the needle removes a narrow cylinder of tissue that is submitted for patho-
enters the skin, 1 mL of air is introduced into the biopsy logic rather than cytologic analysis. Whenever feasible, CNB
syringe. Then, without the application of suction, the needle of both palpable and nonpalpable lesions is performed under
is advanced into the lesion. Once the needle is in place, strong ultrasonographic guidance, which permits real-time documen-
suction is applied. tation of the needle’s position within the lesion. For lesions not
If the lesion is cystic, all fluid is aspirated, at which point visualized on ultrasonography or for suspicious microcalcifica-
the mass should disappear. Ultrasonography can confirm the tions, stereotactic guidance may be employed instead. A pre-
complete collapse of a cyst or help direct the needle to an operative diagnosis of malignancy obtained via CNB enables
undrained portion of the cyst. The fluid need not be sent for the surgeon to perform a single-stage operative procedure. It
analysis unless it is bloody or is associated with a residual may also help lower the positive margin rate for patients under-
palpable mass or an incompletely collapsed cyst as seen on going breast-conserving therapy (BCT), thereby reducing the
ultrasonography. If the fluid is to be sent for analysis, it is need for reexcision and improving the cosmetic outcome.15
injected directly into the pathologic preservative. The patient Various automatic, rotational, and vacuum-assisted devices
is reexamined 4 to 8 weeks after successful aspiration. If the may be employed to perform CNB; in what follows, we briefly
same cyst has recurred, aspiration should be repeated and the discuss these devices [see Technique, below]. When CNB is per-
new aspirate sent for cytologic analysis. formed with a 14-gauge needle, as is the case with Tru-Cut
If the lesion is solid, the needle is moved back and forth (Cardinal Health, Dublin, Ohio) devices and spring-loaded
within the lesion along a 5 to 10 mm tract until tissue is guns, up to 30% pathologic upgrading may be seen on subse-
visualized in the hub of the needle. (This oscillation of the quent surgical excision.1 When CNB is done with a larger needle
needle along the same tract is the most effective way of obtain- (8 to 11 gauge), as is the case with image-guided vacuum-
ing a cellular, diagnostic specimen.) Suction is released while assisted and rotational devices, a greater volume of tissue is
the needle is still within the lesion, and the needle is then delivered; consequently, less pathologic upgrading is seen.16
withdrawn. The contents of the needle are expelled onto pre- With the vacuum-assisted core biopsy (VACB) devices currently
pared glass slides, spread into a thin smear, and fixed accord- available, it is possible to remove all radiographic evidence of the
ing to the preferences of the cytology laboratory. The syringe lesion. It is therefore common practice with all core biopsies to
may be rinsed so that a cellblock can be prepared for further place a titanium clip or another surrogate marker at the biopsy
analysis. The lesion should be sampled twice to ensure that a site to facilitate future localization procedures. In addition, a clip
sufficiently cellular sample has been obtained. should be placed at the biopsy site if the patient has a larger
12/09
cancer for which neoadjuvant chemotherapy is required; some Semiautomated gun biopsy When a spring-loaded semiauto-
such lesions exhibit a complete clinical response to chemother- matic biopsy gun is used, the tip of the needle should abut
apy and thus are no longer radiographically visible at the time of the lesion in such a way that the biopsy trough will be in the
definitive operative treatment. Two-view postbiopsy mammog- lesion after the device is fired. Ideally, the repeat passes should
raphy should be performed to confirm accurate placement of the sample different portions of the lesion and avoid any necrotic
clip and adequate sampling of the lesion at the time of biopsy. areas that have been visualized.
Vacuum-assisted core biopsy Vacuum-assisted rotational cut-
Technique ting devices employ a 7- to 11-gauge probe with a distal sam-
pling trough and an inner rotating cutter. The sampling trough
Palpation-guided biopsy In this setting, a manual Tru- can be placed either in the center of the lesion or directly under
Cut–type device or, more commonly, a spring-loaded semi- it. The probe is attached to a vacuum system, which draws the
automatic biopsy gun is used to obtain the specimen. The target tissue into the trough. Once the tissue has been drawn
skin is prepared, and a local anesthetic is infiltrated superfi- into the trough, the inner rotating cutter is advanced and cuts
cially via a 25-gauge needle. A nick is made in the skin with a core from it. The tissue core is then delivered by the vacuum
a No. 11 blade to permit easy entry of the biopsy needle (usu- system through the barrel of the probe and into a proximal
ally a 14-gauge needle). As with FNA biopsy (see above), the collection chamber. The probe can be rotated up to 360° and
lesion is held steady in the nondominant hand while the can retrieve multiple samples through a single insertion in the
biopsy needle is advanced into the periphery of the lesion. skin. The larger tissue volumes obtained with these rotational
Next, the needle is manually advanced through the center of VACB devices have reduced the incidence of atypical ductal
the lesion (if a manual device is used), or the gun is fired (if hyperplasia or ductal carcinoma in situ (DCIS) upgrades on
a spring-loaded device is used). Finally, the needle is with- subsequent excisional biopsies.5
drawn to retrieve the core. Four to five cores, each from a Cryoassisted core biopsy In a cryobiopsy, a thin (19-gauge)
separate pass, should be obtained to ensure that the lesion is solid needle is placed in the middle of the targeted tissue. The
not undersampled. Pressure is applied over the lesion and the tip is then cooled to approximately 10°C, a temperature that
biopsy tract for 10 to 15 minutes to ensure adequate hemo- freezes the tissue to the needle but does not cause tissue ne-
stasis. The nick in the skin is closed with an adhesive strip crosis. An outer rotating cutting cannula (10 gauge) is then
(e.g., Steri-Strip, 3M, St. Paul, Minnesota). advanced over the inner localizing needle. The device is re-
moved from the breast, and the single specimen is removed.
Ultrasound-guided biopsy This technique may be As with the semiautomatic biopsy gun, multiple passes into
employed for both palpable and nonpalpable lesions. The the breast are still required. However, the local anesthetic ef-
lesion that is to undergo biopsy is centered on the screen of fect of the cooling process, the ability of the device to spear
the ultrasound device. A local anesthetic is injected superfi- and stabilize a lesion, and the absence of a firing gun–type ac-
cially, first along the anticipated biopsy tract and then both tion make cryobiopsy advantageous, particularly for a mobile
anterior and posterior to the lesion; this latter maneuver helps lesion that lies close to the skin or the chest wall.
ensure that there is a safe distance between the lesion and the
skin or the chest wall. A nick is made in the skin with a No. Stereotactic-guided biopsy Lesions that are visible on
11 blade. The biopsy needle is then inserted through the skin, mammography—including small solid lesions, asymmetrical
with care taken to keep it in a plane parallel to the footplate densities, and suspicious groups of microcalcifications—can
of the ultrasound probe as it passes through the breast tissue. often be targeted and subjected to core biopsy under
The biopsy itself can be either performed in a freehand stereotactic guidance.17 Stereotaxy refers to the use of three-
manner or directed with a needle guide attached to the probe. dimensional coordinates to localize and identify the lesion
The ideal final positions of the tip and shaft vary, depending and determine the precise positioning of the tissue to be sam-
on the particular biopsy device selected for the procedure [see pled.18 This outpatient procedure commonly makes use of a
Figure 2]. Regardless of which device is used, the tip and shaft mounted VACB gun, similar to the handheld VACB device
of the needle should be visualized throughout the entire previously described (see above). Stereotactic biopsy is appro-
approach to and biopsy of the lesion. Prefire and postfire priate for lesions that are clearly visible on digital images and
images should be obtained that show the needle in proximity identifiable on stereotactic projections. Lesions that lie close
to and within the lesion, respectively. Four to five good cores to the chest wall or in the subareolar region may not be ame-
are required for adequate sampling. Once the biopsy is com- nable to stereotactic biopsy and are often best approached via
plete, pressure is applied over the lesion and the biopsy tract, open biopsy with needle localization (see below). Likewise,
and a Steri-Strip is placed. To facilitate closure of larger entry lesions in thinly compressible breasts may not be amenable to
sites, a single subcuticular stitch may be used. stereotactic biopsy, because firing of the needle may result in
Brisk bleeding may occur during and immediately after the a through-and-through injury to the breast. Certain stereo-
procedure, but it usually can be controlled by the application tactic systems may not be suitable for patients who are unable
of direct pressure. Patients are restricted from engaging in to lie prone or are morbidly obese. It should be kept in mind
strenuous activity for 24 hours after biopsy. Bruising may that stereotactic biopsy is a diagnostic procedure and is not
result, but it typically resolves within days. Other potential intended for therapeutic purposes. On the whole, it is safe,
complications include hematoma, fat necrosis, a palpable and the complication rate is acceptably low.
lump, and infection; however, such events are uncommon. Depending on the system being employed, the patient
Most patients receiving oral anticoagulants can be switched either lies prone on the stereotactic table or sits upright. With
to a subcutaneous alternative that can be stopped on the the breast compressed craniocaudally or mediolaterally, ste-
morning of the procedure. reotactic digital imaging is then performed to visualize the
12/09
a Semiautomatic Biopsy Gun stereotactic imaging. The biopsy device is then removed, the
Postfire edges of the skin incision are approximated with Steri-Strips,
Prefire and a compressive bandage is applied. Typically, 1 g of tissue
(equivalent to approximately 10 to 12 samples with an 11-gauge
probe) is sufficient for diagnosis. Once the procedure is over
and the breast has been released from compression, a two-view
mammography should be obtained to verify that the clip was
accurately placed and to document that the targeted lesion was
adequately sampled.
Vacuum Draws Tissue into Trough; Needle
b VACB is Rotated and Lifted for Next Specimen Magnetic resonance imaging–guided biopsy Contrast-
enhanced magnetic resonance imaging (MRI) has been found
to be a highly sensitive method for detecting breast cancer,
especially those that are nonpalpable or are unable to be
viewed using conventional radiographic methods. A stereo-
tactic method similar to the one described above has been
developed using a VACB to perform an incisional biopsy
under MRI guidance. Similarly, the patient is placed prone
and the targeted breast undergoes mediolateral compression.
c Cryobiopsy Outer Cutting Cannula Using MRI, a software program calculates the three-
Advances dimensional coordinates for the biopsy device. The VACB
gun is used outside the magnet, so MRI compatibility is not
required. After several tissue samples are removed, the result-
ing cavity is directly visualized to ensure precise tissue removal.
A metallic marking clip can be placed during the procedure
to facilitate future surgical excision if a diagnosis of cancer is
determined. The procedure is generally well tolerated. Bleed-
Initial Tip Position
ing and hematoma are the most commonly encountered com-
Figure 2 Core-needle biopsy. The positioning of the needle plications. Compared to conventional stereotactic biopsy,
shaft and tip varies with the particular biopsy device being MRI-guided biopsy has a significantly higher cost. MRI-
used. (a) For manual or semiautomatic guns that fire through guided biopsy is a promising modality but requires further
the lesion, the position of the tip before firing should be at the investigation as there are few long-term studies to determine
edge of the lesion. Keeping the needle shaft parallel to the histopathologic correlation and the false negative rate.19–21
chest wall or the skin keeps these structures from being
injured when the gun is fired or the core is manually ob-
tained. (b) For most vacuum-assisted devices, multiple cores Interpretation of Results
can be obtained through a single placement of the device
within the breast. For diagnostic biopsies performed under CNB is a highly accurate diagnostic tool: the false negative
ultrasonographic or stereotactic guidance, the needle may be rate is only 1 to 2%,22 which is comparable to that of open
placed in the center of the lesion and rotated up to 360° in wire-localized biopsy. When pathologic evaluation reveals
specified intervals. (c) For cryobiopsy, the tip of the needle fibroadenoma, microcalcifications within benign fibrocystic
should be advanced through the center of the lesion toward tissue, or other comparably benign pathologic conditions,
the far edge of the lesion before firing. This step stabilizes the there is no need for any special follow-up, and routine screen-
lesion. The outer cutting and rotating cannula is then fired ing mammography may be resumed. However, when biopsy
over the inner needle. VACB = vacuum-assisted core biopsy. of the targeted mass lesion fails to yield a mass diagnosis or a
biopsy specimen from a group of clustered calcifications is
devoid of microcalcifications on pathologic review, the discor-
dant result should be viewed with some suspicion and should
targeted lesion and calculate its location in three dimensions, be considered an indication for open biopsy. Subsequent exci-
and a suitable probe insertion site is identified. The skin is sional biopsy is also indicated when CNB reveals atypical
prepared, and a small amount of buffered 1% lidocaine with hyperplasia, radial scar, lobular carcinoma in situ (LCIS), or
epinephrine is administered. The skin at the insertion site is papilloma. The rationale is that the excisional biopsy may
punctured with a No. 11 blade, the probe is manually result in a pathologic upgrade to cancer. For example, open
advanced to the prefire site, and the position of the probe is biopsy after a CNB indicative of atypical ductal hyperplasia
confirmed by means of stereotactic imaging. The device is may reveal DCIS in approximately 40% of patients when
then fired, repeatedly cutting, rotating, and retrieving samples CNB was performed with a 14-gauge automated gun. The use
until the desired amount has been removed. Targeted removal of larger (e.g., 11-gauge) core biopsy devices has reduced the
of suspicious microcalcifications is confirmed with specimen frequency of this finding to approximately 20%,23 but it has
mammography. not eliminated the need for excision. False positive results are
Once the biopsy is complete, an inert metallic clip is deploy- rare with CNB; therefore, a diagnosis of malignancy may be
ed into the biopsy site through the probe for future localiza- believed, and a one-stage definitive surgical procedure may
tion; deployment and positioning are initially confirmed by then be planned without further biopsy.
12/09
Touch Preparation of Cores a

For an immediate but preliminary diagnosis, cytologic
touch preparation of fresh cores may be performed in the
office.24 The tissue is blotted to remove any gross blood, the
45° 45°
core is gently smeared along a glass slide, and the slide is then
immediately fixed in 70% ethanol. A layer of cells is left on
the surface of the slide for cytologic evaluation, whereas the
core is preserved for permanent evaluation. This procedure
has a diagnostic accuracy of nearly 90%. Although the false
negative rate is approximately 25%, an immediate diagnosis
is obtained in 75% of patients.18 Like all preliminary diagno- b
ses, touch preparation diagnoses should be treated with cau-
tion until the final results of histopathologic evaluation are
available.
pe rc u t a n e ou s e xcisi o n a l b i o p sy
In some instances, patient preference may dictate com-
plete removal of a mass regardless of its benign appearance.
As an alternative to open biopsy (see below), percutaneous
excision of small masses may be performed.25–27 This proce-
dure can be performed in an outpatient setting with the
c
patient under local anesthesia. Some of the devices used for
percutaneous excision are vacuum assisted and remove the
mass as multiple cores, whereas others deliver large intact
samples in a single pass [see Figure 3]. Although such
approaches clearly show promise for future surgical treat-
ment of breast cancer, these percutaneous devices are
Figure 3 Percutaneous excisional biopsy. This procedure
currently approved by the US Food and Drug Administra- may be performed by means of several different methods.
tion (FDA) only for excision of benign masses. Lesions found (a) One approach is to employ a vacuum-assisted device,
to be harboring cancer should undergo subsequent open which is placed with the trough under the lesion and the shaft
surgical reexcision. Excision of lesions that are close to the parallel to the posterior aspect of the lesion. The needle is
skin or the chest wall or are larger than 2 to 3 cm in diam- then lifted anteriorly as it is rotated first 45° clockwise, then
eter may prove technically challenging with percutaneous back to the center position (0°), and finally 45° counterclock-
techniques; open excisional biopsy [see Open Biopsy, below] wise to remove the entire lesion in multiple cores. (b) Another
may be preferable for such lesions. option is to employ an electrosurgical device such as the
Ovation (Rubicor Medical, Inc., Redwood City, California),
o p e n b iops y which circumscribes the mass with a cutting wire loop while
concurrently deploying a retractable plastic bag that encapsu-
The vast majority of open breast biopsies are now per- lates the lesion and retracts it through the skin en bloc.
formed with either local anesthesia alone or local anesthesia (c) A third option is to employ a device such as the Intact
with intravenous sedation. Breast Lesion Excision System (Intact Medical Corp., Natick,
Massachusetts), which circumscribes the mass with a
Technique radiofrequency wand and delivers it en bloc.
Various options for incisions are available [see Figure 4]. If
the pathology is unclear, the incision is placed directly over
the lesion to minimize tunneling through breast tissue. The For diagnostic biopsies, the surgeon should orient the spec-
incision should be long to ensure that the mass, together imen, and the pathologist should ink all margins. Meticulous
with a small rim of grossly normal tissue, can be excised as hemostasis should be achieved before closure to prevent the
a single specimen and be oriented so that it can be included formation of hematomas that could complicate subsequent
within any future lumpectomy or mastectomy incision should definitive oncologic resection. A cosmetic subcuticular skin
the lesion prove malignant. Resection of overlying skin is not closure is preferred.
necessary unless the lesion is extremely superficial. Histori-
cally, surgeons performing open biopsies have generally needle (wire )-localization breas t biop s y
employed curvilinear incisions placed within the resting lines Lesions that are not amenable to stereotactic core biopsy
of skin tension [see Figure 4, a and b]. Currently, however, may be excised by means of needle (wire)-localization breast
some surgeons are advocating the use of radial incisions, biopsy (NLBB). Such lesions include those that are close to
particularly for medial, lateral, and inferior lesions.15 If a pre- the chest wall or under the nipple, as well as those occurring
vious CNB proved the lesion to be benign (e.g., fibroade- in a thin breast, where firing the needle may cause it to pass
noma) but the patient still favors excision, it is acceptable to through the opposite side of the breast. Radiographic evidence
move the incision to a circumareolar position or another less of a radial scar is also an indication for NLBB: a core patho-
visible site. logic diagnosis of such a scar would ultimately necessitate
12/09
a b c
Unknown Pathology
or Cancer
Benign
Pathology
d e f
Figure 4 Open biopsy. (a) For biopsy-proven benign masses, a circumareolar incision generally provides excellent cosmesis
and a well-hidden scar. If the lesion is too far from the nipple, curvilinear incisions are traditionally employed instead. Alterna-
tively, medial, lateral, and inferior incisions may be placed in a radial fashion. (b) For lesions of unknown pathology, incisions
should be placed directly over the lesion and should be oriented so that they will be included within a subsequent mastectomy
incision if margins prove positive and mastectomy is indicated. As with benign lesions, either curvilinear or radial incisions may
be employed. Circumareolar incisions should be avoided in this setting because reexcision to provide clear margins, as is
indicated in the case of malignancy, can necessitate excision of a portion of the nipple-areola complex and can commit the
surgeon to a mastectomy. In cases where reexcision is indicated, avoidance of incisions in the so-called no man’s land may
improve cosmesis in that it allows future reconstructive efforts to include advancement of the nipple-areola complex if desired.
Various oncoplastic incisions may be employed as alternatives for (c) medial, (d ) central, or (e, f ) superior lesions.
open excision. Finally, reexcision is required when stereotactic operating room with the wire entry site indicated on them.
or ultrasound-guided CNB reveals lesions determined to be The incision is placed as directly as possible over the mass to
high risk on pathologic evaluation (e.g., atypical hyperplasia, minimize tunneling through breast tissue. With superficial
LCIS, papilloma, carcinoma, or lesion whose pathologic lesions, the wire entry site is usually close to the lesion and
status is discordant with radiographic findings). In these thus may be included in the incision. With some deeper
circumstances, wire localization may be performed on the lesions, the wire entry site is on the shortest path to the lesion
residual lesion, a clip placed at the time of CNB, or another and so may still be included in the incision. Once the incision
surrogate marker (see below). To bracket a more extensive is made, a block of tissue is excised around and along the wire
area of calcifications, multiple wires may be placed, especially in such a way as to include the lesion [see Figure 5, a and b].
if previous CNB revealed atypia or malignancy in the area. This process is easier and involves less excision of tissue if the
localizing wire has a thickened segment several centimeters in
Technique length that is placed adjacent to or within the lesion. The wire
The lesion to be excised is localized by inserting a thin itself can then be followed into breast tissue until the thick
needle and a fine wire under mammographic, ultrasono- segment is reached, at which point the excision can be
graphic, or MR guidance immediately before operation. To extended away from the wire to include the lesion in a fairly
facilitate incision placement, images should be sent to the small tissue fragment.
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a c
a b
1c
m
1c
m
1c 1c
m m 1 cm
1 cm 1 cm
1 cm
Figure 6 Hematoma ultrasound-guided excision. (a) The

b
hematoma is localized in two planes with intraoperative ultra-
sonography, and 1 cm margins are marked off around it.
Dissection then proceeds down toward the chest wall in
a block fashion. Excision of the hematoma is confirmed
by ultrasonography of the specimen ex vivo. (b) as well
as by direct visualization of the hematoma in the gross
specimen.31,32
excised if the surgeon has some idea of the likely location of

the missed lesion. If, however, the surgeon suspects that the
wire was dislodged before or during the procedure, then the
incision should be closed, and repeat localization and biopsy
should be performed later. In addition to wire dislocation or
transection, wire localization is occasionally associated with
Figure 5 Needle-localization breast biopsy. (a) The mam-
vasovagal reactions. Alternatives to wire localization include
mographic abnormality is localized preoperatively. The
hematoma ultrasound-guided (HUG) excision (see below),
relation between the wire, the skin entry site, and the lesion is
noted by the surgeon. The skin incision is placed over the carbon marking,28 use of methylene blue dye,29 and place-
expected location of the mammographic abnormality. (b) The ment of radioactive seeds.30
tissue around the wire is removed en bloc with the wire and
sent for specimen mammography. Tunneling and piecemeal Hematoma ultrasound-guided excision In patients
removal are to be avoided. (c) It is sometimes necessary to who have undergone CNB, particularly those who have
insert the localizing wire from a peripheral site to localize a undergone VACB, the hematoma at the biopsy site can often
deep or central lesion. The incision should be placed directly serve as a physiologic marker that accurately guides intraop-
over the expected location of the lesion, not over the wire erative localization [see Figure 6].31,32 This procedure, referred
entry site. The dissection is extended into breast tissue to
to as HUG excision, renders wire placement unnecessary and
identify the wire a short distance from the lesion. The free
can facilitate operative scheduling. The hematoma is local-
end of the wire is pulled into the wound, and the biopsy is
performed as previously described.99 ized in two planes using ultrasound guidance and 1 cm
margins are marked off around the lesion; dissection is then
continued down toward the chest wall in a block fashion.
With many lesions, the wire entry site is in a fairly periph- Excision of the hematoma can be confirmed by ultrasonogra-
eral location relative to the position of the lesion, which means phy of the specimen ex vivo, as well as direct visualization of
that including the wire entry site in the incision would result the hematoma in the gross specimen. Another variation of the
in excessive tunneling within breast tissue. In such cases, the procedure includes localization of the tumor with MRI and
incision is placed over the expected position of the lesion infusion of the patient’s own blood into the lesion for future
[see Figure 5c], the dissection is extended into breast tissue to localization and surgical excision.31
identify the wire a few centimeters away from the lesion itself,
and the free end of the wire is pulled up into the incision. radioisotope-guided occult lesion localization
A generous block of tissue is then excised around the wire. As widespread mammographic screening programs have
Intraoperative ultrasonography may be useful for identifying been employed, there has been an increase in the detection of
the tip of the needle and facilitating excision, particularly in nonpalpable breast lesions requiring improved localization
the case of a deep lesion or biopsy site in a large breast. techniques for biopsy and/or excision. Radioisotope-guided
Radiography should be performed intraoperatively on all occult lesion localization (ROLL) is one such modality using
wire-localized biopsy specimens to confirm excision of the an intratumorally injected radiotracer to identify the lesion
lesion. If the lesion was missed, another tissue sample may be intraoperatively by use of a gamma probe.33 Contraindications
12/09
to the ROLL procedure include patients with a history of

a b
albumin allergy attributed to the injection of a colloid into the
breast lesion.34 The ROLL procedure has shown a decrease
in the volume of breast tissue excised while preserving surgi-
cal margins. Patients have reported less pain and an improved
cosmetic result with this procedure.34–36 Clinical trials have
shown adequate excision rates when compared with the
needle-localization technique. Combination with the sentinel
lymph node (SLN) mapping procedure has been successfully
described in the literature.37–39 Further investigation with ran-
domized clinical trials is currently underway.
Technique
c
Lesions are identified by image guidance using either ultra-
sonography or stereotactic mammography, and intratumoral
injection of a radionuclide-labeled colloid is performed prior
to surgery. The procedure can be performed using local anes-
thesia with or without sedation. Intraoperatively, a handheld
gamma-detecting probe is used to identify the area with the
maximum radioactivity, and a small incision is made in the
skin overlying this site. Determination of excision volume is
made by review of preoperative lymphoscintigraphic imaging
and decreased detection of radioactivity in the resection bed.
Surgical specimens should undergo radiographic evaluation to
confirm removal of the lesion.
Terminal Duct Excision

Terminal duct excision is the procedure of choice in the Figure 7 Terminal duct excision. (a) A radial incision is
made within the areola. (b) The involved duct is identified by
surgical treatment of pathologic nipple discharge.40 The goal
means of blunt dissection and removed along with a core of
is to excise the discharging duct with as little additional
breast tissue. (c) If no single duct is identified, the entire
tissue as possible to maintain cosmesis. To this end, the sur- subareolar ductal complex is excised from immediately
geon should carefully note the precise position of the offend- beneath the nipple dermis to a depth of 4 to 5 cm within
ing duct at the time of the initial examination. To ensure breast tissue.40,42
accurate ductal identification, intraductal injection of meth-
ylene blue has been used to aid in visualization of the subareolar duct complex must be excised from immediately
involved ductal system prior to major duct excision. Other beneath the nipple dermis to a depth of 4 to 5 cm within the
methods used in conjunction with terminal duct excision to breast tissue. The breast tissue should be reapproximated
limit the volume of tissue removed include ductography and beneath the nipple to prevent retraction of the nipple or
ductoscopy.41 indentation of the areola.
ope r a t iv e te c h n i q ue
The patient is instructed to refrain from manually express- Minimally Invasive Techniques
ing her discharge for several days before operation. After local The next step in the evolving application of minimally inva-
anesthesia (with or without sedation) is administered, the sur- sive techniques to breast cancer is to determine whether abla-
geon attempts to express the discharge. If this attempt is suc- tive local therapies can safely substitute for standard surgical
cessful, the edge of the nipple is grasped with a forceps, and extirpation. Cryotherapy, interstitial laser therapy, radio-
a fine lacrimal duct probe (000 to 0000) is gently inserted into frequency ablation (RFA), microwave ablation, and high-
the discharging duct. A radial incision is made within the intensity focused ultrasound ablation have all been studied as
areola at the same clock position as is occupied by the drain- means of eradicating small breast cancers.43 In most of these
ing duct [see Figure 7 ]; this incision is preferred to a cir- techniques, a probe is placed percutaneously into the breast
cumareolar incision because it is believed to preserve more lesion under imaging guidance, and tumor cell destruction is
nipple sensation and function.42 The nipple skin flap is raised, achieved by means of either heat or cold.
and the duct containing the wire is excised with a margin of To date, experience with ablative breast therapies has been
surrounding tissue from just below the nipple dermis to a limited, and long-term follow-up has not been carried out.
depth of 4 to 5 cm within the breast tissue. The electrocau- There is some evidence that patients who have small, well-
tery should be employed with particular caution in the super- defined, unifocal cancers without an extensive intraductal
ficial portions of the dissection to prevent devascularization component may have greater success with these techniques.43
of the nipple-areola complex. If it is not possible to pass the Lesions in close proximity to the pectoralis major muscle or
lacrimal duct probe into the discharging duct or it is unclear the skin should be isolated by injecting normal saline to
which duct has resulted in the pathologic discharge, the entire prevent thermal injury. Most of the time, these minimally
12/09
invasive techniques are well tolerated and can be performed

in an outpatient setting. Additionally, superior cosmesis is
achieved by leaving the ablated tissue in situ without loss of
tissue volume, thus preventing breast deformity and scarring.
However, most of the initial studies of ablative breast thera-
pies involved subsequent surgical excision to obtain histologic
evidence of cell death. Unfortunately, when ablative therapies
are used alone, the benefits of pathologic assessment of the
specimen, including evaluation of margin status, are lost.
Limiting factors include the ability of current imaging modal-
ities to detect residual disease, thereby identifying patients
who may need subsequent surgical intervention. Clearly,
minimally invasive ablative approaches to breast cancer are
technically feasible and safe, and they do appear to offer some
potential advantages; however, it remains to be determined to
what extent they are oncologically appropriate.
cry o a b l a t ion
Cryotherapy has been successfully used in the treatment of
nonresectable liver tumors. It destroys targeted tissue by
Figure 8 Cryoablation. The needle is placed through the
alternately freezing (-40°C) and thawing the lesion. Intracel-
center of the lesion, and argon gas is delivered to create a
lular ice formation and osmotic and ischemic injury are
local temperature of −40°C. The resulting iceball is well
believed to contribute to the mechanism of tissue destruction. visualized by ultrasonography.
Because of the natural analgesic effect of cold, cryoablation is
generally a well-tolerated procedure that can be performed in
lower. An iceball is thereby formed that is well visualized by
an outpatient setting using local anesthesia with minimal
ultrasonography [see Figure 8]. In a tightly coupled system,
need for pain-controlling medications.
helium is then delivered to thaw the lesion. For adequate
Patients with a biopsy-proven fibroadenoma who want
necrosis to occur, two freeze-thaw cycles must be performed;
their mass removed but desire an alternative to open or per-
the exact specifications of these cycles depend on the size of
cutaneous surgical excision may be candidates for cryoabla-
the lesion.
tion. Clinically, resorption of the fibroadenoma increases over
time, with 12-month follow-up studies reporting a significant inters titial las er therap y
reduction in lesion volume. Despite the occasional residual
Interstitial laser therapy causes hyperthermic (80°C to
disease noted when cryoablation is used to treat larger masses,
100°C) cell death and coagulative tissue necrosis by delivering
both hospital- and community-based studies have reported
energy through a fiberoptic probe. Precise targeting with the
that patient satisfaction rates are higher than 90% with this
use of an MRI-guided laser or stereotactic mammography is
procedure.44
required. Benefits of this treatment include the use of local
The role of cryotherapy in the treatment of primary malig-
anesthesia only. One reported complication with significant
nant disease has recently been explored. Immunologic activa-
morbidity included gaseous rupture of the tumor.46 Small stud-
tion from the cryoablative technique may provide an effective
ies employing surgical excision following laser treatment have
tumor-specific response.45 Early studies reveal the degree
shown complete ablation to be inconsistent. Smaller tumors
of tumor destruction achieved by cryotherapy to be inconsis-
were more likely to be completely ablated.50,51 Complete tumor
tent.46–48 Larger clinical trials are currently in the planning
destruction has been difficult to ensure with this technique.
stages, and the efficacy of this treatment for selected patient
Further investigation and long-term follow-up are required.
populations remains investigational.
Use of the cryoprobe has also been explored as an alterna- Technique
tive to needle localization for excision of nonpalpable lesions A 16-gauge needle with a thermal sensor is inserted into
prior to BCT. Theoretically, the ability to palpate previously the center of the tumor using image guidance. The stylet is
nonpalpable lesions may reduce reexcision rates for positive then replaced with a laser fiber, and the tissue is heated to
margins. Pilot studies have shown decreases in resected 80°C to 100°C. For larger lesions, multiple laser fibers may
tissue volume, improved cosmesis, and improved patient sat- be placed. A thermal sensor needle is placed 1 cm away from
isfaction with a consistently negative margin status.49 Clearly, the laser needle to monitor peripheral temperatures and
the use of cryoablation in this role also requires further ensure an ablative zone of 2.5 to 3.0 cm. Tumor destruction
examination. is confirmed by ultrasonography or MRI.50
Technique radiofrequ ency ablation

A 12-gauge cryoprobe is inserted into the center of the Like cryotherapy, RFA has also been extensively used to
lesion under ultrasonographic guidance. To freeze the lesion, treat liver tumors. RFA is a minimally invasive thermal abla-
inert argon gas is delivered through the tip of the probe in tion technique in which frictional heat is generated by intra-
such a way as to create a local temperature of −40°C or cellular ions moving in response to alternating current. It is
12/09
currently the most promising ablative method for small breast mastectomy include patient preference, the inability to achieve
cancers; however an accurate treatment algorithm remains to clean margins without unacceptable deformation of the breast,
be developed.50 Complications include superficial skin burning the presence of disease in multiple quadrants (multicentric
and temporary elevation of body temperature. Early studies disease), previous chest wall irradiation, pregnancy, the pres-
with RFA followed by immediate or delayed surgical resec- ence of severe collagen vascular disease (e.g., scleroderma),
tion have shown incomplete ablation of tumors.46 Incomplete and the lack of access to a radiation therapy facility.
ablations were attributed to large tumor size (> 2 cm) and the
presence of multifocal disease.43
Partial Mastectomy
Technique Partial mastectomy—also referred to as wide local excision
A large-gauge probe is placed into the center of the tumor or lumpectomy—involves excision of all cancerous tissue to
using image guidance. A star-shaped set of electrodes is microscopically clear margins. Although 1 cm margins are the
deployed from the tip of the probe to deliver heat at a tem- goal, many surgeons consider 2 mm margins to be adequate
perature of 95°C, which is maintained for 15 minutes followed for reducing the risk of local recurrence.57 Hence, reexcision
by a period of cooling for 1 minute. Postprocedural MRI may is indicated whenever margins are either positive or too close
help confirm complete tumor destruction after RFA and (< 2 mm). Partial mastectomy is commonly performed with
other ablative techniques. the patient under local anesthesia, with or without sedation.
The addition of an axillary staging procedure (a common
micr owa v e a b l a t i o n event) usually necessitates general anesthesia, but in select
Microwave ablation is an investigational technique similar circumstances, local or epidural anesthesia may suffice.
to RFA causing tumor necrosis by generation of frictional heat
using two microwave phased array applicators. Because of the op erative techniqu e
higher water content of cancer tissue (compared to adipose An incision is placed directly over the lesion to minimize
and glandular tissue), agitation of intracellular water molecules tunneling through breast tissue; it should be oriented so as to
causes temperature elevation of the breast lesion, leading to be included within a subsequent mastectomy incision if mar-
tissue necrosis. Image guidance is usually performed to local- gins prove positive. As with open biopsy (see above), curvi-
ize the lesion. Complications have included skin flap necrosis linear incisions have been the standard, but radial incisions are
and mild skin burns overlying the treatment area. Pilot stud- now being advocated by some surgeons, particularly for upper
ies have shown a reduction in the size of the tumor; however, outer, medial, lateral, and inferior lesions. A radial incision
further prospective trials are needed to investigate the use of facilitates excision of tumors that extend in a ductal distribu-
microwave ablation as a treatment modality for invasive tion, preserves the contour of the breast, and permits easier
cancer.52–55 Current investigations into the added benefit of reexcision if margins prove positive [see Figure 4b]. With cur-
microwave ablation in conjunction with neoadjuvant chemo- rent oncoplastic techniques,58,59 lesions in the central, medial,
therapy are promising.54 or superior portions of the breast can be resected with mini-
mal cosmetic deformity [see Figure 4, c, d, e, and f ]. Resection
focu s e d u l t r a so un d a b l a t i o n of a portion of the overlying skin is not necessary unless the
Focus ultrasound ablation (FUS) is a modality used to lesion is extremely superficial.
incur cellular death by thermal injury from an ultrasonic To obtain clear margins, a 1 to 1.5 cm margin of normal-
energy source. One of the benefits of FUS is that no implant- appearing tissue should be removed beyond the edge of the
able device is required, allowing the procedure to be per- palpable tumor or, if excisional biopsy has already been
formed through the intact skin. Additionally, larger tumors performed, around the biopsy cavity. In the case of nonpal-
and lesions with an irregular shape can be ablated using this pable lesions diagnosed by means of CNB, wire localization
technique. Image guidance is required to make sure the lesion is performed, and 2 to 3 cm of tissue should be excised
is adequately ablated including a 2 cm margin, in keeping around the wire to obtain an adequate margin. Intraopera-
with the oncologic principles of breast conservation surgery. tive ultrasonography may reduce the rate of positive margins
Short-term follow-up studies ablating smaller tumors have by allowing visualization of the tumor edge or the previous
shown contradictory results with FUS regarding complete biopsy site.60
tumor necrosis. A palpable lump following the procedure is The specimen should be oriented by the surgeon and the
noted by most patients from local tissue edema; however, this margins inked by the pathologist; this orientation is useful if
is transient and usually resolves within 1 to 2 weeks. Con- reexcision is required to achieve clean margins. Reexcision of
traindications to FUS include multifocal, deep lesions and any close (< 2 mm) margins may be performed during the
tumors in close proximity to the skin and nipple.54–56 same surgical procedure if the specimen margins are assessed
immediately by the pathologist. If the specimen was not ori-
ented, the entire biopsy cavity should be reexcised. Surgical
Surgical Options for Breast Cancer clips may be left in the lumpectomy site to help the radiation
There are several surgical options for primary treatment of oncologist plan the radiation boost to the tumor bed or to
breast cancer. It should be emphasized that for most patients, direct partial-breast irradiation. In the closure of the incision,
partial mastectomy (lumpectomy) to microscopically clear hemostasis should be meticulous: a hematoma may delay
margins coupled with axillary staging and radiation therapy adjuvant therapy. Deep breast tissue should be approximated
yields long-term survival equivalent to that associated with only if such closure does not result in significant deformity of
mastectomy and axillary staging. Currently, indications for breast contours. A cosmetic subcuticular closure is preferred.
12/09
Wearing a support bra during the day and night can reduce a b
shearing of fragile vessels.15
a cc e ler a t e d pa r t ial - b r e a st i r r a d i a t i o n w i t h
ba llo o n ca t h e t e r
Historically, whole-breast irradiation has been the standard
treatment to reduce the risk of local recurrence after BCT.
Long-term follow-up of patients who have received BCT
demonstrates, however, that only 1 to 3% of recurrences
within the breast arise at a significant distance from the pri-
mary cancer site (i.e., in other breast quadrants); the remain- c d
der develop near the original biopsy site.57,61 These data pro-
vide the rationale for the approach known as accelerated
partial-breast irradiation (APBI), in which a shortened course
of high-dose radiation is delivered to the tissue surrounding
the lumpectomy cavity (the region theoretically at greatest
risk). Decreasing the volume of tissue receiving radiation
therapy allows for patients to undergo a shorter course of
therapy (approximately 1 week).62 Several different APBI
techniques have been developed, including placement of inter-
stitial catheters, use of a localized external beam, single-dose
Figure 9 Accelerated partial-breast irradiation with balloon
intraoperative treatment, implantation of radioactive beads or catheter. (a) The lumpectomy cavity is evaluated by means of
seeds, and insertion of a balloon catheter into the lumpectomy ultrasonography. (b) The trocar is inserted through a
site. Although long-term follow-up has not been carried out, separate entry site under ultrasonographic guidance.
the short-term results reported for some APBI techniques (c) The uninflated balloon catheter is advanced through the
indicate that in most centers, recurrence rates have been low, trocar path. (d ) Under ultrasonographic visualization, the
with good cosmesis and only mild chronic toxicity.63 balloon is inflated with saline or contrast material. An
The technique of APBI can be illustrated by considering the anterior distance of at least 7 mm between the catheter and
MammoSite Radiation Therapy System (Cytyc Corp., Palo the chest wall or skin is confirmed.
Alto, California), in which a balloon catheter is inserted into
the surgical cavity after lumpectomy to provide partial-breast
irradiation (see below). Although the catheter may also be A trocar (supplied with the insertion kit) is inserted into the
inserted at the time of the original operation, it is preferable cavity via the peripheral entry site and then removed. Removal
to wait for final pathologic evaluation to confirm clear mar- of the trocar allows for the evacuation of the postlumpectomy
gins; if the catheter is inserted and margins are found to be seroma and prevents underdosage of tissue around the cavity.
positive, it will have to be replaced (a costly process). The The shape of the cavity and skin-to-cavity distance are visual-
optimal time for insertion of the APBI balloon is within 2 to ized by means of ultrasonography, and a catheter of appropri-
3 weeks from the final procedure. Postoperative insertion may ate shape (ovoid or spherical) and volume (30 to 65 mL) is
be done either percutaneously under ultrasonographic guid- advanced through the newly formed tract. Saline is then infil-
ance or by means of an open technique. Once the catheter is trated to inflate the catheter balloon to the maximum volume
in place, a radiation source (iridium 192) is delivered into the that the cavity can accommodate. A small amount of radio-
balloon via a high–dose rate remote afterloader. graphic contrast may also be infused to aid in visualization.
The cavity is then reimaged to confirm that the catheter is an
Technique adequate distance (7 mm) from the skin. If the distance is
For safe and effective delivery of radiotherapy through the inadequate, the balloon volume is reduced. If it is not possible
MammoSite balloon catheter, the lumpectomy cavity must be to keep the catheter at least 7 mm from the skin while main-
able to conform its shape to that of an ovoid or spherical taining a balloon volume of at least 30 mL, conversion to an
catheter without significant air pockets, able to accommodate open approach is indicated.
a volume of at least 30 mL (the volume of the smallest avail-
able balloon), and able to maintain a minimum distance of Open approach The cavity is reopened through the
7 mm from the skin with the catheter in place. In addition, if original skin incision. Occasionally, a thick rind may form
a percutaneous technique is being considered, the surgeon around the residual seroma; this rind may be excised to
should be comfortable with ultrasonography (which will be reduce tension and increase the volume of the cavity. If nec-
employed for initial visualization of the lumpectomy cavity). essary, the anterior skin may be excised in the form of an
If the above criteria seem reasonably attainable, one may pro- ellipse to provide improved anterior coverage of the catheter,
ceed with a percutaneous approach [see Figure 9]. and the subcutaneous tissue may be pulled together over the
catheter and the cavity to help ensure adequate coverage and
Percutaneous approach A site peripheral to the scar is sufficient distance from the skin. A peripheral site is chosen
chosen as the entry site for the balloon catheter, and a local for insertion of the catheter. After the skin is closed, ultra-
anesthetic is injected along the proposed catheter tract. sonography is employed to confirm that the distance from the
12/09
skin is adequate. A topical antibiotic is applied at the insertion a

site; no anchoring stitch is necessary. Correct positioning of
the catheter is confirmed by a postplacement treatment-
planning computed tomographic (CT) scan that is evaluated
by the radiation oncologist.
Mastectomy
The goal of a mastectomy is to remove all breast tissue—
including the nipple, the areola, and the pectoral fascia—
while leaving viable skin flaps and a smooth chest wall for b
application of prosthesis. This should be the objective whether
the mastectomy is performed for cancer treatment or for pro-
phylaxis. Skin-sparing mastectomy (SSM) performed in con-
junction with immediate reconstruction is discussed elsewhere
[see Breast Reconstruction, below]. Proper skin incisions and
good exposure are the key components of a well-performed
mastectomy. Mastectomy usually calls for general anesthesia,
but it may be performed with thoracic epidural anesthesia or
local anesthesia in select circumstances.
ope r a t iv e te c h n i q ue c
The traditional mastectomy incision is an elliptical one that

is placed either transversely across the chest wall or at an
upward angle toward the axilla. It should be fashioned in such
a way as to include the nipple-areola complex and any incision
from a previous biopsy [see Figure 10a]. Ideally, the upper and
lower skin flaps should be of similar length so that there is no
redundant skin on either flap. The outline of the incision may
be established by using the following five steps:
1. The lateral and medial end points are marked.
2. The breast is pulled firmly downward.
3. To define the path of the upper incision, a straight line is
drawn from one end point to the other across the upper
surface of the breast.
4. The breast is pulled firmly upward.
5. To define the path of the lower incision, a straight line is
drawn from one end point to the other across the lower
surface of the breast.
The outlined incision is then checked to confirm that it can
be closed without either undue tension or redundant skin.
Dog-ears or lateral skin folds can be prevented by extending Figure 10 Mastectomy incisions. (a) Elliptical incisions
the incision medially or laterally to remove all the skin that incorporate traditional lumpectomy incisions. (b) In large-
contributes to the forward projection of the breast. The clo- breasted women with excess breast skin, traditional ellipses
sure should be fairly snug intraoperatively while the arm is can easily incorporate previous radial and superior-pole
extended; significant slack will be created when the arm is oncoplastic incisions. (c) In smaller-breasted women,
returned to the patient’s side. The medial and lateral end sigmoid, modified Wise, or other oncoplastic mastectomy
points of the incision may be adjusted upward or downward incisions may be needed to incorporate previous radial
to include any previous biopsy incisions. lumpectomy incisions.
As noted [see Partial Mastectomy, above], there is increas-
ing acceptance of the use of radial and oncoplastic incisions Once the incision is made, the next step is to create even
for BCT. In a small percentage of women, persistently positive and viable flaps. In most patients, there is a fairly well-defined
margins may dictate conversion from BCT to mastectomy. In avascular plane between subcutaneous fat and breast tissue.
large-breasted women with excess breast skin, traditional This plane is identified by pulling the edges of the incision
elliptical incisions can easily incorporate any previous radial upward with skin hooks and beginning a flap that is 8 to
or superior-pole oncoplastic incisions that may have been 10 mm thick. After an initial release of the skin edge, the
performed [see Figure 10b]. In smaller-breasted women, how- desired plane is developed by applying firm tension down-
ever, sigmoid, modified Wise, or other oncoplastic mastec- ward on the breast tissue and away from the skin at a 45°
tomy incisions may be needed to incorporate previous angle. The fine fibrous attachments between breast tissue
lumpectomy incisions [see Figure 10c]. and subcutaneous fat (Cooper ligaments) are then divided
12/09
with the electrocautery or a blade, and crossing vessels are preoperatively with the patient in a sitting position. Several
coagulated or ligated as they appear. To protect both arterial options are available for SSM. For CNB-diagnosed tumors
supply to and venous drainage from the skin flap, one must that are not superficial, a circumareolar incision may be
refrain from excessive ligation or cauterization of vessels on employed, with a lateral extension for exposure if necessary.
the flap. For most women, flap viability is not an issue. For Different incisions may be used if it proves necessary to incor-
diabetics, smokers, and other patients with diffuse small porate previous incisions or to remove skin anterior to super-
vessel disease, however, it is a serious consideration. In such ficial tumors. A separate axillary incision may be useful when
patients, flaps should be no longer than necessary with no axillary dissection or SLNB is being performed. CNB sites
excess tension, and extra care should be taken to preserve generally are not included in the excised skin segment; the
flap vessels. Patients should be warned that even with these surgeon may opt to excise them through a separate skin ellipse.
measures, there may be some skin necrosis along the inci- Intraoperatively, flaps are created in a circular fashion to opti-
sion. Such necrosis is best treated with gradual débridement mize exposure. Although optimal cosmesis is part of the ratio-
of the eschar. nale for SSM, cosmetic considerations should never be allowed
Flaps are raised superiorly to the clavicle, medially to the to compromise the extent of the dissection in any way.
sternum, inferiorly to the inframammary fold, and laterally to
the border of the latissimus dorsi. The pectoral fascia is nip p le-s p aring mas tectomy
incised both superiorly and medially. Inferiorly, the fascia of Following mastectomy or SSM, many patients report dis-
the abdominal muscles is not divided. The pectoralis major, satisfaction with the reconstruction of their nipple areolar
the abdominal muscles, and the anterior serratus muscle form complex using skin grafting or tattooing. Nipple-sparing mas-
the deep border of the dissection. The pectoral fascia is tectomy (NSM) eliminates the need for reconstruction by
removed with the breast specimen and may be separated preservation of the dermis and epidermis of the nipple-areola
from the muscle with either the electrocautery or a blade. complex during the initial procedure. Several initial studies
In a simple mastectomy, the dissection proceeds around have shown NSM to be an oncologically safe procedure in
the lateral edge of the pectoralis major but stops before enter- those patients appropriately selected.66–71 Contraindications
ing the axillary fat pad (unless the procedure is being done in to NSM include larger tumors (> 2 cm), centrally located
conjunction with SLNB). A single closed suction drain is lesions with a small tumor-to-nipple distance, and lympho-
placed through a separate lateral stab wound in such a way vascular invasion.72
that it extends under the lower flap and a short distance Several types of incisions have been described, including
upward along the sternal border of the dissection. periareolar with lateral extension, transareolar with lateral
A modified radical mastectomy essentially consists of an extension, and inframammary fold incisions. These typically
axillary node dissection added to a simple mastectomy. At the allow for good exposure and dissection of the retroareolar
lateral edge of the dissection, the border of the latissimus dorsi structures.73 Elevation of the areola off of the breast paren-
is exposed, as is the lateral border of the pectoral muscle. chyma should be performed with sharp dissection to prevent
Retraction of these two muscles provides excellent exposure thermal injury to the nipple from electrocautery. The lactifer-
for the axillary dissection [see Axillary Dissection, below]. Some ous ducts are transected at the base of the nipple papilla. Skin
surgeons prefer to remove the breast from the chest wall first, flaps are raised in a manner similar to that of SSM or con-
whereas others leave the breast attached to provide tension for ventional mastectomy. On removal of the subcutaneous
the axillary dissection. On completion of the procedure, two breast, the remaining nipple tissue is removed with sharp dis-
closed suction drains are placed, one in the axilla and another section. A small (2 to 3 mm) rim of peripheral subcutaneous
under the lower flap and extending to the midline. tissue should be preserved behind the nipple to prevent par-
After either a simple or a modified radical mastectomy, the tial or complete nipple necrosis. Pathologic evaluation of the
skin is closed and a dressing applied according to the sur- excised lactiferous ducts for tumor involvement is imperative
geon’s preference. Early arm mobilization is encouraged.
skin - spa r in g m a s t ec t o m y
SSM, which consists of resection of the nipple-areola com- a b c
plex, any existing biopsy scar, and the breast parenchyma,
followed immediately by breast reconstruction, has become
an increasingly popular approach for women requiring mas-
tectomy.64 With this approach, the inframammary fold and
contour of the breast are preserved, and a generous skin enve-
lope remains in situ for reconstruction; cosmetic results are
thereby optimized. In addition, SSM is oncologically safe and
is not associated with an increased incidence of local recur-
rence.65 The recurrences that do occur typically develop
below the skin flaps and thus are easily detectable; deep
Figure 11 Shown is (a) the recommended placement of the
recurrences beneath the reconstruction are comparatively traditional circumareolar incision for skin-sparing mastec-
uncommon. tomy. (b) Separate incisions may be used to excise previous
The incision for SSM with immediate reconstruction should lumpectomy incisions or to gain access to the axilla.
be planned in collaboration with the plastic surgeon [see (c) A lateral extension can provide further exposure for flap
Figure 11], and the inframammary fold should be marked development or axillary staging.
12/09
and mandates complete removal of the nipple if in situ or the National Surgical Adjuvant Breast and Bowel Project
invasive disease is present. (NSABP) B-27 trial suggest that in patients undergoing neo-
One of the most concerning complications to NSM includes adjuvant therapy, SLNB may be performed either before or
nipple or areolar necrosis, which not only negatively impacts after therapy, with no significant differences in identification
cosmesis but can cause loss of the reconstructed implant. and false negative rates86; however, this suggestion is not uni-
Additional complications include lack of sensation to the versally accepted.87 Contraindications to SLNB include the
nipple, change in nipple pigmentation, and improper nipple presence of clinically positive axillary nodes, previous axil-
positioning following reconstruction.74 Currently, long-term lary surgery, and pregnancy or lactation. Large or locally
follow-up to investigate local recurrence rates for NSM is advanced breast cancers commonly give rise to a positive
lacking. However, NSM appears to be a good option for SLN but are not a contraindication to the procedure in that
those patients undergoing prophylactic mastectomy or those some patients may still be spared the morbidity of a full axil-
with small, peripheral tumors or in situ disease. lary dissection.
Lymphatic Mapping and SLNB Axillary Dissection

The pathologic status of the axillary nodes is the single Before the advent of SLNB, axillary dissection was routinely
most important prognostic factor for outcome after treatment performed in breast cancer patients. It provided prognostic
of breast cancer. The growing recognition of the morbidity information that guided subsequent adjuvant therapy, afforded
of traditional axillary dissection (lymphedema and sensory excellent local control, and may have contributed a small over-
deficits), together with the increased capability of mammog- all survival benefit.
raphy to detect smaller, potentially node-negative invasive Axillary dissection includes resection of level I and level II
breast cancers, has given rise to the development of SLNB as lymph nodes [see Figure 12a].88 The superior border of the
an axillary staging procedure. SLNB is a minimally invasive dissection is formed by the axillary vein; the lateral border of
means of identifying the first node or nodes draining the the dissection is formed by the latissimus dorsi; the medial
breast and hence the first node or nodes to which tumor may border is formed by the pectoral muscles and the anterior ser-
spread. In experienced hands, a negative SLNB reliably pre- ratus muscle; and the inferior border is formed by the tail of
dicts a tumor-free axilla (false negative rate, 5 to 9%); there- the breast. Level II nodes are easily removed by retracting the
fore, when such a result is obtained, no further nodes need to pectoralis major and the pectoralis minor medially; it is not
be removed and the patient can be spared the morbidity of a necessary to divide or remove the pectoralis minor. Level III
traditional axillary node dissection.75–77 Surgeons competent nodes are not removed unless palpable disease is present.
in SLNB should be able to identify the SLN with at least Axillary dissection, either alone or in conjunction with
90% accuracy and a false negative rate lower than 5%.78 It is lumpectomy or mastectomy, usually calls for general anes-
recommended that surgeons first learning the technique use thesia, but it may be performed with thoracic epidural anes-
axillary dissection as a backup for the first 20 procedures to thesia. To facilitate identification and preservation of motor
gain experience in identifying the SLN. Currently, axillary nerves within the axilla, the anesthesiologist should refrain
dissection is recommended for patients who have a positive from using neuromuscular blocking agents. In the absence of
SLN; however, prospective, randomized trials are required to neuromuscular blockade, any clamping of a motor nerve or
determine the extent to which this step is necessary in SLN- too-close approach to a motor nerve with the electrocautery
positive patients. will be signaled by a visible muscle twitch.
The most common method of identifying the SLN invol-
ves injection of both a vital blue dye and a radionuclide.79–82
The radionuclide is first injected into the subareolar lym- s tru ctu res to be p res erved
phatic plexus, either preoperatively or, in some centers, A number of vascular structures and nerves passing through
intraoperatively.80 Because the breast and its overlying skin the axilla must be preserved during axillary dissection [see
drain to the same few SLNs,82 peritumoral, intradermal, and Figure 12b]. These structures include the axillary vein and
subareolar injections are all acceptable approaches; subareo- artery; the brachial plexus; the long thoracic nerve, which
lar injection has the advantage of being expeditious and innervates the anterior serratus muscle; the thoracodorsal
accurate in cases of multicentric (as well as unicentric) dis- nerve, artery, and vein, which supply the latissimus dorsi; and
ease.79 The vital blue dye is then injected, commonly in the the medial pectoral nerve, which innervates the lateral por-
subareolar plexus, and the breast is massaged for 5 minutes tion of the pectoralis major.
to stimulate lymphatic flow. Lymph nodes that are “hot” The axillary artery and the brachial plexus should not be
(i.e., radioactive), blue, or both, as well as palpable nodes, exposed during axillary dissection. If they are, the dissection
are removed for evaluation by frozen-section analysis or has been carried too far superiorly, and proper orientation at
touch-print cytology. a more inferior position should be established. In some
SLNB has also been employed in DCIS patients, but, in patients, there may be sensory branches of the brachial plexus
general, its use should be limited to patients with extensive superficial (and, rarely, inferior) to the axillary vein laterally
DCIS who are undergoing mastectomy (in the event of near the latissimus dorsi; injury to these nerves results in
occult invasive disease). Some investigators recommend numbness extending to the wrist. To prevent this complica-
SLNB for patients with extensive DCIS who are undergoing tion, the axillary vein should initially be identified medially,
BCT (in whom CNB may have missed an area of invasion),83 under the pectoralis major. Medial to the thoracodorsal nerve
whereas others caution against this practice.84,85 Results from and adherent to the chest wall is the long thoracic nerve of
12/09
Bell. The medial pectoral nerve runs from superior to the extended posteriorly onto the latissimus dorsi as necessary for
axillary vein to the undersurface of the pectoralis major, pass- exposure. Skin flaps are raised to the level of the axillary vein
ing through the axillary fat pad and across the level II nodes; and to a point below the lowest extension of hair-bearing skin,
it has an accompanying vein whose blue color may be used either as an initial maneuver or after the initial identification
to identify the nerve. If a submuscular implant reconstruction of key structures.
[see Breast Reconstruction, below] is planned, preservation of The key to axillary dissection is obtaining and maintaining
the medial pectoral nerve is especially important to prevent proper orientation with respect to the axillary vein, the
atrophy of the muscle. thoracodorsal bundle, and the long thoracic nerve. After the
The intercostobrachial nerve provides sensation to the pos- incision has been made, the dissection is extended down into
terior portion of the upper arm. Sacrificing this nerve gener- the true axillary fat pad through the overlying fascial layer.
ally leads to numbness over the triceps region. In many The fat of the axillary fat pad may be distinguished from
women, the intercostobrachial nerve measures 2 mm in diam- subcutaneous fat on the basis of its smoother, lipomalike tex-
eter and takes a fairly cephalad course near the axillary vein; ture. There may be aberrant muscle slips from the latissimus
when this is the case, preservation of the nerve will not inter- dorsi or the pectoralis major; in addition, there may be an
fere with node dissection. Sometimes, however, the nerve is extremely dense fascial encasement around the axillary fat
tiny, has multiple branches, and is intermingled with nodal pad. It is important to divide these layers early in the dissec-
tissue that should be removed; when this is the case, one tion. The borders of the pectoralis major and the latissimus
should not expend a great deal of time on attempting to pre- dorsi are then exposed, which clears the medial and lateral
serve the nerve. If the intercostobrachial nerve is sacrificed, it borders of the dissection.
should be transected with a knife or scissors rather than with The axillary vein and the thoracodorsal bundle are identi-
the electrocautery, and the ends should be buried to reduce fied next. As discussed (see above), the initial identification of
the likelihood of postoperative causalgia. the axillary vein should be made medially, under the pectora-
lis major, to prevent injury to low-lying branches of the bra-
chial plexus. Sometimes, the axillary vein takes the form of
o pe ra tiv e t e chn iq u e several small branches rather than a single large vessel. If this
The incision for axillary dissection should be a transverse is the case, all of the small branches should be preserved.
or curvilinear one made in the lower third of the hair-bearing The thoracodorsal bundle may be identified either distally
skin of the axilla. For cosmetic reasons, it should not extend at its junction with the latissimus dorsi or at its junction with
anteriorly onto the pectoralis major; however, it may be the axillary vein. The junction with the latissimus dorsi is
a b Thoracodorsal
Artery
Thoracodorsal
II III Nerve
2nd Rib
Latissimus Long Thoracic Thoracodorsal

Dorsi Nerve Vein
Figure 12 Axillary dissection.88 (a) Shown are axillary lymph node levels in relation to the axillary vein and the muscles of the
axilla (I = low axilla, II = midaxilla, III = apex of axilla). (b) Shown is a view of the structures of the axilla after completion of
axillary dissection.
12/09
within the axillary fat pad at a point two thirds of the way level of node involvement. A closed suction drain is placed
down the hair-bearing skin of the axilla, or approximately through a separate stab wound. (Some practitioners prefer not
4 cm below the inferior border of the axillary vein. Occasion- to place a drain and simply aspirate postoperative seromas as
ally, the thoracodorsal bundle is bifurcated, with separate necessary.) A long-acting local anesthetic may be instilled into
superior and inferior branches entering the latissimus dorsi; the axilla—a particularly helpful practice if the dissection was
this is particularly likely if the entry point appears very high. done as an outpatient procedure.
If the bundle is bifurcated, both branches should be pre-
served. The thoracodorsal bundle may be identified at its
Breast Reconstruction
junction with the latissimus dorsi by spreading within axillary
fat parallel to the border of the muscle and looking for the The vast majority of women undergoing a partial or
blue of the thoracodorsal vein. Identification is also facilitated complete mastectomy are candidates for breast reconstruc-
by lateral retraction of the latissimus dorsi. The long thoracic tion and should be offered a plastic surgery consultation
nerve lies just medial to the thoracodorsal bundle on the chest before undergoing definitive surgical treatment. Reconstruc-
wall at this point and at approximately the same anterior- tion is covered by insurance and may be done either at the
posterior position. It may be identified by spreading tissue time of the oncologic surgery (immediate reconstruction) or
just medial to the thoracodorsal bundle and then running the as a delayed procedure (delayed reconstruction). Despite
index finger perpendicular to the course of the long thoracic early concerns and debate, studies show that neither mode of
nerve on the chest wall to identify the cordlike nerve as it reconstruction interferes with detection of recurrent disease
moves under the finger. Once the nerve is identified, axillary nor does it significantly delay subsequent adjuvant therapy.
tissue may be swept anteriorly away from the nerve by blunt
rep air of p artial mas tectomy defec ts
dissection along the anterior serratus muscle; there are no
(oncop las ty)
significant vessels in this area.
The junction of the thoracodorsal bundle with the axillary Recently, there has been an increase in the proportion of
vein is 1.5 to 2.0 cm medial to the point at which the axillary breast cancer patients treated with partial mastectomy fol-
vein crosses the latissimus dorsi. The thoracodorsal vein lowed by radiation therapy, an approach referred to as BCT.
enters the posterior surface of the axillary vein, and the nerve This trend is in part attributable to increased mammographic
and the artery pass posterior to the axillary vein. Generally, screening that has led to the detection of earlier breast cancers
one or two scapular veins branch off the axillary vein medial and the use of neoadjuvant chemotherapy, where significant
to the junction with the thoracodorsal vein. These are divided clinical responses can obviate the need for a traditional
during the dissection and should not be confused with the mastectomy. Alarmingly, 20 to 30% of patients who undergo
thoracodorsal bundle. BCT report having a poor cosmetic result in the treated
The axillary vein and the thoracodorsal bundle having been breast.89
identified, the pectoralis major is retracted medially at the The term oncoplasty has been used to describe techniques
level of the axillary vein, and the latissimus dorsi is retracted to improve the cosmesis of the breast after oncologic resec-
laterally to place tension on the thoracodorsal bundle. Once tion. Techniques integral to plastic surgery are often incorpo-
this exposure is achieved, the axillary fat and the nodes are rated and include local tissue rearrangement, purse-string
cleared away superficial and medial to the thoracodorsal defect closure, breast reduction techniques, local pedicled
bundle to the level of the axillary vein. Superiorly, dissection flaps, and lower abdominal flaps.89,90 The ultimate goal is to
proceeds medially along the axillary vein to the point where obtain a natural-appearing breast with improved cosmesis
the fat containing level II nodes crosses the axillary vein. To compared to partial mastectomy alone.
improve exposure, the fascia overlying the level II extension
of the axillary fat pad should be incised to release tension and rep air of mas tectomy defects
expose the lipomalike level II fat. As noted [see Structures to Options for breast reconstruction continue to evolve and
Be Preserved, above], the medial pectoral nerve passes onto include, but are not limited to, implants with or without
the underside of the pectoralis major in this area and should tissue expansion, the transverse rectus abdominis myocutane-
be preserved. One or more small venous branches may pass ous (TRAM) flap, the latissimus dorsi myocutaneous flap,
inferiorly from the medial pectoral bundle; particular atten- and various other free flaps. Patient preference and lifestyle,
tion should be paid to preserving the nerve when ligating the availability of suitable autologous tissue, and the demands
these venous branches. imposed by additional cancer therapies are variables that can
The next step in the dissection is to reflect the axillary fat influence the timing and choice of the optimal reconstructive
pad inferiorly by dividing the medial attachments of the axil- technique [see Figure 13].
lary fat pad along the anterior serratus muscle. Care must be If the need for postmastectomy radiation therapy is definite
taken to preserve the long thoracic nerve. Because there are or unclear at the time of mastectomy (i.e., final pathology
no significant vessels or structures in the tissue anterior to the results are not available), a delayed reconstruction may be
long thoracic nerve, this tissue may be divided sharply, with chosen because of an increased risk of complications related
small perforating vessels either tied or cauterized. Finally, the to the reconstructed breast. An expander is typically placed at
axillary fat is freed from the tail of the breast with the elec- the time of mastectomy to preserve the breast skin envelope,
trocautery or a knife. and the definitive reconstructive plan is formulated once the
There is no need to orient the axillary specimen for the final pathologic results have become available and the radia-
pathologist, because treatment is not affected by the anatomic tion therapy has been completed.91
12/09
re co n s t ru ct ion opt i o n s New Jersey) are acellular dermal matrices derived from
human cadaver skin that may be sewn to the pectoralis muscle
Prosthetic Implants and the inframammary fold to reinforce the lower pole of the
The simplest method of reconstruction is to place a saline- breast and enlarge the breast pocket so that it may accom-
or silicone-filled implant beneath the pectoralis major. How- modate a tissue expander or implant.93 This measure may
ever, even after SSM, the pectoralis major is usually so tight reduce postoperative pain and improve cosmesis, as well as
that expansion of this muscle and the overlying skin is neces- facilitate immediate implant placement in smaller-breasted
sary before an implant that matches the opposite breast can women. Porcine-derived dermal matrices are also available
be inserted. A tissue expander is typically placed and serial and may be used as an alternative to the aforementioned.
expansions are performed on an outpatient basis until an The major advantages of implant reconstruction are
appropriate-size breast pocket has been attained. The time reduced operative time, faster recuperation, and a reasonably
required to complete the expansion process usually ranges good cosmetic outcome. These advantages must be weighed
from 3 to 6 months after mastectomy and is dependent mostly against the fact that this method is a two-stage approach and
on the desired breast size, the thickness of the mastectomy that obtaining symmetry with the contralateral native breast
skin flaps, and the patient’s ability to tolerate the expansion.92 can be difficult and often requires a mastopexy (breast lift)
A second operative procedure is then required to exchange with or without an implant augmentation.94 The cosmetic
the expander for a permanent implant. The nipple-areolar result may also deteriorate over time as a consequence of
complex is constructed at a later date. AlloDerm (LifeCell capsule formation or implant migration, resulting in replace-
Corp., Branchburg, New Jersey) and Flex HD (MTF, Edison, ment of the implant each decade.
Patient is scheduled for mastectomy Patient has undergone breast-conserving

therapy with radiation therapy
Assess patient’s desires and operative fitness.
Patient does not desire Patient desires reconstruction Significant Tumor does not recur,
reconstruction or is unable and is able to tolerate deformity results and no significant
to tolerate reconstructive reconstructive operation deformity results
operation
Determine whether radiation No reconstruction
Fit patient with prosthesis. therapy will be needed. is indicated.
Radiation therapy is Need for radiation therapy Radiation therapy is Tumor recurs
unnecessary is uncertain (final pathology necessary (tumor is T3,
Perform mastectomy.
results are not available) ≥ 4 axillary nodes are
Perform immediate reconstruction positive, or skin or chest
with SSM. Perform delayed-immediate wall involvement is apparent)
Reconstruction method depends reconstruction.
on patient preference, Place expander at the time Perform delayed
comorbidities, and body habitus: of SSM. reconstruction.
• Implant with tissue expansion Await final pathology results.
• Autologous tissue reconstruction Determine whether radiation
(TRAM flap, latissimus dorsi flap, therapy will be needed.
or, if standard flap is not suitable,
free flap)
Perform nipple-areola
reconstruction at a later date.
Radiation therapy is unnecessary Radiation therapy

is necessary
Complete delayed reconstruction 2 wk later.
Reconstruction method depends on patient preference,
comorbidities, and body habitus:
Perform autologous tissue reconstruction (TRAM
• Implant with tissue expansion
flap, latissimus dorsi flap, or, if standard flap is not
• Autologous tissue reconstruction (TRAM flap, latissimus
suitable, free flap).
dorsi flap, or, if standard flap is not suitable, free flap)
Perform nipple-areola reconstruction at a later date
Perform nipple-areola reconstruction at a later date.
for mastectomy cases.
Figure 13 Algorithm outlining the major steps in breast reconstruction after mastectomy. SSM = skin-sparing mastectomy;
TRAM = transverse rectus abdominis myocutaneous.
12/09
Autologous Tissue Pedicled myocutaneous flaps In a pedicled TRAM flap

An alternative approach to reconstruction that continues to reconstruction, the contralateral rectus abdominis is transferred
evolve is the transfer of vascularized muscle, skin, fat, or a along with overlying skin and fat based on the superior epigas-
combination of these from a donor site to the mastectomy tric vessels to create a breast mound. This procedure yields a
defect. The transferred tissue may be relocated either on flatter abdominal contour but calls for a long transverse
a vascular pedicle or as a free tissue transfer requiring a abdominal incision and necessitates repositioning of the umbi-
microsurgical anastomosis. Although autologous tissue pro- licus. The major advantages of TRAM flap reconstruction are
cedures can be lengthy and are associated with a longer that it provides enough tissue to match most contralateral
recovery period, they often require fewer revision and sym- breasts and that it offers the option of performing bilateral
metry procedures.95 With autologous tissue reconstruction, it TRAM flap procedures in healthy candidates who desire or
is possible to create a natural-appearing breast without the require bilateral reconstruction. Patients who have undergone
need for a breast implant, often sparing the patient a contra- abdominal procedures that compromise the TRAM flap’s vas-
lateral breast procedure to obtain symmetry.94 The most cular supply are not ideal candidates for TRAM reconstruc-
commonly used pedicled myocutaneous flaps are the TRAM tion. Postoperative discomfort is greater with TRAM flap
flap [see Figure 14] and the latissimus dorsi flap [see Figure 15]. reconstruction than with other flap reconstructions because of
Recent advances have led to the conception of perforator the extent of the abdominal wall dissection and defect.
flaps such as the deep inferior epigastric perforator (DIEP) In a pedicled latissimus dorsi myocutaneous flap recon-
flap and the superficial inferior epigastric artery (SIEA) flap, struction, the ipsilateral latissimus dorsi is transferred along
which allow for safe and reliable tissue transfer with minimal with overlying skin and fat based on the thoracodorsal vessels
donor-site morbidity. to create a breast mound. The operative technique for the
The major advantage of autologous tissue reconstruction is latissimus dorsi flap reconstruction is complex, requiring
that it generally yields a superior cosmetic result and provides intraoperative changes in patient position (unless the onco-
variability in breast volume and shape96; in addition, the logic surgeon is willing to perform the mastectomy with the
reconstructed breast has a softer, more natural texture than a patient in a lateral decubitus position). Patients who have
breast that has undergone implant reconstruction. The main undergone irradiation of the breast, the chest wall, or the
drawbacks are the magnitude of the surgical procedure (involv- axilla (including irradiation of the thoracodorsal vessels) may
ing both a prolonged operating time and longer inpatient hos- not be eligible for this procedure. A major advantage of the
pitalization), the potential need for blood transfusion, and the latissimus dorsi flap is that its donor site is associated with
morbidity related to the donor site. Smokers and patients with less postoperative discomfort than the abdominal donor site
significant vascular disease may not be ideal candidates for of the TRAM flap. In addition, transfer of the latissimus dorsi
autologous tissue reconstruction. Partial necrosis of the trans- results in substantially less functional impairment than trans-
ferred flap may create firm areas; on rare occasions, complete fer of the rectus abdominis. One major drawback is that in
necrosis and consequent loss of the flap can occur. many women, the latissimus dorsi is not bulky enough to
a b Deepithelialized c
Mastectomy Flap Configured to Areas

Defect Form Breast Mound
Skin and Superior Fascial

Subcutaneous Epigastric Pedicle Closure
Tissue Resection
Fascial Remaining Anterior Abdominal

Resection Rectus Sheath Scar
Figure 14 Breast reconstruction after mastectomy: transverse rectus abdominis myocutaneous (TRAM) flap. (a) The infraum-
bilical flap is designed. The TRAM flap is tunneled subcutaneously into the chest wall cavity. Blood supply to the flap is maintained
from the superior epigastric vessels of the rectus abdominis. (b) Subcutaneous fat and deepithelialized skin are positioned under
the mastectomy flaps as needed to reconstruct the breast mound. (c) The fascia of the anterior rectus sheath is approximated to
achieve tight closure of the abdominal wall defect and to prevent hernia formation. The umbilicus is sutured into its new position.
12/09
a b
Pectoral Muscle
Thoracodorsal
Submuscular
Vessels
Implant
Skin Island Latissimus

Dorsi
Latissimus Dorsi
Figure 15 Breast reconstruction: latissimus dorsi flap Breast reconstruction after mastectomy: latissimus dorsi myocutaneous
flap with submuscular implant. With this flap, addition of an implant is often required to provide the reconstructed breast with
adequate volume and projection. (a) The myocutaneous flap is elevated; it is important to maintain the blood supply to the flap
from the thoracodorsal vessels. The flap is tunneled subcutaneously to the mastectomy defect. (b) The latissimus dorsi is sutured
to the pectoralis major and the skin of the inframammary fold so that the implant is completely covered by muscle.
Free myocutaneous and perforator flaps Free-flap

reconstruction options are used primarily when other autolo-
gous and implant reconstruction options are not available, do
not provide sufficient tissue volume, or have failed. They are
more complex procedures, requiring microvascular anasto-
moses, and carry a higher risk of total flap loss. Although,
R historically, the free TRAM flap and the free gluteal artery
flap (GAP) have been the most often employed techniques,
the introduction of perforator flaps (DIEP, SIEA, superior
GAP, inferior GAP) has added options to the reconstructive
20 surgeon’s armamentarium. Preoperatively, CT angiography
[see Figure 16] has replaced duplex ultrasonography as the
gold standard for evaluation of donor vessel caliber and pat-
ency.96 Perforator flaps are supplied by blood vessels that per-
forate through or around overlying muscles to vascularize the
C overlying skin and fat. During flap harvest, these perforators
F W4 must be meticulously dissected free from the surrounding
muscle, which is preserved intact and left in its natural posi-
Figure 16 Preoperative computed tomographic angiography
tion. The free tissue flap is then anastomosed to recipient
of the inferior epigastric arterial system, the basis for free
transverse rectus abdominis myocutaneous (TRAM), deep
vessels, and the donor site is closed without the need of addi-
inferior epigastric perforator (DIEP), and superficial inferior tional support such as mesh or biologics.97 Ideally, they pro-
epigastric artery (SIEA) flaps, used for autologous breast vide adequate tissue for reconstruction without the level of
reconstruction. donor-site morbidity seen with the free TRAM or other myo-
cutaneous free flaps.98 The disadvantages of perforator flaps
include the considerable technical expertise and long operat-
provide symmetry with the contralateral breast; consequently, ing time required, as well as the greater potential for flap loss
to match the size of the opposite breast, the flap must be (because these flaps have a more tenuous blood supply than
supplemented with an implant. Thus, the drawback of the the standard TRAM flap).
implant’s limited life span is added to the drawbacks associ-
ated with autologous tissue reconstruction. Financial Disclosures: None Reported.
12/09
References
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assessment of 51 procedures and implications motherapy in breast cancer: results from
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Acknowledgment
73. Sacchini V, Pinotti JA, Barros AC, et al. before and after neoadjuvant chemotherapy:
Nipple-sparing mastectomy for breast timing is important. Am J Surg 2005; The authors wish to acknowledge Rena B. Kass,
cancer and risk reduction: oncologic or 190:517–20. MD, FACS, and Wiley W. Souba, MD, ScD,
technical problem?. J Am Coll Surg 2006;203: 88. Kinne DW. Primary treatment of breast can- FACS, for their contributions to the previous ren-
704–14. cer. In: Hellman S, Harris JR, Henderson IC, dition of this chapter on which they have based
74. Sookhan N, Boughey JC, Walsh MF, et al. editors. Breast diseases. Philadelphia: JB Lip- this update.
Nipple-sparing mastectomy—initial experi- pincott; 1991. Figures 2, 3, 5 to 11 , and 13 to 15 Alice Y. Chen.
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3 BREAST, SKIN, AND SOFT TISSUE 6 LYMPHATIC MAPPING AND SENTINEL NODE BIOPSY — 1
6 LYMPHATIC MAPPING AND

SENTINEL NODE BIOPSY
David W. Ollila, MD, FACS, Karyn B. Stitzenberg, MD, MPH, and Nancy Klauber-Demore, MD,
FACS*
With an estimated 194,280 new cases in the United States in survival is approximately 40% lower in patients who have
2009, breast cancer is among the most common malignancies lymph node metastases than in those who do not.2 As a result,
treated by US surgeons.1 Meanwhile, the incidence of mela- accurate nodal staging is important for stratifying patients
noma is rising faster than for all other solid malignancies. In into different risks groups that can be used to direct further
2009, there were an estimated 68,720 new cases of invasive therapy.
melanoma in the United States.
Elective Lymph Node Dissection
Over the past 25 years, significant strides have been made
in the management of these two diseases from the standpoint Until the early part of the 1990s, elective lymph node dis-
of both surgical and adjuvant therapy. For both diseases, section (ELND) was the mainstay of the surgeon’s armamen-
the presence or absence of lymph node metastases is highly tarium for nodal staging of melanoma patients. ELND is the
predictive of patient outcome and is the most important prog- complete surgical removal of the closest nodal basin in
nostic factor for disease recurrence and cancer-related mor- patients with clinically negative lymph nodes. In contrast,
tality. As a result, nodal staging is a critical component of the therapeutic lymph node dissection (TLND) is the complete
staging workup and of treatment planning. The focus of this surgical removal of the draining nodal basin known to have
chapter is the role of nodal staging for both diseases. histopathologically confirmed nodal metastases. Three pro-
No patient with tumor-free regional lymph nodes derives spective, randomized trials failed to demonstrate better sur-
any therapeutic benefit from a complete regional lymphade- vival in melanoma patients treated with ELND than in
nectomy. For patients with clinically negative nodal basins, patients undergoing wide local excision (WLE) alone as
the development of intraoperative lymphatic mapping and primary surgical therapy.3–5
sentinel node (SN) biopsy has made it possible to map lym- With ELND offering no overall survival advantage, a more
phatic pathway from a primary tumor to the initial draining accurate method to identify the approximately 20% of mela-
node(s) (i.e., the SN or SNs) in the regional nodal basin. noma patients who presented with nodal metastasis was
This is the lymph node most likely to harbor metastatic nodal needed. In the 1970s, Roth and colleagues were attempting
disease, if any exists. It has been demonstrated in both breast to identify the nodal basin at risk by injecting colloidal gold
cancer and melanoma that the pathologic status of the SN, around a patient’s primary melanoma site.6 This was a very
when performed by an experienced team, is to be concordant crude technique that identified only the basin at risk and not
with the pathologic status of the entire nodal basin. Integra- the specific node at risk. Alternative newer-generation radio-
tion of these techniques, along with increasingly detailed pharmaceuticals and improved gamma detection devices were
and sophisticated pathologic examination of the SN, into the needed.
surgical treatment of melanoma and breast cancer offers the An alternative method of identifying the node at risk for
potential for more conservative nodal basin operations, lower harboring metastatic disease was first described by Wong
morbidity, and more accurate disease staging. and colleagues using a feline model.7 They demonstrated
that a vital blue dye (Lymphazurin, Hirsch Industries, Inc.,
Richmond, VA) injected into the dermis of the cat would
Lymphatic Mapping and SN Biopsy for Melanoma travel via the dermal lymphatics to the regional nodal basin.
The following year, in human melanoma patients, Morton
rationale and colleagues demonstrated the feasibility of lymphatic
Assessment of Nodal Status mapping and SN biopsy using vital blue dye injected.8 These
investigators showed that the SN is the first node in the
Approximately 20% of melanoma patients have nodal
regional lymphatic basin into which the primary melanoma
metastases at the time of diagnosis. The presence of lymph
consistently drains (although not necessarily the closest to the
node metastases is the single most powerful predictor of
primary lesion). They harvested the SN separately from the
recurrence and survival in melanoma patients. Five-year remainder of the regional nodes and found that the patho-
logic status of the SN was highly accurate at predicting the
* The authors and editors gratefully acknowledge the contribu- pathologic status of the entire nodal basin, which was also
tions of the previous authors, Seth P. Harlow, MD, David N. surgically removed in all of the patients studied. These find-
Krag, MD, FACS, Douglas S. Reintgen, MD, FACS, Freder- ings suggested that melanoma patients could be accurately
ick L. Moffat Jr, MD, FACS, and Thomas G. Frazier, MD, staged with procedures that were far less extensive than
FACS, to the development and writing of this chapter. complete regional nodal dissections.
03/11
preoperative evaluation Increasingly, surgeons are caring for patients who have
undergone previous nodal surgery. Over time, patients
Selection of Patients develop alternate lymphatic drainage pathways after nodal
The risk of nodal metastases in any one individual mela- surgery. Although localization rates tend to be lower under
noma patient depends on a number of factors, including these circumstances, the accuracy of the SN for predicting
primary tumor thickness, presence of ulceration, and mitotic the status of the nodal basin remains high.24,25 Preoperative
rate.9,10 lymphoscintigraphy is critical, even for breast cancer patients,
SN biopsy is most likely to alter therapy in patients who because the altered lymphatic pathways may result in drain-
have a significant risk of nodal metastases but a low risk of age to less common nodal basins. Because development of
systemic disease. As a result, the subgroup of patients with new drainage pathways takes time, accuracy is related to the
intermediate-thickness melanomas (1.0 to 4.0 mm) is the amount of time that has elapsed since the first procedure.
group most likely to benefit from SN biopsy. In patients with For patients in whom the previous nodal procedure was per-
melanomas between 0.76 and 1.0 mm thick, the risk of nodal formed less than 6 months previously, the reliability of the
metastasis is approximately 5 to 6%,11–16 and a balanced dis- SN is doubtful.
cussion should be held with the patient including other Breast cancer and melanoma are frequently diagnosed in
factors such as ulceration, mitotic rate greater than 1, male women of childbearing age, so the safety of lymphatic map-
sex, and axial location.17 Patients with thin melanomas and ping during pregnancy needs to be discussed. Sentinel lymph-
multiple risk factors may be at high enough risk to warrant adenectomy generally requires general anesthesia, so the
SN biopsy. risks of surgery during pregnancy need to be considered. In
On the opposite end of the spectrum are patients with thick addition, there are potential risks related specifically to the
melanomas (> 4.0 mm). For these patients, the risk of sys- lymphatic mapping. Neither isosulfan blue dye nor methylene
temic metastases is as high as 50 to 60%, whereas the risk of blue dye has been tested for safety during pregnancy. In the
nodal metastases ranges from 40 to 50%. ELND was not absence of data, it is recommended that these be avoided.
recommended for such patients in the past because of this Although radiation is teratogenic, studies suggest that the
high risk of systemic disease. However, even among patients levels of radiation associated with lymphoscintigraphy are low
with thick melanomas, survival is better for those with nega- and safe.26–28 No adverse events have been documented in
tive nodes than for those with microscopic nodal disease.18 reported case series to date.29,30
As a result, patients with thick melanomas and no obvious operative planning: positioning and anesthesia
systemic metastases may benefit from SN biopsy to stage the
Patients should be prepared to undergo wide excision of
nodal basin. This is particularly important if the presence of
the primary melanoma site (if not previously performed) and
nodal metastases will change the adjuvant treatment plan
SN biopsy during the same operative session. Depending on
from observation to active systemic therapy.
the location of the primary lesion, it may be possible to per-
The available data suggest that lymphatic mapping is appli-
form the two procedures with the patient in a single position;
cable to all primary body sites, including the head and neck
however, often the patient must be repositioned during the
(the most technically demanding sites).19,20 The best results
procedure to afford the surgeon adequate access to the differ-
are achieved with a combination mapping approach that
ent locations. The choice of anesthesia varies, depending on
employs both a vital blue dye and a radiocolloid. The proce-
the size and location of the wide excision and the anatomic
dure is associated with slightly higher false negative rates in
depth of the SNs. In very selected cases, local anesthesia
patients with head and neck melanoma than in those with
may be appropriate, but for most lesions, general or regional
melanoma of the trunk or extremities (10% versus 1 to 2%). anesthesia is preferable.
Nevertheless, the false negative rates with head and neck
melanoma are still low enough to justify offering lymphatic operative technique
mapping to patients. Although the technical details of lymphatic mapping and
SN biopsy for melanoma vary from institution to institution,
Special Circumstances the reported results of the different approaches have been
very similar. Proper performance of these procedures requires
The extent of any operation done at the primary site before close collaboration between the nuclear medicine physician,
SN biopsy may affect the success of the biopsy procedure. the surgeon, and the pathologist, with each member playing
In patients who have had an appropriate 1 or 2 cm margin a critical role in the process.
resection and then large areas of tissue undermining or have
undergone reconstruction with a rotational flap or Z-plasty Step 1: Injection of Radiolabeled Tracer and Lymphoscinti-
to close the oncologic resection defect, the normal lymphatic graphy
channels may be disrupted. Such disruption may render SN On the day of the procedure, the patient reports to the
biopsy inaccurate. Nevertheless, there have been reports of nuclear medicine suite for injection of the radiolabeled tracer
SN biopsy being performed successfully after previous WLE.21 and preoperative lymphoscintigraphy. It is crucial to have a
These patients may have more SNs in more regional nodal mechanism in place by which the location of the primary
basins than patients in whom the primary tumor has not melanoma site can be reliably communicated to the nuclear
been resected with curative intent, but at present, there is no radiologist. Some melanoma biopsy sites are difficult to
unequivocal evidence that previous WLE of the primary locate, particularly if multiple skin biopsies have already been
lesion increases the risk of postoperative nodal relapse.22,23 performed.
03/11
A radiolabeled agent is then selected; the most common of secondary nodes. There have, however, been several
choices are technetium-99m (99mTc)–labeled sulfur colloid reports of SN procedures being accurately performed 16 to
(TSC) and 99mTc-labeled antimony trisulfide colloid (T- 24 hours after tracer injection.19 Because TSC is retained in
ATC). The dose of the tracer and the volume of the injectate the SN dendritic cells, the SNs can still be easily identified
are largely determined by the location and size of the primary after 6 hours, whereas the radioactivity at the injection site
tumor site but generally can be kept to 0.5 mCi or less and and resultant background interference may be diminished
1 mL or less, respectively. Injections are made intradermally because of the short half-life of technetium (6 hours).
around the circumference of the lesion or biopsy site, and
Step 2: Intraoperative Lymphatic Mapping and Identification
dynamic scans are taken 5 to 10 minutes after injection.
of SN
Although the location of the SN may be marked on the skin
by the radiologist to assist the surgeon, this location may vary It is our practice to review the lymphoscintigram when the
slightly with changes in patient position and should therefore patient arrives in the preoperative holding area. For patients
be confirmed by the surgeon with the gamma probe in the who had either ambiguous drainage or no drainage, we
operating room. To allow complete and accurate nodal stag- evaluate the patient with the gamma probe before deciding
ing, all regional basins at risk should be marked, along with on positioning. Probe evaluation, whether performed in the
any in-transit nodes that are identified [see Figure 1]. If there preoperative holding area or in the operating room, begins by
is no migration of TSC after approximately 60 to 90 minutes, defining the diffusion zone around the primary tumor site,
then a second injection of filtered TSC is performed. If where SN identification is not possible. The area between this
no migration occurs, the nuclear medicine physician com- diffusion zone and the possible nodal drainage sites is then
municates this directly with the operating surgeon. mapped for possible in-transit nodes by means of a systematic
The surgical procedure should be carried out no more than but expeditious evaluation for radioactive “hot spots.” The
6 to 8 hours after TSC injection. Activity in the SNs usually gamma probe is moved in a linear fashion between the diffu-
reaches its maximum 2 to 6 hours after injection; waiting sion zone and the nodal basin. It is then shifted medial or
longer to carry out the procedure may increase the labeling lateral to the previous line, and the process is repeated until
the entire area is evaluated. The location of a radioactive
hot spot is confirmed by identifying a discrete location where
the radioactive counts are higher than the counts found in the
tissue 1 to 2 cm more proximal to the injection site (the
background skin count). The counts from the hot spot and
the background are recorded. The hot-spot site is marked on
the skin to allow more direct dissection to the SN.
Concomitant use of a vital blue dye is favored by many
surgeons and is our preferred method. The blue dye is com-
plementary to the radiolabeled tracer; the combination of the
two marking agents improves the chances of identifying the
SN and facilitates node retrieval. The blue dye is injected into
the dermis immediately adjacent to the melanoma. For lesions
on an extremity, the dye may be injected along the proximal
margin of the lesion or biopsy site; for lesions on other areas,
it should be injected circumferentially. The general recom-
mendation is to wait 5 to 10 minutes after injecting the dye
Figure 1 Lymphatic mapping and sentinel lymph node before initiating SN retrieval.
(SLN) biopsy for melanoma. In-transit nodal areas are To minimize the dissection required for node resection, the
identified in 5% of melanoma patients; this is the reason why incision for the SN biopsy should be made through the hot
preoperative lymphoscintigraphy is performed for primary spot identified by the gamma probe. The incision should also
sites on either the upper or the lower extremity. In a patient be situated so that it can be incorporated into a longer inci-
with a melanoma on the left hand (a), the injection site and
sion should the finding of a positive SN necessitate perfor-
the left hand are raised above the head, and cutaneous
lymphatic flow into an epitrochlear node can be seen. This
mance of a TLND. The gamma probe is placed in a sterile
in-transit node then emits a lymphatic vessel flowing to the sheath and used again after the incision is made to guide
left axilla. By definition, the SLN is the first node in the chain further dissection. If blue dye was used, the surgeon can visu-
that receives primary lymphatic flow. The epitrochlear node ally follow the blue lymphatic channels to the blue-stained
and any axillary nodes are nodes in series. Hence, the SN.
epitrochlear node is the SLN and thus is the only node that An SN is defined as either (1) all radioactive nodes with
must be harvested. In a patient with a primary melanoma on an ex vivo node to background ratio greater than 10:1, (2) a
the left flank (b), there are two separate afferent lymphatics, node that either is blue or clearly has a blue-stained lymphatic
one leading to an SLN in the left axilla and the other leading
vessel entering it, or (3) a firm palpable node. When an SN
to an in-transit node on the left flank. These are nodes in
parallel in that they both receive primary lymphatic flow from is removed, the ex vivo radioactivity count in the node is
the skin site. Hence, the two nodes are equally at risk for recorded. This count is then used as a reference for determin-
metastatic disease, and both are considered sentinel nodes ing which, if any, of the remaining nodes in that basin (some
and must be harvested. of which may be potential SNs) should be removed. In our
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view, if the radioactivity count in the hottest remaining node undergoing SN biopsy was 4.6%, compared with 23.2% in
in the basin is less than 10% of the ex vivo count in the hot- 444 patients undergoing completion lymph node dissection
test SN, none of the remaining nodes should be considered (CLND).38
SNs.19,31 Any nodes with radioactivity counts exceeding this
outcome evaluation
10% threshold, however, should be removed.
Once an SN is identified, it should be dissected out with Ideally, level I evidence from a prospective, randomized,
as little trauma to the surrounding tissues as possible. Lym- controlled trial would demonstrate that lymphatic mapping
phatic channels to the node should be identified and either and SN biopsy are superior to close nodal observation as the
tied or clipped to reduce the risk of postoperative seroma treatment of choice for melanoma patients. The Multicenter
formation. Because the gamma probe can localize SNs with Selective Lymphadenectomy Trial (MSLT-1; Donald
great accuracy, routine dissection of motor nerves is not Morton, principal investigator) was designed to compare
required; however, knowledge of the likely location of the WLE and SN biopsy to WLE and close observation in patients
motor nerves is critical for preventing inadvertent injury to with intermediate-thickness melanomas. A detailed descrip-
these structures during dissection. tion of the trial has been published.39 Briefly, all patients with
After SN removal, a final count of the SN biopsy bed is intermediate-thickness melanomas eligible for the trial (Bres-
taken to document that all significantly radiolabeled nodes low thickness 1.2 to 3.5 mm) were randomized in a 60:40
have been accounted for and removed. In addition, the ratio to WLE and SN biopsy or to WLE and watchful wait-
tissues are examined for blue-stained lymphatic channels or ing. All patients with a tumor-involved SN went on to an
lymph nodes regardless of radioactivity. (As noted, blue stain- immediate TLND. For patients in the watchful waiting
ing confers SN status even if the node is not radioactive.) arm, a delayed TLND was performed if clinically apparent,
Firm tumor-involved nodes with obstructed afferent lym- pathologically confirmed nodal disease was identified.
phatics may divert lymph flow to non-SNs, and such diver- After the third interim analysis, the Data Safety Monitoring
sion is a significant cause of false negative SN biopsy results. Board insisted that the data be released to the public because
Consequently, the final step is to palpate for grossly suspi- several secondary end points had been met. Most impor-
cious nodes. If grossly suspicious nodes are identified after all tantly, melanoma-specific survival in patients with nodal
relevant SNs have been removed, the suspicious nodes should disease was improved for patients in the SN biopsy arm com-
also be removed. pared with watchful waiting. Patients with a tumor-involved
SN who underwent immediate LND had a 5-year survival
Step 3: Pathologic Evaluation of SN advantage compared with those in the watchful waiting
The optimal extent of pathologic evaluation of SNs in arm who developed a nodal basin metastasis: 72.3% versus
patients with melanoma has been the subject of some debate. 52.4% (hazard ratio 0.51, 95% confidence interval 0.32 to
SN biopsy allows pathologists to focus their efforts on one 0.81, p = .004).39 These results continue to hold up after the
node or a small number of nodes, and this focus has led to a fourth interim analysis with 10-year survival advantage of
process of ultrastaging. Several good methodology articles 63.2% versus 36.5% (p < .001).40
describing the handling and processing of SN are available in To date, the primary end point, improved overall survival,
the literature.32,33 Our current institutional protocol has been has not been met. Although this has led some critics to advo-
published.34 Briefly, the SN is bivalved and then serially sec- cate abandoning SN biopsy in melanoma patients,41 several
tioned at 1 to 2 mm section across both halves. The nodal clarifications need to be emphasized. First, no lymph node–
sections are first evaluated with hematoxylin-eosin (H&E) negative patient ever derives a survival benefit from under-
stain. If no obvious metastases are identified, the immunohis- going nodal operation, whether ELND or SN biopsy. Given
tochemical stains are applied, S-100 and MART-1. This that the incidence of nodal metastases in patients with
enables the pathologist to identify tiny (less than 1 mm) intermediate-thickness melanoma, as defined by the MSLT-
deposits of metastatic melanoma. 1, would be expected to be around 20%, 80% of patients
enrolled on the trial could not possibly derive a survival
complications advantage. These patients who cannot benefit dilute the
Complications of SN biopsy are quite uncommon. Allergic observed magnitude of effect for those who do benefit.
reactions to the blue dyes occur in less than 1% of patients Second, SN biopsy is not proposed as a therapeutic proce-
but can range in severity from mild urticaria to anaphylaxis; dure but rather as a highly sophisticated staging procedure.
thus, the surgical team and the anesthesia team should always On MSLT-1, the patients with a tumor-involved SN subse-
quently underwent a directed TLND. The results of MSLT-
be prepared for this uncommon but potentially serious prob-
1 demonstrate a clear survival advantage in performing the
lem.35,36 In experienced hands, motor nerve injury is rare. In
TLND early in an association with a tumor-involved SN
a series of 47 patients who had head and neck melanomas
as opposed to later, when palpable lymphadenopathy is
with SN drainage to the parotid region, there were no perma-
detected.
nent injuries to the facial nerve when the SN was removed
without formal nerve dissection.37 Similar results have been
reported for nodes in the posterior triangle of the neck and in Lymphatic Mapping and SN Biopsy in Breast Cancer
the axilla. The incidence of wound complications is quite low
(1.7% wound complication rate; 3.0% seroma rate), as is the rationale: assessment of nodal status
incidence of postbiopsy lymphedema (0.7%). In the Sunbelt In early breast cancer, as in melanoma, the pathologic
Melanoma Trial, the complication rate in 2,120 patients status of the regional lymph nodes is the most important
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predictor of outcome. The presence of regional lymph node chemotherapy is highly controversial. Several recent studies
metastases in breast cancer reduces 5-year survival by 28 to have shown a low false negative rate for patients with T3
40%.42,43 Prognostic factors related to primary tumor charac- tumors who have an SN procedure prior to neoadjuvant che-
teristics have consistently been shown to be inferior to nodal motherapy,51–55 as well as those authors advocating the proce-
status as predictors of overall survival. In addition, axillary dure after the neoadjuvant chemotherapy.56–58 Several good
lymph node dissection in the setting of breast cancer is supe- reviews of the controversy are published.59–61 The remainder
rior to observation and at least equivalent to irradiation for of this chapter deals with patients who present with unifocal,
regional disease control in clinically node-negative patients.44 T1 or T2, clinically node-negative breast cancer.
There is some evidence that adequate regional disease control
may confer a small survival benefit.45 operative planning: positioning and anesthesia
Invasive breast cancer has a relatively high rate of nodal Patients should be placed in the supine position, with all
metastasis in clinically node-negative patients. The risk of potential nodal sites within the operative field. Although SN
metastasis is clearly related to the size of the primary tumor,
biopsy may be performed with the patient under local
but it is significant (15% or higher) even in patients with early
anesthesia, we favor general anesthesia for this procedure,
(T1a) lesions.46,47 The primary nodal drainage basin for the
particularly when it is done in conjunction with the breast
breast is the ipsilateral axilla; however, drainage to extra-
excision.
axillary sites (e.g., the internal mammary lymph node chain,
the supraclavicular nodes, and the intramammary nodes) is operative technique
also reported. Other potential sites of lymphatic drainage not-
withstanding, the recommended surgical procedure for evalu- Step 1: Injection of Radiolabeled Tracer and Lymphoscinti-
ating the regional lymph nodes in clinically node-negative graphy
breast cancer patients has been level I and II axillary lymph In the United States, the radiocolloid most commonly
node dissection (ALND). Such dissections are, however, employed for SN biopsy in breast cancer patients is TSC,
associated with a significant risk of long-term morbidity, pri- which may be used either unfiltered or filtered (< 220 nm)
marily related to the risk of lymphedema in the affected arm. The 99mTc dose generally ranges from 0.45 to 1.0 mCi, and
For this reason, SN biopsy was developed and investigated the injectate volume ranges from 4 to 8 mL. Several routes
as a possible substitute for standard ALND in the treatment
of tracer injection have been investigated for SN biopsy in
of breast cancer patients with clinically uninvolved axillary
breast cancer patients, primarily in response to the difficulties
lymph nodes.
sometimes associated with peritumoral injection (e.g., delayed
preoperative evaluation tracer uptake and wide diffusion zones that can overlap the
nodal basins). These routes include intradermal or subdermal
Selection of Patients injection in the area overlying the tumor, subareolar injection,
All clinically node-negative patients with a diagnosis of and periareolar injection. The rationale for the development
invasive breast cancer are potential candidates for SN biopsy. of these alternatives is that there is significant overlap between
Ideal candidates are those patients with unifocal lesions less the lymphatic vessels of the breast skin and those of the breast
than 5 cm in greatest dimension who have no history of parenchyma. Multiple studies have confirmed that the use of
previous axillary surgery or previous cancer treatment. Per- these injection routes yields high localization rates and results
forming an SN biopsy after a previous excisional biopsy is in accurate removal of SNs that reflect the pathologic nodal
technically feasible. Patients who have undergone extensive status of individual patients. A notable deficiency of these
previous breast procedures (e.g., breast reduction, placement techniques, however, has been the low reported rate of tracer
of breast implants, or multiple open biopsies) may have sig- migration to nodes outside the axilla, particularly to the inter-
nificant alterations in the lymphatic pathways; however, accu- nal mammary lymph node chain. This result is thought to be
rate identification of the SN can still be accomplished with
attributable to a unique set of lymphatic channels deep in the
proper planning of the injection sites. Patients with multifocal
breast parenchyma, separate from the overlying skin, that
tumors or multicentric breast cancers also require thoughtful
drain to the internal mammary chain.
planning of the injection sites, although there is some evi-
The various tracer injection methods have not been directly
dence suggesting that using periareolar injection sites may
allow the procedure to be performed accurately in patients compared; thus, at present, the optimal route of injection can
with multifocal disease.48 For patients who will be undergoing be inferred only by comparing studies from different institu-
mastectomy with immediate breast reconstruction, perform- tions. The potential importance of the extra-axillary sites is
ing SN biopsy as an outpatient procedure prior to the planned not entirely clear, but it appears that these sites may be the
mastectomy may facilitate surgical planning depending on the sole locations of metastatic disease in as many as 20% of the
need for postmastectomy radiation or ALND.49 However, the node-positive patients from whom they are removed.62,63
false negative rate of SN biopsy may be higher in cases with Most patients in whom SNs are found outside the axilla have
large additive tumor burden.50 additional SNs in the axillary basin.
For patients who present with inflammatory breast A thorough literature review on the use of different routes
carcinoma or who present with palpable adenopathy and of injection and the associated rates of SN localization by
pathologically confirmed metastatic nodal disease, there is nodal basin, node positivity rates, and false negative rates
absolutely no role for SN biopsy at the time of presentation. has been performed. This review included those studies in
The role of SN biopsy in patients who present with large which a radiolabeled tracer was used for SN identification
breast cancers and are scheduled to receive neoadjuvant (either by lymphoscintigraphy or by intraoperative gamma
03/11
probe localization) and in which the location of the SN basins

and the pathologic status of the SNs could be ascertained.
The results of previous reviews of almost 9,000 patients indi-
cated that all of the approaches have acceptable SN retrieval
rates but that the rates are slightly higher with the more
superficial ones (i.e., the dermal, subareolar, and periareolar
techniques).62,64–67 There are, however, significant differences
in the locations of the SN basins identified with the different
methods: with the superficial injection techniques, drainage
is essentially confined to the axillary basin, whereas with the
deeper injection techniques, as many as 22% of patients are
found to have nodal basins outside the axilla. Approximately
16 to 21% of the extra-axillary SNs will be found to have
metastatic disease if removed. The clinical ramifications of
these findings are that some patients may be understaged if
the extra-axillary sites are not evaluated, and such understag- Figure 2 Lymphatic mapping and sentinel node (SN) biopsy
ing may affect the recommendations for systemic adjuvant for breast cancer. A small incision is made in the axilla on the
basis of the hot-spot location. The SNs identified are both
therapy.
radioactive and stained blue.
Whether the breast cancer is palpable or nonpalpable,
we prefer that the injection is guided by ultrasonographic
evidence. If an excisional biopsy was previously performed, basin (some of which may be potential SNs) should be
the tracer should be injected into the breast parenchyma removed. In our view, if the radioactivity count in the hottest
rather than into the biopsy cavity; it will not diffuse out of the remaining node in the basin is less than 10% of the ex vivo
cavity. This is also best done under ultrasonographic guid- count in the hottest SN, none of the remaining nodes should
be considered SNs, and none should be removed.67 Any
ance. In addition, injections should not be made into the ret-
nodes whose radioactivity counts exceed this 10% threshold,
romammary fat or the pectoral fascia, because doing so would
however, should be removed.
lead to wide diffusion of tracer throughout the chest area,
A final count of the SN biopsy bed is then taken to docu-
which would make nodal identification very difficult.
ment that all significantly radiolabeled SNs have been
In breast cancer patients, the timing of SN biopsy after
accounted for and removed. In addition, the tissues are exam-
tracer injection is not of critical importance. Good results
ined for blue-stained lymphatic channels or lymph nodes
have been obtained with injection-to-biopsy intervals ranging
regardless of radioactivity; as noted, blue staining confers SN
from 30 minutes to 24 hours. The usual recommendation is
status even if the node is not radioactive. Finally, when it
to wait 1 to 2 hours.
appears that all relevant SNs have been removed, as con-
Step 2: Intraoperative Lymphatic Mapping and Removal of firmed by the final bed count, the tissues are palpated for
SN grossly suspicious nodes. Firm tumor-involved nodes with
obstructed afferent lymphatics may divert lymph flow to non-
Once the patient is asleep, the vital blue dye (Lympha-
SNs, and such diversion is a significant cause of false negative
zurin) is injected either peritumorally, into the parenchyma
SN biopsy results.
surrounding an excisional biopsy, intradermally, or subareo-
Once an SN is identified, it should be dissected out with
larly depending on surgeon preference. The breast is gently
as little trauma to the surrounding tissues as possible. Lym-
massaged for 5 to 10 minutes to enhance transport of the dye phatic channels to the node should be identified and either
to the SNs. Our approach begins by performing a primary tied or clipped to reduce the risk of postoperative seroma
survey of the potential nodal sites with the handheld gamma formation. Because the gamma probe can localize SNs with
detector. Using one of the commercially available handheld great accuracy, routine dissection of motor nerves is not
gamma probes, an axillary hot spot is identified, and then a required; however, knowledge of the likely location of the
small incision is made. The gamma probe, sterile sheathed, motor nerves is critical for preventing inadvertent injury to
is inserted into the wound and guides the dissection to the these structures during dissection.
radioactive node(s). During the dissection, the surgeon looks
for blue-stained lymphatic channels and nodes [see Figure 2]. Step 3: Pathologic Evaluation of SN
Most of the time, the radiocolloid and the vital blue dye iden- Pathologic SN evaluation in breast cancer patients has
tify the same SNs. The SNs are then carefully removed, and two main aspects. The first is intraoperative evaluation of the
the lymphatic vessels entering them are tied or clipped off SN when the pathologic status of the node is being used to
whenever possible. determine the need for ALND; the second is permanent
An SN is defined as either (1) all radioactive nodes with an evaluation of the nodes to determine whether micrometa-
ex vivo node to background ratio greater than 10:1, (2) a static disease is present. Both have conflicting views in the
node that either is stained blue or clearly has a blue-stained literature.
lymphatic vessel entering it, or (3) a firm palpable node. Two techniques are commonly employed for intraoperative
When an SN is removed, the ex vivo radioactivity count in evaluation of SNs: frozen-section analysis and touch-imprint
the node is recorded. This count is then used as a reference cytology. Frozen-section histopathology is available in most
for determining which, if any, of the remaining nodes in that hospitals, and all surgical pathologists have some experience
03/11
with it. This technique has a drawback, however, in that it and then serially sectioned at 1 to 2 mm section across both
sometimes uses up a large portion of the SN, leaving a rem- halves. The nodal sections are first evaluated with H&E stain.
nant that is insufficient for permanent paraffin-embedded In 1999, the College of American Pathologists issued a con-
sections. In addition, the sectioning of radioactive nodes on sensus statement recommending that the staging of SNs be
a cryostat raises radiation safety issues for the pathologists. based on routine histologic evaluation of the nodes cut at
Studies of frozen-section techniques of evaluating SNs for approximately 2 mm intervals.72 Routine use of cytokeratin
metastatic breast cancer report false negative rates of 27 and IHC staining should not be adopted as standard until its
32%.64,68 When 60 frozen sections are made from each SN, significance is demonstrated in clinical trials.
the false negative rate can be reduced to about 5%,64,69 but at
the cost of 45 to 60 minutes of operating time and loss of complications
tissues for permanent histopathologic evaluation. Frozen sec- The complications of SN biopsy in breast cancer patients
tion is far more effective in detecting macrometastatic disease are similar to those seen in melanoma patients.73 There is a
(sensitivity 92%) than micrometastatic disease (sensitivity minor (< 1%) risk of allergic reactions to the blue dye.74
17%), and the volume of nodal metastases is highly corre- There is a small risk of sensory or motor nerve injury or
lated with tumor size.70 In comparison, touch-imprint cytol- lymphedema whenever an axillary node procedure is per-
ogy consumes much less time and tissue, is far more accurate formed; this risk is substantially reduced, although not entirely
(false negative rate 0.8%),71 and does not contaminate the eliminated, with SN biopsy.75 With an internal mammary SN
cryostat. It has also been applied to the evaluation of lumpec- biopsy, there is a risk of pneumothorax from unintended
tomy margins [see Figure 3]. The chief limitation of the touch- opening of the parietal pleura. This risk is very small with
imprint method is that for optimal results, it requires a careful technique, however, and the problem can almost
pathologist who is highly skilled in the cytologic evaluation of always be corrected by closing the wound around a rubber
lymph nodes. Some centers use rapid immunohistochemical catheter inserted through a small stab incision and removing
(IHC) analysis for cytokeratin staining to detect tumor cells it at the end of a positive pressure breath given by the anes-
in touch-imprint or frozen-section specimens, anticipating
thesiologist. Surgical site infections occur in fewer than 1%
that detection of such cells can thereby be improved, particu-
of cases, and small seromas occur in about 10%.
larly in patients with invasive lobular or well-differentiated
ductal carcinomas. outcome evaluation
The optimal extent of pathologic evaluation of SNs in
The first report of SN biopsy in breast cancer, published in
patients with breast cancer has been the subject of some
1993, described the use of the gamma probe localization
debate. SN biopsy allows pathologists to focus their efforts
technique for SN identification.76 A second report, published
on one node or a small number of nodes, and this focus has
the following year, described the use of the vital blue dye
led to a process of ultrastaging. Several good methodology
technique for SN identification.77 Since these initial feasibility
articles describing the handling and processing of SN are
reports, many single-center and multicenter studies have
available in the literature.32,33 Our current institutional proto-
been published that achieved remarkably similar results using
col has been published previously.34 Briefly, the SN is bivalved
either or both of these techniques.
The early studies of SN biopsy tended to use either a radio-
labeled tracer or a vital blue dye alone. The first trial in which
the two agents were used together was published in 1996.65
This study documented an improvement in SN localization
and a 0% false negative rate, albeit in a small series of patients.
Subsequent multicenter trials incorporating larger study
groups yielded more reliable indications of the applicability of
these techniques to the overall surgical community. In one
such study, surgeons from 11 centers performed SN biopsies
and confirmatory axillary dissection in clinically node-
negative patients with invasive breast cancer.66 The overall
success rate for identifying and removing an SN was 93%, the
pathologic accuracy rate for predicting the presence of nodal
metastases from the SNs removed was 97%, and the patho-
logic false negative rate was 11.4%. A subsequent multicenter
trial, using a combination of blue dye staining and the gamma
probe technique in most patients, reported an SN retrieval
Figure 3 Lymphatic mapping and sentinel node biopsy for rate of 88% and a pathologic false negative rate of 7.2%.67
breast cancer. In touch-imprint cytology, slides are touched A third trial, using the gamma probe technique, reported an
to tissue from a “hot” specimen, and cells on the section SN retrieval rate of 87% and a pathologic false negative rate
or the margin are exfoliated onto the slide for cytologic
of 13%.78 A fourth trial, using both blue dye staining and
preparation. Shown are (a) permanent histology of an
infiltrating ductal carcinoma extending down to an inked
the gamma probe technique, reported an SN retrieval rate of
margin and (b) a touch preparation demonstrating bizarre 86% and a pathologic false negative rate of 4%.79
malignant cells from the sampling of the margin. The To evaluate the true efficacy of a new technology, a
advantages of this technique are that the entire margin can be prospective trial needs to be performed, and the first one
sampled and that tissue is not lost in the cryostat. completed was by Veronesi and colleagues.80 In this trial, 516
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evaluable patients were randomly assigned to undergo either The question in the SN era remains: in patients with H&E-
SN biopsy with confirmatory axillary dissection (257 patients) detected metastases, what, if anything, should be done to the
or SN biopsy with axillary dissection done only if the biopsy remainder of the axillary nodes? Two prospective, random-
yielded positive results (259 patients). At a median follow-up ized trials were designed to answer this very important ques-
point of 46 months, no significant survival differences were tion. The first is the European Organisation for Research and
reported, and there were no regional nodal recurrences in Treatment of Cancer (EORTC) AMAROS (after mapping of
either arm. Admittedly, the study size was small and the the axilla: radiotherapy or surgery) trial in which patients with
follow-up relatively short, but still there was no significance an H&E-detected SN metastasis were randomized to axillary
in axillary failure in patients who received only an SN radiation versus a completion ALND. The trial finished
biopsy. accrual in 2008 but, because of a lower than expected event
The National Surgical Adjuvant Breast and Bowel Project rate, had to reopen to accrual. The other important trial is
(NSABP) undertook a trial very similar to that of the Milan ACOSOG Z0011, in which patients with H&E-detected
group, NSABP B-32. Breast cancer patients with clinically metastases were randomized to completion ALND or obser-
node-negative axillae were randomized to undergo SN biopsy vation. At ASCO 2010, Giuliano and colleagues, for the first
with mandatory ALND or SN biopsy with ALND if the SN time, stated that there was no difference in overall survival
revealed metastatic breast cancer.81 Between 1999 and 2004, between the two groups (completion ALND 91.9% versus
5,611 patients were accrued and randomized. The technical observation 92.5%) or disease-free survival (82.2% versus
details have been published81; previously, the SN identifica- 83.8%, p = .13).84 Thus, in a large phase III trial, albeit
tion on the trial was 97% and the false-negative rate was underpowered, there is not even a trend toward a survival
9.7%, very consistent with some of the early breast SN advantage in patients receiving ALND. Routine ALND
reports. At the 2010 meeting of the American Society of following a positive SN adds nothing to the patient’s overall
Clinical Oncology (ASCO 2010), Krag and colleagues stated survival.
for the first time that there was no difference in overall sur-
vival, disease-free survival, or locoregional recurrences, thus
providing level I evidence that the SN biopsy is an accurate Radiation Exposure Guidelines and Policies
and safe alternative to routine ALND in clinically node- The amount and type of radioactivity injected in the course
negative breast cancer patients.82 of lymphatic mapping and SN biopsy are relatively limited.
The American College of Surgeons Oncology Group Typically, from 0.4 to 1.2 mCi of 99mTc is injected. This
(ACOSOG) undertook an SN trial designed to evaluate the agent is a pure gamma emitter with a short half-life (6 hours);
incidence and prognostic significance of SN and bone marrow thus, the risks of potentially harmful beta radiation are
micrometastases in patients with early-stage breast cancer. avoided. The total radiation dose used is quite small—only
ACOSOG Z0010 was a phase II trial in which all patients about 5% of that used in common nuclear scanning tech-
enrolled underwent a SN biopsy and bilateral iliac crest bone niques (e.g., bone scans). It has been estimated that a maxi-
marrow aspirates. If the SNs were negative by H&E stain, mum of 0.45 Gy could be absorbed at the injection site. Of
then they were submitted to the central laboratory for IHC hospital workers, the surgeon is exposed to the highest levels
stains. From April 1999 through May 2003, 5,539 patients of radiation. A study from Walter Reed Army Medical Center
were enrolled. At ASCO 2010, Cote and colleagues presented found that the hands of surgeons performing lymphatic
for the first time the unblinded SN IHC results.83 There was mapping and SN biopsy were exposed to an average of 9.4 ±
no difference in overall survival in patients with IHC-detected 3.6 mrem per operation.85 Therefore, on the basis of skin
metastases compared with tumor-free SN (95.1% versus dosage recommendations set by the Nuclear Regulatory
95.8%, p = .53). Thus, the routine examination of SN with Commission, a surgeon would have to perform more than
IHC in patients with invasive ductal carcinoma should not be 5,000 SN procedures a year to incur more than the minimal
performed. level of risk.
The advent of the SN has reopened the debate regarding The low risk notwithstanding, proper handling of radioac-
the impact of ALND on overall survival. One of the earliest tive specimens is recommended. All such specimens should
NSABP studies, B-04, randomized patients to either radical be handled as little as possible for at least 24 to 48 hours
mastectomy, total mastectomy with delayed ALND if and should be appropriately labeled. Physicians performing
necessary, or total mastectomy and radiotherapy.44 There was these procedures should develop guidelines for handling and
no overall survival difference between the three arms of the processing specimens in accordance with their institution’s
trial, but the trial was not powered to detect a small survival radiation safety policies.
advantage. Patients receiving an ALND appeared to have
improved the locoregional recurrence rate. Financial Disclosures: None Reported
References
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Is routine intraoperative frozen-section ex- Multicenter trial of sentinel node biopsy for tive sentinel node. Presented at American
amination of sentinel lymph nodes in breast breast cancer using both technetium sulfer Society of Clinical Oncology Annual
cancer worthwhile? Ann Surg Oncol 2000;7: colloid and isosulfan blue dye. Ann Surg Meeting; 2010 March; Chicago, IL.
651–5. 2001;233:51–9. 85. Miner TJ, Shriver CD, Flicek PR, et al.
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cancer. Ann Surg Oncol 1998;5:689–94. Surg Oncol 2002;9:248–55. 1999;6:75–82.
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3 BREAST, SKIN, AND SOFT TISSUE 7 EVOLVING MOLECULAR THERAPEUTICS AND
THEIR APPLICATIONS TO SURGICAL ONCOLOGY — 1
7 EVOLVING MOLECULAR
THERAPEUTICS AND THEIR
APPLICATIONS TO SURGICAL
ONCOLOGY
Melissa Heffler, MD, Vita Golubovskaya, PhD, and Kelli Bullard Dunn, MD, FACS, FACRS
Despite advances in both medical and surgical therapy for tyrosine autophosphorylating carboxy-terminal tail. The
cancer, the majority of cancer deaths result from metastasis. majority of RTKs function in pairs, and activation induces
Traditionally, chemotherapy has been the mainstay of ther- dimerization [see Figure 1].1,3,4 Dimerization then triggers a
apy for systemic disease. However, even the most effective phosphorylation cascade involving the cytosolic non-RTKs
chemotherapeutic agents are rarely curative. Moreover, toxic- [see Figure 2]. These non-RTKs relay intracellular signals by
ity is common and can be debilitating and dose limiting. additional protein phosphorylation.4 Many processes involved
It has proven difficult to find an agent that is toxic to cancer in tumor progression and metastasis, including proliferation,
cells but does not in some way damage healthy cells. This angiogenesis, migration, and cell survival, are influenced
treatment paradox has prompted a revolution in drug devel- by dimerization, autophosphorylation, and the resulting
opment. Increasingly, research efforts are focusing on the downstream signal cascade.1,3 Although these processes are
development of agents that target molecules that are specific necessary for normal cell turnover, mutations can alter the
to tumor cells. The ability of cancer cells to resist apoptosis, expression or activation of TKs and thereby lead to uncon-
proliferate unchecked, and detach and metastasize results trolled activation in cancer cells.5 To date, the 58 RTKs that
from activation and dysregulation of complex signaling have been described are classified into over 20 families based
cascades that in normal cells are controlled by intrinsic on molecular structure and the sequence of the kinase
checkpoints and regulatory processes. Better understanding domain.2,5,6 Of these, approximately 30% have been found to
of these pathways, and of their checks and balances, has led be either mutated or unregulated in cancer.5 Several RTKs
to the development of agents that specifically target these are now known to play important roles in tumorigenesis and
processes in tumor cells. Agents are generally classified based have become effective therapeutic targets. For example, c-kit
on mechanism of action; however, overlap exists, and class is unregulated in gastrointestinal stromal tumors (GISTs)
lines are often blurred. The following summary describes and acute myelogenous leukemia (AML), HER-2 is elevated
historic targeted therapies that have laid the groundwork for in breast cancer, and RET is altered in the multiple endocrine
current investigations and outlines current breakthroughs neoplasia (MEN) disorders.5 These and other RTKs, there-
that are revolutionizing the way cancer is treated. The ulti- fore, provide potential targets for molecular therapeutics.
mate goal of molecular therapeutics is to develop agents that
  
are lethal only to tumor cells, that maintain efficacy without
developing resistance, and that possess acceptable toxicities Delineating the role of TKs in tumorigenic processes such
that make them well tolerated by patients. as invasion, angiogenesis, and proliferation prompted the
development of several tyrosine kinase inhibitors (TKIs) that
target either the receptor or the ligand that promotes the
Tyrosine Kinase Inhibitors downstream signal cascade.1 The resulting flood of TKIs has
  been variably classified by the target receptor or ligand, the
signaling pathway affected, or their molecular structure.
Tyrosine kinases (TKs) are enzymatic proteins that cata- For the purposes of this review, TKIs are classified based
lyze the phosphorylation and activation of other signaling on molecular structure: (1) monoclonal antibodies, (2) small
proteins.1 As their name implies, the target of these kinases is molecule kinase inhibitors, and (3) multitargeted kinase
the tyrosine residue on a variety of proteins. TKs have long inhibitors [see Table 1].
been known to play a role in cancer progression, and as such,
inhibition of TKs has been at the forefront of targeted cancer Monoclonal Antibodies
therapy. TKIs were first introduced to the anticancer armamen-
TKs are classified as either receptor or nonreceptor kinases. tarium with the development of imatinib mesylate for the
Fifty-eight membrane-spanning receptor tyrosine kinases treatment of chronic myelogenous leukemia (CML), and this
(RTKs) have been identified.2 Structurally, the lipophilic monoclonal antibody revolutionized therapy for this disease.
transmembrane domain is flanked by an immunoglobulin- The majority of patients with CML possess the t(9;22) trans-
like, ligand-binding extracellular head and an intracellular location mutation (Philadelphia chromosome) that fuses the
DOI 10.2310/7800.2208
10/11
NF-1
Figure 1 Activation of a receptor tyrosine kinase induces dimerization and downstream phosphorylation of nonreceptor
tyrosine kinases. Major signaling cascades include the RAS/RAF/MAPK pathway, MEK pathway, and PI3 kinase/AKT pathway.
Adapted with permission from Zhu Y, Parada LF. The molecular and genetic basis of neurological tumours. Nat Rev Cancer
2002:2:616–26. EGFR= epidermal growth factor receptor; ERK= extracellular signal-related kinase; GAP= GTPase-activating
proteins; GEF= guanosine exchange factors; MEK= mitogen-activated protein kinase; NF1= neurofibromin gene;
PDGFR= platelet-derived growth factor receptor; PI3K= phosphotidylinositol-3 kinase.
Abl TK to the Bcr gene on chromosome 22.1,7 Transcription tumors. Currently, there are several clinical trials designed to
and translation of this mutation produce two TKs, p190 and test the efficacy of imatinib in other solid tumors, including
p210, both of which are involved in hematopoietic stem cell colorectal cancer, ovarian cancer, prostate cancer, and thy-
proliferation and inhibition of apoptosis.1 Imatinib blocks the roid cancer.10 Nevertheless, despite successes with this agent,
adenosine triphosphate (ATP)-binding site on these proteins, prolonged use of imatinib has resulted in the development of
hindering activation and downstream signaling. In clinical resistant tumors. The most common mechanism of resistance
trials, this early TKI improved long-term survival in CML by appears to involve mutations in the kinase domain of bcr-abl,
prolonging periods of remission and has been an effective which then prevent binding of the drug.11 As a result, current
treatment modality for both newly diagnosed patients and research is focusing on overcoming this limitation.
those who have failed interferon-alfa therapy.8 Another RTK that has been identified as a target for mono-
The success of imatinib in the treatment of CML raised the clonal antibody inhibition is epidermal growth factor receptor
question of whether this agent might be useful for treating 2 (EGFR2, ErbB2), also known as human epidermal receptor
solid tumors. The recognition that imatinib also inhibits the 2 (HER-2).12 This RTK can bind a wide array of growth
c-kit and platelet-derived growth factor receptor (PDGFR) factors, thereby inducing dimerization and stimulating down-
TKs led to trials treating tumors with mutations in these stream activation of either the RAS/MAPK, PI3 kinase/Akt/
molecules.9 For example, GISTs are well known to express mTOR, or other signaling pathways, which promote cell
c-kit, and imatinib has been highly successful in treating these proliferation and migration and inhibit apoptosis.12,13 HER-2
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Figure 2 Regulation of the cell cycle involves a highly complex sequence of events. The interaction of cyclin-dependent kinases
(CdKs) and cyclins determines progression through different phases of the cell cycle. Adapted from SABiosciences. Cyclins and
cell cycle regulation. Available at: www.sabiosciences.com (accessed October 2010).
is overexpressed in many malignancies, and between 20 and Trastuzumab has demonstrated efficacy against both early-
30% of advanced breast cancers express this receptor.12,14 and late-stage breast cancer and is currently the standard of
Trastuzumab is a humanized monoclonal antibody that care for HER-2-positive tumors.17,18 This agent was first used
inhibits activation of the HER-2 receptor by binding to the as adjuvant therapy for node-positive or advanced node-
extracellular domain and blunting the activation of down- negative breast cancer with HER-2 gene amplification. In
stream signaling.12 In addition, trastuzumab has been shown the National Surgical Adjuvant Breast and Bowel Project
to affect breast cancer cells by inducing cell cycle arrest at G1 (NSABP) B-31 and North Central Cancer Treatment Group
via upregulation and translocation of p27 from cytosol to (NCCTG) N9831 trials, trastuzumab was studied as a con-
nuclei.15,16 These findings have led to clinical use of this drug jugate to the established treatment regimen of doxorubicin
for treating HER-2-positive breast cancer. and cyclophosphamide plus paclitaxel.19 The Herceptin
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Table 1 Tyrosine Kinase Inhibitors Like trastuzumab, cetuximab is a monoclonal antibody

that targets EGFRs by binding to the extracellular domain.3,28
Monoclonal antibodies
Imitinib
The development of this drug began with the identification
Trastuzumab of a murine monoclonal antibody (called 225) that could
Cetuximab bind EGFR and inhibit activation of the intracellular TK
Panitumumab domain of the receptor. The downstream effects of 225
Small molecule inhibitors included increased apoptosis and cell cycle arrest in G1.29
Gefitinib Experimental data were promising; however, concern about
Erlotinib the use of a mouse monoclonal antibody in the human popu-
Multitargeted inhibitors lation and the potential for antimouse antibody response
Lapatinib prompted chimerization of the antibody with human IgG1.30,31
Dasatinib The resulting chimeric antibody (C225, cetuximab) per-
Sunitinib formed better than the original 225 antibody in inhibiting
Axitinib
Vandetanib tumor growth in vivo.31,32 In addition, early studies demon-
strated the efficacy of cetuximab in improving progression-
free survival and overall response rate in metastatic colorectal
tumors that had developed resistance to chemotherapeutic
Adjuvant (HERA) and Breast Cancer International Research agents such as irinotecan.3,33 Moreover, patients with
Group (BCIRG) 006 trials then examined the efficacy of metastatic colorectal cancer refractory to oxaliplatin and fluo-
adjuvant trastuzumab for 1 or 2 years following different ropyrimidine (5-FU) experienced prolonged progression-free
chemotherapy regimens (HERA) or as an addition to the survival when cetuximab was given in conjunction with
regimen of anthracycline, cyclophosphamide, and docetaxal irinotecan compared with irinotecan alone. These results
(BCIRG 006).20 In all four trials, both disease-free survival established the combination regimen as a standard of care for
and overall survival were improved in the groups that received refractory metastatic colorectal cancer.3 In 2004, cetuximab
trastuzumab. In addition, patients who received trastuzumab either in combination with irinotecan or as a single agent was
developed fewer metastases and had lower mortality com- approved by the Food and Drug Administration (FDA) for
pared with patients who received chemotherapy alone. Unfor- the treatment of metastatic colorectal cancers that express
tunately, side effects observed in these studies and attributed EGFR and are refractory to irinotecan- or oxaliplatin-based
to trastuzumab treatment were congestive heart failure and a therapies.3,34,35
measurable decline in left ventricular ejection fraction.19,20 As cetuximab was increasingly used to treat refractory
Further investigation revealed that the risk of cardiac failure metastatic colorectal cancer, it became clear that this agent
was greatest in patients who received anthracycline, and is most effective in a subset of patients.33,36–38 Specifically,
although there is evidence that this untoward effect was cur- tumors possessing a mutation in the K-ras gene responded
tailed with the concomitant administration of epirubicin, it poorly to cetuximab, whereas tumors with wild-type K-ras
remains a real concern for many patients and physicians.21 responded well.39–41 The consensus that K-ras status is a
Thus, trastuzumab should not be given with anthracycline, predictive marker for response to cetuximab therapy has led
and close monitoring of cardiac function is recommended. to current recommendations that patients be tested for the
Although trastuzumab has traditionally been administered mutation prior to the initiation of treatment.42,43
In 2001, Shin and colleagues studied the combined effect
in conjunction with chemotherapy in advanced HER-2-
of cetuximab and cisplatin in patients with recurrent or
positive disease, more recent work has focused on using this
late-stage squamous carcinoma of the head and neck.30 In this
drug as a single agent in early disease in an effort to delay the
study, 67% of patients demonstrated a major response with
use of other, more toxic chemotherapy.17 In addition, the
the addition of cetuximab.30 This drug also showed efficacy
recent phase III Trastuzumab for Gastric Cancer (ToGA)
in improving the response rates in patients with head
trial has suggested that trastuzumab may be a reasonable
and neck cancer when combined with cisplatin, 5-FU, and
adjunct to capecitabine and cisplatin or 5-fluorouracil (5-FU)
radiation.32 As such, in 2006, cetuximab was approved by
and cisplatin for patients with HER-2-positive gastric or the FDA for the treatment of squamous cell carcinoma of the
gastroesophageal junction cancer. Patients who received head and neck in combination with radiation therapy or as a
trastuzumab experienced 13.8-month median overall survival single agent in cases refractory to platinum-based regimens.44
compared with 11.1 months for those receiving chemother- Thus, cetuximab has demonstrated efficacy for the treatment
apy alone, decreasing the rate of death by 26%.22,23 Trials of several cancers that in the past have been difficult to treat,
are also under way to test the efficacy of trastuzumab in and the recognition of optimal applications is growing.
combination with other targeted therapies. For example, Although still under active investigation for more general use,
trastuzumab-DM1 is a combination of the monoclonal this agent holds promise for treating a variety of cancers.
antibody and the maytansine derivative DM1, a drug that Another human monoclonal antibody that targets EGFR,
interferes with microtubule formation. Preclinical studies panitumumab, has a different mechanism of action. Panitu-
demonstrate efficacy in lapatinib and trastuzumab-refractory mumab functions by binding to the site of epidermal growth
breast cancer cells, and this combination is currently in phase factor and tumor necrosis factor–a (TNF-a) binding on the
II clinical trials for the treatment of breast cancer.24,25 Pre- EFGR.45 The antibody is then internalized and downregu-
liminary data show an approximately 40% overall response lates EGFR production, induces apoptosis, and inhibits
rate in metastatic disease after 6 months.26,27 tumor growth and cell cycle progression.45 Panitumumab has
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been approved by the FDA for the treatment of EGFR- of resistance has been a concern and, as such, has led to
expressing metastatic colorectal cancer refractory to fluor- the development of second-generation TKIs that are capable
opyrimidine-, irinotecan-, or oxaliplatin-based therapies.46 of inhibiting multiple TKs. These molecules are designed
Similar to cetuximab, however, several studies have identified to inhibit not only EGFR/HER-2 activation, for example,
K-ras mutation as a predictive marker for panitumumab but also downstream cell signaling molecules such as the
response and thus recommend that K-ras status be identified src family of kinases and proteins such as c-kit, HER-2, and
prior to the initiation of treatment.43 Recent work also has PDGFR.65
identified additional markers that have the potential to Lapatinib is an EGFR and HER-2 inhibitor that has been
predict tumor response to monoclonal antibodies, such as extensively studied in the treatment of breast cancer. The
cetuximab and panitumumab. For example, BRAF, N-ras, unique feature of this inhibitor is the extended binding time
and PIK3CA have been suggested as potential biomarkers for to EGFR that prolongs its inhibitory effect. As a single agent,
response to anti-EGFR therapy and hold promise for further only modest clinical benefit was appreciated in phase II trials.
personalizing cancer treatment.47,48 However, lapatinib appears to be effective when used in
Finally, other similar agents, such as pertuzumab, an combination with other agents. For example, in patients with
antibody that prevents dimerization of HER-2 receptors, are metastatic breast cancer who overexpress HER-2, treatment
being developed and tested.49 In vitro, pertuzumab demon- with lapatinib plus capecitabine markedly improved
strated synergy with trastuzumab in inhibiting breast cancer progression-free survival. Also, patients receiving the com-
cell growth. A phase I trial demonstrated that this drug was bination regimen showed 51% reduction in risk of disease
well tolerated and produced promising preliminary clinical progression, decreased incidence of central nervous system
results.49,50 (CNS) metastases, and decreased volume of existing CNS
metastases.27 In 2007, lapatinib in combination with
Small Molecule TKIs capecitabine was approved by the FDA for use in advanced
Gefitinib is a small molecule inhibitor that targets the breast cancers that overexpress HER-2. In addition, in 2010,
epidermal growth factor receptor 1 (EGFR1/HER-1) by the FDA approved the combination of lapatinib and letrozole
inhibiting autophosphorylation.27 This small molecule binds in postmenopausal women with advanced breast cancers who
the intracellular TK domain of the receptor.51,52 Gefitinib was overexpress HER-2 and are hormone receptor positive. The
originally approved for the treatment of non–small cell lung combination regimen significantly improved progression-free
cancer in 2003. However, in 2005, its use was limited only to survival.66
patients who had previously benefited from the drug after two Another of the second-generation, multitargeted TKIs,
clinical trials demonstrated no advantage in patients with dasatinib, has demonstrated increased inhibitory activity
non–small cell lung tumors that overexpressed EGFR.53 As against Bcr-Abl compared with imatinib in vitro and is
clinical testing has continued, the results with gefitinib treat- currently approved for the treatment of CML in patients
ment have been mixed. Recent data from the North-East who have developed resistance to imatinib or are otherwise
Japan Study Group indicated that first-line gefitinib pro- intolerant of the drug.8,65 In the SRC/ABL Tyrosine kinase
longed progression-free survival in patients with metastatic inhibition Activity Research Trials of dasatinib (START-C)
non–small cell lung cancer with EGFR mutation(s) compared trial, 53% of patients who received dasatinib achieved a com-
with carboplatin and paclitaxel.54 In contrast, other studies plete cytogenic response and 62% achieved a major cytogenic
have failed to show any improvement in survival.55,56 Interest- response after 24 months.8,67 Although this investigation
ingly, gefitinib appears to reverse drug resistance in breast involved the initiation of dasatinib treatment after failure of
cancer cells that overexpress Pgp, a multidrug resistance imatinib, there is speculation and early evidence that it may
protein, suggesting that this may also be a therapeutic target be effective as a first-line agent. Initial studies have suggested
for this agent.57 that the rate of remission at 24 months was superior with
Erlotinib is another small molecule inhibitor of EGFR initial treatment of dasatinib when compared with initial
autophosphorylation that binds the kinase domain of the treatment with imatinib.8,68
receptor and inhibits cell proliferation and cell cycle pro- Additional multitargeted agents are also under develop-
gression. In preclinical trials, erlotinib effectively inhibited ment. For example, neratinib inhibits both EGFR (ErbB1),
activation of EGFR in colorectal cancer cells, inhibited in HER-2 (ErbB2), and HER-4 (ErbB4), and in a phase I study
vivo growth of squamous cell head and neck cancer cells that for use against solid tumors, the agent was well tolerated and
overexpress EGFR, and inhibited in vivo growth of non–small showed promising clinical activity.69 A phase II trial of its use
cell lung cancer cells.58–60 In a large randomized, placebo- against advanced breast cancer supported early findings,
controlled, double-blind trial studying patients with advanced and further studies are under way for the treatment of breast
non–small cell lung cancer (stage IIIB or IV), erlotinib ther- cancer and other solid tumors.10,70
apy prolonged progression-free and overall survival and was Another group of TKIs that target multiple receptors is
subsequently approved as second-line therapy for treating difficult to classify because these agents affect a variety of
non–small cell lung cancer in 2004.61–64 Later, erlotinib kinases and downstream signaling cascades. For example,
was approved in combination with gemcitabine for treating some of these molecules inhibit angiogenesis by blocking the
pancreatic cancer (2005) and as maintenance therapy for vascular endothelial growth factor receptor (VEGFR) while
non–small cell lung cancer (2010).64 also inhibiting TKs such as c-kit and HER-2. One such
inhibitor is sunitinib, a molecule that inhibits c-kit, PDGFR-
Multitargeted Inhibitors a, CSF-1 receptor, and VEGFR-1, -2, and -3.27 The FDA
Despite the demonstrated efficacy of monoclonal antibod- approved its use in advanced renal cell carcinoma after it
ies and small molecule inhibitors of TKIs, the development demonstrated efficacy by improving progression-free survival
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and overall survival compared with interferon alfa.71,72 Suni- overall response rate.86 Early clinical trials in glioblastoma
tinib has also been used successfully to treat GISTs that have and medullary thyroid cancer also have shown promising
developed resistance to imatinib and is FDA approved for use results.87,88 At present, the indications for the use of these
in that setting.71,73,74 agents, both alone and in combination with other drugs, are
Other clinical trials test sunitinib’s efficacy in a variety of evolving and await the results of clinical trials.
settings, and a phase II study using sunitinib for treating TKIs are the prototype for targeted therapeutics. These
thyroid cancer that was resistant to radioactive iodine showed agents have been widely studied, and new and increasingly
that 3% of patients had a complete response, 29% showed a effective molecules are under development. Interestingly, one
partial response, and 46% maintained stable disease.75 In consistent theme with TKIs is the ability of biomarkers such
addition, for metastatic breast cancer patients who failed as K-ras mutation and EGFR overexpression to predict
treatment with anthracyclines and taxanes, sunitinib treat- response. This improved understanding of the molecular
ment helped some (5%) achieve stable disease.76 Despite mechanisms underlying carcinogenesis and tumor response
these promising results, toxicity has emerged as a concern to therapy increasingly is leading to a more individualized
with this agent. For example, in the study treating metastatic approach to cancer treatment.
breast cancer, dose modification was necessary in 56% of
patients as a result of adverse effects.76 Similarly, in a study
Angiogenesis Inhibitors
combining sunitinib with cyclophosphamide and methotrex-
ate, of the 15 patients studied, three developed neutropenia  
and five developed mucositis.27 In another phase I dose-
Angiogenesis is one of the earliest events in tumor growth.89
escalation study combining sunitinib and capecitabine in
patients with solid tumors, five grade 3 adverse effects Hypoxic conditions provoke tumor microvascular formation
emerged: abdominal pain, mucosal inflammation, fatigue, by not only inciting proangiogenic signals but also inhibiting
neutropenia, and hand-foot syndrome.77 Similar side effects antiangiogenic signals.90–92 The proangiogenic factors released
have been reported in other clinical trials, and one trial was include, but are not limited to, vascular endothelial growth
terminated early because of the high incidence of neutrope- factors (VEGFA, -B, -C, -D, and -E), basic fibroblast growth
nia, febrile neutropenia, and fatigue.27 Interestingly, in one factor (bFGF), interleukin-8, placentalike growth factors
study of efficacy against hepatocellular carcinoma, the neu- (PLGF-1 and -2), neurophilins (NRP1 and NRP2), trans-
tropenia and skin toxicities seemed to correlate with response forming growth factors (TGFs), fibroblast growth factor
to therapy, overall survival, and time to tumor progression, (FGF), and platelet-derived growth factor (PDGF).3,89,93 The
suggesting that those toxicities may be a marker for tumor effects of these proangiogenic proteins can be classified based
response.78 on the mechanism by which they stimulate microvascular
Axitinib is another inhibitor of several RTKs, including all formation.89 For example, some stimulate new growth of
VEGFRs (1, 2, and 3), PDGFR-b, and c-kit.27 This agent has vasculature from preexisting blood vessels, whereas others
shown promise in phase I studies and was initially thought to induce the formation of de novo vascular channels.94 VEGFR
have few severe side effects (hypertension was most common). stimulation activates intracellular phospholipase Cc (PLC-c),
Phase II studies have suggested a benefit to adding axitinib protein kinase C (PKC) and the MAPK pathway, PI3 kinase,
to docetaxel for patients with metastatic breast cancer and Akt/PKB (protein kinase B), nuclear factor kB (NF-kB), and
in combination with gemcitabine for treating metastatic endothelial nitric oxide syntheses and inhibits proapoptotic
pancreatic cancer.27,79 In the phase II trials, however, toxicity proteins, thereby inducing endothelial cell survival, prolifera-
appeared to be greater than suggested in the phase I trials tion, and migration and increasing vasodilation, vascular
(febrile neutropenia, fatigue, stomatitis, diarrhea, hyperten- remodeling, and vessel permeability.95 In addition, hypoxia-
sion), and a phase III trial combining the agent with gem- inducible factors (HIFs) are transcription factors that are
citabine was terminated early because of a lack of improved activated under hypoxic conditions and serve as a major
survival.27,80 Clinical trials continue to investigate the use of stimulus for angiogenesis.89
axitinib for the treatment of a variety of solid tumors, includ- Folkman’s hypothesis suggests that approximately 2 mm3 is
ing, but not limited to, renal cell carcinoma, hepatocellular the critical tumor size at which further growth and survival
carcinoma, colorectal cancer, lung cancer, and melanoma.10 depend on an autonomous vascular network.96 The resulting
Finally, vandetanib is a molecule that inhibits EGFR, the neovasculature is tortuous and irregular, and although not
kinase domain of VEGFR2, and ret autophosphorylation that efficient enough to satisfy the oxygen needs of the growing
is currently in the early stages of clinical investigation.27,81–85 tumor, these networks are able to promote growth and metas-
Phase I data suggest that although this agent is well tolerated, tasis.89 The most important cell involved in this process is the
it provided no clinical benefit for patients with multiple vascular endothelial cell, and its growth is primarily regulated
myeloma.81 Early clinical trials for use against refractory non– by VEGF activation of the VEGFR. In normal tissues,
small cell lung cancer, however, were more promising, VEGFR2 appears to be the major inducer of angiogenesis,
prompting the initiation of phase III investigations for its use whereas the relatively weak signal cascade of VEGFR1 may
in that disease.83,85 The Ziprasidone Observational Study of actually decrease angiogenesis. VEGFR3 is involved in
Cardiac Outcomes (ZODIAC) trial examined the effect of embryologic and postnatal angiogenesis and lymphangiogen-
vandetanib with docetaxel on previously treated non–small esis. In cancer, VEGFR1 and -2 appear to be the receptors
cell lung cancer; compared with patients who received most involved in tumor angiogenesis.3 Both VEGF and
docetaxel with placebo, patients who received vandetanib had VEGFRs have emerged as logical targets for drugs seeking to
significantly longer progression-free survival and an improved inhibit angiogenesis.42,89
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  cancer patients who receive bevacizumab compared with

Bevacizumab is the prototypical angiogenesis inhibitor. chemotherapy alone. As a result, the Oncologic Drugs
This anti-VEGFA antibody reduces the amount of effective Advisory Committee of the FDA has recommended with-
circulating VEGFA and thereby prevents VEGFR activa- drawing the approval of bevacizumab as first-line treatment
tion.42 Bevacizumab has shown efficacy in suppressing endo- for metastatic breast cancer.110 The FDA is currently review-
thelial cell adhesion and proliferation in vitro and suppressing ing the data on this drug, and the decision regarding possible
peritoneal dissemination of gastric cancer in a murine revocation of approval is pending.111
model.97,98 Clinical efficacy was first demonstrated in colorec- Toxicity, although not prohibitive, is common, and the
tal cancer. In stage IV disease, bevacizumab in combination most common adverse effects are rash, hepatotoxicity
with irinotecan, 5-FU, and folinic acid (leucovorin) (elevated liver function tests), proteinuria, diarrhea, myelo-
(FOLFIRI) induced higher response rates and prolonged suppression, fatigue, infection, pain, nausea/vomiting, and
progression-free and overall survival compared with tradi- hypokalemia.104,105,107,112 In addition, the BRiTE study found
tional chemotherapy.99 In 2004, bevacizumab was approved several rare, but more severe, side effects. New onset or
by the FDA as a first-line treatment for metastatic colorectal worsening hypertension was seen in 22% of patients, and
cancer and in 2006 as second-line treatment in combination hypertension was implicated in eight serious adverse events.
with oxaliplatin, folinic acid, and 5-FU (FOLFOX4).100,101 Additional less common but serious adverse events included
The efficacy of bevacizumab has subsequently been tested in postoperative wound healing complications (4%), grade 3 to
other tumor types, including pancreatic and hepatocellular 4 bleeding (2.2%), arterial thromboembolic events (2%), and
carcinoma, renal cell carcinoma, neuroendocrine tumors, gastrointestinal perforation (2%). The majority of bleeding
non–small cell lung cancer, and breast, brain, and ovarian events were gastrointestinal. Significant postoperative wound
cancers.10 healing complications occurred following major surgery and
Despite early enthusiasm about bevacizumab, additional in patients in whom surgery was undertaken within 2 weeks
experience has met with mixed results. The Bevacizumab of the last bevacizumab dose.102 This observation has led
Regimens’ Investigation of Treatment Effects (BRiTE) study, most surgeons to try to avoid operating on patients within 6
an observational cohort study of 1,953 patients with meta- to 8 weeks of bevacizumab therapy. Moreover, the FDA has
static colorectal cancer from 248 United State sites between issued a drug warning and safety labeling update concerning
2004 and 2005, examined the efficacy of bevacizumab com- these adverse effects.101
bined with chemotherapy as first-line treatment for metastatic Aflibercept (VEGF Trap) is a molecule in which the ligand-
colorectal cancer. At 20 months, progression-free survival binding domains of the VEGFR1 and VEGFR2 proteins are
was observed in 22% of patients who had received bevaci- fused with human IgG1, forming a decoy receptor that binds
zumab, whereas disease progression was seen in 79% of the all VEGFs and placental growth factor.27 Preclinical studies
patients. In addition, 66% of patients died during the study have suggested that this agent is well tolerated but have failed
period, and 12% either withdrew from the study or were lost to show significant clinical activity. Definitive recommenda-
to follow-up.102 Similarly, in a phase III study by Stathopou- tions about the use of aflibercept await the results of ongoing
los and colleagues in 2010, median overall survival did not trials.27
differ between groups that received bevacizumab with che- Angiogenesis inhibitors have demonstrated efficacy in a
motherapy (irinotecan, 5-FU, leucovorin) and groups that variety of disease sites; however, they also have limitations.
received chemotherapy alone as the initial treatment for Of particular concern to surgeons are the risk of increased
metastatic colorectal cancer.103 Moreover, in a phase II study bleeding and inhibition of wound healing. Nevertheless,
of bevacizumab with erlotinib for treating recurrent malig- antiangiogenic compounds have proven to be useful in
nant glioma, progression-free survival was not significantly well-selected patients.
improved in patients who received bevacizumab.104 Other
early studies, however, have suggested efficacy in the treat-
ment of other types of cancer. In non–small cell lung cancer, Cell Cycle Inhibitors
the effects on overall survival were inconsistent, but the drug
 
appeared to slow the progression of the disease.105 In vitro
data suggest efficacy in combination with docetaxal for Regulation of the cell cycle involves a highly complex
treatment of breast and prostate cancers.106 In combination sequence of events orchestrated by cyclins and cyclin-
therapy with paclitaxel for metastatic breast cancer, bevaci- dependent kinases (CdKs) [see Figure 3]. The interaction of
zumab improved response rates compared with paclitaxel these molecules is regulated by several naturally occurring
alone.107 cyclin-dependent kinase inhibitors (CdKIs) that prevent
To date, the FDA has approved bevacizumab in combina- binding of CdKs to cyclins. Two families of CdKIs have been
tion with carboplatin and paclitaxel for the treatment of non– identified: the INK4/ARF family and the Cip/Kip family. The
small cell lung cancer and in combination with interferon for INK4/ARF family includes p15, p16, p18, and p19, and the
the treatment of metastatic renal cell carcinoma.101,108,109 It Cip/Kip family includes p21, p27, and p57.113,114 A cell will
has also been approved for use as a second-line single agent exit the quiescent phase, G0, and enter G1 following the
for the treatment of glioblastoma.101 In 2008, bevacizumab production of cyclin D, which is the result of activation of
was approved as first-line treatment in combination with the Ras/Raf/MAPK signal cascade by mitogens. Progression
paclitaxel for metastatic HER-2-negative breast cancer.101 through the cell cycle is permitted to occur when the CdKIs
However, the results of more recent analyses of several clini- do not prevent CdK-cyclin interactions. For example,
cal trials have failed to show any survival advantage in breast cyclin E–CdK2 complex formation promotes cell entry into
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and WEEL.127 Preclinical studies have demonstrated the effi-

cacy of this agent in a variety of cancer cell lines. A phase II
clinical trial of roscovitine for treating resistant non–small
cell lung cancer has recently been completed, and phase I
investigation of its clinical safety in treating any solid tumors
resistant to standard treatment is under way.10
E7070 is a synthetic sulfonamide that inhibits CdK2 and
cyclin E, effectively inhibiting progression through G1 and S
phases.128 In vitro, this agent blocked cell cycle progression in
non–small cell lung cancer cells, and in vivo, it not only
inhibited tumor growth but also induced regression in models
of colon cancer and non–small cell lung cancer.129,130 Four
phase I clinical trials are currently under way evaluating the
use of this agent in solid tumors and melanoma. However,
the results of phase II trials in other disease sites have been
somewhat disappointing. For example, E7070 as a single
agent did not show significant response in non–small cell lung
cancer.131 In 2005, Smyth and colleagues reported similar
Figure 3 Progression through each phase of the cell cycle is results in metastatic melanoma, with the best response being
regulated by cyclin–cyclin-dependent kinase interactions. stable disease in 17% of patients, whereas 58% experienced
Adapted from www.sysmex-lifescience.com (accessed disease progression.132 A phase II study in squamous cell head
October 2010).
and neck cancer was terminated because of the 15 patients
who were treated, none achieved 4 months of progression-
S phase, and cyclin B–CdK1 allows mitosis to occur115,116 [see
free survival.133 In addition, toxicity was concerning in these
Figure 3]. Overall, nine CdKs have been described, and these
trials, prompting some patients to withdraw. Most common
molecules interact with 20 possible cyclins (A to T).115 Given
problems consisted of gastrointestinal upset (nausea, vomit-
that cyclins and CdKs play major roles in controlling progres-
ing, constipation, or diarrhea) and pain at the injection site.131
sion through the cell cycle, they are logically attractive targets
However, more severe side effects, such as anemia, thrombo-
for treating cancer. In addition, there is evidence that CdK
cytopenia, bleeding, and one reported death attributable to
or cyclin production is disrupted in several malignancies,
pulmonary embolus, have also been attributed to E7070
including melanoma and lung, breast, and colorectal
cancers.115,117,118 Several cell cycle inhibitors are currently treatment.132 Since the conclusion of those trials, pharmaco-
under investigation, but clinical results have been mixed, and kinetic studies have been initiated in an effort to identify the
it has been suggested that these agents may have more utility optimal dose of E7070 in combination with other agents in
as chemosensitizers for other agents.115 an attempt to minimize toxicity.134,135
A number of additional cell cycle inhibitors are currently
   undergoing early clinical evaluation for the treatment of
Currently, CdKIs include flavopiridol, roscovitine, E7070, a variety of malignancies [see Table 2]. One such agent is
AZD5438, SNS-032 (BMS-387032), bryostatin-1, PD SNS-032, an aminothiazide-based inhibitor that halts cell
0332991, and SCH 727965. Flavopiridol acts on the G1 and cycle progression by way of CdK2 and -7 inhibition, and
S phases of the cell cycle via inhibition of CdKs 2, 4, 6, and transcription via CdK7 and -9 inhibition.136,137 Interestingly,
9 and has demonstrated early success in vitro by inducing the antitumor efficacy of SNS-032 may also result from inhi-
arrest of cellular growth and inducing apoptosis in chronic bition of VEGF expression, hindering angiogenesis.138 Phase
lymphocytic leukemia (CLL) and colorectal cancer cells.119,120 I investigations of oral bioavailability in patients with meta-
Currently, flavopiridol is useful for treating recurrent CLL, static solid tumors and lymphomas, as well as previously
where it has been shown to induce a clinical response in treated CLL and multiple myeloma patients, indicate that
patients with high-risk genomic features.121 In addition, when oral administration is feasible, and although neutropenia and
given with cytosine arabinoside and mitoxantrone, flavopiri- thrombocytopenia were the most common side effects, the
dol induced complete remission in 67% of patients with AML agent was largely well tolerated.137,139
who had poor-risk features (older age, unfavorable genetic Bryostatin-1 is a macrocyclic lactone derived from Bugula
mutations, or secondary AML).122 Phase I trials indicate drug neritina.140 This natural antineoplastic agent affects protein
tolerability, and phase II trials continue to test this drug’s kinase C levels, inhibits CdK2, and induces p21.115,141
efficacy in a variety of cancers.123 Although promising in preclinical investigations, the results
Roscovitine inhibits cyclin E–CdK2, cyclin B–CdK1, cyclin of phase II studies have shown inconsistent efficacy as a single
H–CdK7, and cyclin T1–CdK9 and prevents progression agent or in combination with other agents. Some trials,
through the S, G2, and M phases of the cell cycle.115 In vitro however, did report disease improvement with bryostatin-1
studies also indicate that this drug induces apoptosis by acti- treatment. Most recently, Barr and colleagues demonstrated
vating p53, suppressing NF-kB, and downregulating Mcl-1 that combination bryostatin-1 and vincristine induced an
(an antiapoptosis protein) in multiple myeloma cells.124–126 It overall response rate of 31% with complete remission of dis-
also inhibits mitosis by decreasing production of promoters of ease in two patients with non-Hodgkin lymphoma.142 Clinical
cell division, such as Aurora-A/B, CDC25C, pololike kinase, trials continue to test this agent under myriad conditions.10
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Table 2 Cell Cycle Inhibitors

Cell Cycle Inhibitor Mechanism of Action Effects Clinical Trials*
Flavopiridol Inhibits CdK 2, 4, 6, 9 G1/S arrest Phase I/II (hematologic and several solid
tumors)
Roscovitine Inhibits cyclin E/CdK2, cyclin S/G2/M arrest Phase I/II (solid tumors)
B/CdK1, cyclin H/CdK7, cyclin
T1/CdK9; p53 activation, nuclear
factor kB, decreases Mcl-1
E7070 Inhibits CdK2, cyclin E G1/S progression Phase I/II (several solid tumors,
melanoma)
SNS-032 Inhibits CdK 2, 7, 9, VEGF Inhibits progression and Phase I (advanced B cell lymphomas,
transcription, angiogenesis several solid tumors)
Bryostatin-1 Affects protein kinase C, CdK2; Cell cycle modulation Phase I/II (combination therapy for
induces p21 hematologic and several solid tumors)
AZD5438 Inhibits CdK1, 2, 9 Affects all phases of cell cycle Trials terminated dues to safety
concerns
*Adapted from www.clinicaltrials.gov.10
CdK = cyclin-dependent kinase; VEGF = vascular endothelial growth factor.
Finally, AZD5438 is one cell cycle inhibitor that exempli- For example, a mutation resulting in the loss of antiapoptotic
fies the difficulty in translating laboratory outcomes to clini- p53 functions can lead to genomic instability and decreased
cal practicality. This agent worked through all phases of the apoptosis. Cancer therapies that target the inappropriate loss
cell cycle by inhibiting CdK1, -2, and -9.115,143 Preclinical of control over apoptosis have been developed to induce
data were promising, but the clinical trials yielded less favor- the intrinsic and extrinsic pathways either independently or
able outcomes. The most recent phase I trial published, together. Recent work has focused on inhibition of pathways
studying patient tolerance of AZD5438 for the treatment of involving the TRAIL receptor, bcl receptors, and inhibitors
recurrent solid malignancies, indicated that weekly dosing of apoptosis proteins (AIPs).147
was more appropriate than continuous. However, safety con-
- 
cerns prompted manufacturer discontinuation of the agent
and thus resulted in early termination of clinical trials.144 Apoptosis inducers can be classified based on their mecha-
Cell cycle inhibitors are in the early stages of evaluation, nism of action. Bortezomib, suberoylanilide hydroxamic acid
and some have shown promising initial results in combination (SAHA), TLK286, ONYX015, FTI-R115777, and 17AAG
with other chemotherapies. However, although tumor cells target protein kinases, proteosomes, and transcriptional
demonstrate accelerated cell turnover and, as such, should be factors. Mapatumumab and lexatumumab target the
most sensitive to these agents, the nonspecific targeting of the proapoptotic proteins TRAILR1 and TRAILR2.
cell cycle can injure normal tissues. Thus, as is the case with Bortezomib is a boronic acid dipeptide and was the first
angiogenesis inhibitors, toxicity remains a major concern and proapoptotic agent used in cancer treatment. Bortezomib
has limited the clinical applicability of some of these drugs. promotes apoptosis by inhibiting the 26S proteosome.148 This
proteosome degrades many cellular proteins, including those
involved in the cell cycle, transcription, and tumor suppres-
Inducers of Apoptosis sion. Early work suggested that 26S proteosome inhibition
promoted apoptosis in multiple myeloma cells and that this
 
molecule stabilized tumor suppressor and cell cycle proteins
Apoptosis is the natural process of programmed cell death, (p53, p21, and p27).148 The Assessment of Proteasome
and two pathways are involved in this process. The extrinsic Inhibition for Extending Remissions (APEX) trial suggested
pathway is mediated by death receptors such as Fas, TNF, superior efficacy of bortezomib over dexamethasone for
and TRAIL, among others. The intrinsic pathway is mito- refractory multiple myeloma.149 Clinical trials also suggest
chondria and apoptosome mediated and can be activated by that this agent may effectively augment the antitumor activi-
radiation and chemotherapy. It includes downstream signal- ties of established chemotherapy regimens. For example, the
ing mediated by bcl-2 and the bcl-2 family of antiapoptotic Velcade as Initial Standard Therapy in Multiple Myeloma
or proapoptotic proteins (e.g., Bid, Bax, Bak), as well as (VISTA) study was a phase III clinical evaluation of bortezo-
caspases and cytochrome-c. These pathways are not mutually mib in combination with melphalan and prednisone as
exclusive; for example, caspases are known to participate in first-line therapy for multiple myeloma. The addition of bort-
both intrinsic and extrinsic pathways. Naturally occurring ezomib to the standard melphalan-prednisone regimen
apoptosis proteins interact with the caspases to either inhibit slowed time to disease progression, increased the incidence of
or induce the innate process of programmed cell death.145,146 partial and complete response, and prolonged the duration of
Although these molecules balance the proapoptotic/ response.150 Further follow-up showed that patients treated
antiapoptotic equilibrium, changes in any number of ele- with a combination of bortezomib, melphalan, and predni-
ments in the signal cascade may disrupt normal apoptosis. sone had better overall survival at 3 years (69% versus 54%),
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and 35% reduced risk of death at 26.7 months when com- tumor cells, TLK286 may be an ideal therapeutic option in
pared with patients who received only melphalan and pre- these refractory tumors.161,162 Preliminary data suggest that
dnisone.151 The FDA approved bortezomib as a second-line TLK286 has little efficacy as a single agent, but combination
therapy for the treatment of mantle cell lymphoma in 2006 with other agents may be useful.163–167 A phase III study
and as first-line therapy for multiple myeloma in 2008.152 comparing TLK286 with doxorubicin or topotecan as a third-
Several clinical trials have studied the efficacy of bortezo- line treatment for refractory ovarian, fallopian, or primary
mib against solid tumors, such as hepatocellular carcinoma peritoneal cancer is currently under way.168
and metastatic rectal cancer.153–155 Bortezomib has also been The adenovirus ONYX015 is an attenuated adenovirus
proposed as a radiosensitizer in combination with 5-FU for that has also shown antitumor activity, although the mecha-
neoadjuvant treatment of locally advanced (stages II and III) nism of action remains poorly understood. It was initially
rectal cancer. However, in a small study, only one of nine thought that the virus selectively invades and replicates in p53
patients treated had a complete pathologic response, arguably mutated cells and binds to and inactivates the p53 gene but
equivalent to 5-FU-based strategies alone.154 At present, there has no effect on normal cells.169,170 However, other studies
are no indications for use of this agent in solid tumors, despite have suggested that its efficacy results from more complex
its efficacy in hematologic malignancies.156 interactions and not just mutated p53.171,172 In 2004, the agent
SAHA inhibits histone deacetylase, thereby suppressing the was approved in China for use against squamous cell head
expression of genes that can promote tumorigenesis.157 In and neck cancer, and in the United States, it has shown
vitro and in vivo studies indicated that histone deacetylase promise in phase I and II trials as combination therapy for
inhibitors such as SAHA downregulate TNF-a receptor–1 patients with solid tumors such as advanced sarcoma and
expression and activation of NF-kB.158 Several clinical trials recurrent head and neck cancer.173–175
have been completed, and in 2006, the agent was approved Another agent that induces apoptosis is FTI R115777, a
by the FDA as a third-line treatment option for cutaneous T methylquinolone farnesyl transferase inhibitor (FTI). Initially
cell lymphoma.159 The trials that led to approval demon- thought to inhibit cell growth and induce apoptosis solely
strated that patients who had previously failed treatment ben- by blocking farnesylation of Ras, it now appears that FTI
efited from treatment with SAHA. Side effects were tolerable, R115777 also induces cell death by disrupting the mitochon-
and the most common adverse effects were fatigue (52%), drial membrane and inducing caspase-9 activation.176 Early
diarrhea (52%), and nausea (40%). More serious effects clinical trials have yielded mixed results. The Children’s
(pulmonary embolism, deep vein thrombosis, myocardial Oncology Group, however, recently reported that although
infarction) occurred in fewer than 10% of patients.159 Addi- the pharmacokinetics were more variable in the pediatric
tional clinical investigations are under way, including a phase population, the agent is well tolerated for the treatment of
III trial of SAHA use against advanced mesothelioma.160 pediatric hematologic malignancies, and further investigation
Several other agents designed to induce apoptosis are under in solid tumors and neurofibromatosis type 1–related
investigation [see Table 3]. TLK286, a modified glutathione plexiform tumors is warranted.177,178
analogue, is metabolized by glutathione S-transferase (GST) 7AAG is an inhibitor of heat shock protein HSP90, a
in the tumor cell cytosol, yielding a molecule that is toxic to molecule that is frequently overexpressed in tumor cells.179
the cell. Because GST is overexpressed in many resistant This agent has been thoroughly studied in vitro and in vivo
Table 3 Inducers of Apoptosis

Inducer of Apoptosis Mechanism of Action Effects Clinical Trials*
Bortezomib Inhibits 26S proteosome Decreased degradation of cell FDA approved as first-line treatment of
cycle and transcription multiple myeloma and as second-line
proteins treatment of mantle cell lymphoma
Suberoylanilide Inhibits histone deacetylase Suppress tumorigenic gene FDA approved as third-line treatment of
hydroxamic acid expression cutaneous T cell lymphoma; phase III
(SAHA) (advanced mesothelioma)
TLK286 Formation of a toxic metabolite Induces apoptosis Phase III (refractory gynecologic
malignancies), combination therapy
ONYX015 Adenovirus; invades and Lyses p53 mutated tumor cells Phase I/II (combination therapy for solid
replicates in p53 mutated cells, tumors)
inactivates p53 gene
FTI-R115777 Blocks farnesylation of Ras, Inhibit cell growth and induce Phase III (colorectal cancer and AML; no
disrupts mitochondrial apoptosis significant improval in progression-free
membrane, induces caspase-9 survival or overall survival, respectively);
activation phase I/II (pediatric leukemias, glioma)
17AAG Inhibits HSP90 Inhibit cell motility and invasion Phase I/II (multiple myeloma)
Mapatumumab TRAILR1 agonist Inhibit TRAIL ligand binding Phase I/II (several solid tumors)
and apoptotic signal cascade
Lexatumumab TRAILR2 agonist
*Adapted from www.clinicaltrials.gov.10
AML = acute myelogenous leukemia; FDA = Food and Drug Administration.
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and affects a variety of cancer cell types by inducing apopto- specific targeted therapeutic approaches have been developed
sis, decreasing growth, potentiating the effects of known using small molecules designed to inhibit FAK kinase activity
chemotherapeutic drugs, and sensitizing tumors to radiother- and activation or to inhibit protein-protein interactions.
apy.180 Phase I and II trials suggest a tolerable safety profile
and disease stability when administered as a single agent or  
in combination with bortezomib.181,182 Initial attempts at FAK inhibition focused on downre-
Another pathway targeted to induce apoptosis involves gulating FAK expression. Early studies demonstrated that
TRAILR1 and TRAILR2. TRAILR1 and TRAILR2 are two transfection of breast cancer cells with dominant negative
TRAIL receptors that are believed to be involved in apoptosis C-terminal FAK-CD decreased adhesion, colonization, and
via FADD and caspase-8 or -10 recruitment and possibly by in vivo tumor growth.191 Moreover, cells transfected with
activation of other signaling pathways involving NF-kB, FAK-silenced RNA (FAKsiRNA) showed increased round-
MAPK, PI3 kinase, and Akt. Initiated by TRAIL ligand ing, decreased growth, and decreased in vivo tumorigenesis.191
binding, this process has been linked to tumorigenesis and is Combination FAK/src inhibition with adenoviral FAK-CD
a promising target for anticancer therapy. Mapatumumab and the src inhibitor PP2 appeared to have a synergistic
(HGS-ETR1) and lexatumumab (HGS-ETR2) are two effect and functioned by increasing apoptosis.192 Thus, FAK
monoclonal antibodies that agonistically bind the TRAILR1 inhibition via silencing FAK expression seems to decrease
and TRAILR2 receptors, respectively.147 The role of mapatu- tumorigenesis in vitro and in vivo.
mumab and lexatumumab in combination with other agents Another approach to FAK inhibition involved either activa-
has been supported by the observation of a synergistic effect tion of p53 or elimination of p53-deficient cells. This indirect
with either antibody and cisplatin or bortezomib in non–small approach was studied by introducing retroviruses that express
cell lung cancer cells and malignant mesothelioma cells or p53 into rapidly dividing p53-deficient cells. A similar tact
with radiotherapy in colorectal cancer cells.183–185 Clinical was applied in the development of AD5CMV-p53, an adeno-
trials are under way for both mapatumumab and lexatu- viral vector encoding p53 that was subsequently used to
mumab.10 Although well tolerated, the clinical response at the replenish p53 deficiency in tumor cells. This approach inhib-
dose of mapatumumab administered was not significant.186 ited lung cancer cell growth in vitro and in vivo.193 Clinically,
Phase I trials also suggested that lexatumumab is safe and phase I and II trials suggest that this agent is both safe and
well tolerated and has promising clinical efficacy.187,188 effective against esophageal squamous cell carcinoma.194,195
Thus, drugs designed to induce apoptosis are showing However, concerns about the safety of a viral vector and
early promise for the treatment of a variety of cancers. about the logistics of production and storage persist.196
Clinical trials suggest that the side effect profile does not limit More recent efforts have focused on the development of
use and that these drugs may be most effective as chemo- or small molecules to inhibit FAK activity. The first FAK inhib-
radio sensitizers. itor that was developed, TAE226, blocks the ATP-binding
site and inhibits FAK phosphorylation at both Y397 and
Y861, a site that is involved with VEGF signaling. This mol-
Focal Adhesion Kinase Inhibitors
ecule showed promise in preclinical in vitro and in vivo trials
  and most recently was found to inhibit angiogenesis in models
of human colon cancer.197 TAE226 has not yet progressed to
Focal adhesion kinase (FAK) is a non-RTK that was iden-
clinical evaluation.
tified at adhesion sites between cells and the extracellular
In addition to TAE226, several other FAK inhibitors have
environment. The 125 kDa protein is encoded by a gene
been developed and are currently in phase I clinical trials.
located on chromosome 8 and houses three domains, the Like TAE226, PF-562,271 blocks the ATP-binding site of
amino-N-terminal domain, the central catalytic domain, and FAK and of Pyk2 (protein-rich tyrosine kinase 2), another
the carboxy-C-terminal domain. FAK activation relies on nonreceptor tyrosine kinase known to bind and activate
autophosphorylation of the Y397 site that is found in the src.198,199 PF-562,271 inhibited in vivo breast cancer cell
N-terminal domain. This is also a binding and activation site growth and metastasis in a murine model and decreased the
for several signaling proteins, such as src, PI3 kinase, and in vivo growth of prostate cancer cells and in vitro growth of
Grb-7. In addition, this region also binds extracellular matrix lung cancer cells.198,200–202 It also has exhibited synergy with
and signaling proteins involved in cell motility, invasion, and sunitinib in the inhibition of hepatocellular tumor growth in
cytoskeletal changes, as well as EGFR, p53, and other mol- vivo.203 Phase I clinical trials employing PF-562,271 for treat-
ecules that are critical for carcinogenesis.189 It is well known ing prostate, pancreatic, and head and neck cancers have
that p53 is mutated in many cancers; interestingly, p53 can recently been completed. Another inhibitor, PF-573,228,
inhibit FAK expression, and FAK can inhibit p53 expression. works similarly and has been found to inhibit breast cancer
In breast cancer cells, p53 mutation is highly correlated with cell migration.200 Interestingly, this agent in combination
FAK overexpression.190 Finally, FAK appears to play a key with tamoxifen decreased proliferation in estrogen receptor–
role in motility and migration, invasion, survival, angiogene- positive breast cancer cells.204 Other FAK inhibitors include
sis, lymphangiogenesis, and proliferation189 [see Figure 4]. PF-04554878, which is currently in phase I clinical trials for
FAK is upregulated in several types of cancer.189 The the treatment of advanced nonhematologic malignancies, and
potential role of FAK activation in cancer growth and pro- GSK2256098, which has completed phase I trials.10
gression has led to the development of several therapeutic PND-1186 is another FAK inhibitor with a different mech-
agents targeting this molecule. Initial attempts were focused anism of action. PND-1186 likely inhibits ATP activity by
on downregulation of FAK expression. Subsequently, more substituting a pyridine ring for the pyramidine ring found in
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Figure 4 Focal adhesion kinase (FAK) plays a key role in a signaling cascade that can lead to some of the tumorigenic
properties of cancer cells. FAK activation induces cell proliferation, motility, survival, invasion, and metastasis. Adapted from
SABiosciences. Retrieved from www.sabiosciences.com (accessed October 2010). EGF = epidermal growth factor;
EGFR = epidermal growth factor receptor; PLC-c = phospholipase Cc.
10/11
other ATP-binding FAK inhibitors.205,206 Early studies show FAK inhibition has been a relatively new approach to
that this molecule increases breast cancer cell apoptosis, targeted cancer therapy. This approach is unique, and early
inhibits in vivo breast cancer cell growth and metastasis, and studies suggest that FAK inhibition, either alone or in com-
inhibits ascites and peritoneal seeding in models of ovarian bination with other agents, may provide novel anticancer
cancer.205,207 regimens.
An obvious concern with any drug is the potential for
toxicity. Theoretically, the more specific the drug, the less
Conclusion
potential it has to produce untoward effects. Although inhib-
iting ATP binding prevents FAK activation, this effect is The oncologic arena is changing. As the understanding
somewhat nonspecific and, as such, raises concern about of the complexities of cell signaling, cell division, apoptosis,
potential toxicity. Specific inhibition of the Y397 phosphory- and angiogenesis, grows, so does the armamentarium of ther-
lation site, without blocking ATP binding, may offer a more apeutic agents against cancer. Some of these agents have
specific target for FAK inactivation. Recently, several small been studied extensively and already are used clinically.
molecule inhibitors that directly target the Y397 autophos- Others that show promise are at the early stages of develop-
phorylation site have been developed.208 One such molecule, ment. The objective of studying these molecules is to develop
1,2,4,5-benzenetetraamine tetrahydrochloride (Y15), binds drugs that selectively target malignant cells while sparing
specifically to the Y397 site, does not affect ATP binding or normal cells. By doing so, not only can efficacy against cancer
Pyk-2, and effectively inhibits FAK activation. In vitro, Y15 be improved, but toxicity can also be minimized. Thus, in
increased detachment and inhibited adhesion of breast cancer addition to more traditional advances in surgical and medical
cells and tumorigenesis in vivo.208 Additional studies have treatment of cancer, targeted therapeutics increasingly will
demonstrated the efficacy of Y15 in inhibiting pancreatic and play a role in surgical oncology. This is an exciting area
neuroblastoma tumor growth in vivo.209–211 In addition, when of development with a substantial collection of established
combined with gemcitabine, these two agents demonstrated regimens and promising new therapies on the horizon.
synergy in inhibiting pancreatic cancer cell growth.211 This
novel small molecule inhibitor of FAK activation, therefore, Financial Disclosure: Dr. Vita Golubovskaya is a co-founder of
holds promise as a potential new therapeutic agent. CureFAKtor Pharmaceuticals.
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188. Wakelee H, Patnaik A, Sikic BI, et al. Phase Pyk2 and Src in linking G-protein-coupled 210. Beierle EA, Ma X, Stewart J, et al. Inhibi-
I and pharmacokinetic study of lexatumum- receptors with MAP kinase activation. tion of focal adhesion kinase decreases
ab (HGS-ETR2) given every 2 weeks in Nature 1996;383:547–50. tumor growth in human neuroblastoma.
patients with advanced solid tumors. Ann 200. Wendt M, Schiemann WP. Therapeutic Cell Cycle 2010;9:1005–115.
Oncol 2010;21:376–81. targeting of the focal adhesion complex 211. Hochwald S, Nyberg C, Zheng M, et al.
189. Golubovskaya VM, Cance WG. Focal adhe- prevents oncogenic TGF-beta signaling A novel small molecule inhibitor of FAK
sion kinase and p53 signaling in cancer cells. and metastasis. Breast Cancer Res 2009;11: decreases growth of human pancreatic
Int Rev Cytol 2007;263:103–53. R68. cancer. Cell Cycle 2009;8:2435–43.
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3 BREAST, SKIN, AND SOFT TISSUE 8 SOFT TISSUE SARCOMA — 1
8 SOFT TISSUE SARCOMA

Aimee M. Crago, MD, PhD, and Samuel Singer, MD, FACS
The term soft tissue sarcoma (STS) defines cancers that develop Etiology
from mesenchymal cells and their progenitors. STS is rare; Factors responsible for the development of sporadic STS
the disease is diagnosed in approximately 10,000 individuals are poorly understood, and few etiologic relationships have
yearly in the United States.1 This represents approximately been definitively characterized. The disease is loosely associ-
1% of adult malignancies and 15% of pediatric malignancies. ated with exposure to various herbicides and environmental
We now recognize that, as rare as STS is, it actually repre- toxins. The clearest of these connections are associations of
sents an umbrella diagnosis encompassing over 50 different vinyl chloride and thorium dioxide (Thorotrast) with hepatic
histologic subtypes of disease. Histologic subtype, in conjunc- angiosarcoma.2 Patients who develop chronic lymphedema,
tion with tumor location, largely defines the biologic behavior often following surgical lymph node dissection, are also at
of a given lesion and the associated clinical prognosis [see risk for the development of angiosarcoma, a clinical scenario
Figure 1]. Approximately half of all STSs occur in the extrem- known as Stewart-Treves syndrome.3
ities and 15% in the retroperitoneum [see Figure 2]. The most Exposure to therapeutic and environmental radiation is a
common histologic subtype in adults is liposarcoma (24% factor that clearly puts patients at risk for the development of
of extremity STS and 45% of retroperitoneal STS); other STS. Radiation-induced sarcomas are defined as those occur-
common subtypes are malignant fibrous histiocytoma ring within the prior radiation field and having a pathologic
(21% of extremity STS) and leiomyosarcoma (21% of confirmation of sarcoma that is histologically distinct from
retroperitoneal STS) [see Figure 3]. the primary cancer.4 In a population-based study of 295,712
Unfortunately, the complexity created by diverse tumor patients with solid or hematologic tumors, those treated with
characteristics means that treatment of STS is similarly radiation therapy had a twofold higher rate of sarcoma devel-
complex. This chapter attempts to simplify the principles opment compared with the general population. For patients
of STS therapy, defining an algorithm for patient evaluation who received radiation before age 55, the rate was fourfold
and treatment while highlighting common indications for higher than in the general population.5 The median interval
diverging from this strategy as dictated by disease subtype between radiation administration and development of
and location. radiation-associated STS is 10 years. The most common
a b
1.0 1.0
0.8 0.8
Disease-Specific Survival
0.6 0.6
0.4 0.4
Desmoid (n = 332)
Liposarcoma (n = 1,107)
Myxofibrosarcoma (n = 343) Extremity (n = 2,318)
0.2 Other (n = 1,778) 0.2 Trunk (n = 577)
MFH/NOS (n = 708) Viscera (n = 764)
Leiomyosarcoma (n = 528) Other (n = 582)
MPNST (n = 129) Retroperitoneal/intra-abdominal (n = 684)
0.0 0.0
0 5 10 15 20 25 0 5 10 15 20 25
Time (years) Time (years)
Figure 1 Disease-specific survival stratified by (a) histologic type and (b) tumor location. Data are derived from all cases of soft
tissue survival evaluated, treated, and followed prospectively at Memorial Sloan-Kettering Cancer Center over a 25-year period.
MFH/NOS = malignant fibrous histiocytoma/sarcoma not otherwise specified; MPNST = malignant peripheral nerve sheath
tumor.
The authors and editors gratefully acknowledge the contributions of the previous authors, Eric Kimchi, MD, Herbert Zeh, MD,
Yixing Jiang, MD, PhD, and Kevin Staveley-O’Carroll, MD, Phd, FACS, to the development and writing of this chapter.
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Other Upper Extremity identified in many histologic subtypes of STS. These include
12% 12% chromosome amplifications, point mutations, and gene
translocations. In many tumors, these genomic alterations
can be used to identify the histologic subtype. For instance,
Trunk well-differentiated and dedifferentiated liposarcoma cells
10% have characteristic chromosome 12 amplifications that result
Lower Extremity in increased levels of MDM2 and CDK4 proteins, which can
28% be stained by immunohistochemistry. In myxoid-round cell
liposarcomas and synovial sarcomas, gene fusion products
(FUS-CHOP and SSX-SYT, respectively) can be detected
by polymerase chain reaction. With gastrointestinal stromal
tumors (GISTs), genetic characterization (c-kit overexpres-
Visceral sion) has been used to identify the tumor; in addition, c-kit
22% overexpression is targeted by imatinib in systemic treatment
of the disease.
Germline mutations have also been associated with devel-
Retroperitoneal/ opment of STS. Examples include Li-Fraumeni syndrome
intra-abdominal (p53 mutation associated with STS and osteosarcoma),
16% neurofibromatosis type 1 (von Recklinghausen disease; NF1
mutation associated with progression of neurofibromas to
Figure 2 Anatomic distribution of all cases of soft tissue
malignant peripheral nerve sheath tumors), and Gardner
sarcomas evaluated, treated, and followed prospectively at
Memorial Sloan-Kettering Cancer Center over a 25-year
syndrome (APC mutation associated with intra-abdominal
period (N = 7,850). desmoid tumors). These syndromes can be inherited. Child-
hood retinoblastoma, Werner syndrome, Gorlin syndrome,
Carney triad, and tuberous sclerosis also carry increased risk
subtypes of radiation-induced sarcoma are angiosarcoma of STS.
(27%), high-grade malignant fibrous histiocytoma (26%),
and leiomyosarcoma (12%). In retrospective and case-control
Tumor Staging and Patient Prognosis
studies, a sarcoma being radiation associated is an indepen-
dent risk factor (by multivariate analysis) for disease-specific T stage for STS is determined not only by tumor size (T1,
death.6 5 cm and below; T2, larger than 5 cm) but also whether the
Although environmental causes for STS are incompletely lesion is superficial (T1a or T2a) or deep (T1b or T2b) to
understood, characteristic molecular changes have been the muscle fascia. Nodal disease (N1) is rare in STS patients;
a b
Desmoid 4% Myxofibrosarcoma MFH/NOS/Undiff
10% 8%
MFH/NOS/Undiff Desmoid 4%
21% MPNST 2%
MPNST 3%
Liposarcoma DSRC 5%
Synovial 10% 45%
GIST 4%
DFSP 4% SFT/HPC 2%
Fibrosarcoma Other 9%
Liposarcoma 4%
24%
Other 12%
Leiomyosarcoma
Leiomyosarcoma
21%
8%
Figure 3 Histopathologic distribution of (a) extremity soft tissue sarcoma (n = 3,123) and (b) retroperitoneal/intra-abdominal
soft tissue sarcoma (n = 1,241). Data are based on all cases of soft tissue sarcoma evaluated, treated, and followed prospectively
at Memorial Sloan-Kettering Cancer Center over a 25-year period. DFSP = dermatofibrosarcoma protuberans; DSRC =
desmoplastic small round cell tumor; GIST = gastrointestinal stromal tumor; MFH/NOS/Undiff = malignant fibrous
histiocytoma/sarcoma not otherwise specified/undifferentiated pleomorphic sarcoma; MPNST = malignant peripheral nerve
sheath tumor; SFT/HPC = solitary fibrous tumor/hemangiopericytoma.
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it does not confer a prognosis as poor as do distant metastases describe extremity and truncal STS and abdominal and
(M1). retroperitoneal STS.
The American Joint Committee on Cancer (AJCC) staging
system for STS includes not only tumor size and the presence     
of nodal and metastatic disease, as in adenocarcinomas, but Diagnosis and Evaluation
also tumor grade7; it is therefore termed TNGM staging. It
Patients with STS of the extremity and superficial trunk
should be noted, however, that the traditional AJCC grading
most commonly present with a palpable mass sometimes
system, which is based on differentiation (well, moderate,
brought to their attention by a minor trauma in the region.
or poor), is not generally applicable to STS. Most sarcoma
After a careful history and physical examination, a magnetic
grading systems incorporate the histology-specific extent of
differentiation, mitotic rate, and necrosis. The most widely resonance imaging (MRI) or computed tomographic (CT)
accepted system, that of the French Federation of Cancer scan is indicated for all but small (< 2 cm), superficial lesions,
Centers Sarcoma Group (FNLCC), uses these three factors which can be evaluated by excisional biopsy. Cross-sectional
to classify sarcomas as low (G1), intermediate (G2), or high imaging provides the size and location of the lesion and
(G3) grade. identifies involvement of adjacent structures. CT is readily
TNGM staging classifies STS into four broad stages.7 available and less expensive, although MRI can provide better
Stage I includes all localized, low-grade tumors. Stage II is soft tissue definition in the extremity. Histologic subtype,
localized intermediate-grade tumors or high-grade, localized which dictates appropriate treatment, is not, in most instances,
tumors that are small and/or superficial. Stage III disease well defined by CT or MRI. The exception to this rule is
represents large (> 5 cm), high-grade tumors. Stage III well-differentiated liposarcoma (atypical lipomatous tumors).
disease also includes STS associated with nodal metastases On cross-sectional imaging, these lesions resemble normal
independent of grade and size. Stage IV disease represents all fat in their signal intensity, appear encapsulated, and are
disease associated with distant metastases. associated with thick, internal septations.10 For tumors located
Outcomes based on TNGM staging are shown in Figure 4. deep to the investing fascia, imaging findings are almost
Although stage is a strong prognostic factor, there is a pathognomonic for this subtype, and further workup is not
significant degree of variability among patients within each warranted. These lesions should be completely excised with,
of the localized disease stages (stage I, II, or III) as relates to when possible, a margin of normal muscle or fascial tissue to
outcome after surgical resection of the primary tumor. One minimize the risk of local recurrence.
reason for this limitation may be that the AJCC system If the STS does not appear consistent with an atypical lipo-
does not incorporate multiple prognostic factors important in matous mass, biopsy is indicated prior to defining a treatment
STS. For example, tumor histology is of significant import; plan. Performed improperly, the biopsy of an extremity mass
malignant peripheral nerve sheath tumors are associated with can result in significant oncologic and cosmetic consequences
poorer disease-specific survival than are myxofibrosarcomas when definitive excision is performed. For this reason, the
[see Figure 1a]. Given these facts, a prognostic nomogram has principles of STS biopsy should be part of the core proce-
been developed from retrospective data collected from 2,163 dural knowledge for all general surgeons. Although incisional
patients treated at Memorial Sloan-Kettering Cancer Center biopsy had been the standard method of diagnosis, core
[see Figure 5] and validated using a prospectively enrolled biopsy provides adequate tissue for evaluation in almost all
cohort of 929 patients treated at the University of California, cases and often leads to accurate diagnosis of histologic type
Los Angeles.8,9 Tumor size, histologic subtype, and site of and grade.11 When performing a core biopsy for suspected
disease are all used to improve prediction of patient outcome. STS, the surgeon or radiologist should first consider where
Prognostic accuracy is further enhanced by the fact that the surgical incision will be placed. The biopsy site will be
variables such as size and patient age can be considered excised at the time of surgery and should, therefore, be placed
continuous variables rather than being divided into a few directly adjacent to the planned surgical incision. If multiple
categories, as they are in staging systems and risk category cores are taken, they should be angled serially toward a
systems. A Web-based version of the STS nomogram is different region of the tumor but always obtained through a
available for general reference (http://www.mskcc.org/mskcc/ single biopsy site.
html/6181.cfm). In the event that core biopsy is insufficient for diagnosis or
the lesion is too small to biopsy in this manner, incisional or
excisional biopsy is performed. Again, careful planning of the
Evaluation and Treatment of Soft Tissue Sarcoma biopsy is essential. The biopsy incision should always be
Surgical excision of STS is the mainstay of our current oriented longitudinally along the limb. This is because the
treatment algorithm. A multidisciplinary approach to the definitive surgery for excision of an STS will require resection
disease is, however, essential, because of the complexity of the biopsy incision with circumferential margins between
involved in histology-based treatment. The risks and benefits 1 and 2 cm (depending on the histologic subtype of the STS).
of radiation and chemotherapy as well as adjuvant and If a biopsy scar is oriented transversely, the diameter of the
neoadjuvant approaches should be carefully weighed when surgical specimen must increase dramatically to obtain
determining the overall treatment plan for a patient with adequate surgical margins. This often means that primary
STS. Prevalence of histologic subtypes, treatment-related closure of the defect is impossible, and a skin graft or muscle
morbidities, and patterns of recurrence are very different for flap is essential to cover the surgical bed.
primary STS of the extremity or superficial trunk versus the All STS patients with high-grade disease should undergo a
abdomen or retroperitoneum. The sections below separately CT scan of the chest to evaluate for pulmonary metastases.
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1.0
0.8
0.6
Stage I (n = 1,881)
Stage II (n = 816)
Stage III (n = 1,871)
0.4
Stage IV (n = 526)
0.2
0.0
0 5 10 15 20 25
Time (years)
Figure 4 Disease-specific survival according to American Joint Committee on Cancer TNGM stage based on all cases of soft
tissue survival evaluated, treated, and followed prospectively at Memorial Sloan-Kettering Cancer Center over a 25-year period.
For those with low-grade disease, the risk of metastasis is incidence of local recurrence, but their disease-free and over-
minimal and chest x-ray is generally adequate and cost- all survival rates were no different from those who underwent
effective. Many STSs are not fluorodeoxyglucose avid; amputation. Patients experiencing a local recurrence were,
therefore, positron emission tomography (PET) has poor in large part, salvaged with additional surgery.12 Limb-sparing
sensitivity for use in the staging of these diseases. surgery is, therefore, currently considered the standard of
After a pathologic diagnosis of STS has been obtained, the care in STS surgery.
histologic subtype and grade have been identified, and the Resections should be carefully planned preoperatively to
patient has been assessed for distal metastases, a multidisci- consider functional outcomes and risks of recurrent local
plinary treatment plan can be defined. In most cases of local- disease and distal progression. Importantly, although many
ized disease, the primary treatment will be resection or, much extremity lesions are associated with what appears on inspec-
less commonly, radiation (discussed below in the context of tion to be a well-defined pseudocapsule, microscopic disease
adjuvant radiation). extends beyond this layer. Therefore, during limb-sparing
procedures, a wide margin (1 to 2 cm) of normal tissue should
Surgical Planning be resected with the specimen to reduce the risk of local
An algorithm for the treatment of extremity STS is shown recurrence. When the tumor abuts a fascial plane of an adja-
in Figure 6. cent muscle, this layer should be resected with the tumor.
Prior to 1981, the standard surgical approach to STS of the When the tumor is superficial, the underlying muscle fascia
extremity was amputation. A randomized, controlled trial, should always be resected.
coordinated at the National Cancer Institute, defined a role When treating extremity STS, the surgeon should consider
for limb-sparing surgery. The trial followed 43 patients with the relationship between the tumor and nearby neurovascular
high-grade tumors treated with amputation or limb-sparing structures. This will allow him or her to inform the patient
resection with adjuvant radiation. Five years after resection, about sensory and motor deficits that may be expected after
patients undergoing limb-sparing surgery clearly had a higher a limb-sparing procedure. It is also vital for surgical planning;
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0 10 20 30 40 50 60 70 80 90 100
Points
5–10
Size (cm)
≤5 > 10
Deep
Depth
Superficial
Lower Extremity Thoracic/Trunk Head/Neck
Site
Upper Extremity Visceral Retro/Intra-abdominal
Lipo Leiomyo Synovial
Histology
Fibro MFH Other MPNT
Age (years)
16 20 30 40 50 60 70 80 90
Total Points
0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320
12 yr Low Gr. SSD

0.04 0.06 0.08 0.1 0.15 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.88
12 yr High Gr. SSD

0.04 0.06 0.08 0.1 0.15 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.88 0.95 0.99
Instructions for Physician: Locate the patient’s tumor size on the Size axis. Draw a line straight upward to the Points axis to
determine how many points toward sarcoma-specific death the patient receives for his tumor size. Repeat this process for the
other axes, each time drawing straight upward to the Points axis. Sum the points achieved for each predictor and locate this
sum on the Total Points axis. Draw a line straight down to either the Low Grade or High Grade axis to find the patient’s
probability of dying from sarcoma within 12 years assuming he or she does not die of another cause first.
Instruction to Patient: “If we had 100 patients exactly like you, we would expect between <predicted percentage from
nomogram - 8%> and <predicted percentage + 8%> to die of sarcoma within 12 years if they did not die of another cause
first, and death from sarcoma after 12 years is still possible.”
Figure 5 Positive nomogram for prediction of sarcoma-specific death (SSD) at 12 years postresection for patients with soft
tissue sarcoma. Fibro = fibrosarcoma; GR = grade; Leiomyo = leiomyosarcoma; Lipo = liposarcoma; MFH = malignant fibrous
histiocytoma; MPNT = malignant peripheral nerve sheath tumor.
nerves, veins, and arteries often limit the extent of the resec- DFSP should be resected en bloc with margins of 2 cm,
tion to be performed. Whenever possible, vascular structures including the underlying fascia, but underlying muscle rarely
are skeletonized and major nerves salvaged by resecting needs to be removed as this subtype generally does not
perineurium. This will preserve limb function, and if a high- penetrate the fascia. Myxofibrosarcoma, however, often
risk lesion is removed with an R1 margin, adjuvant radiation penetrates fascia and invades muscle and is often multifocal
is an option for reducing rates of local recurrence (see below). with skip areas. Therefore, excision should be not only wide
To avoid amputation when major neurovascular structures laterally but also deep with significant surrounding muscle;
are encased by a high-grade tumor, the surgeon may consider again, margins of 2 cm should be resected en bloc with the
advanced maneuvers such as arterial bypass or resection of tumor. With either of these subtypes, more conservative
the sciatic nerve.13 Venous reconstruction is rarely indicated resection leads to a high risk of local recurrence. Although
and when performed is often not successful; compression recurrence of DFSP in the surgical bed is a difficult local
garments are used to control postoperative symptoms. problem, it is almost never associated with distant spread
Preoperative diagnoses of dermatofibrosarcoma protuber- (unless there is histologic evidence of sarcomatous degenera-
ans (DFSP) and myxofibrosarcoma are of particular concern tion). Local recurrence of myxofibrosarcoma, however, is
in planning local resection. These lesions often have micro- potentially more dangerous as it is associated with a high-
scopic tentacles that extend laterally from the lesion.14–16 grade phenotype in as many as 54% of cases. High-grade
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History and physical examination

CT/MRI of primary site
Staging CT or x-ray of chest
Unclear histology Well-differentiated liposarcoma
Wide local excision

Core or excisional biopsy
Low grade High grade
Complete excision with margins 1–2 cm • Rhabdomyosarcoma or Ewing sarcoma (any size)
• > 10 cm, other high-grade subtype excluding dedifferentiated liposarcoma
pleomorphic liposarcoma
• 5–10 cm synovial sarcoma
Limited use of adjuvant therapy round cell liposarcoma
even if margin is close or positive
yes no
Neoadjuvant Complete excision with goal

chemotherapy of 1- to 2- cm surgical margins
Adjuvant radiation therapy if

• Tumor > 5 cm diameter
• Margin is close or positive on pathologic evaluation
and reexcision is not feasible
• Recurrence would require morbid resection
Figure 6 A treatment algorithm for soft tissue sarcoma of the extremity. CT = computed tomography; MRI = magnetic
resonance imaging.
recurrence of myxofibrosarcoma places the patient at signifi- conclusion comes from three large randomized, controlled
cant risk for metastatic disease.15,16 Therefore, every attempt trials. In the first trial, 141 patients with STS of the extremity
should be made to resect myxofibrosarcomas with negative treated with surgery and chemotherapy were randomized to
margins, even when they appear as low-grade lesions. Mul- receive postoperative radiation or no radiation.19 In the
tiple procedures may be required to adequately remove all context of both high- and low-grade tumors, the addition
disease, and reconstruction will often require tissue flaps or a of adjuvant radiation significantly reduced the risk of local
skin graft. recurrence (risk at 9 years of 33% versus 4% for low-grade
Lymph node metastases are rare in STS and generally tumors and 19% versus 0% for high-grade tumors). How-
occur in the context of epithelioid or clear cell variants of ever, radiation afforded no benefit in terms of overall survival.
STS.17 In these cases, sentinel lymph node biopsy has been
Similarly, brachytherapy applied after complete resection of
reported and can give prognostic information as a positive
STS in the extremity and superficial trunk improved local
biopsy defines stage III disease. However, this procedure has
control but did not alter disease-specific survival.20 Moreover,
not been associated with a therapeutic benefit, and no sur-
vival advantage has been reported in patients undergoing local benefit of brachytherapy was restricted to patients who
completion lymph node dissection.18 For these reasons, the presented with high-grade tumors. Because radiation therapy
role of sentinel lymph node biopsy in management of STS can have long-term complications such as joint fibrosis and
remains debatable. secondary malignancies, the potential risk versus benefit of
radiation therapy must be carefully weighed for each patient.
Radiation in Extremity STS Radiation therapy is routinely prescribed for high-risk lesions
Radiation therapy after limb-sparing surgery for STS (> 5 cm and high-grade or recurrent tumors that were not
appears to increase local control but not survival. This previously treated with radiation) with close margins. Given
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the fact that no trial has shown radiation to improve overall typically present with a palpable mass or a mass found inci-
or disease-specific survival, it is reasonable to defer adjuvant dentally on imaging acquired for an unrelated symptom.
therapy when the tumor is low grade or the margin is wide, Patients may have pain and/or symptoms of lower extremity
particularly if a local recurrence could be excised without neural compromise. This is particularly true for those with
amputation or major functional impairment. large retroperitoneal tumors, which often remain undetected
The decision to prescribe radiation therapy is further com- until they reach sizes greater than 10 cm in diameter. Rarely,
plicated in that the modality can be administered either pre- patients with retroperitoneal tumors are diagnosed because of
operatively or postoperatively. A randomized trial compared paraneoplastic syndromes, such as hypoglycemia related to
these strategies by assigning 190 patients with extremity STS leiomyosarcoma or solitary fibrous tumor.
to either adjuvant radiation (66 Gy) or neoadjuvant radiation A preoperative biopsy is usually needed only if there is
(50 Gy).21 This study showed no difference in local control. suspicion of carcinoma, lymphoma, or germ cell tumor or if
It did show an increased rate of wound complications in the mass appears to be not completely resectable; in other
patients treated with radiation prior to resection (35% versus circumstances, biopsy rarely alters the therapeutic plan.
17%). This difference was most pronounced in patients with Regardless of histologic subtype, the goal of operative inter-
STS of the lower extremity. Conversely, patients receiving vention is complete gross resection, which can be achieved in
therapy after resection had a higher risk of long-term fibrotic 80% of patients. The major hindrance to tumor resectability
complications (e.g., joint stiffness), presumably related to the is involvement of the great or visceral vessels. Retroperitoneal
higher dose of radiation.22 Therefore, preoperative radiation lesions can encase the aorta, vena cava, celiac axis, or porta.
therapy can be an excellent choice for patients with tumors In these cases, attempt at resection will leave gross tumor in
adjacent to a joint or tumors located in the upper extremity the surgical bed, and when an R2 resection is anticipated,
that are likely to have close or positive margins. In all other surgery should be considered only as palliative therapy.
settings, the role of radiation therapy is determined from Debulking has not been demonstrated to provide survival
the final assessment of tumor histology, and margin status benefit, and patients with a grossly positive margin have
following resection determines the contribution radiation outcomes that are similar to those of patients undergoing no
may play in the multimodality treatment of extremity STS. operative intervention [see Figure 7].
Involvement of adjacent organs such as the spleen,
Neoadjuvant Chemotherapy pancreas, and bowel does not preclude surgical resection.
No prospective study has definitively shown a benefit to STS associated with these findings can be managed by en
administration of adjuvant chemotherapy in STS patients. bloc resection to achieve R0 or R1 resection. It should be
However, three groups of patients should receive neoadjuvant noted that resection of these organs (excluding the kidney)
therapy [see Figure 6] because of the high risk of metastasis with STS does increase the morbidity associated with
and/or predicted chemosensitivity of a tumor subtype. The surgery.27,28 If the retroperitoneal lesion involves the kidney,
first group includes patients with rhabdomyosarcoma or adequate resection can often be achieved by removing
Ewing sarcoma. Regardless of tumor size, these patients have only the renal capsule with the tumor. This is possible as
a high risk of metastasis and are always treated with chemo- retroperitoneal tumors rarely invade the renal parenchyma.
therapy prior to surgery. The second group encompasses Involvement of the kidney hilum, however, will require a
patients with high-grade tumors that are larger than 10 cm. nephrectomy to obtain adequate margins.
Retrospective studies have demonstrated that neoadjuvant
Visceral Disease
chemotherapy is associated with improved disease-specific
survival among these patients.23 Specifically, neoadjuvant The principles that govern surgical resection of visceral
chemotherapy is considered in patients without significant sarcomas are similar to those noted above for retroperitoneal
comorbidities and with large, high-grade, round cell liposar- tumors. In all instances, a negative resection margin is the
coma, pleomorphic liposarcoma, synovial sarcoma, malignant goal of operative intervention. The most common subtype of
peripheral nerve sheath tumor, or leiomyosarcoma. However, STS in the viscera is GIST; patients present with gastrointes-
dedifferentiated liposarcomas, even when they are large and tinal bleeding or bowel obstruction. These tumors are gener-
high grade, have a low risk of distant metastasis and are rarely ally well circumscribed and can be removed with a 1 cm gross
chemosensitive, so initial treatment is surgery when the margin; anatomic resection has not been shown to improve
lesions are resectable. outcomes. For example, in most cases, a gastric GIST can be
The third group considered for neoadjuvant chemotherapy removed with only a small (1 cm) margin of surrounding
includes patients with moderate-size tumors (5 to 10 cm) tissue, preserving the main body of the stomach. Even with
representing relatively chemosensitive histologies that have a large tumors, this approach allows for preservation of visceral
propensity to metastasize. Round cell liposarcoma, pleomor- organs and minimizes the complexity of reconstruction.
phic liposarcoma, and synovial sarcoma are the most common Adjuvant Therapy in Retroperitoneal and Visceral STS
histologic subtypes treated in this manner.24–26
Retroperitoneal lesions are almost exclusively liposarcoma,
    leiomyosarcoma, or malignant peripheral nerve sheath tumors.
These tumors have low rates of response to chemotherapy,
Retroperitoneal Disease and adjuvant chemotherapy has never been demonstrated to
The retroperitoneum is the second most common site of improve survival in this patient population. Radiation ther-
STS, although retroperitoneal lesions are significantly less apy, however, is more debatable. Several small, retrospective
common than those of the extremity [see Figure 2]. Patients studies have suggested that its use is associated with reduced
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1.0
0.8
R0 (n = 317)
R1 (n = 243)
0.6 R2 (n = 93)
Unresectable (n = 58)
0.4
0.2
0.0
0 5 10 15 20 25
Time (years)
Figure 7 Disease-specific survival according to extent of resection among patients with retroperitoneal soft tissue sarcoma
treated at Memorial Sloan-Kettering Cancer Center over a 25-year period. Outcomes were similar for patients undergoing
incomplete gross resection (R2; n = 93) and for patients with disease judged unresectable at exploration (n = 58).
risks of local recurrence following surgical resection.29 Never- This drug targets the c-kit receptor and is a cytostatic reagent.
theless, no difference in overall survival has been implied, and The effect of adjuvant imatinib therapy in high-risk GIST (at
selection bias and significant differences in surgical manage- least 3 cm in diameter) has been examined in a randomized,
ment between institutions remain confounding factors when controlled trial.31 In patients treated with adjuvant imatinib,
interpreting the literature. We do understand that adjuvant recurrence-free survival at 1 year was increased from 83 to
radiation administered after resection of a retroperitoneal 98%. For this reason, the drug is generally administered in
lesion is associated with significant morbidity. Radiation the adjuvant setting to high-risk patients. Imatinib is also of
enteritis occurs in up to 60% of patients and can lead to use in the neoadjuvant setting.32 It can be prescribed in
chronic malnutrition, enteric fistulization, and bowel obstruc- attempt to reduce the size of the tumor and minimize the
tion.30 Given this drawback of adjuvant radiation therapy, morbidity of resection when surgical resection of a lesion will
neoadjuvant radiation should be considered if surgical resec- prove morbid. Examples of these cases include lesions located
tion is likely to result in positive margins and radiation is to at the gastroesophageal junction or rectal lesions. Imatinib
be prescribed. The neoadjuvant approach limits the morbid- can be prescribed in attempt to reduce the size of the tumor
ity of treatment because it can target the radiotherapy to the and minimize the morbidity or resection.
region at highest risk for microscopic residual disease while
limiting the dose to surrounding viscera.    
GISTs present a unique case for application of adjuvant Following surgical resection of STS, the tumor bed is
treatment because many of them are sensitive to imatinib. evaluated by cross-sectional imaging every 4 to 6 months,
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depending on the grade of the tumor. Local recurrence is 1,000 cases per year in the United States. Standard manage-
observed in approximately 10 to 30% of patients with extrem- ment of the disease has included wide resection in the
ity STS and 50% of patients with retroperitoneal lesions.33 At past. Such procedures may be associated with significant
the time of recurrence, patients should again be staged to rule morbidity; they can result in short bowel syndrome, incisional
out metastatic disease. hernia, or functional impairment of a limb. Desmoids do not
In the context of extremity recurrence, local resectability is metastasize, however, and this has led to a significant shift in
determined as above. Important considerations are the posttreatment algorithms. Current management strategies do not
operative morbidity of limb-sparing surgery and the ability to focus solely on complete eradication of local disease but also
spare the neurovascular bundle. The surgeon should excise on improving functional outcomes for patients with desmoid
not only gross tumor and a margin of normal tissue but also tumors.
the prior surgical incision, drain site, and resected specimen Data supporting current treatment recommendations
bed. Adjuvant or neoadjuvant radiation or chemotherapy have been collected only over the last two decades. Large
may be considered if the patient was not previously treated retrospective series showed no difference in the rates of local
with these modalities. Local recurrence is associated with
recurrence following R1 versus R0 resection. This fact was
poor prognosis when lesions are high grade, recurrences are
the first that suggested clinicians could adopt a function-
greater than 5 cm in diameter, and the recurrence-free inter-
preserving approach when planning surgical resection.40
val is short (less than 16 months).34 Patients whose disease
Subsequently, in the context of recurrent, nonoperable
recurs with these features have an increased risk of disease-
desmoids, it was observed that the growth of tumors was
associated death and should be considered for neoadjuvant
actually self-limited in some cases. An initial period of
chemotherapy or enrolment in clinical trials.
As in the extremity, retroperitoneal recurrence presents a observation was, therefore, proposed to be a safe treatment
difficult problem and is associated with a poor prognosis. If option in patients with recurrent disease.41 The clear benefit
the lesion is isolated, surgical resection can again be used in thought to be associated with early surgical resection was
an attempt to achieve a cure, and its goal should be negative questioned.
margins. Neoadjuvant radiation therapy can be considered. Most recently, an analysis of 142 patients with primary or
As in extremity recurrence, poor prognostic features include recurrent desmoid was reported by Fiore and colleagues.42
large size of tumor recurrence and short disease-free interval, This study examined cases in which a frontline, nonoperative
and patients with these features should be considered for approach was employed. Eighty-three of these patients did
neoadjuvant trials. In addition, retroperitoneal liposarcoma not receive surgery, radiation, or medical treatment at
patients with local recurrence growth rates exceeding 1 cm presentation. They were instead followed with serial imaging
per month have an extremely poor prognosis even after every 3 to 6 months. The 5-year progression-free survival in
aggressive attempts to completely excise all measurable this cohort was 49%. For patients who progressed, surgical
disease. In a retrospective analysis of such patients, surgical resection was considered. If resection would result in signifi-
resection was not associated with increased survival. Thus, cant functional impairment or was not technically feasible,
patients with liposarcoma growth rates greater than 1 cm per a course of medical management with targeted therapies
month should be considered for systemic treatment with or cytotoxic therapy was prescribed in the neoadjuvant
novel targeted therapies or conventional chemotherapy.35 setting or for long-term maintenance. Sorafenib, tamoxifen,
cyclooxygenase-2 inhibitors, imatinib mesylate (Gleevec),
Indications for Metastasectomy
and anthracyclines (Doxil) are currently employed for this
In patients with high-grade STS, surveillance of the surgi- purpose.43 No patient with progressive disease was noted in
cal bed is accompanied by cross-sectional imaging of the the study by Fiore and colleagues to have unexpected
lung, the most common site of metastatic disease (44%). In complications or a poor outcome that could be attributed to
most patients, metastases are treated with chemotherapy.
an initial period of observation. Given these data, many large
The choice of agents is dependent on disease histology and is
sarcoma referral centers now uniformly recommend an initial
beyond the scope of this review. Resection, however, is often
period of observation before undertaking major surgery in the
recommended when disease at the primary site is well
context of desmoid fibromatosis.
controlled and the patient presents with isolated pulmonary
Radiation following resection of desmoids has been
metastases. Patients most likely to benefit from metastasec-
tomy include those with metachronous disease and long advocated in both the adjuvant and neoadjuvant settings.
disease-free intervals, those with slowly growing metastases, Although several analyses have demonstrated an association
and those with a limited number of lesions (one to three). between radiation and reduced local recurrence after surgery,
Patients with metastatic disease have an overall survival of no difference in overall survival has been observed.44,45 The
less than 20% at 5 years, but long-term survival is observed long-term complications associated with radiation in a patient
in patients carefully selected for metastasectomy.36,37 In these population, which is generally diagnosed during their second
patients, surgery alone may be sufficient for cure as no through fourth decade of life, limit its utility. In the context
additional increase in survival has been associated with of a disease that has no metastatic potential, this modality
perioperative chemotherapy.38 is, therefore, almost always reserved for intractable cases
that are symptomatic and have failed all other therapeutic
  options.
Desmoid tumors are rare neoplasms that develop from
mesenchymal stem cells.39 The estimated incidence is only Financial Disclosures: None Reported
10/11
References
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6. Gladdy RA, Qin LX, Moraco N, et al. Do discussion 81–2. with locally recurrent extremity soft tissue
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8. Kattan MW, Leung DH, Brennan MF. ization to preoperative versus postoperative 36. Temple LK, Brennan MF. The role of
Postoperative nomogram for 12-year sarcoma- radiotherapy in extremity soft tissue sarcoma. pulmonary metastasectomy in soft tissue
specific death. J Clin Oncol 2002;20:791–6. Radiother Oncol 2005;75:48–53. sarcoma. Semin Thorac Cardiovasc Surg
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Validation of the postoperative nomogram for Neo-adjuvant chemotherapy for primary 37. Billingsley KG, Burt ME, Jara E, et al.
12-year sarcoma-specific mortality. Cancer Pulmonary metastases from soft tissue
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10. Jelinek JS, Kransdorf MJ, Shmookler BM, postmetastasis survival. Ann Surg 1999;229:
24. Esnaola NF, Rubin BP, Baldini EH, et al.
et al. Liposarcoma of the extremities: MR 602–10; discussion 10–2.
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of survival in adult rhabdomyosarcoma. Ann
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11. Heslin MJ, Lewis JJ, Woodruff JM, Brennan pulmonary resection for metastatic soft-tissue
25. Canter RJ, Qin LX, Maki RG, et al. A syno-
MF. Core needle biopsy for diagnosis of sarcoma of the extremity: a retrospective
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12. Rosenberg SA, Tepper J, Glatstein E, et al. based chemotherapy and improves risk Aggressive fibromatosis (desmoid tumor) is
The treatment of soft-tissue sarcomas of the stratification for patients. Clin Cancer Res derived from mesenchymal progenitor cells.
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13. Brooks AD, Gold JS, Graham D, et al. Resec- discussion 95–7. 41. Phillips SR, A’Hern R, Thomas JM. Aggres-
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assessment of functional status. Ann Surg MF. Histologic subtype and margin of resec- and limb girdles. Br J Surg 2004;91:1624–9.
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14. Farma JM, Ammori JB, Zager JS, et al. for retroperitoneal liposarcoma. Ann Surg Desmoid-type fibromatosis: a front-line
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15. Mentzel T, Calonje E, Wadden C, et al. analysis of 500 patients treated and followed 43. de Camargo VP, Keohan ML, D’Adamo DR,
Myxofibrosarcoma. Clinicopathologic analy- at a single institution. Ann Surg 1998;228: et al. Clinical outcomes of systemic therapy
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variant. Am J Surg Pathol 1996;20:391–405. 29. Pawlik TM, Pisters PW, Mikula L, et al. tumor). Cancer 2010;116:2258–65.
16. Huang HY, Lal P, Qin J, et al. Low-grade Long-term results of two prospective trials 44. Francis WP, Zippel D, Mack LA, et al.
myxofibrosarcoma: a clinicopathologic analy- of preoperative external beam radiotherapy Desmoids: a revelation in biology and treat-
sis of 49 cases treated at a single institution for localized intermediate- or high-grade ment. Ann Surg Oncol 2009;16:1650–4.
with simultaneous assessment of the efficacy retroperitoneal soft tissue sarcoma. Ann Surg 45. Ballo MT, Zagars GK, Pollack A, et al.
of 3-tier and 4-tier grading systems. Hum Oncol 2006;13:508–17. Desmoid tumor: prognostic factors and
Pathol 2004;35:612–21. 30. Kinsella TJ, Sindelar WF, Lack E, et al. outcome after surgery, radiation therapy,
17. Fong Y, Coit DG, Woodruff JM, Brennan Preliminary results of a randomized study of or combined surgery and radiation therapy.
MF. Lymph node metastasis from soft tissue adjuvant radiation therapy in resectable adult J Clin Oncol 1999;17:158–67.
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3 Breast, Skin, and Soft Tissue 9 Benign Breast Disease — 1
9 Benign Breast Disease

Helen Cappuccino, MD, FACS, Ermelinda Bonaccio, MD, and Swati Kulkarni, MD, FACS*
Clinicians should have an understanding of the evaluation  

and management of breast disorders. One in two women will Screening mammography refers to the imaging of asymp-
consult a health care provider for a breast-related complaint tomatic women to detect early, clinically occult breast
during her lifetime.1 The fundamental task facing a physician cancers. Mammography is the only breast imaging modality
who is evaluating a patient with a breast concern is to deter- proven to reduce mortality from breast cancer. The Swedish
mine whether the abnormality is benign or malignant. Even Two-County Trial updated their data in 2000 and demon-
though most breast complaints do not result in a diagnosis strated a 32% reduction in breast cancer mortality in women
of cancer, any woman presenting with a breast complaint invited to screening.5 Based on the findings from these trials,
should receive a comprehensive evaluation. In this chapter, women should begin annual screening mammography at age
we focus on the evaluation and management of benign breast 40. There are subgroups of women at high risk for breast
conditions. carcinoma who may benefit from screening at a younger age,
although no randomized controlled trials support these
Screening Recommendations recommendations.6 Currently, there is no accepted upper age
limit for mammographic screening; however, the presence of
In the absence of a specific breast complaint, breast cancer
significant comorbidities reducing life expectancy to less than
can be detected by screening. The three main methods of
10 years should be considered when ordering a screening
breast cancer screening are breast self-examination (BSE),
mammogram in women over the age of 70.
clinical breast examination (CBE), and screening mammog-
Digital mammography is becoming more common in many
raphy.2 American Cancer Society (ACS) screening guidelines
centers. Results from a large prospective multicenter trial
for women aged 40 years and older specify that mammogra-
comparing digital to conventional film mammography
phy and CBE should be included as part of an annual health
demonstrated no significant difference in cancer detection
examination.3 In addition, health care providers should tell
rates.7 However, digital mammography was found to be more
women about the benefits and limitations of BSE, stressing
sensitive than film in three subgroups: women less than
the importance of promptly reporting any new breast
50 years of age, women with radiographically dense breasts,
symptoms. There is currently no role for routine screening
and women who were pre- or perimenopausal.8
ultrasonography or screening magnetic resonance imaging
(MRI) in the general population.
Evaluating Breast Complaints and Masses
 -
In BSE, the patient inspects and palpates both breasts and 
axillae. One might assume that instruction in BSE would Evaluation of a woman with a breast complaint should
improve breast cancer detection. However there is no conclu- include a thorough history, a physical examination, and
sive evidence that BSE is of significant value in this regard. appropriate diagnostic studies. A complete history of the
Many self-detected tumors are found incidentally, not during current complaint should include onset, duration, and pro-
BSE. Furthermore, the best technique for BSE and optimal gression of symptoms. Precipitating and ameliorating factors
frequency has not been established. The ASC recommends should be noted, as should the relationship of palpable abnor-
counseling patients on the benefits and limitations of BSE as malities, pain, and tenderness to the menstrual cycle. Recent
a part of the breast cancer screening process that also includes history of trauma to the breast, prior infections, fine-needle
mammography and CBE.3 aspirations (FNAs), core biopsies, and surgical biopsies
should also be recorded. Medical records, including operative
   reports and corresponding pathology and radiographic
In CBE, a qualified health care professional carries out a reports, should be reviewed carefully. The treating clinician
complete examination of the breasts and axillae. As with should obtain and review prior breast imaging as part of the
BSE, there is little evidence indicating that annual or semian- patient’s history.
nual CBE increases breast cancer detection rates.4 Neverthe- Symptoms or complaints involving the breast should be
less, it is prudent for the clinician to include CBE as part of evaluated in the context of historical breast cancer risk data.
the physical examination performed on every female patient. Historical risk data include (1) history of the duration and
type of hormone use (oral contraceptives and hormone
* The authors and editors gratefully acknowledge the contribu- replacement therapy); (2) reproductive history (age at men-
tions of the previous authors, Doreen M. Agnese, MD, FACS, arche, age at menopause, age at first live birth, number of
Stephen P. Povoski, MD, FACS, and Wiley W. Souba, MD, gestations and completed pregnancies); and (3) complete
ScD, FACS, to the development and writing of this chapter. family history of all malignancies on both the maternal and
Indicates the text is tied to a SCORE learning objective. Please see the
HTML version online at www.acssurgery.com. DOI 10.2310/7800.S03C09
05/10
Abnormal screening mammogram

with normal physical examination
Additional imaging including ultrasonography

Additional mammogram views
Scre
BI- RADS 1, 2 BI-RADS 3 (probably benign) BI-RADS 4, 5

Back to routine screening schedule Do 6 - month mammogram Do image - guided biopsy
follow-ups for1 year, up to 24 months
Rea
Nipple and Skin Changes
Blanching erythema
Fever, warmth, pain (elevated white blood cells) Nipple excoriation
Asp
Consistent with infection
Empiric antibiotics to cover gram Topical steroids for 7–14 days

positive cocci for Nor
Shor
clini
Resolution No improvement Improvement No improvement

Revert to normal screening Imaging and skin punch biopsy Short -term clinical follow-up Skin punch biopsy
Imaging per screening protocol Imaging
05/10
Abnormal physical examination
Breast pain Nipple discharge Palpable mass or thickening
No mass Mass
Physiologic Pathologic
Screening per standard recommendation See workup for mass Bilateral Bloody
Multiple ducts Single duct
Milky Single breast
Heme Spontaneous
Reassure; holistic measures Per abnormal mammogram

Mammography
Mass No mass
Ductography
See workup for mass Endocrine workup Excision (see text)
28 year old 28 year old

Aspirate (discard fluid) if symptomatic Ultrasonography Mammography +ultrasonography
Normal Worrisome physical Nonsuspicious solid Suspicious solid Solid or complex Simple cyst Normal
examination (consistent with
Short-term Bilateral mammography Core biopsy Aspirate (discard
clinic follow-up Mammography fibroadenoma) + core - needle biopsy fluid) if
Follow up by physical symptomatic
examination and
ultrasonography in 6
months
High suspicion Low suspicion 6-month
Core biopsy follow-up
05/10
the paternal side, including the age at diagnosis. The remain- initial screening mammogram in these patients is given a final
der of the patient’s general history should be evaluated assessment 0 [see Table 1]. Women with a Breast Imaging
with a focus on significant medical problems that may impact Reporting and Data System (BI-RADS) 1 or 2 should
surgical planning. Medications and supplements that may continue to undergo routine annual mammography.8 Women
contain estrogen-like substances and social history (especially with a BI-RADS 3 should undergo short-term follow–up,
tobacco, alcohol, work, exercise, and even sexual history as it which typically involves an ipsilateral mammogram in
pertains to breast stimulation) can be relevant. 6 months followed by a bilateral study at 12 and 24 months.
A finding in this category should have a less than 2%
 
risk of malignancy based on morphologic and distribution
The breasts should be thoroughly examined in the upright features.9,10 Any interval progression at follow-up should
and supine positions. Breast asymmetry and overall appear- prompt a biopsy. Patients with a BI-RADS category 4 or 5
ance of the skin, nipples, and areola should be observed with lesion require a tissue diagnosis. As an adjunct to diagnostic
the patient upright. Any erythema, induration, peau d’orange, mammography, high-frequency breast ultrasonography is
nipple retraction, and ulceration should be noted. Occult skin often used in the diagnostic workup of a mass and can dis-
retraction can be demonstrated by having the woman raise tinguish between a solid and a cystic lesion. If a solid mass
her hands above her head and then place them against her is visualized sonographically, ultrasound-guided core-needle
hips. Bimanual examination of the breast tissue can facilitate biopsy (CNB) can be performed for pathologic diagnosis.
identification of masses in women with dense breast tissue. In
the supine position, turning the patient to either side to dis-   
perse breast tissue facilitates a more thorough examination
Breast biopsies should be performed percutaneously when-
for women with larger breasts. For the ptotic breast, palpa-
ever possible, using stereotactic, ultrasound, or MRI guid-
tion of the breast tissue between the thumb and index finger
ance. CNB with an automated gun or vacuum-assisted device
of the same hand may be useful. Location, mobility, and
has been confirmed in multiple studies to be a reliable alter-
characteristics of masses and thickening should be noted,
native to surgical excision.11,12 Stereotactic (mammographic)
including size, firmness, presence of smooth or irregular
guidance is typically used to biopsy indeterminate or suspi-
borders, overlying skin changes, consistency, and areas of
cious calcifications as well as masses or densities that are
tenderness. Drawings or digital images can be made to docu-
sonographically occult. Ultrasound guidance is used to biopsy
ment physical findings. All tissue between the clavicle and
costal margins should be palpated, from the lateral sternal masses that can be visualized sonographically and is the most
border to the posterior axillary line. Patients should also be cost-effective type of image-guided core biopsy.13 MRI guided
checked for nipple discharge. Axillary, clavicular, and cervical CNB is reserved for lesions that are occult to conventional
lymph node basins should also be palpated in the upright imaging. The benefit of CNB over FNA is that it provides
and supine positions. The presence of adenopathy, including tissue for histologic rather than cytologic evaluation.
the size, consistency (hard versus soft), number, laterality, With any image-guided approach, it is important to
location, and mobility of the lymph nodes, should be confirm that the pathologic results are concordant with the
documented. imaging findings. Treatment decisions should be based on
both pathologic findings and the appearance of the abnormal-
  ity on diagnostic imaging. Discordant imaging and pathologic
findings should prompt a surgical biopsy.
Diagnostic Mammo-
graphy and Targeted   
Ultrasonography
As mentioned previ-
ously, screening mam- MRI is an imaging modality that uses strong magnetic
mography refers to fields to create a cross-sectional image. Breast MRI requires
imaging of an asymp- a specific coil and peripheral intravenous injection of a
tomatic woman. Diagnostic mammography, on the other gadolinium-based contrast medium. Contrast-enhanced
hand, refers to imaging a woman with either a clinical com- breast MRI has been shown to have a high sensitivity for
plaint (a palpable lump, thickening, focal pain, discharge) or detection of invasive breast cancer and can find both invasive
an abnormal screening mammogram. The initial workup of and in situ carcinomas that are occult to conventional
an abnormal screening mammogram involves additional imaging. In practice, use of breast MRI is predominantly
mammographic imaging directed by a radiologist, which limited to women diagnosed with breast carcinoma and
determines if the perceived abnormality is a real lesion. Spot women at increased risk of developing breast cancer.
and rolled views (with or without magnification) can some- At present, there is no indication for the use of positron
times demonstrate that the perceived abnormality was emission tomographic scans in the diagnostic workup of
actually only the result of overlapping glandular tissue and breast diseases outside a clinical trial. A number of new
there is no underlying lesion. The diagnostic mammogram modalities are being investigated, such as positron emission
report would then be given a final assessment 1 mammography, breast-specific gamma imaging, tomosynthe-
(negative), and the patient should return to annual screening sis, and coned-beam computed tomography. Although
mammography. some of these modalities are approved by the Food and
When an abnormality is detected and the patient needs Drug Administration (FDA), they are not currently standard
additional mammographic and/or sonographic imaging, the practice.
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Table 1 American College of Radiology Breast Imaging Reporting and Data System (BI-RADS)
Category Assessment Description/Recommendation
0 Additional imaging evaluation required Additional imaging recommended
1 Negative finding Nothing to comment on; routine screening recommended
2 Benign finding Negative mammogram, but interpreter may wish to describe a finding;
routine screening recommended
3 Probably benign finding Very high probability of benignity; short-interval follow-up suggested to
establish stability
4 Suspicious abnormality Probability of malignancy; biopsy should be considered
5 Abnormality highly suggestive of malignancy High probability of cancer; appropriate action should be taken
The report generated after the diagnostic workup is completed will have a final assessment of 1 to 5. The Breast Imaging Reporting and Data System (BI-RADS)
lexicon was developed to standardize mammographic reports.6 It defines the final assessment categories, which informs the referring physician about the likelihood
of malignancy.
General Management of Clinical Findings in the patient or the clinician. It is important to distinguish this
Breast vague breast thickening or nodularity from a discrete or
dominant breast mass. In clinical practice, the first step in
 
evaluating a nodular area is to compare it with the corre-
A dominant breast mass is defined as a discrete lump that sponding area of the opposite breast. Symmetrical tender
is distinctly different from the surrounding breast tissue. nodularity—for example, in the upper outer quadrant of both
Overall, approximately 10% of dominant breast masses are breasts—is rarely pathologic. These areas often represent
malignant. The workup and management of a discrete breast fibrocystic changes that may resolve with time and thus
mass are governed by the age of the patient, the patient’s should be followed clinically. Asymmetrical areas of vague
family and medical history, the physical characteristics of the thickening in premenopausal women should be reexamined
palpable lesion, and findings on diagnostic imaging. after one or two menstrual cycles. If the asymmetry persists,
  the patient should undergo mammography if she is 35 years
of age or older and has not undergone a mammogram within
The likelihood of malignancy is greater when the patient is the last 6 months. If the mass is clinically suspicious, a surgi-
40 years of age or older and when the mass is solid, hard, cal biopsy for adequate sampling should be performed even
immobile and has irregular borders. Appropriate imaging
in the setting of negative imaging.
studies, including mammography and ultrasonography
should be done. In women over 30 years of age or with a
significant family history of breast cancer, contralateral mam- Management of Specific Benign Breast Complaints
mography is indicated to rule out synchronous lesions. If the
mass is clinically suspicious, CNB or surgical biopsy should 
be performed for tissue diagnosis even in the setting of One of the most
negative imaging. common complaints for
which a woman seeks a
 
doctor’s opinion is mas-
Cysts are a common cause of dominant breast masses, talgia. Mastalgia (breast
particularly in premenopausal women. They can be differen- pain) can be cyclical or
tiated from solid lesions by means of ultrasonography. noncyclical and may be
Sonographically, simple cysts tend to be oval, lobulated, and idiopathic. Often it is related to other common processes that
anechoic, with well-defined borders. Complex cysts with occur in the breast, such as fibrocystic change or infection.
indistinct walls or solid components are more likely to be
Two thirds of women will complain about mastalgia during
associated with carcinoma; therefore, imaging-guided aspira-
the course of their lives.14 Its cause is poorly understood. A
tion, biopsy, or both should be performed. For asymptomatic
history of the onset and course of the pain are important,
simple cysts, no further intervention is required. For symp-
especially as it relates to a woman’s menstrual cycle. Although
tomatic cysts, FNA is appropriate. If the mass does not disap-
pear completely after aspiration, then biopsy of any residual rarely a presenting complaint of breast cancer, mastalgia often
solid component should be performed. Clear fluid should causes considerable concern for patients. Mastalgia resolves
not be sent for cytologic analysis because of the high likeli- spontaneously in 20 to 30% of cases but can recur in up to
hood of a false positive result. Bloody fluid obtained from a 60% of women. Some studies suggest a relationship with
cyst aspiration should be sent for cytologic examination. caffeine intake, premenstrual syndrome, and serum hormone
levels.15 Frequently, after a complete history and physical
    examination to rule out a malignancy, the clinician is left
Normal breast texture is often heterogeneous, particularly treating mastalgia of unknown etiology. Many women respond
in premenopausal women. Vague thickening or tender or well to reassurance14,16 and simple interventions, such as
nontender areas of nodularity are frequently detected by the wearing a properly fitted bra and reducing caffeine intake.
05/10
Commonly used remedies, including evening primrose oil, trimester to as late as 2 years postpartum. Elevated thyroid-
vitamin E, and vitamin B6, have limited evidence supporting stimulating hormone (TSH) levels can also be associated with
their use to relieve symptoms.17,18 If simple interventions are elevated prolactin levels.
not successful, consideration can be given to pharmacologic Nipple discharge characterized as nonbloody but darker
agents including nonsteroidal antiinflammatory drugs green or brown is associated with ductal ectasia, a benign
(NSAIDs), danazol, bromocriptine, and tamoxifen.15,18,19 In condition characterized by dilated ducts resulting from
extreme and otherwise nonresponsive cases, surgical excision obstruction with keratin plugs, and subsequent inflammation
of the tender area can be used.20 and secretions. Ductal ectasia can arise in one or multiple
ducts. Dilated ducts are visualized on ultrasonography and on
 
ductography. The characteristics of the discharge from ductal
Fibrocystic change is often referred to by the misnomer ectasia can be similar to those seen with papillomas and
fibrocystic disease. It is a common finding in women who are ductal carcinoma in situ (DCIS) and are therefore included
menstruating, occurring almost exclusively between the ages in the differential diagnosis of pathologic nipple discharge.
of 30 and 50. Fibrocystic change is characterized by lumpy Bloody nipple discharge can appear as bright red, rusty,
or “cobblestone” breasts with ridges of tissue appreciated on brown, or green and is considered pathologic. It is character-
palpation. The change is considered a normal variant. If a istically unilateral and emanates from a single duct. Although
dominant mass is found in a woman with fibrocystic breasts, the most common etiology of this remains a solitary intra-
diagnostic imaging and biopsy should be undertaken to ductal papilloma, DCIS and invasive breast cancer can also
rule out malignancy. Symptoms generally improve with oral present with pathologic discharge. Of patients presenting
contraceptive use and abate with menopause. Treatment with such a discharge, 17% have malignancy, 65% have
is geared toward symptomatic relief using the agents listed papillomas, and the remainder have other benign lesions.23
above for mastalgia and reassuring the patient that there is no A thorough physical examination that includes a search for
worrisome etiology or increased risk of developing breast signs of an endocrine disturbance should be conducted (e.g.,
cancer. thyromegaly, visual field defects). As part of the breast evalu-
 : ,  ,  ation, if nipple discharge is not apparent, the clinician should
 gently squeeze the nipple to determine whether the discharge
is coming from a single duct or multiple ducts and whether
Nipple discharge is the third most common breast the discharge is bilateral. The breast should be evaluated for
complaint after mastalgia and breast mass.21 In the majority the presence of a discrete mass that may be associated with
of cases, the discharge is caused by noncancerous processes,
an underlying carcinoma.
including (1) physiologic discharge, (2) ductal ectasia, and
Historical and physical findings suggestive of an endocrine
(3) intraductal papilloma. However, malignancy should be
disorder should prompt the clinician to order TSH and
ruled out as part of the workup for nonphysiologic discharge.21
prolactin levels. An MRI of the brain should be ordered to
For women presenting with this concern, the clinician should
rule out a prolactin-secreting tumor of the pituitary if
elicit a history that includes the characteristics of the dis-
prolactin levels are elevated. In women of childbearing age, a
charge. The initial question to the patient should be whether
pregnancy test should also be ordered as part of the workup
the discharge is spontaneous or self-induced. If self-induced,
of galactorrhea. Women with medication-induced bilateral
the patient should be counseled to stop eliciting the discharge.
discharge should be counseled about the etiology and
If spontaneous, the characteristics are important in determin-
reassured.
ing the cause, including whether it is unilateral or bilateral,
For patients who are found to have pathologic discharge,
milky, bloody, clear, posttraumatic, or cyclical. The history
should also include questions pertaining to symptoms associ- the diagnostic workup should begin with bilateral diagnostic
ated with an endocrine disorder (hypothyroidism) or to an mammography. If imaging reveals a focal lesion or microcal-
intracranial etiology such as a pituitary tumor (amenorrhea, cifications, tissue diagnosis should be obtained. Ductography
visual disturbances, and headache). A history of recent may be able to identify an intraductal lesion and guide
medication changes should also be taken because numerous surgical planning. Ductography involves cannulating the
medications are associated with galactorrhea (H2 receptor discharging duct with a small catheter and then injecting a
antagonists, antihypertensives, antidepressants, and antido- small amount of radiographic contrast medium. Magnified
paminergic agents).21 mammographic views are then obtained, and lesions within
To understand physiologic nipple discharge, an under- the duct are identified as either a filling defect or an abrupt
standing of breast physiology is critical. During pregnancy, cutoff. More recently, ductoscopy, which uses a flexible or
high circulating levels of estrogen result in development of rigid fibroscopic ductoscope to cannulate the nipple, can be
the breast into a predominantly glandular structure. With used to isolate areas of pathology for excision. In skilled
parturition, estrogen production decreases, resulting in hands, it can be combined with (brush) cytology for improved
prolactin secretion and increased secretory activity, whereas accuracy.24,25
oxytocin results in “letting down” or ejection of milk into The role of cytologic analysis remains controversial. FNA
the ducts. A suckling infant or similar stimuli (i.e., sexual is also unreliable in evaluating patients with drainage and/or
breast stimulation, postthoracotomy syndrome)22 may result papillomatous disease26 (and many feel that even CNB of
in oxytocin release. Any of these conditions can result in endoductal lesions remains inadequate for definitive diagno-
physiologic discharge, which is usually milky and bilateral. sis of these lesions).27–30 Therefore, surgical excision is recom-
Pregnancy can result in galactorrhea from the second mended given the incidence of concomitant premalignant
05/10
and malignant disease in the setting of pathologic nipple dis- FNA may be performed. A pathologic diagnosis demonstrat-
charge.27,31 When the location of the intraductal pathology is ing atypia (on FNA), atypical ductal hyperplasia (ADH),
identified prior to surgical resection, a more limited resection atypical lobular hyperplasia (ALH), lobular carcinoma in situ
(i.e., single duct excision) of the disease is possible.32 If the (LCIS), or radial scar requires formal surgical excision with
duct is peripheral in the breast, the duct can be localized via needle localization to rule out the presence of invasive carci-
needle localization. When possible, single duct excision is noma or DCIS. CNB of these lesions understages findings
preferred because it preserves nipple sensation and the ability related to these diagnoses in up to 30% of cases.35–39 These
to breastfeed. In cases where the focal pathology cannot be lesions may be an independent risk factor for the develop-
isolated preoperatively, or in the case of multiduct involvement of carcinoma38 [see Evaluation of Patients at High Risk
ment, a major duct excision is more appropriate. This involves for Breast Cancer, below].
removing all of the central lactiferous ducts and sinuses,
preventing further discharge. Both procedures can be done  
on an outpatient basis and require only local anesthesia and Fat necrosis can masquerade as breast cancer. It often
intravenous sedation. presents as a firm, irregular mass within breast tissue, which
 :   is occasionally tender. The patient’s history is helpful in pro-
  viding clues to this diagnosis and will often include a history
of trauma, reduction mammoplasty, or prior breast surgery.
Fibroepithelial lesions encompass a spectrum of breast Large cavity size, postoperative hematoma, or infection, as
abnormalities ranging from the fibroadenoma (FA) to the well as adjuvant radiation, can increase the likelihood of fat
phyllodes tumor (PT). FAs are the most common benign necrosis. A compromise to the surrounding parenchymal
breast lesions and occur most frequently in the second and blood supply is thought to be the underlying factor in its
third decades of life. Their natural history is one of stability development. Diagnostic mammography and ultrasonogra-
or slow growth. Patients will often give a history of a solitary phy can aid in the diagnosis. Loss of speculation, compress-
nontender nodule. Physical examination will usually demon-
ibility, oil cysts, and the presence of eggshell calcifications
strate a well-defined solitary, rubbery, and mobile nodule.
are suggestive of a benign etiology. Review of prior films is
Ultrasonography is particularly useful in younger women and
necessary to determine the stability of the lesion.40 Ultraso-
demonstrates a well-defined oval or round hypoechoic mass
nography or stereotactic CNB is appropriate if there is doubt
with discrete margins. Mammography should be obtained (in
about the diagnosis and will reveal chronic inflammatory
addition to ultrasonography) in women over 35 years of age
cells, lymphocytes, histiocytes, fat necrosis, and saponifica-
and typically demonstrates a well-defined radiopaque mass
tion. Should the physician opt for short-term clinical follow-
with smooth borders. If the history, physical examination,
up (1 to 2 months) instead of biopsy, it is important to have
and imaging are consistent with an FA, careful clinical follow-
up is reasonable with ultrasonography and CBE at 6-month a patient who will be compliant with keeping follow-up
intervals to assess the stability of the lesion. When the diag- visits.41
nosis is uncertain, CNB should be performed. For women 
who request excision of a benign FA, enucleation of the lesion
is adequate. Conversely, if the lesion increases in size during In the pregnant patient with complaints of a mass or ten-
clinical follow-up, surgical excision is recommended to rule derness, the clinician should bear in mind the hormonally
out a PT. stimulated status of the breast, resulting in increased tender-
PTs are unusual, representing only 0.3 to .5% of breast ness. However, any mass or thickening in the breast requires
neoplasms.33 They have the same clinical appearance and prompt evaluation in the pregnant patient. Malignancy should
imaging characteristics as FAs, but unlike FAs, they are always be ruled out, particularly in older, childbearing-age
characterized by a clinical history of rapid growth and have women. A galactocele, which is a collection of milk within
larger dimensions. With increased screening, more PTs are an obstructed, dilated duct, can form during pregnancy,
being discovered mammographically. Given that these lesions lactation, or recent postlactation. A patient may complain of
do not have any features on imaging that would be helpful a tender nodule within the breast tissue. A mammogram will
in differentiating them from FAs, CNB is recommended. demonstrate a well-circumscribed mixed-density lesion, and
However, it can be difficult to differentiate between FA and ultrasonography will reveal a corresponding partially cystic
PT on CNB. A pathologic diagnosis of a fibroepithelial lesion mass. Simple aspiration can be both diagnostic and therapeu-
on CNB necessitates excision to rule out a PT. Tumors are tic, providing relief. Malignancy should always be in the
classified histologically as low, intermediate, or high grade. differential, particularly in older women of childbearing
Although most PTs have minimal metastatic potential, they years.
have a proclivity for local recurrence and should be excised
 
with at least a 1 cm margin. Local recurrence has been
correlated with excision margins but not with tumor grade or Mondor disease is thrombophlebitis of the superficial veins
size.34 The most common site of metastasis from malignant of the breast. It is characterized by the finding of a tender and
PT is the lungs. often inflamed cord palpated on the patient’s breast. After a
thorough history and physical examination of the patient’s
  ,  ,  breasts, treatment should consist of NSAIDs, analgesics, and
,      antibiotics. If there is evidence of infection, or should the
During the course of a patient’s workup for a suspicious condition fail to improve, surgical excision is appropriate for
physical finding or image-detected abnormality, CNB or definitive management and diagnosis.42
05/10
 drainage. Intravenous antibiotics should be considered for

Gynecomastia, or a breast mass in male breast tissue, is women with elevated temperature and white blood cell count.
usually a benign condition in adolescent males and presents Other skin conditions in the breast include sebaceous cysts
as discoid, subareolar, rubbery thickening of the breast tissue. and hidradenitis suppurativa. Appropriate antibiotics should
be given, and surgical excision is often required for resolution
In the absence of any other findings, such as testicular pathol-
of the symptoms. Fungal (candidal) infections involving the
ogy, or a history of ingestion or use of substances associated
breast are a common complaint in women with large, pendu-
with gynecomastia, these patients should be reassured and
lous breasts. The lower breast and inframammary crease are
reexamined. In the case of especially prominent, large, or
common locations for the characteristic erythematous moist
symptomatic gynecomastia, surgical excision is reasonable. In
patches. Treatment includes keeping the area clean and dry
the mature male population, a physical examination and his-
and topical antifungal powders or creams.
tory are vitally important. Soft, diffuse enlargement is a result
In nonlactating women, benign processes involving the
of medication in 20 to 25% of cases.43 Gynecomastia can also nipple are often the result of trauma or damage to the nipple
be due to hormonal, physiologic, or idiopathic factors and or subareolar ducts. Smoking is associated with periductal
can usually be managed nonoperatively and with serial exam- mastitis, which can present with pain, inflammation, nipple
inations. Many medications resulting in gynecomastia are felt retraction, and discharge. Appropriate antibiotics and abscess
to do so by elevating prolactin levels comparatively. If the aspiration or drainage are the recommended treatments.
gynecomastia is attributable to medication, switching the Trauma, dry skin, or dermatitis can lead to excoriation of the
patient off the medication will often result in regression over nipple. Allergic or atopic dermatitis frequently occurs as a
the course of a few months. For men who would like to avoid result of allergies to clothing, dyes, perfumes, and detergents.
surgery, some success has been noted in treating gynecomas- Treatment is symptomatic, with removal of the offending
tia with tamoxifen, raloxifene, and aromatase inhibitors.44,45 agent and a course of topical steroids. Short-term clinical
However, a finding of a solitary hard mass, especially with follow-up (1 to 2 weeks) is essential to ensure resolution of
findings of adenopathy and skin changes, requires aggressive the symptoms. Breast cancer, including Paget disease of the
workup, including mammogram and tissue diagnosis, usually nipple, can present with these symptoms, and it is vital that
with CNB. the surgeon make an accurate diagnosis. If there is no
improvement of the symptoms in 2 weeks, punch biopsy of
   
the nipple should be done.
Common breast skin
and nipple changes
include bacterial infec- Evaluation of Patients at High Risk for Breast Cancer
tions (mastitis, celluli- Significant morbidity and cost are associated with breast
tis, with or without cancer treatment. Approximately one third of women diag-
underlying abscess), nosed with breast cancer will succumb to the disease. This
fungal infections, and has led to efforts to provide primary prevention to high-risk
dermatitis. In lactating women. A number of factors have been identified that increase
women, mastitis is generally the result of poor hygiene. breast cancer risk [see Table 2].47 These risk factors include
Women will often give a history of an abrasion or crack in the (1) mutations in genes that confer a predisposition to breast
nipple. Symptoms typically include erythema, tenderness,
and swelling of the breast. Staphylococcus aureus is the most Table 2 Magnitude of Known Breast Cancer Risk Factors
common organism identified. Treatment involves continued
Relative risk < 2
breastfeeding and antibiotics. The choice of antibiotics should Early menarche
take into consideration the safety of the breastfeeding infant.46 Late menopause
Nonresolution of the infection with a course of appropriate Nulliparity
antibiotics should prompt the surgeon to consider the Age > 35 first birth
Hormone replacement therapy
presence of an underlying abscess or an antibiotic-resistant Obesity
organism. Fluid from an abscess should be sent for Gram Alcohol use
stain and culture to ensure the appropriate choice of antibi- Proliferative breast disease
otic. If the symptoms persist in the absence of the above Prior breast biopsies
causes, inflammatory breast cancer should be considered, Relative risk 2–4
followed by appropriate imaging, punch biopsy of the skin, One first-degree relative with breast cancer
and percutaneous biopsy of any underlying lesion. Radiation exposure
In nonlactating women, cellulitis of the breast typically Prior breast cancer
Mammographic density
occurs in the lower half of the breast and is more commonly
found in women who are overweight, have large, pendulous Relative risk > 4
Two first-degree relatives with breast cancer
breasts, or have poor personal hygiene. Breast abscesses are
Gene mutation
more frequently seen in women with a history of diabetes, Lobular carcinoma in situ
rheumatoid arthritis, chronic steroid use, chronic granuloma- Ductal carcinoma in situ
tous lobular mastitis, and trauma.46 Treatment includes anti- Atypical hyperplasia
biotics and identification of an underlying abscess followed Adapted from: Morrow M, Jordan VC. Managing breast cancer risk. 1st
by aspiration or drainage. Aspiration should always precede edition. Hamilton, ON: BC Decker Inc; 2003. p. 302.
05/10
cancer48; (2) hormonal and reproductive factors47,49–51; (3) should have screening mammography performed annually,
environmental factors, including diet and lifestyle character- beginning 10 years before the earliest age at which cancer was
istics of developed Western nations52; (4) prior radiation to diagnosed in a first-degree relative.64 For women with known
the chest wall as a teenager or young adult53; (5) a history genetic mutations and other women from families with an
of prior breast cancer, radial scar, or other premalignant autosomal dominant pattern of breast cancer transmission,
lesions37,54,55; and (6) increased mammographic density.56 annual mammographic screening should begin at age 25.64
Recognition of factors that increase breast cancer risk facili- There are several prospective nonrandomized trials which
tates appropriate screening and clinical management of indi- were designed to assess the benefit for adding yearly screen-
vidual patients. It must be recognized, however, that most ing breast MRI for women at high risk for breast cancer.65–69
women have none of the known risk factors for breast cancer, These studies demonstrated that breast MRI is more sensitive
and the absence of these risk factors should never prevent full than mammography. The ACS recently published recom-
evaluation or biopsy of a suspicious breast lesion. mendations for the use of screening breast MRI as an adjunct
Approximately 10% of all breast cancers are hereditary.57 to mammography. Annual screening with breast MRI is rec-
Hereditary breast cancer is characterized by early age of ommended for the following: (1) BRCA mutation carriers;
onset, bilateral disease and disease in other organ sites. (2) first-degree relatives of a BRCA mutation carrier who
Therefore, an accurate and complete family history, includ- have never been tested; (3) women with a lifetime risk of 20
ing all malignancies, is essential for quantifying a woman’s to 25% based on risk models that are predominantly depen-
genetic predisposition to breast cancer. Questions about dent on family history; (4) women with a history of radiation
breast cancer in family members should go back several to the chest between the ages of 10 and 20 years; (5) women
generations, with age at diagnosis recorded if available. Any with Li-Fraumeni syndrome (mutations in the p53 gene)
personal history of cancer should be recorded, with particular and their first-degree relatives; and (6) women with Cowden
attention paid to breast, ovarian, and endometrial cancers. and Bannayan-Riley-Ruvalcaba syndromes (mutations in the
BRCA1 and BRCA2 account for the majority of hereditary PTEN gene) and first-degree relatives.70
breast cancers. The lifetime risk of breast cancer in these indi- It is important to remember that although the sensitivity of
viduals can be as high as 85%. Mutations in these genes are breast MRI for cancer is high, the specificity is relatively low
associated with other malignancies, most notably ovarian, and can result in high recall and biopsy rates.70 Breast MRI
pancreatic, and prostate cancer. Specific founder mutations should be used as an adjunct to mammography and not a
in BRCA1 and BRCA2 occur within certain ethnic groups
replacement. Mammography and MRI can be done simulta-
(e.g., Ashkenazi Jews).57 Surgeons should also be aware of
neously or alternating with each other at 6-month intervals to
mutations in other genes that are commonly associated with
coincide with the CBE. Given the specificity of breast MRI
an increased risk of breast cancer, including mutations in
and the fact that many enhancing lesions seen on breast MRI
p53 (Li-Fraumeni syndrome), mutations in the PTEN gene
are occult to conventional imaging modalities, it is essential
(Cowden syndrome), and hereditary diffuse gastric cancer
that any facility performing screening breast MRI should
syndrome (CHD1). Tests that detect mutations in these
have the capability for MRI-guided breast biopsy.
genes are commercially available. Clinicians should consult
Chemopreventive strategies are designed either to block
a licensed genetic counselor to determine appropriate
the initiation of the carcinogenic process or to prevent (or
candidates for testing.
reverse) the progression of the premalignant cells to an inva-
Genetic testing has significantly improved our ability to
sive cancer.71 Only tamoxifen and raloxifene are currently
define breast cancer risk for the subset of women who have a
FDA approved for chemoprevention in breast cancer. Both
mutation. For women without a known genetic predisposi-
tion, the Gail58 and Claus models59 are two tools that can are selective estrogen receptor modulators (SERMs). Large
screen women who may be at increased risk and would there- multicenter randomized trials demonstrated the efficacy of
fore benefit from enhanced surveillance and chemopreven- these agents in the primary prevention setting for women
tion. It should be noted that these mathematical models at increased risk of breast cancer based on a Gail score of
define population-based risk, not individual risk. 1.67 or a personal history of ADH or LCIS. The overall risk
Histologic markers of risk include both ductal and lobular of invasive breast cancer was reduced by 50% after treatment
atypia, radial scar, and lobular carcinoma in situ (LCIS). for 5 years and limited to estrogen receptor (ER)-positive
Atypia and radial scar confer a fourfold increased risk of breast cancers in these high-risk women. Raloxifene is
developing breast cancer.60,61 LCIS is associated with an currently approved only for postmenopausal women and has
increased lifetime risk of subsequent carcinoma between 20 the added benefit of treating postmenopausal osteoporosis.
and 25%. Pleomorphic LCIS, a pathologically distinct entity It is noteworthy, however, that raloxifene was not found to
of LCIS, appears to be associated more frequently with inva- prevent noninvasive breast cancers in this trial.72
sive cancer.62,63 At present, women with these high-risk lesions The hot flashes, deep vein thrombosis, and endometrial
should be offered screening and chemoprevention. cancer associated with tamoxifen have made it an unattract-
Currently, there are three options for women to manage ive option for many women. This has generated interest in
their risk: (1) enhanced surveillance, (2) chemoprevention, identifying other chemopreventive agents. Aromatase inhibi-
and (3) prophylactic mastectomy. For women with LCIS or tors, which are used to treat ER-positive breast cancers in
a family history of breast carcinoma, surveillance should postmenopausal women, reduce the risk of contralateral
include twice-yearly CBE. Mammography should be per- cancers and may have a role to play in chemoprevention. In
formed annually after the diagnosis of LCIS or atypical addition, gonadotropin-releasing hormone agonists, mono-
hyperplasia. Women with a family history of breast cancer terpenes, lignans, retinoids, rexinoids, vitamin D derivatives,
05/10
and inhibitors of tyrosine kinase are all undergoing evaluation mastectomy must be weighed against the irreversibility and
in clinical or preclinical studies with a view to assessing their the psychosocial consequences of the procedure.
potential chemopreventive activity. Whether any of these Research involving high-risk women is challenging because
compounds will play a clinically useful role in preventing of the large numbers of women who must be recruited and
breast cancer remains to be seen. followed for many years and because of the cost associated
For those women at significant risk of breast cancer attrib- with such an undertaking. Improved risk assessment tools
utable to genetic predisposition, bilateral prophylactic mas- that can aid in improved risk stratification are under active
tectomy can be considered. High-risk women who underwent investigation.75 Current trials are focused on identifying and
this procedure, compared with those who did not, had their using intermediate biomarkers of breast cancer risk to test
breast cancer risk reduced by at least 90%.73 Oopherectomy potential chemopreventive agents.
also confers up to a 50% breast cancer risk reduction in
premenopausal women.74 The benefits of prophylactic Financial Disclosures: None Reported.
References
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4 THORAX 1 DYSPHAGIA — 1
1 DYSPHAGIA
P. James Villeneuve, MDCM, PhD, FRCSC, and R. Sudhir Sundaresan, MD, FRCSC, FACS*
The term dysphagia, derived from the Greek dys- (with diffi- substances must be sought out as an expedient assessment of
culty) and -phagia (to eat), describes difficulty in the transfer severity and consideration of immediate surgery must be
of food or liquid boluses from the mouth to the stomach. made.
Dysphagia is a common complaint, with at least 35% of
patients above the age of 50 complaining of weekly dysphagia Location
and up to 60% of nursing home residents suffering feeding Patients will self-localize symptoms to the cervical, retroster-
difficulties as a result of dysphagia.1,2 nal, or epigastric regions. Studies have demonstrated accurate
There are two forms of dysphagia. Oropharyneal dysphagia localization, by patient history, to within 4 cm of the culprit
results from a functional impairment in the initiation of lesion in up to 74% of cases.5 Accuracy seems best for
swallowing, including the oral and pharyngeal phases [see proximal lesions.
Sidebar Normal Swallowing Mechanism], and often results
from systemic neurologic or myopathic syndromes [see Solid or Liquid
Table 1]. Esophageal dysphagia relates to intrinsic functional Intolerance to both liquids and solids suggests a functional
(motor) and anatomic abnormalities of the esophagus that or neuromuscular cause of dysphagia. Difficulties with solid
result in swallowing difficulties [see Table 2].1,3 food only strongly implicates a mechanical or anatomic causes
This chapter outlines the basic physiology of the swallow- of dysphagia6; a progression from purely solid food dysphagia
ing mechanism and proposes an evaluative and diagnostic to both solid and liquid dysphagia suggests narrowing
approach to difficulties with swallowing. The technical details attributable to an evolving mechanical obstruction.
of specific procedures employed in the definitive treatment of
certain causes of dysphagia are described in later chapters of Onset and Progression
this volume. The temporal pattern of symptom onset and duration also
gives valuable information as to possible causes for dysphagia.
Intermittent, nonprogressive symptoms suggest an intrinsic
Evaluation
motor dysfunction (such as diffuse esophageal spasm) or a
A systematic approach mechanical cause such as a web or ring. If the symptoms
to the patient with dys- have been present for a short period of time or are rapidly
phagia is mandatory. A progressive, a malignant etiology must be ruled out.
thorough history and
complete physical exam- Associated Symptoms
ination allow for an A history of anorexia or weight loss suggests an underlying
accurate assessment of malignancy. Passive regurgitation of food particles may
likely etiologies. Con- arise from achalasia or a cricopharyngeal diverticulum.
founding diagnoses, such as angina pectoris, thyroid goiter, Retrosternal chest pain, once cardiac etiologies have been
and pharyngitis, should be eliminated. eliminated, may be present in cases of esophageal spasm or
important elements to elicit on history gastroesophageal reflux. However, dysphagia secondary to
peptic strictures and adenocarcinoma are without symptoms
Timing of Dysphagia of gastroesophageal reflux disease (GERD) in up to 25 to
Immediate coughing, choking, or regurgitation suggests 35% of cases.7 Medication lists must be examined to rule out
oropharyngeal causes for dysphagia. A sensation of food culprit medications (alendronate, doxycycline, nonsteroidal
“sticking” or getting “caught” or the delayed regurgitation of antiinflammatory drugs [NSAIDs], and mycophenolate
food suggests esophageal causes of dysphagia.2 Patients mofetil [MMF]) that may cause drug-induced esophageal
reporting the constant presence of symptoms not associated injury.8
with swallowing difficulties may have globus sensation, which
physical examination
is a benign, nonpainful fullness in the neck or throat.4
The esophagus is a deep-seated structure that does not
Painful Swallowing lend itself to direct physical assessment. Although a thorough
Odynophagia is not typically associated with dysphagia; physical examination should follow a complete history,
its presence should prompt consideration of infectious or information gathered is useful only in inferring potential
inflammatory etiologies. Exposure and ingestion of caustic diagnoses. A detailed and accurate history is the mainstay of
clinical assessment in patients who present with dysphagia.
* The authors and editors gratefully acknowledge the contribu- The head and neck are examined for the size of the thyroid
tions of the previous author, Ahmad S. Ashrafi, MD, FRCSC, gland, as well as for the presence of any lymphadenopathy
to the development and writing of this chapter. or masses. A careful examination of cranial nerves may
DOI 10.2310/7800.S04C01
04/10
Patient presents with difficu
Obtain a complete h
Perform a thorough physica
No odynophagia present
Determine if symptoms are consistent with

oropharyngeal or esophageal etiology.
Oropharyngeal dysphagia Esophageal dysphagia
Perform barium swallow. Perform barium swallow.

If no pharyngoesophageal diverticulum found, consider
neurologic, myopathic and metabolic etiologies. P
Assess for risk of aspiration.
Dysphagia is secondary to systemic condition Clinical findings and barium swallow are Barium
consistent with primary motor disorder diverti
Focus on underlying cause (e.g., scleroderma,
Assess patient with manometry and endoscopy. Treat a
diabetes mellitus, alcoholism, amyloidosis,
Parkinson disease, Crohn disease, or myxedema).
Patient has pharyngoesophageal

(Zenker) diverticulum
Patient has achalasia Patient has other primary motor
disorder (DES, hypertensive LES, If diverticulum is ≥ 2 cm, treat with
nutcracker esophagus) cricopharyngeal myotomy and
Perform laparoscopic esophagomyotomy
diverticulectomy or, alternatively,
with modified (i.e., anterior or posterior
Treat medically. with cricopharyngeal myotomy
partial) fundoplication.
In rare circumstances, consider and diverticulopexy.
myotomy. If diverticulum is < 2 cm, treat with
cricopharyngeal myotomy alone.
Patient has esophageal web Patient has Barrett esophagus Patient has peptic
Treat with endoscopic dilatation. Rule out dysplasia. Treat with endosco
Perform surveillance endoscopy. and perform brush
Treat GERD symptoms medically out malignancy.
or surgically as appropriate.
Give PPls
Consider manomet
study.
Consider antireflux
DES = diffuse esophageal spasm; LES = lower esophageal sphincter; GERD = gastroesophageal reflux disease; PPI = proton pump inhibitor; NPO = nil per os;
CT = computed tomography; PET = positron emission tomography; EUS = endoscopic ultrasound.
04/10
ifficulty swallowing
ete history.
ysical examination.
Present has odynophagia
Determine if patient has ingested a caustic chemical.
No caustic ingestion Caustic ingestion has occurred
Assess for inflammatory and infectious etiologies. Secure airway and resuscitate.
Perform a barium swallow. Perform flexible endoscopy.
Perform flexible endoscopy and biopsy as appropriate. NPO, intravenous antibiotics and total parenteral nutrition (TPN).
Assess anatomy and residual lumen with barium swallow after 2-3 weeks.
arium swallow reveals esophageal Barium swallow suggests fixed

iverticular disease mechanical obstruction
reat according to anatomic level of diverticulum. Assess patient with endoscopy.
Patient has midesophageal Patient has epiphrenic diverticulum

diverticulum
Assess patient with manometry and
Lesions result from periesophageal endoscopy.
inflammation and are frequently If symptoms are absent or mild,
asymptomatic; dysphagia is rare. manage conservatively.
If there are no significant symptoms, If significant symptoms are present,
they need not be treated, and manage surgically with myotomy,
therapy focuses on underlying divertioulectomy, and partial
inflammatory condition. fundoplication.
eptic stricture Patient has Schatzki ring Patient has esophageal cancer
doscopic dilatation, If lesion is asymptomatic, no treatment Perform esophagoscopy for pathologic

rush biopsy to rule is required. diagnosis.
y. If lesion is symptomatic, treat with Rule out distant metastatic disease with CT
endoscopic dilatation and medical or PET. EUS may aid in locoregional staging.
(or, if necessary, surgical) therapy for Treat surgically according to stage of disease.
GERD. If cancer is localized and patient is medically
fit, perform esophagectomy.
ometry and 24 hr pH
eflux surgery.
04/10
Normal Swallowing Mechanism adapted from Matsuo

and Palmer25
Swallowing was previously described using a three-phase sequential
model, whereby the position of the food bolus was used to identify
the oral, pharyngeal, and esophageal phases. Later reports expanded
this into a four-stage model by dividing the oral phase into prepara-
tory and propulsive stages. These early models accurately depicted
liquid swallows but were inadequate to model solid food boluses.
The process model accounts for swallowing of solid foods by
expanding the oral phase into stage I, transport, food processing,
and stage II, transport. The pharyngeal and esophageal phases are
common to both liquid and solid transport.
Oral Phases of Liquid Swallowing
Preparatory Liquid is held against hard palate by tongue and

sealed posteriorly by contact between tongue
and soft palate
Propulsive Sequential contact between tongue and hard
palate coupled with relaxation of seal between
posterior tongue and soft palate squeezes
liquid into pharynx
Oral Phases of Solid Swallowing
Stage I transport Food is positioned against occlusive

tooth surfaces by tongue movement.
Oral food processing Coordinated movements of the jaw, in
concert with the tongue, cheek, soft
palate, and hyoid bone movement.
This results in masticated, moistened
food that is optimal for further
swallowing.
Stage II transport Food bolus is positioned on the tongue
surface. Sequential contact between
the tongue and hard palate coupled
with relaxation of seal between
posterior tongue and soft palate
propels food into the pharynx.
Pharyngeal Phase
This rapid phase must achieve airway protection while facilitating passage of boluses through the upper esophageal sphincter (UES) to the
esophagus proper. Airway protection is achieved by concerted closure of the vocal cords and laryngeal movement (anteriorly and superiorly)
with concomitant tilting of the epiglottis to seal the laryngeal vestibule. Food propulsion follows: the soft palate rises to block retrograde
passage into the nasopharynx. Pharyngeal constrictors sequentially contract from cranial to caudal, shortening the pharynx and propelling
the food bolus downward. This “pharyngeal pump” can generate pressures of up to 200 mm Hg. The UES has a resting pressure of between
16 and 118 mm Hg and is closed at rest. Active opening of the UES is achieved by relaxation of the cricopharyngeus, traction by the strap
muscles, and distending pressure of the descending food bolus.
Esophageal Phase
Both the UES and the lower esophageal sphincter (LES) remain closed at rest to prevent reflux. Autonomic efferent signals mediate peri-
stalsis; an initial wave of relaxation preceding the food bolus is followed by a wave of contraction, resulting in transit through the esophagus
into the stomach. Primary esophageal peristalsis is triggered by voluntary swallowing but autonomously propagates at 2 to 5 cm/s through
the striated muscles of the upper third of the esophagus, slowing as peristalsis passes into the smooth muscles of the lower esophagus. Sec-
ondary esophageal peristalsis is involuntary and arises in response to esophageal distention or irritation. It is thought that these waves of
peristalsis serve to keep the esophagus clear. Tertiary esophageal waves can arise normally between swallows but are often nonpropulsive.
The sidebar figure demonstrates normal waveforms and propagation of peristalsis in swallowing. It is evident that coordination between
the different anatomic levels of the esophagus is required for effective swallowing. The high-pressure contraction in the pharynx is coordi-
nated with full relaxation of the UES. This allows transfer of swallowed material into the esophagus proper, where peristaltic pressures of
up to 80 mm Hg are noted. Orderly progression of moderate-amplitude waves through the esophageal body occurs. The LES relaxes early
in response to swallowing and slowly regains its resting pressure of 10 to 25 mm Hg in concert with distal esophageal transport.
demonstrate deficits contributing to oropharyngeal dyspha- indicate a paraneoplastic syndrome or a primary autoimmune
gia, and corresponding neurologic assessment may reveal disorder. Murmurs or thrills on cardiac auscultation may
signs of a cerebrovascular accident (CVA), myasthenia gravis, represent atrial enlargement (secondary to mitral valvular
or Parkinson disease. The chest and abdomen are examined stenosis), causing extrinsic esophageal compression. Refer to
for the presence of subcutaneous nodules or masses that may Table 1 and Table 2 for specific causes of oropharyngeal and
indicate underlying malignancy. Dermatologic rashes may esophageal dysphagia.
04/10
Table 1 Etiologies of Oropharyngeal Dysphagia When reflux disease is suspected, extended pH monitoring
is invaluable in assessing the presence and severity of GERD.
Systemic conditions
Motility disorders are best diagnosed using manometric
Cerebrovascular accident
Myasthenia gravis techniques.
Intrinsic motor disorders In cases where extrinsic compression is suspected or
Cricopharyngeal (Zenker) diverticulum demonstrated, cross-sectional imaging using computed
Fixed mechanical obstruction tomography (CT) or magnetic resonance imaging (MRI)
Oropharyngeal cancer
Webs may be useful in identification of malignant masses or vascu-
Previous surgical/radiation treatment lar anomalies (aberrant subclavian vessels, aortic aneurysms,
or Kommerell diverticulae).11,12 Dysphagia lusoria is a rare
entity in which dysphagia results from extrinsic vascular
compression of the esophagus from an aberrant right subcla-
vian artery, which arises from the thoracic aorta and typically
diagnostic tests
courses posterior to the esophagus [see Figure 1].
Many diagnostic tests The assessment of esophageal cancer also requires cross-
can be used to assess sectional imaging with CT and fluorodeoxyglucose–positron
dysphagia, including emission tomography (PET). The use of PET is highly sensi-
endoscopic, radiologic, tive for the detection of unsuspected metastatic lesions in
and manometric modali- patients deemed candidates for curative resection on the basis
ties. The application of of CT alone.13
these should be predicated by the history.
In cases of suspected or confirmed caustic ingestion, the
first test is emergent upper flexible endoscopy to assess the Management of Esophageal Dysphagia
anatomic extent of damage and to grade the injury.9 In all
motor disorders
other cases of dysphagia, the barium swallow is the ideal
first test as it is readily available, cost-effective, and rapidly Motility disorders affect the smooth muscle of the distal
performed. Information can be gained from the barium study esophagus and the lower esophageal sphincter (LES). Symp-
regarding anatomic relations, esophageal transit patterns, and toms typically include dysphagia to solids and liquids;
the presence or absence of mass lesions and diverticulae. The noncardiac chest pain may also be present.
safety and diagnostic yield of subsequent upper endoscopy
Achalasia
are enhanced.
Upper endoscopy allows for a visual assessment of mucosa; Ninety-eight percent
diagnostic and therapeutic maneuvers such as biopsies, of all cases of achalasia
brushings, and dilatations can be performed. are idiopathic. The dis-
Endoscopic ultrasonography (EUS) is an emerging diag- ease is thought to result
nostic modality that allows for assessment of the esophageal from a loss of inhibitory
wall and surrounding tissues. This permits the characteriza- neurons in the Auerbach
tion of esophageal masses (depth of invasion, T stage) and plexus, altering neural input to the LES and preventing
an assessment of adjacent lymphadenopathy (N stage), and normal relaxation.14 Achalasia affects females and males
guides endoscopic fine-needle aspiration biopsies. EUS- equally at a rate of 1 per 100,000 individuals per year. The
guided biopsies have excellent predictive value in the assess- usual presentation is between 20 and 50 years, but it has been
ment of lymph node involvement in cases of esophageal described in all age groups. The disease is slowly progressive,
carcinoma.10 and presentation is typically at advanced stages. Symptoms
include progressive dysphagia to both solids and liquids,
accompanied by regurgitation of food particles, chest pain,
and weight loss. GERD-like symptoms were present in up to
Table 2 Etiologies of Esophageal Dysphagia 48% of patients in a study of 32 patients15; these symptoms
Systemic conditions are a consequence of stasis esophagitis (secondarily to
Scleroderma fermentation of retained food) rather than reflux of gastric
Diabetes mellitus acid.
Intrinsic motor disorders Plain x-rays may reveal an air-fluid level in the distal
Secondary to GERD
Achalasia
esophagus, and a barium swallow will demonstrate a dilated
Esophageal spasms and atonic esophagus with the pathognomonic “bird’s-
Fixed mechanical obstruction beak” narrowing of the gastroesophageal junction (GEJ) [see
Webs Figure 2]. Long-standing achalasia may manifest with an
Neoplasms
extremely dilated and tortuous esophagus (often described
Extrinsic compression
Inflammatory as a sigmoid esophagus) [see Figure 3]. Manometric findings
Eosinophilic esophagitis of aperistalsis and failure of LES relaxation are key in estab-
HSV/CMV/Candida lishing the diagnosis. Resting LES pressures may be normal
CMV = cytomegalovirus; GERD = gastroesophageal reflux disease; HSV = or elevated. Endoscopic assessment is required to visually
herpes simplex virus. assess mucosal appearance to rule out cancer.
04/10
Right common Left subclavian

carotid artery T artery
Left common
carotid artery
Left common
carotid artery
Right common
carotid artery Left subclavian
T artery
Aortic arch
Figure 1 Dysphagia lusoria. Contrast-enhanced CT scan of the upper chest at the level of the clavicular heads (a) and near the
carina (b) demonstrating the retroesophageal course of the right subclavian artery (arrow) causing compression of the esopha-
gus (arrowhead) against the trachea (T) and right carotid artery. One can appreciate the idea of a “vascular ring” in such cases
causing esophageal compression.
Treatment modalities for achalasia must achieve enhanced esophagus, and hyper-
LES compliance and lower resting LES pressures. Medical tensive LES. These dis-
management with calcium channel blockers or nitrates has orders are traditionally
no meaningful benefit. Endoscopic management includes considered separate enti-
endoscopically injected botulinum toxin, or balloon dilata- ties; however, the mano-
tion, to mechanically disrupt the lower esophageal muscle metric findings and the
fibers. Recurrent dysphagia (up to 50%) has been noted in mainstays of medical treatment are similar.
some studies at 5 years after balloon dilatation, with a 5% DES is a dysmotility syndrome of unknown etiology. It is
periprocedural risk of esopheageal rupture.16 In comparison, characterized in 50% of patients by intermittent dysphagia to
a laparoscopically performed Heller esophagomyotomy with solids and liquids. Up to 5% of patients with unexplained
partial anterior (Dor) fundoplication is considered to be the chest pain are found to have DES on manometric testing.7
standard of care in terms of both durable outcomes (90 to Evidence for DES on manometry includes periodic pro-
95% resolution of dysphagia) and low complication rates.14 longed, multipeaked, high-amplitude contractions in more
Long-standing achalasia is a risk factor for esophageal than one in five wet swallows, with observation of normal
squamous cell carcinoma, and tumors of the GEJ may peristalsis in intervening periods. Incomplete LES relaxation
present with symptoms similar to those of achalasia. or hypertensive LES may also be observed. Figure 4 demon-
strates the classic corkscrew appearance that is observed in
Dysmotility Syndromes some cases of DES.
Motility disorders can be considered within a spectrum Nutcracker esophagus presents more commonly with
that includes diffuse esophageal spasm (DES), nutcracker chest pain rather than dysphagia. Manometry also forms the
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Figure 3 Sigmoid esophagus. Barium study demonstrates

dilated esophagus with right-sided deviation and tortuous
course of the distal esophagus. Treatment most often involves
resection of diseased esophagus with conduit interposition.
diverticulae involve all

layers of the esophageal
wall, whereas false diver-
ticulae involve only the
Figure 2 Achalasia. Barium swallow demonstrates the
proximal dilatation and classic “bird’s beak” narrowing at the mucosal layer. Both
esophagogastric junction, consistent with achalasia, in a 22- types of diverticulae can
year-old woman being evaluated for dysphagia. also be classified by the
mechanism underlying their formation: True diverticulae
usually form in the midesophagus and are most often related
mainstay of diagnosis: a normal peristaltic pattern is noted, to extrinsic traction from extramural inflammation in adja-
with extremely increased pressure amplitudes of more than cent mediastinal lymph nodes. These are also referred to as
180 mm Hg. In contrast to DES, normal peristalsis is not traction diverticulae. False diverticulae relate to dysmotility
observed within trains of high-pressure waves. Barium and consist of the mucosa being extruded through external
swallow is of normal appearance. muscular layers above a high-pressure zone and are thus
Hypertensive LES may be found in isolation but often pulsion-type diverticulae.
coexists with other dysmotility syndromes. Resting pressures Intramural pseudodiverticulosis is a rare cause of dysphagia
at the LES by manometry are found to be 45 mm Hg or characterized by multiple outpouchings of the esophageal
greater. wall; these outpouchings represent the dilatation of submu-
Treatment for DES, nutcracker esophagus, and hyperten- cosal glands.17 Although a benign condition, complications
sive LES is based on smooth muscle relaxation using nitrates related to infection, inflammation, perforation, stricture, and
such as isosorbide dinitrate or calcium channel blockers such bleeding have been reported. The mainstay of treatment
as diltiazem. Balloon dilatation may be effective for isolated is reduction of inflammation and dilatation of strictures as
hypertensive LES. necessary.
Pharyngoesophageal diverticulae (Zenker diverticulum)
Esophageal Diverticulae are the most common diverticulae observed. These pulsion-
Diverticulae are classified according to the degree to which type false diverticulae arise in the Killian triangle and are
the esophageal wall is involved in the outpouching: true located just superior to the cricopharyngeus muscle. The
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exposure of the proximal esophagus and pharynx to low pH

refluxate results in cricopharyngeal spasm and loss of normal
coordination.
Symptoms of a cricopharyngeal diverticulum include
dysphagia, halitosis, throat discomfort, a palpable mass, and
regurgitation of undigested food. Some patients may suffer
from recurrent aspiration pneumonia and in severe cases may
develop lung abscesses.
The first diagnostic test should be a barium swallow
[see Figure 5], which will delineate the size and position of
the diverticulum. Initial assessment by endoscopic means is
not recommended as there is a sizable risk of perforating the
pouch with the endoscope.
Treatment is surgical and must include the division of the
cricopharyngeus muscle. Smaller pouches may be treated by
myotomy alone, whereas those larger than 2 cm should
Figure 4 Diffuse esophageal spasm. The classic corkscrew

appearance of the esophagus is evident in this barium study
in a middle-aged patient presenting with dysphagia and
intermittent chest pain.
basis for the formation of a Zenker diverticulum is pharyngo-

cricopharyngeal dyscoordination. When the cricopharyngeal
sphincter fails to immediately and fully relax during swallow-
ing, the pharyngeal pump mechanism produces extremely
high pressures. As a result of these high pressures, progressive
bulging of the mucosa occurs in the posterior midline through
a potential gap between the pharyngeal constrictors and the
cricopharyngeus muscles (the Killian space). There has been
a long-standing appreciation of an association between the Figure 5 Pharyngoesophageal diverticulum. A large Zenker
pathologic severity of gastroesophageal reflux and the devel- diverticulum is shown in an elderly patient who presented
opment of Zenker diverticulae: it is thought that repeated with dysphagia, recurrent pneumonia, and regurgitation.
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be excised.18 Endoscopic (transoral) approaches to diverticu- thought to be progressive neuropathy and subsequent fibro-
lostomy have also been described.19 sis. Common diseases associated with secondary dysmotility
Midesophageal diverticulae are not typically associated include rheumatologic syndromes, such as scleroderma, and
with dysphagia. These true diverticulae are formed by trac- diabetes mellitus.
tion from extraesophageal inflammation, most often granulo-
matous disease in subcarinal lymph nodes. Midesophageal mechanical obstruction
diverticulae are usually asymptomatic, and treatment is Webs
focused on the underlying inflammatory process.
A web is a thin muco-
Epiphrenic diverticulae arise in the distal esophagus. These
sal fold that protrudes
pulsion-type diverticulae are associated with underlying
into the esophageal
esophageal dysmotility20,21 and are also occasionally an iso-
lumen. Congenital webs
lated finding [see Figure 6]. In the absence of symptoms,
are rare and usually
expectant management is appropriate. When dysphagia is
restricted to the pediat-
present, surgical management is necessary. The surgical
ric population. These
approach, understood to incorporate “triple therapy,” must
are located in the middle and lower thirds of the esophagus.7
include (1) excision of the diverticulum, (2) an esophageal
Acquired webs are normally located in the postcricoid cervi-
myotomy, and (3) an antireflux procedure.22,23
cal esophagus and are mostly asymptomatic. Etiologies for
Secondary Motor acquired webs include iron deficiency anemias (Plummer-
Disorders Vinson and Paterson-Kelly syndromes) and dermatologic
diseases. Webs are twice as common in female patients.
In secondary dysmotil-
Dysphagia occurs intermittently with solids, and when
ity syndromes, the
symptoms arise, the orifice of the web is found to be less
esophageal symptoms
than 1.3 cm. Diagnosis is by barium swallow, and treatment
are a manifestation of a
involves mechanical dilatation using Savary bougies or
generalized systemic
endoscopic balloons. Underlying anemias and dermatologic
process. The etiology is
conditions should also undergo assessment and appropriate
treatment.
Rings
Esophageal rings are
typically located in the
lower third of the esoph-
agus. Two types are typ-
ically described: muscu-
lar rings and mucosal or
Schatzki rings.
Muscular rings are rarely associated with dysphagia and
are often found incidentally in children undergoing barium
swallow for other reasons. Schatzki rings are located at the
Z-line (squamocolumnar junction) and are almost always
seen in patients with GERD [see Figure 7]; consequently, the
upper surface of a Schatzki ring is covered by squamous
epithelium, whereas the lower surface is covered by columnar
epithelium. Associations with eosinophilic esophagitis and
GERD have been proposed. Diagnosis and treatment are as
for esophageal webs.
Peptic Stricture
Peptic stricture was
previously found in up
to 10% of patients with
GERD and represents
the end stage of reflux-
associated ulcerative
esophagitis [see Figure 8]. The incidence of peptic strictures
has been drastically reduced with the increased use of effec-
tive antireflux medications, chiefly the proton-pump inhibi-
Figure 6 Giant epiphrenic diverticulum. Barium swallow tors (PPIs).
shows an epiphrenic diverticulum in an elderly female with Symptoms are described as progressive in nature and
progressive dysphagia and weight loss; cancer was initially involve initial solid food dysphagia, progressing to liquid
suspected. dysphagia. A history of reflux symptoms will also be elicited.
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stricture must be kept. Treatment of isolated peptic strictures

includes acid suppression and endoscopic dilatation. In the
past, peptic strictures were usually an indication for surgical
correction; however, recent clinical experience with careful
repeated dilatations combined with effective acid suppression
Figure 7 Schatzki ring. Barium swallow demonstrates a ring

in a middle-aged man with severe gastroesophageal reflux
disease symptoms and recent-onset dysphagia.
Initial assessment is by barium swallow. Peptic strictures

are short segment, circumferential, and located at the
squamocolumnar junction. A high index of suspicion for
concomitant Barrett esophagus or frank cancer at the site of
Figure 9 Midesophageal squamous cell carcinoma. Shown is

the classic appearance of a midesophageal squamous cell
Figure 8 Severe ulcerative esophagitis. Shown is the carcinoma. Mucosal irregularity is apparent within the lesion,
appearance of severe ulcerative esophagitis, annular stric- along with proximal dilatation and shouldering at the upper
ture, and evidence of esophageal shortening. The caliber of and lower borders. Bronchoscopy confirmed anterior
the narrowed segment suggests a benign etiology. penetration of tumor into the airway mucosa.
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therapy (using PPIs) has rendered surgical treatment an

uncommon occurrence.
Cancer
Dysphagia is the presenting complaint in the majority
of patients with esophageal cancer. The temporal course is
usually short and rapidly progressive. Weight loss is a promi-
nent feature. Locally advanced cancers causing airway fistu-
lization may present with aspiration (swallow-cough sequence)
[see Figure 9]. Evaluation and staging should proceed as per
established guidelines.
odynophagic syndromes
Caustic Ingestion
Caustic agents are found in many household cleaning
products. Ingestion is typically accidental but may be related
to a suicide attempt. The pH of the offending agent (less
than 2 or greater than 12), the volume ingested, and the total
contact time with the esophageal muscosa are the determi-
nants of the severity of the esophageal injury.8 Immediate
flexible endoscopy is required to assess the degree and
severity of the injury.9 Frank perforation or instability man-
dates immediate surgical exploration and resection. Sites
most commonly affected include the distal esophagus and
stomach; there is relative sparing of the upper pharynx and
esophagus because of rapid transit through these regions.
Injuries will mature into strictures, which require serial
assessment by barium studies starting 4 weeks after the
initial injury [see Figure 10]. Repeated dilatations are
Figure 10 Caustic ingestion. Barium swallow from a
typically required, although these procedures are technically
22-year-old patient after ingestion of toilet cleaner showing a challenging and sometimes dangerous as a result of the
long, stringlike lumen spanning the midesophagus to the intense fibrosis, which virtually obliterates the esophageal
stomach. Dilatation was impossible, and esophageal resection lumen. A large majority of these patients do not have
with colonic interposition was performed. satisfactory results with dilatation as a result of an inability to
Figure 11 Dysphagia and odynophagia secondary to tuberculous lymphadenitis in the neck and mediastinum arising in an
immunocompromised patient with chronic HIV infection. (a) Computed tomography image showing extensive necrotizing
inflammation in the mediastinal lymph nodes (long arrow), air within the esophagus (arrowhead), and a collection of extralumi-
nal air in the mediastinum (short arrow). (b) Contrast swallow study using water-soluble contrast, showing extravasation of
contrast into the mediastinum (arrowhead) and fistulization between the esophagus and the right bronchial tree (arrow).
Esophagoscopy showed extensive destruction of the esophagus by the mediastinal infection and multiple small fistulae into the
airway. A covered self-expanding esophageal stent was inserted to block the fistula, followed by aggressive antituberculous
therapy. The fistula healed, and the patient continues to do well clinically.
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establish an esophageal lumen or an inability to maintain an based on the infectious agent involved. Rarely, extrinsic infec-
adequate lumen despite repeated dilatations. Resection and tion of the esophagus (originating in neighboring necrotizing
reconstruction using colonic interposition become necessary. mediastinal lymph nodes) can occur, causing dysphagia,
odynophagia, and other potentially disastrous complications
Eosinophilic Esophagitis [see Figure 11].
This rare inflammatory condition is characterized by eosin-
ophilic infiltrates isolated to the esophagus.24 Intermittent
Conclusion
dysphagia to solid food and pain are commonly noted,
and associated manometric abnormalities (hypercontractility) Evaluation of the patient presenting with dysphagia repre-
are found in up to 60% of patients. Barium studies and sents a challenge for the surgeon. A careful history is key in
endoscopy are often normal in appearance. Glucocorticoids determining likely etiologies. The barium swallow should
and leukotriene antagonists represent currently accepted be the first diagnostic test to be considered, with endoscopy
treatment.7 to follow. Esophageal manometry represents the gold stan-
dard for diagnosing benign, functional (motor) disorders.
Infections Treatment is varied and depends on the etiology of the
Infectious causes of dysphagia associated with odynophagia dysphagia.
include intrinsic infections such as esophageal candidiasis,
herpetic infections, and cytomegaloviral illness. Treatment is Financial Disclosures: None reported
References
1. Cook IJ, Kahrilas PJ. AGA technical review 10. Peng HQ, Greenwald BD, Tavora FR, et al. 18. Lerut A, Luketich JD, Bizekis C. Esophageal
on management of oropharyngeal dysphagia. Evaluation of performance of EUS-FNA in diverticulae. In: Patterson G, Cooper J,
Gastroenterology 1999;116:455–78. preoperative lymph node staging of cancers Deslauriers J, et al, editors. Pearson’s thoracic
2. Saud B, Szyjkowski RD. A diagnostic of esophagus, lung, and pancreas. Diagn & esophageal surgery. Vol 2. Philadelphia:
approach to dysphagia. Clin Fam Pract 2004; Cytopathol 2008;36:290–6. Churchill Livingstone Elsevier; 2008. p. 702–
6:525–46. 11. Sitzman TJ, Mell MW, Acher CW. Adult- 13.
3. Spechler SJ. AGA technical review on treat- onset dysphagia lusoria from an uncommon 19. Hillel AT, Flint PW. Evolution of endoscopic
ment of patients with dysphagia caused by vascular ring: a case report and review of surgical therapy for Zenker’s diverticulum.
benign disorders of the distal esophagus. the literature. Vasc Endovasc Surg 2009;43: Laryngoscope 2009;119:39–44.
Gastroenterology 1999;117:233–54. 100–2. 20. D’Journo XB, Ferraro P, Martin J, et al.
4. Allescher HD. Globus sensation and hyper- 12. Wu JY, Chen HY, Shu CC, Yu CJ. Kom- Lower oesophageal sphincter dysfunction
dynamic upper esophageal sphincter: another merell diverticulum, right-sided aorta, and is part of the functional abnormality in
piece in the puzzle? Gastroenterology 2009; left aberrant subclavian artery in a patient epiphrenic diverticulum. Br J Surg 2009;96:
137:1847–9. with dysphagia. J Thorac Cardiovasc Surg 892–900.
5. Wilcox CM, Alexander LN, Clark WS. 2009 Mar 25. [Epub ahead of print]. 21. Rice TW, Goldblum JR, Yearsley MM, et al.
Localization of an obstructing esophageal Myenteric plexus abnormalities associated
13. Flanagan FL, Dehdashti F, Siegel BA, et al.
lesion. Is the patient accurate? Dig Dis Sci
Staging of esophageal cancer with 18F-fluo- with epiphrenic diverticula. Eur J Cardiotho-
1995;40:2192–6.
rodeoxyglucose positron emission tomo- rac Surg 2009;35:22–7.
6. Rice T. Dilation of peptic esophageal stric-
graphy. AJR Am J Roentgenol 1997;168: 22. Kilic A, Schuchert MJ, Awais O, et al. Surgi-
tures. In: Patterson G, Cooper J, Deslauriers
J, et al, editors. Pearson’s thoracic & esopha- 417–24. cal management of epiphrenic diverticula in
geal surgery. Vol 2. Philadelphia: Churchill 14. Williams VA, Peters JH. Achalasia of the the minimally invasive era. J Soc Laparoen-
Livingstone Elsevier; 2008. p. 251–60. esophagus: a surgical disease. J Am Coll. Surg dosc Surg 2009;13:160–4.
7. Lawal A, Shaker R. Esophageal dysphagia. 2009;208:151–62. 23. Varghese TK Jr, Marshall B, Chang AC, et al.
Phys Med Rehabil Clin N Am 2008;19:729– 15. Spechler SJ, Souza RF, Rosenberg SJ, et al. Surgical treatment of epiphrenic diverticula:
45, viii. Heartburn in patients with achalasia. Gut a 30-year experience. Ann Thorac Surg
8. Pace F, Antinori S, Repici A. What is new in 1995;37:305–8. 2007;84:1801–9.
esophageal injury (infection, drug-induced, 16. West RL, Hirsch DP, Bartelsman JF, et al. 24. Rothenberg ME. Biology and treatment of
caustic, stricture, perforation)? Curr Opin Long term results of pneumatic dilation in eosinophilic esophagitis. Gastroenterology
Gastroenterol 2009;25:372–9. achalasia followed for more than 5 years. Am 2009;137:1238–49.
9. Cheng HT, Cheng CL, Lin CH, et al. Caus- J Gastroenterol 2002;97:1346–51. 25 Matsuo K, Palmer JB. Anatomy and physio-
tic ingestion in adults: the role of endoscopic 17. Van LW, Urbain D, Reynaert H. Esophageal logy of feeding and swallowing: normal and
classification in predicting outcome. BMC intramural pseudodiverticulosis. Clin Gastro- abnormal. Phys Med Rehabil Clin N Am
Gastroenterol 2008;8:31. enterol Hepatol 2007;5:A22. 2008;19:691–707, vii.
04/10
4 THORAX 2 COUGH AND HEMOPTYSIS — 1
2 COUGH AND HEMOPTYSIS

Shahriyour Andaz, MD, FACS, FRCS, and Svetlana Danovich, DO, PhD
Cough is one of the most common symptoms in patients of interstitial lung diseases (e.g., idiopathic pulmonary fibro-
seeking medical attention from the office-based physician.1 sis or sarcoidosis).
In the United States, it accounts for approximately 30 to The airway sensory receptors are either primarily mechan-
50 million physician visits each year, and more than $1 billion ically sensitive (low-threshold mechanoreceptors) or primar-
is spent annually on its workup and treatment.2 Despite ily chemically sensitive (chemosensors or, alternatively,
its massive burden on health care resources, cough is often nociceptors). Mechanoreceptors are of two types: rapidly
dismissed as an unimportant irritation rather than a symptom adapting receptors (RARs) and slowly adapting receptors
of major socioeconomic importance.3 Hemoptysis, however, (SARs). They are sensitive to many mechanical stimuli,
may not be as common a presenting complaint, and even including changes in lung volume, airway smooth muscle
mild hemoptysis is distressing to many patients and physi- constriction, and airway wall edema. As their names suggest,
cians and calls for prompt attention and diagnosis. It may RARs display rapid adaptation (i.e., a rapid reduction in the
range in severity from mild blood streaking in sputum to number of action potentials) during sustained lung inflations,
massive hemorrhage that, if left untreated, can lead to shock whereas SARs adapt slowly to this stimulus. RARs and SARs
and rapid death from blood loss and asphyxiation. Every case have different mechanical activation profiles. Thus, RARs
of hemoptysis warrants a thorough clinical evaluation. Cough may be activated during both inflation and deflation of the
and hemoptysis can result from a wide variety of conditions, lungs (including lung collapse). SARs, on the other hand,
ranging from fairly non–life-threatening causes (e.g., bronchi- display activity during tidal inspirations, peaking just prior to
tis) to life-threatening ones (e.g., lung cancer). Because the initiation of expiration. Even though the RARs and SARs
both cough and hemoptysis may be signs of urgent or life- are not chemosensitive, they do get activated secondary
threatening disease, patients who present with either or both to airway smooth muscle contraction, mucous secretion, or
of these symptoms should undergo a thorough, methodical edema formation caused by bradykinin and capsaicin.
workup consisting of a detailed history, a careful physical Chemically sensitive airway afferent fibers become recruited
examination, and appropriate diagnostic studies. during airway inflammation or irritation. They are typically
activated by a wide range of chemicals, including capsaicin,
bradykinin, adenosine, and prostaglandin E2. Chemosensors
Cough are stereotypically defined by their responsiveness to the
definition irritant chemical capsaicin and, hence, the expression of the
capsaicin receptor. The transient receptor potential cation
Cough is a forceful release of air from the lungs that can channel, subfamily V, member 1 (TRPV1), also known as the
be heard. Coughing protects the respiratory system by clear- capsaicin receptor, is a protein that, in humans, is encoded
ing it of irritants and secretions. Although people can cough by the TRPV1 gene. This protein is a member of the TRPV
voluntarily, a cough is usually a reflex triggered when an irri- group of the transient receptor potential family of ion chan-
tant stimulates one or more of the cough receptors found at nels. TRPV1 is a nonselective cation channel that may be
different points in the respiratory system. activated by a wide variety of exogenous and endogenous
Cough is a reflex defense mechanism that consists of an physical and chemical stimuli. The best known activators of
acute rapid inspiratory phase followed by an equally rapid TRPV1 are heat greater than 43°C and capsaicin, the pun-
and forceful expiratory phase against a closed glottis. Rapid gent compound in hot chili peppers. Airway chemosensors
opening of the glottis and brisk forceful expulsion result in are sometimes thought of as high-threshold mechanosensors.
the clearance of inhaled pathogens, aeroallergens, irritants, Within this group are fibers that are not readily excited
particulate matter, secretions, and aspirate.4 Impaired cough by mechanical stimulation (e.g., bronchoconstriction, lung
reflexes significantly increase the risk of pulmonary infection inflations, light touch) but can be activated using severe
from retained secretions. Cough helps maintain airway mechanical manipulations (e.g., lung hyperinflation, forceful
function and lung capacity for gas exchange.5,6 punctate stimuli) and one or more chemical stimuli (e.g.,
The cough reflex is initiated by the irritation of cough capsaicin, bradykinin, adenosine).9–12
receptors that exist not only in the epithelium of the upper Afferent fibers from cough receptors in the airways con-
and lower respiratory tract but also in the pericardium, lower verge via the vagus nerve on brainstem sites in the nucleus
esophagus, stomach, and diaphragm.7,8 These receptors can tractus solitarus. The nucleus tractus solitarius is connected
be triggered by chemical and mechanical stimuli such as for- to respiratory-related neurons in the central respiratory
eign bodies, irritant particles, fumes, and extrinsic pressure generator that coordinate the efferent cough response.13 Sen-
from masses (e.g., lung cancer), edema from pulmonary sation of the cough reflex can also arise in the brainstem
parenchymal infection (e.g., pneumonia or abscess), or pul- neurons. Higher cortical centers can also voluntarily inhibit
monary parenchymal fibrosis resulting from any of a variety or produce cough.14,15
DOI 10.2310/7800.2045
12/11
clinical evaluation The cause of cough can be determined from a comprehen-

Guidelines from the American College of Chest Physicians sive history and physical examination. In fact, some studies
distinguish three categories of cough based on duration: estimated that the cause of cough is found in up to 80% of
cases from the history and physical examination alone.17,18
• Acute cough, lasting less than 3 weeks The initial approach to the diagnosis of cough is a careful and
• Subacute cough, lasting between 3 and 8 weeks detailed review of the history of the patient’s cough, especially
• Chronic cough, lasting more than 8 weeks16 its features, including time of occurrence, frequency, dura-
tion, precipitating or aggravating factors, whether it is pro-
Cough can be the first indication of serious pulmonary
ductive or nonproductive, and the color of the expectorant.19
or extrapulmonary pathologic conditions; the differential
In the study of 71 immunocompetent patients with chronic
diagnosis of cough includes infectious, inflammatory, and
cough productive greater than 30 mL of sputum/day, all
neoplastic conditions and many pulmonary disorders [see
patients underwent careful evaluation, including chest
Table 1]. The most common cause of acute, transient cough
radiography, and other tests being selectively administered,
is the common cold. The most prevailing genesis in a series
including sinus x-rays, allergy evaluation, pre- and post-
of 184 patients with subacute cough (lasting 3 to 8 weeks)
bronchodilator spirometry, methacholine challenge, barium
was postinfectious cough (48%), postnasal drip (33%), and
swallow, sputum culture, sputum cytology, fiberoptic bron-
cough-variant asthma (16%).4 The most frequent etiology of
choscopy, and studies of cardiac function. A specific cause of
chronic cough includes asthma, postnasal drip, sinusitis,
chronic cough was determined in 97%: postnasal drainage
chronic bronchitis, and reflux disease. The etiology of chronic
syndrome (40%), asthma (24%), GERD (15%), acute and
cough can be multifactorial. For example, in a study of 88
chronic bronchitis (11%), bronchiectasis (4%), and left
consecutive unselected immunocompetent patients referred
ventricular failure (3%).4
to pulmonary outpatient clinic for evaluation of chronic
cough, 39% had a single cause of cough, 42% had two causes, management
and 17% had three causes. The most common causes of
chronic cough were gastroesophageal reflux disease (GERD) Acute Cough
(71.6%), postnasal drip syndrome (67%), asthma (23.9%), Pneumonia (bacterial, viral, and aspiration) can present
and bronchiectasis (8%). When considering only patients with fever, cough, and shortness of breath. Patients may also
with cough for at least 3 weeks, who are nonsmokers and complain of pleuritic chest pain. Diagnosis is often made on
not on angiotensin-converting enzyme (ACE) inhibitors, with a chest x-ray, sputum, and blood cultures, and treatment is
normal or nearly normal and stable chest radiographs, 99.4% directed toward the causative organism.
will have GERD, postnasal drip syndrome, and/or asthma.17 Asthmatic patients can develop cough in response to vari-
ous provoking factors (allergens, cold, and exercise) and may
not always be associated with airflow obstruction, wheezing,
or dyspnea. The cough is often nocturnal, and the diagnosis
Table 1 Differential Diagnosis of Cough is supported by bronchial hyperresponsiveness using a bron-
Acute infections
chial challenge test using nebulized methacholine or hista-
Acute bronchitis mine and spirometry flow rates.20 Cough can be the first sign
Viral and bacterial pneumonias of worsening of asthma; physicians should look for a fall in
Pertussis early-morning peak flows [see Figure 1].
Chronic infections
Bronchiectasis Chronic Cough
Tuberculosis
Cystic fibrosis
Airway diseases Chronic bronchitis Chronic bronchitis accounts for
Asthma about 10% of cases of chronic cough.21 The typical patient is
Chronic postnasal drip a smoker experiencing productive cough. There is a wide
Chronic bronchitis spectrum of the disease, from mild early-morning sputum
Parenchymal diseases
production to a chronic variety in patients with severe dis-
Emphysema
Chronic interstitial lung fibrosis abling chronic obstructive airway diseases.22–28 In a smoker, a
Sarcoidosis chronic cough is not a particularly worrisome symptom; how-
Tumors ever, if the character of the cough or the quality of the sputum
Primary lung carcinoma changes, further workup is indicated to look for a possible
Benign airway tumors
superimposed infection or neoplasm.27 Any degree of hemop-
Mediastinal tumors
Cardiovascular diseases tysis in a former smoker should be taken seriously, especially
Congestive heart failure if it is not associated with an infection. A chest x-ray may not
Pulmonary embolism be diagnostic, and evaluation with chest computed tomo-
Other diseases graphy (CT) and/or bronchoscopy may be indicated.27,28
GERD
Treatment consists of cessation of smoking, antibiotics,
Recurrent aspiration
Endobronchial stents bronchodilators, and oral or inhaled steroids [see Figure 2].
Drugs
ACE inhibitors Postnasal drip Postnasal drip, also known as upper
ACE = angiotensin-converting enzyme; GERD = gastroesophageal reflux
airway cough syndrome, occurs when excessive mucus is
disease. produced by the nasal membrane. The excess mucus
12/11
ACUTE COUGH
1. History
2. Physical examination
3. Investigations +
_ (depending on clinical evaluation)
Exacerbation of Environmental Infectious etiology Cardiovascular

previous conditions exposure
COPD e.g., chemicals, Upper respiratory tract CHF
Asthma dust, allergens infection e.g., viral Pulmonary embolus
Bronchitis
Lower respiratory tract
infections e.g., bacterial
pneumonia
Figure 1 Acute cough algorithm for the management of patients over 15 years of age with cough lasting less than 3 weeks. CHF
= congestive heart failure; COPD = chronic obstructive pulmonary disease.
accumulates in the back of the nose and trickles down the Reflux disease GERD is commonly implicated as a cause
throat. It is characterized by a sensation of nasal secretions of of chronic cough. In fact, it may be the only symptom in
a drip at the back of the throat, often accompanied by the GERD.32 Typically, symptoms of acid reflux, other than
frequent need to clear the throat, and is associated with nasal cough, are heartburn, chest pain, a sour taste, and regurgita-
discharge or nasal stiffness. Nasal secretions irritate the larynx tion. Reflux of gastric contents to the larynx can cause reflux
and trachea, leading to activation of the cough reflex arc.29 laryngitis with thickening, redness, and edema of the posterior
Postnasal drip occurs during the day or night and may be larynx.33–35 The diagnosis is difficult to make if the typical
worse at night. Generally, the diagnosis is made on the basis symptoms of reflux and heartburn are absent. As awareness
of the history and the symptom complex. The symptoms may of reflux-induced asthma and cough grows, more patients
be vague at times, and the diagnosis is confirmed only when are being evaluated with barium studies and esophageal pH
the patient responds to empirical therapy. In recalcitrant monitoring, which often provide the correct diagnosis when
cases, an otolaryngologic examination may be required to clinical evaluation cannot.
exclude sinus disorders. Physical examination may reveal
nasal edema, mucopurulent secretions, and the typical cob- Tumors In smokers, a change in the nature of cough or
blestone appearance of the posterior pharyngeal wall.29 CT hemoptysis should alert the physician to an underlying carci-
scanning of the sinuses may be required if the diagnosis noma.27 There may be associated weight loss and weakness.
is uncertain. Steroid nasal sprays, antihistamines, and nasal Malignant central tumors tend to be squamous cell carcinoma
irrigations with saline are useful for ameliorating symptoms. or small cell cancers and can have associated mediastinal
lymphadenopathy detected as hilar or mediastinal fullness on
Medications Cough is a well-recognized complication of a chest x-ray and confirmed on CT scans. Carcinoid tumors,
ACE inhibitor therapy.30 ACE inhibitors are prescribed for for the most part, tend to be central endobronchial lesions,
the treatment of hypertension and heart failure; 2 to 33% of causing obstruction to the lumen of the bronchus, and appear
patients report a dry cough.31 The cough can arise within a as smooth, round, fleshy, and highly vascular lesions on bron-
few hours of taking the drug but can also become apparent choscopy. Not uncommonly, patients with a carcinoid tumor
after only a few weeks or months; it improves within days or of the airway will have been treated with inhalers and steroids
weeks of withdrawal of the drug but can take longer to resolve for years because of the presumptive diagnosis of asthma.
completely. ACE inhibitor cough can be caused by the accu- Patients with malignant fistulas between the airway and the
mulation of bradykinin and prostaglandin, which directly esophagus either from the cancers eroding the lumens or as a
sensitize cough receptors. Cough may also result from nonse- result of breakdown after radiotherapy present with copious
lective beta-blocker therapy or may develop as a consequence secretions and foul breath. These patients usually have
of idiosyncratic reactions to a variety of drugs and herbal advanced disease and are best palliated with covered stents in
remedies. the trachea and/or the esophagus.
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CHRONIC COUGH
1. History
2. Physical examination
3. Chest x-ray (CXR)
Normal CXR Abnormal CXR
History of exposure No history of exposure and

1. Smoking cause suggested
2. ACE-1
3. Environmental Upper airway cough syndrome
No response (UACS): start empirical treatment
No response
toxins despite optimum
Discontinue exposure Asthma: start empirical treatment treatment
Gastroesophageal reflux disease
(GERD): start empirical treatment
Further investigations to consider:

• Sputum analysis
• Bronchoscopy
• CT scan
Figure 2 Chronic cough algorithm for the management of
• 24 hr esophageal pH monitoring
patients over 15 years of age with cough lasting more than
• Sinus imaging
8 weeks. ACE = angiotensin-converting enzyme; CT =
computed tomographic. • Environmental assessment
Other conditions associated with cough Bronchiecta- common occurrence. Mild CHF with symptoms of orthop-
sis cough is associated with extensive secretions from nea at night may be associated with coughing. The diagnosis
overproduction, together with reduced clearance, of airway is made on the basis of a history of orthopnea and associated
secretions36 The patient produces mucoid or mucopurulent cardiac risk factors or valvular disease, followed by cardiac
sputum, sometimes accompanied by fever, hemoptysis, and echocardiography. Occasionally, the presence of a small
weight loss.36 Cough can be the only presenting symptom. unrecognized tracheobronchial foreign body can lead to
Bronchiectasis can be associated with postnasal drip and chronic irritation of the bronchial epithelium and then to a
rhinosinusitis, asthma, GERD, and chronic bronchitis.37 persistent cough; this presentation is more common in
children than in adults.39 The diagnosis is usually made by
Bronchiectasis can lead to clubbing of the fingers. Common
performing bronchoscopy in a patient who is believed to be
pathogens cultured from sputum include Haemophilus influ-
harboring a foreign body on the basis of chest imaging.
enzae, Staphylococcus aureus, and Pseudomonas aeruginosa.37
Eosinophilic bronchitis is a rare cause of chronic cough
Patients with immotile cilia syndrome (Kartagener syndrome) that may be suspected in patients with no other clearly
will have other hallmarks of disease, such as situs inversus, explainable diagnosis.40,41 Patients typically have a history
sinusitis, and recurrent otitis.38 Diagnosis is made by the delay of atopy, and the diagnosis is made on the basis of clinical
(over 12 minutes) in the patient’s ability to taste the saccha- suspicion and the results of bronchial epithelial biopsy.
rine placed on the anterior nares. Treatment is directed at the Steroids are the mainstay of treatment. Chronic cough can be
recurrent infections in the sinuses, ears, and chest. a prominent symptom of occupational exposure in glass
A chronic cough may also be a consequence of congestive workers exposed to low-molecular-weight irritants, hydro-
heart failure (CHF) (from any cause), although this is not a chloric acid, and organic oils.42,43
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In the occasional patient, a chronic cough may be of [see Figure 3] results in the destruction of the cartilage and is
psychogenic origin. Such a cough classically occurs during associated with proliferation of bronchial arteries in the
the daytime and is absent when the patient is asleep. This is smaller bronchi (third and fourth generation), resulting in
described as short and explosive and usually has been trig- massive hemoptysis.36 Hemoptysis in tuberculosis results
gered by a precipitating upper respiratory tract infection that from the development of false aneurysms (Rasmussen aneu-
leads to a “sensation of a trickle in the throat” and has sub- rysm) of the bronchial or pulmonary artery as they traverse
sequently persisted. It can be socially disruptive. The main- the walls of a tuberculous cavity or occasionally from a bron-
stay of treatment is creating an awareness in the patient and cholith (calcified lymph gland) eroding through the bronchus.
encouraging voluntary suppression of the cough and attempts Broncholithiasis is also seen in histoplasmosis infections.
at increasing the time interval between coughs.44,45 Various benign and malignant primary epithelial and soft
tissue tumors have been associated with hemoptysis. The
Hemoptysis majority of primary airway tumors are malignant, with squa-
mous cell carcinoma and adenoid cystic carcinoma being the
definition primary malignancies most frequently seen in the trachea.56–62
Hemoptysis is defined as expectoration of blood originating In the case of primary lung cancers, massive hemorrhage is
from the lower airways (tracheobronchial or pulmonary rare. Terminal bleeding in primary lung cancer is usually
parenchymal). Hemoptysis can be traces or massive, poten- associated with a cavitary squamous cell cancer and involves
tially resulting in asphyxia by flooding the airways. By defini- major vessels adjacent to the main tracheobronchial air-
tion, a loss of over 600 mL over 24 hours is considered ways.63,64 Endobronchial carcinoid tumors are highly vascular
massive. However, even as little as 150 mL of rapid blood and appear as smooth, cherry red endobronchial tumors seen
loss in a patient with compromised pulmonary functions can on bronchoscopy. Care must be taken when performing a
be disastrous because the total dead space of the airway is biopsy of endobronchial tumors such as a carcinoid tumor as
150 mL. serious hemorrhage can result. Tumors arising from adjacent
structures such as the esophagus and thyroid can erode the
history
tracheobronchial tree, resulting in hemoptysis.
Hemoptysis dates back to 400 BC, when Hippocrates Trauma from penetrating injuries and iatrogenic injuries
described hemoptysis in patients with advanced phthisis caused by the Swan-Ganz catheter and transbronchial
(Latin, from Greek, from phthinein, to waste away). Greek biopsies can result in hemorrhage. Granulation tissue in a
physicians recognized hemoptysis as being caused by under- tracheobronchial stent placed for malignant tracheobronchial
lying tuberculosis. In 1938, Eloesser suggested lobectomy for
hemoptysis.46 In 1941, Pitkin performed the first pneumonec-
tomy in a patient with bronchiectasis,47 and in 1973, Remy
and colleagues reported the first case of bronchial arterial
embolization.48
surgical anatomy
There are two major sources of independent arterial inflow
to the lungs: an anatomically consistent pulmonary circuit
with the inflow through the pulmonary artery and return via
the pulmonary veins and a highly variable and complex bron-
chial arterial system originating from the arch of the aorta,
intercostals, or other arterial branches that supply the
esophagus, mediastinal lymph glands, and spinal artery.
A bronchial artery greater than 2 mm is considered patho-
logic, and the bronchial arteries play the dominant role in
hemoptysis as these vessels are subjected to higher systemic
pressures.49 As a rule, the blood seen in the sputum is derived
from either the pulmonary arteries or the bronchial arteries;
only rarely does it come from the pulmonary veins.50–52
Although the bronchial arteries provide less blood flow than
the pulmonary arteries do, they supply the bulk of the blood
received by the airways and, accordingly, are the source of the
blood in most cases of hemoptysis.
etiology
Inflammatory processes, including bronchitis, bronchiecta-
sis, tuberculosis, fungal infections, lung abscess, and cystic
fibrosis, account for 60 to 70% of cases of hemotypsis, with
tumors being responsible for 23%.53,54 In 7 to 34% of patients
with hemoptysis, no identifiable cause can be found after
careful evaluation.55 Acute or chronic bronchitis leads to
airway inflammation and is usually minor. Bronchiectasis Figure 3 Bronchial angiogram in bronchiectasis.
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disease can bleed, requiring bronchoscopy and fulguration. Endoscopy: diagnostic and therapeutic The key is
Massive hemoptysis from a tracheostomy should alert the to determine the side and site of bleeding, and bronchoscopy
physician to the possibility of a tracheoinnominate fistula. is particularly effective if performed within 48 hours of presen-
Mitral stenosis results in pulmonary congestion leading to tation.50–52 Bronchoscopy should preferably be carried out in
hemoptysis. Other cardiovascular causes include pulmonary a dedicated suite or the operating room by an experienced
infarction, septic emboli,63 and congenital diseases resulting bronchoscopist with access to a variety of methods to arrest
in pulmonary hypertension, for example, Eisenmenger com- the hemorrhage using balloon catheters, endobronchial lasers,
plex and primary pulmonary hypertension. Arteriovenous or endobronchial fulguration. Flexible bronchoscopy can be
fistulas are a rare cause of massive hemoptysis.65 Patients with used for diagnostic purposes when the bleeding is minimal;
Rendu-Osler-Weber syndrome may have telangiectasis of the however, in patients with massive hemoptysis, a rigid
skin or superficial mucous membranes. bronchoscope will allow not only rapid evacuation of
active bleeding but also the use of other modalities to stop
diagnosis the hemorrhage. Selective ventilation with a double-lumen
endotracheal tube may be used to temporize a critical
History and Physical Examination situation.
Taking a detailed history is essential to differentiate true
hemoptysis from other sources of hemorrhage, such as the Angiography: diagnostic and therapeutic Failure to
upper airways or blood being aspirated from the gastrointes- identify the source of hemorrhage at bronchoscopy should
tinal (GI) tract. A history of coughing must be obtained. A prompt systematic bilateral angiography of the bronchial,
history of spitting, epistaxis or nausea, vomiting, heartburn, nonbronchial, and pulmonary vascular bed. Direct evidence
and abdominal pain may differentiate other sources of the of extravasation of blood into the bronchi or the lung paren-
bleeding, that is, the upper airway or the GI tract. The physi- chyma occurs only during active hemorrhage. On occasion,
cian must determine the duration and quantify the bleeding the source of bleeding is a systemic vessel from the subcalvian,
(e.g., a teaspoon, a cupful), the presence of clots, and other intercostal, or phrenic vessels.66 Most often, we rely on indi-
respiratory symptoms, such as shortness of breath, chronic rect evidence of the bleeding vessel, as suggested by vascular
cough, and chest pain. Direct observation is sometimes the hypertrophy and tortuosity [see Figure 4], and aneurysm
best way to quantify the bleeding. Obtaining a history of pre- formation and collateral circulation [see Figure 5 and Figure 6].
vious cardiac or pulmonary diseases, smoking, and medica- Bleeding from the pulmonary vasculature resulting in hemop-
tions, including blood thinners such as aspirin, clopidogrel, tysis is seen in less than 10% of patients with massive hemop-
or warfarin, is vital. Clinical evaluation may reveal clubbing tysis, especially in patients with arteriovenous malformations,
in patients with chronic disease such as bronchiectasis, calf lung abscess, and Rasmussen aneurysm seen in tuberculosis.66
tenderness, or swelling in deep vein thrombosis, and the pres- Bronchial arteriography and embolization should be con-
ence of telangiectasias, suggesting hereditary telangiectasia, sidered in patients in whom resection is contraindicated [see
Table 3]. Embolization can result in dramatic relief of hemor-
may help narrow the differential diagnosis [see Table 2].
rhage. Unfortunately, the majority of patients with massive
Investigations hemoptysis do not survive, dying of suffocation, and the goal
of the treating physician should be to identify and treat these
Noninvasive investigations Routine chest x-rays are patients before they experience their final bleeding.
insensitive. Chest CT with contrast can often identify the
cause of hemoptysis, especially for parenchymal lesions. CT
scanners capable of three-dimensional helical reconstruction
are especially useful in this regard. The coagulation
profile should be determined and, if abnormal, corrected
aggressively.
Table 2 Differential Diagnosis of Hemoptysis

Tracheobronchial disease
Acute or chronic bronchitis
Bronchiectasis
Neoplasms
Foreign bodies
Trauma
Tracheoinnominate fistula
Parenchymal disease
Infection
Interstitial lung disease
Pulmonary embolism
Pulmonary arteriovenous malformations
Miscellaneous conditions
Mitral valve disease
Coagulopathy
Figure 4 Bronchial arteriogram showing tortuosity.
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Table 3 Contraindications to Surgical Resection

FEV1 < 40% of predicted
Unable to localize site at bronchoscopy
Unresectable cancer
Metastatic disease
Coagulopathy
Systemic disorder
Bilateral lung involvement
FEV1 = forced expiratory volume in 1 second.
hemoptysis are threefold: aspiration prevention, bleeding

cessation, and treatment of the underlying cause. Any patient
with significant hemoptysis should be admitted to a moni-
tored unit and evaluated promptly. Initial medical manage-
ment consists of sedatives, cough suppressants, supplemental
oxygen, and bed rest with dependent positioning of the
pathologic side. Most cases of minor hemoptysis usually
settle down with conservative measures. Patients with mas-
sive hemoptysis are, however, best monitored in intensive
Figure 5 Collateral circulation from the subclavian artery. care units. Interventional techniques described earlier using
bronchoscopy (flexible or rigid) and arteriography with
embolization as required are used in stabilizing the patient.
Surgical
Surgery is best performed once the acute situation is under
control and the site has been identified. There should be
no medical contraindications, and the patient must have
adequate pulmonary reserve. Pulmonary resection is the most
effective method for controlling and preventing recurrent
bleeding in most patients. Emergency surgery has a signifi-
cantly higher morbidity and mortality than elective surgery.
Surgical resection prior to hospital discharge must be consid-
ered in patients with massive hemoptysis even if the bleeding
is stabilized as the recurrence rate is high (> 30%).67 Surgical
procedures depend on the pathology and pulmonary reserve.
For benign disease and in patients with poor reserve, a
limited resection may be appropriate, whereas in patients
with malignant disease and with better pulmonary functions,
a more radical approach with a lobectomy or even a
pneumonectomy may be necessary.
summary
Figure 6 Collateral channels from phrenic artery.
Hemoptysis must always be taken seriously. Death from
massive hemoptysis occurs from asphyxiation. Every attempt
management must be made to localize the site of bleeding. Whenever
possible, attempts must be made to control massive hemor-
Medical rhage by interventional techniques. Elective resection has less
As with any potentially serious condition, evaluation of the morbidity and mortality than emergency surgery.
“ABCs” (i.e., airway, breathing, and circulation) is the initial
step. The overall goals of management of the patient with Financial Disclosures: None Reported
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4 THORAX 3 CHEST WALL MASS — 1
3 CHEST WALL MASS

Michael E. Friscia, MD, and John C. Kucharczuk, MD
Chest wall masses are relatively uncommon in clinical prac- Table 1 Framework for Classification of Primary and
tice. Together they encompass a variety of different processes, Secondary Chest Wall Masses
which may be benign or malignant. Unfortunately, few sur-
Primary masses of the chest wall
geons have a working knowledge of the etiology, evaluation,
treatment, and prognosis of patients with primary or second- Benign masses
ary chest wall masses. Often unfamiliarity leads to inappropri- Infectious masses
ate diagnostic studies, delays in treatment, and frustration for Soft tissue neoplasms
the patient and surgeon alike. The intent of this chapter is to
Bone and cartilage neoplasms
review the clinical presentation and diagnostic procedures
required to evaluate and treat a patient presenting with a Malignant masses
chest wall mass. We begin with the formulation of a clinical Soft tissue malignant neoplasms
algorithm to streamline the evaluation, diagnosis, and treat-
Bone and cartilage malignant neoplasms
ment of patients with chest wall masses and conclude with a
review of the specific causes of chest wall masses. Secondary masses of the chest wall
The chest wall contains a number of distinct tissues, includ- Tumor invasion from contiguous organs
ing skin, fat, muscle, bone, cartilage, lymphatics, blood ves-
Metastasis from distant organs
sels, and fascia. Each of these component tissues has the
capability of producing either a benign or a malignant pri-
mary chest wall mass. The chest wall is also in intimate prox-
The next step is to decide whether to pursue a tissue diag-
imity to a number of organs, which may cause a mass by
nosis prior to proceeding with definitive therapy. For lesions
extension of a malignancy or infection. These include the
less than 3 cm, whether suspected of being benign or malig-
breast, the lung, the mediastinum, and the pleura. Addition-
nant, excisional biopsy is performed for diagnosis and treat-
ally, because of the large surface area of the chest wall, it can
ment. For lesions greater than 3 cm that can produce significant
be the site of metastasis from distant malignancies, including
morbidity with resection, a preoperative tissue diagnosis is
carcinomas and sarcomas. The primary framework for clas-
obtained.
sification of chest wall masses is shown in Table 1.
Fine-needle aspirations (FNAs) are technically simple and
can be performed in the office at the initial patient evaluation
but are best used when metastasis is suspected. Lack of his-
Clinical Evaluation tology and tissue architecture severely limits the use of FNA
The initial evaluation of these in distinguishing benign from malignant primary chest wall
patients begins with a careful his- tumors. In these cases, a core-needle biopsy or incisional
tory noting the symptoms associ- biopsy is performed. Both techniques provide tissue for his-
ated with the mass and the history tology, and both must be performed so that the biopsy track
of its growth. A personal history of will be completely excised at the time of definitive surgery.
malignancy should raise concern Given the easy access to most chest wall masses, many
for a metastatic lesion. A complete patients will tolerate a core-needle biopsy in the office, which
physical examination is performed can expedite the diagnostic process.2
to evaluate other sites of disease and delineate comorbid
medical conditions that will impact the patient’s candidacy
for resection. Previous radiographs, if available, are reviewed Benign Primary Masses of the Chest Wall
to determine the rapidity of the growth. If the mass is pal-
infectiou s mas s es of the ches t wall
pable, its size and characteristics (hard versus soft, fixed
versus mobile) are noted. Sternal Infections
A computed tomographic (CT) scan of the chest is required Primary sternal osteomyelitis is
if chest wall involvement of an intrathoracic lesion is sus- rare but may be seen in intravenous
pected. For primary chest wall masses, magnetic resonance drug abusers. Much more common
imaging (MRI) can be useful for further characterization. An is osteomyelitis following median
MRI allows delineation of tissue planes and the relationships sternotomy. Approximately 1 to 3%
to major neurovascular structures.1 Chest radiography is often of median sternotomies for cardiac
performed initially but is of little use. surgery are complicated by sternal
DOI 10.2310/7800.S04C03
08/09
Evaluation of Chest Wall Mass
Patient presents with chest wall mass
Obtain clinical history:

• Growth of mass
• Associated symptoms
• Previous chest radiographs (if available)
Perform physical examination:
• Other disease sites or comorbid conditions
• Size and salient characteristics of mass (if palpable)
Determine whether mass is primary or secondary.
Chest wall mass is primary Chest wall mass is secondary
Consider MRI for further Control primary underlying disease process.

characterization of lesion Perform needle biopsy to confirm diagnosis.
if desired. Consider definitive treatment after primary
Assess size of mass. process is controlled.
Mass is < 3 cm Mass is ≥ 3 cm
Perform excisional biopsy for diagnosis Perform incisional biopsy for diagnosis.
and treatment.
Mass represents benign lesion Mass represents malignant lesion
Consider resection for confirmation of Perform radical resection with reconstruction.

diagnosis or for management of symptoms.
wound infection.2 The risk factors for this complication Sternoclavicular Joint Infections
include diabetes, use of bilateral internal mammary arteries, Sternoclavicular joint infections present as painful palpa-
and reoperation.3 These patients present with pain, drainage, ble masses overlying the sternoclavicular joint, as shown in
and systemic signs of infection. Most of these infections have Figure 1. These infections are often associated with intrave-
deep extension into the mediastinum as well as sternal osteo- nous drug abuse, infected indwelling subclavian catheters,
myelitis. When sternal osteomyelitis is suspected, a CT scan and trauma. The majority of patients have some underlying
of the chest can help determine the extent of mediastinal risk factor, including diabetes, hepatic or renal insufficiency,
soilage, but, generally, the patient is taken directly to the or a history of systemic sepsis. The diagnosis is made by a
operating room for exploration and sternal débridement. combination of history, physical examination, and MRI of
Aggressive surgical débridement of the bone and cartilage the chest with attention to the sternoclavicular joint. The
with flap closure is associated with the best clinical typical findings include a collection around the joint and
outcomes.4 abnormal signal intensity in the bone and cartilage [see
Special mention must be made of the patient who presents Figure 2]. Treatment consists of wide resection of the sterno-
after sternotomy with a pulsating sternal mass. These clavicular joint, including the proximal third of the clavicle
patients have a pseudoaneursym of the underlying aorta and as well as débridement of the manubrium.5 The proximal
are at risk for exsanguination. They should undergo an portion of the first or second ribs can be involved and also
emergent CT angiogram or aortogram to confirm the diag- requires resection. Immediate reconstruction is performed
nosis. They must then be taken directly to the operating by rotation of a pectoralis muscle flap into the resection
room, where they are placed on cardiopulmonary bypass cavity. Postoperatively, the patients are treated with 6 weeks
through femoral cannulation and are cooled to hypothermia of intravenous antibiotics. Most require intensive postopera-
prior to opening the sternum as repair may require circula- tive physical therapy to restore strength, function, and mobil-
tory arrest. ity in the upper extremity.
08/09
benign neop las ms of the ches t wal l

The benign neoplasms of the
chest wall are shown in Table 2.
Benign soft tissue neoplasms of
the chest wall usually present as
slowly growing, painless masses.
Often plain radiographs and a CT
scan of the chest are obtained,
although they are not always neces-
sary. On examination, benign soft tissue lesions are usually
soft and mobile. The CT scan shows a homogeneous mass
without necrosis, infiltration of associated soft tissue, or
destruction of associated bone. Small (< 3 cm) soft tissue
lesions are completely removed by excisional biopsy for defin-
itive diagnosis and treatment. Larger lesions (> 3 cm) are
approached with a core-needle biopsy first to rule out a malig-
nant soft tissue neoplasm. If the lesion is confirmed to be
Figure 1 Sternoclavicular joint infections present as painful benign, it is resected with close negative margins to minimize
palpable masses overlying the joint. the size of the surgical defect. If it is determined to be malig-
nant, an aggressive wide excision is performed with immediate
reconstruction.
Desmoid tumors deserve special mention in that they are
borderline neoplasms.7 These tumors generally arise in the
muscle and fascia around the shoulder. Although they appear
histologically benign, they can infiltrate adjacent structures
and have a high tendency for local recurrence, which can
make surgical treatment for recurrence morbid and disfiguring.
For these reasons, desmoid tumors are best treated with
radical surgical excision. The largest current series demon-
strates that a positive surgical margin is associated with an
89% recurrence rate, whereas with a negative margin, recur-
rence is less than 20%.8
Benign Bone and Cartilage Neoplasms

Osteochondroma is a benign cartilaginous neoplasm that
can occur in any bone that undergoes enchondral bone forma-
tion. Essentially, these tumors are hamartomas of the growth
plate. The knee is the most common site of occurrence. In the
Figure 2 A computed tomographic (CT) scan shows the

typical appearance of sternoclavicular joint infection, Table 2 Benign Neoplasms of the Chest Wall by Site
including fluid collection around the joint and tissue of Origin
stranding.
Benign soft tissue neoplasms
Lipoma
Fibroma
Osteomyelitis of the Rib Hemangioma
Osteomyelitis of a rib presents as a painful, swollen mass Granuloma
overlying an infected segment of rib. Often a draining sinus
Neurofibroma
tract is present. The diagnosis is made on a clinical basis. A CT
scan of the chest is obtained to rule out underlying intratho- Elastoma
racic pathology such as an empyema. Treatment is resection of Desmoid
the infected bone with soft tissue coverage of the defect. Care
Benign bone and cartilage neoplasms
is taken to avoid contamination of the underlying pleural cavity
during rib resection. In children, the diagnosis can be facili- Osteochondroma
tated by the use of ultrasonography, which demonstrates oblit- Chondroma
eration of the intermuscular planes adjacent to the infected rib Fibrous dysplasia
and pericostal edema.6 As with adults, the range of pathologic
organisms recovered can be quite wide. Eosinophilic granuloma
08/09
chest, they arise in the metaphyseal Table 3 Primary Malignant Chest Wall Masses According
regions of the anterior ribs. Most to Tissue of Origin
are asymptomatic and found on a Malignant chest wall masses—soft tissue
screening chest radiograph where
an eccentric growth pattern is noted Liposarcoma
at the costochondral junction. Leiomyosarcoma
The diagnosis is made from a Rhabdomyosarcoma
characteristic pattern of stippled
Malignant fibrous histiocytoma
calcification within the tumor on plain x-ray. In children, they
are followed unless causing pain or increasing in size; in Angiosarcoma
postpubescent and adult patients, they are resected to confirm Malignant chest wall masses—cartilage and bone
the diagnosis and rule out malignancy.
Solitary plasmacytoma
Chondromas are the next most common benign neoplasm
of the chest wall. They occur along the costochondral Chondrosarcoma
junctions between the anterior ribs and the sternum. Unfor- Osteosarcoma
tunately, the distinction between chondroma and chondro- Ewing sarcoma
sarcoma cannot be made on clinical or radiographic grounds;
therefore, excision is required for diagnosis. This results in a Synovial cell sarcoma
significant surgical defect, which usually requires complex
reconstruction, including prosthetic material to provide rigid
structure and soft tissue coverage.
Fibrous dysplasia is a benign cystic lesion of the medullary
cavity of the rib that usually presents as a painless lesion
incidentally found on a screening chest x-ray. Medullary
replacement by fibrous tissue creates a radiolucent appear-
ance on an x-ray. These lesions are treated conservatively and
simply followed. Local resection is indicated if pain develops
or the lesion enlarges on serial x-rays.
Malignant Primary Masses of the Chest Wall

Malignant soft tissue lesions of the chest wall constitute a
large number of diverse pathologies. The primary malignant
masses of the chest wall are listed in Table 3.
so ft t is s u e
Sarcomas are the most common
Figure 3 Shown is the appearance of a chest wall sarcoma on
primary malignant neoplasm of the physical examination. Such lesions can be quite large.
chest wall. On examination, sarco-
mas of the chest wall can be quite
sizable, as shown in Figure 3. They
are painless in half of the patients. prognostic factors for disease-free survival. This is consistent
The clinical finding is a hard, fixed with other studies that suggest that age, gender, symptoms, and
mass. No calcifications are visible on size do not significantly impact survival.11 The French Sarcoma
a CT scan of the chest, but bony invasion is common. The Group published its retrospective series of soft tissue sarcomas
treatment is wide surgical excision. Gordon and colleagues of the trunk wall in 2009, which included 283 patients with
reported the largest surgical series of patients with soft tissue chest wall sarcomas treated primarily with surgery.12 Overall
sarcomas of the chest wall in 1991.9 The study included 149 survival at 5 and 10 years was 57% and 52%, respectively.
patients who had undergone resection at the Memorial Sloan- Interestingly, 22% of patients in this study had a previous his-
Kettering Cancer Center in New York. The 5-year survival rate tory of radiation therapy, which adversely affected survival.
was 66%. Unfortunately, the study also included 32 patients Currently, no good data are available to recommend
who had desmoid tumors, which are not histologically classi- neoadjuvant treatment, which has become routine in the
fied as sarcomas or as malignant. A large retrospective study treatment of soft tissue sarcomas of the extremities. A single-
containing 55 surgically treated patients with soft tissue sarco- institution, multidisciplinary experience with primary chest
mas of the chest wall was reported from a single institution in wall sarcomas was reported from The University of Texas
Brazil in 2005.10 In this series, fibrosarcoma accounted for M.D. Anderson Cancer Center in 2001.13 The retrospective
nearly 53% of the cases. With wide surgical resection, the review included patients with sarcomas of soft tissue, carti-
authors reported disease-free survival rates of 75% at 5 years lage, and bone origin, as well as desmoid tumors. The cumu-
and 64% at 10 years. The histologic grade of the tumor and lative 5-year survival was 64%, which is to be expected from
the type of surgical resection were found to be independent surgery alone.
08/09
ca r t il a ge a n d b o n e preoperative chemotherapy followed by complete surgical

Solitary plasmacytoma represents an uncommon chest wall resection.23
mass caused by a localized collection of monoclonal plasma Synovial sarcomas are rare but may arise on the trunk,
cells. Histologically, the plasma cells are identical to those where they present as a palpable chest wall mass. Despite the
seen in patients with multiple myeloma; however, unlike name, these lesions do not arise from synovial cells or joint
patients with multiple myeloma, they are confined to a single cavities. They were originally named based on the appearance
site. Patients generally present with pain and often have under light microscopy; however, these tumors are now
pathologic rib fractures. With soft tissue involvement, a pal- known to arise from pluripotential mesenchymal cells.24 The
pable mass becomes evident. Tissue is required to make the most important prognostic factor is tumor size.25 Limited data
diagnosis either by FNA, core-needle, or small incisional suggest that although there may be an objective response to
biopsy. The specimen should be sent for flow cytometry, neoadjuvant chemotherapy, there is no detectable benefit on
which confirms the clonal nature of the cells.14 Definitive local survival.26 The current recommendation is aggressive surgical
radiotherapy is the treatment of choice for solitary bone plas- resection. Patients with very large tumors or positive surgical
macytoma.15 Although local control is achieved in over 90% margins receive postoperative adjuvant treatment.
of patients with radiation alone, about 50% of patient prog-
ress to multiple myeloma within 2 years and require systemic
treatment.16 Secondary Masses of the Chest Wall
Chondrosarcoma is the most common primary malignant Secondary chest wall masses
tumor of the chest wall. Chondrosarcomas are found along arise as direct extensions of a malig-
the anterior sternal border or the costochondral arches and nancy from a contiguous organ.
are more common in males than in females. The primary Breast and lung cancer are the most
symptom leading to evaluation is pain. The best imaging common. The initial evaluation
modality is CT; however, there are no distinguishing radio- centers on staging the underlying
graphic characteristics to provide a definitive diagnosis, and disease. For example, a patient
core or incisional biopsy is required.17 Complete surgical with a chest wall mass attributable
resection with adequate surgical margins and immediate to direct invasion of a primary lung
reconstruction is the treatment of choice. The Scandinavian cancer should undergo a staging workup to determine the
Sarcoma Group published the largest series of patients with extent of disease. If the patient is deemed an appropriate can-
chest wall chondrosarcoma.18 Ninety-seven patients were didate for resection and is medically operable, he or she should
treated with surgery; wide excision was associated with a 92% undergo pulmonary resection with en bloc chest wall resec-
10-year survival and a 4% local recurrence rate, compared tion.27 Following resection, the patient should be referred for
with a 47% 10-year survival and a 73% local recurrence rate adjuvant chemotherapy. The intent is cure, and the outcomes
when margins were positive. are stage specific.
Ewing sarcoma is an aggressive primary malignant bone Unfortunately, most women presenting with a chest wall
tumor that presents in children and adolescents with a pain- mass from breast cancer have a local recurrence. Resection
ful, enlarging mass often associated with fever and malaise. with reconstruction can be performed in this situation, but
Ewing sarcoma was initially distinguished from osteosarcoma the benefit remains unclear. The Memorial Sloan-Kettering
because of its sensitivity to radiation. Although the cellular Cancer Center reported on 38 women who underwent
origin of Ewing sarcoma remains unclear, there appears to be extensive chest wall resection for recurrent breast cancer with
a spectrum of tumors that share the same genetic transloca- a 0% operative mortality rate, but the 5-year survival rate was
tion and are referred to as the Ewing family of tumors.19 The only 18%, and by 5 years, 87% of the patients had local
initial role of surgery in primary chest wall Ewing sarcoma is recurrence.28 Currently, chest wall resection of locally recur-
to obtain tissue for diagnosis. With smaller rib lesions, this rent breast cancer must be considered on a case-by-case
may be in the form of an excisional biopsy. Therapeutically, basis.
these tumors are best approached with multimodality treat- A large necrotic ulcer of the chest wall presenting after
ment, including preoperative chemotherapy followed by radiation therapy to the chest wall for previous malignancy
complete resection of residual disease.20 A review of three should raise the suspicion for osteoradionecrosis. This is a
multi-institutional trials from the Pediatric Oncology Group locally destructive lesion characterized by infection and
in 2003 suggested that the likelihood of a complete resection necrosis. The first step is to perform biopsies of the area to
is improved with neoadjuvant chemotherapy followed by ensure that the lesion does not represent tumor recurrence.
wide resection in patients with Ewing sarcoma and closely The preferred treatment is wide excision to healthy tissue and
related primitive neuroectodermal tumors of the chest wall.21 local or free flap coverage of the soft tissue defect, avoiding
If the resection is complete and the pathologic margins are the use of prosthetic material whenever possible. Close col-
negative, no radiation therapy is given. The avoidance of laboration with a plastic and reconstructive surgeon is critical
radiation therapy may be particularly important in children to operative planning and success.29
and adolescents because of the risk (10 to 30%) of develop-
ing a radiation-induced malignancy over their lifetime.22
Askin tumors are a small round cell tumor of the thoracopul- Conclusions
monary region and are members of the Ewing family of Chest wall masses are relatively unusual in clinical practice.
tumors. They are best managed by diagnostic biopsy and Most surgeons have limited experience in diagnosis and
08/09
treatment. In general, it is important to move quickly to gist to make the diagnosis and an oncologist to assist in treat-
establish a tissue diagnosis as a physical examination and a ment planning to optimize patient outcome.
radiographic study often cannot distinguish a benign from a
malignant chest wall mass. The very unusual tumors will
often require consultation with a highly specialized patholo-
Financial Disclosures: None reported.
References
1. Fortier M, Mayo JR, Swensen SJ, et al. MR survival. Ann Thorac Surg 1986;41: 20. Saenz NC, Hass DJ, Meyer P, et al. Pediatric
imaging of chest wall lesions. Radiographics 597–601. chest wall Ewing’s sarcoma. J Pediatr Surg
1994;14:597–606. 12. Salas S, Bui B, Stoeckle E, et al. Soft tissue 2000;35:550–5.
2. Toumpoulis IK, Anagnostopoulos CE, sarcomas of the trunk wall (STS-TW): a study 21. Shamberger RC, LaQuaglia MP, Gebhardt
DeRose JJ, Swistel DG. The impact of deep of 343 patients from the French Sarcoma MC, et al. Ewing sarcoma/primitive neuroec-
sternal wound infection on long-term survival Group (FSG) database. Ann Oncol 2009; todermal tumor of the chest wall: impact of
after coronary artery bypass grafting. Chest 20:1127–35. initial versus delayed resection on tumor mar-
2005;127:464–71. 13. Walsh GL, Davis BM, Swisher SG, et al. gins, survival and use of radiation therapy.
3. Ridderstolpe L, Gill H, Granfeldt H, et al. A single-institutional, multidisciplinary appr- Ann Surg 2003;238:563–8.
Superficial and deep sternal wound complica- oach to primary sarcomas involving the 22. Paulussen M, Ahresn S, Lehnert M, et al.
tions: incidence, risk factors and mortality. chest wall requiring full-thickness resec- Second malignancies after Ewing tumor
Eur J Cardiothorac Surg 2001;20:1168–75. tions. J Thorac Cardiovasc Surg 2001;121: treatment in 690 patients from a cooperative
4. DeFeo M, Gregorio R, Della Corte A, et al. 48–68. German/Austrian/Dutch study. Ann Oncol
Deep sternal wound infection: the role of 14. Jennings CD, Foon KA. Recent advances in 2001;12:1619–30.
early debridement surgery. Eur J Cardiotho- flow cytometry: application to the diagnosis 23. Veronesi G, Spaggiari L, De Pas T, et al. Pre-
rac Surg 2001;19:811–6. of hematologic malignancy. Blood 1997;90: operative chemotherapy is essential for con-
5. Song HK, Guy TS, Kaiser LR, Shrager JB. 2863–92. servative surgery of Askin tumors. J Thorac
Current presentation and optimal surgical 15. Dimopoulos MA, Moulopouls LA, Maniatis Cardiovasc Surg 2003;125:429–9.
management of sternoclavicular joint infec- A, Alexanian R. Solitary plasmacytoma of 24. Miettinen M, Virtanen I. Synovial sarcoma: a
tions. Ann Thorac Surg 2002;73:427–31. bone and asymptomatic multiple myeloma. misnomer. Am J Pathol 1984;117:18–25.
6. Bar-Ziv J, Barki Y, Maroko A, Mares AJ. Rib Blood 2000;96:2037–44. 25. Deshmukh R, Mankin H, Singer S. Synovial
osteomyelitis in children. Early radiologic and 16. Liebross RH, Ha CS, Cox JD, et al. Solitary sarcoma: the importance of size and location
ultrasonic findings. Pediatr Radiol 1985;15: bone plasmacytoma: outcome and prognostic for survival. Clin Orthop Relat Res 2004;
315–8. factors following radiotherapy. Int J Radiat 419:155–61.
7. Hayry P, Reitamo JJ, Totterman S, et al. The Oncol Biol Phys 1998;41:1063–7. 26. Singer S, Baldini EH, Demetri GD, et al.
desmoid tumor. Analysis of factors possibly 17. Murphey MD, Flemming DJ, Boyea SR, Synovial sarcoma: prognostic significane of
contributing to the etiology and growth et al. Enchondroma versus chondrosarcoma tumor size, margin of resection and mitotic
behavior. Am J Clin Pathol 1982;77:674–80. in the appendicular skeleton: differentiating activity for survival. J Clin Oncol 1996;14:
8. Abbas AE, Deschamps C, Cassivi SD, et al. features. Radiographics 1998;5:1213–37. 1201–8.
Chest wall desmoid tumors: results of surgical 18. Widhe B, Bauer HC; Scandinavian Sarcoma 27. Burkhart HM, Allen MS, Nichols FC, et al.
intervention. Ann Thorac Surg 2004;78: Group. Surgical treatment is decisive for Results of en bloc resection for bronchogenic
1219–23. outcome in chondrosarcoma of the chest wall: carcinoma with chest wall invasions. J Thorac
9. Gordon MS, Hadju SI, Bains MS, et al. Soft a population-based Scandinavian Sarcoma Cardiovasc Surg 2002;123:670–5.
tissue sarcomas of the chest wall. J Thorac Group study of 106 patients. J Thorac Car- 28. Downey RJ, Rusch V, Hsu FI, et al. Chest wall
Cardiovasc Surg 1991;101:843–54. diovasc Surg 2009;137:610–4. resection for locally recurrent breast cancer: is
10. Gross JL, Younes RN, Haddad FJ, et al. Soft- 19. Delattre O, Zucman J, Melot T, et al. it worthwhile? J Thorac Cardiovasc Surg
tissue sarcomas of the chest wall: prognostic The Ewing family of tumors—a subgroup of 2000;119:420–8.
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11. King Rm, Pairolero PC, Trastek VF, et al. chimeric transcripts. N Engl J Med 1994; Radiation-related wounds of the chest wall.
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08/09
4 THORAX 4 PLEURAL EFFUSION — 1
4 PLEURAL EFFUSION
Michael A. Maddaus, MD, FACS, and Rafael S. Andrade, MD, FACS
Approach to the Patient with a Pleural Effusion Table 2 Causes of Transudative and Exudative Pleural
Pleural effusion is a common problem in surgical practice. Effusion
It results from perturbations of normal pleural fluid transport, Type of Effusion Cause
which are produced by three main mechanisms: abnormali- Transudative Congestive heart failure
ties in Starling equilibrium, increased capillary and mesothe- Cirrhosis
lial permeability, and interference with lymphatic drainage. Nephrotic syndrome
Acute atelectasis
These mechanisms are associated with a variety of different
Renal failure
causes [see Table 1].1,2 Often more than one mechanism is Peritoneal dialysis
involved. An inflammatory effusion, for instance, is marked Postoperative state
by increases in capillary and mesothelial permeability, which Myxedema
Postpartum state
lead to elevated intrapleural oncotic pressure.
Pleural effusion is classified as either transudative or exuda- Exudative Pneumonia
tive, depending on the chemical composition of the fluid. Malignancy
Infection
A transudate is an ultrafiltrate of serum and has a low total Esophageal perforation
protein content (f 3 g/dL); an exudate is the result of Hemothorax
increased permeability and has a high total protein content. Chylothorax
Increased pleural permeability results from complex inflam- Pseudochylothorax
Connective tissue diseases
matory mediator interactions between the mesothelium Drug-induced pleuritis
(whose cells play an active role in inflammation, phagocyto- Pancreatitis
sis, leukocyte migration, tissue repair, antigen presentation, Uremia
coagulation, and fibrinolysis3,4) and the capillary endothe- Postmyocardial infarction (Dressler
syndrome)
lium. The distinction between transudative and exudative Chronic atelectasis
pleural effusion is clinically significant in that the two types Radiation therapy
of effusion have different causes [see Table 2].1,4 Asbestos esposure
Meigs syndrome
Ovarian hyperstimulation
Transudative or exudative Pulmonary embolus
Table 1 Pathophysiologic Mechanisms of Pleural Effusion
Mechanism Specific Alteration Cause Clinical Evaluation
Abnormality in Increased capillary Increased venous A complete history,
Starling and lymphatic pressure (e.g.,
equilibrium hydrostatic biventricular heart physical examination,
pressure failure, renal and clinical acuity are
failure) the initial tools used
Decreased capillary Hypoproteinemia for diagnosing pleural
oncotic pressure (e.g., nephrotic effusion. Important
syndrome) facts from a patient’s
Decreased Ex vacuo effusion history (e.g., respira-
intrapleural (e.g., atelectasis) tory symptoms, pain,
hydrostatic
pressure
extrathoracic symptoms, duration of symptoms, previous
medical conditions, and risk factors for cardiopulmonary
Increased intrapleu- Inflammation (e.g., diseases or cancer) can raise the index of suspicion for an
ral oncotic infection, cancer,
pressure autoimmune effusion and provide guidance regarding possible causes.
disease) Careful physical examination of the chest can detect an effu-
Increase in Increased filtration Inflammation (e.g., sion, and many physical signs may provide clues to the cause.
capillary and infection, cancer, Physical signs that are particularly useful for diagnostic
mesothelial autoimmune purposes include jugular venous distention and tachycardia
permeability disease) (suggestive of congestive heart failure); lymphadenopathy,
Interference with Obstruction Cancer, structural digital clubbing, and localized bone tenderness (suggestive
lymphatic abnormalities of lung cancer); and ascites (suggestive of ovarian tumors or
drainage
cirrhosis).
DOI 10.2310/7800.2047
12/10
C
Approach to the Patient with a
Pleural Effusion
Findings are adequate for diagnosis
Assess respiratory status.
Patient is not in respiratory distress Patient is in respiratory distress
Transudative effusion is Exudative effusion is Nature of effusion is unclear

suspected suspected
Treat underlying cause.
Suspected cause is PSI (PPE) Suspected cause is other Suspected cause is malignancy,
condition esophageal perforation,
[See Table 3.] hemothorax, or chylothorax
Patient's condition improves Patient's condition does not mprove
Provide clinical and radiologic Treat with pleurodesis or long-term

follow-up. drainage.
12/10
Clinical evaluation and chest x-ray suggest pleural effusion
Findings are inadequate for diagnosis
Perform US or CT.
Pleural pathology is not complex Pleural pathology is complex
Perform VATS.
Perform thoracentesis (with or without

imaging guidance) or tube
thoracostomy.
Drainage is successful Drainage is unsuccessful
Analyze pleural fluid sample (total protein Perform VATS.

concentration, with or without LDH concentration).
Effusion is transudative Effusion is exudative
Suspected cause is PSI (PPE) Suspected cause is malignancy Suspected cause is nonmalignant
condition other than PSI (PPE)
[See Table 3.] Perform cytologic tests.
Perform cell count with differential.
Assess levels of triglycerides, cholesterol,
amylase, chylomicrons, rheumatoid factor,
and antinuclear antibodies.
Cytology is positive Cytology is negative
Treat malignancy (with or without Perform pleural biopsy.

pleurodesis or long-term drainage).
Test results are positive Test results are negative
Treat underlying cause Treat with pleurodesis or

(with or without pleurodesis long-term drainage.
Biopsy is positive Biopsy is negative
or long-term drainage).
Treat malignancy (with or without
pleurodesis or long-term drainage).
12/10
Pleural effusion can occur in a wide variety of clinical Supine chest radiographs are less sensitive than other chest
situations, however, and it often evades clinical detection by radiographs. With these images, suspicion of an effusion
history and physical examination. Consequently, imaging is triggered by increased homogeneous density of the lower
tests are indispensable in the workup of a patient with a hemithorax, loss of normal diaphragmatic silhouette, blunt-
possible pleural effusion. Pleural fluid analysis, pleural biopsy, ing of the lateral costophrenic angle, or apical capping [see
and thoracoscopy may also be required for evaluation. Figure 2].8
Ultrasonography
Investigative Studies Chest ultrasonograms are more reliable for detecting and
localizing small (5 to 100 mL) or loculated pleural effusions

than chest radiographs are.5,9,10 Ultrasonography is particu-
Chest Radiography larly helpful for guiding thoracentesis for small-volume
effusions and for assessing pleural effusions in critically ill
To be detectable on a standard upright posteroanterior
patients.6,11
chest radiograph, an effusion must have a volume greater
than 150 mL. If the volume is 150 to 500 mL, the lateral Computed Tomography of Chest
costophrenic angle will be blunted; if the volume is greater
Computed tomography (CT) of the chest is a very sensitive
than 500 mL, a meniscus will be created.5,6 A lateral decubi-
tool for evaluating pleural effusion. Free-flowing fluid causes
tus chest radiograph can detect minute effusions (< 50 mL), a sickle-shaped opacity in the most dependent portion of
and as a general rule, a layering effusion that is at least 1 cm the thorax, and even small effusions are readily detected [see
thick is accessible to thoracentesis.6,7 A loculated effusion Figure 3]. CT may also reveal clues to the cause of the effu-
may appear as a so-called pseudotumor on a chest radiograph sion, such as a fluid-fluid level (suggestive of acute hemor-
and typically will not layer freely on a lateral decubitus radio- rhage), pleural thickening and enhancement (suggestive of
graph. Subtle changes on an upright chest radiograph (e.g., pleural space infection [PSI] [see Figure 4]), calcified pleural
accentuation of a fissure, elevation of a hemidiaphragm or plaques (suggestive of asbestosis), and diffuse irregular nodu-
increased separation between the lung and subdiaphragmatic larity and pleural thickening (suggestive of pleural metastases
gas [see Figure 1]) may also signal an effusion. Additional or mesothelioma). CT is especially useful for characterizing
findings on a standard chest radiograph (e.g., laterality, the loculated effusions, for differentiating pleural thickening or
size of the cardiac silhouette, the position of the mediasti- pleural masses from pleural effusion, for distinguishing
num, pulmonary parenchymal changes, pleural calcifications, between effusion and lung abscess, and for guiding and
and osseous abnormalities) may point to a specific cause. monitoring closed drainage of effusions.6,10,12,13
Magnetic resonance imaging (MRI) of the chest provides
no useful information beyond what can be obtained with CT.
Figure 1 Posteroanterior chest radiograph of a patient with Figure 2 Supine chest radiograph of a patient with bilateral
bilateral pleural effusion reveals increased separation pleural effusion shows increased homogeneous density of the
between the left lung and subdiaphragmatic gas (arrows). lower hemithoraces.
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Techniques for Bedside Thoracentesis and Tube Thoracos-

tomy] is indicated. Thoracentesis may also have therapeutic
value in that drainage of fluid may relieve dyspnea. Absolute
contraindications to thoracentesis include a lack of coopera-
tion on the patient’s part, clinical instability with hemody-
namic or respiratory compromise, severe coagulopathy,
and high-pressure ventilation. Relative contraindications to
thoracentesis include a nonlayering effusion, loculations, and
previous thoracic trauma, chest tube placement, or surgery.
A large effusion can be drained without any special imaging
guidance other than an upright posteroanterior and lateral
chest radiograph. Thoracentesis for a small or loculated effu-
sion is best done with ultrasound guidance; success rates are
as high as 97%.15
The incidence of complications associated with thoracen-
tesis varies, depending on the experience of the operator
and on the use of imaging guidance. Pneumothorax occurs in
3 to 20% of patients, of whom approximately 20% require
tube thoracostomy [see Sidebar Techniques for Bedside
Figure 3 Computed tomographic scan of the chest shows a Thoracentesis and Tube Thoracostomy]. Patients commonly
free-flowing, sickle-shaped, right-sided effusion. experience pain and cough with lung reexpansion during
drainage. Reexpansion pulmonary edema is an uncommon
MRI is neither efficient nor cost-effective in standard complication that can occur with rapid drainage of a large-
evaluation of pleural effusion.12,14 volume effusion. It is common practice to drain no more than
1 to 1.5 L at a time, even though no evidence supports this

practice. Experimental data suggest that active aspiration
If the cause of a pleu- of fluid can cause high negative intrapleural pressures, poten-
ral effusion cannot be tially precipitating edema formation; gravity drainage may
explained by the clinical be preferable to minimize the chance of edema. Additional
circumstances (e.g., con- potential complications include so-called dry tap, vasovagal
gestive heart failure or a reaction, hemorrhage, hypovolemia, and PSI.10,16–18
recent surgical proce-
dure), diagnostic thora-   
centesis [see Sidebar Assessment of a
pleural fluid sample is
guided, to some extent,
by the clinical context
in which the pleural
effusion occurs. When
the cause of the effu-
sion is unknown, eval-
uation of a pleural fluid
sample typically includes measurement of total protein and
lactate dehydrogenase (LDH) concentrations, a cell count
with differential, cause-specific testing, and microbiologic
and cytologic analysis.
Biochemical Analysis of Pleural Fluid

A total protein concentration higher than 3 g/dL is some-
times used as the main criterion for distinguishing a transu-
date from an exudate; however, the use of this criterion may
result in misclassification of as many as 15% of effusions.
According to Light and colleagues’ criteria,19 which have a
sensitivity of 99% and a specificity of 98% for identifying
exudates, an effusion is an exudate if one of the following
three findings is present:
1. A pleural fluid–to–serum protein ratio higher than 0.5
Figure 4 Chest computed tomographic scan of a patient with 2. A pleural fluid–to–serum LDH ratio higher than 0.6
right-side empyema shows a loculated effusion. The pleura is 3. A pleural fluid LDH concentration higher than two thirds
enhanced with intravenous contrast. of the upper limit of the serum reference range
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Techniques of Bedside Thoracentesis and Tube Thoracostomy

Bedside Thoracentesis
Bedside thoracentesis should be performed on a bed or an examination table (as a safeguard if hypotension develops). The patient should
be upright and seated (provided that he or she is awake and cooperative), with the arms leaning comfortably on a bedside table and the back
facing the surgeon.
The proper intercostal space for catheter insertion is determined through physical examination and radiologic evaluation of the effusion;
generally, the ninth or 10th intercostal space in the midscapular line is a good choice. The area is prepared and anesthetized with 1% lido-
caine, 3 to 5 mg/kg, with care taken not to injure the intercostal bundle. To confirm that the catheter is in the correct location, we recom-
mend drawing a small amount of pleural fluid at the time of local anesthetic infiltration. Several thoracentesis kits with one-way valves are
available. Fluid should be allowed to drain by gravity; however, to minimize the risk of reexpansion pulmonary edema, drainage should not
exceed 1.5 L. Frequently, a dry cough and pleuritic pain develop as drainage approaches its end. To minimize anxiety, the patient should
be warned about this possibility in advance. After the completion of thoracentesis, a chest radiograph should be obtained.
Bedside Tube Thoracostomy
Bedside tube thoracostomy should be performed with the patient supine. The side on which the thoracostomy will be created should be
elevated, and the patient’s ipsilateral arm should be abducted. Supplemental oxygen should be supplied. Monitoring must include, at the
least, continuous oxygen saturation plethysmography and intermittent measurement of blood pressure and heart rate. Tube thoracostomy is
potentially very painful; accordingly, in a nonemergency situation, every effort should be made to minimize pain and anxiety. We usually
administer intravenous ketorolac about 30 to 60 minutes before the procedure. During preparation for chest tube placement, narcotics and
sedatives should be administered intravenously; additional doses should then be administered at the beginning of and during the procedure.
The ideal location for chest tube placement is determined by clinical and radiographic examination. The area is prepared and draped
widely, and a local anesthetic is used at a near-maximum dosage, with care taken to anesthetize skin, subcutaneous tissue, muscle, and
periosteum. A 1.5 cm skin incision is made, a soft tissue tunnel is created with blunt instrument and finger dissection, the upper edge of the
rib is identified clearly, and additional local anesthetic is applied to the periosteum and the intercostal muscles. The subcutaneous tunnel
should generally be directed posteriorly so that the chest tube will sit along the posterior chest wall and will not be trapped in a fissure. The
intercostal muscle is pierced bluntly, and digital examination of the pleural space is performed to confirm that an intrapleural location has
been reached and to search for abnormalities such as adhesions or tumor implants. The chest tube is then directed to the desired location
with the aid of a clamp. As with thoracentesis, fluid should be allowed to drain by gravity, but drainage should not exceed 1.5 L. If the
effusion exceeds 1.5 L, the chest tube should be clamped and the remaining fluid allowed to drain intermittently in 200 mL aliquots every
2 hours. Immediately after completion of the procedure, a chest radiograph should be obtained to verify lung expansion and confirm the
position of the chest tube. When chest tube output falls below 200 mL/day and reexpansion of the lung is verified, pleurodesis should be
performed. We recommend that patient-controlled analgesia be employed while the chest tube remains in place.
The size of the chest tube is determined by the suspected cause and by the radiologic characteristics of the effusion. For a free-flowing
transudative effusion, a small (20 to 24 French) chest tube or even a pigtail catheter usually suffices; for a thick exudative effusion or a
hemothorax, a tube as large as 40 French may be required.
A 1997 meta-analysis of the diagnostic value of tests used presence of a neutrophilic effusion does not exclude malig-
to distinguish transudates from exudates did not find any test nancy. Pleural fluid lymphocytosis, in which lymphocytes
or combination of tests to be clearly superior.20 The choice account for more than 50% of WBCs, most frequently is
of a test for this purpose is therefore a matter of individual indicative of malignancy (occurring in 50% of malignant effu-
preference. If only one test is to be performed, measurement sions), tuberculosis (occurring in 15 to 20% of tuberculous
of the total protein concentration is the most practical choice effusions), or chylothorax.26 Pleural fluid eosinophilia, in
in view of its accuracy and availability. which eosinophils account for more than 10% of WBCs, can
Assessment of pleural fluid pH and glucose levels may be be caused by a wide variety of benign and malignant con-
used adjunctively for risk stratification in patients with PSI, ditions—even, in some cases, by the mere presence of air
but the clinical utility of these measurements is not well or blood in the pleural space. Approximately one third of
established (see below).21 eosinophilic effusions are idiopathic. As a rule, the presence
There are numerous substances whose concentrations can of mesothelial cells is of little diagnostic value; the exception
be measured to help determine the specific cause of a pleural to this rule is that if such cells account for more than 5% of
effusion, such as triglycerides, chylomicrons, and cholesterol WBCs, a tuberculous effusion is unlikely.23,27
(to help diagnose chylothorax); amylase (to help diagnose
esophageal perforation or pancreatitis); rheumatoid factor (to Microbiologic Tests
help diagnose rheumatoid effusion); antinuclear antibodies If a PSI is suspected, Gram staining and standard bacterial
(to help diagnose lupus pleuritis); carcinoembryonic antigen cultures are indicated. If tuberculous pleurisy is a possibility,
(to help diagnose malignancy); and adenosine deaminase (to acid-fast stains and mycobacterial cultures should be per-
help diagnose tuberculous pleurisy).3,22–25 formed. Fungal, viral, and parasitic PSIs are uncommon;
accordingly, special stains and cultures for these conditions
Cell Counts are indicated only if dictated by a specific clinical setting.28
Analysis of the number and type of white blood cells
(WBCs) present in pleural fluid is often diagnostically useful. Cytologic Tests
Pleural effusions can be categorized according to the type Cytologic testing of pleural fluid is routinely performed
of WBC that is predominant. Generally, pleural fluid whenever the cause of an effusion is unclear. The diagnostic
neutrophilia points to acute inflammation (e.g., from PSI or yield for malignancy varies depending on the stage of the dis-
pulmonary infarction) as the underlying cause; however, the ease, but it generally is in the range of 50 to 60% (higher in
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patients with bulky pleural tumors). Repeat cytologic testing ultrasonography. Chest tube thoracostomy does not require
may increase the yield to more than 70%,10,29 and testing of ultrasonographic guidance and may be a safer choice for
three or more samples may increase the yield to 90%.30 patients on high-pressure ventilation.
    
In approximately 25% of patients with exudative effusion, Pleural effusion is associated with malignancy in 30 to
the cause remains unknown after clinical evaluation, imaging, 65% of patients, and approximately 75% of patients with
and pleural fluid analysis. The next step in the evaluation of malignant effusion have lung or breast cancer.35 The principal
such patients is pleural biopsy. aim of therapy is to relieve dyspnea and to limit the number
Percutaneous pleural biopsy is an infrequently used tool of procedures and hospital days that patients with a limited
that has a diagnostic yield of 57% for carcinoma. Its low yield life expectancy must endure.
for malignant effusion can be explained by the uneven dis- Drainage can be achieved by means of thoracentesis, chest
tribution of pleural metastases. For tuberculous pleurisy, tube placement, or VATS. Thoracentesis is a valuable option
however, the diagnostic yield of percutaneous pleural biopsy for initial patient evaluation, particularly in the office setting.
is 75%, and the yield rises to 90% when this procedure is Because malignant pleural effusion recurs rapidly unless
combined with pleural fluid culture. In about 10 to 20% of patients undergo effective systemic or local treatment, repeat
patients with exudative pleural effusion, laboratory analysis thoracentesis is generally not recommended for anything
of pleural fluid and percutaneous biopsy fail to produce a other than urgent relief of symptoms. Chest tubes are
specific diagnosis.18 The contraindications and complications placed primarily with the intention of performing bedside
associated with percutaneous pleural biopsy are similar to pleurodesis.
those associated with thoracentesis.31 Small-bore subcutaneously tunneled catheters may be
Video-assisted thoracoscopic surgery (VATS) is also employed for long-term management of malignant pleural
employed for pleural biopsy; its diagnostic yield in this setting effusions. Long-term drainage is preferable in patients with a
is 92% for malignancy and nearly 100% for tuberculous very short life expectancy (f 3 months), patients who have a
pleurisy. VATS is a therapeutic procedure as well, allowing poor performance status, and patients with a trapped lung.36
the surgeon to perform pleurodesis, decortication, or pleurec- Two options are available: the Pleurx catheter (Denver Bio-
tomy if necessary. VATS pleural biopsy is typically performed medical, Golden, Colorado) [see Figure 5] and the Tenckhoff
with the patient under general anesthesia, but if the patient peritoneal dialysis catheter. With either device, the procedure
is highly debilitated, it can be done with regional and local is essentially the same: the catheter is inserted with the patient
anesthesia.32 Procedure-specific complications include hypox- under local or general anesthesia, the patient is discharged
emia, hemorrhage, prolonged air leakage, subcutaneous on the day of or the day after insertion, and the pleural fluid
emphysema, and empyema, each of which occurs at a rate is drained either according to a schedule or on an as-needed
of about 2%. The mortality associated with diagnostic thora- basis. Small-bore tunneled catheters are comfortable, but
coscopy ranges from 0.01 to 0.09%.29,31 When VATS is per- patients may object to having a permanent catheter or to
formed to remove a suspected malignant lesion, a protective undergoing home-based procedures. In 20 to 70% of patients
plastic device is required to minimize the possibility of tumor with a permanent catheter, pleurodesis develops within 4 to
seeding. Incisional tumor seeding after a VATS biopsy is rare 6 weeks. Patients with malignant pleural effusions secondary
but can occur at any time after the procedure (reported range to breast or gynecologic cancers are more likely to develop
2 weeks to 29 months).33 pleurodesis (about 70%) than patients with lung cancer
If mesothelioma is suspected, pleural biopsy (through a (about 40%).37 Catheter removal is easily done in the office
5 cm incision) is the preferred diagnostic procedure. Ideally, setting with local anesthetic. Technical failures and infection
the biopsy incision should be placed at the location of a
potential thoracotomy incision so that future excision of the
biopsy scar can be accomplished in a manner that minimizes
the risk of local tumor recurrence.34
Management
      

Pleural effusion devel-
ops in as many as 60%
of intensive care unit
(ICU) patients evalu-
ated with ultrasono-
graphy.11 When pleural
effusion occurs in the
ICU, drainage should
be liberally employed to
optimize the patient’s hemodynamic and respiratory status Figure 5 Shown is a Pleurx catheter after placement and
and to detect PSI early. Thoracentesis can be done in criti- subcutaneous tunneling. The vacuum container is not
cally ill ventilator-dependent patients with the help of bedside connected.
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may occur in as many as 20% of patients with permanent long-term drainage. Table 3 summarizes practical guidelines
catheters, but very few patients require operative for the definitive management of malignant pleural effusion.
management.38–41
Pleuroperitoneal shunting has been advocated as an   
alternative for long-term management of malignant pleural PSI can be caused by a variety of factors, including
effusions. However, experience with this mode of drainage pneumonia, trauma, and intrathoracic procedures. It has a
is limited and the potential for technical complications is wide clinical spectrum, ranging from a small parapneumonic
high.42,43 effusion (PPE) to a pus-filled pleural space (empyema) with
Recurrence of malignant pleural effusion is best prevented respiratory compromise and sepsis. (The terms PSI and PPE
by using sclerosants to induce pleurodesis. The sclerosant are often used interchangeably.) PSI can be classified accord-
may be instilled either via a bedside tube thoracostomy ing to its pathophysiologic stage (exudative, fibrinopurulent,
or thoracoscopically; a median hospitalization of 6.5 days or organizing) or its anatomic appearance (nonloculated
is required.38 Of the various sclerosants available, talc is versus loculated or noncomplicated versus complicated). The
the most efficacious, with an overall success rate of 80 to term empyema is commonly reserved for the most advanced
96%.44–46 The ideal talc dose has not been determined; the stage of PSI.58
usual dose is 4 or 5 g. Talc pleurodesis with a 5 g dose has The pathophysiology of PSI or PPE can be divided into
generally proved efficient and safe. For obvious reasons, three stages. The exudative stage is characterized by the
simultaneous bilateral talc instillation should be avoided.44 A development of an exudative effusion secondary to increased
phase III intergroup study (Cancer and Leukemia Group B pleural permeability; the pleural space is often sterile initially,
9334) that compared bedside talc slurry pleurodesis versus but if it is left untreated, bacterial infection is likely to ensue.
thoracoscopic talc insufflation pleurodesis found no differ- The fibrinopurulent stage is marked by the progressive depo-
ence in outcome at 30 days; however, subgroup analysis sition of fibrin and the increasing presence of WBCs; gradual
revealed that thoracoscopic talc insufflation pleurodesis angioblastic and fibroblastic proliferation leads to extensive
was superior in patients with primary lung cancer or breast fibrin deposits, and the effusion becomes loculated (com-
cancer.47 Thoracoscopically guided talc pleurodesis can be plicated). The organizing stage starts as early as 1 week after
performed with an operative mortality of less than 1%.48,49 infection, with increasing collagen deposition and lung entrap-
Pain and fever are frequent side effects of talc pleurodesis, ment; after 3 or 4 weeks, the organized collagen has formed
but the main concern is the possible development of acute a peel. The pleural fluid is grossly purulent. Eventually, dense
lung injury (ALI) and respiratory failure. Respiratory failure fibrosis, contraction, and lung entrapment develop.59,60
is reported to occur in approximately 1 to 4% of patients. In most patients, PSI is caused by bacteria. The most
The cause of respiratory failure secondary to talc pleurodesis common pathogens are Staphylococcus aureus, Streptococcus
is not clear and is probably related to multiple factors (e.g., pneumoniae, enteric gram-negative bacilli, and anaerobes.
talc dose, talc absorption, underlying lung disease, reexpan- Approximately 30 to 40% of cultures are polymicrobial. In a
sion pulmonary edema, systemic inflammatory response, subgroup of patients, there is sterile pus in the pleural space
tumor burden, and lymphatic obstruction). There is no as a consequence of either previous antimicrobial therapy or
definitive evidence that the talc dose is correlated with the bacterial autolysis. The pathogens identified vary according
incidence of ALI; respiratory failure has been reported even to the cause of PSI. For instance, S. aureus and S. pneumoniae
with a 2 g talc dose.44,50–54 Moreover, a recent multicenter predominate in PPE, S. aureus in postthoracotomy PSI,
prospective cohort study reported a 0% incidence of acute mixed oropharyngeal organisms in PSI resulting from esoph-
respiratory distress syndrome in 558 patients undergoing talc ageal perforation,28 and acid-fast bacteria in tuberculous
pleurodesis (4 g dose).55 empyema.61
Iodopovidone (10%; 20 mL) is a very effective and
inexpensive alternative for chemical pleurodesis that is of Parapneumonic Effusion
value in the setting of limited financial resources.56,57 PPE occurs in as many as 57% of patients hospitalized
Treatment of malignant pleural effusion must be individu- with pneumonia, and pneumonia accounts for 42 to 73%
alized. The key factors governing the choice of treatment
approach are the (1) patient’s performance status, (2) prog-
nosis, (3) patient’s choice, (4) ability of the lung to reexpand, Table 3 Practical Guidelines for Definitive Management
of Malignant Pleural Effusion
and (5) pleural tumor bulk. Patients who have poor perfor-
mance status (e.g., those with advanced tumors or significant Patient Chemical Long-Term
Characteristics Pleurodesis Drainage
comorbid conditions) or a very poor short-term prognosis
should undergo the least invasive treatment—namely, drain- Performance status
age only. Patients who have better functional status and are Good Yes Yes
expected to survive longer should preferably undergo thora- Poor No Yes
coscopically guided talc pleurodesis, but it is not unreason- Life expectancy
able for a patient to elect to have long-term drainage in this > 6 mo Yes Yes
scenario. Pleural tumor bulk is important in that bulky pleu- 3–6 mo Individualize Yes
ral lesions will interfere with pleurodesis. The lung’s ability to
< 3 mo No Yes
reexpand after drainage of a malignant effusion is significant
Bulky pleural Individualize Yes
because if the lung is atelectatic as a result of airway obstruc-
implants
tion or trapped as a result of pleural seeding, no agent will be
Trapped lung No Yes
able to induce pleurodesis, and the best treatment will be
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of cases of PSI. In most cases, early PPE is effectively Tube thoracostomy alone may be appropriate for category
treated by timely antibiotic therapy aimed at the underlying 3 patients with free-flowing effusion. With loculated effusion,
pneumonia.21,28 however, the key to successful therapy is breaking down the
In 2000, a panel convened by the Health and Science fibrin septations. Evidence from three small randomized,
Policy Committee of the American College of Chest Physi- controlled trials suggested that intrapleural fibrinolytic
cians (ACCP) reviewed the available literature with the aim therapy has an advantage over tube thoracostomy alone
of developing an evidence-based clinical practice guideline for patients with category 3 or 4 PPE; a large trial is being
for the treatment of PPE.21 The panel formulated a clear and conducted to address this specific issue.59 To date, only one
relatively simple classification system that used pleural anat- randomized study, including 20 patients with category 3 or
omy and bacteriology to stratify patients according to the risk 4 PPE, has compared VATS with fibrinolytic therapy. The
of a poor outcome [see Table 4]. It then made therapeutic primary treatment success rate was significantly higher in the
recommendations on the basis of this classification. Some VATS treatment group, the duration of chest tube drainage
authors have used pleural fluid chemistry test results (e.g., was less, and the total hospital stay was shorter.63 VATS
pH and glucose concentration) as additional criteria for allows not only adequate drainage and visualization of the
categorizing PPE; for example, a pleural fluid pH lower than pleural space but also decortication of the lung if required;
7.20 or a glucose level lower than 60 mg/dL has been con- however, if decortication cannot be thoroughly accomplished
sidered suggestive of moderate risk. To date, however, the by means of VATS and satisfactory lung expansion cannot be
clinical utility and decision thresholds of pH and glucose achieved, a thoracotomy should be performed.64,65
values have not been well defined. Accordingly, the panel The principles of PPE treatment can be applied to PSI
omitted pleural fluid chemistry from its guidelines. from any cause, but in view of the paucity of reliable data,
The ACCP Health and Science Policy Committee caution should be exercised.
evaluated six primary management approaches: no drainage,
therapeutic thoracentesis, tube thoracostomy, fibrinolytic Posttraumatic PSI
therapy, VATS, and open surgery. Overall, pooled outcomes PSI occurs in about 1 to 5% of patients who have sustained
favored patients treated with fibrinolytics, VATS, and open blunt or penetrating thoracic injury. The incidence of PSI
surgery. However, the success of an approach is related to the in the setting of trauma increases with the number of chest
patient’s risk category. The recommendations for drainage in tubes placed and with the duration of chest tube drainage.
relation to risk category are general guidelines, based on level The effect of an undrained hemothorax on the risk of PSI has
C and D evidence (with level C referring to historically con- not been completely defined, and prophylactic antibiotics
trolled series and case series and level D to expert opinion). have not been shown to reduce the incidence of PSI.58
With these recommendations (and their limitations) in mind, As noted (see above), the general guidelines for the
treatment should be tailored to the specific situation of each treatment of PPE apply to the treatment of posttraumatic
patient. PSI.
Iatrogenic PSI
Category 1 and 2 PPE PPE in categories 1 (very low
risk) and 2 (low risk) can be treated with antibiotic therapy Iatrogenic PSI develops when a preexisting pleural effusion
directed at the underlying pneumonia. Some patients with is inoculated with bacteria during an invasive procedure (e.g.,
category 2 PPE may require drainage for relief of dyspnea thoracentesis or tube thoracostomy). The presence of fluid in
through either thoracentesis or tube thoracostomy. the pleural space appears to be a prerequisite for infection.58
A bronchopleural fistula (BPF) is by definition a PSI and
Category 3 and 4 PPE Drainage options for category 3 therefore has a similarly broad spectrum of clinical presenta-
(moderate risk) and 4 (high risk) PPE include tube thoracos- tion. The overall incidence of BPF after lobar resection is
tomy alone, tube thoracostomy with intrapleural fibrinolytic approximately 1%; it is somewhat higher after resections
therapy, VATS drainage, and open surgical drainage. These for inflammatory diseases than after resections for cancer.
various approaches are not mutually exclusive: in some cases, The incidence of BPF after pneumonectomy varies depend-
patient outcomes may be optimized by a combination of ing on the side on which the pneumonectomy was done, the
treatment modalities.62 indications for surgery, the extent of preoperative irradiation,
Table 4 Categorization of Parapneumonic Effusion by Risk of Poor Outcome

Risk of Poor
Pleural Space Anatomy Pleural Fluid Bacteriology Category Outcome Drainage
Minimal free-flowing effusion (< 10 mm on lateral Culture and Gram stain results 1 Very low No
decubitus x-ray) unknown
Small to moderate free-flowing effusion (> 10 mm Negative culture and Gram stain 2 Low No
but < 50% hemithorax)
Large free-flowing effusion (> 50% hemithorax), Positive culture or Gram stain 3 Moderate Yes
loculated effusion, or effusion with thickened
parietal pleura (as seen on contrast-enhanced CT) Pus 4 High Yes
CT = computed tomography.
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and the comorbid conditions present. In a report encompass- Lymphoma-related chylothorax is caused principally
ing 464 pneumonectomies for cancer, the incidence of BPF by obstruction and usually develops on the left side [see
was 8.6% after right pneumonectomy and 2.3% after left Figure 6]. In a stiff and infiltrated duct, minor triggers (e.g.,
pneumonectomy.66,67 a Valsalva maneuver) can lead to duct rupture. Although
Almost every PSI after a lung resection is synonymous with patients with chylothorax often have extensive disease, supra-
BPF, and operative management is generally required. diaphragmatic disease is not always present. Lymphoma-
related chylothorax is best managed with thoracentesis and
Tuberculous PSI with therapy directed at the underlying cause. If first-line
Pleural effusion is common in patients with clinically therapy fails, thoracoscopic talc pleurodesis is recommended;
evident pulmonary tuberculosis. Most cases of tuberculous a small series reported 100% resolution of lymphoma-related
effusion are secondary to hypersensitivity and resolve chylothorax with thoracoscopic talc pleurodesis. If the chylo-
spontaneously. Tuberculous empyema is relatively rare; it is thorax does not respond to any of these approaches, it may
typically the result of active pleural infection by acid-fast respond to thoracic duct ligation or pleuroperitoneal shunt-
bacteria.61 ing. Chylothorax in the presence of lymphoma-related chy-
Tuberculous PSI is also treated in accordance with the lous ascites is a difficult problem that is generally refractory
general treatment guidelines for bacterial PSI. Chronic to most forms of therapy (although pleurodesis is occasionally
tuberculous PSI may present specific problems, such as drug successful).49,68,69,74,75
resistance and impaired ability (or even inability) to reexpand Pseudochylothorax is a rare disorder associated with the
the lung. Surgical procedures performed to manage chronic formation of persistent exudates that last for months or years.
The most common cause is tuberculosis; the second most
tuberculous empyema include VATS, standard open decorti-
common cause is rheumatoid arthritis. Biochemical analysis
cation, thoracoplasty, parietal wall collapse, open drainage,
of pleural fluid from patients with pseudochylothorax reveals
myoplasty, and omentopexy.61
very high cholesterol levels (> 200 mg/dL) and the presence
   of cholesterol crystals. Treatment is generally conserva-
tive.24,25
Chylothorax is the presence of chyle in the pleural space as
a consequence of blockage of or damage to the thoracic duct    
or one of its tributaries. The rate at which chyle flows through In a small percentage of patients, the cause of pleural effu-
the thoracic duct can be higher than 100 mL/hr; thus, sion remains unknown despite extensive diagnostic evalua-
large amounts of chyle can leak into the pleural space.68 tion. Eventually, most cases of idiopathic effusion turn out to
The principal causes of chylothorax are surgical trauma be caused most frequently by tuberculosis and other granulo-
and malignancy (70 to 80% are caused by non-Hodgkin matous diseases, malignancy, and pulmonary embolism; less
lymphoma).49,68,69 Congenital chylothorax is more often common causes include constrictive pericarditis, subphrenic
attributable to malformation of the thoracic duct than to birth abscess, connective tissue diseases, drug-induced pleuritis,
trauma.24 peritoneal dialysis, and cirrhosis.23 In the management of
The diagnosis of chylothorax is made by measuring triglyc- persistent benign or idiopathic effusion, talc pleurodesis has
eride levels in pleural fluid. Levels higher than 110 mg/dL a high success rate and minimal long-term implications.76,77 A
are highly suggestive of chylothorax, levels between 50 and chronic drainage catheter (i.e., Pleurx) can be used for refrac-
100 mg/dL are equivocal, and levels lower than 50 mg/dL tory pleural effusion in patients with congestive heart failure;
rule out chylothorax.24 A pleura-to-serum triglyceride ratio however, prolonged use (> 4 months) can lead to empyema.78
higher than 1 can be a useful indicator70; the presence of
chylomicrons is synonymous with chylothorax.25
Treatment of chylothorax depends on its cause and sever-
ity. Postoperative chylothorax may be treated initially with
conservative measures (e.g., with a nihil per os [NPO] regi-
men, total parenteral nutrition, and administration of octreo-
tide). However, drainage totaling more than 500 mL/day is
considered to predict failure of conservative management.
Thoracic duct ligation is the surgical treatment of choice and
can often be performed thoracoscopically. To help identify
the leak intraoperatively, it may be helpful to administer
100 to 200 mL of heavy cream or olive oil orally 2 to 3 hours
before operation.71,72 Early surgical intervention is important
because the ongoing loss of lymph has significant effects
on fluid homeostasis, nutrition, and immunocompetence
(secondary to lymphocyte loss). In the early postligation
period, medical management should be continued to allow
any small leaks to seal. An alternative to surgical ligation that Figure 6 Chest computed tomographic scan shows left-side
has evoked some interest is transabdominal percutaneous chylothorax secondary to lymphoma. Subtle mediastinal
embolization of the thoracic duct. This technique requires lymphadenopathy obstructing the thoracic duct (arrow) is
significant expertise.73 apparent.
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Hence, in the setting of a benign, refractory pleural effusion, purposes of lubrication. The structure of the intercellular
a chronic drainage catheter should be considered only as a junction in the mesothelial cells of the pleura is similar to that
last resort. in the endothelial cells of the venules, which suggests that the
pleural mesothelial cell layer may be as leaky as the venular
endothelium.3,4,80
Pleura: Basic Facts
  
 
The amount of pleural fluid in an adult is 1 to 10 mL
The pleura is a continuous membrane that covers the and forms a 10 µm thick layer.1,3,79,80 Fluid exchange across
parietal and visceral surfaces of the thorax. In adults, it has the pleural surface depends on three mechanisms: (1) passive
an estimated surface area of 2,000 cm2.79 Light microscopy filtration following Starling equilibrium, (2) active solute
shows the pleura to have five layers: (1) a mesothelial cell transport, and (3) lymphatic clearance. In the normal pleura,
layer; (2) a mesothelial connective tissue layer with basal Starling equilibrium favors the flow of fluid in a parietal-
lamina; (3) a superficial elastic layer; (4) a loose connective to-visceral direction.79 The rate at which fluid traverses
tissue layer with adipose tissue, blood vessels, nerves, and the pleura ranges from 20 to 160 mL/day in adults; maximal
lymphatic vessels; and (5) a deep fibroelastic layer. The pari- lymphatic clearance is believed to be approximately 700 mL/
etal pleura establishes a pleurolymphatic communication on day.2,79,81–84
the diaphragm to allow clearance of large (> 1,000 nm) par- The chemical composition of normal pleural fluid is similar
ticles and cells from the normal pleural space. The structure to that of interstitial fluid. The protein concentration is typi-
of this pleurolymphatic communication consists of stomata 2 cally 1 to 2 g/dL. The concentration of high-molecular-weight
to 12 µm in diameter, which overlie bulblike lymphatic chan- proteins (e.g., LDH) is approximately half that seen in
nels (lacunae) separated by a layer of loose connective tissue serum. Cell counts in normal pleural fluid range from 1,400
(the membrana cribriformis). to 4,500 cells/µL; macrophages account for the majority of
Electron microscopy reveals microvilli on the mesothelial the cells.3,80
cell surface of the pleura. The main function of these micro-
villi is to enmesh glycoproteins rich in hyaluronic acid for Financial Disclosures: None Reported
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4 THORAX 5 SOLITARY PULMONARY NODULE — 1
5 SOLITARY PULMONARY NODULE

Taine T.V. Pechet, MD, FACS*
Assessment of a Solitary Pulmonary Nodule

The solitary pulmo- Table 1 Differential Diagnosis of Solitary
nary nodule (SPN) is Pulmonary Nodule
a common finding
Behavior Category Disease
that is observed in
more than 150,000 Benign Vascular disease Arteriovenous malformations
persons each year in Pulmonary artery aneurysm
the United States.1 An Infection Mycobacterium avium
SPN is defined as a complex infection
single radiographically Aspergilloma
Histoplasmosis
visible pulmonary
Echinococcosis
lesion that is less than 3 cm in diameter, is completely sur- Blastomycosis
rounded by pulmonary parenchyma, and is not associated Cryptococcosis
with atelectasis or adenopathy.2 Any pulmonary lesion larger Coccidioidomycosis
than 3 cm is considered a mass and as such has a greater Ascariasis
likelihood of being malignant.3,4 SPNs are detected on Dirofilariasis
routine chest radiography at a rate of 1 in 500 x-rays, but with Inflammatory Rheumatoid nodule
the growing use of computed tomographic (CT) scanning, condition Sarcoidosis
they are now being diagnosed with increasing frequency. Wegener granulomatosis
The differential diagnosis of an SPN is broad and includes Congenital Foregut duplication cyst
vascular diseases, infections, inflammatory conditions, con- abnormality
genital abnormalities, benign tumors, and malignancies [see Other Rounded atelectasis
Table 1]. Although most SPNs are benign, as many as one Pulmonary amyloidosis
third represent primary malignancies, and nearly one quarter Benign tumor Hamartoma
may be solitary metastases.1,5,6 Various approaches have been Lipoma
developed to aid in the characterization and identification Fibroma
of SPNs. Certain clinical characteristics—such as greater age,
Malignant Primary lung Non–small cell lung cancer
history of tobacco use, and previous history of cancer—have cancer Squamous cell carcinoma
been shown to increase the likelihood that the SPN is Adenocarcinoma
malignant.7 Some authors have attempted to use the Bayes Large cell cancer
theorem, logistic regression models, or neural network analy- Bronchoalveolar carcinoma
sis to predict the likelihood of malignancy.7–9 Such methods Small cell lung cancer
Carcinoid
are highly sensitive and specific, but they are cumbersome Lymphoma
and of limited clinical applicability.
Metastatic cancer Colon cancer
Testicular cancer
Clinical Evaluation Melanoma
Sarcoma
Once an SPN has been identified, it is necessary to Breast cancer
determine whether the lesion is benign or malignant and what
further investigations should be pursued. Evaluation should
generally be governed by the dictum “malignant until proven factors influencing probability of malignancy
otherwise.” The basis for an initial assumption of malignancy
is the observation that the overall 5-year survival rate is low A number of factors influence the probability that an SPN
(10 to 15%) once a diagnosis of lung cancer is established.10 is malignant. Those most strongly associated with lung cancer
Appropriate evaluation involves careful assessment of the are age, smoking history, and occupational history. Pulmo-
patient’s history and risk factors for malignancy in conjunc- nary function test results indicative of a severe obstructive
tion with the results of radiographic studies [see Investigative ventilatory impairment are also associated with an increased
Studies, below] to develop an individualized care plan. likelihood of malignancy.11 In addition, the presence of
endemic granulomatous disease has been shown to increase
* The authors and editors gratefully acknowledge the con- the probability that an SPN is harboring cancer.7
tributions of the previous author, Shamus Carr, MD, to the The radiographic appearance of an SPN, particularly on
development and writing of this chapter. a CT scan, also influences the probability of malignancy
DOI 10.2310/7800.S04C05
05/10
SPN is seen on chest x-ray or CT scan
Obtain history and perform thorough physical

examination. SPN
Assessment of a Solitary Review previous diagnostic images (if available). or n
Pulmonary Nodule
Obta
SPN is < 1.0 cm and patient is at low risk SPN is 1.0–3.0 cm
Obtain follow-up CT scan at 3 mo. Assess probability of malignancy on the basis of

salient characteristics (age, smoking history, lesion
size, lesion margin).
Probability of cancer is low P

Consider PET.
Risk of surgical complication is high

Consider PET, or obtain tissue diagnosis via TTNB
or bronchoscopy, as warranted by clinical situation
SPN is unchanged SPN has grown
Consider PET scanning if Tissue diagnosis is obtained

nature of lesion is indeterminate.
Otherwise, assume malignancy
and resect lesion via VATS
or thoracotomy after staging Pathology is indeterminate
investigations.
Consider PET, or proceed to metastatic evaluation,
as warranted by clinical situation.
PET scan is obtained PET scan is not obtained
PET scan is negative PET scan is positive and

lesion is suspicious
Obtain follow-up CT scans at 3-, 6-, or 12-month intervals.
SPN has remained unchanged for > 2 yr SPN has grown
Lesion is probably benign; treat appropriately. Consider PET scanning if nature of lesion is indeterminate. Otherwise,
assume malignancy and resect lesion via VATS or thoracotomy
after staging investigations.
SPN = solitary pulmonary nodule; CT = computed tomography; PET = positron emission tomography; VATS = video assisted thoracic surgery; TTNB =
trans-thoracic needle biopsy.
05/10
SPN has arisen or grown since previous images, SPN has remained unchanged for > 2 yr
or no previous images are available for review
Obtain CT scan. Lesion is probably benign; treat appropriately.
SPN is > 3.0 cm

sis of Lesion is considered a mass and thus is more
y, lesion likely to be malignant.
Probability of cancer is intermediate Probability of cancer is high
Risk of surgical complicatons is low

via TTNB
situation.
Obtain tissue diagnosis via TTNB or bronchoscopy,
or proceed to metastatic evaluation and resection,
as warranted by clinical situation.
ined Tissue diagnosis is not obtained
Pathology is malignant
on,
ained
Carry out metastatic evaluation. If results are negative,

resect lesion via VATS or thoracotomy. If results are
positive, treat appropriately.
05/10
[see Investigative Studies, Imaging, Computed Tomography, Investigative Studies

below]. The size, contour, internal characteristics, and growth
imaging
rate of the nodule are all potentially significant indicators of
malignant disease [see Table 2]. Chest Radiography
(X-Ray)
Age
Whereas the pre-
Lung cancer is rare before the age of 40 years, but its inci-
valence of lung cancer
dence steadily increases from that point until the age of 80.5
is low in comparison
Above the age of 70, the likelihood that an SPN is malignant
with that of breast
increases.8 After the age of 80, the incidence of malignancy
or prostate cancer, the
in an SPN seems to level off or even decrease.12 mortality for lung cancer exceeds that for breast, prostate,
Environmental Exposures and colon cancer combined. As noted [see Clinical Evalua-
tion, above], the overall 5-year survival rate for lung cancer
The link between cigarette smoking and lung cancer has
patients is poor, in part because lung cancer is frequently
been well established since the 1950s, and the incidence of
diagnosed at a more advanced stage than other forms of
lung cancer in smokers is directly correlated with the number cancer. Several trials performed before the advent of CT
of pack-years of smoking.13 The surgeon general’s report from scanning evaluated chest radiography for early screening
2004 states that “the evidence is sufficient to infer a causal of lung cancer but were unable to demonstrate that such
relationship between smoking and lung cancer.”14 There is screening yielded better survival.18–20 One explanation for
also ample evidence of a causal relationship between environ- these disappointing results may be that fewer than 10% of
mental tobacco exposure, termed “secondhand smoke,” and lung cancers are stage I at presentation.18
lung cancer.15 Although chest radiography is ineffective as a screening
Radon exposure is the second leading cause of lung cancer tool for early-stage lung cancer, it remains a valuable investi-
in America, and cigarette smoking further increases the gative tool in the evaluation of SPNs. If an SPN’s appearance
risks associated with radon exposure.16 Asbestos exposure in on chest x-rays has not changed for more than 2 years, the
combination with cigarette smoking also places patients at SPN will be benign in more than 90% of cases. In such cases,
significantly increased risk for lung cancer. Patients with only yearly follow-up is typically required; additional diag-
a history of workplace exposure to a radioactive substance nostic tests are usually unnecessary.21,22 Therefore, an effort
(e.g., uranium or plutonium) are at increased risk for lung should always be made to obtain old chest radiographs if they
cancer, but this association is not as well documented as the are known to exist.
association of lung cancer with tobacco use. Miners of heavy
metals (e.g., nickel, cadmium, and silica) are also at increased Computed Tomography
risk, and a variety of other environmental toxins, from The advent of CT scanning has led to an increase in the
diesel exhaust through vinyl, have been associated with the number of SPNs detected.23 But, of course, it has also led to
development of lung cancer.15 There is some evidence to an increase in the number of benign SPNs found. Advocates
suggest that patients with idiopathic pulmonary fibrosis and of CT scanning for assessment of SPNs base their argument
pneumoconiosis are at increased risk for bronchoalveolar cell on two central points. First, as many as 83% of CT-detected
carcinoma.17 stage I malignancies are not visible on chest x-ray.24 Second,
non–small cell lung cancer (NSCLC) is the malignancy most
commonly identified, and the survival rate for stage I NSCLC
is relatively high in comparison with more advanced disease
Table 2 Factors Affecting Malignant Probability of
stages. In patients whose SPN proves to be NSCLC, the
Solitary Pulmonary Nodule8
5-year survival rate is 67% for stage IA disease. This figure
Likelihood Ratio for falls rapidly as the disease stage rises: the 5-year survival rate
Factor Malignancy
is 55% for stage IIA NSCLC and only 10% for stage IIIA
Spiculated margins on CT scan 5.54 NSCLC with mediastinal nodal metastasis.25
Age > 70 yr 4.16 Numerous studies have evaluated the use of screening
Lesion size 2.1–3.0 cm 3.67
CT both in the general population and in at-risk groups
consisting of older patients with a smoking history.24,26,27 The
Doubling time < 465 days 3.40 greatest drawback to screening CT is the high false positive
History of smoking 2.27 rate: nodules are identified on 23 to 66% of all CT scans,
Age 50–69 yr 1.90 depending on the thickness of the slices,12,24 and nearly 98%
of these nodules are eventually determined to be benign.
Lesion size 1.1–2.0 cm 0.74
Sequential CT scanning is often required to determine
Lesion size < 1 cm 0.52 whether an SPN is benign or malignant. In 10 to 15% of
Smooth margins on CT scan 0.30 patients, however, this determination cannot be made even
No history of smoking 0.19 when two CT scans are compared. Such patients may be
assessed with other imaging modalities (e.g., positron emis-
Doubling time > 465 days 0.01 sion tomography [PET]) or may be referred for transthoracic
CT = computed tomographic. needle biopsy (TTNB) or other invasive diagnostic tests.
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Controversy exists in both the literature and in clinical are typically malignant (sensitivity 98%; specificity 73%).40
practice around the optimal intervals for follow-up CT scan- Lesions that enhance by 15 to 20 HU should be considered
ning after initial identification of an SPN. In the literature, indeterminate.
the recommended interval between initial CT scanning and Because most SPNs are benign and because the risk of
repeat CT scanning has ranged from 1 month to 1 year.12,24,27 misdiagnosing a malignant lesion is so great, it is important
These varying recommendations are based on what is con- to make use of all of the data obtained from CT scanning in
sidered the doubling time for an SPN. In a study from 2000 the effort to make cost-effective, logical decisions regarding
that included 13 patients with a known diagnosis and lesions further evaluation or treatment. Careful evaluation of the
less than 10 mm in diameter at initial evaluation, volumetric size, contours, and internal characteristics of an SPN on
growth rates were measured to establish the doubling times successive CT scans, balanced by the patient’s risk profile,
of the nodules.10 The doubling times ranged from 51 days including age, smoking history, and environmental exposures,
to more than 1 year. For malignant lesions, the average dou- provides the framework for developing an individualized
bling time was less than 177 days, whereas for benign lesions, evaluation strategy
it was more than 396 days. New volumetric modeling meth-
ods have been developed that may be capable of detecting Positron Emission Tomography
conformational changes over much shorter intervals, but they PET is an imaging modality that employs radiolabeled
remain infrequently used.28 Because the doubling time is con- isotopes of fluorine, carbon, or oxygen; the most commonly
siderably shorter for malignant lesions than for benign lesions, used isotope is 18F-fluorodeoxyglucose (FDG). The rationale
a repeat CT scan should typically be performed for most for FDG-PET scanning in the evaluation of SPNs is based
lesions 3 months after the initial study. If the lesion is visibly on the higher metabolic rate of most malignancies and the
larger on the repeat scan, it is likely malignant, and diagnos- preferential trapping of FDG in malignant cells.41 However,
tic evaluation should progress toward presumed resection. increased FDG activity can also occur in benign SPNs,42,43
If, however, the lesion has neither regressed nor progressed, especially those arising from active granulomatous diseases44,45
a follow-up CT scan closer to 12 months is warranted; or inflammatory processes.46 These benign diseases can
the precise timing remains controversial and should be produce false positive PET scans and thereby reduce the
determined on the basis of individual patient and SPN char- sensitivity of the test. Conversely, some malignancies—bron-
acteristics. The Fleischner Society Statement from the choalveolar carcinoma and carcinoid tumors, in particular—
Radiological Society of North America provides commonly have low metabolic activity and commonly produce false
cited guidelines for the radiographic evaluation of nodules, negative PET scans.47–51 Thus, a negative PET scan is not a
with recommendations divided into size categories and particularly helpful result, and it is necessary to follow the
recommendations that range from 3 to 12 months.29 lesion with serial CT scans. Accuracy calculations for PET
The morphologic characteristics of an SPN visualized on a scanning vary widely, with some of the highest sensitivity and
CT scan can be extremely helpful in characterizing the prob- specificity figures reported in an early meta-analysis identify-
ability of malignancy [see Differential Diagnosis, below]. Size, ing sensitivity of 96% and specificity of 77%.52 More recent
margin appearance, cavitation, and attenuation are important pooled sensitivity and specificity figures were 87% and 83%,
criteria. Air bronchograms, ground-glass opacity, and adja- with specificity ranging from 40 to 100%.39
cent vascular distortion patterns can also help suggest malig- Efforts have been made to improve the sensitivity and
nancy. Although an SPN with a spiculated margin is perhaps specificity of PET scanning in the diagnosis of SPNs. One
most suspicious for malignancy, one fifth of lung cancers may such effort involves the use of the standardized uptake value
have well-defined margins.30,31 Within areas of ground-glass (SUV), which is a numerical indication of the activity con-
opacity, characteristic changes, such as the development of centration in a lesion, normalized for the injected dose.53
nodularity and solid attenuation, have been identified that In many studies, an SPN is considered malignant when its
increase the probability of malignancy.32–34 Other CT charac- SUV is higher than 2.5. Because of the methodology used to
teristics may point more toward a benign condition. For calculate SUV, however, small tumors (< 1.0 cm) may have
example, although cavitation may occur in either benign or an SUV lower than 2.5 and still be malignant. Their small
malignant lesions, SPNs with walls thinner than 4 mm are volume causes their true activity concentration to be under-
much more likely to be benign, whereas those with walls estimated, with the result that their SUV drops below the
thicker than 16 mm are more likely to be malignant.35 Intra- threshold value for malignancy. In one prospective study of
nodular fat is a reliable indicator of a hamartoma, a benign patients with SPNs, the overall sensitivity of FDG-PET scan-
lesion, and is seen in as many as 50% of hamartomas.36 In ning was 79% and the overall specificity was 65%.54 When
addition, calcification is most commonly associated with the SPN was smaller than 1.0 cm, however, all of the scans
hamartomas and other benign nodules. Unfortunately, were negative, even though 40% of the nodules were malig-
between one third and two thirds of benign lesions visualized nant. Another effort involves recent technology combining
are not calcified, and as many as 6% of malignant lesions PET and CT scans. CT-PET fusion imaging is clinically
are calcified.31,37,38 Finally, increased enhancement (measured available in many locales, and combination imaging has been
in Hounsfield units [HU]) after injection with intravenous found to be particularly important for staging.55,56
contrast is strongly suggestive of malignancy and has been In cases where the SPN is larger than 8 mm and no pre-
included in the American College of Chest Physicians (ACCP) vious radiographs or CT scans are available for comparison,
consensus recommendations.39 Lesions that enhance by less PET scanning can provide information that may facilitate
than 15 HU are most likely benign (positive predictive value the decision whether to follow the lesion closely or to proceed
99%), whereas lesions that enhance by more than 20 HU with tissue acquisition. ACCP consensus recommendations
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include the use of PET scanning in select lesions greater than 80%, depending on the size of the lesion, the incidence
8 mm identified in patients with low to moderate pretest of malignancy in the study population, and the proximity
probability of malignancy.39 Cost analysis is also an important of the lesion to the bronchial tree.64,65 For SPNs smaller than
criterion in considering PET scanning. One study that exam- 1.5 cm, the yield drops to 10%.66 Even though bronchoscopy
ined the cost-effectiveness of PET in the evaluation of SPNs has a low complication rate (about 5%), its low diagnostic
concluded that it was cost-effective for patients who had an yield for malignancy limits its utility in the evaluation of
intermediate pretest probability of a malignant SPN and who SPNs.
were at high risk for surgical complications.57 In all other New technology has allowed the application of guidance
groups, PET was not cost-effective, and CT led to similar techniques to the field of bronchoscopy. Ultrasound trans-
outcomes (in terms of quality-adjusted life-years) and to ducers affixed to the tip of a bronchoscope, endobronchial
lower costs. ultrasonography (EBUS), has become an important tool
in mediastinal staging, with EBUS-transbronchial needle
biopsy aspiration (EBUS-TBNA) sensitivities in the range of 92%
If an SPN displays characteristics suggestive of malignancy, and specificities of 98% reported.67 Electromagnetic naviga-
a tissue diagnosis should be obtained. In many cases, the tional bronchoscopy (ENB) uses three-dimensional CT
appropriate form of tissue acquisition will be excisional biopsy reconstructions to provide guidance for bronchoscopic sam-
by wedge resection, often followed by anatomic lung resec- pling of peripheral lesions. The diagnostic yield for peripheral
tion. Traditionally, excisional biopsy was performed, accept- lesions is in the range of 70%,68 and experience within the
ing the morbidity associated with thoracotomy. Especially for community is growing. ENB is a technique that can provide
peripheral lesions, however, video-assisted thoracic surgery tissue from central nodules as well as an alternative to TTNB
(VATS) has now supplanted thoracotomy as the procedure or VATS for peripheral lesions, and offers the ability to place
of choice. However, several alternative biopsy techniques may a fiducial marker for subsequent radiation therapy guidance.
be performed in place of resection, including TTNB and
bronchoscopy. Excisional Biopsy
The decision to proceed to excisional lung biopsy (open
Transthoracic Needle Biopsy or VATS) must be carefully considered. The risk-to-benefit
Lesions that are between 1.0 and 3.0 cm in diameter should ratio of excisional biopsy for an individual patient is
be considered for TTNB. The diagnostic yield of this pro- determined by clinical characteristics affecting perioperative
cedure for SPNs is excellent, reaching 95% in some studies. morbidity and mortality, as well as by the expected risk of
The reported sensitivity ranges from 80 to 95% and the malignancy in the SPN.
specificity ranges from 50 to 88%.58–60 A study of 222 patients Resection is the reference standard for tissue acquisition.
who underwent TTNB for an SPN reported a positive The morbidity associated with VATS is less than that associ-
predictive value of 98.6% and a negative predictive value of ated with thoracotomy; accordingly, when VATS lung biopsy
96.6%61; however, several other studies reported false nega- is technically feasible, it is preferable to open lung biopsy.
tive rates ranging from 3 to 29%.58,62 The complication rate The overall morbidity is lower than 1% for VATS wedge
associated with TTNB is relatively high—potentially as high resection, compared with 3 to 7% for the equivalent open
as 30% and rarely lower than 10%, in even the most experi- procedure. Patients who have undergone VATS resection
enced hands.59,63 Most commonly, a pneumothorax results; experience less pain, have shorter hospital stays, and recover
however, chest tube placement is required only if the patient sooner than those who have undergone open biopsy.69–71
becomes symptomatic, a situation that occurs in approxi- A technical consideration that must be contemplated when
mately 50% of cases. In the absence of symptoms, obser- VATS is planned is possible conversion to thoracotomy.
vation with serial chest x-rays is generally appropriate. If The conversion rate for VATS to thoracotomy has been
no increase in the size of the pneumothorax is observed, reported to be as high as 33%, but there is evidence to sug-
the patient can be discharged with the expectation that the gest that this rate can be significantly reduced with careful
pneumothorax will resolve. patient selection and increasing experience in minimally inva-
For lesions smaller than 1.0 cm, the risk-to-benefit ratio of sive techniques.72,73 For example, modern experience with
TTNB rises to the point where other techniques are typically VATS techniques has demonstrated a low conversion rate
preferred. The utility of TTNB depends primarily on the of 2.5% in a series of 1,100 patients undergoing the more
characteristics of the SPN—in particular, its location. complex VATS lobectomy procedure.74
Nodules that are central or close to the diaphragm or the Peripheral SPNs more than 1.0 cm in diameter are the
pericardium are less well suited to this technique than those lesions best suited to VATS excision. As SPNs become
at other sites. smaller and more central, they become harder to identify, and
the rate of conversion to thoracotomy or the need to perform
Bronchoscopy an anatomic resection increases. A wide variety of techniques
Bronchoscopy has a well-established role in the evaluation have been employed to improve the identification of SPNs
of central SPNs, which are amenable to direct visualization for VATS, ranging from dye staining through guide-wire
and biopsy. Most SPNs, however, are not central. Various localization. One of the more recent developments has
adjunctive measures, including transbronchial needle biopsy been the use of technetium-labeled microalbumin combined
and cytology brushings, are employed to improve the yield with a gamma probe to successfully resect 96% of lesions
of bronchoscopy. For SPNs between 2.0 and 3.0 cm in diam- using thoracoscopic techniques.75 Despite demonstrated
eter, the diagnostic yield of bronchoscopy ranges from 20 to cost-effectiveness,76 however, none of these techniques have
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achieved wide acceptance, and most surgeons rely on digital patients with metastatic head and neck cancer and, occasion-
palpation combined with radiographic guidance. ally, for those with metastatic melanoma.82 Recent reports
with modern chemotherapeutic strategies and resection
have suggested that prolonged survival is possible in colorec-
Differential Diagnosis
tal cancer metastatic to the lung, with 5-year survival of
malignant lesions 67%.83 Improved outcomes are thought to be more likely
in colorectal cancer patients with less than two pulmonary
Non–Small Cell Lung Cancer metastases.84
As noted, NSCLC is the malignancy most frequently
benign lesions
identified in an SPN. Most lung cancer patients are asymp-
tomatic, and those who are symptomatic usually have Pulmonary Hamartoma
advanced disease, including mediastinal lymph node involve-
Pulmonary hamartomas are the most common benign
ment. Arterial invasion has also been shown to have an
pulmonary tumors and the third most common cause of
adverse effect on survival in patients with early-stage
SPNs overall. Most (90%) arise in the periphery of the lung,
NSCLC.77 The most common sites of metastases are the
but endobronchial hamartomas are seen as well. Because they
lymph nodes, the brain, the bones, and the adrenal glands.
are most common in the periphery, hamartomas are usually
Accordingly, it is essential to perform a metastatic evaluation
asymptomatic. When a potential hamartoma appears as an
that focuses on these areas before proceeding with resection.
SPN on a chest x-ray, CT scanning is warranted for further
Adenocarcinoma and squamous cell carcinoma remain
evaluation.
the most common types of NSCLC, but bronchoalveolar car-
Certain typical CT findings suggest that the SPN is likely
cinoma is a well-differentiated subtype that has a prolonged
to be a hamartoma. One such finding is a particular pattern
doubling time. Because of its slow growth rate, it may be
of calcification. Calcification is more common in benign
missed by PET scan.49 Bronchoalveolar carcinoma may pres-
lesions than in malignant tumors. Four patterns of calcifica-
ent as an SPN, particularly with a ground-glass appearance,
as airspace disease, or as multiple nodules. tion are considered benign: central, diffuse, laminated, and
“popcornlike.” The first three patterns are most commonly
Small Cell Lung Cancer associated with an infectious condition (e.g., histoplasmosis
Small cell carcinoma accounts for approximately 20% of or tuberculosis). The popcornlike pattern, however, indicates
lung cancers. Typically, it presents as a central mass in that the lesion is probably a hamartoma. Unfortunately,
association with significant nodal disease, often accompanied calcification is present in only about 50% of benign lesions,
by distant metastases.78 Small cell carcinoma typically has a and only about 50% of hamartomas are calcified.31 It is
very short doubling time. Paraneoplastic syndromes are more important to remember that pulmonary carcinoid tumors and
common with small cell lung cancer than with NSCLC. metastases to the lung (especially those from osteosarcomas,
chondrosarcomas, or synovial cell sarcomas) may also have
Pulmonary Carcinoid Tumor calcifications. Another reliable marker of a hamartoma is the
Pulmonary carcinoid tumors are uncommon neuroendo- finding of fat within the lesion on a CT scan; however, fewer
crine neoplasms that account for 1 to 2% of lung cancers.79 than 50% of hamartomas demonstrate this characteristic.
They are classified as either typical or atypical, depending on PET scanning, particularly the correlation between PET
their histology, but represent a spectrum of neuroendocrine and CT findings on PET-CT, has been suggested as a useful
tumors.80 Either type of carcinoid may present as an SPN, diagnostic tool.85
usually in the fifth or sixth decade of life. Typical carcinoid
Inflammatory Nodules
tumors have a very long doubling time—up to 80 months—
and thus may be mistaken for benign lesions.81 Atypical Sarcoidosis is known as the great mimicker, but it rarely
carcinoid tumors have a much shorter doubling time and are presents as an SPN.86 Most commonly, it presents as hilar
more likely to show an increase in size on serial CT scans. and mediastinal lymphadenopathy and diffuse parenchymal
Typical carcinoid tumors have an extremely low incidence involvement. When it does present as an SPN, it is almost
of recurrence and are not usually associated with nodal invariably a solid lesion, hardly ever a cavitary one. The inci-
metastasis. dence of sarcoidosis is highest in African-American women
between 20 and 40 years of age. If sarcoidosis is suspected
Metastatic Malignancies during the evaluation of an SPN, an elevated angiotensin-
Metastases to the lung frequently appear as smooth, round, converting enzyme level supports the diagnosis, but a normal
well-demarcated lesions. They often are multiple, tend to be level does not exclude it. If a biopsy is performed, the pres-
found in the better vascularized lower lung zones, and rarely ence of noncaseating granulomas on pathologic evaluation
are associated with mediastinal adenopathy. Most pulmonary helps establish the diagnosis. If a diagnosis of sarcoidosis is
metastases derive from the lungs, the colon, the testicles, suspected, PET scanning has been suggested as an effective
the breasts, melanomas, or sarcomas. Treatment tends to be method to identify extrathoracic sites of disease to target for
palliative, based on the diagnosis of the primary tumor, but pathologic confirmation.87
it may be curative in cases of metastatic sarcoma or testicular Pulmonary rheumatoid nodules are present in fewer than
carcinoma. In patients with these cancers, limited wedge 1% of patients with rheumatoid arthritis.88 They are usually
resection of a metastasis to the lung has been shown to confer associated with rheumatoid nodules in other parts of the
a survival advantage; this measure may also be beneficial for body but may precede any systemic manifestations of the
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disease. Pulmonary rheumatoid nodules, although generally patient exhibits systemic manifestations of amyloidosis, the
asymptomatic in themselves, arise from underlying rheu- diagnosis can be confirmed only by biopsy of the nodule.42
matoid activity. When the underlying disease is active, the Rounded atelectasis usually presents as a pleura-based
nodules may grow, simulating malignancy. An elevated serum nodular density that occurs secondary to pleural scarring and
rheumatoid factor level is typical and helps confirm the thickening. An effort should be made to look for associated
diagnosis. pleural plaques resulting from asbestos exposure. The CT
Wegener granulomatosis is a necrotizing vasculitis that scan usually demonstrates an SPN with a “comet tail.” Biopsy
affects both the upper and the lower respiratory tract, as well is not required unless mesothelioma is strongly suspected or
as the kidneys. It presents with an SPN in approximately 20% the SPN is seen to have grown on successive CT scans.
of patients.89 If vasculitis is suspected during evaluation of
an SPN, laboratory studies should include testing for cyto-
plasmic antineutrophil cytoplasmic antibodies (c-ANCAs); Management
a positive result on this test is highly suggestive of Wegener The ACCP attempted to provide evidence-based guide-
granulomatosis. Treatment includes the cytotoxic drug lines to direct the evaluation of patients with SPNs 8 to
cyclophosphamide, either alone or in combination with 10 mm in diameter in their 2007 consensus statement.39
corticosteroids. Unfortunately, few, if any, randomized controlled trials exist
to direct management. Most clinicians rely on a combination
Infectious Nodules
of single-institution studies, a few prospective trials, and clin-
An SPN can also represent an infectious granuloma caused ical acumen to assess a given patient’s risk profile to inform
by tuberculosis, atypical mycobacterial diseases, histoplas- decisions on invasive and noninvasive testing. The initial step
mosis, coccidioidomycosis, or aspergillosis. Such granulomas in decision making is to confirm that the lesion is, in fact,
frequently have a cavitary appearance on CT scans. Occa- new, and to compare current chest x-rays or CT scans with
sionally, a chest x-ray taken with the patient in different any previous images that are available. An SPN whose size
positions shows shifting of the position of the cavity’s con- has been stable for 2 years on diagnostic images will be benign
tents or a crescent of air around the mass (the Monod sign).90 90 to 95% of the time. If no previous images are available for
This radiographic finding is characteristic of a mycetoma,
comparison, the patient should undergo a clinical evaluation
usually aspergilloma. Depending on the circumstances—in
to determine their risk profile. This evaluation must be
particular, on whether there has been significant hemoptysis
individualized according to the characteristics of the patient
and whether pulmonary function is reasonably well pre-
and the lesion. On the basis of the patient’s age, exposure and
served—many of these lesions are best treated with resection.
smoking history, the size of the SPN, and the characteristics
Others are best diagnosed by noninvasive techniques and
of the lesion’s borders, an SPN for which no previous
treated with antimicrobial therapy.
diagnostic images are available can be initially classified
Pulmonary dirofilariasis is a rare but well-attested cause of
as having a low, intermediate, or high probability of cancer
SPNs that is the consequence of infestation of human lungs
[see Table 3].7,95,96 This classification governs the subsequent
by the canine heartworm Dirofilaria immitis. This organism is
workup. Whereas a patient with a high-probability SPN needs
transmitted to humans in larval form by mosquitoes that have
ingested blood from affected dogs.91 Because humans are not a complete evaluation progressing toward resection with min-
suitable hosts for this organism, the larvae die and embolize imal delay, the same strategy would not be cost-effective for
to the lungs, where they initiate a granulomatous response. a patient with a low-probability SPN. It is important not to
Typically, these lesions are pleura based, and the diagnosis is subject a patient with a high-probability SPN to studies that
made at the time of resection.92 Once the diagnosis is made, will not change clinical management or outcome: doing so
no further therapy is required. will delay diagnosis and treatment unnecessarily.
Echinococcosis is a hydatid disease caused by the tape- At this point in the evaluation, if the nature of the SPN is
worm Echinococcus granulosus. It is endemic to certain areas still indeterminate and the lesion is larger than 1 cm, there
of the world where sheep and cattle are raised. Normally, it may be a role for PET or PET-CT scanning. If PET scanning
is ingested incidentally; the parasite penetrates the bowel wall yields negative results, the SPN is likely benign, and follow-
and travels to the lungs in 10 to 30% of cases.93,94 A complete up CT scanning is appropriate. If PET scanning yields
blood count usually demonstrates peripheral eosinophilia. If positive results and the patient is at high surgical risk, TTNB,
echinococcosis is suspected, a hemagglutination test, which bronchoscopy, or guided bronchoscopy may be performed to
has a sensitivity of 66 to 100% and a specificity of 98 to 99%
for Echinococcus, should be performed. TTNB should not be
performed because there is a risk that cyst rupture triggers an Table 3 Initial Assessment of Probability of Cancer in
Solitary Pulmonary Nodule
anaphylactic reaction to the highly antigenic contents. Patients
may be treated with anthelmintic agents, but the incidence of Characteristics Probability of Cancer
persistent or recurrent disease is high. Accordingly, surgical of Patient or
Lesion Low Intermediate High
resection should be considered.
Patient age (yr) < 40 40–60 > 60
other considerations
Patient smoking Never < 20 pack-yr g20 pack-yr
Pulmonary amyloidosis may present in either a diffuse or history smoked
a nodular form. The prognosis is most favorable when it Lesion size (cm) < 1.0 1.1–2.2 g2.3
presents as an asymptomatic SPN. Typically, the nodule is
well defined and between 2 and 4 cm in diameter. Unless the Lesion margin Smooth Scalloped Spiculated
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establish a diagnosis. If, however, the patient is at reasonable be benign. If the lesion has grown visibly between scans, it is
surgical risk, proceeding directly to VATS resection (and, probably malignant, and proceeding with resection for diag-
potentially, to lobectomy) offers the best chance of cure for a nosis and treatment is appropriate. The likelihood that nodal
probable carcinoma. metastases will develop in a closely followed SPN smaller
For patients with SPNs smaller than 1.0 cm, the optimal than 1.0 cm is low.73 If the SPN proves to be malignant,
approach may be to perform serial CT scanning at an initial scanning at 3-month intervals is unlikely to alter the eventual
3-month interval for a minimum of 2 years. The rationale outcome. Society guidelines continue to be refined in an
for this approach is based on the difficulty of identifying effort to provide helpful recommendations.
these lesions with VATS, the low likelihood of establishing a
diagnosis with TTNB, and the possibility that the lesion may Financial Disclosures: None Reported.
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4 THORAX 6 PARALYZED DIAPHRAGM — 1
6 PARALYZED DIAPHRAGM
Matthew O. Hubbard, MD, Raymond P. Onders, MD, FACS, and Philip A. Linden, MD, FACS*
Diaphragmatic dysfunction may be unilateral or bilateral, muscles of inspiration more, may experience dyspnea in the
with symptoms ranging from dyspnea only on extreme supine position and related sleep disturbances with daytime
exertion to ventilator dependence. The etiology, treatment, fatigue, and may suffer from chronic respiratory failure.
and prognosis are quite different in unilateral and bilateral Infants and young children depend on the diaphragm to
paralysis. A paralyzed hemidiaphragm may occur in isolation achieve adequate vital capacities because they have a more
or as part of a systemic disease, whereas bilateral diaphrag- compliant chest wall, weaker accessory muscles of respira-
matic paralysis usually occurs as result of a traumatic or tion, and a more mobile mediastinum than adults. Unilateral
neuromuscular degenerative process. The symptoms related paralysis may cause severe respiratory compromise requiring
to a paralyzed diaphragm are explained by both the loss of mechanical ventilation; bilateral diaphragmatic paralysis
muscular action of the diaphragm in respiration and the loss almost always requires prompt ventilator support.
of anatomic domain between the thorax and abdomen.
Unilateral dysfunction usually results from transection,     
bruising, stretching, or manipulation of one of the phrenic The most common causes of diaphragmatic paralysis are
nerves. A paralyzed hemidiaphragm may restrict a patient’s listed in Table 1. The most common causes of unilateral
vital capacity by almost 20% in a seated position and up to paralysis are neoplastic invasion, idiopathic, and iatrogenic.
40% in a supine position. Compression of the lower lobe of Malignancies account for roughly one third of cases of
the lung may result in ventilation-perfusion mismatch. A diaphragm paralysis. Neoplasms of bronchogenic origin are
small but significant reduction in the arterial oxygenation most common, although malignancies of the mediastinum,
may be seen, although hypercarbia is usually not present.1 including thymomas, lymphomas, and germ cell tumors, can
These alterations are usually well tolerated in a young, healthy also result in interruption of the phrenic nerve input to the
patient, with the sole symptom being dyspnea on exertion. A diaphragm. The phrenic nerve can be damaged by either
patient at the extremes of life (early childhood or late adult- direct mediastinal invasion of a tumor or metastasis of a
hood) or suffering from underlying lung diseases, obesity, or tumor to the mediastinal lymph nodes with subsequent lymph
other systemic disorders may be more adversely affected by node enlargement. Overall, only about 10% of patients with
unilateral diaphragmatic paralysis. unexplained diaphragmatic paralysis will regain function of
Bilateral dysfunction may be attributable to central nervous the diaphragm.3
system disorders (central hypoventilation resulting in dimin- Phrenic nerve damage can occur during thoracic and cervi-
ished central triggering of the diaphragms), diffuse nerve cal surgery as well as during cervical vein catheter insertion
dysfunction (disorders such as amyotrophic lateral sclerosis and has even been described as a result of cervical chiroprac-
[ALS]), or spinal cord injury (SCI) above C5. Bilateral paral- tic manipulation. Injury to the phrenic nerve during cardiac
ysis causes more severe respiratory symptoms than unilateral surgery has fallen dramatically with the transition from topi-
paralysis. Vital capacity can be reduced 45 to 50% from pre- cal ice slushes to cooling jackets but still may occur as a result
dicted in patients with bilateral paralysis.2 Arterial hypoxemia of stretching, compression, or sectioning. The use of cautery
can be seen as a result of ventilation-perfusion mismatches at during high dissection of the internal mammary artery near
the lung bases, and hypercarbia may result from a decrease the first rib may also injure the nerve. Patients with an
in tidal volume and minute ventilation. Assisted ventilation elevated hemidiaphragm on chest radiographs at the time of
(either noninvasive or invasive) is usually required. discharge after cardiac surgery have a 20% chance at 1 year
Clinical Evaluation Table 1 General Causes of Unilateral and Bilateral

Diaphragmatic Paralysis
 Neoplasm invasion
In adults with a paralyzed hemidia- Phrenic nerve injury: surgical section or stretching, cooling,
chiropractic cervical manipulation, cervical venipuncture, birth
phragm, the most common complaint
trauma, cervical disk surgery, blunt or penetrating chest
is typically dyspnea on exertion. Often trauma
there are no symptoms at rest. Neuritis: brachial neuritis, herpes zoster infection,
Bilateral diaphragmatic paralysis results in more severe mononeuritis multiplex, paraneoplastic neuritis
symptoms than unilateral paralysis, resulting in profound CNS or spinal cord disorders: neuralgic amyotrophy, stroke,
multiple sclerosis, rhizotomy, infantile spinomuscular atrophy,
respiratory compromise. Patients depend on accessory
Arnold-Chiari malformation, syringomelia
Nerve compression: cervical spondylosis, mediastinal lymph
* The authors and editors gratefully acknowledge the contribu- node enlargement, substernal goiter
tions of the previous authors, Bryan F. Mayers, MD, FACS, Miscellaneous: diabetes mellitus, carbon monoxide poisoning,
upper abdominal surgery, liver transplantation
and Benjamin D. Kozower, MD, to the development and
writing of this chapter. CNS = central nervous system.
DOI 10.2310/7800.2049
12/10
Evaluation of Elevated Hemidiaphragm
Patient presents with elevated hemidiaphragm on chest x-ray
Obtain clinical history:

• Previous operations (iatrogenic phrenic nerve injury)
• Malignancy involving phrenic nerve
• Respiratory symptoms (exertional dyspnea, cough, difficulty in sleeping)
• GI symptoms (dysphagia, dyspepsia)
• Cardiac symptoms (dysrhythmia)
Perform physical examination:
• Auscultation for decreased breath sounds
• Percussion to assess diaphragmatic excursion
Order investigative studies:

• Inspiratory and expiratory chest x-ray (to confirm elevated
hemidiaphragm)
• Fluoroscopy and sniff test (to distinguish diaphragmatic
paralysis from weakness)
• Cervical phrenic nerve stimulation (to clarify diagnosis in
patients on mechanical ventilation when sniff test is
inconclusive—rarely necessary)
Patient is asymptomatic or has only Patient has significant symptoms (e.g., dyspnea,
mild symptoms recurrent pneumonia, chronic bronchitis, chest pain,
poor exercise tolerance, cardiac dysrhythmia, or functional
Treat conservatively: gastric disorder)
• Physical therapy
• Pulmonary rehabilitation Order further tests as required:
• Weight loss • Pulmonary (pulmonary function tests)
• Consider enrollment in trial of unilateral • Cardiac (ECG, echocardiography)
diaphragmatic pacing • GI (gastric motility study)
Treat surgically with diaphragmatic plication (open or thoracoscopic).
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of continued diaphragmatic dysfunction. Injury can occur

during dissection of mediastinal vessels during lobectomy.
Typically, this is more common on the right than the left (the
phrenic nerve courses closer to the hilum on the right than
on the left) and may be more commonly injured after upper
lobectomies than lower (the nerve courses closer to the supe-
rior pulmonary vein than the inferior vein). The phrenic
nerve is at risk during a supraclavicular (or scalene) lymph
node biopsy as it courses directly anterior to the anterior
scalene muscle. The phrenic nerve is also at risk during
thymectomy as perithymic tissue often extends bilaterally
near both phrenic nerves. If one nerve is invaded by a
thymoma, it should be resected en bloc with the thymoma
provided that the other nerve is healthy and can be spared.
Cautery should generally be avoided within 1 cm of the
phrenic nerve. Typically, morbidity surrounding injuries to
the phrenic nerves is minimal. Exceptions to this, however,
are in pediatric patients undergoing open heart surgery,
patients post–lung transplantation, and those adult patients
with preexisting respiratory compromise. This may result in
a failure to wean from mechanical ventilation after surgery.
 
At rest, adult patients with a paralyzed diaphragm may
Figure 1 Chest radiograph showing left diaphragmatic
appear asymptomatic or have the nonspecific complaints paralysis in a breast cancer patient with malignant
discussed above. On physical examination, diminished breath adenopathy involving the left phrenic nerve near the left main
sounds are heard on the affected base, with decreased excur- pulmonary artery.
sion of the diaphragm noted on percussion. Paradoxical
inward motion of the ipsilateral abdominal wall may also be
seen.4 for paralysis. This test may be unobtainable in patients with
A patient with bilateral diaphragmatic paralysis is much severe weakness or on mechanical ventilation.5
more likely to become symptomatic, complaining of the Ultrasound evaluation can also be used to evaluate
symptoms above, and is also subject to the neurologic or suspected diaphragmatic paralysis and may be slightly more
neuromuscular complaints related to the underlying etiology. sensitive than fluoroscopy.6 Using ultrasonography, a para-
Physical examination almost always reveals significant use of lyzed diaphragm fails to increase in thickness during inspira-
accessory inspiratory muscle use. Tachycardia and tachypnea tion compared with a normally functioning diaphragm. This
are usually present. Characteristically, paradoxical inward was seen in single patients comparing paralytic hemidia-
movement of the abdominal wall is seen with inspiration.4 phragms with the contralateral leaflets and also comparing
experimental and control patients. Rarely, equivocal noninva-
Investigative Studies sive testing may be augmented with phrenic nerve stimulation
with electromyographic measurement of nerve latency; this
Diaphragmatic paralysis is usually
may be helpful with patients being supported by mechanical
discovered following an inspiratory
ventilation.7
chest radiograph, which may demon-
strate an elevated diaphragmatic
dome with sharpened and deepened Management
costovertebral and costophrenic sulci
[see Figure 1]. With left-sided paralysis, the stomach may   
rotate with the greater curvature facing cephalad and showing 
two fluid levels corresponding to the inverted fundus and Surgical treatment of diaphrag-
body.4 matic paralysis should be reserved
Fluoroscopy or ultrasonography can be used for functional for patients with moderate to severe
evaluation of the diaphragm in patients with suspected paral- symptoms of respiratory compromise. Adult patients with
ysis. Elevation of the diaphragm above the normal range, mild symptoms, such as dyspnea on exertion, would benefit
paradoxical movement with inspiration (especially while from conservative treatment focusing on physical therapy,
sniffing, the “sniff test”), and a mediastinal swing during pulmonary rehabilitation, and weight loss.
respiration may all be seen. All of these findings may also be The standard treatment of diaphragmatic paralysis is plica-
seen in other respiratory ailments and require a good deal of tion of the affected diaphragm, first performed by Bisgard in
judgment to evaluate. The “sniff test,” rapidly inhaling with 1947 to treat congenital eventration of the diaphragm in an
a closed mouth, should show a paradoxical upward motion of infant with respiratory distress. Several descriptions of plica-
the diaphragm of at least 2 cm to be considered a positive test tion of the diaphragm exist in the literature for diaphragmatic
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paralysis and eventration, varying in suture placement and a transabdominal and transthoracic approach.9 This proce-
surgical approach. Developments in phrenic nerve repair and dure allows for protection of the phrenic nerve branches and
diaphragm pacing (DP) have emerged in recent years. vessels. This has also been described through a thoracoscopic
approach in children and adults: a three-port technique using
    anterior and posterior thoracic ports at the sixth and eighth
A posterolateral incision at the seventh or eighth intercostal interspaces, respectively, for plication, and a subcostal port
space provides access to the thoracic cavity for a plication used for grasping and displacing the central tendon of the
procedure. Four to six parallel rows of nonabsorbable suture diaphragm through the abdomen.10
with pledgets should be placed in an anteroposterior orienta- A study of plication in 17 patients (16 men, one woman),
tion within the central tendon of the diaphragm. Ideally, with an average age of 54 years, showed subjective improve-
these sutures should not strike the phrenic vessels and ment in dyspnea score, as well as objective improvement in
nerve branches. The phrenic vessels often course under the FVC, TLC, and FRC, as well as arterial oxygenation, at
diaphragm and are not visible from above [see Figure 2]. 6 months.11 These results were maintained in the six patients
Thoracoscopic approaches to diaphragmatic plication who were followed for more than 5 years. A different study
have been described. One study of 25 patients undergoing of 15 patients with a mean follow-up of 10 years after
video-assisted thoracoscopic diaphragm plication showed plication showed continued improvement in FVC, FEV1,
that forced vital capacity (FVC), forced expiratory volume FRC, and TLC by 11.8%, 15.4%, 26%, and 13.3%,
at 1 second (FEV1), functional residual capacity (FRC), respectively.12
and total lung capacity (TLC) improved by 17%, 21.4%, Infants and children who suffer from diaphragmatic paraly-
20.3%, and 16.1%, respectively, at 6 months.8 Symptomatic sis are much more susceptible to respiratory compromise.
dyspnea also improved, and 17 patients were able to return These children are much more likely to require mechanical
to work. ventilation and to be exposed to the complications therein.
Radial plication of the muscular portion of the diaphragm, Diaphragmatic plication has been shown to be an effective
avoiding the mediastinal pleura, has been described through means to wean children from mechanical ventilation.13
Figure 2 Several parallel rows of sutures are placed in the muscular portion and central tendon of the diaphragm and tied with
the aid of a knot pusher. A pledget should be placed at the ends of the suture if the diaphragm is thinned.
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     ventilation in 145 subjects with ALS showed a decreased
Some cases of diaphragmatic paralysis result from trau- respiratory decline and improved survival with pacing.19 After
matic or iatrogenic severing of the phrenic nerve. Case reports conditioning the diaphragm with the DP, the rate of decline
of direct repair of the phrenic nerve using microsurgery in FVC fell from 2.62% per month to 1.25% per month.
techniques have been described in adults and children by Respiratory compliance increased 18% from improving
posterior lobe ventilation.
end-to-end anastomosis and sural nerve graft techniques; an
The use of DP for the treatment of ventilator dependence
improvement in diaphragmatic function occurred as early as
following iatrogenic diaphragmatic paralysis is currently
6 months after surgery.14 Repair of the phrenic nerve can be
under sporadic investigation
performed for simple transection, whereas sural nerve graft-
ing is used for replacement of phrenic nerve segments that Surgical Technique of Laparoscopic Diaphragm Pacing
were resected en bloc with tumor. There are no reports of For DP to be effective, the phrenic nerve must be intact
nerve repair in large numbers of patients. and able to provide intramuscular conduction pathways.
  Unfortunately, many patients with tetraplegia have sustained
injury to the phrenic motor neurons in the spinal cord and/or
Indications for Diaphragm Pacing phrenic rootlets. Prior to implantation, an assessment of
Direct phrenic nerve pacing and intramuscular DP phrenic nerve function should be performed. In patients with
systems were designed to replace or delay the need for patients ALS or central hypoventilation, fluoroscopy of the diaphragm
requiring long-term positive pressure mechanical ventilation can also be done to see that volitional diaphragm movement
via tracheostomies. In the 1980s, Mortimer and colleagues is intact, commonly referred to as a sniff test.
showed that the diaphragm could be directly stimulated Paralytic agents cannot be used during the pacer insertion
at the motor point (area of phrenic nerve insertion) of the procedure as the diaphragm has to be stimulated during the
diaphragm to provide ventilation.15 operation. The surgery is described in four phases: exposure,
The initial clinical indications for phrenic nerve or DP have mapping, implantation, and routing. The exposure consists
been cervical SCIs and congenital central hypoventilation of the setup for the standard laparoscopy with the initial port
syndromes. SCI involves the disruption of the signal pathway supraumbilical for adequate visualization of the diaphragm.
Two lateral subcostal 5 mm ports are placed for the mapping
from the respiratory center in the brain to the respiratory
probe for each side, and these are used initially to completely
nerves (primarily the phrenic nerves), whereas central
divide the falciform ligament, which allows easier visualiza-
hypoventilation syndromes generally involve a decreased
tion of the medial aspect of the right diaphragm and easier
respiratory drive. Central hypoventilation is a rare diagnosis,
exit of the pacing electrodes through a 12 mm epigastric
affecting one in 50,000 live births; these children require
port. The epigastric port is used for the diaphragm implant
permanent nighttime positive pressure ventilation unless
instrument.
phrenic nerve pacing is possible.
Mapping involves finding the point on the abdominal
Of 11,000 new SCIs each year in the United States, slightly
side of the diaphragm where stimulation causes the greatest
more than half are affected by quadriplegia, with only 4%
diaphragm excursion. The mapping instrument has flexible
requiring long-term mechanical ventilation. In a prospective
tubing inside a rigid cannula that connects to the operating
worldwide trial of DP in this group, 50 patients were
room suction. The working part of the mapping instrument
implanted.16 The average age was 36 years (range 18 to has a circular electrode that can be stimulated when tempo-
74 years), and the time from injury to implantation was rarily attached to the diaphragm by the suction [see Figure 3].
5.6 years (range 0.3 to 27 years). Ninety-eight percent of the Stimulation is applied in either a twitch or burst mode from
patients had DP-stimulated tidal volumes above 5 to 7 cc/kg the clinical station through a connecting cable. Mapping
for 4 or more continuous hours, with 50% using DP for con- allows qualitative and quantitative data to be obtained.
tinuous 24-hour ventilation. Age and time from injury directly Quantitatively, changes in abdominal pressures are measured.
affect the conditioning time needed to achieve independent Qualitatively, observation of the diaphragm contraction is
ventilation, with younger and more recently injured patients performed. The stronger the stimulated contraction, the
weaning from the ventilator faster.17 In a long-term analysis closer the mapping probe is to the motor point of the
of 24 patients, 60% reported fewer secretions, and 95% diaphragm. The primary electrode site is identified at the
reported greater freedom and independence. This multicenter location of maximal pressure change in each hemidiaphragm.
trial led to approval by the Food and Drug Administration in A secondary electrode site is identified as either a backup
June 2008. to the primary site or at a location in each hemidiaphragm
DP is used in patients with ALS (Lou Gehrig disease), that recruits another region (e.g., anterior, lateral, or poste-
where respiratory insufficiency is the major cause of mortal- rior) of the diaphragm at a similar magnitude. On the right
ity. There is a significant risk of impending respiratory failure diaphragm, the motor point is just lateral to the central
and death when FVC falls below 25 to 30%.18 In this group tendon, and on the left diaphragm, the motor point tends to
of patients, the goal is to delay the need for mechanical ven- be much more lateral because the phrenic nerve travels on the
tilation by implanting the DP and stimulating the muscle to lateral aspect of the pericardium and enters the diaphragm
maintain diaphragm strength prior to end-stage weakness. more laterally.
The results of a multicenter prospective trial comparing Once the primary and secondary electrode sites are identi-
noninvasive ventilation with DP combined with noninvasive fied in each hemidiaphragm, the implantation phase begins.
12/10
electrodes will be tunneled subcutaneously to an area in the

upper chest or abdomen at a site deemed appropriate by
the surgeon and patient’s caregivers. An additional indifferent
electrode will be placed subcutaneously through a separate
percutaneous exit site.
Electrode evaluation is performed by adjusting individual
stimulus parameters (amplitude, pulse width, rate, and fre-
quency) so that a comfortable level of stimulation can be
identified for the diaphragm conditioning sessions. The DP
system will be set to provide a tidal volume that provides 15%
above the basal needs (5 to 7 cc/kg) and that the patient can
easily tolerate. For SCI patients and for ALS patients, the
highest setting that causes no discomfort will be used.
ALS patients begin conditioning by pacing five 30-minute
sessions a day. Continuous positive airway pressure (CPAP)
or noninvasive ventilation may still be needed to maintain an
upper airway and can be used in conjunction with the DP
Figure 3 A laparoscopic mapping probe is being held onto system. A weaning program for SCI patients is begun where
the left diaphragm with suction and receives electrical stimuli the DP unit is turned on and the ventilator is turned off. The
from an external clinical station. The blue marks were placed patients are placed back on the ventilator when they feel
at the locations of the strongest contractions. uncomfortable or if their tidal volumes start dropping because
of diaphragm fatigue. Initially, patients may tolerate only
15 minutes of DP. If the DP system is implanted early after
an SCI, the patient can be rapidly transitioned from the
An intramuscular electrode is introduced into the abdominal mechanical ventilator to DP. Figure 5 shows the system
cavity with the electrode delivery instrument. The implant attached to a pediatric patient for whom weaning will be
instrument needle is inserted into the diaphragm at an started the day of surgery. The diaphragm can recover quite
angle so that the electrode lead travels parallel to the plane of rapidly from training, so patients and their caregivers can
the diaphragm prior to exit, and the delivery instrument is repeat a session every hour. The length of time it takes to go
withdrawn [see Figure 4]. The electrode is then tested to more than 4 continuous hours depends on the amount of
ensure that the desired response to twitch stimuli is achieved, time the patient and caregivers devote to this process.
and if the response is not adequate, the electrode may be The future application for temporary use in the intensive
withdrawn and another implanted. Once all four electrodes
care unit (ICU) has some excellent theoretical possibilities,
are implanted, they are brought out through the epigastric
but well-designed trials will need to be done to identify the
port, keeping the right and left sides separated. Excess elec-
actual role of DP in the ICU.
trode length is kept in the abdomen on top of the liver. The
Financial Disclosures: Dr. Raymond P. Onders has received
research grants from Synapse Biomedical Inc, Oberlin, OH.
Figure 4 The electrode implant device houses the electrode

in the needle and is placed into the diaphragm tangentially. Figure 5 The diaphragm pacing system has already been
Countertraction can be applied by a second instrument to programmed for conditioning and is attached via percutane-
help deploy the electrode, which has a small barb on the end ously placed diaphragm electrodes in this spinal cord–injured
of it. child for early conditioning and weaning from the ventilator.
12/10
References
1. Clague HW, Hall DR. Effect of posture on 8. Freeman RK, Wozniak TC, Fitzgerald EB. restoration of diaphragmatic function. Chest
lung volume: airway closure and gas exchange Functional and physiological results of video- 1983;84:642–4.
in hemidiaphragmatic paralysis. Thorax assisted thoracoscopic diaphragm plication 15. Peterson DK, Nochomovitz ML, DiMarco
1970;34:523–6. in adult patients with unilateral diaphragm AF, Mortimer JT. Intramuscular electrical
2. Molho M, Katz I, Schwartz E, et al. Familial paralysis. Ann Thorac Surg 2006;81:1853–7. activation of the phrenic nerve. IEEE Trans
bilateral paralysis of the diaphragm. Chest 9. Shoemaker R, Palmer G, Brown JW, et al. Biomed Eng 1986;33:342–51.
1987;91:466–7. Aggressive treatment of acquired phrenic 16. Onders RP, Elmo M, Khansarinia S, et al.
3. Piehler JM, Pairolero PC, Gracey DR, et al. nerve paralysis in infants and small children. Complete worldwide operative experience in
Unexplained diaphragmatic paralysis: a Ann Thorac Surg 1981;32:250–9. laparoscopic diaphragm pacing: results and
harbinger of malignant disease? J Thorac 10. Wiener DC, Jaklitsch MT. Surgery of the dia- differences in spinal cord injured patients and
Cardiovasc Surg 1982;84:861–4. phragm: a deductive approach. In: Selke FW, amyotrophic lateral sclerosis patients. Surg
4. Fraser RS, Muller NL, Colman N, Pare PD, del Nido PJ, Swanson SJ, editors. Sabiston & Endosc 2009;23:1433–40. [Epub 2008 Dec
editors. The diaphragm. In: Diagnosis of Spencer surgery of the chest. 7th ed. Philadel- 6].
diseases of the chest. 4th ed. Philadelphia: phia: Elsevier Saunders; 2005. p. 501–15. 17. Onders RP, Elmo MJ, Ignagni AR. Dia-
W.B. Saunders Company; 1999. p. 2987– 11. Graham DR, Kaplan D, Evans CC, et al. phragm pacing stimulation system for
3010. Diaphragmatic plication for unilateral dia- tetraplegia in individuals injured during
5. Alexander C. Diaphragm movements and phragmatic paralysis: a 10-year experience. childhood or adolescence. J Spinal Cord Med
the diagnosis of diaphragmatic paralysis. Clin Ann Thorac Surg 1990;49:248–51. 2007;30:25–9.
Radiol 1966;17:79–83. 12. Higgs SM, Hussain A, Jackson M, et al. 18. Benditt JO. Respiratory complications of
6. Houston JG, Fleet M, Cowan MD, et al. Long term results of diaphragmatic plication amyotrophic lateral sclerosis. Semin Respir
Comparison of ultrasound with fluoroscopy for unilateral diaphragm paralysis. Eur J Crit Care Med 2002;23:239–47.
in the assessment of suspected hemidiaphrag- Cardiothorac Surg 2002;21:294–7. 19. Onders R, Katirji B, So Y, et al. Multicenter
matic movement abnormality. Clin Radiol 13. Simansky DA, Paley M, Refaely Y, et al. study results of motor point stimulation for
1995;50:95–8. Diaphragm plication following phrenic nerve condidtioning the diaphragm of patients with
7. Wilcox P, Baile EM, Hards J, et al. Phrenic injury: a comparison of paediatric and adult amyotrophic lateral sclerosis/motor neuron
nerve function and its relationship to atelecta- patients. Thorax 2002;57:613–6. disease: preliminary trend toward slowed
sis after coronary artery bypass surgery. Chest 14. Merav AD, Attai LA, Condit DD. Successful respiratory decline and improved survival.
1988;93:693–8. repair of a transected phrenic nerve with Amyotroph Lateral Scler 2009;10:60–1.
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4 THORAX 7 OPEN ESOPHAGEAL PROCEDURES — 1
7 OPEN ESOPHAGEAL PROCEDURES

Cameron D. Wright, MD, FACS
The remarkable developments in diagnosis, imaging, and occult metastases that would preclude curative resection for
surgical treatment of esophageal diseases over the past 15 esophageal cancer.
years have resulted in markedly better patient outcomes, and Esophageal manometry, 24-hour esophageal pH testing,
the morbidity and mortality associated with surgery of the and nuclear studies for assessment of esophageal and gastric
esophagus have been substantially reduced. In particular, the transit provide functional data that can facilitate the diagnosis
operative techniques employed to treat esophageal disease and treatment of GERD, achalasia, and other disorders of
have advanced considerably as a result of the successful the esophagus. They are useful complements to standard
introduction of minimally invasive approaches to the esopha- investigations (e.g., ciné barium swallow and endoscopy).
gus. For a number of diseases (e.g., achalasia and routine Complete preoperative investigation of all patients, even
antireflux surgery), minimally invasive procedures have those with classic histories and physical findings, is manda-
proved to be as effective as their open counterparts while tory. The data from anatomic and functional testing allow
causing less postoperative morbidity. The growing stature of the surgeon to plan the operation more appropriately and
minimally invasive approaches does not, however, diminish effectively (e.g., deciding on the need for esophageal length-
the importance of the equivalent open approaches. In this ening in patients with paraesophageal hernias or choosing
chapter, we describe common open operations performed to between a complete and a partial fundoplication in patients
excise Zenker diverticulum, to manage complex gastroesoph- with hernias associated with varying degrees of esophageal
ageal reflux disease (GERD), and to resect esophageal and dysmotility).
proximal gastric tumors.
optimization of patient health status
Patients with obstructing esophageal diseases are often
General Preoperative Considerations
elderly, debilitated, and malnourished. Although months of
methods of patient assessment insufficient nutrition cannot be corrected in the space of a
few hours, anemia, dehydration, and electrolyte abnormali-
The functional results achieved with esophageal procedures
ties can be mitigated by means of intravenous support and
become more predictable when the approach to preoperative
appropriate laboratory monitoring. If esophageal obstruction
patient evaluation is precise and reproducible. The ciné
prevents oral intake, endoscopic dilation of the stricture,
barium swallow remains the most cost-effective method for
accompanied by either nasogastric intubation or percutane-
initial evaluation of esophageal anatomy and function. It
ous endoscopic gastrostomy (PEG), is often indicated; the
should be employed before endoscopy because the results
patient should then be able to resume at least a liquid diet.
may direct the endoscopist’s attention to particular areas
Caution should be used when addressing esophageal obstruc-
of concern. In addition, endoscopic examination alone is
tion in preoperative patients before induction therapy is given.
often insufficient for assessing esophageal motility disorders
Most surgeons prefer not to have a PEG tube placed in the
or defining the complex anatomy of a paraesophageal hiatal
stomach for fear of compromising its blood supply when an
hernia.
esophagectomy is planned. Alternative options include a
Endoscopic ultrasonography (EUS) is an extension of the
nasogastric tube, a jejunostomy tube, or total parenteral
visual mucosal examination. The information it can provide
nutrition. If weight loss has exceeded 10%, enteral nutrition,
about the extension of mass lesions beyond the confines of
comprising at least 2,000 kcal/day of a high-protein liquid
the esophageal wall is helpful in planning surgical resection.
diet, should be administered for at least 10 days before the
In addition, EUS can differentiate benign stromal tumors
operation. Cardiovascular, renal, hepatic, and respiratory
from cystic or malignant neoplasms on the basis of character-
function should be documented and optimized. If the patient
istic echogenicity patterns. EUS-FNA (fine-needle aspira-
is aspirating, the esophagus should be evacuated and the
tion) is used to confirm suspected nodal metastases seen
patient should be given nothing by mouth until after the
during the EUS examination. The combination of EUS and
operation. Aspiration pneumonia should always be corrected
computed tomography (CT) permits highly precise anatomic
preoperatively.
assessment of esophageal neoplasms, definition of the extent
of local invasion, and identification of regional metastases.
Functional imaging with photodynamic or vital staining Cricopharyngeal Myotomy and Excision of Zenker
allows accurate diagnosis of dysplastic or malignant mucosal Diverticulum
lesions in their earliest stages. Positron emission tomography
(PET) yields similar results by localizing metabolically preoperative evaluation
active tissue regionally or at distant sites. The combination of Patients who are candidates for cricopharyngeal myotomy
morphologic data from high-resolution CT and functional usually present with difficulty initiating swallowing, cervical
data from PET is particularly effective for identifying dysphagia, and a history of pulmonary aspiration. These
DOI 10.2310/7800.S04C07
02/10
symptoms of cricopharyngeal dysfunction may or may not be cartilage is palpated and marked. A 6 cm skin incision is
associated with a Zenker diverticulum. Ciné contrast studies made, either obliquely along the sternocleidomastoid muscle
may reveal poor pharyngeal contractility, pulmonary or nasal [see Figure 1] or transversely in a skin crease at the level of
aspiration, abnormalities of the upper esophageal sphincter, the cricoid. The platysma is divided in the same line. Self-
pharyngeal pouches, or other structural abnormalities in the retaining retractors are inserted. The anterior border of the
distal esophagus. Barium is the usual contrast agent as it is sternocleidomastoid muscle is incised throughout its length.
inert if aspirated. The omohyoid muscle and the sternohyoid and sternothyroid
Zenker diverticulum is a pulsion diverticulum that arises muscles are retracted [see Figure 2]. The sternocleidomastoid
adjacent to the inferior pharyngeal constrictor, between the muscle is retracted laterally to expose the carotid sheath
oblique fibers of the posterior pharyngeal constrictors and the and the internal jugular vein. The middle thyroid vein is
cricopharyngeus muscle. This mucosal outpouching results ligated and divided, and the thyroid gland and the trachea are
from a transient incomplete opening of the upper esophageal retracted medially by the assistant’s finger to minimize the
sphincter. The diverticulum ultimately enlarges, drapes over risk of injury to the underlying recurrent laryngeal nerve.
the cricopharyngeus, and dissects behind the esophagus There is no need to encircle the esophagus or to dissect in the
into the prevertebral space. The pouch usually deviates to tracheoesophageal groove. The deep cervical fascia is divided.
one side or the other; accordingly, the side on which the
The inferior thyroid artery is divided as laterally as possible.
deviation occurs must be determined by means of a barium
The carotid sheath is retracted laterally, and dissection is
swallow so that the appropriate operative approach can be
carried down to the prevertebral fascia [see Figure 2]. The
selected. Esophageal motility studies (not usually performed)
endoscope placed in the diverticulum is palpated, and the
may show either incomplete upper esophageal relaxation on
pouch is dissected away from the cervical esophagus up as far
swallowing or poor coordination of the upper esophageal
relaxation phase with pharyngeal contractions. Upper gastro- as the pharyngoesophageal junction. The flexible endoscope
intestinal (GI) endoscopy is performed preoperatively to exclude is then removed from the pouch and advanced into the
the presence of a pharyngeal or esophageal carcinoma and to thoracic esophagus so that it can be used as a stent for the
assess the upper GI anatomy. If there is evidence of GERD, cricopharyngeal myotomy. Dissection of the pharyngeal
proton pump inhibitors (PPIs) are given. pouch is then completed.
In symptomatic patients (e.g., those with dysphagia,
nocturnal cough, or recurrent pneumonia from aspiration),
surgical therapy is indicated regardless of whether a pouch is
present or how large it may be. Such treatment involves cor-
recting the underlying cricopharyngeal muscle dysfunction
with a cricopharyngeal myotomy. If there is a diverticulum
larger than 2 cm, it should be excised in addition to the cri-
copharyngeal myotomy. Alternatively, the diverticulum may
be managed via endoscopic obliteration of the common wall
between the pharyngeal pouch and the esophagus with either
a stapler or a laser. Cricopharyngeal incoordination may
be temporarily relieved by injecting botulinum toxin into the
cricopharyngeus.
operative planning
The patient is placed on a clear fluid diet for 2 days before
the operation. With the patient under general anesthesia,
the trachea is intubated with a single-lumen endotracheal
tube. Cricoid pressure is applied to prevent aspiration of
diverticular contents. A soft roll is placed behind the shoul-
ders to extend the neck. The patient is placed in a 20° reverse
Trendelenburg position, and the legs are wrapped with pneu-
matic calf compressors to prevent deep vein thrombosis
(DVT). With the endotracheal tube placed to the side of
the mouth, a preliminary flexible esophagogastroscopy is per-
formed to empty the diverticulum of all food and to examine
the esophagus and the stomach. The scope is then brought
back up into the oropharynx and moved into the pouch. The
location of the diverticulum (on the left or the right side) is
confirmed by turning off the room lights and noting which
side is transilluminated by the gastroscope. Figure 1 Cricopharyngeal myotomy and excision of Zenker
diverticulum. A soft roll is placed behind the shoulders to
operative technique extend the neck. The head is turned to the side opposite the
incision. The cricoid cartilage is palpated and marked. The
Step 1: Incision and Dissection of Pharyngeal Pouch
skin is incised obliquely along the sternocleidomastoid
The patient lies with the head turned away from the side muscle, as shown, or transversely in a skin crease at the level
on which the incision is made (usually the left). The cricoid of the cricoid.
02/10
laryngeal nerve. The stapler is fired, and the diverticulum is

excised. The staple line is cleaned with an antiseptic solution,
and the incision is filled with saline. The esophagus is insuf-
flated with air to determine whether mucosal leakage has
occurred, and the esophagoscope is removed; any mucosal
leaks found are closed with fine absorbable sutures. In the
absence of a stapler, the best way of excising the sac is to
make a series of short incisions through the neck of the
sac with scissors, suturing the edges after each cut with
absorbable monofilament sutures (the so-called cut-and-sew
technique). The esophagoscope ensures that the esophageal
lumen is not narrowed. If an esophagoscope is not used, then
a Maloney dilator (50 to 54 French) is used to ensure that
excessive esophagus is not removed.
Step 4: Drainage and Closure

Once hemostasis has been achieved, a short vacuum drain
is placed through the skin into the retroesophageal space.
The platysma is repaired with absorbable sutures, and the
skin is closed with a subcuticular absorbable suture. Nasogas-
tric intubation is unnecessary. Prokinetic agents and PPIs
Figure 2 Cricopharyngeal myotomy and excision of Zenker are administered to prevent gastroesophageal reflux. A
diverticulum. The sternocleidomastoid is incised along the water-soluble contrast study can be done the day after the
anterior border so as to expose the omohyoid muscle and the operation. If the results are normal, the patient is started
sternohyoid and sternothyroid muscles, which are retracted. on a liquid diet, the drain is removed, and the patient is
The thyroid gland and the trachea are retracted medially by discharged on liquids for 1 week.
the assistant’s finger, and the inferior thyroid artery is ligated
and divided laterally to avoid injury to the recurrent laryngeal complications
nerve.
The main complications associated with cricopharyngeal
myotomy are recurrent laryngeal nerve trauma (occurring in
Step 2: Myotomy 1% of cases), fistulas (1%), hematoma formation, infection
(2%), aspiration, and recurrence (4%). Hematomas and
The esophageal myotomy is started approximately 1 cm
infections must be drained promptly. Fistulas usually close
below the cricopharyngeus on the posterolateral esophageal
once the prevertebral space is drained and the associated
wall [see Figure 3a]. The esophageal muscle is divided
infection is controlled. Aspiration is the most serious compli-
down to the mucosa, which is recognizable from its bluish
cation after cricopharyngeal myotomy. Gastroesophageal
coloration with the submucosal plexus overlying it. The
reflux may contribute to oropharnygeal dysphagia. Division
esophageal muscle is dissected away from the mucosa with a
of the upper esophageal sphincter in a patient with an
right-angle dissector and divided with either a knife, scissors,
incompetent esophagogastric junction may lead to massive
or a low-intensity diathermy unit. The myotomy is then
tracheobronchial aspiration. Therefore, documented severe
continued proximally through the cricopharyngeus and up
gastroesophageal reflux, gastroesophageal regurgitation, and
into the muscular wall of the hypopharynx for 1 to 2 cm if no
severe distal esophagitis may be relative contraindications
diverticulum is present. The hypopharynx is distinguished by
a pronounced submucosal venous plexus. The muscle is then to cricopharyngeal myotomy until the lower esophageal
swept off the mucosa for 120°. sphincter defect has been remedied with an antireflux
operation.
Step 3: Freeing or Excision of Diverticulum
outcome evaluation
If there is a diverticulum less than 2 cm in diameter, the
cricopharyngeus is transected and the muscularis around Of patients with a Zenker diverticulum, at least 90% expe-
the diverticulum is freed. The myotomy is extended onto the rience excellent results from surgical treatment. Of patients
hypopharynx for 1 to 2 cm. The diverticulum is then sus- without a Zenker diverticulum, one third experience excellent
pended to the back wall of the pharynx to prevent food from results, another third show moderate improvement, and the
easily entering it. It should not be sutured to the prevertebral remaining third show no improvement.1 Patients with poor
fascia, because the passage of sutures through the diverticu- pharyngeal contractility in conjunction with normal upper
lum can contaminate the fascia or intervertebral disk, leading esophageal sphincter function show little improvement with
to an increased risk of infection. cricopharyngeal myotomy. Patients with oropharyngeal dys-
If the diverticulum is more than 2 cm in diameter, it is phagia secondary to neurologic involvement who have intact
excised with a linear stapler loaded with 2.5 mm staples, voluntary deglutination, adequate pulsion of the tongue,
which is placed at the base of the sac and pressed firmly and normal phonation may show improvement with crico-
against the esophagoscope [see Figure 3b]. Particular care pharyngeal myotomy. Appropriate selection of patients for
must be taken at this point so as not to injure the recurrent cricopharyngeal myotomy leads to better surgical outcomes.
02/10
Figure 3 Cricopharyngeal myotomy and excision of Zenker diverticulum. (a) The diverticulum is dissected away from the
esophagus, and an esophageal myotomy is started approximately 3 cm below the cricopharyngeus. The myotomy is continued
proximally through the cricopharyngeus, and the muscle around the diverticulum is freed. (b) A linear stapler is placed at the
base of the sac and pressed firmly against the esophagoscope. The stapler is fired, and the diverticulum is excised.
Transthoracic Hiatal Hernia Repair the esophagus, patients in whom the hiatal hernia coexists
Unlike most operations on the esophagus, which are extir- with an esophageal motility disorder or morbid obesity, and
pative procedures, hiatal hernia repair with fundoplication is patients who have undergone multiple previous abdominal
a reconstructive procedure, the aim of which is to restore a operations. The transthoracic repair is particularly useful
high-pressure zone at the esophagogastric junction that when a previous open abdominal procedure has failed. In this
prevents reflux but also permits comfortable swallowing. situation, the reasons for such failure, whether technical or
Currently, this repair is usually accomplished via minimally tissue related, should be assessed so that a compensatory
invasive approaches. The degree of tension on the hiatal strategy can be devised.
repair sutures, the length of the esophagus, the quality of the preoperative evaluation
crural tissue itself, and the caliber of the esophageal hiatus
after repair all must be assessed. In certain patients, laparo- Symptomatic Evaluation
scopic reconstruction of a competent gastroesophageal high- All patients being considered for fundoplication to treat
pressure zone may be very difficult and may demand a degree GERD must undergo a comprehensive evaluation to deter-
of skill not yet achievable by laparoscopy. The most common mine whether there is indeed an anatomic substrate for their
indications for transthoracic hiatus hernia repair are a failed symptoms and what the most appropriate form of repair is.
previous repair and a hostile abdomen. Specifically, a history of heartburn and effortless regurgitation
The long-term success of antireflux surgery, whether done should be sought. Dysphagia and odynophagia are not typi-
via the transthoracic approach or by means of laparoscopy, cally associated with hiatal hernia unless there is a significant
depends on three factors: (1) a tension-free repair that paraesophageal component. Persistent dysphagia may reflect
maintains a 4 cm long segment of esophagus in the intra- the presence of a stricture or a neoplasm. Reflux-induced
abdominal position, (2) durable approximation of the diaphrag- esophageal spasm may present with occasional episodes of
matic crura, and (3) correct matching of the fundoplication cervical dysphagia, but the transient nature of the symptoms
technique according to the peristaltic function of the esopha- easily differentiates this condition from dysphagia caused by
gus. The transthoracic approach should be considered when- a fixed obstruction. Chest pain that radiates toward the back
ever the standard abdominal approaches to hiatal hernia after meals and is relieved by nonbilious vomiting may indi-
repair carry an increased risk of failure or complication—for cate the presence of an incarcerated intrathoracic stomach
example, in patients who have a foreshortened esophagus that is hindering the emptying of the paraesophageal compo-
associated with a massive hernia and an incarcerated intra- nent. Atypical chest pain from cholelithiasis, peptic ulcer, or
thoracic stomach, patients with severe peptic strictures of coronary artery disease may confound the diagnosis.
02/10
Imaging or blood streaks appear on the dilator. Sudden pain during

Radiographic investigation should begin with a ciné barium dilation is an ominous sign and calls for immediate investiga-
swallow, which will yield valuable information regarding tion with a swallow study using a water-soluble contrast agent
the length of the esophagus, its peristaltic function, and the (e.g., Gastrografin, Schering AG, Berlin, Germany). Subcu-
integrity of the mucosal surface. The gastric views can be taneous emphysema in the neck or mediastinal air on a plain
used for qualitative assessment of distal emptying. Any para- chest radiograph may also indicate an injury to the esopha-
esophageal component will be clearly demonstrated, along gus. Perforation must be definitively ruled out before the
with any associated organoaxial volvulus. A simple barium patient can be discharged.
swallow often yields the most useful information for manag- Highly stenotic strictures that do not allow the passage
ing the complex problem of recurrent hiatal hernia and a of a standard adult endoscope may be associated with a
slipped Nissen fundoplication. distorted and a steeply angulated esophagus. In such cases,
Next, esophagogastroscopy should be performed to exam- the use of a pediatric endoscope may permit directed place-
ine the mucosa for the presence of esophagitis, Barrett ment of a guide wire through the stricture; fluoroscopy is a
mucosa, stricture, or malignancy. The locations of any lesions useful adjunct for this purpose. A series of progressively larger
observed, along with the position of the squamocolumnar Savary-Gillard dilators may then be passed over the guide
junction, should be carefully documented in terms of their wire to enlarge the lumen and allow subsequent endoscopic
distance from the incisors. All strictures must undergo cup biopsy. As a rule, less tactile feedback is available during
or brush biopsy to rule out an occult malignancy. The pres- wire-guided dilation than during passage of standard
ence of severe esophagitis raises the possibility of acquired Maloney-Hurst bougies. Increased pressure is required to
shortening of the esophagus secondary to transmural inflam- pass the Savary-Gillard dilators because of the resistance
mation and contraction scarring. Every effort should be made caused by the wire passing through the dilator itself. It is
to measure the length of the esophagus accurately. essential that the wire be well lubricated and not be allowed
to dislodge proximally between the sequential insertions of
Dilation progressively larger dilators. The caveats that apply to blind
If a stricture is found during esophagoscopy, a decision dilation also apply to wire-guided dilation.
must be made about whether to attempt esophageal dilation. Patients whose esophagus can be dilated to 48 French
This procedure carries the risk of perforation and should be and who are candidates for antireflux surgery may undergo
performed only after careful consideration. If the stricture is subsequent intraoperative dilation to 54 to 60 French.
diagnosed at the time of the initial endoscopic examination, Patients who cannot be dilated to 48 French and fail to
it is advisable to perform only the brush biopsy at this point, achieve comfortable swallowing should be classified as having
deferring dilation to a subsequent visit. Delaying dilation a nondilatable stricture and should be considered for trans-
gives the surgeon time to reassess the anatomy depicted on hiatal esophagectomy [see Resection of Esophagus and
the barium swallow, to decide whether wire-guided dilation Proximal Stomach, below].
is necessitated by angulation of the esophagus, to obtain
informed consent, to assemble the requisite equipment, and Functional Evaluation
to plan sedation for what is often an uncomfortable proce- Esophageal manometry permits quantitative assessment
dure. If a malignancy is suspected at the time of the initial of peristalsis, a capability that is critically important for
endoscopic examination, dilation should be avoided. In this determining which type of fundoplication is most suitable
situation, repair is impossible; thus, if iatrogenic perforation for reconstructing a nonoccluding high-pressure zone at the
of a malignant stricture occurs, the surgeon will have to esophagogastric junction. Stationary pH tests measure the
attempt emergency resection in an inadequately prepared capacity of the esophagus to clear acid, its sensitivity to
patient in whom proper staging is unlikely to have been instilled acid, the relation of reflux episodes to body position,
completed. and the correlation between changes in esophageal pH and
The standard flexible adult esophagoscope is approximately the subjective symptoms of heartburn. Ambulatory 24-hour
32 French in caliber. In advancing the scope into the stric- pH testing allows further quantification of reflux episodes
ture, only very gentle pressure should be necessary. As a rule, with respect to duration, frequency, and association with
a mild stricture that is not associated with steep angulation patient symptoms.
of the esophagus will readily accept passage of the endoscope
operative planning
and will be amenable to subsequent blind dilation with
Hurst-Maloney bougies. The transthoracic hiatus hernia repair may be completed
After successful passage, the scope is removed, and sequen- with either a partial fundoplication (as in the 240° Belsey
tial insertion of progressively larger dilators (starting at 32 Mark IV procedure) or a complete fundoplication (as in
French) into the stricture is attempted. The weight of the the 360° Nissen procedure). Acquired shortening of the
dilator alone should be sufficient to effect its passage, with esophagus may necessitate lengthening of the esophagus by
little or no forward force applied. Although the patient will means of a Collis gastroplasty, in which the portion of
be able to swallow comfortably only after satisfactory passage the gastric cardia along the lesser curvature and directly
of a dilator at least 48 French in caliber, it is essential never contiguous to the distal esophagus is fashioned into a tube
to try to force passage. To this end, the surgeon must take [see Operative Technique, Step 6a, below].
careful note of the subtle signs of increasing resistance A thoracic epidural catheter is placed for regional analgesia.
transmitted through the dilator. Sequential dilation should General anesthesia is administered, and flexible esophagos-
be stopped whenever significant resistance is encountered copy is performed by the operating team. Insufflation should
02/10
be done with as little air as is practical, particularly in the case

of large paraesophageal hernias. The extent of the pathologic
condition is documented, and the absence of malignancy is
verified. The stomach is decompressed with suction, and the
endoscope is removed. A nasogastric tube is placed while the
patient is supine.
Tracheal intubation is performed with a double-lumen
endotracheal tube. A Foley catheter is placed. Subcutaneous
heparin is administered for DVT prophylaxis, and pneumatic
calf compression devices are applied. Antibiotic prophylaxis
is provided.
The patient is positioned for a left thoracotomy. The table
is flexed to distract the ribs. The right leg is bent at the hip
and knee while the left leg is kept straight. Pillows are placed
between the legs, and all pressure points are padded. The
arms are positioned so that the humeri are at right angles to
the chest and the elbows are bent 90°.
operative technique
Step 1: Incision and Entry into Chest

A standard left posterolateral thoracotomy is performed.
The latissimus dorsi is divided. The serratus fascia is incised,
but the muscle itself can generally be preserved. For most Figure 4 Transthoracic hiatal hernia repair. The lung is
patients, the sixth interspace is the most appropriate incision retracted, and the inferior pulmonary ligament is divided to
site for exposing the hiatus. The seventh interspace can the level of the inferior pulmonary vein. The mediastinal
also be used, particularly if the patient is tall or has a hyper- pleura overlying the esophagus is incised to expose the
extended chest as a result of chronic pulmonary disease. The esophagus from the level of the carina to the diaphragm. The
esophagus and both vagi are encircled just below the inferior
paraspinal muscles are elevated away from the posterior
pulmonary vein with a Penrose drain. Vessels supplying the
aspect of the adjacent ribs, and a 1 cm segment of the rib esophagus and arising from the adjacent aorta are ligated and
below the selected interspace is resected to facilitate expo- divided.
sure. The chest is then entered, and the lung and the pleural
space are thoroughly inspected. The leaves of the retractor
are spread slowly over the course of the next several minutes right chest. This can generally be done with a small sponge
so as not to cause iatrogenic rib fractures. on a stick. If a tear occurs, it should be closed with absorbable
Step 2: Mobilization of Esophagus and Excision of Hernia Sac suture material to prevent accumulation of blood and fluid on
the right side during the operation.
The inferior pulmonary ligament is divided with the Dissection is continued inferiorly to expose the right and
electrocautery to the level of the inferior pulmonary vein left crura. The left crus is generally more robust and is certain
[see Figure 4]. The mediastinal pleura overlying the esophagus to be easily seen with this exposure. Its medial fibers may be
is longitudinally incised to expose the esophagus from the attenuated and may blend into the hernia sac superiorly. The
level of the carina to the diaphragm. Particular care is taken sac should be incised 1 cm above the muscle fibers because
to avoid injury to the vagi. Vessels supplying the esophagus the muscle alone will not hold sutures well for the subsequent
and arising from the adjacent aorta are cauterized and divided. repair. Skeletonization of the crural muscle must be avoided;
A few larger vessels may have to be ligated with 2-0 silk. The it is the fibroconnective tissue that provides the most tensile
esophagus is encircled just below the inferior pulmonary vein strength. The hernia sac is dissected away from the left
with a wide Penrose drain [see Figure 4]. The two vagi are crus in an anterior-to-posterior direction. The right crus is
mobilized and carried with the esophagus. (The right vagus generally less robust than the left. In the case of a previous
is located along the right anterior border of the descending failed repair, the right crus may be very difficult to see,
aorta and can easily be missed.) being obscured from the operator’s view by the intrathoracic
The esophagus is then elevated, and mobilization is stomach. Dissection of the right crus is best accomplished in
circumferentially completed in the direction of the diaphragm, a posterior-to-anterior direction.
starting from the level of the carina. In cases of giant para- Once the sac is circumferentially freed from the crura, dis-
esophageal hernia or reoperation for a failed repair, the stom- section proceeds cephalad along the esophagus. To minimize
ach will have a large intrathoracic component. Dissection the risk of vagal injury, the sac should be incised parallel to
continues inferiorly to separate the sac from the pericardium the esophagus.
anteriorly and the aorta posteriorly. The right pleura is closely
approximated to the esophagus for 2 to 5 cm above the Step 3: Division of Phrenoesophageal Membrane and
diaphragm; in the presence of a substantial hiatal hernia and Gastrohepatic Ligament
its sac, it may be difficult to identify. The right pleura should The esophagus is retracted anteriorly to expose the
be gently dissected away from the sac without entry into the posteriorly located phrenoesophageal membrane, which is
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then divided to yield entry into the lesser sac. The remainder
of the phrenoesophageal membrane is elevated with a right-
angle clamp as it courses anteriorly, yielding a view of the
spleen below. The esophagus and the stomach are thus com-
pletely mobilized from the left crus. The esophageal branch
of the left phrenic artery, visible near the left vagus, is divided
near the crus.
The uppermost portion of the gastrohepatic ligament is
found along the undersurface of the right crus. It is divided
with the electrocautery. The Belsey artery, a communicating
branch between the left gastric artery and the inferior phrenic
artery, lies in this area and may have to be ligated directly. It
is vital to divide the gastrohepatic ligament down to the level
of the left gastric artery. The caudate lobe of the liver must
be clearly visible beneath the right crus. This opening is
essential for subsequent passage of the fundoplication wrap
behind the esophagus.
Step 4: Mobilization of the Stomach

The highest short gastric arteries are ligated between ties to
permit mobilization of the fundus. Excessive traction must be
avoided to prevent splenic injury. Three or four vessels are
usually divided. The esophagogastric junction is elevated well Figure 5 Transthoracic hiatal hernia repair. The esophago-
gastric junction is mobilized by dividing the phrenoesopha-
into the chest, and any organoaxial rotation of the stomach is
geal ligament and some short gastric vessels. No. 1 silk
released as the short gastric vessels are divided. It is crucial sutures are passed through the exterior aspect of the right
that ligation be limited to the vessels along the greater crus (with care taken to avoid the adjacent inferior vena cava)
curvature. Inadvertent ligation of the vessels along the lesser and through the left crus.
curvature can easily occur, especially if there was a previous
operation. Loss of blood supply from the branches of the left
gastric artery along the lesser curvature will lead to ischemia
Next, the suture is brought out through the right crus, with
of the Collis gastroplasty tube and will predispose to either
care taken to prevent injury to the aorta or entry through the
leakage at the staple line or subsequent stricture formation.
right pleura. Three to five crural repair stitches are then
In the case of a redo repair, the previous fundoplication
placed at 1 cm intervals, from posterior to anterior. The
often will have slipped down onto the cardia or even onto
sutures should be staggered slightly so that the needle entry
the body of the stomach. Generally, the inner aspect of the
points are not all in a straight line; this measure helps prevent
previous fundoplication can be freed from the esophagus
longitudinal shredding of the muscle fibers when the sutures
without any difficulty; rarely will any major dissection have
are placed under tension. The sutures are held together with
been done in this area during the original operation. The hemostats but left untied at this point in the operation.
vagi will be found within the wrap and should be specifically Placement of traction on the last suture should close the
visualized. Because of scarring, it may be difficult to see the defect while still allowing easy passage of one finger along the
point at which the previous fundoplication attaches to itself. esophagus. The final decision on whether to tie this last
Not uncommonly, a serosal tear develops on the fundus as suture or to cut it out is made later, after construction of the
the wrap is undone. Any areas of concern can be reinforced fundoplication. It is better to err on the side of an overly
with a simple stitch of 4-0 silk. Mobilization is complete narrow opening: removing a suture is easier than having
when the fundus is restored to its original anatomic position to place an extra one at a time when exposure is less than
and the greater curvature can be followed down to the left optimal.
gastroepiploic artery.
Step 6: Assessment of Esophageal Length and Removal of
Step 5: Closure of Crura Anterior Fat Pad
Because the right crus is often quite attenuated, it is crucial After placement of the crural stitches, an assessment of
to incorporate an adequate amount of tissue into the repair. the esophageal length is made. Ideally, the stomach can easily
An Allis or Babcock clamp is placed at the apex of the hiatus be reduced into the abdomen without placing tension on the
and into the central tendon so that both crura can be placed thoracic esophagus. When esophageal foreshortening is found,
under tension. The esophagus is retracted anteriorly, and a a Collis gastroplasty is performed [see Step 6a, below].
No. 1 silk suture is passed through the most posterior aspect If an esophageal stricture is present, the assistant performs
of the left crus, with care taken to avoid the adjacent spleen dilation by passing a tapered bougie orally while the surgeon
[see Figure 5]. A notched spoon retractor is placed through supports the esophagus. The anteriorly located esophageal
the hiatus and into the abdomen behind the left crus. The fat pad is removed in anticipation of the gastroplasty, with
spleen is thus protected while the suture is brought through care taken not to injure the vagi located on either side [see
the left crus. Figure 6].
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again oversewn with a continuous seromuscular nonabsorb-

able monofilament suture. Two clips are placed at the supe-
rior aspect of the wrap. These, along with the previously
placed clips, help confirm both the length and the location of
the wrap on chest x-ray.
Once the fundoplication is complete, the dilator is removed
and the wrap is reduced into the abdomen. Two mattress
sutures of 2-0 polypropylene are placed to secure the top
of the fundoplication to the underside of the diaphragm.
The crural sutures are then sequentially tied, from the most
posterior one to the most anterior. When the final suture is
tied, one finger should still be able to pass through the hiatus
alongside the esophagus.
Step 8: Drainage and Closure

A nasogastric tube is passed into the stomach and secured.
Hemostasis is verified, and a single thoracostomy tube is
placed. The wound is closed in layers. A chest x-ray is per-
formed to verify the position of the tubes and the location of
the clips marking the wrap. The patient is then extubated in
the operating room (OR) and transported to the recovery
Figure 6 Transthoracic hiatal hernia repair. The anterior fat area.
pad is removed from the esophagus with sharp dissection,
postoperative care
with care taken to avoid injury to the vagi.
Patients typically remain in the hospital for about 5 days.
The nasogastric tube is left on low suction and removed on
postoperative day 3. Patients then begin liquid oral intake,
advancing to a full-fluid diet as tolerated. Early ambulation is
Step 6a: Collis Gastroplasty encouraged to prevent respiratory complications. Judicious
In a Collis gastroplasty for a short esophagus, a stapler is use of analgesics and antiemetics minimizes nausea and
used to form a 4 to 5 cm neoesophagus out of the proximal vomiting. The thoracostomy tube is removed as drainage
stomach, thereby effectively lengthening the esophagus and subsides. The epidural and Foley catheters are generally
transposing the esophagogastric junction more distally. A removed later the same day. A barium swallow is performed
large-caliber Maloney bougie (54 French for women, 56 on postoperative day 5 to verify the position of the wrap, to
French for men) is placed in the esophagus to prevent ensure that there is no significant esophageal obstruction,
narrowing of the lumen as the stapler is fired. The bougie is and to provide a qualitative impression of gastric emptying.
advanced well into the stomach so that its widest portion rests Gastroparesis secondary to vagal nerve dysfunction may be
at the esophagogastric junction. The bougie is held against apparent.
the lesser curvature, and the fundus is retracted away at a Once patients can tolerate a soft solid diet, they are dis-
right angle to the esophagus with a Babcock clamp. A 60 mm charged home with instructions about the gradual resump-
gastrointestinal anastomosis (GIA) stapler loaded with 3.5 mm tion of a normal diet at home. Large meals and carbonated
staples is applied immediately alongside the bougie on the beverages should be avoided in the early postoperative
greater curvature side [see Figure 7a] and fired, simultane- period.
ously cutting and stapling the cardia. The staple line is over-
complications
sewn with nonabsorbable 4-0 monofilament suture material
on both sides [see Figure 7b]. Two metal clips are placed to The root causes of the complications arising after transtho-
mark the distal extent of the gastroplasty tube, denoting the racic hiatal hernia repair are often technical; thus, the best
new esophagogastric junction. prevention, in most cases, is meticulous surgical technique.
Mobilization of the stomach with ligation of short gastric
Step 7: Fundoplication and Reduction of Wrap into Abdomen vessels may result in injury to the spleen. Injury to the vagi
The fundus is passed posteriorly behind the esophagus and predisposes to gastric dysfunction, early satiety, and so-called
brought up against the anterior stomach, with care taken to gas-bloat syndrome. Poor crural approximation increases the
avoid torsion of the fundal wrap. The fundus is then wrapped chances that the repair will fail. Dehiscence allows upward
either over the lower 2 cm of the esophagus, if no gastroplasty migration of the wrap into the chest or the development of
was done, or over a 2 cm length of the gastroplasty tube while a paraesophageal hernia. The gastroplasty may leak at the
the bougie is in place. The seromuscular layer of the fundus staple line. Overzealous dissection along the lesser curvature
is approximated to that of the esophagus or the gastroplasty can devascularize the cardia and cause ischemic stenosis
tube and that of the adjacent anterior stomach with two of the gastroplasty tube. Torsion of the fundus results in
interrupted 2-0 silk sutures [see Figure 8]. When tied, the perforation and sepsis. Excessive distraction of the ribs can
wrap should still be loose enough to accommodate a finger lead to pain and splinting with subsequent atelectasis or
alongside the esophagus. The fundoplication sutures are pneumonia. Inadequate mobilization of the fundus may place
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Figure 7 Transthoracic hiatal hernia repair. (a) If esophageal foreshortening is present, a Collis gastroplasty is performed. A
54 French Maloney bougie is inserted through the esophagogastric junction. A 4 to 5 cm neoesophagus is formed with a 60 mm
gastrointestinal anastomosis stapler loaded with 3.5 mm staples. (b) Both the fundal staple line and the lesser curvature staple
line are oversewn with nonabsorbable monofilament suture.
excessive tension on the wrap and promote later disruption slowly and remain distended after meals. A wrap that is too
and recurrent reflux. A slipped Nissen can result when the tight or too long results in persistent dysphagia.
wrap is inadequately fixed to the esophagus or the gastro- Recurrent heartburn and regurgitation call for evaluation
plasty tube and the stomach telescopes through the intact with contrast studies and esophagoscopy. The barium swal-
fundoplication to assume an hourglass configuration. This low is the most useful test for assessing whether the repair
event leads to varying degrees of heartburn, regurgitation, has failed. If there is an anatomic condition that is responsible
and dysphagia because the proximal pouch tends to empty for recurrent symptoms (e.g., slipping of the fundoplication
or disruption of the crural repair), reoperation is usually
necessary; continued medical treatment of symptoms related
to a structural failure invariably proves to be of little use. A
barium swallow may also identify gastroparesis secondary to
vagal nerve injury. Nuclear transit studies for gastric empty-
ing will help confirm this diagnosis. Dysphagia that is not
related to recurrent reflux, ulceration, or stricture usually
responds to dilation; reoperation is not required if the barium
swallow shows contrast flowing through the esophagus and
an intact wrap beneath the diaphragm. Given that patients
with long-standing reflux are at higher risk for Barrett dyspla-
sia and esophageal adenocarcinoma, it is important to
perform endoscopy to rule out malignancy.
outcome evaluation
Transthoracic hiatal hernia repair yields good to excellent
results in more than 85% of patients undergoing a primary
repair. Approximately 75% of patients who have previously
undergone hiatal hernia repair experience symptomatic
improvement.2
Resection of Esophagus and Proximal Stomach

In the remainder of the chapter, we describe the standard
Figure 8 Transthoracic hiatal hernia repair. The fundus is open techniques for resection of the esophagus and the
passed behind the esophagus and sewn to the neoesophagus esophagogastric junction. The technique of esophagectomy is
and the anterior stomach over a 2 cm length with interrupted largely surgeon dependent, with often strong preferences
2-0 silk sutures. expressed for a particular operative approach. There is a
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paucity of definitive evidence as to which technique is supe- Imaging

rior. Transhiatal esophagectomy is commonly performed to Esophagoscopy with biopsy and contrast-enhanced CT
treat end-stage benign esophageal disease and carcinomas of of the chest and the upper abdomen are required before
the cardia and the lower esophagus. Esophageal resection esophagectomy. If performed, the esophagogram identifies
through a combined laparotomy–right thoracotomy approach the location of the tumor and may indicate whether it extends
(Ivor Lewis esophagectomy) is ideal for cancers of the middle into the proximal stomach. Esophagoscopy allows direct
esophagus but is also used by many for lower third cancers. assessment of the mucosa, precise localization of the tumor,
A three-hole esophagectomy (also known as a McKeown and collection of tissue for histologic study. Retroflexion
esophagectomy) is sometimes preferred for its excellent expo- views of the stomach, after distention with air, are particularly
sure of all lymph node stations. The gastric conduit may be important if proximal gastric invasion is suspected, in which
anastomosed to the cervical esophagus either high in the right case distal esophagectomy and total gastrectomy with recon-
chest (as in an Ivor Lewis esophagectomy) or in the neck (as
struction of alimentary continuity by means of intestinal
in a transhiatal esophagectomy or three-hole esophagectomy).
interposition may be required. In cases of midesophageal
The left thoracoabdominal approach is less commonly used
cancer, bronchoscopy is mandatory to rule out airway involve-
but may be indicated for resection of the distal esophagus
ment. The carina and the proximal left mainstem bronchus
and the proximal stomach in the case of a bulky tumor that
are the sites most at risk for local invasion.
is locally aggressive. Although the traditional anastomosis of
Contrast-enhanced CT scans of the chest and abdomen are
the gastric conduit is in the left chest, it may also be placed
standard. Thoracic and abdominal CT scans yield informa-
in the neck.
tion on the extent of any celiac or mediastinal adenopathy,
preoperative evaluation the degree of esophageal thickening, and the possibility of
invasion of the adjacent aorta or tracheobronchial tree. The
Thorough preoperative preparation is essential for a good
lung parenchyma is assessed for metastatic nodules, as are the
postoperative outcome. Smoking cessation and a graded
liver and the adrenal glands. When the distal extent of tumor
regimen of home exercise will help minimize postoperative
cannot be defined as a result of near-complete obstruction on
complications and encourage early mobilization. Schematic
endoscopy, a prone abdominal CT scan can help differentiate
diagrams have proved useful for educating patients and shap-
a tumor at the gastric cardia from a collapsed but normal
ing their expectations about quality of life and ability to swal-
low after esophagectomy. Illustrations, by emphasizing the stomach. If the obstruction is not complete, the stomach
anatomic relations, greatly facilitate discussion of potential can be distended with air (through either the ingestion of
complications (e.g., hoarseness from recurrent laryngeal nerve effervescent granules or the passage of a small-bore nasogas-
injury, pneumothorax, anastomotic leakage, mediastinal tric tube) to improve visualization. A prone CT scan also
bleeding, and splenic injury). yields improved imaging of the gastrohepatic and celiac lymph
Potential postoperative problems (e.g., reflux, regurgita- nodes by allowing the stomach to fall away from these adja-
tion, early satiety, dumping, and dysphagia) must be discussed cent structures. Metastatic cancer in the celiac lymph nodes
before operation. Such discussion is particularly relevant for portends a poor prognosis.
patients undergoing esophagectomy for early-stage malignant PET is useful for the detection of occult distant metastases
tumors or for high-grade dysplasia in Barrett mucosa. These that preclude curative resection. Suspicious areas should
patients generally have no esophageal obstruction and may undergo needle biopsy or laparoscopic or thoracoscopic
be completely asymptomatic; accordingly, their expectations assessment. Similarly, pleural effusions must be tapped for
about postoperative function may be quite different from cytologic evaluation. Invasion of mediastinal structures and
those of patients with profound dysphagia secondary to the presence of distant metastases are contraindications to
near-complete esophageal occlusion. Support groups in which esophagectomy.
patients with upcoming operations can contact patients who At present, EUS, although quite sensitive for detection
have already undergone treatment have proved to be highly of paraesophageal adenopathy, is incapable of accurately
beneficial to all parties. Realistic expectations improve the differentiating reactive lymph nodes from nodes invaded by
chances of a satisfactory outcome. malignancy. EUS-FNA of suspicious lymph nodes should
be done if possible. This is often not possible because of
Evaluation of Operative Risk intervening tumor in the wall of the esophagus. CT and PET
Preoperative assessment should include a thorough review have limitations; thus, locoregional involvement may not
of the patient’s cardiopulmonary reserve and an estimate be recognized before resection is attempted. In patients who
of the level of operative risk. Spirometry, arterial blood gas are marginal candidates for surgical treatment and in whom
analysis, and exercise stress testing should be considered. metastatic disease is suspected, laparoscopy has been advo-
Even when a transhiatal esophagectomy is planned, patients cated for histologic evaluation of small superficial liver
should be assessed with an eye to whether they can tolerate a nodules, peritoneal abnormalities, and celiac nodes. Although
laparotomy and a thoracotomy, in case the latter is made this approach adds to the cost of investigation, it can save the
necessary by findings that become apparent only at the time patient from having to undergo a major operation for what
of operation. Thoracic epidural analgesia should be adminis- would later prove to be an incurable condition.
tered for pain control. If a transthoracic approach is taken,
a double-lumen endotracheal tube should be placed for Neoadjuvant Therapy
separate lung ventilation before beginning the chest portion Patients with esophageal cancer who are candidates for
of the resection. resection may benefit from neoadjuvant chemotherapy and
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concurrent radiation therapy. In particular, patients with Generally, patients are admitted to the hospital on the day
good performance status and locally advanced disease should of the operation. Thoracic epidural analgesia is administered,
be considered for such therapy. To date, no randomized trials both intraoperatively and postoperatively, and appropriate
have conclusively demonstrated a survival benefit with this antibiotic prophylaxis is provided. Heparin, 5,000 U subcu-
approach, but several series have documented a 20 to 30% taneously, is given before induction, and pneumatic calf com-
rate of complete response with no viable tumor found at the pression devices are applied. A radial artery catheter is placed
time of resection. After chemoradiation, patients are restaged to permit continuous monitoring of blood pressure. Central
with a CT. PET after treatment may yield spurious results in venous access is rarely required. General anesthesia is admin-
that inflammatory conditions can mimic the increased tracer istered via an uncut single-lumen endotracheal tube. Flexible
uptake seen in malignant tissue. Microscopic disease cannot esophagoscopy is performed (if it was not previously per-
be assessed, and scarring from radiation may further conformed by the surgical team). A nasogastric tube is placed
found the situation by preventing tracer uptake in areas that before final positioning and draping.
actually harbor malignancy. The patient is placed in the supine position with a small
If there are no contraindications to surgical treatment, rolled sheet between the shoulders. The arms are secured
resection is scheduled 4 to 6 weeks after the completion of to the sides, and the head is rotated to the right with the
neoadjuvant therapy. This interval allows time for patients to neck extended. The neck, the chest, and the abdomen are
return to their baseline activity level and for any induced prepared as a single sterile field. The drapes are placed so
hematologic abnormalities to be corrected. Previous chemo- as to expose the patient from the left ear to the pubis. The
radiation therapy does not make transhiatal esophagectomy operative field is extended laterally to the anterior axillary
significantly more difficult or complicated. Many tumors are lines to permit placement of thoracostomy tubes as needed.
downstaged and less bulky at the time of resection. In centers A self-retaining table-mounted retractor is used to facilitate
with experience in this approach, the rates of bleeding and upward and lateral traction along the costal margin.
anastomotic leakage remain low.
Ivor Lewis Esophagectomy
operative planning
At many institutions, Ivor Lewis esophagectomy is pre-
Transhiatal Esophagectomy ferred because it provides excellent direct exposure for dissec-
In transhiatal esophagectomy, the stomach is mobilized tion of the intrathoracic esophagus in that it combines a right
through an upper midline laparotomy, the esophagus is mobi- thoracotomy with a laparotomy. This procedure should be
lized from adjacent mediastinal structures via dissection especially considered when there is concern regarding the
through the hiatus without the use of a thoracotomy, and the extent of esophageal fixation within the mediastinum. One
stomach is transposed through the posterior mediastinum advantage of Ivor Lewis esophagectomy is that an extensive
and anastomosed to the cervical esophagus at the level of local lymphadenectomy can easily be performed through
the clavicles. The main advantages of this approach are (1) a the right thoracotomy. Any attachments to mediastinal struc-
proximal surgical margin that is well away from the tumor tures can be freed under direct vision. Whether any regional
site, (2) an extrathoracic esophagogastric anastomosis that lymph node dissection is necessary is highly controversial; no
is easily accessible in the event of complications, and (3) significant survival advantage has yet been demonstrated.
reduced overall operative trauma. Single-center studies Long-term survival after Ivor Lewis resection is equivalent to
throughout the world have shown transhiatal esophagectomy that after transhiatal esophagectomy.3
to be safe and well tolerated, even in patients who may have The main disadvantages of the Ivor Lewis procedure are
significantly reduced cardiopulmonary reserve. Long-term (1) the physiologic impact of the two major access incisions
survival is equivalent to that reported after transthoracic employed (a right thoracotomy and a midline laparotomy)
esophagectomy. and (2) the location of the anastomosis (in the chest).
Although transhiatal esophagectomy has been used for Incision-related pain may hinder deep breathing and the
resection of tumors at any location in the esophagus, it is best clearing of bronchial secretions, resulting in atelectasis and
suited for resection of tumors in the lower esophagus and pneumonia. The use of thoracic epidural catheters for pain
at the esophagogastric junction. It should also be considered management has greatly improved pain-related respiratory
for certain advanced nonmalignant conditions of the esopha- complications. Complications of the intrathoracic anastomo-
gus. Nondilatable strictures of the esophagus may occur as sis may be hard to manage. Although the anastomotic leakage
an end-stage complication of gastroesophageal reflux. Intrac- rate associated with Ivor Lewis esophagectomy has typically
table reflux after failed hiatal hernia repair may not be been 5% or lower—and thus substantially lower than the
amenable to further attempts at reconstruction of the esoph- rate cited for the cervical anastomosis after transhiatal
agogastric junction and thus may call for esophagectomy. esophagectomy—intrathoracic leaks are much more danger-
Because of the high cervical anastomosis, transhiatal esopha- ous and difficult to handle than intracervical leaks. In many
gectomy is less likely to predispose to postoperative reflux and cases, drainage of the leak will be incomplete and empyema
recurrent stricture formation than transthoracic esophagec- will result. Reoperation may prove necessary to manage
tomy would be. Achalasia may result in a sigmoid mega- mediastinitis.
esophagus and dysphagia that cannot be managed without
removal of the esophagus. Transhiatal esophagectomy per- Three-Hole Esophagectomy
mits complete removal of the thoracic esophagus and, in the Three-hole esophagectomy is performed when the surgeon
majority of patients, restoration of comfortable swallowing desires direct exposure to all phases of dissection, extensive
without the need for a thoracotomy. lymph node clearance, and an anastomosis in the neck. The
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right chest is opened first, and the intrathoracic esophagus artery is palpated. The lesser sac is generally entered near the
and the regional lymph nodes are dissected and mobilized midpoint of the greater curvature. The transition zone
free. The patient is then turned supine for the abdominal and between the right gastroepiploic arcade and the short gastric
neck phase, very similar to a transhiatal esophagectomy. arteries is usually devoid of blood vessels.
Dissection then proceeds along the greater curvature
Left Thoracoabdominal Esophagogastrectomy toward the pylorus. The omentum is mobilized from the right
The left thoracoabdominal approach is indicated for large gastroepiploic artery. Vessels are ligated between 2-0 silk ties,
gastroesophageal junction tumors and resection of the distal and great care is exercised to avoid placing excessive traction
esophagus and the proximal stomach when removal of the on the arterial arcade. A 1 cm margin is always maintained
stomach necessitates the use of an intestinal substitute to between the line of dissection and the right gastroepiploic
restore swallowing. This approach can also be used for very artery. Venous injuries, in particular, can occur with injudi-
obese patients to obtain optimal exposure. If the proximal cious handling of tissue. The ultrasonic scalpel is particularly
stomach must be resected for adequate resection margins efficient and effective for mobilization of the stomach; again,
to be obtained, then the distal stomach may be anastomosed this instrument must be applied well away from the gastro-
to the esophagus in the left chest. This operation can be epiploic arcade. Dissection is continued rightward to the level
associated with significant esophagitis from bile reflux. Con- of the pylorus. It should be noted that the location of the
sequently, many surgeons prefer to resect the entire stomach gastroepiploic artery in this area may vary; often it is at some
and the distal esophagus and then to restore swallowing unexpected distance from the stomach wall. Posterior adhe-
with a Roux-en-Y jejunal interposition anastomosed to the sions between the stomach and the pancreas are lysed so that
residual thoracic esophagus. Alternatively, some surgeons the lesser sac can be completely opened.
use this approach for most cancers and routinely place the The assistant’s left hand is then placed into the lesser sac
anastomosis in the left neck. Similar to other transthoracic to retract the stomach gently to the right and place the short
approaches, the use of a thoracic epidural catheter for pain gastric vessels on tension. The Penrose drain previously
control ameliorates pain-related respiratory complications. placed around the esophagus facilitates exposure by retract-
operative technique ing the cardia to the right. Dissection along the greater cur-
vature proceeds cephalad. The vessels are divided well away
Transhiatal Esophagectomy from the wall of the stomach to prevent injury to the fundus.
Transhiatal esophagectomy is best understood as consist- Clamps should never be placed on the stomach. A high short
ing of three components: abdominal, mediastinal, and cervi- gastric artery is typically encountered just adjacent to the left
cal. The abdominal portion involves mobilization of the crus. Precise technique is required to prevent injury to the
stomach, pyloromyotomy (if performed), and placement of a spleen. The Penrose drain [see Step 2, above] is exposed as
temporary feeding jejunostomy. the peritoneum is opened over the left crus. Mobilization of
the proximal stomach and liberation of the distal esophagus
Step 1: incision and entry into peritoneum A midline are thereby completed.
laparotomy is performed from the tip of the xiphoid to the Once the stomach has been completely mobilized along
umbilicus. The peritoneum is opened to the left of the mid- the greater curvature, it is elevated and rotated to the right
line so that the falciform and the preperitoneal fat may be [see Figure 10]; the left gastric artery and associated nodal
retracted en bloc to the right. Body wall retractors are placed tissues can then be visualized via the lesser sac. The superior
at 45° angles from the midline to elevate and distract both edge of the pancreas is visible, and the remaining posterior
costal margins. The retractors are placed so as to lift up the attachments of the stomach are divided along the hiatus and
costal margin gently and open the wound. The abdomen is the left crus. These may be quite extensive if there has been
then inspected for metastases. a history of pancreatitis or preoperative radiation therapy.
If the operation is being done for malignant disease, a final
Step 2: division of gastrohepatic ligament and mobi- determination of resectability can be made at this point.
lization of distal esophagus The left lobe of the liver is Tumor fixation to the aorta or the retroperitoneum can be
mobilized by dividing the triangular ligament and then folded assessed. Celiac and para-aortic lymph nodes can be palpated
to the right and held in this position with a moist laparotomy and, if necessary, sent for biopsy. The left gastric artery and
pad and a deep-bladed self-retaining retractor. Next, the vein are then ligated proximally, either through the lesser sac
gastrohepatic ligament is divided. Occasionally, there is an or directly through the divided gastrohepatic ligament. All
aberrant left hepatic artery arising from the left gastric artery nodal tissue is dissected free in anticipation of subsequent
[see Figure 9]. The peritoneum over the right crus is incised, removal en bloc with the specimen.
and the hiatus is palpated; the extent and mobility of any
tumor may then be assessed. The peritoneum over the left Step 4: mobilization of duodenum and pyloromyotomy
crus is similarly divided, and the esophagus is encircled with The duodenum is mobilized with a Kocher maneuver. Care-
a 2.5 cm Penrose drain. Traction is applied to draw the ful attention to the superior extent of this dissection is critical.
esophagogastric junction upward and to the right; this mea- Adhesions to either the porta hepatis or the gallbladder must
sure facilitates exposure of the short gastric arteries coursing be divided to ensure that the pylorus is sufficiently freed for
to the fundus and the cardia. later migration to the diaphragmatic hiatus.
Gastric drainage can be provided by a pyloromyotomy and
Step 3: mobilization of stomach The greater curvature is performed by most surgeons. The pyloromyotomy is begun
of the stomach is inspected, and the right gastroepiploic 1 to 2 cm on the gastric side of the pylorus. The serosa and
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Figure 9 Transhiatal
esophagectomy. The
duodenum is mobilized,
and the gastrohepatic and
gastrocolic omenta are
divided.
the muscle are divided with a small scalpel to expose the ligament of Treitz completes the abdominal portion of the
submucosa; generally, these layers of the stomach are robust, transhiatal esophagectomy.
making the proper plane easy to find.
Dissection is extended toward the duodenum with the aid Step 6: exposure and encirclement of cervical esophagus
of a fine-tipped right-angle or tonsil clamp. The duodenal The cervical esophagus is exposed through a 6 to 8 cm inci-
submucosa, recognizable by its fatty deposits and yellow col- sion along the anterior edge of the left sternocleidomastoid
oration, is exposed for approximately 0.5 cm. The duodenal muscle [see Figure 1] that is centered over the level of the
submucosa is usually much more superficial than expected, cricoid cartilage. The platysma is divided to expose the
and accidental entry into the duodenum often occurs just omohyoid, which is divided at its tendon. The strap muscles
past the left edge of the circular muscle of the pylorus. Should are divided low in the neck at their origin on the back of the
entry into the lumen occur, a simple repair using interrupted manubrium. The esophagus and its indwelling nasogastric
fine monofilament (4-0 or 5-0 polypropylene) sutures to close tube can be palpated.
the mucosa is performed. Small metal clips are applied to The carotid sheath is retracted laterally, and blunt dissec-
the knots of the traction sutures before removal of the ends; tion is employed to reach the prevertebral fascia. The inferior
these clips serve to indicate the level of the pyloromyotomy thyroid artery is ligated laterally; the recurrent laryngeal nerve
on subsequent radiographic studies. A tag of omentum can is visible just deep and medial to this vessel. No retractor
be easily sutured over the myotomy site for an added layer other than the surgeon’s finger should be applied medially:
of security. My own preference is not to perform a pyloromy- traction injury to the recurrent laryngeal nerve will result in
otomy primarily to reduce the possibility of postoperative both vocal cord palsy and uncoordinated swallowing with
bile reflux, which is very problematic to treat. In addition, aspiration. In particular, metal retractors must not be used
I remain unconvinced that pyloromyotomy helps gastric in this area. The tracheoesophageal groove is incised close to
drainage that much. With the availability of balloon dilation, the esophageal wall while gentle finger traction is applied
it is now simple to enhance emptying postoperatively if cephalad to elevate the thyroid cartilage toward the right.
needed. Many studies have confirmed that not performing a This measure usually suffices to define the location of the
pyloromyotomy is safe. nerve.
The esophagus is then encircled by passing a right-angle
Step 5: feeding jejunostomy Placement of a standard clamp posteriorly from left to right while the surgeon’s finger
Weitzel jejunal feeding tube approximately 30 cm from the remains in the tracheoesophageal groove. The tip of the
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Figure 10 Transhiatal esophagectomy. After the stomach has been completely mobilized along the greater curvature, it is
elevated and rotated to the right. The left gastric vessels are suture-ligated and divided. A 1 cm margin of the diaphragmatic
crura is taken in continuity with the esophagogastric junction, providing ample clearance of the tumor and improved exposure of
the lower mediastinum. A denotes the aorta, E denotes the esophageal hiatus.
clamp is brought into the pulp of the fingertip. The medially are divided, and the periesophageal adhesions are lysed.
located recurrent laryngeal nerve and the membranous tra- Mobilization of the distal esophagus under direct vision is
chea are thereby protected from injury. The clamp is brought thus completed up to the level of the carina.
around, and a narrow Penrose drain is passed around the Three specific maneuvers are now carried out. First, the
esophagus [see Figure 11]. Blunt finger dissection is employed plane posterior to the esophagus is developed [see Figure 12].
to develop the anterior and posterior planes around the The surgeon’s right hand is advanced palm upward into the
esophagus at the level of the thoracic inlet. hiatus, with the fingers closely applied to the esophagus. The
volar aspects of the fingers run along the prevertebral fascia,
Step 7: mediastinal dissection Some authors describe elevating the esophagus off the spine. A moist sponge stick is
this portion of the procedure as a blunt dissection, but, in placed through the cervical incision, also posterior to the
fact, the vast majority of the mediastinal mobilization is done esophagus. The sponge is advanced toward the right hand,
under direct vision. Narrow, long-handled, handheld, curved which is positioned within the mediastinum. As the sponge
Harrington retractors are placed into the hiatus and lifted up is advanced into the right palm, the posterior plane is
to expose the distal esophagus. Caudal traction is placed on completed.
the esophagus, allowing excellent visualization of the hiatus Second, the anterior plane is developed [see Figure 13].
and the distal esophagus. Long right-angle clamps are used This is often much more difficult than developing the poste-
to expose these attachments. Vascularity in this area is often rior plane because the left mainstem bronchus may be quite
minimal, and hemostasis can easily be achieved with either close to the esophagus. Again, the surgeon’s right hand is
the electrocautery, ultrasonic scalpel, metal clips, or ties. placed through the hiatus, but it is now palm down and ante-
The left crus can be divided to facilitate exposure. Paraesoph- rior to the esophagus. The fingertips enter the space between
ageal lymph nodes are removed either en bloc or as separate the esophagus and the left mainstem bronchus. The hand is
specimens. Dissection is continued cephalad with the electro- gently advanced, and the airway is displaced anteriorly. A
cautery and a long-handled right-angle clamp. The two vagi blunt curved suction handle is employed from above as a
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Figure 11 Transhiatal esophagectomy. Once the cervical

esophagus is exposed through an incision along the left
sternocleidomastoid muscle, strap muscles are divided and
retracted, and the cervical esophagus is dissected away from
the left and right recurrent laryngeal nerves.
Figure 12 Transhiatal esophagectomy. The plane posterior to
the esophagus is developed by placing the surgeon’s right
hand into the hiatus along the prevertebral fascia. A moist
substitute finger. It is advanced along the anterior aspect of sponge stick is placed through the cervical incision posterior
the esophagus through the cervical incision. The right hand to the esophagus, and the posterior plane is completed.
guides the tip of the suction handle beneath the bronchus.
Lateral displacement of the handle allows further mobiliza-
tion of the bronchus away from the esophagus. Completion Step 8: proximal transection of esophagus and
of the anterior and posterior planes usually results in a highly delivery into abdomen The nasogastric tube is retracted
mobile esophagus. to the level of the cricopharyngeus, and the esophagus is
Third, the lateral attachments of the upper and middle divided with a cutting stapler 5 to 6 cm distal to the muscle.
esophagus are divided. Upward traction is applied with the The esophagus is then removed via the abdomen [see Figure
Penrose drain previously placed around the cervical esopha- 14]. Retractors are placed in the hiatus, and the mediastinum
gus, allowing further dissection at the level of the thoracic is inspected for hemostasis. Both pleurae are inspected. The
inlet. Lateral attachments are pushed caudally into the medi- lungs are inflated so that it can be determined which pleural
astinum, and traction applied to the esophagus from below space requires thoracostomy drainage. The mediastinum is
allows these attachments to be visualized inferiorly through packed with dry laparotomy pads from below. A narrow pack
the hiatus and then isolated with long right-angle clamps and is placed into the thoracic inlet from above. Chest tubes are
divided with the electrocautery. Caution must be exercised so then placed as required along the inframammary crease in the
as not to injure the azygos vein. Dissection on the right side anterior axillary line. The drainage from these tubes should
must therefore be kept close to the esophagus. Once the last be closely monitored throughout the rest of the operation to
lateral attachment is divided, the esophagus is completely free ensure that any bleeding from the mediastinal dissection does
and can be advanced into the cervical wound. not go unnoticed.
Close monitoring of arterial blood pressure is maintained
throughout. Transient hypotension may occur as a result Step 9: excision of specimen and formation of gastric
of mediastinal compression and temporary impairment of tube The gastric fundus is grasped, and gentle tension is
cardiac venous return as the surgeon’s hand or retractors are applied along the length of the stomach. The esophagus is
passed through the hiatus. Vasopressors are never required held at right angles to the body of the stomach, and the fat in
for management: simple repositioning of the retractors or the gastrohepatic ligament is elevated off the lesser curvature;
removal of the dissecting hand usually results in prompt all lymph nodes are thus mobilized. A point approximately
restoration of normal blood pressure. Placement of the patient midway along the lesser curvature is selected. The blood
in a slight Trendelenburg position is often helpful. vessels traversing this area from the right gastric artery are
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ligated to expose the lesser curvature. The distal resection

margin is then marked; it should be 4 to 6 cm from the
esophagogastric junction, extending from the selected point
on the lesser curvature to a point medial to the fundus. A
60 mm GIA stapler loaded with 3.5 or 4.8 (depending on the
thickness of the stomach) mm staples is then used to transect
the proximal stomach, proceeding from the lesser curvature
toward the fundus [see Figure 15]. Resection of the cardia
along with the adjacent portion of the lesser curvature effec-
tively converts a J-shaped stomach into a straight tube and
harvests many left gastric territory lymph nodes.
For maximizing the length of the gastric tube, several
technical points are critical. Tension must be maintained on
the stomach as the stapler is serially applied. The stapler
should be simply placed on the stomach and fired: no attempt
should be made to telescope tissue into the jaws because to
do so would effectively reconstitute the curve of the stomach
and diminish its upward reach. Typically, five or six staple
loads are required.
The specimen is removed, and frozen-section examination
is done on the distal margin. The completed staple line is
then oversewn with a continuous Lembert suture of 4-0
polypropylene. Once again, tension is maintained along the
stomach to prevent any foreshortening of the lesser curvature.
The use of two separate sutures, each reinforcing half of the
staple line, is helpful in this regard. Alternatively, interrupted
4-0 sutures can be used.
Figure 13 Transhiatal esophagectomy. The anterior plane is Step 10: advancement of stomach into chest or neck
developed by placing the surgeon’s right hand through the The mediastinal packs are removed, and hemostasis is
hiatus anterior to the esophagus. The fingertips enter the
verified in the chest. The stomach is inspected as well. The
space between the esophagus and the left mainstem bronchus,
to be met by a blunt suction handle passed downward
ends of any short gastric vessels that were divided with the
through the cervical incision. The lateral attachments of the
esophagus are divided from above downward as far as the
aortic arch.
Figure 14 Transhiatal esophagectomy. The

esophagus is divided in the neck and delivered
into the abdomen. Retractors are placed in
the hiatus, and any vessels entering into the
esophagus are clipped and divided. The vagi are
also clipped and divided.
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Figure 15 Transhiatal esophagectomy. A gastric tube is formed by stapling along the lesser curvature of the stomach from the
junction of the right and left gastric vessels to the top of the fundus. This staple line is oversewn with either an interrupted or a
continuous fine suture, with care taken not to foreshorten the gastric tube. The gastric tube is made at least 5 cm wide to avoid
undo ischemia.
ultrasonic scalpel are now tied so that subsequent manipula- for hemostasis, as is the splenic hilum. It may be necessary to
tion does not precipitate bleeding. The stomach is oriented reconstitute the hiatus with one or two simple sutures of 1-0
so that the greater curvature is to the patient’s left. There silk placed through the crura. These sutures must be placed
must be no torsion. The anterior surface of the fundal tip with care to ensure that injury to the gastroepiploic arcade
should be marked with ink so that proper orientation of does not occur at this late point in the procedure. The hiatus
the stomach can be confirmed after its passage into the neck. is narrowed, but not so much that three fingers cannot be
The stomach can usually be advanced through the posterior easily passed alongside the gastric conduit. This reconstitu-
mediastinum without any traction sutures or clamps. The tion will help prevent herniation of other abdominal contents
surgeon’s hand is placed palm down on the anterior surface alongside the gastric conduit. The liver is returned to its ana-
of the stomach, with the fingertips about 5 cm proximal to tomic position, thus also preventing any subsequent hernia-
the tip of the fundus. The hand is then gently advanced tion of bowel into the chest. The pylorus is generally found
through the chest, pushing the stomach ahead of itself. The at the level of the diaphragm. The laparotomy is then closed
tip of the fundus is gently grasped with a Babcock clamp as in the usual fashion. The viability of the fundus in the neck
it appears in the neck. To prevent trauma at this most distant incision is checked periodically as the abdominal portion of
aspect of the gastric tube, the clamp should not be ratcheted the procedure is completed.
closed.
No attempt should be made to pull the stomach up into Step 11: cervical esophagogastric anastomosis The
the neck: the position of the fundus is simply maintained construction of the esophagogastric anastomosis is the most
as the surgeon’s hand is removed from the mediastinum. important part of the entire operation: any anastomotic
Further length in the neck can usually be gained by gently complication will greatly compromise the patient’s ability to
readvancing the hand along the anterior aspect of the stom- swallow comfortably. Accordingly, meticulous technique is
ach. This measure uniformly distributes tension along the essential.
tube and ensures proper torsion-free orientation in the chest. A seromuscular traction suture of 4-0 polyglactin is placed
The stomach is pushed up into the neck rather than drawn through the anterior stomach at the level of the clavicle and
up by the clamp. drawn upward, thus elevating the fundus into the neck wound
A useful alternative approach for positioning the gastric and greatly facilitating the anastomosis.
tube involves passing a large-bore Foley catheter through the The site of the anterior gastrotomy is then carefully selected:
mediastinum from the neck incision. The balloon is inflated, it should be midway between the oversewn lesser curvature
and a 50 cm section of a narrow plastic laparoscopic camera staple line and the greater curvature of the fundus (marked
bag is tied onto the catheter just above the balloon. The gas- by the ligated ends of the short gastric vessels). The staple
tric tube is positioned within the bag, and suction is applied line on the cervical esophagus is removed, and the anterior
through the catheter, creating an atraumatic seal between the aspect of the esophagus is grasped with a fine-toothed forceps
stomach and the surrounding plastic bag. As the bag is drawn at the level of the planned gastrotomy. A straight DeBakey
upward through the neck with gentle traction on the Foley forceps is then applied across the full width of the esophagus
catheter, the stomach advances through the mediastinum. to act as a guide for division. The esophagus is cut with a new
The stomach is not secured to the prevertebral fascia in any scalpel blade at a 45° angle so that the anterior wall is slightly
way. longer than the posterior wall; the anterior wall then forms
The feeding jejunal tube is brought out the left midabdo- the hood of the anastomosis. The fine-toothed forceps is used
men through a separate stab incision. The hiatus is inspected to maintain orientation of the esophagus throughout. Two
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full-thickness stay sutures of 4-0 polyglactin are placed, one

at the midpoint of the anterior cut edge of the esophagus and a
one at the corresponding location posteriorly. The posterior
stitch is placed from inside the lumen, and the needle is left
on the suture for later use.
A small gastrotomy is then performed with a needle-tipped
electrocautery using cutting current. The incision is obliquely
oriented, with the cephalad extent proceeding slightly
medially. The needle from the stay suture previously placed
on the posterior wall of the esophagus is then passed the
full thickness of the cephalad aspect of the gastrotomy [see
Figure 16a]. Traction on this untied suture brings the esoph-
agus toward the stomach. A 45 mm endoscopic stapler loaded
with 3.5 mm staples is used to form the back wall of the
anastomosis. The thicker portion of the device (the cartridge)
is advanced cephalad into the esophagus, with the narrower
portion (the anvil) in the gastric lumen [see Figure 16b].
The tip of the stapler should be aimed toward the patient’s
right ear. Tension is applied to the stay suture holding the
esophagus and stomach together so as to bring tissue into the
jaws of the device. The portion of the fundus extending b
beyond the stapler is then rotated medially to ensure that the
new staple line is well away from the one previously placed
along the lesser curvature. This is a crucial point: crossing of
the two staple lines may create an ischemic area that can give
rise to a large leak in the postoperative period.
The stapler is then closed, holding the esophagus and
stomach together, but not yet fired. The position of the
nasogastric tube should be maintained just at the level of the
cricopharyngeus during the construction of the anastomosis.
This positioning keeps the tube out of the operative field and
protects it from being entrapped by the jaws of the stapler;
it also facilitates subsequent passage of the tube into the
gastric conduit once the posterior wall of the anastomosis is
complete. Two suspension sutures are placed on either side
c
of the closed stapler, one toward the tip and the other near
the heel of the jaws. These four sutures alleviate any potential
tension on the staple line by approximating the muscular
layer of the esophagus to the seromuscular layer of the stom-
ach. The suspension sutures are tied, and the stapler is fired,
thereby completing the posterior portion of the anastomosis
[see Figure 16c].
The anterior portion of the anastomosis is closed in two
layers. The inner layer consists of a continuous 4-0 polydiox-
anone suture placed as full-thickness inverting stitches,
and the second layer consists of interrupted seromuscular Figure 16 Transhiatal esophagectomy. (a) After the proximal
Lembert sutures [see Figure 17]. The lateral and medial end of the stomach tube is delivered into the neck, the
corners of the anastomosis, where the staple line meets the esophagus is cut at a 45° angle so that the anterior wall is
handsewn portion, merit extra attention. These corners are longer than the posterior wall. A gastrotomy is placed
quite fragile, and excessive traction may result in dehiscence between the oversewn lesser curvature staple line and the
progressing cephalad along the staple line in a zipperlike greater curvature of the fundus. A full-thickness suture is
fashion. The inner layer should therefore be started at each placed through all layers of the esophagus and all layers of the
corner, incorporating the last 5 mm of the staple line. Once gastrotomy. (b) An endoscopic gastrointestinal anastomosis
several stitches have been placed from the two corners, the stapler is used to form the back wall of the anastomosis. The
nasogastric tube can be passed through the anastomosis. thicker portion of the device (the cartridge) is advanced
cephalad into the esophagus, with the narrower portion (the
The nasogastric tube is properly positioned when the most
anvil) in the gastric lumen. The tip of the stapler should be
distal black marker is at the nares. The inner layer is then
aimed toward the patient’s right ear. The staple line must
completed as the two sutures are tied at the midpoint. be well away from the lesser curvature staple line. Two
suspension sutures are placed on either side of the closed
Step 12: drainage, closure, and completion x-ray The stapler, one toward the tip and the other near the heel of the
incision is irrigated. The strap muscles are not reapproxi- jaws. (c) The stapler is fired to complete the posterior portion
mated but are merely attached loosely to the underside of the of the anastomosis.
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a ice chips in the mouth. The thoracic epidural catheter is

removed the afternoon after the chest tube is removed. The
diet is gradually advanced so that a soft diet is begun on
postoperative day 5 or 6. A barium swallow is performed on
postoperative day 6 in preparation for hospital discharge on
day 7 or 8.
Ivor Lewis Esophagectomy
Steps 1 through 5 Esophagoscopy is performed to con-
firm the location of the tumor. Steps 1 through 5 of an
Ivor Lewis esophagectomy are virtually identical to the first
five steps (i.e., the abdominal portion) of a transhiatal esoph-
b agectomy. Once complete mobilization of the stomach is
verified, the pylorus is manually advanced to the level of
the diaphragm to ensure that it is not being tethered by the
duodenum or the greater omentum. Although it is possible to
form the gastric tube in the chest, it is easier to do in the
abdomen. Similar to step 9 in a transhiatal esophagectomy, a
5 to 6 cm wide gastric tube is created. The proximal divided
stomach is sewn to a large Penrose drain. The other end of
the drain is sutured to the tip of the gastric tube so that it
can be pulled into the chest when needed. A jejunostomy is
performed, and the laparotomy is closed.
Figure 17 Transhiatal esophagectomy. The anterior portion

Step 6: exposure and mobilization of esophagus The
of the anastomosis is completed with (a) an inner layer patient is shifted to the left lateral decubitus position and
consisting of a continuous 4-0 polydioxanone suture and redraped. Single-lung ventilation is instituted, and the chest
(b) an outer layer consisting of interrupted sutures. is entered through a right fifth interspace thoracotomy. The
inferior pulmonary ligament is divided, and the lung is
retracted cephalad. The esophagus is mobilized from the
level of the diaphragm to a point above the azygos vein [see
sternocleidomastoid muscle with two interrupted 4-0 polyglac-
Figure 18], which can be divided with a vascular stapler. I
tin sutures. The platysma is reconstituted with interrupted
prefer not to divide the vein as the azygos helps keep the
4-0 polyglactin sutures. The nasogastric tube is secured.
stomach conduit in the midline for comfortable swallowing.
A chest x-ray is obtained in the OR to verify the position The pleura overlying the esophagus is divided to the level of
of the drains and the absence of any abnormal collections in the thoracic inlet, superior to the azygos vein. The esophagus
the chest. Patients are extubated in the OR and transported is encircled with a Penrose drain in the retrotracheal region.
to the anesthetic recovery area. Extubation should be carried The pleura is then divided to the level of the diaphragm, with
out only when the health care team is confident that subse- care taken to stay close to the right bronchus and the pericar-
quent reintubation is unlikely to be necessary. Emergency dium and avoid injury to the thoracic duct. The soft tissue
reintubation after a cervical anastomosis is hazardous in that between the esophagus and the aorta posteriorly and between
vigorous neck extension may threaten the suture line. Once the esophagus and the trachea or the pericardium anteriorly
patients are awake and alert, which is usually 3 to 4 hours is dissected free and maintained en bloc with the esophagus.
after the operation, they are taken to the general ward. As a Periesophageal and subcarinal nodes are thereby mobilized
rule, admission to an intensive care unit is not required unless [see Figure 18b].
there are substantial comorbidities or intraoperative concerns.
To prevent excessive traction on the anastomosis, the neck Step 7: excision and removal of specimen The hiatus
should be maintained in a flexed position with two pillows is incised, and the abdomen is entered. The stomach is drawn
placed behind the head. up into the chest, with care taken not to place excessive trac-
In certain patients, a stapled anastomosis may be impracti- tion on the gastroepiploic pedicle. The esophagus is divided
cal. In patients with a bull-neck habitus, for example, a partial proximally at least 5 cm away from any grossly evident tumor,
sternal split may be required for adequate exposure of the typically just below the thoracic inlet. The esophageal speci-
cervical esophagus, and a handsewn true end-to-end anasto- men is removed from the operative field, and proximal and
mosis (EEA) may be necessary. In addition, patients who distal margins are sent for frozen-section examination. [see
have previously undergone antireflux surgery may have a Figure 19]. The stomach is positioned in the posterior medi-
relatively short gastric tube that will necessitate an end-to-end astinum with care to avoid any twisting.
reconstruction.
Patients should, if possible, begin walking the morning Step 8: intrathoracic esophagogastric anastomosis
after the operation. An incentive spirometer should be con- The site of the esophagogastric anastomosis should be about
stantly within arm’s length of the patient, and hourly use of 2 to 4 cm above the azygos vein. Several interrupted sutures
this device should be encouraged. The nasogastric tube is are used to secure the transposed stomach to the adjacent
removed on postoperative day 3, and the patient is allowed pleura. The staple line on the esophagus is removed, and a
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Figure 18 Ivor Lewis esophagectomy. (a) The lung is retracted, and the azygos vein is stapled and divided. The esophagus and
the vagi are mobilized from the level of the diaphragm to the thoracic inlet. (b) Dissection en bloc via right thoracotomy of the
thoracic duct, the azygos vein, the ipsilateral pleura, and all periesophageal tissue in the mediastinum. The specimen includes
the lower and middle mediastinal, subcarinal, and right-side paratracheal lymph nodes.
gastrotomy is performed in preparation for a side-to-side through the stomach. The proximal esophagus is dilated suf-
functional EEA [see Figure 20]. With the aid of full-thickness ficiently to accommodate at least a 25 mm head. The anvil is
traction sutures, the esophagus is positioned along the surface placed into the distal esophagus and secured with a purse-
of the stomach and well away from the oversewn staple line string suture. The tip of the stapler is brought out through
defining the gastric resection margin. The posterior aspect of the apical wall of the stomach and attached to the anvil. The
the anastomosis is completed with an endoscopic GIA stapler stapler is then fired to create the EEA, and the gastrotomy
as described earlier [see Transhiatal Esophagectomy, Step 11, is closed. The advantages of this technique are its relative
above, and Figure 16 and Figure 17]. A nasogastric tube is simplicity and the theoretical security of a completely stapled
passed, and the anterior wall is completed in two layers. The anastomosis; the main potential disadvantage is the risk of
first layer consists of a full-thickness continuous 3-0 polydiox- postoperative dysphagia resulting from an overly narrow
anone suture; the second consists of interrupted absorbable anastomotic ring.
sutures approximating the seromuscular layer of the stomach After completion of the anastomosis, the stomach is
to the muscular layer of the esophagus. inspected for any potential redundancy or torsion in the
Two alternative methods of anastomosis are sometimes chest. To prevent torsion, the stomach is anchored to the
used: (1) a totally handsewn end-to-side anastomosis and (2) pericardium and pleura with nonabsorbable sutures. The
a totally stapled EEA. I prefer a handsewn anastomosis, diaphragmatic hiatus is then inspected: it should allow easy
although it is no longer in vogue. An outer layer of inter- passage of two fingers into the abdomen alongside the
rupted 4-0 silk is used followed by a mucosal layer of inter- transposed stomach. Interrupted sutures may be used to
rupted inverting 4-0 silk [see Figure 20]. The stapled circular approximate the edge of the crura to the adjacent stomach
technique involves opening the previously placed gastric wall, thereby preventing any later herniation of abdominal
staple line and advancing the handle of an EEA stapler contents into the pleural space.
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Figure 19 Ivor Lewis esophagec-

tomy. (a) After full mobilization of
the esophagus, the gastric conduit
(sutured to the divided proximal
stomach) is pulled up into the chest.
(b) An open anastomosis is begun at
or above the level of the azygos vein.
Step 9: drainage and closure A chest tube is placed. endotracheal tube is replaced by a standard single-lumen
The tip of the chest drain is positioned alongside the stomach tube. Thereafter, the operation proceeds exactly like a trans-
at the level of the anastomosis. Fine gut sutures secured to hiatal esophagectomy with steps 1 through 12. The medias-
the adjacent parietal pleura will help maintain the position of tinal phase is, of course, much easier because all of the
the tube. The thoracotomy is then closed in the standard dissection was done in the thoracotomy phase of the
fashion. operation.
Patients should begin walking on postoperative day 1. The Patients should begin walking on postoperative day 1.
nasogastric tube is generally removed on postoperative day 3. The nasogastric tube is generally removed on postoperative
Oral intake is not begun at this point; feeding is accomplished day 3. Oral intake is not begun at this point; feeding is accom-
via the temporary jejunostomy. A barium contrast study is plished via the temporary jejunostomy. A barium contrast
performed approximately 5 to 7 days after the operation. If study is performed approximately 5 to 7 days after the opera-
there is no anastomotic leakage, oral intake is initiated and tion. If there is no anastomotic leakage, oral intake is initiated
advanced as tolerated. The chest tube and epidural catheter and advanced as tolerated. The chest tube and epidural
are removed, usually on day 4. Patients are generally catheter are removed, usually on day 4. Patients are generally
discharged from the hospital by postoperative days 8 to 10. discharged from the hospital by postoperative days 8 to 10.
Three-Hole Esophagectomy Left Thoracoabdominal Esophagogastrectomy

Step 1: thoracotomy phase Esophagoscopy is performed Step 1: incision and entry into peritoneum The patient
to confirm the location of the tumor. A double-lumen endo- is placed in the right lateral position, with the hips rotated
tracheal tube is placed. The first step is a right thoracotomy backward about 30°. An exploratory laparotomy is performed
and mobilization of the esophagus and the regional lymph through an oblique incision extending from the tip of the
nodes, similar to step 6 of an Ivor Lewis esophagectomy. The sixth costal cartilage to a point about halfway between the
chest is closed after esophageal mobilizaton is performed. sternum and the umbilicus. The peritoneal cavity is carefully
examined to rule out peritoneal and hepatic metastases. The
Step 2: abdominal and cervical phase The patient region of the cardia is palpated, and the mobility of the tumor
is turned back to the supine position. The double-lumen is assessed. If there is minor involvement of the crura or the
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Figure 20 Ivor Lewis esophagectomy.

The two-layer anastomosis is per-
formed with fine 4-0 sutures in an
interrupted fashion. It is important to
locate the gastrostomy away from the
turned-in lesser curve suture line to
avoid ischemia. (a) Posterior layer.
(b) Posterior inner mucosal layer.
(c) Anterior mucosal layer. (d) After
the anterior seromuscular layer is
done, local pleura is used to cover the
anastomosis to buttress it and to keep
the conduit in the middle of the
mediastinum. The anastomosis can
also be completed as in a transhiatal
esophagectomy or with an end-to-end
anastomosis [see Figure 16 and
Figure 17].
tail of the pancreas, resection may still be possible; however, divided. The tumor is mobilized; the plane of the dissection
if the tumor is firmly fixed or there are peritoneal or hepatic is kept close to the aorta on the left, and, if necessary, the
metastases, resection should be abandoned. A feeding jeju- right parietal pleura is taken in continuity with the lesion.
nostomy, an esophageal stent, or both may be inserted to About 1 cm of the crura is taken in continuity with the tumor
improve swallowing and allow nutrition. to provide good local clearance. The stomach is then mobi-
lized in much the same way as in a transhiatal esophagectomy
Step 2: assessment of gastric involvement and incision [see Figure 9].
of diaphragm The extent to which the tumor involves the
stomach determines whether a total gastrectomy or a proxi- Step 4: assessment of pancreatic involvement and
mal gastrectomy is indicated along with the distal esophagec- hepatic viability The lesser sac is opened through the
tomy. If no metastases are found, the incision is extended and greater omentum so that it can be determined whether the
the chest is opened with a left posterolateral incision through primary tumor involves the distal pancreas. If so, it is reason-
the sixth interspace. If the thoracic component of the tumor able to resect the distal pancreas, the spleen, or both in con-
appears to be resectable, the costal margin is divided. It is tinuity with the stomach; if not, the short gastric vessels are
advisable to remove a 1 to 2 cm segment of the costal margin ligated and divided, with the spleen preserved. The lesser
to facilitate repair of the diaphragm at the end of the opera- omentum is detached from the right side of the esophagus
tion and reduce postoperative costal margin pain. The dia- and the hilum of the liver and then divided down to the area
phragm is incised radially. Alternatively, a circumferential of the pylorus, with the right gastric artery and vein preserved.
incision may be made about 2 cm from the costal margin to There is often a hepatic branch from the left gastric artery
reduce the risk of postoperative diaphragmatic paralysis. running through the gastrohepatic omentum. If this hepatic
branch is of significant size, a soft vascular clamp should be
Step 3: division of pulmonary ligament and mobiliza- placed on the artery for 20 minutes so that the viability of the
tion of esophagus and stomach The pulmonary ligament liver can be assessed. If the liver is viable, the artery is suture-
is divided, and the mediastinal pleura is incised over the ligated and divided.
esophagus as far as the aortic arch. The esophagus is mobi-
lized above the tumor and is retracted by a Penrose drain. Step 5: division of greater omentum and short gastric
The esophageal vessels are carefully dissected, ligated, and vessels The greater omentum is divided, with care taken to
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preserve the right gastroepiploic artery and vein. These two to the cervical esophagus through a left neck incision; alter-
vessels are suture-ligated and divided well away from the natively, the left colon is interposed between the gastric stump
stomach. Ligation and division of the short gastric vessels and the cervical esophagus. If the resection margin is ade-
allow complete mobilization of the greater curvature of the quate, the tip of the stomach tube is anastomosed to the
stomach. Dissection is extended downward as far as the esophagus by any of the previously described techniques
pylorus. The stomach is turned upward, and the left gastric [see Figure 22].
vessels are exposed through the lesser sac [see Figure 10]. The The anastomosis is then performed with the stapling tech-
lymph nodes along the celiac axis and the left gastric artery nique previously described for transhiatal esophagectomy [see
are swept up into the specimen, and the gastric vessels are Figure 16 and Figure 17]. A nasogastric tube is passed down
either suture-ligated or stapled and divided. into the gastric remnant. The tube is sewn to the pericardium
and the endothoracic fascia to prevent torsion or herniation
Step 6: choice of partial or total gastrectomy At this into the pleural space.
time, the surgeon determines whether the whole stomach
must be resected to remove the gastric part of the cancer or Total gastrectomy with Roux-en-Y esophagojejunos-
whether a partial (i.e., proximal) gastrectomy will suffice. tomy If the surgeon decides that a total gastrectomy is
If the surgeon decides that resection of the proximal stom- necessary, the right gastroepiploic and right gastric vessels are
ach will remove all of the tumor while leaving at least 5 cm suture-ligated and divided distal to the pylorus. The duode-
of tumor-free stomach, a proximal esophagogastrectomy is num is divided just distal to the pylorus with a linear stapler.
performed [see Figure 21]. A gastric tube is fashioned with a The staple line is inverted with interrupted 3-0 nonabsorb-
linear stapler [see Transhiatal Esophagectomy, Step 9, above, able sutures and covered with omentum to prevent duodenal
and Figure 15]. The staple line is oversewn with inverting 3-0 stump blowout.
or 4-0 sutures. Because the vagus nerves are divided and gas- The esophagus is then mobilized up to the level of the
tric stasis may result, a pyloromyotomy may be performed, inferior pulmonary vein. Two retaining sutures are placed in
much as in a transhiatal esophagectomy. the esophageal wall. A monofilament nylon purse-string
The proximal gastric resection margin is covered with suture is placed around the circumference of the proximal
a sponge and turned upward over the costal margin. The esophagus in preparation for stapling. The resected specimen
stomach tube is then brought up through the hiatus and into is sent to the pathologist for examination of the margins.
the thorax behind the proximal esophageal resection margin A jejunal interposition is then fashioned by using the
[see Figure 21]. The margin should be at least 10 cm from the Roux-en-Y technique. One or two jejunal arteriovenous
proximal end of the esophagogastric cancer. If the esophageal arcades are divided to mobilize enough jejunum to allow
resection margin is not adequate, the stomach tube is anastomosis to the thoracic esophagus [see Figure 23]. A 25
mobilized and brought to the left neck and then anastomosed or 28 mm EEA stapler is passed through the jejunum into the
Figure 21 Left thoracoabdominal

esophagogastrectomy. The diaphragm is
incised radially sparing major branches of
the phrenic nerve. The pulmonary
ligament is divided, and the esophagus is
mobilized above the tumor and retracted
with a Penrose drain. The esophageal
vessels are ligated and divided. The
tumor and the esophagus are mobilized
off the aorta down to the hiatus; 1 cm of
the diaphragmatic crura is taken in
continuity with the tumor to provide local
clearance. The stomach is then mobilized
in much the same way as in a transhiatal
esophagectomy and brought through the
diaphragmatic hiatus [see Figure 9].
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a b
c d
Figure 22 Left thoracoabdominal esophagogastrectomy: proximal esophagogastrectomy with esophagogastrostomy. The

esophagus is sewn to the tip of the stomach tube, halfway between the lesser curvature suture line and the greater curvature.
(a) The Sweet anastomosis developed at the Massachusetts General Hospital. The outer posterior layer is performed with fine
4-0 silk sutures. A serosal “button” is inscribed with a scalpel down to the level of the submucosal vascular plexus. Fine 4-0 silk
sutures are used to ligate these vessels so they do not obscure the anastomosis while it is being performed. (b) The gasric button
is excised, and the inner posterior layer is anastomosed with interrupted 4-0 silks. This is continued anteriorly as well. (c) The
outer anterior layer is performed also with interrupted 4-0 silks. (d) A tag of omentum from the high greater curve is sutured
over the anastomosis to buttress it. Alternatively, an anastomosis can be fashioned with the stapling technique used in
transhiatal esophagectomy or with an end-to-end anastomosis [see Figure 16 and Figure 17].
esophagus, fired, and removed. The jejunum is anchored to absorbable suture. The skin and the subcutaneous tissue are
the pericardium and the proximal esophagus. The duodenal closed in the usual fashion.
loop is anastomosed to the jejunum at least 45 to 50 cm distal
to the esophagojejunal anastomosis to minimize bile reflux postoperative care
[see Figure 23]. The blind end of the jejunal loop is then As a rule, patients are not routinely admitted to the inten-
stapled closed. sive care unit after esophagectomy; however, individual
After careful irrigation of the chest, the first step in the practices depend on the distribution of skilled nursing and
closure is to repair the diaphragm around the hiatus. The physiotherapy personnel. Early ambulation is the mainstay of
gastric or jejunal interposition is sewn to the crura with postoperative care. As a rule, patients are able to walk slowly,
interrupted nonabsorbable sutures. The remainder of the with assistance, on postoperative day 1. Patient-controlled
diaphragm is closed with interrupted nonabsorbable 0 mat- epidural analgesia is particularly useful in facilitating good
tress sutures. A chest tube is placed into the pleural space pulmonary toilet and minimizing the risk of atelectasis or
close to but not touching the anastomosis. The final sutures pneumonia.
in the peripheral part of the diaphragm are placed but are The nasogastric tube is removed on postoperative day 3 or
not tied until the ribs are brought together with pericostal 4; jejunostomy tube feedings are gradually started at the same
sutures. The left lung is reexpanded. The costal cartilages are time. Once bowel function normalizes, patients are allowed
not approximated but are left to float free. If the ends of the small sips of liquids. Chest tubes are removed as pleural
costal margin are abutting, another 2 cm of costal cartilage drainage subsides. By postoperative day 6, most patients have
should be removed to reduce postoperative pain. Thoracic progressed to a soft solid diet. Dietary education is provided,
and abdominal skin layers are closed with a continuous focusing primarily on eating smaller and more frequent meals,
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recognized preoperative impairment of pulmonary reserve

should be considered for transhiatal esophagectomy. Existing
pulmonary function can be optimized through incentive spi-
rometry, use of bronchodilators, and physical rehabilitation.
Chronic nocturnal aspiration from esophageal obstruction
should be watched for in the postoperative patient; the
head of the bed should be elevated 30° to 45° as a preventive
measure. Effective pain control is essential to prevent post-
operative atelectasis. Routine use of patient-controlled
thoracic epidural analgesia should be considered. Deep
breathing, early ambulation, and chest physiotherapy encour-
age the clearing of bronchial secretions. Certain patients
will require nasotracheal aspiration or bronchoscopy for
pulmonary toilet.
Tracheobronchial Injury
On rare occasions, lacerations of the membranous trachea
or the left mainstem bronchus occur during esophagectomy.
When such injuries occur during transthoracic resection,
management is relatively simple, thanks to the already excel-
lent operative exposure. Direct suture repair and tissue rein-
forcement with adjacent pleura or a pedicle of intercostal
muscle provide safe closure in almost all cases. When tra-
cheobronchial injuries occur during transhiatal esophagec-
tomy, they are less obvious but no less urgent. This rare
complication arises during mediastinal dissection. Typically,
the anesthetic team notes a loss of ventilatory volume, and
the surgeon may detect the smell of inhalational agents in the
operative field. Bronchoscopy should be promptly performed
to identify the site of the injury. The uncut endotracheal tube
is then advanced over the bronchoscope and past the site of
Figure 23 Left thoracoabdominal esophagogastrectomy: total the laceration to restore proper ventilation. High tracheal
gastrectomy with Roux-en-Y esophagojejunostomy. A jejunal injuries can usually be repaired by extending the cervical
interposition is fashioned with the Roux-en-Y technique. One incision and adding a partial sternotomy. Injury to the carina
or two jejunal arteriovenous arcades are divided to mobilize or the left mainstem bronchus must be repaired via a right
enough jejunum for anastomosis to the thoracic esophagus.
thoracotomy.
A 25 or 28 mm end-to-end anastomosis stapler is passed
through the jejunum into the esophagus. The jejunum is Bleeding
anchored to the pericardium and the proximal esophagus.
The duodenal loop is anastomosed to the jejunum at least 45 Hemorrhage should be rare during esophagectomy. In
to 50 cm distal to the esophagojejunal anastomosis. The blind routine situations, blood loss should amount to less than
end of the jejunal loop is then stapled closed. 500 mL. The blood supply to the esophagus consists of small
branches coming from the aorta, which are easily controlled
and generally constrict even if left untied. Splenic injuries
avoiding bulky foods (e.g., meat and bread) in the early post- sometimes occur during mobilization of the stomach. The
operative period, and taking measures to minimize postpran-
resultant hemorrhage can be immediate or delayed; blood
dial dumping. Patients are also taught how to care for their
loss may be significant, and splenectomy is usually required.
temporary feeding jejunostomy. Consumption of caffeine and
Precise dissection around the left gastric artery is vital: the
carbonated beverages is usually limited during the first few
bleeding vessels may retract, and attempts at control may
weeks after discharge.
result in injury to the celiac artery or its hepatic branches.
A barium swallow is performed on postoperative day 7 to
Similarly, peripancreatic vessels may be difficult to control if
verify the integrity of the anastomosis and gastric emptying.
inadvertently injured during the Kocher maneuver.
Patients are usually discharged on postoperative day 7 or 8.
Bleeding that arises during the mediastinal stage of the
The feeding jejunostomy is left in place until the first postop-
transhiatal esophagectomy generally subsides with packing if
erative evaluation, which usually takes place 2 to 3 weeks
it derives from periesophageal arterial branches. Brisk loss of
after the operation. The feeding tube is removed during that
dark blood usually signifies injury to the azygos vein. The first
visit if oral intake and weight are stable.
step in addressing such injuries is to pack the mediastinum
complications of esophagectomy quickly so as to allow the anesthetic team to stabilize the
patient and restore volume. Chest tubes are immediately
Pulmonary Impairment placed to allow detection of any free hemorrhage into the
Atelectasis and pneumonia should be considered pleural space. Precise localization of the bleeding site may
preventable complications of esophagectomy. Patients with then follow. Injury to the azygos vein may be addressed via
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an upper sternal split; however, when the exposure is poor, fat stimulates a brisk flow of chyle and greatly facilitates
the surgeon should not hesitate to proceed to a full sternot- visualization of any thoracic duct injury.
omy. Bleeding from the subcarinal area is usually bright red Right-side chyle leaks are approached via either a thora-
and may involve bronchial arteries or small periesophageal cotomy or video-assisted thoracoscopy. The magnification
vessels arising from the aorta, both of which can usually be and excellent illumination associated with thoracoscopy
controlled through the hiatus with a long-handled pistol-grip are partially counterbalanced by the constraints imposed by
clip applier or electrocautery. port placement and limited tissue retraction. The inferior
pulmonary ligament is divided, and the posterior mediasti-
Laryngeal Nerve Injury num is inspected for extravasation of milky fluid. Any visible
Injury to the recurrent laryngeal nerve is a major potential sources of chyle leakage can be controlled with clips or suture
complication of transhiatal esophagectomy. Traction neuro- ligatures. In some cases, mass ligation of the thoracic duct at
praxia may be temporary and require no specific treatment. the level of the diaphragm, incorporating all of the soft tissue
Permanent injury will lead to hoarseness and impaired pro- between the aorta and the azygos vein, may be required.
tection of the airway during deglutition. Pneumonia from Left-side leaks can be difficult to manage. The subcarinal
aspiration is a major problem. Meticulous protection of the area is typically involved; this is the level at which the thoracic
nerve during the cervical stage should minimize the incidence duct crosses over from the right. Exploration should begin on
of this complication. If laryngeal nerve injury becomes appar- the left side. If the leak cannot be visualized, a right-side
ent in the postoperative period, early medialization of the approach may be necessary to control the thoracic duct as it
affected cord should be performed by an otolaryngologist to first enters the chest.
enhance the ability of the patient to cough and to prevent Anastomotic Leakage
aspiration.
Of particular concern is the risk of bilateral nerve injury The consequences of anastomotic complications after
after a transthoracic esophagectomy with a cervical esophago- esophagectomy vary considerably in severity, depending on
their location and cause. The cervical anastomotic leaks that
gastric anastomosis (i.e., a so-called three-hole esophagec-
may develop after transhiatal esophagectomy are generally
tomy). Any dissection of the upper esophagus performed
simple to treat. Leaks in the early postoperative period are
through the right chest should be done as close to the esoph-
usually related to technical factors (e.g., excessive tension
agus as possible to avoid placing traction on the right recur-
across the anastomosis). A nonviable stomach may not give
rent laryngeal nerve; the subsequent left cervical dissection
rise to obvious signs; thus, any possibility of ischemia in the
may put the left recurrent laryngeal nerve at risk for damage.
transposed stomach must be addressed promptly. Tachycar-
Bilateral paralysis of the vocal cords is very poorly tolerated
dia, confusion, leukocytosis, cervical wound drainage, and
and has a devastating impact on quality of life.
neck tenderness may or may not be present.
Chylothorax The morbidity of an open cervical wound is not high—it is
certainly lower than that of an untreated leak. Accordingly,
Thoracic duct injuries typically present by postoperative
any clinical suspicion of a leak should prompt a diagnostic
day 3 or 4. Dyspnea and pleural effusion may be noted if
contrast swallow study using dilute barium. Large leaks are
thoracostomy tubes are not in place. Thoracentesis yields an
manifested as persistent collections of contrast material out-
opaque, milky fluid. In patients who already have a chest
side the esophagus. Although such leaks rarely extend into
drain in place, there is typically a high volume of serous
the pleural space, any fluid in the chest must be drained so
drainage in the first 2 postoperative days. As enteral nutrition that its nature can be determined. The neck wound is opened
is established and dietary fat is reintroduced, the fluid assumes by removing the sutures and performing gentle digital explo-
a characteristic milky appearance. In most cases, the gross ration of the prevertebral space behind the esophagus as the
appearance is diagnostic, and there is rarely a need to confirm finger is advanced into the mediastinum; this is usually done
the diagnosis by measuring the triglyceride level. A thoracos- at the bedside and requires little, if any, patient sedation.
tomy drain is placed to monitor the volume of the chyle leak Saline-moistened gauze packing is changed three or four
if one is not present. Chest x-rays should be obtained to verify times a day. Prolonged or copious cervical drainage may call
complete drainage of the pleural space and full expansion of for supplemental deep wound aspiration with a Yankauer
the lung. suction handle. Administering water orally during aspiration
Patients with chylothorax should be converted to fat-free facilitates removal of any necrotic debris. A fetid, malodorous
enteral nutrition. Persistent drainage exceeding 500 mL per breath associated with sanguineous discharge from the naso-
day is an indication for early operation and ligation of the gastric tube and purulent fluid in the opened neck incision
thoracic duct; high-volume chyle leaks are unlikely to close are ominous signs that should prompt early esophagoscopy.
spontaneously. Prolonged loss of chyle causes significant Diffuse mucosal ischemia may indicate the presence of a
electrolyte, nutritional, and immunologic derangements that nonviable stomach; reoperation with completion gastrectomy
may prove fatal if allowed to progress. Accordingly, patients and proximal esophagostomy is required to treat this rare
with persistent chyle leakage should undergo operation within catastrophic complication.
1 week of diagnosis. A feeding tube is placed in the duode- Generally, leaks that occur more than 7 days after opera-
num before operation if a jejunostomy tube is not already tion are small and are related to some degree of late ischemic
in place. Jejunal feeding with 35% cream at a rate of 60 to disruption along the anastomosis. They can usually be man-
80 mL/hr is maintained for at least 4 hours before operation. aged by opening the cervical wound at the bedside and pack-
Feeding is continued even during the procedure: the enteral ing the site with gauze. Oral diet is advanced as tolerated. It
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may be noted that the volume of the leak is markedly greater specifically sought: these are the major quality-of-life issues
or less depending on the position of the head during swallow- for postesophagectomy patients.4 Reflux and regurgitation
ing. Accordingly, before discharge, patients are taught how to may complicate any form of alimentary reconstruction after
temporarily adjust their swallowing and how to manage their esophagectomy, although cervical anastomoses are less likely
dressing changes. Applying gentle pressure to the neck wound to be associated with symptomatic reflux than intrathoracic
and turning the head to the left may help the patient ingest anastomoses are. Reflux symptoms generally respond to
liquids with minimal soiling of the open neck incision. dietary modifications, such as smaller and more frequent
Dysphagia, even with an opened neck incision, should be meals. Regurgitation is usually related to the supine position
treated by passing tapered esophageal dilators orally between and thus tends to be worse at night; elevating the bed and
2 and 4 weeks after surgery. When a bougie at least 48 French avoiding late meals may suffice for symptom control. Dump-
in caliber can be passed through the anastomosis, the patient ing is exacerbated by foods with high fat or sugar content.
can usually swallow comfortably. The size of the leak often Dysphagia may be related to narrowing at the anastomosis or,
decreases after dilation as food is allowed to proceed prefer- in rare instances, to poor emptying of the transposed stom-
entially into the stomach. To maximize the diameter of the ach. Anastomotic strictures are most commonly encountered
anastomosis and reduce the likelihood of a symptomatic stric- as a sequel to a postoperative leak. There may be excessive
ture, subsequent dilations should be scheduled at 2-week scarring at the anastomosis, associated with local distortion
intervals for the next few months. or angulation. Specific tests for gastric atony include nuclear
When a routine predischarge barium swallow after trans- medicine gastric emptying studies using radiolabeled food.
hiatal esophagectomy raises the possibility of an anastomotic A simple barium swallow may indicate an incomplete
leak in an asymptomatic patient, the question arises of pyloromyotomy as a cause of poor gastric emptying; balloon
whether the wound should be opened at all. For small, dilation often corrects this problem.
contained leaks associated with preferential flow of contrast Any form of anastomotic leak will increase the incidence
material into the stomach, observation alone may suffice in of late stricture. Dysphagia may be treated by means of pro-
selected cases. Patients must be closely watched for fever or gressive dilation with Maloney bougies. This procedure is
other signs of major infection. Given the quite low morbidity performed in the outpatient clinic and often does not require
of cervical wound exploration, the surgeon should not sedation or any other special patient preparation. Complica-
hesitate to drain the neck if the patient’s condition changes. tions are rare if due care is exercised during the procedure.
The incidence of anastomotic leakage is low after Ivor As noted [see Transthoracic Hiatal Hernia Repair, Preopera-
Lewis resection, but the consequences are significant. Leaks tive Evaluation, Dilation, above], it is essential that the caliber
presenting early in the postoperative period are usually related of the dilators be increased gradually and that little or no
to technical problems and are difficult to manage; those force be applied in advancing them. The appearance of blood
presenting later are generally related to some degree of isch- on a withdrawn dilator signals a breach of the mucosa;
emic tissue loss. Patients who have received radiation therapy further dilation should be done cautiously lest a transmural
or are nutritionally depleted may be especially vulnerable to injury results. Comfortable swallowing, of liquids at least, is
problems with anastomotic healing. A contrast swallow with usually achieved after the successful passage of a 48 French
dilute barium is the best method of evaluating the anastomo- bougie. It is preferable, however, to advance dilation until at
sis. Leaks may be manifested either as a free flow of contrast least a 54 French bougie can be passed with ease. For late
into the pleural space or as a contained fluid collection. strictures that are particularly difficult to dilate, endoscopic
Small leaks that drain immediately into properly placed examination and histologic evaluation may be required to
thoracostomy tubes can usually be managed by giving antibi- rule out a recurrent tumor. CT of the chest should also be
otics and withholding oral intake. Local control of infection performed whenever there is unexplained weight loss or
generally results in spontaneous healing. Anastomotic disrup- fatigue late after esophagectomy.
tions that are large or are associated with a major pleural The Savary system of wire-guided dilators has been
collection typically necessitate open drainage with decortica- particularly helpful in the management of tight or eccentric
tion; percutaneous drainage may be considered as a prelimi- strictures. Patients are generally treated in the endoscopy
nary approach in selected patients. Persistent soiling of the suite. Temporary sedation with intravenous fentanyl and
mediastinum and the pleural space is fatal if untreated. midazolam is required. Fluoroscopy can be used to confirm
Early esophagoscopy is strongly advised to evaluate the proper placement of a flexible-tip wire across the stricture.
viability of the gastric remnant. Ischemic necrosis of the Serial wire-guided dilation can then be performed with
stomach necessitates reexploration, decortication, takedown confidence and increased patient safety.
of the anastomosis, gastric débridement, return of any viable
stomach into the abdomen, closure of the hiatus, and proxi- outcome evaluation
mal diversion with a cervical esophagostomy. Repair or revi-
sion of the anastomosis in an infected field is certain to fail Transhiatal Esophagectomy
and should never be considered. In certain cases, diversion A 2001 study from the University of Michigan presented
via a cervical esophagostomy and a completion gastrectomy data on 1,085 patients who underwent transhiatal esophagec-
may be required. tomy without thoracotomy, of whom 74% had carcinoma
and 26% had nonmalignant disease.5 Transhiatal esophagec-
Late Complications tomy was completed in 98.6% of the patients; the remaining
At every postoperative visit, symptoms of reflux, regurgita- 1.4% were converted to a transthoracic esophagectomy as
tion, dumping, poor gastric emptying, and dysphagia must be a result of either thoracic esophageal fixation or bleeding.
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Previous chemotherapy or radiation therapy did not preclude reflux symptoms. In some patients, the gastric interposition
performance of a transhiatal esophagectomy. Nine patients rotates into the right posterolateral thoracic gutter, resulting
experienced inordinate intraoperative blood loss; three died in postprandial gastric tension and rendering them more
as a result. The overall hospital mortality was 4%. The over- susceptible to aspiration. Compared to transhiatal esophagec-
all 5-year survival rate for patients undergoing transhiatal tomy, extended transthoracic esophagectomy is associated
esophagectomy is approximately 20% for adenocarcinoma of with higher pulmonary morbidity but no difference in opera-
the cardia and the esophagus and 30% for squamous cell tive mortality or in 5-year survival. A post hoc subset analysis
carcinoma of the esophagus. did suggest a survival advantage of transthoracic resection
The stapled anastomosis described earlier [see Operative with one to eight positive lymph nodes.7,8
Technique, Transhiatal Esophagectomy, Step 8, above] Three-Hole Esophagectomy
reflects numerous refinements introduced at the University of
Michigan. The endoscopic GIA stapler has a low-profile head Three-hole esophagectomy is also associated with low
anastomotic leak rates and mortality similar to Ivor Lewis
that is ideally suited to the tight confines of the neck, enabling
esophagectomy.9 Again, patients are advised to elevate the
the surgeon to fashion a widely patent side-to-side functional
head of the bed and to continue taking acid blockers if
EEA with three rows of staples along the back wall. The rate
they have any reflux symptoms. In some patients, the gastric
of anastomotic stricture is markedly lower with this anasto-
interposition rotates into the right posterolateral thoracic
mosis than with a totally handsewn anastomosis. As regards
gutter, resulting in postprandial gastric tension and rendering
postoperative function, stomach interposition through the
them more susceptible to aspiration. A special note should be
posterior mediastinum after transhiatal esophagectomy is made that cervical leaks with a three-hole esophagectomy can
associated with low rates of aspiration and regurgitation. be more problematic than with a transhiatal esophagectomy
Esophageal reflux and esophagitis—commonly seen with presumably because of the wide opening of the mediastinum
intrathoracic esophagogastric anastomoses—are usually not resulting in a greater tendency of leaks to track down into the
clinically significant problems with this approach. Patients mediastinum.
are advised to elevate the head of their bed and to continue
taking acid blockers for about 3 months after the operation. Left Thoracoabdominal Esophagogastrectomy
Approximately one third will require esophageal dilation Left thoracoabdominal esophagogastrectomy is also associ-
for dysphagia after the operation. Some 7 to 10% experience ated with anastomotic leakage rates and operative mortalities
postvagotomy dumping symptoms, which, in most cases, can of less than 3%.3,10 Approximately 5% of patients will require
be controlled by simply avoiding high-carbohydrate foods esophageal dilation. Reconstructions involving anastomosis
and dairy products. of the distal stomach to the esophagus are associated with a
higher incidence of bile gastritis and esophagitis. Of all the
Ivor Lewis Esophagectomy operations we have described, this one results in the lowest
Ivor Lewis esophagectomy is associated with anastomotic postoperative quality of life. Accordingly, most surgeons
leakage rates and operative mortalities of less than 3%.3,6 prefer to carry out a total gastrectomy. Swallowing is restored
Approximately 5% of patients will require anastomotic dila- with a Roux-en-Y jejunal interposition.
tion. Again, patients are advised to elevate the head of the
bed and to continue taking acid blockers if they have any Financial Disclosures: None Reported.
References
1. Crescenzo DG, Trastek VF, Allen MS, et al. 6. Visbal AL, Allen MS, Miller DL, et al. Ivor esophageal carcinoma. Ann Thorac Surg
Zenker’s diverticulum in the elderly: is opera- Lewis esophagogastrectomy for esophageal 2001;72:1918.
tion justified? Ann Thorac Surg 1998;66: cancer. Ann Thorac Surg 2001;71:1803. 10. Akiyama H, Miyazono H, Tsurumaru M,
347. 7. Hulscher JBF, van Sandick JW, de Boer AG, et al. Thoracoabdominal approach for carci-
2. Stirling MC, Orringer MB. Continued et al. Extended transthoracic resection com- noma of the cardia of the stomach. Am J Surg
assessment of the combined Collis-Nissen pared with limited transhiatal resection for 1979;137:345.
operation. Ann Thorac Surg 1989;47:224. adenocarcinoma of the esophagus. N Engl J
3. Mathiesen DJ, Grillo HC, Wilkens EW Jr. Med 2002;347:1662.
Transthoracic esophagectomy: a safe ap- 8. Omloo JMT, Lagarde SM, Hulscher JBF,
proach to carcinoma of the esophagus. Ann et al. Extended transthoracic resection com- Acknowledgments
Thorac Surg 1988;45:137. pared with limited transhiatal resection for
4. Finley RJ, Lamy A, Clifton J, et al. Gastro- adenocarcinoma of the mid/distal esophagus. The authors and editors gratefully acknowledge
intestinal function following esophagectomy Five year survival of a randomized clinical the contributions of the previous authors, John
for malignancy. Am J Surg 1995;169:471. trial. Ann Surg 2007;246:992. Yee, MD, FRCSC, and Richard J. Finley, MD,
5. Orringer MB, Marshall B, Iannettoni MD. 9. Swanson SJ, Battirel HF, Bueno R, et al. FACS, FRCSC, to the development and writing
Transhiatal esophagectomy for treatment of Transthoracic esophagectomy with radical of this chapter.
benign and malignant esophageal disease. mediastinal and abdominal lymph node
World J Surg 2001;25:196. dissection and cervical esophagastrostomy for Figures 1 through 23 Tom Moore
02/10
4 THORAX 8 MINIMALLY INVASIVE ESOPHAGEAL PROCEDURES — 1
8 MINIMALLY INVASIVE
ESOPHAGEAL PROCEDURES
Francesco Palazzo, MD, Piero M. Fisichella, MD, Marco G. Patti, MD, FACS
The development of laparoscopic surgery over the past should be investigated, and symptoms should be graded with
20 years has caused a significant shift in the treatment of respect to their intensity both before and after the operation.
benign esophageal diseases. Nonetheless, a diagnosis of GERD should never be based
In the first part of the 1990s, it became clear that treatment solely on symptomatic evaluation. Some assert that the
of benign esophageal disorders with minimally invasive diagnosis can be made reliably from the clinical history,9 so
procedures yielded results comparable to those of treatment that a complaint of heartburn should lead to the presumption
with traditional operations while causing minimal postopera- that acid reflux is present; however, testing of this diagnostic
tive discomfort, reducing the duration of hospitalization, strategy demonstrates that symptoms are far less sensitive
shortening recovery time, and permitting earlier return to and specific than is usually believed.10 For instance, a study
work.1,2 Consequently, minimally invasive surgery was increas- from the University of California, San Francisco (UCSF),
ingly considered as first-line treatment for achalasia, and found that of 822 consecutive patients referred for esopha-
laparoscopic fundoplication was considered more readily and geal function tests with a clinical diagnosis of GERD (based
at an earlier stage in the management of gastroesophageal on symptoms and endoscopic findings), only 70% had abnor-
reflux disease (GERD). mal reflux on pH monitoring.11 Heartburn and regurgitation
Since then, minimally invasive esophageal procedures were no more frequent in patients who had genuine reflux
have continued to evolve, thanks to better instrumentation than in those who did not; thus, symptomatic evaluation, by
and improved surgical expertise. In addition, with greater itself, could not distinguish between the two groups.
experience and longer follow-up, it has become possible to The response to proton pump inhibitors (PPIs) is a better
analyze techniques and their results more rigorously. For predictor of abnormal reflux. For example, in the UCSF
instance, whereas a few years ago a left thoracoscopic Heller study just cited, 75% of patients with GERD reported a
myotomy was considered the procedure of choice for achala- good or excellent response to PPIs, compared with only 26%
sia, the current procedure of choice is a laparoscopic Heller of patients without GERD.11 Similarly, a study involving
myotomy with partial fundoplication, which has proved to be multivariate analysis of factors predicting outcome after
better at relieving dysphagia and controlling postoperative laparoscopic fundoplication identified a clinical response to
reflux.3–6 Similarly, whereas total fundoplication and partial acid suppression therapy as one of three factors predictive
fundoplication were initially considered equally effective in of a successful outcome, the other two being an abnormal
treating GERD,7 total fundoplication is currently used even 24-hour pH score and the presence of a typical primary
when peristalsis is weak. Long-term results have, in fact, symptom (e.g., heartburn).12 In addition, a 2007 report found
shown that although the dysphagia rates of the two proce- that patients with a body mass index (BMI) of 35 kg/m2 or
dures are similar, total fundoplication achieves better control greater experienced higher failure rates after laparoscopic
of reflux than partial fundoplication.8 Nissen fundoplication.13 These data support the theory that
In this chapter, we focus on minimally invasive approaches GERD in morbidly obese patients has a different pathophys-
to the treatment of GERD and esophageal motility disorders. iology and may warrant a different therapeutic approach
The standard open counterparts of these operations are (e.g., laparoscopic Roux-en-Y gastric bypass [see 5:7 Surgical
described elsewhere [see 4:7 Open Esophageal Procedures]. Treatment of Morbid Obesity]).14
Upper Gastrointestinal Series

Laparoscopic Nissen Fundoplication An upper GI series is useful for diagnosing and character-
izing an existing hiatal hernia. The size of the hiatal hernia
preoperative evaluation
helps predict how difficult it will be to reduce the esophago-
All patients who are candidates for a laparoscopic gastric junction below the diaphragm. In addition, large
fundoplication should undergo a preoperative evaluation hiatal hernias are associated with more severe disturbances
that includes the following: (1) symptomatic evaluation, (2) of esophageal peristalsis and esophageal acid clearance.15
an upper gastrointestinal (GI) series, (3) endoscopy, (4) Esophagograms are also useful for determining the location,
esophageal manometry, and (5) ambulatory pH monitoring. shape, and size of a stricture and for suggesting the presence
of a short esophagus.
Symptomatic Evaluation
The presence of both typical symptoms (heartburn, regur- Endoscopy
gitation, and dysphagia) and atypical symptoms of GERD Endoscopy is typically the first test performed to confirm a
(cough, asthma, chest pain, dental erosions, and hoarseness) symptom-based diagnosis of GERD. This approach has two
DOI 10.2310/7800.S04C08
07/08
pitfalls. First, even though the goal of endoscopy is to assess and specificity in detecting and characterizing gastroesophageal
the mucosal damage caused by reflux, mucosal changes are reflux, and the results have been shown to be highly
absent in about 50% of GERD patients.11 Second, major reproducible.20
interobserver variations have been reported with esophageal Although this technology is still not widely available, it has
endoscopy, particularly for low-grade esophagitis.16 In one already been demonstrated to be useful in the workup of patients
study, for instance, 60 (24%) of 247 patients with negative with GERD refractory to PPIs and patients with respiratory
results on pH monitoring had been diagnosed as having grade symptoms of unknown origin.21
I or II esophagitis.11 Endoscopy is also valuable for excluding
gastric and duodenal pathologic conditions and detecting the operative planning
presence of Barrett’s esophagus. The patient is placed under general anesthesia and intubated
Esophageal Manometry with a single-lumen endotracheal tube. Abdominal wall relax-
ation is ensured by the administration of a nondepolarizing
Esophageal manometry provides useful information about muscle relaxant, the action of which is rapidly reversed at the
the motor function of the esophagus by determining the
end of the operation. Adequate muscle relaxation is essential
length and resting pressure of the lower esophageal sphincter
because increased abdominal wall compliance allows increased
(LES) and assessing the quality (i.e., the amplitude and prop-
pneumoperitoneum, which yields better exposure. An orogastric
agation) of esophageal peristalsis. In addition, it allows proper
tube is inserted at the beginning of the operation to keep
placement of the pH probe for ambulatory pH monitoring
the stomach decompressed; it is removed at the end of the
(5 cm above the upper border of the LES).
procedure.
Ambulatory pH Monitoring The patient is placed in a steep reverse Trendelenburg posi-
Ambulatory pH monitoring is the most reliable test for the tion, with the legs extended on stirrups. The surgeon stands
diagnosis of GERD, with a sensitivity and specificity of about between the patient’s legs. To keep the patient from sliding as a
92%.17 It is of key importance in the workup for the following result of the steep position used during the operation, a bean
four reasons. bag is inflated under the patient, and the knees are flexed
only 20° to 30°. A Foley catheter is inserted at the beginning of
1. It determines whether abnormal reflux is present. In the the procedure and usually is removed at the end. Because
UCSF study mentioned earlier,11 pH monitoring yielded increased abdominal pressure from pneumoperitoneum and the
normal results in 30% of patients with a clinical diagnosis steep reverse Trendelenburg position decrease venous return,
of GERD, thereby obviating the continuation of inappro- pneumatic compression stockings are always used as prophylaxis
priate and expensive drugs (e.g., PPIs) or the performance
against deep vein thrombosis.
of a fundoplication. In addition, pH monitoring prompted
The equipment required for a laparoscopic Nissen fundopli-
further investigation that in a number of cases pointed
cation includes five 10 mm trocars, a 30° laparoscope, a hook
to other diseases (e.g., cholelithiasis and irritable bowel
cautery, and various other instruments [see Table 1]. In addition,
syndrome).
we use a three-chip camera system that is separate from the
2. It establishes a temporal correlation between symptoms
laparoscope.
and episodes of reflux. Such a correlation is particularly
important when atypical GERD symptoms (e.g., cough operative technique
and chest pain) are present because 50% of these patients
A total fundoplication is the procedure of choice. A partial
experience no heartburn and 50% do not have esophagitis
on endoscopy.18 fundoplication [see Laparoscopic Partial (Guarner) Fundoplica-
3. It allows staging on the basis of disease severity. Specifi- tion, below] is performed only when peristalsis is absent.22,23 The
cally, esophageal manometry and pH monitoring identify operation may be divided into nine key steps as follows.
a subgroup of patients characterized by worse esophageal
motor function (manifested by a defective LES or by
abnormal esophageal peristalsis), more acid reflux in the
distal and proximal esophagus, and slower acid clearance. Table 1 Instrumentation for Laparoscopic Nissen
These patients more frequently have Barrett metaplasia Fundoplication
and experience respiratory symptoms; thus, they might Five 10 mm trocars
benefit from early antireflux surgery.19 30° scope
4. It provides baseline data that may prove useful postopera- Graspers and needle holder
Babcock clamp
tively if symptoms do not respond to the procedure.
L-shaped hook cautery with suction-irrigation capacity
Scissors
Multichannel Intraluminal Impedance and pH Com- Laparoscopic clip applier
bined multichannel intraluminal impedance and pH testing LigasSure™ Vessel Sealing System*
(MII-pH) has the ability to detect episodes of reflux, regardless Fan retractor
Endo Stitch device†
of the pH of the refluxate, by identifying changes induced by Penrose drain
the presence of a bolus in the esophagus; the episodes are 2-0 silk sutures
then simply classified as acid or nonacid on the basis of con- 56 French esophageal bougie
comitantly recorded pH values. Studies of healthy persons *(Valleylab, Boulder, CO)
have demonstrated that MII-pH possesses increased sensitivity †(Autosuture, Norwalk, CT)
07/08
Step 1: Placement of Trocars take down the short gastric vessels is placed through the same
Five 10 mm trocars are used for the operation [see Figure 1]. port, it will not reach the upper short gastric vessels. If ports
Port A is placed about 14 cm below the xiphoid process; it can D and E are too low, the dissection at the beginning of the
also be placed slightly (2 to 3 cm) to the left of the midline to procedure and the suturing at the end are problematic.
be in line with the hiatus. This port is used for insertion of the Other mistakes of positioning must be avoided as well. Port
scope. Port B is placed at the same level as port A but in the left C must not be placed too medially, because the fan retractor
midclavicular line. It is used for insertion of the Babcock clamp; may clash with the left-hand instrument; the gallbladder fossa is
insertion of a grasper to hold the Penrose drain once it is in place a good landmark for positioning this port. Port A must be placed
surrounding the esophagus; or insertion of an instrument to take with extreme caution in the supraumbilical area: its insertion site
down the short gastric vessels. Port C is placed at the same level is just above the aorta, close to its bifurcation. Accordingly, we
as the previous two ports but in the right midclavicular line. It initially inflate the abdomen to a pressure of 18 mm Hg just for
is used for insertion of the fan retractor, the purpose of which is placement of port A; increasing the distance between the
to lift the lateral segment of the left hemiliver and expose the abdominal wall and the aorta reduces the risk of aortic injury.
esophagogastric junction. We do not divide the left triangular We also recommend directing the port toward the coccyx. Once
ligament. The fan retractor can be held in place by a self- port A is in place, the intraperitoneal pressure is reduced to
retaining system fixed to the operating table. Ports D and E are 15 mm Hg. A Hasson cannula can be used in this location,
placed as high as possible under the costal margin and about particularly if the patient has already had one or more midline
5 to 6 cm to the right and the left of the midline so that they are incisions. Maintaining the proper angle (60° to 120°) between
about 15 cm from the esophageal hiatus; in addition, they should the axes of the two suturing instruments inserted through ports
be placed so that their axes form an angle of 60° to 120°. These D and E is also important: if the angle is smaller, the instruments
ports are used for insertion of the graspers, the electrocautery, will cover part of the operating field, whereas if it is larger, depth
and the suturing instruments. perception may be impaired. Finally, if a trocar is not in the ideal
position, it is better to insert another one than to operate through
Troubleshooting If the ports are placed too low in the an inconveniently placed port.
abdomen, the operation is made more difficult. If port C is too If the surgeon spears the epigastric vessels with a trocar,
low, the fan retractor will not retract the left lateral section of the bleeding will occur, in which case we prefer to ligate the vessel
liver well, and the esophagogastric junction will not be properly under laparoscopic guidance. We favor the Carter-Thomason
exposed. If port B is too low, the Babcock clamp will not reach CloseSure System (Inlet Medical, Inc., Eden Prairie, MN) to
the esophagogastric junction, and when the instrument used to ligate the vessel securely with 0 absorbable suture. Once hemo-
stasis is obtained, the surgeon simply repositions the trocar away
from the vessels.
Step 2: Division of Gastrohepatic Ligament; Identification of

Right Crus of Diaphragm and Posterior Vagus Nerve
Once the ports are in place, the gastrohepatic ligament is
divided. Dissection begins above the caudate lobe (segments 1
and 9) of the liver, where this ligament usually is very thin, and
continues toward the diaphragm until the right crus is identified.
The crus is then separated from the right side of the esophagus
by blunt dissection, and the posterior vagus nerve is identified.
The right crus is dissected inferiorly toward the junction with the
left crus.
Troubleshooting An accessory left hepatic artery originat-

ing from the left gastric artery is frequently encountered in
the gastrohepatic ligament. If this vessel creates problems of
exposure, it may be divided; in our experience, doing so has not
caused problems. In dissecting the right crus from the esopha-
gus, the electrocautery should be used with particular caution.
Because the monopolar current tends to spread laterally, the
posterior vagus nerve may sustain damage simply from being in
proximity to the device, even when there is no direct contact. A
better alternative is to use a bipolar instrument.
Step 3: Division of Peritoneum and Phrenoesophageal

Membrane above Esophagus; Identification of Left Crus of
Diaphragm and Anterior Vagus Nerve
The peritoneum and the phrenoesophageal membrane above
the esophagus are divided with the electrocautery, and the ante-
Figure 1 Laparoscopic Nissen fundoplication. Illustrated is rior vagus nerve is identified. The left crus of the diaphragm is
the recommended placement of the trocars. dissected downward toward the junction with the right crus.
07/08
Troubleshooting Care must be taken not to damage the CT); the sutures are tied intracorporeally. Exposure is pro-
anterior vagus nerve or the esophageal wall. To this end, the vided by retracting the esophagus upward and toward the
nerve should be left attached to the esophageal wall, and patient’s left with the Penrose drain. The lens of the 30°
the peritoneum and the phrenoesophageal membrane should be laparoscope is angled slightly to the left by moving the light
lifted from the wall by blunt dissection before they are divided. cable of the scope to the patient’s right. The first stitch should
be placed just above the junction of the two pillars. Addi-
Step 4: Division of Short Gastric Vessels tional stitches are placed 1 cm apart, and a space of about
The 5 mm laparoscopic LigaSure Vessel Sealing System 1 cm is left between the uppermost stitch and the esophagus.
(Valleylab, Boulder, CO) is introduced through port B. A
grasper is introduced by the surgeon through port D, and an Troubleshooting Care must be taken not to spear
assistant applies traction on the greater curvature of the stomach esophageal wall with the needle. So as not to limit the space
through port E. Dissection begins at the level of the middle por- available for suturing, the bougie is not placed inside the
tion of the gastric body and continues upward until the most esophagus during this part of the procedure.
proximal short gastric vessel is divided.
Step 7: Insertion of Bougie into Esophagus and through
Troubleshooting There are two problems to watch for Esophagogastric Junction
during this part of the procedure: (1) bleeding, either from the The esophageal stethoscope and the orogastric tube are
short gastric vessels or from the spleen, and (2) damage to the removed, and a 56 French bougie is inserted by the anesthe-
gastric wall. siologist and passed through the esophagogastric junction
Bleeding from the short gastric vessels is usually caused by under laparoscopic vision. The crura must be snug around
excessive traction or by division of a vessel that is not completely the esophagus but not too tight: a closed grasper should slide
coagulated. Vessels up to 5 mm in diameter can be taken down easily between the esophagus and the crura.
with the LigaSure device. Damage to the gastric wall can be
caused by a burn from the electrocautery used to dissect between Troubleshooting The most worrisome complication
vessels or by traction applied with the graspers or the Babcock during this step is perforation of the esophagus. This can be
clamp. prevented by lubricating the bougie and instructing the anes-
Step 5: Creation of Window between Gastric Fundus, Esophagus, thesiologist to advance the bougie slowly and to stop if any
and Diaphragmatic Crura; Placement of Penrose Drain around resistance is encountered. In addition, it is essential to remove
Esophagus any instruments from the esophagogastric junction and to
open the Penrose drain; these measures prevent the creation
The esophagus is retracted upward with a Babcock clamp
of an angle between the stomach and the esophagus, which
applied at the level of the esophagogastric junction. By means of
can increase the likelihood of perforation. The position of the
blunt and sharp dissection, a window is created under the
bougie can be confirmed by pressing with a grasper over the
esophagus between the gastric fundus, the esophagus, and the
esophagus, which will feel full when the bougie is in place.
left pillar of the crus. The window is enlarged with the LigaSure
device, and a Penrose drain is passed around the esophagus. Step 8: Wrapping of Gastric Fundus around Lower Esophagus
This drain is then used for traction instead of the Babcock clamp
The gastric fundus is gently pulled under the esophagus
to reduce the risk of damage to the gastric wall.
with the graspers. The left and right sides of the fundus are
wrapped above the fat pad (which lies above the esophago-
Troubleshooting The two main problems to watch
gastric junction) and held together in place with a Babcock
for during this part of the procedure are (1) creation of a left
clamp introduced through port B. (The Penrose drain should
pneumothorax and (2) perforation of the gastric fundus.
be removed at this point because it is in the way.) Usually,
A left pneumothorax is usually caused by dissection done
three 2-0 silk sutures are used to secure the two ends of the
above the left pillar of the crus in the mediastinum rather
wrap to each other. The stitches do not include the esopha-
than between the crus and the gastric fundus. This problem
gus. Two coronal stitches are then placed between the top of
can be avoided by properly dissecting and identifying the left
pillar of the crus. the wrap and the esophagus, one on the right and one on the
Perforation of the gastric fundus is usually caused by push- left. Finally, one additional suture is placed between the right
ing a blunt instrument under the esophagus and below the side of the wrap and the closed crura.
left pillar without having done enough dissection. Care must To avoid the risk of injuring the inferior vena cava at the
be exercised in taking down small vessels from the fundus beginning of the dissection, some surgeons use a different
when the area behind the esophagus is approached from the method—the so-called left crus approach.22 In this approach, the
right: the anatomy is not as clear from this viewpoint, and operation begins with identification of the left crus of the dia-
perforation can easily occur. Sometimes, perforation is caused phragm and division of the peritoneum and the phrenoesopha-
by the use of a monopolar electrocautery for dissection. An geal membrane overlying it. The next step is division of the short
electrocautery burn can go unrecognized during dissection gastric vessels, starting midway along the greater curvature of the
and manifest itself in the form of a leak during the first 48 stomach and continuing upward to join the area of the previous
hours after operation. dissection. When the fundus has been thoroughly mobilized,
the peritoneum is divided from the left to the right crus, and the
Step 6: Closure of Crura right crus is dissected downward to expose the junction of the
The diaphragmatic crura are closed with interrupted 2-0 right and left crura. With this technique, the vena cava is never
silk sutures on an Endo Stitch device (Autosuture, Norwalk, at risk. In addition, the branches of the anterior vagus nerve and
07/08
the left gastric artery are less exposed to danger. This technique pulled under the esophagus) or from inadvertent electrocautery
can be very useful, particularly for management of very large burns during any part of the dissection. A leak will manifest itself
paraesophageal hernias and for second antireflux operations [see during the first 48 hours. Peritoneal signs will be noted if the
Reoperation for GERD, below]. spillage is limited to the abdomen; shortness of breath and a
pleural effusion will be noted if spillage also occurs in the chest.
Troubleshooting To determine whether the wrap is going The site of the leak should always be confirmed by a contrast
to be floppy, the surgeon must deliver the fundus under the study with barium or a water-soluble contrast agent. Optimal
esophagus, making sure that the origins of the short gastric management consists of laparotomy and direct repair. If a
vessels that have been transected are visible. Essentially, the perforation is detected intra-operatively, it may be closed
posterior wall of the fundus is being used for the wrap. If the laparoscopically.
wrap remains to the right of the esophagus without retracting Almost every patient experiences some degree of dysphagia
back to the left, then it is floppy, and suturing can proceed. If postoperatively. This problem usually resolves after 4 to 6 weeks,
not, the surgeon must make sure that the upper short gastric during which period patients receive pain medications in an
vessels have been transected and the posterior dissection com- elixir form and are advised to avoid eating meat and bread. If,
pleted. If tension is still present after these maneuvers, it is however, dysphagia persists beyond this period, one or more of
probably best to perform a partial wrap [see Laparoscopic Partial the following causes is responsible.
(Guarner) Fundoplication, below]. 1. A wrap that is too tight or too long (i.e., > 2.5 cm).24
Damage to the gastric wall may occur during the delivery of 2. Lateral torsion with corkscrew effect. If the wrap rotates
the fundus. Atraumatic graspers must be used, and the gastric to the right (because of tension from intact short gastric
fundus must be pulled gently and passed from one grasper to vessels or because the fundus is small), a corkscrew effect
the other. Sometimes, it is helpful to push the gastric fundus is created.
under the esophagus from the left. The wrap should measure no 3. A wrap made with the body of the stomach rather than the
more than 2 to 2.5 cm in length and, as noted, should be done fundus. The relaxation of the LES and the gastric fundus
with no more than three sutures. The first stitch is usually the is controlled by vasoactive intestinal polypeptide and nitric
lowest one; it must be placed just above the fat pad where the oxide25,26; after fundoplication, the two structures relax
esophagogastric junction is thought to be. simultaneously with swallowing. If part of the body of the
If the anesthesiologist observes that peak airway pressure has stomach rather than the fundus is used for the wrap, it will
increased (because of a pneumothorax) or that neck emphysema not relax as the LES does on arrival of the food bolus.
is present (because of pneumomediastinum), the pneumoperi- 4. Choice of the wrong procedure. In patients who have
toneum should be reduced from 15 mm Hg to 8 or 10 mm Hg severely abnormal esophageal peristalsis (as in end-stage
until the end of the procedure. Pneumomediastinum tends to connective tissue disorders), a partial wrap is preferable. A
resolve without intervention within a few hours of the end of the 360° wrap may cause postoperative dysphagia and gas
procedure. Small pneumothoraces (usually on the left side) tend bloat syndrome.
to resolve spontaneously, rendering insertion of a chest tube
unnecessary. Larger pneumothoraces (> 20%), however, call for If the wrap slips into the chest, the patient may experience
the insertion of a small (18 to 20 French) chest tube. dysphagia and regurgitation.The diagnosis is confirmed by
means of a barium swallow. This problem can be prevented by
Step 9: Final Inspection, Removal of Instruments and Ports using coronal sutures and by ensuring that the crura are closed
from Abdomen, and Closure of Port Sites securely.
After hemostasis is obtained, the instruments and the ports Paraesophageal hernia may occur if the crura have not been
are removed from the abdomen under direct vision. We usually closed or if the closure is too loose. We believe that closure of
close all port sites with 0 absorbable suture material using the the crura not only is essential for preventing paraesophageal
Carter-Thomason CloseSure System. hernia but also is important from a physiologic point of view, in
that it acts synergistically with the LES against stress reflux.
Troubleshooting If any areas of oozing were observed, Sometimes, it is possible to reduce the stomach and close the
they should be irrigated and dried with sponges rolled into a crura laparoscopically. More often, however, because the crural
cigarettelike shape before the ports are removed. In addition, if opening is very tight and the gastric wall is edematous, laparo-
some grounds for concern remain, the oozing areas should be scopic repair is impossible and laparotomy is preferable.
examined after the pneumoperitoneum is decreased to 7 to postoperative care and outcome evaluation
8 mm Hg to abolish the tamponading effect exerted by the high
Postoperative care and outcome evaluation of laparoscopic
intra-abdominal pressure.
Nissen fundoplication are considered elsewhere in conjunction
All the ports should be removed from the abdomen under
with the discussion of partial fundoplication [see Laparoscopic
direct vision so that any bleeding from the abdominal wall can
Partial (Guarner) Fundoplication, Postoperative Care and
be readily detected. Such bleeding is easily controlled, either
Outcome Evaluation, below].
from inside or from outside.
complications
Laparoscopic Partial (Guarner) Fundoplication
A feared complication of laparoscopic Nissen fundoplication
is esophageal or gastric perforation, which may result either from preoperative evaluation and operative planning
traction applied with the Babcock clamp or a grasper to the Preoperative evaluation and operative planning are essentially
esophagus or the stomach (particularly when the stomach is the same for partial (Guarner) fundoplication as for Nissen
07/08
fundoplication. This operation should be performed only in that raised concerns about long-term durability of the proce-
patients with the most severe abnormalities of esophageal peri- dure.31 This study has been criticized on the grounds that many
stalsis: it is less effective than a 360° wrap for long-term control of the patients were taking PPIs for reasons other than reflux
of reflux.8 In addition, laparoscopic partial fundoplication may symptoms and that the reflux status was not assessed by pH
be performed after laparoscopic Heller myotomy for achalasia monitoring. A 2006 study aimed at critically assessing 10-year
[see Laparoscopic Heller Myotomy with Partial Fundoplication, outcomes reported results from 100 consecutive patients after
below].27 complete and partial fundoplication.32 In this series, the rate of
symptomatic control of reflux symptoms at 5 and 10 years was
operative technique 90%, with fewer than 10% of patients using antiacid medica-
The first seven steps in a Guarner fundoplication are identical tions at 10 years; only one patient required reintervention
for persistent dysphagia. Similar results were documented
to the first seven in a Nissen fundoplication. The wrap, however,
in subsequent studies,33,34 confirming laparoscopic Nissen
differs in that it extends around only 240° to 280° of the esoph-
fundoplication as an effective long-term treatment for GERD.
ageal circumference. Once the gastric fundus is delivered under
the esophagus, the two sides are not approximated over the
esophagus. Instead, 80° to 120° of the anterior esophagus is left Laparoscopic Heller Myotomy with Partial
uncovered, and each of the two sides of the wrap (right and left) Fundoplication
is separately affixed to the esophagus with three 2-0 silk sutures, Minimally invasive surgical procedures for primary esopha-
with each stitch including the muscle layer of the esophageal geal motility disorders (achalasia, diffuse esophageal spasm
wall. The remaining stitches (i.e., the coronal stitches and the [DES], nutcracker esophagus [NE] and hypertensive LES
stitch between the right side of the wrap and the closed crura) [H-LES]) yield results that are comparable to those of open
are identical to those placed in a Nissen fundoplication. procedures but are associated with less postoperative pain and
with a shorter recovery time.35 Today, laparoscopic Heller
postoperative care myotomy with partial fundoplication has supplanted left thora-
Currently, our average operating time for a laparoscopic coscopic myotomy as the procedure of choice for esophageal
fundoplication is approximately 2 hours. We start patients on a achalasia.3–6 Long-term studies demonstrated that even though
soft mechanical diet on the morning of postoperative day 1 and left thoracoscopic myotomy led to resolution of dysphagia
usually discharge them after 23 to 48 hours. The recovery time in about 85% to 90% of patients, it had the following four
typically ranges from 10 to 14 days. drawbacks.
outcome evaluation 1. Gastroesophageal reflux developed postoperatively in

about 60% of patients because no fundoplication was
The initial results of laparoscopic fundoplication obtained performed in conjunction with the myotomy.3 With the
in the early 1990s indicated that the operation was effective in laparoscopic approach, in contrast, a partial fundoplica-
controlling reflux but that postoperative dysphagia occurred tion can easily be performed, which prevents reflux in
more often than had been anticipated.7 Many experts thought the majority of patients3,4 and corrects many instances of
that this problem could be avoided by tailoring the fundoplica- preexisting reflux arising from pneumatic dilatation.3 A
tion to the strength of esophageal peristalsis as measured by prospective, randomized, double-blind clinical trial that
esophageal manometry.7 Accordingly, partial fundoplication compared Heller myotomy alone with Heller myotomy
(240°) was recommended for patients with impaired peristalsis, and Dor fundoplication clearly demonstrated that the
and total fundoplication (360°) was recommended for those addition of a fundoplication is essential: the incidence of
with normal peristalsis. The short-term results of this tailored postoperative reflux (as measured by pH monitoring) was
approach were promising.7 Gradually, however, it became 48% in patients who underwent myotomy alone but
evident that a partial fundoplication was not as durable as a total only 9% in those who underwent myotomy and Dor
fundoplication8 and that a total fundoplication was not associ- fundoplication.36
ated with a higher incidence of postoperative dysphagia even in 2. The extension of the myotomy onto the gastric wall (clearly
patients with weak peristalsis.28,29 the most critical and challenging part of the operation)
These findings suggest that the initial problems with post- proved difficult because of poor exposure, with the conse-
quent risk of a short myotomy and persistent dysphagia.
operative dysphagia were primarily attributable to unknown
With the laparoscopic approach, in contrast, excellent
technical factors that were largely eliminated from the procedure
exposure of the esophagogastric junction is easily achieved,
as surgeons garnered more experience with it. As a result, total
and the myotomy can be extended onto the gastric wall for
fundoplication is currently considered the procedure of choice
about 2 to 2.5 cm.3,37
for patients with GERD, regardless of the strength of their 3. Double-lumen endotracheal intubation and single-lung
esophageal peristalsis. ventilation were required, with the patient in the right
In a 2007 study, pre- and postoperative manometric results lateral decubitus position. In contrast, the setting for a
were reviewed in 71 patients who underwent laparoscopic laparoscopic myotomy (the same as that for a laparoscopic
fundoplication. Not only did LES pressure increase after the fundoplication) is much easier for the patient, the anesthe-
procedure, but distal esophageal amplitude also increased in siologist, and the operating room personnel. In addition,
patients with abnormal preoperative motility, with normalization most surgeons have by now acquired substantial experi-
of peristalsis occurring in the majority of patients.30 A 2001 ence with laparoscopic antireflux procedures and thus are
report found that 62% of fundoplication patients were using more familiar and comfortable with laparoscopic exposure
antireflux medications 10 years after the operation, a finding of the distal esophagus and the esophagogastric junction.
07/08
4. The average postoperative hospital stay was about 3 days Either a Dor or a Guarner fundoplication [see Laparoscopic
because of the chest tube left in place at the time of the Partial (Guarner) Fundoplication, above] may be performed in
operation and the discomfort arising from the thoracic conjunction with a Heller myotomy. The Dor fundoplication is
incisions. After a laparoscopic Heller myotomy, the hospi- an anterior 180° wrap. Its advantages are that (1) it does not
tal stay is only 1 or 2 days; there is no need for a chest require posterior dissection and the creation of a window
tube, and patients are more comfortable. between the esophagus, the stomach, and the left pillar of the
crus; (2) it covers the exposed esophageal mucosa after comple-
Although there is now a consensus on the preferred
tion of the myotomy; and (3) it is effective even in patients with
treatment of achalasia, there is no such general agreement on
GERD.41 Its main disadvantage is that achieving the proper
the treatment of the remaining primary esophageal motility
geometry can be difficult, and a wrong configuration can lead to
disorders (i.e., DES, NE, and H-LES). We reported our
dysphagia even after a properly performed myotomy.42 The
experience comparing thoracoscopic and laparoscopic
advantages of the Guarner fundoplication are that (1) it is easier
approaches to these disorders and found (1) that laparoscopic
to perform; (2) it keeps the edges of the myotomy well sepa-
myotomy was superior to thoracoscopic myotomy in relieving rated; and (3) it might be more effective than a Dor procedure
dysphagia in patients with DES and H-LES, and (2) that the in preventing reflux. Its main disadvantages are that (1) it
two approaches yielded equally disappointing results with requires more dissection for the creation of a posterior window,
respect to relieving chest pain in patients with NE, the surgi- and (2) it leaves the esophageal mucosa exposed.
cal treatment of which remains elusive.38 These results
support the view that laparoscopic Heller myotomy should Steps 1 through 6
be the standard surgical treatment for achalasia, DES, and Steps 1, 2, 3, 4, 5, and 6 of a laparoscopic Heller myotomy
H-LES. Accordingly, we would consider surgical intervention are essentially identical to the first six steps of a laparoscopic
(laparoscopic Heller myotomy) in an NE patient only in an fundoplication. Steps 5 and 6, however, are necessary only if a
attempt at relieving severe dysphagia. posterior partial fundoplication is to be performed. Care must
We no longer perform a long myotomy via a right thoraco- be taken not to narrow the esophageal hiatus too much and push
scopic approach. the esophagus anteriorly.
preoperative evaluation Step 7: Intraoperative Endoscopy
All candidates for a laparoscopic Heller myotomy should At the beginning of a surgeon’s experience with laparo-
undergo a thorough and careful evaluation to establish the scopic Heller myotomy, intraoperative endoscopy is an
diagnosis and characterize the disease.39 important and helpful step; however, once the surgeon
An upper GI series is useful. A characteristic so-called bird’s has gained adequate experience with this procedure and
beak is usually seen in patients with achalasia. A dilated, sigmoid has become familiar with the relevant anatomy from a
esophagus may be present in patients with long-standing laparoscopic perspective, it may be omitted.
achalasia. A corkscrew esophagus is often seen in patients with
diffuse esophageal spasm. Endoscopy is performed to rule out a Troubleshooting The most worrisome complication dur-
tumor of the esophagogastric junction and gastroduodenal ing intraoperative endoscopy is perforation of the esophagus.
pathologic conditions. This complication can be prevented by having the procedure
Esophageal manometry is the key test for establishing the done by an experienced endoscopist who is familiar with
diagnosis of esophageal achalasia. The classic manometric achalasia.
findings are (1) absence of esophageal peristalsis and (2) an LES
that fails to relax appropriately in response to swallowing. Step 8: Initiation of Myotomy and Entry into Submucosal
Ambulatory pH monitoring should always be done in patients Plane at Single Point
who have undergone pneumatic dilatation to rule out abnormal The fat pad is removed with the LigaSure device to provide
gastroesophageal reflux. In addition, pH monitoring should be clear exposure of the esophagogastric junction. A Babcock clamp
performed postoperatively to detect abnormal reflux, which, if is then applied over the junction, and the esophagus is pulled
present, should be treated with acid-reducing medications.39 downward and to the left to expose the right side of the esopha-
In patients older than 60 years who have experienced the gus. The myotomy is performed at the 11 o’clock position. It is
recent onset of dysphagia and excessive weight loss, secondary helpful to mark the surface of the esophagus along the line
achalasia or pseudoachalasia from cancer of the esophagogastric through which the myotomy will be carried out [see Figure 2].
junction should be ruled out. Endoscopic ultrasonography or The myotomy is started about 3 cm above the esophagogastric
computed tomography can help establish the diagnosis.40 junction. Before it is extended upward and downward, the
proper submucosal plane should be reached at a single point; in
operative planning this way, the likelihood of subsequent mucosal perforation can
Patient preparation (i.e., anesthesia, positioning, and instru- be reduced.
mentation) is identical to that for laparoscopic fundoplication.
Troubleshooting The myotomy should not be started
operative technique close to the esophagogastric junction, because at this level the
Many of the steps in a laparoscopic Heller myotomy are the layers often are poorly defined, particularly if multiple dilatations
same as the corresponding steps in a laparoscopic fundoplica- or injections of botulinum toxin have been performed. At the
tion. The ensuing description focuses on those steps that differ preferred starting point, about 3 cm above the esophagogastric
significantly. junction, the esophageal wall is usually normal. As a rule, we do
07/08
Figure 2 Laparoscopic Heller myotomy with partial Figure 3 Laparoscopic Heller myotomy with partial
fundoplication. The proposed myotomy line is marked on the fundoplication. The myotomy is extended proximally and
surface of the esophagus. distally.
not open the entire longitudinal layer first and then the circular
layer; we find it easier and safer to try to reach the submucosal
plane at a single point and then move upward and downward vagus nerve while removing the fat pad. Treatment with botuli-
from there. In the course of the myotomy, there is always some num toxin occasionally results in fibrosis with scarring and loss
bleeding from the cut muscle fibers, particularly if the esophagus of the normal anatomic planes; this occurs more frequently at
is dilated and the wall is very thick. After the source of the bleed- the level of the esophagogastric junction.
ing is identified, the electrocautery must be used with caution. If a perforation seems possible or likely, it should be sought
The most troublesome bleeding comes from the submucosal as described earlier [see Step 7: Intraoperative Endoscopy,
veins encountered at the esophagogastric junction (which are above]. Any perforation found should be repaired with 5-0
usually large). In most instances, gentle compression is prefer- absorbable suture material, with interrupted sutures employed
able to electrocautery. A sponge introduced through one of the for a small perforation and a continuous suture for a larger one.
ports facilitates the application of direct pressure. When a perforation has occurred, an anterior fundoplication is
usually chosen in preference to a posterior one because the
Step 9: Proximal and Distal Extension of Myotomy stomach will offer further protection against a leak.
Once the mucosa has been exposed, the myotomy can safely
be extended [see Figure 3]. Distally, it is extended for about 2 to Step 10 (Dor Procedure): Anterior Partial Fundoplication
2.5 cm onto the gastric wall; proximally, it is extended for about Two rows of sutures are placed. The first row (on the left
6 cm above the esophagogastric junction. Thus, the total length side) comprises three stitches: the uppermost stitch incorporates
of the myotomy is typically about 8 to 8.5 cm [see Figure 4]. We the gastric fundus, the esophageal wall, and the left pillar of the
find it useful to alternate between a dolphin-nose grasper and crus [see Figure 5], and the other two incorporate only the gastric
using a curved micrograsper during extension of the myotomy; fundus and the left side of the esophageal wall [see Figure 6]. The
this makes the dissection safer, in that it allows the muscle fibers gastric fundus is then folded over the myotomy, and the second
to be separated from the mucosa before being transected. row (also comprising three stitches) is placed on the right side
between the fundus and the right side of the esophageal wall,
Troubleshooting The course of the anterior vagus nerve with only the uppermost stitch incorporating the right pillar
must be identified before the myotomy is started. If this nerve of the crus [see Figure 7 and Figure 8]. Finally, two additional
crosses the line of the myotomy, it must be lifted away from the stitches are placed between the anterior rim of the hiatus and the
esophageal wall, and the muscle layers must then be cut under superior aspect of the fundoplication [see Figure 9]. These stitches
it. In addition, care must be taken not to injure the anterior remove any tension from the second row of sutures.
07/08
Figure 4 Laparoscopic Heller myotomy with partial Figure 6 Laparoscopic Heller myotomy with anterior partial
fundoplication. The myotomy is approximately 8 cm long, fundoplication (Dor procedure). The second and third
extending distally for about 2 to 2.5 cm onto the gastric wall stitches in the first row incorporate only the fundus and the
and proximally for about 6 cm above the esophagogastric left side of the esophageal wall.
junction.
Figure 5 Laparoscopic Heller myotomy with anterior partial Figure 7 Laparoscopic Heller myotomy with anterior partial
fundoplication (Dor procedure). The uppermost stitch in the fundoplication (Dor procedure). The uppermost stitch in the
first row incorporates the fundus, the esophageal wall, and second row incorporates the fundus, the esophageal wall, and
the left pillar of the crus. the right crus.
07/08
Troubleshooting Efforts must be made to ensure that the

fundoplication does not become a cause of postoperative dys-
phagia. Accordingly, we always take down the short gastric ves-
sels, even though some authorities suggest that this step can be
omitted.4,40 In addition, the gastric fundus rather than the body
of the stomach should be used for the wrap, and only the upper-
most stitch of the right row of sutures should incorporate the
right pillar of the crus.41
Step 10 (Guarner Procedure): Posterior Partial Fundoplication

Alternatively, a posterior 220° fundoplication may be per-
formed. The gastric fundus is delivered under the esophagus,
and each side of the wrap (right and left) is attached to the
esophageal wall, lateral to the myotomy, with three sutures [see
Figure 10].
Step 11: Final Inspection and Removal of Instruments and

Ports from Abdomen
Step 11 of a laparoscopic Heller myotomy is identical to step
9 of a laparoscopic Nissen fundoplication.
complications
Delayed esophageal leakage, usually resulting from an electro-
cautery burn to the esophageal mucosa, may occur during the
first 24 to 36 hours after operation. The characteristic signs and
Figure 8 Laparoscopic Heller myotomy with anterior partial symptoms are chest pain, fever, and a pleural effusion on the
fundoplication (Dor procedure). The second and third chest x-ray. The diagnosis is confirmed by an esophagogram.
stitches in the second row incorporate only the fundus and the Treatment options depend on the time of diagnosis and on the
right side of the esophageal wall. size and location of the leak. Early, small leaks can be repaired
directly. If the site of the leak is high in the chest, a thoracotomy
Figure 9 Laparoscopic Heller myotomy with anterior partial Figure 10 Laparoscopic Heller myotomy with posterior
fundoplication (Dor procedure). Two final stitches are placed partial fundoplication (Guarner procedure). Each side of the
between the superior portion of the wrap and the anterior rim posterior 220° wrap is attached to the esophageal wall with
of the hiatus. three sutures.
07/08
is recommended; if the site is at the level of the esophagogastric preoperative evaluation

junction, a laparotomy is preferable, and the stomach can be Preoperative evaluation is essentially the same as that for
used to reinforce the repair. If the damage to the esophagus is laparoscopic Heller myotomy.
too extensive to permit repair, an esophagectomy [see 4:7 Open
Esophageal Procedures] is indicated. operative planning
Dysphagia may either persist after the operation or recur after The patient is placed under general anesthesia and intu-
a symptom-free interval. In either case, a complete workup is bated with a double-lumen endotracheal tube so that the left
necessary, and treatment is individualized on the basis of the lung can be deflated during the procedure. As for a left
specific cause of dysphagia. Reoperation may be indicated [see thoracotomy, the patient is placed in the right lateral decubi-
Reoperation for Esophageal Achalasia, below]. tus position over an inflated bean bag. The instrumentation
Abnormal gastroesophageal reflux occurs in 7 to 20% of is similar to that for a laparoscopic Nissen or Guarner
patients after operation.3,4 Because most patients are asympto- fundoplication. Instead of conventional trocars, four or five
matic, it is essential to try to evaluate all patients postoperatively thoracoports with blunt obturators are employed, because
with manometry and prolonged pH monitoring. Reflux should insufflation of the thoracic cavity is not required. The
be treated with acid-reducing medications. myotomy can be performed with a monopolar hook cautery,
postoperative care bipolar scissors, or an ultrasonic scalpel. A 30° scope and
a 45° scope are essential for thoracoscopic procedures. In
We do not routinely obtain an esophagogram before initiating addition, an endoscope is used for intraoperative endoscopy.
feeding. Patients are started on a soft mechanical diet on the
morning of postoperative day 1, and this diet is continued for operative technique
the rest of the first week. Patients are discharged after 24 to 48
hours and are able to resume regular activities in 7 to 14 days. Step 1: Placement of Thoracoports
Five ports are usually placed [see Figure 11]. Port A, used
outcome evaluation for the 30° scope, is inserted in the sixth intercostal space
The results obtained to date with laparoscopic Heller myo- about 3.5 to 5 cm behind the posterior axillary line. Port B,
tomy and partial fundoplication are excellent and are generally used for the lung retractor, is placed in the third intercostal
comparable to those obtained with the corresponding open space about 1.25 to 2.5 cm anterior to the posterior axillary
surgical procedure: dysphagia is alleviated or eliminated in more line. Port C, used for insertion of a grasper, is placed in the
than 90% of patients.3,6,42 These results have been confirmed sixth intercostal space in the anterior axillary line. Port D,
in long-term follow-up outcome studies. One report from the used for insertion of the instrument employed for the
University of Padua found that at a minimum of 6 years myotomy, is placed in the seventh intercostal space in the
after surgical intervention, 85% of myotomy patients were midaxillary line. Port E is placed in the eighth intercostal
satisfied.43 space between the anterior axillary line and the midaxillary
In a 2008 report describing our experience with 113 patients line. This port is optional: it is needed in about 30% of
treated for achalasia with laparoscopic Heller myotomy and cases to allow the surgeon to obtain further exposure of
Dor fundoplication, we found that at a median follow-up of the esophagogastric junction through retraction of the
45 months (range, 7 months to 12.5 years), 80% experienced diaphragm.
complete relief of dysphagia after the operation.44 The remaining
20% required endoscopic dilatation, which was successful in Troubleshooting A common mistake is to insert port
50% of the cases. We have observed a significant change in the A too anteriorly. This port must be placed well beyond the
treatment algorithm for this condition: gastroenterologists now
typically refer these patients for surgical treatment before any
other therapy has been instituted, reserving endoscopic dilata-
tion for cases where operative treatment has failed.45 Overall,
combined treatment yields a success rate of about 90%.
Historically, the presence of a sigmoid-shaped esophagus has
been considered a contraindication to performing a myotomy to
treat longstanding achalasia, making esophagectomy the only
option. In the study just mentioned,44 we subdivided the patients
according to the degree of esophageal dilatation and observed
the responses to surgery in the various groups. Even in those
cases where the esophageal diameter exceeded 6 cm and the
esophagus was sigmoid, the outcomes of laparoscopic myotomy
were not significantly different.44
Left Thoracoscopic Myotomy

Currently, we would consider a left thoracoscopic myotomy
for patients in whom multiple previous abdominal procedures
(done to treat other diseases) would preclude a laparoscopic Figure 11 Left thoracoscopic myotomy. Illustrated is the
approach. recommended placement of the thoracoports.
07/08
posterior axillary line to provide the best angle for the 30° Troubleshooting The endoscope placed inside the
scope. Often, the other ports are placed one or two intercos- esophagus at the beginning of the procedure plays an impor-
tal spaces too high. This mistake hampers the performance of tant role. In the early stages of the procedure, it allows
the most delicate portion of the operation, the myotomy of identification of the esophagus via transillumination. When
the distal portion of the esophagus and the stomach. the light intensity of the 30° scope is turned down, the esoph-
Sometimes, chest wall bleeding occurs as a consequence agus appears as a bright structure. In addition, tilting the tip
of port insertion. This bleeding will obscure the operating of the endoscope brings the esophagus into view as it is lifted
field and therefore must be stopped before the intrathoracic from the groove between the aorta and the heart.
portion of the procedure is begun. This is accomplished
either by using the cautery from the inside or by applying Step 4: Initiation of Myotomy and Entry into Submucosal
a stitch from the outside if an intercostal vessel has been Plane at Single Point
damaged. As in a laparoscopic Heller myotomy, it is helpful to mark
the surface of the esophagus along the line through which the
Step 2: Retraction of Left Lung and Division of Inferior
myotomy will be carried out. The myotomy is started halfway
Pulmonary Ligament
between the diaphragm and the inferior pulmonary vein.
Once the ports are in place, the deflated left lung is retracted Again, the proper submucosal plane should be reached at a
cephalad with a fan retractor introduced through port B. This single point before the myotomy is extended upward and
maneuver places tension on the inferior pulmonary ligament, downward.
which is then divided. After the ligament is divided, the fan
retractor can be held in place by a self-retaining system fixed Troubleshooting Troubleshooting for this step is essen-
to the operating table. tially the same as that for step 8 of a laparoscopic Heller
myotomy, with the exception that here the myotomy is started
Troubleshooting Before the inferior pulmonary liga- 4 to 5 cm (rather than 3 cm) above the esophagogastric
ment is divided, the inferior pulmonary vein must be identi- junction.
fied to prevent a life-threatening injury to this vessel. If oxygen
saturation decreases, particularly in patients with lung dis- Step 5: Proximal and Distal Extension of Myotomy
ease, the retractor should be removed and the lung inflated Once the mucosa has been exposed, the myotomy can
intermittently. safely be extended proximally and distally [see Figure 13]. We
Step 3: Division of Mediastinal Pleura and Dissection of usually extend the myotomy for about 5 mm onto the gastric
Periesophageal Tissues wall, without adding an antireflux procedure.3,4 Typically, the
total length of the myotomy is about 6 cm for patients with
The mediastinal pleura is divided, and the tissues overlying
achalasia.
the esophageal wall are dissected until the wall of the esoph-
agus is visible. This maneuver varies in difficulty depending
Troubleshooting Proximally, the myotomy is extended
on the width of the space between the aorta and the pericar-
all the way to the inferior pulmonary vein only in cases of
dium (which sometimes is very small) and on the size and
shape of the esophagus. Large (sigmoid) esophagi tend to vigorous achalasia (high-amplitude simultaneous contractions
curve to the right, which makes identification of the wall dif- associated with chest pain in addition to dysphagia) or diffuse
ficult. If the esophagus is not immediately apparent, it can be
easily identified in the groove between the heart and the aorta
by means of transillumination provided by an endoscope [see
Figure 12].
Figure 12 Left thoracoscopic myotomy. The esophagus may

be identified by means of transillumination from the Figure 13 Left thoracoscopic myotomy. Shown are the distal
endoscope. and proximal extensions of the myotomy.
07/08
esophageal spasm; otherwise, it is limited to the distal 5 to postoperative care

6 cm of the esophagus. If a longer myotomy is needed, the Patients are started on a liquid diet the morning of post-
lung is displaced anteriorly and the myotomy extended to operative day 1; on postoperative day 2, they are started on
the aortic arch. a soft mechanical diet, which is continued for the rest of the
Distally, the myotomy is continued for 5 mm past the first week. We do not routinely obtain an esophagogram
esophagogastric junction. The endoluminal view provided by before starting feedings. The chest tube is removed after
the endoscope is useful for assessing the location of the 24 hours if the lung is fully expanded and there is no air leak.
esophagogastric junction. Often, the stomach is distended Patients are discharged after 48 to 72 hours and are able to
by the air insufflated by the endoscope and pushes the resume regular activities in 7 to 10 days.
diaphragm upward, thereby limiting the view of the esopha-
gogastric junction. If sucking air out of the stomach does not outcome evaluation
resolve this problem, an additional port (i.e., port E) may be The results obtained with thoracoscopic myotomy are
placed in the eighth intercostal space, and a fan retractor generally comparable to those obtained with corresponding
may be introduced through this port to push the diaphragm open surgical procedures. In a 1999 study from UCSF, 26
down. (87%) of the first 30 patients with achalasia who were
Because the myotomy of the gastric wall is the most treated in this fashion experienced good or excellent results
challenging part of the operation, good exposure is essential. [see Table 2].3 At present, however, this procedure is rarely
It is at this level that an esophageal perforation is most likely used to treat esophageal achalasia: laparoscopic Heller
to occur. The risk is particularly high in patients who have myotomy and Dor fundoplication is now the treatment of
undergone pneumatic dilatation or injection of botulinum choice.45
toxin, both of which may lead to the replacement of muscle
layers by scar tissue and the consequent loss of the regular
Reoperation for GERD
planes. Perforations recognized in the operating room can be
repaired by thoracoscopic intracorporeal suturing or, if this Currently, an increasing number of patients are being seen
fails, by thoracotomy and open repair. The gastric fundus for evaluation and treatment of foregut symptoms after
can be used to buttress the repair. If it is unclear whether a laparoscopic antireflux surgery. These patients are treated as
perforation has occurred, the esophagus should be covered follows.
with water and air insufflated through the endoscope; preoperative evaluation
bubbling will be observed over the site of any perforation
present. Some degree of dysphagia, bloating, and abdominal
discomfort is common during the first 6 to 8 weeks after a
Step 6: Insertion of Chest Tube and Removal of Thoracoports fundoplication. If these symptoms persist or heartburn
A 24 French angled chest tube is inserted under direct and regurgitation occur, a thorough evaluation (with barium
vision through port D or port E. The ports are removed swallow, endoscopy, esophageal manometry, and pH moni-
under direct vision, and the thoracic wall is inspected for toring) is carried out with the aim of answering the following
bleeding. three questions:
complications 1. Are the symptoms attributable to persistent gastroesopha-

geal reflux?
As with laparoscopic Heller myotomy, delayed esophageal 2. Are the symptoms attributable to the fundoplication
leakage is a common postoperative complication, and treat- itself?
ment options are similar. 3. Can the cause of the failure of the first operation be
If the myotomy is not extended far enough onto the gastric identified and corrected by a second operation?
wall, residual dysphagia occurs. To prevent this problem, the
distal extent of the myotomy should be assessed by means of Many patients report heartburn after a fundoplication. It is
endoscopy with the goal of including 5 mm of the gastric often assumed that this symptom must be the result of a failed
wall. Patients with residual dysphagia must be evaluated operation and that acid-reducing medications should be
by means of esophageal manometry, which will document restarted. In most cases, however, this assumption is mistaken:
the extent of the residual high-pressure zone and the
pressure within it. The myotomy can be easily extended by a
laparoscopic approach, and a Dor fundoplication can be Table 2 Results of Thoracoscopic Myotomy in 30
added. Patients with Achalasia3
If, on the other hand, the myotomy is extended too far onto
the gastric wall, abnormal gastroesophageal reflux occurs. Results Patients (% of Total)
Some patients present with heartburn; others are asympto-
Excellent (no dysphagia) 21 (70)
matic. It is essential to evaluate patients postoperatively with
manometry and prolonged pH monitoring. Mild reflux can Good (dysphagia < once/wk) 5 (17)
be treated with acid-reducing medications, particularly in
elderly patients. In younger patients, abnormal reflux should Fair (dysphagia > once/wk) 3 (10)
be corrected with a laparoscopic partial fundoplication Poor (persistent dysphagia) 1 (3)
(e.g., Dor fundoplication).
07/08
postoperative pH monitoring yields abnormal results in only the diaphragm (short esophagus), esophageal lengthening
about 20% of patients.46 The value of manometry lies in its can be accomplished by adding a thoracoscopic Collis
ability to document the changes caused by the operation at the gastroplasty to the fundoplication. To date, however, we
level of the LES and the esophageal body. The pH monitoring have never found this step to be necessary.
assesses the reflux status and determines whether there is a
correlation between symptoms and actual episodes of reflux. If complications
abnormal reflux is in fact present, the therapeutic choice is Because the risk of gastric or esophageal perforation or damage
between medical therapy and a second operation. to the vagus nerves is much higher during a second antireflux
Other patients complain of dysphagia arising de novo after the operation, the surgeon must proceed with extreme care, making
operation. This symptom is usually attributable to the operation sure to identify structures completely before dividing them.
itself and may occur in the absence of abnormal reflux. In Most perforations are recognized and repaired intraoperatively.
addition to manometry and pH monitoring, a barium swallow Leaks manifest themselves during the first 48 hours. Peritoneal
is essential to define the anatomy of the esophagogastric junc- signs are noted if the spillage is limited to the abdomen;
tion. A study from the University of Washington found that the shortness of breath and a pleural effusion are noted if spillage
anatomic configurations observed could be divided into three also occurs in the chest. The site of the leak should always be
main types: (1) type I hernia, in which the esophagogastric confirmed by means of a contrast study with barium or a water-
junction was above the diaphragm (subdivided into type IA, soluble agent. Perforation is best handled with laparotomy and
with both the esophagogastric junction and the wrap above the direct repair of the leak.
diaphragm, and type IB, with only the esophagogastric junction
outcome evaluation
above the diaphragm); (2) type II hernia, a paraesophageal con-
figuration; and (3) type III hernia, in which the esophagogastric Whereas the success rate is around 80 to 90% for a first anti-
junction was below the diaphragm and there was no evidence of reflux operation, it falls to 70 to 80% for a second such opera-
hernia but in which the body of the stomach rather than the tion. In our view, a second operation should be attempted by an
fundus was used for the wrap.47 In 10% of patients, however, expert team only if medical management fails to control heart-
the cause of the failure could not be identified preoperatively.38 burn or dilatation has not relieved dysphagia.
Some patients present with a mix of postprandial bloating,
nausea, and diarrhea. These symptoms may be the result of Reoperation for Esophageal Achalasia
damage to the vagus nerves. Radionuclide evaluation of gastric
Laparoscopic Heller myotomy improves swallowing in more
emptying often helps quantify the problem.
than 90% of patients. What causes the relatively few failures
operative planning reported is still incompletely understood. Typically, a failed
Heller myotomy is signaled either by persistent dysphagia or by
Patient preparation (i.e., anesthesia, positioning, and instru-
recurrent dysphagia that develops after a variable symptom-free
mentation) for a reoperation for reflux is identical to that for the
interval following the original operation.
initial laparoscopic fundoplication.
A complete workup (routinely including barium swallow,
operative technique endoscopy, manometry, and pH monitoring) is required before
treatment is planned. In addition, it is our practice to review the
We do not routinely attempt a second antireflux operation video of the first operation to search for technical errors that
laparoscopically. To provide a stepwise technical description might have been responsible for the poor outcome. Such errors
that would be suitable for all reoperations for reflux is impossi- typically fall into one of the following three categories.
ble, because the optimal procedure depends on the original
approach (open versus laparoscopic), the severity of the adhe- 1. A myotomy that is too short either distally or proximally. If
sions, and the specific technique used for the first operation the myotomy is too short distally, a barium swallow shows
(total or partial fundoplication). The key goals of reoperation for persistent distal esophageal narrowing and manometry shows
reflux are as follows. a residual high-pressure zone. If the myotomy is too short
proximally, it will be apparent from the barium swallow.
1. To dissect the wrap and the esophagus away from the 2. A constricting Dor fundoplication. Often, manometry and
crura. This is the most difficult part of the operation. The pH monitoring yield normal results, but a barium swallow
major complications seen during this part of the procedure shows slow passage of contrast media from the esophagus
are damage to the vagus nerves and perforation of the into the stomach. In one study from UCSF,40 problems with
esophagus and the gastric fundus. Dor fundoplications occurred in four (4%) of 102 patients.
2. To take down the previous repair. The earlier repair must Analysis of the video records of the first operations showed
be completely undone and the gastric fundus returned to that in three of the four patients, all the stitches in the right
its natural position. If the short gastric vessels were not suture row had incorporated the esophagus, the right pillar of
taken down during the first procedure, they must be taken the crus, and the stomach, thereby constricting the myotomy.
down during the second. In one patient, the short gastric vessels had not been taken
3. To dissect the esophagus in the posterior mediastinum so down, and the body of the stomach rather than the fundus
as to have enough esophageal length below the diaphragm had been used for the fundoplication.
and avoid placing tension on the repair. 3. Transmural scarring caused by previous treatment.
4. To reconstruct the cardia. The same steps are followed In patients treated with intrasphincteric injection of
as for a first-time repair. If, after extensive esophageal botulinum toxin, transmural fibrosis can sometimes be
mobilization, the esophagogastric junction remains above found at the level of the esophagogastric junction. This
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unwelcome finding makes the myotomy more difficult and esophageal mucosa during the dissection. A small hole can
the results less reliable. be repaired, but a larger laceration might necessitate an
esophagectomy. This option should always be discussed with
There are two treatment options for persistent or recurrent
the patient before the operation. It is our belief that the
dysphagia after Heller myotomy: (1) pneumatic dilatation
and (2) a second operation tailored to the results of pre- surgeon attempting a reoperation after a failed attempt at
operative evaluation. In a 2002 study,48 pneumatic dilatation surgical treatment of achalasia should perform a laparotomy,
was successfully used to treat seven of 10 patients who expe- even though several reports have stressed the feasibility of
rienced dysphagia postoperatively; of the remaining three laparoscopic reoperation after a failed myotomy.49
patients, two required a second operation and one refused Overall, about 10 to 20% of patients experience some
any treatment. degree of dysphagia after a Heller myotomy. Pneumatic dila-
Reoperation for achalasia is technically challenging. It is of tation, a second myotomy, or both should always be tried
paramount importance to avoid perforating the exposed before an esophagectomy is considered.
References
1. Hinder RA, Filipi CJ, Wetscher G, et al. 15. Patti MG, Goldberg HI, Arcerito M, et al. reflux and defective peristalsis. Surg Endosc
Laparoscopic Nissen fundoplication is an Hiatal hernia size affects the lower esophageal 2002;16:909.
effective treatment for gastroesophageal sphincter function, esophageal acid exposure, 29. Novitsky YW, Wong J, Kercher KW, et al.
reflux disease. Ann Surg 1994;220:472. and the degree of mucosal injury. Am J Surg Severely disordered esophageal peristalsis is
2. Pellegrini CA, Wetter LA, Patti MG, et al. 1996;171:182. not a contraindication to laparoscopic Nissen
Thoracoscopic esophagomyotomy: initial 16. Bytzer P, Havelund T, Moller Hansen J. fundoplication. Surg Endosc 2007;21:950.
experience with a new approach for the Inter-observer variation in the endoscopic 30. Herbella FA, Tedesco P, Nipomnick I, et al.
treatment of achalasia. Ann Surg 1992;216: diagnosis of reflux esophagitis. Scand J Effect of partial and total laparoscopic fundo-
291. Gastroenterol 1993;28:119. plication on esophageal body motility. Surg
3. Patti MG, Pellegrini CA, Horgan S, et al. 17. Fuchs KH, DeMeester TR, Albertucci M. Endosc 2007;21:285
Minimally invasive surgery for achalasia: an 8 Specificity and sensitivity of objective diagno- 31. Spechler SJ, Lee E, Ahnen D, et al. Long
year experience with 168 patients. Ann Surg sis of gastroesophageal reflux disease. Surgery term outcome of medical and surgical thera-
1999;230:587. 1987;102:575. pies for gastroesophageal reflux disease:
4. Zaninotto G, Costantini M, Molena D, et al. 18. Patti MG, Arcerito M, Tamburini A, et al. follow-up of a randomized controlled trial.
Treatment of esophageal achalasia with lapa- Effect of laparoscopic fundoplication on JAMA 2001;285:2331.
roscopic Heller myotomy and Dor partial gastroesophageal reflux disease–induced 32. Dallemagne B, Weerts J, Markiewicz S, et al.
anterior fundoplication: prospective evalua- respiratory symptoms. J Gastrointest Surg Clinical results of laparoscopic fundoplica-
tion of 100 consecutive patients. J Gastroin- 2000;4:143. tion at ten years after surgery. Surg Endosc
test Surg 2000;4:282. 19. Diener U, Patti MG, Molena D, et al. Esoph- 2006;20:159.
5. Ackroyd R, Watson DI, Devitt PG, et al. ageal dysmotility and gastroesophageal reflux 33. Morgenthal CB, Shane MD, Stival S, et al.
Laparoscopic cardiomyotomy and anterior disease. J Gastrointest Surg 2001;5:260. The durability of laparoscopic Nissen fundo-
partial fundoplication for achalasia. Surg 20. Mainie I, Tutuian R, Shay S, et al. Acid and plication: 11-year outcomes. J Gastrointest
Endosc 2001;15:683. non-acid reflux in patients with persistent Surg 2007;11:693.
6. Finley RJ, Clifton JC, Stewart KC, et al. symptoms despite acid suppressive therapy: 34. Kelly JJ, Watson DI, Chin KF, et al. Laparo-
Laparoscopic Heller myotomy improves a multicentre study using combined ambula- scopic Nissen fundoplication: clinical out-
esophageal emptying and the symptoms of tory impedance-pH monitoring. Gut 2006;55: comes at 10 years. J Am Coll Surg 2007;205:
achalasia. Arch Surg 2001;136:892. 1398. 570.
7. Patti MG, Arcerito M, Feo CV, et al. An 21. Hirano I, Richter JE; Practice Parameters 35. Patti MG, Pellegrini CA, Arcerito M, et al.
analysis of operations for gastroesophageal Committee of the American College of Comparison of medical and minimally inva-
reflux disease: identifying the important Gastroenterology. ACG practice guidelines: sive surgical therapy for primary esophageal
technical elements. Arch Surg 1998;133:600. esophageal reflux testing. Am J Gastroenterol motility disorders. Arch Surg 1995;130:609.
8. Horvath KD, Jobe BA, Herron DM, et al. 2007;102:668. 36. Richards WO, Torquati A, Holzman MD,
Laparoscopic Toupet fundoplication is an 22. Horgan S, Pellegrini CA. Surgical treatment et al. Heller myotomy versus Heller myotomy
inadequate procedure for patients with severe of gastroesophageal reflux disease. Surg Clin and Dor fundoplication for achalasia: a
reflux disease. J Gastrointest Surg 1999;3: North Am 1997;77:1063. prospective randomized, double-blind clini-
583. 23. Patti MG, Robinson T, Galvani C, et al. cal trial. Ann Surg 2004;240:405.
9. Sonnenberg A, Delco F, El-Serag HB. Total fundoplication is superior to partial 37. Oelschlager BK, Chang L, Pellegrini CA.
Empirical therapy versus diagnostic tests in fundoplication even when esophageal peri- Improved outcome after extended gastric
gastroesophageal reflux disease: a medical stalsis is weak. J Am Coll Surg 2004;198: myotomy for achalasia. Arch Surg 2003;138:
decision analysis. Dig Dis Sci 1998;43:1001. 863. 490.
10. Johnsson F, Joelsson B, Gudmundsson K, 24. Patterson EJ, Herron DM, Hansen PD, et al. 38. Patti MG, Gorodner MV, Galvani C, et al.
et al. Symptoms and endoscopic findings Effect of an esophageal bougie on the inci- The spectrum of esophageal motility dis-
in the diagnosis of gastroesophageal reflux dence of dysphagia following Nissen fundo- orders: implications for diagnosis and treat-
disease. Scand J Gastroenterol 1987;22:714. plication: a prospective, blinded, randomized ment. Arch Surg 2005;140:442.
11. Patti MG, Diener U, Tamburini A, et al. Role clinical trial. Arch Surg 2000;135:1055. 39. Patti MG, Diener U, Molena D. Esophageal
of esophageal function tests in the diagnosis 25. Guelrud M, Rossiter A, Souney PF, et al. The achalasia: preoperative assessment and post-
of gastroesophageal reflux disease. Dig Dis effect of vasoactive intestinal polypeptide on operative follow-up. J Gastrointest Surg 2001;
Sci 2001;46:597. the lower esophageal sphincter in achalasia. 5:11.
12. Campos GM, Peters JH, DeMeester TR, Gastroenterology 1992;103:377. 40. Moonka R, Patti MG, Feo CV, et al. Clinical
et al. Multivariate analysis of factors pre- 26. Tottrup A, Svane D, Forman A. Nitric oxide presentation and evaluation of malignant
dicting outcome after laparoscopic Nissen mediating NANC inhibition in opossum pseudoachalasia. J Gastrointest Surg 1999;3:
fundoplication. J Gastrointest Surg 1999;3: lower esophageal sphincter. Am J Physiol 456.
292. 1991;260:G385. 41. Watson DI, Liu JF, Devitt PG, et al. Out-
13. Morgenthal CB, Lin E, Shane MD, et al. 27. Champion JK, Delisle N, Hunt T. Laparo- come of laparoscopic anterior 180-degree
Who will fail laparoscopic Nissen fundoplica- scopic esophagomyotomy with posterior par- partial fundoplication for gastroesophageal
tion? Preoperative prediction of long-term tial fundoplication for primary esophageal reflux disease. J Gastrointest Surg 2000;4:
outcomes. Surg Endosc 2007;21:1978. motility disorders. Surg Endosc 2000;14: 486.
14. Herbella FA, Sweet MP, Tedesco P, et al. 746. 42. Patti MG, Molena D, Fisichella PM, et al.
Gastroesophageal reflux disease and obesity: 28. Oleynikov D, Eubanks TR, Oelschlager BK, Laparoscopic Heller myotomy and Dor fun-
pathophysiology and implication for treat- et al. Total fundoplication is the operation doplication for achalasia: analysis of successes
ment. J Gastrointest Surg 2007;11:286. of choice for patients with gastroesophageal and failures. Arch Surg 2001;136:870.
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43. Costantini M, Zaninotto G, Guirroli E, et al. treatment of esophageal achalasia: a decade after laparoscopic Heller myotomy for
The laparoscopic Heller-Dor operation of change. J Am Coll Surg 2003;196:698. achalasia. Ann Surg 2002;235:186.
remains an effective treatment for esophageal 46. Lord RVN, Kaminski A, Oberg S, et al. 49. Iqbal A, Tierney B, Haider M, et al.
achalasia at a minimum 6-year follow-up. Absence of gastroesophageal reflux disease in Laparoscopic re-operation for failed Heller
Surg Endosc 2005;19:345. a majority of patients taking acid suppression myotomy. Dis Esoph 2006;19:193.
44. Sweet MP, Nipomnick I, Gasper WJ, et al. medications after Nissen fundoplication.
The outcome of laparoscopic Heller myo- J Gastrointest Surg 2002;6:3.
tomy for achalasia is not influenced by the 47. Horgan S, Pohl D, Bogetti D, et al. Failed
degree of esophageal dilatation. J Gastrointest antireflux surgery: what have we learned from
Surg 2008;12:159. reoperations? Arch Surg 1999;134:809.
Acknowledgment
45. Patti MG, Fisichella PM, Perretta S, et al. 48. Zaninotto G, Costantini M, Portale G, et al.
Impact of minimally invasive surgery on the Etiology, diagnosis and treatment of failures Figures 1 through 13 Tom Moore.
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4 THORAX 9 CHEST WALL PROCEDURES — 1
9 CHEST WALL PROCEDURES

Bryon J. Boulton, MD, and Seth D. Force, MD
Chest wall procedures are an important component of any there was a significant difference in maximum voluntary
thoracic surgeon’s practice. The approach to these proce- ventilation.3 In a study that compared 37 patients who had
dures is somewhat different from the approach to esophageal undergone surgical repair of pectus excavatum both with
or pulmonary resections and requires specific knowledge of normal persons and with persons who had uncorrected defor-
thoracic musculoskeletal anatomy, as well as of the different mities, no differences in physical working capacity among
types of autologous and artificial grafts available for chest wall the three groups were noted.4 Other studies have reported
reconstruction. Broadly, chest wall procedures may be divided improvements in exercise tolerance and regional ventilation
into those performed to treat congenital chest wall disease and perfusion after surgical repair of pectus excavatum.5,6 On
and those done to treat acquired disease. In what follows, we the other hand, some investigators have reported decreases in
describe the major surgical techniques in both categories and pulmonary function in symptomatic patients after corrective
review the pitfalls that may accompany them. surgery. One group attributed this result to overly aggressive
resection in very young patients that led to growth restriction
of the chest wall; accordingly, they recommended delaying
Procedures for Congenital Chest Wall Disease
surgical repair until 6 to 8 years of age.7
Congenital chest wall defects arise from abnormal develop- Severe pectus excavatum has also been reported to cause
ment of the sternum, the costal cartilages, and the ribs. Such cardiac dysfunction secondary to sternal compression of the
defects include pectus excavatum (funnel chest), pectus cari- right ventricle. Several early studies found stroke volume and
natum (pigeon chest), cleft sternum, and Poland syndrome cardiac output to be lower in exercising upright patients than
(absence of the breast and the underlying pectoralis muscle in supine patients.8,9 However, improvement in cardiac func-
and ribs). Of these, pectus excavatum is by far the most tion after pectus excavatum repair has not been universally
common, accounting for more than 90% of all congenital documented. In one study, first-pass radionuclide angiocar-
chest wall procedures; accordingly, the ensuing discussion diography failed to show any improvements in left ventricular
focuses on the surgical aspects of pectus excavatum repair. function after repair of pectus excavatum.10 At present, there
repair of pectus excavatum is no consensus on the cardiopulmonary benefits of pectus
excavatum repair, and the major reasons for surgical treat-
Preoperative Evaluation ment are still patient discomfort and dissatisfaction with
Because pectus excavatum occurs in varying degrees of appearance.
severity, patients may seek surgical treatment for any of a
Operative Technique
number of different reasons, such as shortness of breath, early
fatigue with exercise, or simple dissatisfaction with their A number of different procedures have been employed to
appearance. Thus, one of the most important tasks for sur- treat pectus excavatum, but, for present purposes, we focus
geons treating pectus excavatum is determining which patients on (1) the Ravitch procedure (and variations thereof) and (2)
are candidates for operative management. In an attempt to the Nuss procedure. For historical reasons, the turnover tech-
facilitate this determination, the Congenital Heart Surgery nique, originally described by Judet and Judet11 and later
Nomenclature and Database Project has developed a classifi- employed by Wada and colleagues,12 warrants a brief men-
cation system for pectus excavatum, in which a deformity less tion. Wada and colleagues’ series included 199 patients whose
than 2 cm in depth is classified as mild, a deformity 2 to 3 cm deformities were corrected with a version of this technique;
in depth is classified as moderate, and a deformity greater good results were achieved in 63% of patients, and there were
than 3 cm in depth is classified as severe.1 A computed only three instances of partial sternal necrosis. Today, how-
tomography (CT)–based index has also been devised, in ever, the turnover technique is rarely used because of the
which the transverse chest diameter is divided by the antero- good results that can be achieved with techniques that do not
posterior diameter; an index greater than 3.2 is considered carry a risk of sternal necrosis. It is usually reserved for
indicative of severe disease.2 extreme cases of pectus excavatum, which often include
These classification attempts notwithstanding, the precise deformities of the sternum in addition to abnormalities of the
indications for surgery remain unclear. Many studies have costal cartilages.
attempted to show that the depressed sternum leads to pul-
monary compromise, but, for the most part, these studies Ravitch procedure Repair of pectus excavatum is
have had small sample sizes and have employed differing based on the principle that the deformity is secondary to
measures of lung function, both of which have made accurate abnormal growth of the costal cartilages. Accordingly, correc-
comparisons difficult. In one study that included 25 US Air tion involves (1) resection of the abnormal cartilages, (2)
Force personnel with symptomatic pectus excavatum, lung a transverse anterior sternal osteotomy to allow anterior
volumes were comparable to those in normal persons, but displacement of the sternum, and (3) sternal fixation to
DOI 10.2310/7800.S04C09
07/10
prevent posterior displacement after the repair. Most of the extent of cartilage removal depends on the individual defect
variations in the Ravitch procedure have to do with the use present but usually includes the third rib.
of different sternal fixation techniques. Step 3: sternal osteotomy An osteotomy is made in the
Step 1: initial incision and exposure Either a midline upper anterior table of the sternum with either a periosteal
incision or a bilateral inframammary incision is made [see elevator or a small reticulating bone saw [see Figure 3a], and
Figure 1a, b]; the latter incision yields superior cosmetic the posterior table of the sternum is fractured. The sternum
results, especially in female patients, but necessitates the can then be angled anteriorly. When the desired angle is
elevation of large subcutaneous skin flaps to the level of the reached, the osteotomy is closed with three interrupted
angle of Louis or the sternal notch superiorly and to the nonabsorbable sutures or with microplates and screws [see
xiphoid process inferiorly. The pectoralis muscles are then Figure 3b, c]. At this point, rotational sternal defects can
mobilized from the chest wall, beginning medially and probe corrected by making anterior and posterior lateral osteoto-
ceeding laterally until the costal cartilages are exposed [see mies on either side of the sternum and then closing the
Figure 1c]. osteotomies with sutures or microplates.
Step 2: resection of abnormal cartilages For each abnormal Step 4: sternal fixation Sternal fixation can be accom-
costal cartilage, the anterior perichondrium is scored with plished by any of several means. Posterior sternal support can
the electrocautery along the length of the cartilage, and the be achieved by placing a Kirschner wire or retrosternal bar
cartilage is dissected from the perichondrium with a perios- that is secured to the periosteum of the rib and left in place
teal elevator [see Figure 2a]. The posterior plane between the for approximately 3 months after operation [see Figure 4].
cartilage and the perichondrium is then developed in one Alternatively, the sternum can be supported with a piece of
area, and the cartilage is divided with a scalpel between the polypropylene mesh or with two polypropylene sutures
jaws of a right-angle clamp [see Figure 2b]. The cut end of the sutured to the xiphoid process and then brought around the
cartilage is grasped with a clamp, and the rest of the cartilage right and left second ribs.13
is dissected from the perichondrium. Once the correct plane Step 5: closure and drainage The pectoralis muscles are
is established, the dissection can be facilitated by gently push- reapproximated in the midline, closed suction drains are
ing the perichondrium off the cartilage with a finger. The placed in the subcutaneous flaps, and the subcutaneous layer
entire cartilage should be removed from the sternum to the and the skin are closed. To prevent seroma formation, one
rib, with every attempt made to maintain the integrity of closed suction drain may be placed posterior to the pectoralis
the perichondrium. During this part of the procedure, the muscles and another between the pectoralis muscles and the
xiphoid process is also detached from the sternum. The subcutaneous layer; the right pleural space may then be
Figure 1 Repair of pectus excavatum: Ravitch procedure. The procedure begins with a midline incision (a) or a bilateral
inframammary incision (b). The pectoralis muscles are then dissected off the chest wall (c).
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a b
Figure 2 Repair of pectus excavatum: Ravitch procedure. (a) The anterior perichondrium is opened, and the abnormal cartilage
is dissected free with a periosteal elevator. (b) The cartilage is divided.
Figure 3 Repair of pectus excavatum: Ravitch procedure. (a) An osteotomy is made in the upper sternum. (b) The sternum is
angled anteriorly; when the desired angle is reached, the osteotomy is closed. (c) Shown is a lateral view of the sternal angle
before and after correction.
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Figure 5 Repair of pectus excavatum: Nuss procedure.

Incisions are made on either side of the chest. A Crawford
vascular clamp is inserted through the right intercostal space
and advanced along the sternum and out the left intercostal
space.
When the bar is correctly positioned, it is sutured to the chest

Figure 4 Repair of pectus excavatum: Ravitch procedure. wall musculature with an absorbable suture on one end and
Sternal fixation is accomplished through placement of a a permanent suture on the other.
retrosternal bar. The bar is usually left in place for 2 years. Excellent results
have been reported.15 Significant complications include bar
displacement necessitating reoperation (9.2% of procedures),
pneumothorax (4.8%), infection (2%), and pleural effusion
opened anteriorly and a right pleural tube placed through a
(2%). Rare complications include cardiac injury, thoracic
separate incision.14
outlet syndrome (TOS), pericarditis, and sternal erosion
caused by the bar.
Nuss procedure Minimally invasive repair of pectus
excavatum, also referred to as the Nuss procedure, has gained Outcome Evaluation
popularity over the past decade.
In general, the results of pectus excavatum repair are good,
Step 1: configuration of bar The patient is placed in the
and the overall complication rate is low. In one study, 90%
supine position with the arms abducted, and marks are made
of 76 patients operated on over a 30-year period experienced
on either side of the chest at spots that correspond to the
excellent outcomes, and only one patient required reopera-
deepest point of the defect. The bar that will be used for the
tion for a recurrent defect.14 The incidence of complications
repair is shortened to a length equivalent to the measured
(pleural effusions, pneumonia, and wound seromas) was
distance between the two midaxillary lines minus 1 cm. A
14%.14 In another study, no operative deaths occurred in
complex series of bends are then placed in the bar to match
more than 800 repairs, and only a few cases of serious infec-
its contours to those of the patient’s deformity.
tions and bleeding were reported.16 Other investigators have
Step 2: initial incisions and creation of intrathoracic tunnel
reported rare complications arising from the migration of
Incisions are made in the right and left midaxillary lines at the
sternal support bars and wires.17
level of the marks, and a subcutaneous flap is raised from
each incision and extended to the defect. A Crawford vascu- repair of pectus carinatum
lar clamp or a Lorenz pectus introducer is then placed through
the right intercostal space under thoracoscopic visualization Operative Technique
and advanced along the posterior sternum and out the Surgical repair of pectus carinatum resembles surgical
corresponding left intercostal space [see Figure 5]. repair of pectus excavatum in several respects. The same skin
incision is employed, and the pectoralis major muscles are
Step 3: placement and fixation of bar An umbilical elevated in a similar manner. Subperichondrial resection of
tape is pulled through the anterior mediastinum and attached the abnormal cartilages is then carried out, usually extending
to the bar, which is then gently pulled, with the concave side to the second costal cartilage. Next, a generous V-shaped
up, through the intercostal space. A Lorenz pectus bar rotator osteotomy is made in the upper portion of the sternum at the
is employed to flip the bar over, and the ends of the bar are point of maximal protrusion, which is usually near the inser-
positioned in the subcutaneous space [see Figure 6]. Occa- tion of the second cartilage. Occasionally, a second osteotomy
sionally, for proper alignment, the bar may have to be removed is required near the caudal end of the sternum to facilitate
and rebent, or stabilizers may have to be placed alongside it. elevation of the manubrium and depression of the sternum.
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a b
Figure 6 Repair of pectus excavatum: Nuss procedure. (a) The pectus bar is pulled into the tunnel opened by the vascular
retractor and then flipped to provide the desired chest contour. (b)The ends of the bar are then sutured to the chest wall
musculature.
Finally, the osteotomy is closed with nonabsorbable mono- axilla, and the chest are prepared and draped into the sterile
filament sutures, drains are placed, and soft tissue is closed field.
as in a pectus excavatum repair.
Step 1: initial incision and exposure An incision is
Outcome Evaluation
made just below the axillary hair line and extended from the
The results of pectus carinatum repair are generally com- pectoralis major to the latissimus dorsi [see Figure 7]. The
parable to those of pectus excavatum repair. Most patients subcutaneous tissue is incised down to the chest wall with
experience good outcomes, and operative morbidity is low. the electrocautery, with care taken to stay perpendicular to
the axis of the chest. Dissection is then begun along the chest
Procedures for Acquired Chest Wall Disease wall and carried toward the first rib. The intercostal brachial
transaxillary first rib resection for thoracic

outlet syndrome
Preoperative Evaluation
TOS results from compression of the subclavian blood
vessels or the brachial plexus as these structures exit the
bony thorax. Symptoms may be primarily vascular (e.g.,
arm swelling or loss of pulse) or neurogenic (e.g., pain and
paresthesias). The workup for TOS includes a detailed phys-
ical examination, as well as imaging and nerve conduction
studies.
Operative Planning
Surgical treatment of TOS typically involves resection of
the first rib, which widens the thoracic outlet and relieves the
neurovascular impingement. First rib resection can be accom-
plished via several different approaches, including posterior,
supraclavicular, infraclavicular, transthoracic, and transaxil-
lary. I focus here on the transaxillary approach, which pro-
vides good exposure of the first rib and allows the surgeon to
avoid the subclavian blood vessels and the brachial plexus.
Regardless of the specific surgical approach followed, any
surgeon embarking on a first rib resection must have a detailed
knowledge of the thoracic outlet to keep from injuring the
neurovascular structures in the area.
Operative Technique
The patient is placed in the lateral decubitus position, and
the affected arm is kept at a 90° angle either by an arm holder
or, alternatively, by an assistant. Care must be taken not Figure 7 Transaxillary first rib resection. Shown are the
to hyperabduct or hyperextend the shoulder. The arm, the transaxillary incision and the thoracic outlet anatomy.
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nerve is identified where it exits between the first and Step 4: closure The incision is closed without drainage.
second ribs. This nerve should be spared: dividing it leads to If the pleura was inadvertently entered, air may be aspirated
numbness of the upper inner biceps region. from the chest with a red rubber tube, which is removed
before the subcutaneous tissue is closed. One authority
Step 2: dissection and division of anterior portion of recommends further neurolysis of the C7 to T1 nerve roots
first rib When the first rib is encountered, it is dissected and the middle and lower trunks of the brachial plexus, as
from the periosteum with a periosteal elevator. Dissection is well as resection of the anterior and middle scalene muscles
continued anteriorly along the rib until just past the subcla- up into the neck.18
vian vein, at which point a right-angle clamp can be passed Complications
around the rib in the subperiosteal plane. A Gigli saw or a
Surgical complications include injuries to the subclavian
first rib cutter is then used to divide the anterior portion of
vein and artery (leading to massive blood loss), the brachial
the rib [see Figure 8a].
plexus, the phrenic nerve, the long thoracic nerve, and the
Next, the first rib is retracted inferiorly to permit visualiza-
thoracic duct.
tion of the anterior scalene muscle, which is then divided at
its attachment to the rib. To prevent thermal injury to the Outcome Evaluation
phrenic nerve, a scalpel rather than an electrocautery is used The long-term results of first rib resection appear to be
to divide the muscle [see Figure 8b]. Care should also be taken independent of the exposure technique employed. Good
not to injure the subclavian vein and artery, which lie anterior results, defined as relief of major symptoms, have been
and posterior to the anterior scalene muscle, respectively. As reported in as many of 90% of patients in the first year and
an alternative, the anterior scalene muscle may be divided in as many as 70% of patients 5 to 10 years after operation.
before the anterior portion of the rib is cut. Considerable debate continues over the preferred surgical
approach. but, to date, no studies have shown any one
Step 3: dissection and division of posterior portion of approach to have significant advantages over any of the
first rib The subperiosteal dissection is continued posteri- others.
orly, freeing the first rib from the pleura, the subclavian
vessels, and the brachial plexus. The posterior portion of the chest wall resection
rib is then divided with a first rib cutter as close as possible Chest wall resection has become a critical component of
to the articulation of the rib with the transverse process. Every the thoracic surgeon’s armamentarium. It may be performed
effort should be made to keep from injuring the C8 and T1 to treat either benign conditions (e.g., osteoradionecrosis,
nerve roots. osteomyelitis, and benign neoplasms) or malignant disease.
a b
Figure 8 Transaxillary first rib resection. (a) The anterior portion of the first rib is cut. (b) The anterior scalene muscle is then
divided.
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Preoperative Evaluation expected, every attempt should be made to spare major

Preoperative imaging studies may include chest x-ray, chest muscle groups so that these muscles can be used later to
CT [see Figure 9], and magnetic resonance imaging if verte- cover any prosthetic material used in reconstruction.
bral involvement is suspected. The other preoperative tests Operative technique
ordered are much the same as those required for any other
Step 1: initial incision and exposure The usual inci-
large thoracic procedure, including pulmonary function test-
sion is a standard posterolateral thoracotomy incision through
ing, nutritional assessment, and cardiac stress testing in
the fifth interspace.
patients who are older or have a history of cardiac disease.
Operative Planning Step 2: determination of extent of required chest wall

Operative planning for chest wall resection should include resection As soon as the pleura is opened, the surgeon
should palpate the tumor to evaluate the extent of chest wall
establishing the extent of the resection, weighing options for
involvement, which determines the extent of the resection.
chest wall stabilization, and deciding on the method of tissue
Removal of uninvolved ribs may make reconstruction of the
coverage to be employed. A multidisciplinary approach,
chest wall more complicated. For example, posterior resec-
involving the participation of a neurosurgeon and a plastic
tions that do not require removal of the fifth rib are protected
surgeon, may be required.
by the scapula, so reconstruction is unnecessary. If the fifth
The technique of chest wall resection is essentially the
rib is removed, however, the tip of the scapula will tend to
same for benign conditions as for malignant ones and is
become stuck under the sixth rib with shoulder movement;
mainly dependent on the location of the lesion. For malig-
this is very uncomfortable for the patient, and chest wall
nant tumors of the chest wall, a 5 cm margin, or at least
reconstruction will therefore be required at the time of
resection of one uninvolved rib above and below the tumor,
resection.
is required. Additionally, any involved skin and any biopsy At this point, the surgeon should also rule out diffuse
site must be resected along with the chest wall specimen. For pleural disease before proceeding with resection. In some
infection or osteoradionecrosis, the resection must include all cases, the tumor can be removed by means of extrapleural
nonviable skin and underlying bone; if it does not, skin and dissection, without any need for chest wall resection. If there
muscle flaps may not heal properly. Any destroyed lung tissue is any suspicion of chest wall involvement, however, chest
may also have to be resected along with the chest wall speci- wall resection is mandatory because leaving any tumor behind
men. In addition, recurrent cancer must be ruled out before guarantees a recurrence.
the operation can proceed. A particular challenge is posed by The extent of the chest wall resection is marked with the
breast cancer patients who have already had muscle flaps for electrocautery on the outside of the thoracic cavity. At least
breast reconstruction; in these patients, tissues other than one grossly uninvolved rib should be included both above
muscle (e.g., omentum) may be required for tissue coverage and below the tumor.
after chest wall resection.
Step 3: completion of anterior boundary of resection
Standard Chest Wall Resection
Initially, the periosteum over the lowest rib to be resected is
In cases in which a concomitant lung resection is required, scored, and a periosteal elevator is used to separate the inter-
the chest wall resection is usually performed first; this costal bundle from the rib. Alternatively, the intercostal
measure renders the lung more mobile and facilitates the bundle can be doubly ligated and divided at the anterior
pulmonary resection. The lateral decubitus position is the resection margin. Once the intercostal vessels are cleared
best choice for most combined lung–chest wall procedures, from the lowest rib, the electrocautery is used to divide the
whereas the supine position is preferable for isolated anterior pleura below the rib toward the anterior boundary of the
chest wall procedures. If a larger chest wall resection is resection. The rib is then divided with a rib cutter, with care
taken to ensure a margin of at least 5 cm from the tumor [see
Figure 10]. Next, the intercostal bundle of the next higher rib
is ligated and divided, the intercostal muscle is divided with
the electrocautery, and the rib is cut with a rib cutter in the
same manner as the previous rib. This process is repeated
until the anterior boundary of resection is completed. A
subperiosteal plane is then developed over the highest rib
to be resected, the adjacent intercostal bundle is separated
from the rib, and the parietal pleura is divided with the
electrocautery.
Step 4: completion of posterior boundary of resection

If the tumor margin does not involve the vertebrae, the
posterior portion of the chest wall resection is identical to the
anterior portion [see Step 3, above]. If, however, the tumor
appears to encroach on the head of the rib or the transverse
process, it will be necessary to disarticulate the rib from
Figure 9 Chest computed tomographic scan reveals a large the transverse process or, in the latter situation, remove the
pulmonary and chest wall mass. transverse process entirely.
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failure to do so will result in bleeding and possibly in leakage

of cerebrospinal fluid (CSF). If bleeding occurs, it can be
controlled with bipolar electrocauterization and temporary
packing with a hemostatic agent. The hemostatic agent must
not be left in place permanently, because it may expand or
result in a neural foramen hematoma, and either of these
events can lead to spinal cord compression and significant
neurologic injury. If at any time the surgeon feels uncomfort-
able about ongoing intercostal bleeding or a possible CSF
leak, intraoperative neurosurgical consultation should be
obtained. In cases in which the tumor involves the transverse
process, this structure must be removed from the vertebral
body with an osteotome and a mallet or with a first rib cutter.
If the tumor has invaded the vertebral body and resection
is still being considered, neurosurgical consultation should
be obtained. Generally, if the tumor involves more than
one quarter of the vertebral body or extends into multiple
vertebral levels, it is considered unresectable.
Step 5: lung resection (if required) Once the posterior

chest wall margin has been completed, the lung resection (if
required) is performed. The entire lung–chest wall specimen
is then submitted for pathologic examination, and histopath-
ologic margins are obtained both on the lung and on the chest
wall. If the chest wall margins are positive, the involved area
Figure 10 Chest wall resection. The anterior and posterior must be trimmed back and a new margin submitted.
margins of the required resection are determined. The
anterior margin is completed first. Step 6: chest wall reconstruction Chest wall recon-
struction is required for all anterior defects and for posterior
Disarticulation of the rib from the transverse process is defects that involve any rib lower than the fourth rib. Recon-
performed by dissecting the paraspinal ligament and erector struction can be performed either with polypropylene or
spinae muscles away from the spine with the electrocautery, Gore-Tex (W. L. Gore and Associates, Flagstaff, Arizona)
thereby exposing the joint between the head of the rib and mesh or with a polypropylene-methylmethacrylate sandwich.
the transverse process. The ligaments attaching the rib to the The latter is employed when rigid reconstruction is warranted
transverse process are then incised with the electrocautery, (as in anterior reconstruction); it not only provides added
and an osteotome is inserted into the joint, which is then protection of pleural and mediastinal structures but also
levered anteriorly and posteriorly to disarticulate the rib from creates a better cosmetic effect by recreating the shape of the
the transverse process [see Figure 11]. The intercostal neuro- chest wall.
vascular bundle must be ligated and divided at this point: To create the polypropylene-methylmethacrylate sandwich,
two pieces of polypropylene mesh are cut to the size of the
defect. A thin layer of methylmethacrylate cement is spread
on one of the mesh pieces, and the other piece is then applied
over the methylmethacrylate layer. As this sandwich begins to
harden, it is molded to the contours of the chest wall, with
care taken to protect the patient’s skin against injury from the
heat given off by the hardening cement. When the sandwich
is sufficiently hardened, it is sewn to the ribs with 0 polypro-
pylene sutures [see Figure 12a]. The sutures may be passed
around the uppermost and lowermost ribs and may be
placed directly through the anterior and posterior margins
[see Figure 12b]. If rib disarticulation was required to com-
plete the posterior margin, holes may be drilled in the trans-
verse processes and the sutures passed through these holes;
alternatively, the sandwich may be sutured to the paraspinal
ligament.
If polypropylene or Gore-Tex mesh is used without cement,
it should be cut to a size smaller than that of the defect. Thus,
the mesh will effectively be stretched when it is sutured to the
chest wall, and any laxity in the reconstruction will thereby
be alleviated.
Figure 11 Chest wall resection. Depicted is disarticulation of Step 7: closure and drainage The serratus anterior and
the rib from the transverse process. the latissimus dorsi are closed in the standard fashion, as
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Figure 12 Chest wall resection. (a) A polypropylene-methylmethacrylate sandwich is created by spreading a layer of
methylmethacrylate cement between two pieces of polypropylene mesh. When sufficiently hardened, the sandwich is sutured to
the ribs. (b) Photograph shows a polypropylene-methylmethacrylate sandwich sutured in place.
are the subcutaneous and skin layers. With the exception of Muscle or omental flaps with split-thickness skin grafts may
pleural tubes, drains are not routinely used. Special attention be required for coverage; thus, preoperative consultation with
should be paid to postoperative analgesia: patients who have an experienced plastic surgeon is advisable. A particular
undergone extensive resections often experience considerable concern is what to use to reconstruct the chest wall. Various
pain and are therefore prone to atelectasis and pneumonia. tissues (e.g., fascia lata and ribs) have been employed, but
Epidural analgesia should be employed routinely in such an easier substitute that works quite well is an absorbable
cases. synthetic mesh (e.g., Vicryl). The mesh is sewn to the ribs as
Troubleshooting If chest wall infection is a possibility previously described [see Step 6, above], and the tissue flap
(as with osteoradionecrosis or osteomyelitis), alternative is placed on top of the mesh, followed by a skin graft [see
reconstructive techniques are required to obviate concerns Figure 13b, c]. Alternatively, some authors recommend the
about superinfection resulting from the use of synthetic mate- use of muscle or myocutaneous flaps without rigid chest
rial. In particular, radiation injury may involve all layers of the wall reconstruction after resection, particularly in infected
chest wall, necessitating very large resections [see Figure 13a]. fields.19
a b c
Figure 13 Chest wall resection. The presence of osteoradionecrosis may necessitate very large resections and resulting defects
(a). Such defects may be covered with absorbable mesh (b), followed by an omental flap (c) or a muscle flap.
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Outcome evaluation The results achieved after major infected bone. Once the tissue deep to the manubrium has
chest wall resection have generally been excellent. One study been dissected, a small band retractor is placed beneath the
reviewed 200 patients who underwent resection and recon- manubrium, and an oscillating sternal saw is used to resect
struction over a 25-year period.20 The reconstructions ranged the lateral portion of the manubrium, adjacent to the SCJ.
from relatively straightforward two-rib resections to more Alternatively, a rongeur may be used to débride infected bone
complex forequarter amputations. The indications for resec- from the manubrium. All tissue should be sent for culture.
tion were lung cancer (38%), osteoradionecrosis (29%), chest Severe infections may necessitate more extensive resection
wall tumor (27%), and osteomyelitis (16%). Immediate of bone or soft tissue, but if the infection is caught early,
reconstruction was performed in 98% of patients. The major simple resection of the SCJ is generally curative. In more
muscle flaps used were latissimus dorsi (20%), rectus abdom- extensive resections, muscle flap coverage may be required,
inis (17%), pectoralis major (16%), and serratus anterior but in simple SCJ resections, good results can be obtained
(9%). Free flaps were used in only 9% of cases, and by using only deep closed suction drainage, followed by
split-thickness skin grafts were required in 12% of patients. multilayer closure of the wound. To prevent any recurrent
Reconstruction was performed with Prolene mesh (25%), osteomyelitis, antibiotics should be continued for several
Marlex mesh (11%), Vicryl mesh (6%), or a polypropylene- weeks after resection.
methylmethacrylate sandwich (6%). Operative mortality was
7%, and major morbidity occurred in 24% of patients. Most Resection of manubrium for cancer Manubrial resec-
of the morbidity was accounted for by pneumonia (14%) and tions may be required for rare cases of primary or metastatic
acute respiratory distress syndrome (6%). cancers.
Manubrial and Clavicular Resection Because of the relative paucity of tissue overlying the
manubrium, cancers in this area may involve the dermis. In
Resection of the manubrium or the clavicle may be neces-
such cases, it may be necessary to resect skin along with the
sary if these structures become infected or involved with
specimen. Alternatively, if the skin is not involved, an upper
tumors. Clavicular and manubrial resections follow the same
midline incision may be employed. The incision is carried
operative approach as other chest wall resections. Specifi-
down circumferentially to the chest wall, with care taken to
cally, attention must be paid to how much bone to resect,
maintain a 2 to 3 cm margin from the tumor. The clavicles
how to reconstruct the defect, and how to provide tissue
and ribs are divided in the same fashion as for chest wall and
coverage.
clavicular resections [see Figure 14a]. Associated structures
(e.g., the thymus) can be resected along with the manubrium;
Resection of sternoclavicular joint for infection
Clavicular resections are rarely performed but may be required these tumors rarely involve the innominate vein.
to treat tumors, vascular compression from healed fractures, A polypropylene-methylmethacrylate sandwich is useful for
or infection. Occasionally, infections involve the sternocla- reconstruction of this area of the chest wall [see Figure 14b].
vicular joint (SCJ). Patients with osteomyelitis of this joint The patch is secured to the remaining ribs and clavicles with
are often immunosuppressed and may have had an indwelling 0 polypropylene sutures. Coverage is then provided with a
subclavian vein catheter that became infected. In a study of pectoralis major advancement flap or, if skin was excised, a
seven patients who underwent SCJ resection for infection, pedicled pectoralis myocutaneous flap. A pleural drain may
five of six patients initially treated with antibiotics and simple be placed if either pleural space was entered, but this measure
drainage experienced recurrences, whereas six of six patients is not routinely employed.
treated with resection of the joint and pectoralis muscle Open Chest Drainage (Eloesser Flap)
advancement flaps were cured. None of the patients experi-
enced problems with arm mobility in the course of long-term Open drainage procedures are usually included in discus-
follow-up.21 sions of treatment of empyema, but they really represent a
An incision is made that extends along the distal clavicle type of chest wall resection. Open drainage techniques for
and curves down onto the manubrium. The soft tissue is empyema were first described in the late 1800s by Poulet and
divided with the electrocautery down to the clavicle and the subsequently by Schede. Graham, who headed the Army
manubrium. The muscular attachments of the pectoralis Empyema Commission during World War I, is credited with
major and the sternocleidomastoid muscle are dissected off the observation that ensuring pleural-pleural symphysis
the clavicle and the manubrium with a periosteal elevator. was the key to preventing the often fatal complication of
Dissection in the subperiosteal plane is then continued pneumothorax.22 Indications for open chest drainage include
circumferentially around the distal clavicle, with special care postpneumonectomy empyema or bronchopleural fistula,
taken to keep from injuring the subclavian vessels that lie long-standing empyema in a patient who cannot undergo
deep to the clavicle. A Gigli saw is passed around the clavicle decortication, and chronic bronchopleural fistula in a
with a right-angle clamp and used to divide the distal clavicle. high-risk patient.
The distal cut end of the clavicle is grasped with a penetrating
towel clamp and bluntly dissected away from the deep Operative technique The technique currently employed
tissue toward the manubrium. Any pockets of infection by most thoracic surgeons follows Symbas’s modification of
encountered should be cultured, drained, and débrided. Eloesser’s open drainage technique.23 This procedure has
At this point, a large separation in the SCJ, caused by the come to be known as the Eloesser flap. Preoperative chest CT
infection, should be apparent. Resection of a small portion is essential for identifying the exact location of the empyema,
of the manubrium is usually required to remove all of the which determines the placement of the incision.
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a b
Figure 14 Manubrial resection and reconstruction. (a) The clavicles and ribs are divided as in clavicular and other chest wall
resections. (b) A polypropylene-methylmethacrylate sandwich may be used to reconstruct the chest wall.
Step 1: initial incision and exposure The patient is placed

in the decubitus position, and a 6 to 8 cm incision is made
over the area corresponding to the most dependent area of
the infected cavity. Symbas employed a U-shaped incision;
however, a simple linear incision can also be used with good
results. The subcutaneous tissue and muscle are then divided
down to the chest wall with the electrocautery.
Step 2: resection of ribs and creation of thoracostomy The
pleural space is opened with the electrocautery, any pus pres-
ent is drained, and the chest cavity is manually and visually
explored. Next, 6 to 8 cm segments of two or three adjacent
ribs are resected according to the same principles employed
for other chest wall resections. The resulting thoracostomy is
large enough to permit drainage and packing. The skin over-
lying this thoracostomy is then marsupialized to the thickened
parietal pleura with absorbable sutures [see Figure 15]. If the
pleura does not possess sufficient integrity to hold the sutures,
they can be placed through the periosteum of the ribs.
Step 3: packing and drainage The wound is irrigated with
normal saline and packed with saline-moistened gauze. Post-
operatively, a chest x-ray should be obtained to rule out
pneumothorax, and twice- to thrice-daily packing is initiated.
Packing is continued on an outpatient basis, and the wound
is monitored. The wound will begin to close over the next
Figure 15 Open chest drainage (Eloesser flap). Once the ribs
several weeks. If the empyema or bronchopleural fistula has have been resected, the skin overlying the thoracostomy is
not healed by the time the wound starts closing, the thoracos- marsupialized to the parietal pleura to permit packing and
tomy will have to be revised. In some cases, this can be open pleural drainage.
07/10
accomplished merely by manually dilating the opening in the demonstrate that patients with flail chest can benefit from
operating room; in others, the entire thoracostomy must be operative repair in selected scenarios. Flail chest can be
revised. In either case, the goal is to maintain a large enough defined as three or more consecutive ribs fractured in two or
opening to allow adequate packing. more locations, clinically creating a segment of the chest wall
Step 4: closure of thoracostomy Once the lung and the that visibly demonstrates paradoxical motion with respiratory
pleural space have healed, the thoracostomy is closed. The variations. In both of these trials, the operative group demon-
procedure for closing the thoracostomy depends on the size strated a reduced number of ventilator days, intensive care
and nature of the remaining defect [see Figure 16a]. For small unit length of stay, and lower incidence of pneumonia. One
defects, simple closure of the skin will suffice. For larger of the trials reported that more of the operative group returned
defects or residual spaces in the pleura, however, muscle flap to work at the 6-month follow-up compared to the non-
closure will be required [see Figure 16b]. Improvements in operative group.26,27 Retrospective reviews and nonrandom-
radiographic techniques and greater emphasis on early inter- ized cohort studies demonstrate that patients with severe flail
vention for empyemas have significantly reduced the need segments without underlying pulmonary contusion are offered
for open chest drainage; however, this technique can still be the greatest advantage in surgical repair of rib fractures.28
valuable in the appropriate clinical situation. Opponents to surgical correction of rib fractures suggest that
the nonoperative groups were not managed with modern
procedures for chest wall fractures⁄trauma strategies, including epidural anesthesia and chest physio-
A recent survey of American trauma, orthopedic, and therapy.29 It is not, however, within the scope of this chapter
thoracic surgeons found that the majority of polled surgeons to argue the merits of the literature surrounding the subject
had not performed a repair on sternal or rib fractures, nor matter but simply to delineate some of the techniques. Other
was there a consensus of surveyed surgeons with agreed upon indications include chest wall defect and pulmonary hernia.
surgical indications. Also, a large majority were unaware of
any published randomized trials addressing rib or sternal Operative planning In preoperative planning, it is
fractures.24 Although rib and sternal fracture repairs have useful to define the location and characteristics of all the rib
been performed for many years, the operative indications fractures with a CT scan, and three-dimensional reconstruc-
remain somewhat controversial. However, there is increasing tion may provide the surgeon with added information to the
consensus that operative fixation of these fractures is under- fracture geometry. As the main complications of the proce-
used; therefore, basic repair techniques are discussed dure are infectious in etiology, removal of chest tubes if
below.25 possible, prior to the operation, is encouraged. The use of an
epidural catheter for pre- and postoperative pain manage-
Repair of Rib Fractures ment should be considered. Many different techniques have
Although there are a number of potential indications for been described, including variations of intramedullary fixa-
operative repair for rib fractures, two recent randomized trials tion, plate attachment, or wiring, but the most commonly
Figure 16 Open chest drainage (Eloesser flap). (a) Photograph shows a right Eloesser flap 8 months after creation.
(b) Photograph shows an Eloesser flap that was closed with a muscle flap.
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employed technique is anterior plating with bicortical screw However, because of the prevalence of median sternotomies
fixation. in cardiac procedures, more operations for sternal fixation are
performed for postoperative chronic sternal nonunion than
Operative technique The patient is intubated with a acute fracture. Sternal fracture nonunion is commonly defined
single-lumen endotracheal tube or a double-lumen tube if as persistent instability after 6 weeks of nonoperative manage-
single-lung ventilation is preferred, but this is not mandatory. ment and is the most common operative indication. Other
The patient is placed in standard lateral decubitus positioning indications include fractures that create paradoxical motion
for a posterior lateral thoracotomy. A muscle-sparing thora- with respirations altering respiratory mechanics, and a multi-
cotomy incision is used if possible, and the scapulothoracic tude of anterior plating systems are available for the surgeon
bursa is incised, giving access to the thoracic cage. This allows to use; other techniques include placement of sternal wires
for fracture site localization, easily accessing ribs 3 to 9. Soft through the fracture fragments.
tissue immediately overlying the fractures is removed with a
periosteal elevator, and the ribs are realigned with the use of Operative planning In the preoperative planning of sur-
bone forceps. Plates of the surgeon’s selection are secured to gical repair, a CT scan with three-dimensional reconstruction
provides added geometric insight to the fracture pattern. In
the ribs with bicortical screw placement. Careful attention is
an attempt to reduce postoperative infectious complications,
placed to ensure that the screws are of the appropriate length
mediastinal or chest tubes should be removed if in place.
to prevent screw tips from entering the pleural space. For
Also, one should consider the use of an epidural catheter for
stabilization of the chest wall, not all the fractured ribs need
postoperative pain management.
to be fixed. Depending on the surgeon’s comfort, single-lung
ventilation can be used, and by inserting a thoracoscope infe-
Operative technique The sternum is exposed using a
rior to the fractures, the pleural space can be visualized and previous surgical incision if present or through a longitudinal
monitored during screw placement. Assuming that satisfac- or transverse incision depending on the need for exposure. If
tory fixation has been accomplished, the pneumothorax can sternal wires are in place, they are removed, and the fibrous
be evacuated on lung reexpansion, and no chest tube would tissue and soft tissue are removed with electrocautery and the
be required. periosteal elevator. If there is a fibrous union, this is removed
as well. Once all fractures are identified, they are reduced
Complications Postoperative complications are primar- using bone forceps. Plates are selected to allow for at least
ily infectious in etiology and include superficial wound infec- three screws to be seated on either side of the fracture.
tions and empyemas. A postoperative pneumothorax should Careful attention is placed ensuring that the screws do not
always be evaluated for on standard postoperative chest x-ray penetrate the inner table of the sternum. The pectus muscles
and if there is any respiratory deterioration, even if the are reapproximated and a drain placed to prevent seroma or
pleural space was not entered during the procedure. Other, hematoma formation. The drain is removed on postoperative
less frequent complications include fixation failures, chronic day 1 or 2 depending on the output.
pain, reactive pleural effusions, and wound hematomas.
Complications Postoperative complications have a low
Repair of Sternal Fractures incidence for sternal fixation procedures and are similar to rib
The diagnosis of sternal fractures is usually suspected fixation, including superficial wound infections, wound hema-
because of pain in the precordial area with tenderness and tomas and seromas, fixation failures, chronic pain, pleural
instability on palpation. There is evidence of increased diag- effusions, and empyemas.
nosis of sternal fracture in the trauma literature as a result of
the increased use of CT scanning in this patient population. Financial Disclosures: None Reported
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anterior chest wall. Plast Reconstr Surg 24. Mayberry JC, Ham LB, Schipper PH, et al. 28. Nirula R, Diaz JJ Jr, Trunky DD, et al. Rib
1979;63:105. Surveyed opinion of American trauma, ortho- fracture repair: indications, technical issues,
20. Mansour KA, Thourani VH, Losken A, et al. pedic, and thoracic surgeons on rib and sternal and future directions. World J Surg 2009;33:
Chest wall resections and reconstruction: a fracture repair. J Trauma 2009;66:875. 14.
25-year experience. Ann Thorac Surg 2002; 25. Richardson JD, Franklin GA, Heffley S, et al. 29. EAST Practice Management Workgroup
73:1720. Operative fixation of chest wall fractures: an for Pulmonary Contusion-Flail Chest
21. Song HK, Guy TS, Kaiser LR, et al. Current underused procedure? Am Surg 2007;73:
2006. Available at: http://www.east.org/tpg/
presentation and optimal surgical manage- 591.
pulmcontflailchest.pdf (accessed October 30,
26. Tanaka H, Yukioka T, Yamaguti Y, et al.
ment of sternoclavicular joint infections. Ann 2009).
Surgical stabilization of internal pneumatic
Thorac Surg 2002;73:427. stabilization? A prospective randomized study
22. Somers J, Faber LP. Historical developments of management of severe flail chest patients.
in the management of empyema. Chest Surg J Trauma 2002;52:727.
Clin N Am 1996;6:404. Acknowledgment
27. Granetzny A, Abd El-Aal M, Emam E, et al.
23. Symbas PN, Nugent JT, Abbott OA, et al. Surgical versus conservative treatment of flail
Nontuberculous pleural empyema in adults. chest. Evaluation of the pulmonary status. Int Figures 1 through 8, 10 through 12, 14, and 15
Ann Thorac Surg 1971;12:69. Cardiovasc Thorac Surg 2005;4:583. Alice Y. Chen
07/10
4 THORAX 10 VIDEO-ASSISTED THORACIC SURGERY — 1
10 VIDEO-ASSISTED THORACIC
SURGERY
Marcelo C. DaSilva, MD, and Scott J. Swanson, MD*
Although Sir Francis Richard Cruise has been credited with laparoscopic staging of esophageal cancer.8 One hundred
performing the first thoracoscopy for evacuation of empyema seventeen patients were accrued; 82 patients (70%) met the
in 1865,1 Hans Christian Jacobaeus coined the term “thora- entry criteria for thoracoscopy. Of those, 57% had positive
coscopy” in an article published in 1910.2 In the latter report, nodes and 43% had all negative nodes. Node-negative status
Jacobaeus described the use of a cystoscope to examine the was confirmed on final pathology in 12 (75%) of 16 patients
chest cavity and to lyse adhesions, allowing the lungs to col- who underwent surgery, whereas three patients had node-
lapse for the treatment of tuberculosis.3 With the introduction positive status in the specimen (19% false negative rate). The
of streptomycin, which revolutionized the treatment of authors concluded that thoracoscopic and/or laparoscopic
tuberculosis, thoracoscopy was relegated to the occasional staging lung and esophageal cancer was feasible and doubled
case report. It was not until the introduction of laparoscopic the number of positive lymph nodes identified by conven-
procedures in the 1980s that surgeons started to apply this tional surgery.
technology to the thoracic cavity. In 1992, Lewis and col- The first multicenter prospective trial to examine standard-
leagues reported 100 consecutive patients who underwent ized VATS lobectomy was CALGB 39802.9 One hundred
video-assisted thoracoscopic surgery, including three lobec- twenty-eight patients were enrolled for VATS lobectomy as
tomies with anatomic hilar dissection.4 From these early defined by one access incision (4 to 8 cm), two 5 mm port
studies, minimally invasive video-assisted thoracic surgery incisions, and no retractor use or rib spreading. The periop-
(VATS) has emerged as a safe and reliable technique. It has, erative morbidity was 7.4% and 30-day mortality was 2.7%,
in many instances, supplanted standard thoracic procedures. both comparable to standards of open thoracotomy in patients
Approximately 20% of all lobectomies now are performed with small (f3 cm) peripheral NSCLC. In 1998, CALGB
thoracoscopically in the United States.5
39803 answered the question of restaging patients with his-
tologic documented stage IIIA NSCLC with VATS on the
Historical Background basis of involved N2 nodes from mediastinoscopy prior
to induction therapy.10 Seventy patients were accrued in
The first single institution prospective randomized trial
10 institutions. Of those, 47 patients (67%) had radiation
comparing VATS to the muscle-sparing open technique for
lobectomy was published by Kirby and colleagues in 1995.6 therapy and 68 (97%) had chemotherapy. The number of
Sixty-one patients undergoing lobectomy for stage I non– incisions ranged from one to four, with a median of three
small cell lung cancer (NSCLC) were randomized to VATS incisions. VATS restaging criteria were met in 40 patients
or open thoracotomy. There was no significant difference in (57%): four had pleural carcinomatosis, 17 had persistent N2
operating time, intraoperative complications, estimated blood disease, and 19 had three negative nodal stations. In addition,
loss, chest tube drainage, length of stay, or postthoracotomy 13 (18.6%) patients in the VATS group had no evidence of
pain between the groups, although it was a small study and persistent N2 disease attributable to unanticipated oblitera-
many VATS patients had a minithoracotomy. In the early tion of nodal tissue. VATS was unsuccessful in 17 (24%)
1990s, the National Institute of Cancer funded an intergroup patients as a result of adhesions or fibrosis and tumor bulk
consortium of thoracic surgeons to investigate the efficacy of preventing nodal access. Of the 53 patients who completed
thoracoscopy and VATS in the diagnosis, staging, and treat- VATS restaging, 21 provided cancer tissue and 31 had histo-
ment of intrathoracic malignancies. Cancer and Leukemia logic tissue obtained during thoracotomy; N2 downstaging
Group B (CALGB) 9335 was the first multicenter, clinical occurred in 32 patients (46%). The sensitivity of VATS was
research phase II trial to look at the feasibility of treating 75%, the specificity was 100%, and the negative predictive
patients with poor cardiopulmonary reserve and T1 periph- value was 75.8%. No deaths occurred, but one airway injury
eral NSCLC by VATS wedge resection or radiotherapy.7 was directly attributed to VATS. The authors concluded that
This clinical trial concluded that VATS wedge resection VATS was feasible and provided pathologic assessment of
in high-risk patients is safe and feasible. The CALGB 9380 ipsilateral nodes in treated IIIA (N2) NSCLC.
phase II clinical trial was designed to determine the feasibil- Eastern Cooperative Oncology Group (ECOG) 2202
ity, morbidity, and mortality for thoracoscopic and/or was the first multi-institutional phase II trial to assess the
feasibility of minimally invasive esophagectomy (MIE) in a
* The authors and editors gratefully acknowledge the contribu- multi-institutional setting.11 Of 106 patients enrolled in this
tions of the previous authors, Raja M. Flores, MD, Bernard study, 99 underwent MIE. Anastomotic leak (7.8%) and
Park, MD, and Valerie W. Rusch, MD, FACS, to the pneumonia (4.9%) were the major complications, whereas
development and writing of this chapter. the mortality rate was 2% (2 of 106), with a mean follow-up
DOI 10.2310/7800.S04C10
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of 19 months, and the estimated 3-year survival rate for the Table 1 Indications and Relative Contraindications for
cohort was 50% (95% confidence interval 35 to 655). The VATS Procedures
authors concluded that MIE was safe and feasible, with low Diagnostic indications
perioperative mortality and morbidity and with oncologic All biopsies: nodules, interstitial lung disease
outcomes similar to those of open esophagectomy. Pulmonary infection in the immunosuppressed patient
The era of VATS is sufficiently mature that enough data Nodal staging of a primary thoracic tumor
Staging a primary extrathoracic tumor
have accrued to compare the efficacy of VATS with that of Trauma: lung laceration, hemothorax diaphragmatic injury
open procedures. In this regard, anatomic pulmonary resec- Therapeutic indications
tion by VATS has led to significant reductions in morbidity, Lung
mortality, and hospital length of stay, allowing patients a Spontaneous pneumothorax
Bullous disease/lung volume reduction
more expeditious return to regular activities. VATS has been Persistent parenchymal airleak
used in the treatment of both benign and malignant diseases Pleural effusion
of the chest. Furthermore, VATS may be used in selected Pleural disease: empyema, fibrothorax, decortication
patients with early-stage lung cancer without breaching Anatomic resection
Lobectomy
oncologic surgical principles.
Segmentectomy
Pneumonectomy
definition Esophageal
The terms “VATS” and “thoracoscopic” refer to totally Benign
thoracoscopic approaches, where visualization is dependent Malignant
Mediastinal
on video monitors, and rib spreading is avoided by using VATS thymectomy for thymoma
a thoracoscope, video monitors, and one to four small (1 to Nodal dissection
2 cm) incisions.12 Pericardial window
Cysts
indications and contraindications Chest wall
Rib resection
The indications for VATS are the same as for conventional Sarcoma
approaches to thoracic surgery. However, tumor size greater First rib for thoracic outlet syndrome
than 6 cm, inability to tolerate single-lung ventilation, and Other
Metastatectomy
previous thoracotomy with obliteration of the pleural space Sympathectomy for hyperhidrosis
[see Table 1] are considered relative contraindications. The Ligation of thoracic duct
individual experience of the surgeon and the complexity Repair/plication of the diaphragm
of the operation also influence the procedures that can be Relative contraindications to VATS pulmonary resection
Intolerance of single-lung ventilation
performed by VATS. Tumor size > 6 cm
Anticipated sleeve resection
preoperative evaluation Hilar lymphadenopathy
The preoperative evaluation of patients undergoing VATS Chest wall or mediastinal involvement
Neoadjuvant radiation therapy or chemotherapy
is similar to that of those undergoing open thoracotomy
procedures. The risks related to surgical resection include VATS = video-assisted thoracic surgery.
perioperative morbidity and mortality and long-term func-
tional disability. Individual patient circumstances increase or insufficiency. It depends directly on the amount of pulmo-
decrease the risks from standard thoracotomy resection and nary reserve of the patient. Operability, on the other hand,
VATS [see Figure 1]. In addition, a discussion of the balance refers to the ability of a patient to survive the proposed pro-
between the risks and benefits of surgical resection by the cedure and its perioperative complications. It depends on the
surgeon and the patient should also include nonstandard patient’s comorbid conditions. However, neither the opera-
treatment options, such as sublobar resections, conventional bility of an individual patient nor the resectability of a tumor
radiotherapy, stereotactic radiotherapy, and radiofrequency should influence the decision concerning the role of a com-
ablation. plete resection on survival.14
A thorough physical examination, past medical history, Pulmonary function testing includes pulmonary spirome-
social history including tobacco smoking and exposure to try, pulmonary hemodynamic response testing, and exercise
arsenic and asbestos, radiologic studies (chest x-rays, com- testing. Pulmonary spirometry is affected by height, age,
puted tomographic [CT] scan, positron emission tomographic weight, sex, race, and posture, as well as arterial oxygenation
[PET]-CT scan, magnetic resonance imaging [MRI]), and and diffusion capacity. Although pulmonary spirometry and
pulmonary function tests are part of the preoperative pre- arterial oxygenation help predict mortality, they are not good
paration. Although thoracoscopic procedures tend to be less predictors of postoperative complications. Diffusion capacity
stressful than open thoracotomy, with fewer cardiopulmonary of the lung for carbon monoxide (DLCO) is a more sensitive
complications (e.g., atrial fibrillation or myocardial infarc- predictor of postoperative complications. DLCO measures
tion),13 it is important to recognize that risk assessment is a the partial pressure difference between inspired and expired
complex process, and the surgeon should focus on determin- carbon monoxide. It relies on the strong affinity and large
ing the individual patient’s resectability and operability. absorption capacity of erythrocytes for carbon monoxide and
Resectability refers to the amount of lung tissue and tumor thus demonstrates gas uptake by the capillaries that is less
that can be safely removed without developing respiratory dependent on cardiac output.15 Thus, value is decreased in
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CXR, ECG Spirometry and

CT, PET-CT scan diffusing capacity
FEV1 > 80% or > 2 L FEV1 < 80% or < 1.5 L

DLCO > 80% predicted DLCO < 80% predicted
Resection Quantitative
(including pneumonectomy) V/Q scan
ppoFEV1 > 40% ppoFEV1 < 40% ppoFEV1 < 30% or

ppoDLCO > 40% ppoDLCO < 40% %ppoFEV1 × %ppoDLCO < 1650
Average risk Perform exercise testing
Resection
·
VO2 max
> 15 mL/kg/min 10–15 mL/kg/min < 10 mL/kg/min
Resection Increased risk Consider nonsurgical

therapy
Figure 1 Preoperative evaluation. CXR = chest x-ray; CT = computed tomographic; ECG = electrocardiogram; DLCO =
diffusing capacity for carbon monoxide; FEV1 = forced expiratory volume in 1 second; PET = positron emission tomographic;
ppo = postoperative; V̇O2 max = maximum oxygen consumption; V/Q = ventilation-perfusion.
patients with emphysema, chronic pulmonary hypertension, with a maximum oxygen consumption (V̇O2 max) less than
and interstitial lung disease. DLCO is an important and inde- 15 mL/kg/min are considered high risk, whereas those with a
pendent predictor of postoperative complications after major V̇O2 max of 16 to 20 mL/kg/min could probably undergo
lung resection, even in patients without COPD.16,17 surgery.
Quantitative ventilation/perfusion (V/Q) scan, along with Flexible bronchoscopy is generally indicated in patients
pulmonary spirometry, is useful for predicting postoperative with hemoptysis, wheezing, and evidence of bronchial
lung function. A calculated predictive postoperative forced obstruction. In patients with lung cancer, bronchoscopy is
expiratory volume in 1 second (ppoFEV1 of less than 40% is always performed to assess endobronchial invasion. If a mass
is found beneath the mucosa or intraparenchyma, endobron-
associated with a 50% mortality rate. The absolute minimum
chial ultrasonography and electromagnetic navigational bron-
ppoFEV1 in patients undergoing lobectomy is 800 mL.
choscopy are potential diagnostic tools, but their discussion
Pulmonary hemodynamic response testing includes the
is beyond the scope of this chapter. Bronchoscopy is also
measurement of pulmonary artery pressure and pulmonary useful for the diagnosis of infectious diseases, such as
vascular resistance. It is an invasive test and requires right tuberculosis, fungus, Pneumocystis pneumonia, and cyto-
heart catheterization. Systolic pulmonary artery pressure megalovirus, prior to a thoracoscopic procedure. Finally, a
greater than 35 mm Hg is associated with a 10-fold decrease multidisciplinary discussion with medical and radiation
in survival rate, and pulmonary vascular resistance greater oncologists is especially useful in patients who are marginal
than 190 dyne is associated with a 90% mortality rate. surgical candidates and serves as a basis for discussing the
Maximum exercise testing is concerned with the amount of proposed surgical procedure and treatment options with the
arterial desaturation that occurs during exercise. Patients patient and appropriate family or surrogates.
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The goal of the preoperative evaluation is to identify those

patients who can tolerate a thoracic surgical procedure. By
integrating the concept of operability and resectability while
achieving a complete surgical resection, along with a thor-
ough preoperative evaluation, the surgeon will be able to
identify a group of patients who would benefit from VATS.
Operative Planning
anesthesia and monitoring
VATS is performed under general anesthesia with single-
lung ventilation. A double-lumen endotracheal tube is gener-
ally used, but an endobronchial blocker may also be employed
to collapse the lung. Alternatively, limited operations such
as diagnostic pleuroscopy and pleural biopsy, insertion of
pleural drainage catheters, or procedures performed on pneu-
monectomy patients can be safely done with a single-lumen
endotracheal tube and intermittent lung ventilation. The Figure 2 Proper patient position in the operating room, with
degree of intraoperative monitoring needed depends on the the patient propped on pontoons.
extent of the planned procedure and on the patient’s general
medical condition. Standard monitoring techniques are used
to measure the patient’s oxygenation, ventilation, circulation,
and temperature.18 Whenever indicated, a peripheral arterial
line, central venous pressure and pulmonary artery (PA)
catheters, and transesophageal echocardiography may be
used. A Foley catheter is inserted at the beginning of the
procedure to monitor urine output. Depending on the pul-
monary reserve of the patient, extent of the procedure, and
postoperative pain, epidural catheters can provide excellent
pain relief, but they are not commonly used for thoracoscopic
procedures because of the time required for insertion and
frequent side effects, such as hypotension and urinary reten-
tion. Alternatively, recent studies have demonstrated the
safety and efficacy of continuous infusion pumps delivering
local anesthetic through a catheter in the extrapleural pocket
during thoracotomy,19 as well as patient-controlled analgesia
for perioperative pain management.
positioning of the patient and port placement
The general technique for VATS is neither simple nor uni-
form. Absolute understanding of thoracic anatomy and video
orientation is critical. Thoracoscopy is made difficult by par- Figure 3 Triangulation technique for port placement in
adoxical motion when the camera and instruments are facing relation to intrathoracic structures and targets.
each other. Preparation and positioning are the same for all
major VATS procedures. The surgeon stands facing the
patient, who is placed in the full lateral decubitus position,
elevated on pontoons [see Figure 2] designed to protect pres-
sure points. Flexing the operating table to open the intercos-
tal spaces (ICSs) for maneuvering instruments can be used
but is not mandatory.
Port placement involves triangulation of the target with
trocar ports [see Figure 3]. Alignment of the thoracoscope and
positioning of the video monitors in the operating room are
of paramount importance. The thoracoscope is usually placed
in the seventh or eighth ICS over the mid-to-anterior axillary
line [see Figure 4]. Additional 1 cm incisions, usually two, are
placed along the line of the standard posterolateral thora-
cotomy incision approximately on the fifth ICS, one at the
anterior axillary line and one at the posterior axillary line. The
incisions are placed such that a triangular configuration is
achieved. This setup facilitates the most efficient use of the
instruments by the surgeon and the assistant. In females,
the skin incision can be made in the inframammary fold for Figure 4 Thoracoscope and trocar placement.
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cosmesis. These incision sites may vary according to the Table 2 Basic Instruments and Equipment Used for
proposed procedure, the location of the pathology, patient VATS Procedures
body habitus, and previous scars. Alternatively, a ring forceps
Standard open thoracotomy set
or endo-Kittner (Ethicon Endo-Surgery, Cincinnati, OH) Standard thoracoscopic instruments set
can be used to inspect the chest cavity and expose the hilum • Thoracoscope, rigid or flexible
to determine the proper position for the other incisions. The 0°, 30°, and 45°
so-called access incision should be placed so as to provide 5 or 10 mm (diameter)
• Endoscopic staplers*
direct access to the hilum. A soft tissue retractor may be used Echelon ENDOPATH 45 and 60 mm
to provide adequate exposure. Intraoperative conversion to a Echelon ENDOPATH ETS 35 or 45 mm
standard thoracotomy will be necessary in approximately 5 to • Thoracoscopic endo-Kittner†
20% of patients undergoing VATS depending on the level of • ENDOPATH 5 mm babcocks, graspers, curved dissector
and scissors*
experience for several reasons, including extensive pleural • EnSeal (bipolar coagulation, mechanical transection of tissue
adhesions and pulmonary lesions that cannot be located tho- allows simultaneous sealing and transection of blood vessels
racoscopically or that necessitate a more extensive resection up to 7 mm)*
than can be accomplished by VATS. • Harmonic shears (for lymph node dissection only,
cut /coagulate vessels up to 5 mm in diameter)*
instrumentation • Specimen retrieval bags
ENDOPOUCH Retriver 224 mL retrival bag, polyure-
The equipment used for VATS comprises (1) a video thane*
camera and tower; (2) monitors, usually two at 45° from the Endo-Catch Gold (10 mm specimen pouch)‡
midline; (3) thoracoscopes and ports; (4) staplers; (5) tho- Endo-Catch II (15 mm specimen pouch)‡
• Endoscopic, surgical irrigation and suction systems
racic instruments (e.g., lung clamps and retractors) that have
been modified for endoscopic use; (6) various devices for * VATS = video-assisted thoracic surgery. Ethicon Endo-Surgery, Cincinnati,
OH
tissue cauterization; and (7) a suction irrigation device [see †
Aspen Surgical, Caledonia, MI
Figure 5]. A basic open thoracotomy tray and instruments ‡
Covidien, Norwalk, CT
should be available in the event of conversion to open
thoracotomy [see Table 2]. telescope with a forward-viewing scope or a 5 or 10 mm
flexible scope can be used. The rigid thoracoscope has an
Video Equipment
excellent resolution. Placing the video camera at the distal
The basic components of all video systems used for thora- end of a flexible thoracoscope, as in the electronic video-
coscopy are similar: a large-screen video monitor, a xenon thoracoscope (EVE-L, Fujinon, Wayne, NJ), yields better
light source, a video recorder, and a printer for still photog- visualization of some relatively inaccessible areas in the chest.
raphy. A second video monitor, either mounted on a cart or The disadvantages of the flexible thoracoscope include
hanging from the ceiling, is connected by cable to the main increased expense and complexity and reduced resolution
monitor and is placed across from it at the head of the compared with rigid systems.20 For most VATS procedures,
operating table. Alternatively, a single monitor can be placed a 10 mm 30° rigid telescope is used. This thoracoscope allows
at the head of the operating table. A CO2 insufflator is used better orientation and visualization around structures such as
for the combined thoracoscopic/laparoscopic procedures, the pulmonary artery and bronchus. Thoracoports are shorter
such as in MIE. and have a corkscrew configuration on the outside that
Thoracoscopes and Thoracoports stabilizes them within the chest wall. The trocar is simply a
blunt-tipped obturator that facilitates passage of the cannula
Both rigid and flexible thoracoscopes can be used for through the chest wall. A long laparoscopic trocar may be
VATS. Depending on individual surgeon preference, level used in morbidly obese patients. Thoracoports are available
of expertise, and comfort zone, a 5 or 10 mm 0° or 30° rigid in several sizes (5, 10.5, 12, and 15 mm in diameter) to
accommodate various instruments.
Staplers
Endoscopic gastrointestinal anastomosis (Endo-GIA) sta-
plers have revolutionized the surgeon’s ability to perform
minimally invasive pulmonary resections. Furthermore, tissue
reinforcements that buttress the staple line with prosthetic
materials (Gore-Tex [W.L. Gore & Associates, Newark, DE]
or bovine pericardium) are highly reliable and provide excel-
lent hemostasis as well as closure of air leaks reducing post-
operative air leakage. The vascular stapler cartridge with six
rows of 2.0 or 2.5 mm staples is designed for division of thin
vascular tissue such as the pulmonary vessels. Some surgeons
are reluctant to use it on hilar vessels because if the stapler
fails mechanically (e.g., cuts without applying both staple
lines properly), life-threatening hemorrhage can ensue.21
Endoscopic staplers that do not cut (transverse anastomosis
[TA] staplers) are also available. Some advocate using two
applications of the endovascular stapling device to minimize
Figure 5 Video and monitors. the risk of transecting the vessel as a consequence of a
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stapling misfire. In this approach, the stapler is first fired single-lung ventilation. The patient is placed in the full lateral
proximally with the knife removed, leaving six rows of staples decubitus position, but depending on the location of the
in place. Next, the stapler is fired again more distally with the target, the patient can be tilted 5° forward or backward.
cutting mechanism intact to transect the vessel, leaving a total Ventilation to the lung being operated on is stopped as soon
of nine rows of staples on the patient side and three rows of as the patient is rotated into the lateral decubitus position, to
staples on the specimen side. ensure that the lung will be thoroughly collapsed by the time
the videothoracoscope is inserted into the pleural space. The
Instruments
incisions are made on the superior aspect of the ribs to avoid
Various types of Pennington and Duval clamps are avail- injury to the neurovascular bundle. A standard thoracoscopy
able. Sponge sticks modified by the introduction of various is performed with three 10 mm incisions: a camera port is
curves and a line of lung clamps are used for retracting lungs, placed in the anterior axillary line in the seventh or eighth
dissecting hilar structures, and holding lymph nodes. The ICS; an anterior or access port is placed between the latissi-
vein retractor and the fan retractor, which can be opened mus dorsi and the pectoralis major muscles in the fourth or
and closed like a fan by turning a knob on the end, can also fifth ICS, and a posterior or working port is placed adjacent
be used during VATS. Vein retractors are best suited for to the scapula in the fifth or sixth ICS. Alternatively, a 5 mm
gentle retraction of hilar or mediastinal structures (e.g., ves- incision can be used for a 5 mm camera, and one working
sels, bronchi, esophagus, or lymph nodes), whereas the fan port ranging from 3 to 10 mm can be used. It is important to
retractor can be used to hold the whole lung during MIE.
orient the instruments and the thoracoscope such that they
In major VATS procedures (e.g., VATS lobectomy), the
face the target within a 180° arc; this positioning prevents
soft tissues of the access incision may be retracted by means
mirror imaging and helps the surgery team develop a three-
of a cerebellar (or Weitlaner [Miltex, Inc, York, PA]) retrac-
dimensional spatial anatomic orientation in the chest. The
tor. This allows the surgeon to dissect and encircle hilar vas-
incisions should also be placed widely distant from each other
cular structures by using two instruments through the same
so that the instruments do not crowd one another. Should it
incision. A Harken clamp (Scanlan, Saint Paul, MN) is useful
become necessary to convert to a thoracotomy, the two upper
in that it is long enough to reach behind a vascular structure,
pass a silk suture to the tip of the instrument, and tie it to an incisions can be incorporated into the thoracotomy incision
endoleader to guide the stapler across these delicate arterial and the lower incision can be used as a chest tube site. When
branches.22 A long Allis forceps is an excellent instrument for a patient is being operated on for an apical lesion, the camera
holding and retracting lymph nodes during a mediastinal port can be placed at the fifth or sixth ICS, and the two
lymph node dissection. Although biopsy forceps have been instrument ports may also be moved higher, toward the axilla,
specifically created for laparoscopy and thoracoscopy, those and the other higher on the posterior chest wall at approxi-
used for mediastinoscopy are, in fact, well suited for thora- mately the third ICS. Also, a fourth port may be helpful for
coscopy. Various curved and right-angle dissecting clamps, the introduction of additional instruments or to palpate the
needle holders, and scissors have been developed. In addi- lesion, depending on its location. An infant Finochietto
tion, standard thoracotomy instruments can be inserted (Medicon, Bedford, VA) or a Weitlaner retractor is used to
through a minithoracotomy incision and used just as they keep the soft tissues from falling into the wound without
would be in an open procedure. spreading the ribs. These are the basic steps on which
modification of the technique will occur depending on the
Devices for Tissue Cauterization pathology, the location of the target being removed, and the
The standard disposable electrocautery device (Bovie Medi- surgeon’s skills.
cal Corporation, Clearwater, FL) with a long tip extension,
or the Harmonic Scalpel (Ethicon Endo-Surgery, Cincinnati,
VATS Procedures for Pleural Disease
OH), the LigaSure vessel sealing system (Covidien, Valley-
lab, Boulder, CO) and the argon beam electrocoagulator operative technique
handpiece are narrow enough to pass through a thoracoport.
These instruments can be used for dissection and cauteriza- One or two 10 mm incisions are made for the videothora-
tion during VATS. The argon beam electrocoagulator coscope and instruments. The videothoracoscope is inserted
(ConMed Corporation, Utica, NY) is a noncontact form of through either a 5 or 10 mm thoracoport at the seventh or
electrocautery that provides hemostasis on raw surfaces (e.g., eighth ICS in the midaxillary line. In cases of pleurodesis,
denuded pulmonary parenchyma or the chest wall after pleu- either by mechanical or talc poudrage, the incisions are used
rectomy) and helps seal air leaks from the surface of the lung. for placement of chest tubes, with a right-angle tube inserted
Instrumentation for videothoracoscopy continues to evolve. over the diaphragm through the lower incision and a straight
Nevertheless, it may still be necessary to combine disposable tube advanced up to the apex of the pleural space through
and nondisposable instruments from different manufacturers the upper incision. Alternatively, a small 19 French Silastic
and to use instruments originally designed for other proce- flexible drain (Blake drain, Ethicon, Somerville, NJ) can be
dures. It is best to maintain a single standard tray that includes placed in the chest cavity as well, but it has to be looped
the basic instruments required for most operations and to add around the base of the lung and over the diaphragmatic
instruments as needed. surface and guided posteriorly along the parietal pleura with
its tip up in the apex.23 Special attention must be paid to the
placement of the incision in patients with suspected malig-
Basic Operative Technique nant mesothelioma because of the propensity of this tumor to
At our institution, VATS is conducted under general implant in incisions and needle tracks. Once the videothora-
anesthesia using a double-lumen endotracheal tube and coscope has been inserted, pleural fluid is drained with
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Yankauer suction tip (Cardinal Health, Dublin, OH) and is the metastasis.25 Improved survival in patients with pulmo-
sent for cytology, microbiology, and chemistry. Inspection of nary metastases appears to be directly linked to the ability to
the cavity is performed, and multiple pleural biopsies are remove all macroscopic tumor. The biology of pulmonary
obtained. Fibrinous debris can be removed by irrigating the metastases may favor VATS resection based on the following
pleural space with a pulsating water irrigation system. This arguments: (1) metastases have been present prior to treat-
technique is particularly useful for the débridement and ment of the primary lesion and in that sense have been
drainage of loculated fibrinopurulent empyema. Talc pou- “missed” for a significant period of time already; (2) as noted
drage for the treatment of malignant pleural effusion can be above, multiple resections do not adversely affect the overall
accomplished by delivering 2 to 6 g of talc in the pleural outcome of patients with metachronously detected metasta-
cavity with a pneumatic atomizer using 10 L of high-flow ses; (3) patients with unresectable disease who have a recur-
O2.24 At the end of the procedure, an intercostal nerve block rence will not be subject to a larger operation, i.e., thoracot-
is performed under the direct vision of the thoracoscope. omy; (4) VATS resection may be less stressful for patients
and therefore result in less immunosuppression, resulting in
troubleshooting
a more favorable disease course; and (5) VATS may permit
In patients with loculated effusion, the thoracoport place- patients to return to their regular work or family schedules
ment must sometimes be modified. The preoperative chest significantly earlier than an open approach. Other consider-
CT scan should help ensure that the ports are placed in areas ations include quality of life and cost of treatment. Historical
where the lung is not adherent to the chest wall. In some data, tumor biology, and recent advances in radiologic and
cases, the pleural space is obliterated by adhesions or tumor. surgical techniques support the use of video-assisted surgery
This event occurs most frequently in patients who have had in the resection of pulmonary metastases, following the
severe inflammatory disease (e.g., pneumonia, empyema, or paramount principle of removing all lesions found on a
tuberculosis) or extensive pleural malignancy (e.g., locally high-resolution CT scan.
advanced malignant mesothelioma). In these circumstances, Anecdotal reports of port-site recurrence also have raised
the anterior thoracoport incision can be extended to a length concerns about VATS as a treatment method in patients with
of 5 to 6 cm, the underlying rib section can be resected, malignancies. However, a 2001 study of 410 patients from a
and the parietal pleura can undergo biopsy. If thoracotomy is prospective VATS database found only one case of port-site
subsequently warranted for therapeutic reasons (e.g., for recurrence.26 The authors concluded that the incidence of
pleurectomy, decortication, or extrapleural pneumonectomy such recurrences could be kept low if surgical oncologic prin-
for mesothelioma), this small incision can be incorporated ciples are respected. These principles include (1) reserving
into the thoracotomy incision. VATS for lesions that can be widely excised; (2) conversion
to an open thoracotomy for definitive or extensive operations;
and (3) meticulous technique for extraction of specimens
VATS Pulmonary Wedge Resection
from the pleural space, with small specimens removed directly
VATS pulmonary wedge resection has become a standard through a thoracoport and larger specimens removed in an
approach to diagnosing small, indeterminate pulmonary nod- endo-bag.
ules and pulmonary infiltrates of uncertain origin, particularly
in immunocompromised patients in whom transbronchial operative technique
biopsy is neither safe nor appropriate. The role of VATS Once general anesthesia has been induced and a double-
wedge resection is less well defined in the management of lumen endotracheal tube inserted, the patient is placed in the
primary lung cancers but may be indicated in patients with full lateral decubitus position. Small subpleural pulmonary
marginal lung function who otherwise would not tolerate a nodules are most easily identified in a fully atelectatic lung
lobectomy. Although no prospective studies have been per- because they protrude from the surrounding collapsed
formed to clearly assess the benefit of pulmonary metastasec- pulmonary parenchyma. Most pulmonary wedge resections
tomy, there is an abundance of retrospective data to indicate are performed as true videothoracoscopic procedures using
a long-term survival benefit from complete pulmonary resec- just three port incisions placed in a triangulated manner [see
tion. The general criteria in selecting patients for pulmonary Figure 4]. The pulmonary nodules to be removed are grasped
metastasectomy include the following: (1) the primary with an endoscopic lung clamp (Pennington, ring forceps, or
neoplasm must be completely controlled or imminently con- Duval) inserted through one instrument port, and wedge
trollable; (2) metastatic lesions must be limited to the lung resection is done with repeated applications of an endoscopic
without evidence of other distant organ involvement; (3) all stapler inserted through the opposite port. An endoscopic
metastases must be resectable with adequate pulmonary lung compression clamp is a linear clamp that can be placed
reserve; and (4) nonavailability of another effective therapy. deep to the lesion to ensure a 1 cm margin from the lesion to
In cases that meet these resection criteria, long-term survival the staple line [see Figure 6]. As the resection is performed, it
rates have been reported to be in the range of 30 and 58% is often helpful to introduce the stapler through each of two
for patients with soft tissue and osteogenic sarcomas, instrument ports to obtain the correct angle for application to
respectively. Similar cure rates have been reported with the the lung. To prevent tumor implantation in the chest wall, all
resection of isolated pulmonary metastases from colon cancer specimens are placed in a disposable endo-bag and brought
(30.5%), renal cell carcinoma (52.4%), head and neck out through a slightly enlarged anterior thoracoport incision.
cancers (48%), and germ cell tumors (59%). Although some At the end of the procedure, intercostal nerve blocks are
melanoma patients with a solitary metastasis may benefit performed under direct vision of the thoracoscope, and a
from pulmonary metastasectomy, most patients with this dis- single chest tube is inserted through the inferior port after the
ease do not survive long-term despite aggressive resection of videothoracoscope is withdrawn.
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surfaces can be cauterized with either the neodymium:

yttrium-aluminum-garnet (Nd:YAG) laser or the argon beam
coagulator. Numerous types of absorbable sealant patches or
materials are also available to control air leaks from areas of
raw pulmonary parenchyma.
Occasionally, after a wedge resection, it is necessary to
suture together the pleural edges over an area of raw pulmo-
nary parenchyma. The suturing can be done directly through
a non–rib-spreading access incision or through port sites. In
the latter case, the ports are removed and a 3-0 polypropylene
suture is passed through the anterior port site with a standard
needle holder. A second needle holder is introduced via the
posterior port site and used in place of a forceps to pick up
and reposition the needle as it is passed through the lung.
The surgeon and the first assistant work together to oversew
the lung, in contrast to the normal practice for an open
procedure, in which the surgeon uses a needle holder and a
forceps to place the sutures.
VATS Procedures for Spontaneous Pneumothorax and

Bullous Disease
Figure 6 Wedge resection, lung compression clamp.
operative technique
troubleshooting VATS is now frequently performed for the management
Several techniques may be used to locate pulmonary of recurrent spontaneous pneumothorax and for bullous
nodules that are either too deep or too small to be easily disease. The approach is similar to that followed in a wedge
visible on simple inspection of the lung. All of these should resection, with three or four port sites being used. The vid-
be used in conjunction with a high-quality preoperative chest eothoracoscope is inserted at the fifth ICS in the midaxillary
CT scan to identify the lung segment in which the nodule is line, and two other port sites are added at the fourth ICS
located. Thoracoscopic examination of the lung nodule can in the anterior and posterior axillary lines. In patients with
be performed by gently running an endo-Kittner or a ring spontaneous pneumothorax, the responsible bulla (which is
forceps on the surface of the lung as a surrogate to digital usually apical in location) is identified, and wedge resection
palpation. With experience, one can “feel” a bump and grasp is done with a tissue-reinforced endoscopic stapler. Bullae
the visceral pleura adjacent to the location. The nodule can can be excised by applying the stapler across the base of
be brought up toward the examining finger placed through the area of bullous disease. They also can be ablated with
one of the ports. Alternatively, under prior CT guidance the argon beam coagulator or the Nd:YAG laser and then
preoperatively, a needle may be inserted into the nodule for suture-plicated if necessary.
intraoperative localization, much like a breast needle localiza- troubleshooting
tion procedure. Localization is accomplished by injecting
methylene blue or by inserting a barbed mammography The placement of port incisions should be determined by
localization needle, which is then cut off at the skin exit site the location of the bullae. Because bullous disease is generally
and later retrieved thoracoscopically. Needle localization apical, port sites are correspondingly higher than for the aver-
techniques are effective, but they also are costly and time- age wedge resection (i.e., at the fourth and sixth ICSs rather
consuming and need to be coordinated with the radiology than at the fifth or sixth and eighth ICSs). The precise place-
team and surgeons. Finally, if careful endoscopic examina- ment should, however, be determined by determining the
tion of the lung fails to reveal the location of a nodule, exact location of the disease site(s) on the preoperative CT
an access incision is added to the videothoracoscopy. Each scans. The main problem after resection for bullous disease
lobe of the lung is sequentially rotated up to this non–rib- is prolonged air leak from the staple line. This problem can
spreading utility thoracotomy for direct digital palpation. be minimized by applying commercially available sleeves
This technique almost always permits identification of a made of bovine pericardium or with tissue-reinforced staplers
nodule when other techniques fail. and by performing pleurodesis. Mechanical pleurodesis is
Pulmonary nodules located on the broad surface of the done with a small gauze sponge passed through a port site.
lung may not be amenable to a wedge resection with an Some surgeons scarify the pleura by cauterizing it with the
endoscopic stapler. Such nodules can be removed by means argon beam coagulator or the Nd:YAG laser, but this is not
of electrocauterization, just as in an open thoracotomy. An as effective as mechanical pleurodesis. Chemical pleurodesis
extension is placed on the handle of the electrocautery device, by talc poudrage should be reserved for older patients with
which is then introduced into the pleural space through either emphysema and bullous disease and avoided in young patients
a port or an access incision. Another approach is to resect the with spontaneous pneumothorax, who might require a thora-
pulmonary nodule with a laser in either contact or noncontact cotomy later in life. Another option in younger patients is a
mode. To minimize bleeding and air leakage, raw pulmonary limited apical pleurectomy. Special angulated instruments
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and blunt dissectors have been designed for this procedure; techniques have been developed.27 VATS pneumonectomy is
however, a parietal pleurectomy is also easily performed with performed with less frequency. There are emerging data using
combinations of standard blunt and sharp instruments. VATS, but this approach is experimental at this point in time.
These tumors are usually larger and centrally located, making
it difficult to assess for the option of a sleeve lobectomy.
VATS Lung Volume Reduction Surgery
Therefore, this operation is best performed through an open
operative technique thoracotomy. However, these operations are done as VATS
procedures using an access incision, which facilitates inser-
VATS may also be applied to the performance of lung
tion of standard thoracotomy instruments, extraction of the
volume reduction surgery (LVRS). If unilateral LVRS is
resected specimen from the pleural space, and performance
planned, the patient is placed in the lateral decubitus posi-
tion, and port placement is similar to that for a patient under- of the technically complex aspects of the procedure, including
going a wedge resection of the upper lobe. Most patients dissection of the hilar vessels and the mediastinal lymph
undergoing LVRS, however, benefit from bilateral LVRS. nodes.
For this procedure, the patient is placed in the standard Two approaches to lobectomy have been developed. One
supine bilateral lung transplantation position, with shoulder involves sequential anatomic ligation of the hilar structures,
rolls placed vertically in an inverted U fashion behind the much as in a standard anatomic lobectomy, and the other
back and with the arms positioned above the head. The involves mass ligation of the pulmonary vessels and the bron-
camera port is placed in the anterior axillary line at the sixth chus. The latter is not considered an anatomic lobectomy;
ICS. A lung compression clamp is placed on the area that therefore, we do not endorse its practice. Both approaches
will be resected. A tissue-reinforced stapler is then inserted require at least two port incisions in addition to the access
into the chest and fired sequentially until the desired area is incision. The sequential anatomic ligation approach has been
excised [see Figure 7]. well described and follows sound surgical oncologic princi-
ples. Accordingly, it is our preferred method of performing
troubleshooting VATS lobectomy. In an effort to standardize the approach,
A major cause of morbidity and mortality with this pro- we define a VATS lobectomy as an anatomic dissection
cedure is the occurrence of air leaks, which sometimes are that is performed entirely under thoracoscopic visualization,
large enough to compromise ventilation significantly. Thus, proceeds in an anterior-to-posterior fashion, and uses a 4 cm
once LVRS has been done on one side, the lung is reex- utility incision, two thoracoscopy ports (one for the camera
panded and any air leaks are carefully assessed. If the leak is and one for retraction), and no rib spreading. Avoiding rib
small, the other side is operated on in the same setting; if the spreading is the key element in VATS lobectomy to prevent
leak is large, the contralateral procedure is postponed to a postoperative pain and trauma to the intercostal nerve
later date. The use of fibrin glue or another commercially bundles, which are responsible for the postthoracotomy pain
available pneumostatic sealant along the staple line should be syndrome. A metastatic survey is performed in all patients
considered to minimize postoperative air leakage. undergoing VATS lobectomy for malignant disease. The
chest is inspected for metastatic pleural and pericardial
implants and effusion, chest wall invasion, adhesions, enlarged
VATS Lobectomy and Pneumonectomy
lymph nodes, and anatomic variations. Radical lymph node
Although VATS lobectomy is much less frequently per- dissection includes evaluation of lymph node levels 2, 4, 7, 8,
formed than VATS pulmonary wedge resection, standard and 9 on the right side. On the left side, it should also include
lymph node levels 5 and 6.
operative technique
Lobectomy (Sequential Anatomic Ligation)

Correct positioning and port placement are essential for
a successful VATS lobectomy. The first port placed is the
camera port. It is usually placed through the seventh or eighth
ICS and should provide visualization of the anterior and pos-
terior hilum and align with the major fissure in a caudal-
cephalic orientation. Whether the port is in the anterior,
middle, or posterior axillary line depends on the level of the
diaphragm as seen from a review of the preoperative chest
x-ray or CT scan, on the location of the target, and on the
side of the procedure.
The anterior or utility port (< 4 cm) should be placed right
over the hilum. The hilum and the fissures will be dissected
through this port. The port usually is created anterior to the
latissimus dorsi in the fourth ICS for upper lobectomies and
in the fifth ICS for lower lobectomies. A soft tissue retractor
may be used to keep the subcutaneous tissue and muscle
Figure 7 Tissue-reinforced stapler is inserted into the chest. away from the incision. The third (posterior) port is usually
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placed where the edge of the lower lobe touches the dia-
phragm under the vision of the thoracoscope either inferior
or posterior to the scapular tip. This port usually is used for
retracting the lung. A ring forceps is placed through the
posterior port, and the upper lobe is retracted laterally to
permit visualization of the superior pulmonary vein. Table 3
shows the general operative steps for VATS lobectomy.28
Right-Side Resections
Right upper lobectomy The initial dissection is carried
out at the anterior hilum. The phrenic nerve is identified, and
the mediastinal pleura is opened posterior to it. This plane is
developed anteriorly, superiorly, and then posteriorly between
the lung and the azygos vein. If any level 10 lymph nodes are
found at this location, they are sampled and sent for frozen
section. This dissection can, for the most part, be accom-
plished with blunt dissection using two endo-Kittners. Next,
the lung is retracted anteriorly and the posterior hilum is
opened to expose the right mainstem bronchus. Further
dissection is carried out to expose the bifurcation of the upper Figure 8 The endoleader looped around the superior
lobe bronchus and the bronchus intermedius. The superior pulmonary vein.
pulmonary vein is dissected from the overlying pleura via the
access incision with long Pearson or Metzenbaum scissors
and DeBakey forceps, similar to an open lobectomy. A
Harken clamp is passed behind the superior pulmonary vein
after clear identification of the middle lobe vein. The superior
pulmonary vein is encircled with an oiled 2-0 silk suture,
which is then tied to the endoleader.29 A lung clamp is placed
through the utility incision, and the upper lobe is retracted
posteriorly. An endovascular stapler is placed through the
posterior port and, guided by the endoleader, is passed behind
the superior pulmonary vein and deployed [see Figure 8].
Once the pulmonary vein has been divided, the truncus
anterior of the pulmonary artery and its variable apical
branches are exposed. A Harken clamp is passed around the
anterior and apical pulmonary arterial branches, and an oiled
2-0 silk suture followed by the endoleader is passed around
these vessels and brought out through the utility incision. The
endovascular stapler is passed though the posterior port and
used to transect the vessels. Transection of the truncus artery
and its branch exposes the right upper lobe bronchus [see
Figure 9]. Dissection is performed to separate the ongoing
pulmonary artery from the bronchus. An endoscopic 4.8 mm
GIA stapler is placed through the posterior port and closed Figure 9 The endoleader looped around the truncus anterior
but not fired until the lung is inflated, demonstrating that the and its branch.
middle lobe bronchus is patent. Once the upper lobe bron-
chus has been divided [see Figure 10], the fissure is completed
with the stapler. The upper lobe is then placed in a large Certain basic surgical concepts—dissection of hilar struc-
surgical tissue endo-bag and removed via the utility incision. tures, passage of a monofilament suture around the structure,
and transection with a stapler—are similar for all lobecto-
mies. However, the order in which structures are transected
and the ports through which staplers are passed differ.
Table 3 Operative Steps for VATS Lobectomy
Step 1 Positioning and incision/thoracoscopic port placement Right middle lobectomy The camera port is placed in
Step 2 Lung mobilization the seventh ICS in the midaxillary line. The anterior or access
Step 3 Isolation and division of pulmonary arterial and venous
branches port is placed in the fifth ICS. The posterior or working port
Step 4 Fissure completion is placed either at the scapula tip or posterior to it in the sixth
Step 5 Bronchial division or seventh ICS. The right middle lobe is retracted laterally,
Step 6 Lymph node dissection and the middle lobe vein is exposed by dissecting it on the
Step 7 Closure
anterior hilum. Once the middle lobe vein is dissected free,
VATS = video-assisted thoracic surgery. it is divided using the same maneuvers as described earlier
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hilum has been opened posteriorly and the inferior pulmo-

nary vein dissected. Next, the apex of the lung is gently
grasped with a ringed forceps and retracted toward the dia-
phragm. This maneuver exposes the paratracheal lymph
nodes. The pulmonary artery is then identified just under the
surface of the pleura at the fissure. The visceral pleura overly-
ing it is opened. A tunnel of visceral pleura is created over the
pulmonary artery by gently pulling the visceral pleura toward
the chest wall and dissecting it with endo-Kittners. This
maneuver allows for identification of the middle lobe bron-
chus. Once this tunnel is developed, the fissure is completed
posteriorly with the endo-stapler. At this point, the lower lobe
pulmonary artery is visualized. A Harken clamp is passed
under the artery, and the artery is dissected. The flat tip of a
35 mm vascular load stapler (white load) is passed under the
pulmonary artery to the lower lobe and the basilar trunk is
transected. The lung is retracted upwards and toward the
anterior mediastinum. The inferior pulmonary vein is then
transected with the same technique as for the pulmonary
artery. The vascular stapler is brought in from the access inci-
sion toward the back while lifting the lung up with the ring
forceps through the posterior port. The lung is then pulled
upwards, the lower lobe bronchus is dissected out, and the
stapler is applied but not fired. The anesthesiologist should
Figure 10 Division of the upper lobe bronchus.
then inflate the middle lobe. Bronchoscopy is also performed,
and the orifice to the middle lobe is visualized. Only after
these maneuvers have been performed is the bronchus to the
using the endovascular stapler. The middle lobe bronchus is
lower lobe transected. The lobe is placed in the endo-bag and
exposed and divided before the artery because it lies anterior
brought out through the access port incision.
to the pulmonary artery to the middle lobe. Caution should
be exercised while dissecting around the middle bronchus Left-Side Resections
so as not to injure the arterial branches to the middle lobe.
Left upper lobectomy The left upper lobectomy is
Maciejewski described two arterial branches of the pulmo-
technically the most challenging approach because of the
nary artery to the middle lobe in 57% of the patients and a
anatomic variability in the pulmonary artery branches as well
single artery penetrating the middle lobe in 43% of patients.30
as a common pulmonary vein trunk that drains to the back
The length of arteries can be up to 30 mm and the diameter
of the left atrium. Maciejewski reported that in most cases of
up to 10.6 mm. The pulmonary artery branches are dissected
free, isolated, and divided with the endovascular stapler. The his series, there were four, and, in a few cases, up to seven,
fissure is completed, and the middle lobe is removed in a branches of the pulmonary artery to the upper lobe, measur-
specimen endo-bag through the access port. ing 30 mm in length and 12 mm in diameter.31 In about 50%
of the cases, the branches were divided in (a) apicoanterior
Right lower lobectomy The camera port is inserted in trunk, (b) lingular, and (c) one or two subsegmental branches.
the seventh ICS in the posterior axillary line. The posterior In 25% of the cases, almost all segmental branches penetrated
port is placed either at the tip of the scapula or immediately into the lobe separately. In 20% of the cases, a single apico-
behind it. The access port is placed directly over the fissure posterior trunk or independent segmental or subsegmental
between the middle and lower lobe at the level of the inferior branches were present. Only in 5% of the cases did the
pulmonary vein. Ring forceps are used to retract the middle branches include the apicoposteroanterior trunk and the
lobe medially and the lower lobe posteriorly. Next, the lower remaining segmental and subsegmental branches.
lobe is retracted superiorly and the inferior pulmonary liga- Although port placement is similar to that for right upper
ment is taken down with either electrocautery device (Bovie) lobectomy, the camera port is placed more posteriorly through
or Harmonic shears (Ethicon Endo-Surgery, Cincinnati, a seventh or sixth ICS in the anterior axillary line, to avoid
OH). Level 9 lymph nodes are taken during this step of the obstruction of the camera view by the heart and the pericar-
operation. Next, the posterior mediastinal pleura is opened at dial fat pad. Once all ports have been placed, dissection of
the level of the inferior pulmonary vein and the dissection the anteroposterior window lymph nodes is carried out. This
continues posteriorly between the posterior hilum and the provides information about metastatic nodal spread. It also
esophagus. If a level 8 lymph node is found at this location, opens up the space around the artery and vein. The posterior
it is removed as well. This dissection is carried out to the level port is placed just behind the tip of the scapula. The lung is
of the azygos vein. The lung is then retracted anteriorly retracted posteriorly, the hilum is opened anteriorly, and the
toward the anterior mediastinum. Next, level 7 (subcarinal) superior pulmonary vein is dissected free. Caution must be
lymph nodes are dissected with two endo-Kittner dissectors exercised during this phase of the dissection to avoid injuring
and removed. At this point, most of the pleura along the the back wall of the vein while it is being dissected off the
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airway. The upper lobe is retracted posteriorly and the lower to avoid impingement on the lingular bronchus. In cases of
lobe is retracted somewhat anteriorly, toward the pericar- incomplete fissure, the fissure between the lingula and lower
dium, splaying out the fissure. The pulmonary artery is usu- lobe should be opened prior to dissection of the pulmonary
ally found in the fissure, where it is visualized as a white, artery to facilitate subsequent arterial exposure.
shiny structure. Dissection of the pulmonary artery creates a
Pneumonectomy
space on the top of the artery, a so-called vascular tunnel that
allows one to complete the fissure with a stapler, thereby This operation is best performed through an open
avoiding problems with air leak. A ringed forceps is placed thoracotomy.
through the fourth ICS to access the incision anteriorly. The
lung is now moved anteriorly. The endo-Kittners are placed VATS Mediastinal Lymph Node Dissection
through the posterior port to dissect the lymph nodes located
above the pulmonary artery as it traverses into the fissure. operative technique
The first apical branch of the pulmonary artery is dissected For biopsy of the aortopulmonary window nodes or
free and transected with an endoscopic GIA vascular stapler anterior mediastinal masses, VATS mediastinal lymph node
introduced via the posterior port. The anterior aspect of dissection is often performed as an alternative to a Chamber-
the fissure is opened with one or two applications of an endo- lain procedure and is thought by some surgeons to provide
scopic GIA stapler introduced via the access incision. The better exposure and a superior cosmetic result. The thoraco-
bifurcation of the left upper and left lower lobe bronchi is scope is inserted at the fifth or sixth ICS in the posterior
identified, and the left upper lobe bronchus is transected with axillary line. Instruments for retracting the lung inferiorly are
an endoscopic GIA stapler with 4.8 mm staples introduced introduced via a port at the seventh ICS in the midaxillary
via the posterior port. A ringed forceps is used to retract line. Instruments for dissecting nodes are introduced through
the stump of the bronchus laterally, which facilitates exposure ports placed at the fourth ICS in the anterior axillary line and
of several branches of the pulmonary artery, including the in the auscultatory triangle. The lymph nodes are dissected
lingular artery. These branches are transected individually via free with graspers (e.g., curved sponge sticks or polyp for-
the posterior port. The fissure is completed with an endo- ceps), scissors, the electrocautery device, and endoscopic
scopic GIA stapler with 4.8 mm staples through the posterior hemostatic clips. A similar approach can be used for biopsy
port and dividing it. The lobe is placed in the endo-bag and of other mediastinal nodes, including the paratracheal and
brought out through the access port incision. A 24 French periesophageal nodes. Dissection of level 4 and level 2 nodes
chest tube is placed toward the apex of the lung. on the right is facilitated by transection of the azygos vein. It
is more difficult to do a complete en bloc subcarinal lymph
Left lower lobectomy The camera port is placed in the node dissection on the left than on the right with this method,
eighth ICS in the posterior axillary line to provide exposure although nodal sampling of this region by means of VATS is
to the posterior hilum and to avoid crowding of the instru- certainly feasible, especially when an access incision is used.
ments. The access port is placed anteriorly in the fifth ICS.
The posterior working port is usually posterior to the scapular troubleshooting
tip in the sixth or seventh ICS. First, the lung is retracted Care should be taken not to injure the phrenic nerve as it
superiorly and the inferior pulmonary ligament is identified courses along the superior vena cava on the right and across
and level 9 lymph nodes are sampled. The left lower lobe is the anterior aspect of the aortopulmonary window on the left.
held superiorly with a ring forceps through the posterior port, The vagus nerve should be visualized and the origin of
with the ligament under tension. A long-tipped electrocautery the recurrent laryngeal nerve avoided during dissection. The
device, or ultrasonic scalpel, divides the ligament at the base recurrent laryngeal nerve is easily injured on the left side,
of the inferior pulmonary vein. Next, the inferior pulmonary where it passes around the ligamentum arteriosum before
vein is completely dissected. Once the inferior pulmonary traveling under the aortic arch; however, it can also be injured
vein has been dissected free, an endoscopic GIA vascular on the right side if mediastinal lymph node dissection is car-
stapler is placed via the utility incision to transect the vessel. ried too high superiorly along the origin of the innominate
The interlobar pulmonary artery is isolated within the fissure. artery.
The branches of the pulmonary artery to the left lower lobe It is unwise to perform a VATS mediastinal lymph node
are of three types: trunk, segmental, and subsegmental. dissection after induction chemotherapy or chemoradiother-
In 70% of the cases, the branches penetrating the basal apy because the lymph nodes will often be densely adherent
segments showed a treelike configuration; in 3% of the cases, to surrounding structures. This is especially true on the right
the segments had a bushlike configuration; and in 27% of side, where the superior mediastinal lymph nodes usually
the cases, the branches had an intermediate anatomic con- adhere densely to the superior vena cava, the azygos vein, and
figuration.32 The basilar trunk and the artery to the superior the right main pulmonary artery. A thoracotomy, with exten-
segment are identified, dissected, and divided with the endo- sive exposure and sharp dissection, is usually required for a
vascular stapler. The superior segmental artery is divided safe and complete mediastinal lymphadenectomy.
first and the basilar trunk next. This strategy avoids injury to All lymphatic branches should be ligated during node
the superior segmental branch with the stapler used to divide biopsy or dissection to prevent a chyle leak. There are often
the basilar branches. Finally, the bronchus to the lower large lymphatic branches in the distal right paratracheal area.
lobe is dissected and divided with an endo GIA 4.8 mm In addition, the thoracic duct can be injured if periesophageal
stapler through the access incision. Attention must be paid or posterior mediastinal lymph nodes are being removed.
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VATS Esophagectomy brought out through the inferior anterior chest wall through
a 1 mm skin incision, providing downward traction on the
operative technique diaphragm and allowing exposure of the distal esophagus.
Transthoracic Approach The intrathoracic esophagus is exposed by dividing the
inferior pulmonary ligament. The mediastinal pleura overly-
The most widely accepted method of performing a thora-
ing the esophagus is opened, and dissection is carried out
coscopic and laparoscopic esophagectomy is the technique
cephalad toward the azygos vein. The azygos vein is divided
developed by Luketich and colleagues.33 All patients undergo
with an endoscopic stapler [see Figure 12]. Care is taken to
bronchoscopy and on-the-table esophagogastroduodenoscopy
preserve the mediastinal pleura above the azygos vein. This
(EGD) to make a final assessment of the location of the
maneuver helps to maintain the gastric tube in the posterior
tumor and the suitability of the gastric conduit for recon-
struction. If the EGD, endoscopic ultrasonography, or CT mediastinum. By keeping the mediastinal pleura intact near
scan findings suggest gastric extension, T4 local extension, the thoracic inlet, it may help to seal the plane around the
or possible metastases, we perform a staging laparoscopy, a gastric tube, preventing downward extension of a cervical
thoracoscopy, or both. Patients are intubated with a double- leak into the chest. Circumferential mobilization of the
lumen tube and placed in the left lateral decubitus position. esophagus is performed up to the level of 1 to 2 cm above the
The surgeon stands on the right and the assistant on the left. carina, including all surrounding lymph nodes; periesopha-
Four thoracoscopic ports are used [see Figure 11]. A 10 mm geal tissue and fat; the plane along the pericardium, aorta,
camera port is placed at the seventh to eighth ICS, just ante- and contralateral mediastinal pleura up to but not including
rior to the midaxillary line. A 5 mm port is placed at the the thoracic duct; and the azygos vein laterally. Esophageal
eighth or ninth ICS, posterior to the posterior axillary line, branches of the aorta are cut with a Harmonic scalpel.
for the Harmonic shears. A 10 mm port is placed in the ante- No effort is made to find the thoracic duct. A Penrose drain
rior axillary line at the fourth ICS; this port is used to pass a is placed around the esophagus to facilitate traction and
fan-shaped retractor to retract the lung anteriorly and allow exposure [see Figure 12].
exposure of the esophagus. The last 5 mm port is placed The entire intrathoracic esophagus is mobilized from the
just posterior to the scapula tip; it is used to place instruments thoracic inlet to the diaphragmatic reflection. As the dissec-
for retraction and countertraction. In most patients, a single tion proceeds toward the thoracic inlet, care is taken to stay
retracting suture (0-Endostitch, US Surgical, Norwalk, CT) near the esophagus to avoid trauma to the posterior membra-
is placed near the central tendon of the diaphragm and nous trachea and the recurrent laryngeal nerves. Once the
esophagus is completely mobilized in the chest, a single 28
French chest tube is inserted through the most anterior and
inferior port and the lung is inflated to search for any air leaks
from the trachea and proximal bronchus. The thoracic ports
are closed, and the patient is turned to the supine position.
The surgeon remains on the patient’s right; the patient is
positioned in the steep reverse Trendelenburg position.
Five abdominal ports (four 5 mm and one 11 mm) are
used for the dissection [see Figure 13]. The gastrohepatic
ligament is divided. The right and left crura of the diaphragm
are dissected; division of the phrenoesophageal membrane is
avoided at this stage of the operation because this may cause
loss of the pneumoperitoneum into the chest cavity and lead
Figure 11 Thoracic port placement for minimally invasive

esophagectomy. Figure 12 Stapling of the azygos vein.
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retracted superiorly, and the left gastric vessels are identified.

The left gastric artery and vein can be divided from the
retrogastric or lessor curve view, depending on the anatomy,
using the Endo-GIA stapler.
pyloroplasty
The Harmonic scalpel is used to open the pylorus, and the
Endo Stitch (2.0, US Surgical) is used to close the pylorus
transversely [see Figure 15]. A gastric tube is then constructed
by dividing the stomach starting at the lesser curvature and
preserving the right gastric vessels with the 4.8 mm stapler
(Endo-GIA II, US Surgical) [see Figure 16]. There is some
variability in the construction of the gastric tube based on the
characteristics of the tumor. It may be necessary to construct
a slightly more narrow tube or to resect some of the proximal
stomach in tumors with significant gastric extension. If gastric
extension of the tumor is significant, the resection of the
stomach is larger and an intrathoracic anastomosis is per-
formed. Currently, we prefer a gastric tube of 5 to 6 cm in
diameter. Extreme caution must be used when manipulating
the gastric tube during mobilization and stapling to avoid
trauma. The most cephalad portion of the gastric tube is then
attached to the esophageal and gastric specimen using two
2-0 endo-sutures. An additional superficial stitch may be
placed on the anterior proximal gastric tube to facilitate
orientation and prevent twisting as the tube is brought up
into the neck [see Figure 17]. A feeding jejunostomy tube
is done laparoscopically. First, a proximal limb of jejunum
(25 cm distal to the ligament of Treitz) is attached to the
anterior abdominal wall in the left lateral quadrant with the
endo-stitch. An additional 10 mm port in the right lower
Figure 13 Abdominal port placement.
quadrant may be inserted to facilitate suturing of the jejunum
to technical difficulties. The stomach is mobilized by dividing

the short gastric vessels using the Harmonic scalpel. The
gastrocolic omentum is divided, with care taken to preserve
the right gastroepiploic arcade [see Figure 14]. The stomach is
Figure 15 Pyloroplasty. (a) Pyloroplasty is performed using

Figure 14 Division of the gastrocolic omentum along the Harmonic shears. (b) Transverse closure of the pyloroplasty
greater curvature of the stomach and dissection of the hiatus. with endo-stitch technique.
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Figure 16 Creation of a gastric tube. (a) The gastric tube is created by dividing the stomach starting at the distal lesser curve,
preserving the right gastric vessels. (b) A 5 to 6 cm in diameter gastric tube is preferred. (c) Division of the gastric tube is from
the esophagus.
to the anterior abdominal wall. A needle catheter (Compact dissection is performed inferiorly until the thoracic dissection
Biosystems, Minneapolis, MN) is placed percutaneously into plane is encountered. This is generally quite easy because the
the peritoneal cavity. Under direct laparoscopic vision, the VATS dissection is continued well into the thoracic inlet. In
guide wire and catheter are directed into the loop of jejunum addition, we leave the Penrose drain around the esophagus
that has been tacked to the anterior abdominal wall. The during the thoracic dissection and push the drain into the
entry site of the needle catheter J tube is tacked completely periesophageal plane at the thoracic inlet so that it is easily
to the anterior abdominal wall for a distance of several visualized during the neck dissection. This maneuver allows
centimeters. the surgeon to pull the Penrose drain out through the neck to
The last step in the abdominal operation is the dissection facilitate the neck dissection. The esophagogastric specimen
of the phrenoesophageal membrane, which was delayed is pulled out of the neck incision and the cervical esophagus
earlier to minimize the risk of losing the pneumoperitoneum is divided high (1 to 2 cm below the cricopharyngeal muscle).
into the mediastinum. The right and left crura are partially The specimen is removed from the field. An anastomosis is
divided to permit easy passage of the gastric specimen and performed between the cervical esophagus and gastric tube
tube through the hiatus and to prevent later gastric outlet using a GIA stapler [see Figure 19]. Next, the surgeon returns
obstruction. to the laparoscopic view and gently pulls downward on the
Next, a 4 to 6 cm horizontal neck incision is made [see pyloroantral area to retrieve any excess gastric tube that
Figure 18]. The cervical esophagus is exposed. Careful may have been pulled up into the chest during the neck
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especially postoperative respiratory insufficiency and cardiac

arrhythmias. As a result, most centers still prefer the standard
open transhiatal or transthoracic approaches to esopha-
gectomy. VATS may also be used in the management of
postoperative chylothorax. The thoracic duct can be ligated
thoracoscopically, although it is sometimes difficult to iden-
tify and ligate the primary site of a postoperative lymphatic
leak without reopening the thoracotomy.
VATS Pericardial Window

operative technique
Some surgeons create a pericardial window by means of
VATS as an alternative to taking the subxiphoid approach
or the left anterior thoracotomy approach. A double-lumen
endotracheal tube is inserted with the patient under general
anesthesia, and the patient is rotated into the right lateral
decubitus position. Three access sites are used, with the
thoracoscope inserted at the seventh ICS in the posterior axil-
lary line and the instruments introduced through two ports,
one at the tip of the scapula and the other at the sixth ICS in
the axillary line. The pericardium is retracted with a grasper
forceps, and scissors are used to resect 8 to 10 cm2 areas of
pericardium both anterior and posterior to the phrenic nerve.
If indicated, talc pleurodesis can be performed to control an
associated pleural effusion. One or two chest tubes are then
inserted through the port-site incisions.
troubleshooting
Figure 17 Pulling up the gastric tube for cervical When a pericardial effusion causes cardiac tamponade,
anastomosis. a subxiphoid approach is preferable to VATS for creating
a pericardial window because it is safer to perform in a hemo-
dynamically unstable patient. A VATS pericardial window
anastomosis and mobilization. The laparoscopic pull is per-
is also inadvisable in patients with constrictive physiology
formed gently and only until the assistant at the neck observes
or with intrapericardial adhesions discovered at the time of
the tube beginning to be pulled down at the level of the anas-
operation. Conversion to an open procedure with formal
tomosis. The esophagogastric cervical anastomosis is placed
pericardiectomy is advisable under these circumstances.
high in the neck, just below the level of the cricopharyngeus,
to ensure adequate removal of any islands of Barrett and to
ensure that any anastomotic leaks will be more likely to drain VATS Procedures for Mediastinal Masses
out via the neck. Three tacking sutures are placed: one
A 1998 multicenter trial aimed at defining the role of VATS
between the left crus and stomach just anterior to the greater
curve arcade; the second on the right side of the gastric tube in the management of mediastinal tumors suggested that
just above the right gastric vessels to the right crus; and VATS can be used safely to diagnose and resect most middle
the third suture anteriorly between the stomach and the and posterior mediastinal masses, especially in view of the
diaphragm. typically benign nature of these tumors.34
VATS thymectomy has been used to treat myasthenia
troubleshooting gravis and thymoma. To date, only anecdotal experience has
The technical problems associated with VATS esophagec- been reported, and no studies examining long-term outcomes
tomy are similar to those associated with open thoracic have been published. Although a VATS approach to myas-
esophagectomy, including thoracic duct injury, recurrent thenia gravis may appear attractive at first, it is not the least
nerve palsy, bleeding from the intercostal vessels, and anas- invasive approach to the thymus. Transcervical thymectomy
tomotic leakage. These problems are best prevented by is a minimally invasive approach to the thymus that does not
obtaining good visualization of the superior and posterior require a chest incision, does not violate the pleural space,
mediastinum, which can be achieved by using a 30° angled and allows most patients to be discharged home the next day.
thoracoscope. The most common reason for conversion to There is still a degree of controversy as to whether complete
thoracotomy is the presence of a locally advanced tumor that thymic resection, including all ectopic thymic tissue, is neces-
necessitates extensive dissection for safe mobilization away sary to obtain clinical remission in patients with myasthenia
from adjacent mediastinal structures. gravis. For patients with a thymic mass, we prefer a trans-
To date, comparison of the results of VATS esophagec- sternal approach. It is imperative to maintain oncologic surgi-
tomy with those of open esophagectomy has not shown cal principles; accordingly, en bloc resection is emphasized so
VATS to yield a significant decrease in major complications, that pleural seeding is avoided and the risk of incomplete
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Figure 18 Neck incision.
resection is minimized. For patients with myasthenia gravis anteriorly so that the lung falls away from the paravertebral
who do not have a thymoma, however, there is a need for region. The port sites are placed anteriorly: the thoracoscope
prospective studies comparing VATS with other surgical is inserted at the fifth ICS in the midaxillary line, a lung
approaches to thymectomy. retractor is inserted at the sixth ICS in the anterior axillary
line, and dissecting instruments are inserted at the second
operative technique and fourth ICSs at the anterior axillary line. The mass is
VATS has been used to resect masses in all of the medias- manipulated with a grasper to expose the posteriorly located
tinal compartments. VATS resection is an ideal approach pedicle, which is then dissected, ligated, and divided with the
to posterior neurogenic tumors that do not extend into the scissors, clip appliers, and electrocautery device.
neural foramen or the spinal canal. With the patient in the For removal of anterior mediastinal masses, the port sites
lateral decubitus position, the operating table is rotated are placed in more posterior locations. The thoracoscope
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Figure 19 Cervical anastomosis. (a) The cervical esophagus is divided high (1 to 2 cm below the cricopharyngeal muscle). (b) A
side-to-side esophagogastric cervical anastomosis is performed using a gastrointestinal anastomosis (GIA) stapler. (c) Closure of
the anastomosis by a 45 mm transverse anastomosis stapler.
is introduced at the fifth ICS at the midaxillary or posterior Generally, however, the triangulated site placement used for
axillary line, and instruments are inserted through two ports, pulmonary wedge resections provides more suitable exposure
one at the second ICS at the midaxillary line and the other than the site placement used for anterior or posterior
at the fifth or sixth ICS at the anterior axillary line. The mass mediastinal masses.
is retracted with a grasper and dissected free with a com-
bination of sharp and blunt dissection, clip appliers, and the troubleshooting
electrocautery device. A similar technique is used to resect The placement of the thoracoports and the positioning of
middle mediastinal masses, most of which are pericardial or the operating team for the resection of posterior mediastinal
bronchogenic cysts. The access sites should be chosen accord- tumors or for thoracic discectomy differ significantly from
ing to the location of the mass on the preoperative CT scan. the usual practice in most other VATS procedures. In place
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of the standard arrangement of trocars in an inverted triangle, possibility, the chest should be included in the operative field
the viewing port is placed in the posterior axillary line and to allow chest tube insertion if required. Because thoracos-
the operating ports in the anterior axillary line. The thoracic copy does not require CO2 insufflation, it is safer in such
surgeon and the neurosurgeon both stand on the anterior side situations.
of the patient, each viewing a monitor on the opposite side.
In addition, a 30° scope is essential for visualizing the
VATS Sympathectomy and Splanchnicectomy
intervertebral disk space.
Removal of dumbbell neurogenic tumors can be accom- Thoracic sympathectomy is known to be the most effective
plished thoracoscopically if immediately preceded by poste- treatment for upper limb hyperhidrosis, and VATS is now an
rior surgical removal of the spinal component of the tumor accepted approach to this operation. The main indication for
via laminectomy and intervertebral foraminotomy. Preopera- splanchnicectomy is intractable abdominal pain from unre-
tive MRI is crucial for defining the extent of the tumor within sectable malignancies (e.g., pancreatic or gastric carcinoma)
the spinal canal. Resection of posterior mediastinal tumors is and chronic pancreatitis. The effects of celiac ganglion blocks
sometimes associated with significant bleeding from intercos- are transient, and surgical manipulation of this area is usually
tal or spinal arteries. If such bleeding occurs, there should be very difficult because of the primary disease process, previous
no hesitation in converting to a thoracotomy. Ideally, anterior operations, or both. In the past, thoracotomy was generally
mediastinal cysts should be resected in toto to prevent considered too invasive an approach to splanchnic denerva-
recurrence. However, if the cysts are firmly adherent to vital tion in these patients. Currently, however, because of the
mediastinal structures, partial excision with cauterization of less invasive nature of thoracoscopy and the quicker recovery
time associated with it, thoracoscopic splanchnicectomy is an
the endothelial lining may be safer.
attractive therapeutic option.
VATS Management of Thoracic Trauma operative technique
The major contraindication to thoracoscopy in thoracic Sympathectomy

trauma is hemodynamic instability. For major life-threatening VATS sympathectomy is performed with the patient under
injuries involving the great vessels and the mediastinum, tho- general anesthesia and a double-lumen tube in place. Several
racotomy is required to obtain expeditious control of injured techniques have been described. Initially, the common prac-
structures. However, hemodynamically stable patients with tice was to use three port sites: one for the thoracoscope at
certain thoracic problems (e.g., diaphragmatic injury; slow, the third ICS in the midaxillary line, one at the third ICS in
continued intrathoracic bleeding; persistent air leakage; and the anterior axillary line, and one at the tip of the scapula.
empyema) may be diagnosed and often treated by means of Currently, the procedure is most often performed with two
VATS.35,36 incisions: one at the fifth ICS at the border of the pectoralis
In the assessment of a trauma patient with a potential and one at the fourth ICS in the anterior axillary line. The
diaphragmatic injury, it is important not to ignore the high pleura is incised and divided from T2 to T5, and the sympa-
incidence of associated intra-abdominal injury. If intra- thetic chain is dissected free with scissors and excised. For
abdominal injury has been ruled out and there is concern complete control of upper limb hyperhidrosis, VATS must be
about the presence of a diaphragmatic tear, thoracoscopic done bilaterally.38,39
assessment of the diaphragm is justified. Such assessment A 1998 study reviewed the long-term results in 630 patients
allows a more thorough evaluation of the entire diaphragm who had undergone thoracoscopic sympathectomy for hyper-
than the laparoscopic approach, which is limited by the liver hidrosis (median follow-up 15 years).40 Of these patients,
on the right side. In the largest series published to date, 60 of 68% were fully satisfied and 26% were only partially satisfied
but nevertheless would agree again to the operation. Hyper-
171 patients who underwent thoracoscopy for penetrating
hidrosis was cured permanently in 93%. Compensatory
chest injuries had diaphragmatic injuries that necessitated
sweating and gustatory sweating occurred in 67% and 47%
repair.37
of cases, respectively. Overall, patients were well satisfied
When a patient has an ongoing intrathoracic problem (e.g.,
with the results and considered the compensatory sweating
persistent bleeding or a large air leak 24 to 48 hours after less of a problem than the original hyperhidrosis.
a traumatic injury), VATS should be considered before a
thoracotomy is done because most problems encountered at Splanchnicectomy
this time (e.g., chest wall bleeding and laceration of the lung The technical aspects of VATS splanchnicectomy are quite
parenchyma) can be managed endoscopically, without the simple: sound knowledge of the splanchnic anatomy and a
need for a thoracotomy. basic set of thoracoscopic instruments are all that is needed.
Single-lung ventilation is required. Three thoracoports are
troubleshooting
placed. A silk stitch is placed in the central tendon of the
The main pitfall in thoracoscopic evaluation of the dia- diaphragm and pulled through the most anterior and inferior
phragm is failure to assess the abdomen appropriately and port to allow better visualization of the splanchnic nerves.
consequent failure to recognize an occult intra-abdominal The camera is also placed through this port. An endoscopic
injury. When laparoscopy is performed in a patient with a grasper and an endoscopic scissors with an electrocautery
diaphragmatic injury, insufflation of CO2 may cause a tension attachment are used to remove the nerve segment from T5 to
pneumothorax to develop on the side of the diaphragmatic T9. The greater and lesser splanchnic nerves are resected.
injury. Accordingly, whenever diaphragmatic injury is a The least splanchnic nerve is rarely visualized.
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troubleshooting pulmonary wedge resections with that of the same operation

Care should be taken to identify the first and second ribs. done by thoracotomy.45 The VATS approach was associated
Division of the sympathetic trunk at the level of the first with substantially shorter hospital stays but also with increased
rib causes Horner syndrome and does not reduce palmar operating room costs; hence, the use of VATS did not result
hyperhidrosis. Division of the rami communicantes rather in any significant overall savings. Since that study, however,
than the main sympathetic trunk reduces the incidence of as some VATS procedures (e.g., pulmonary wedge resection)
undesirable side effects, especially compensatory hyperhidro- have become standard operations and more reusable
sis of the trunk, but its overall success rate in controlling instrumentation has become available, the cost of VATS
upper limb hyperhidrosis is lower. Abolition of only the T2 has undoubtedly decreased. Whether other, more complex
and T3 ganglia may control palmar hyperhidrosis without VATS procedures (e.g., thoracoscopic esophagectomy) are
being as likely to result in unacceptable compensatory truncal cost-effective remains to be determined.
sweating. Some have advocated limited T3 sympathectomy Within this context, the Society of Thoracic Surgeons
for primary hyperhidrosis to prevent compensatory sweat- (STS) and the American Association for Thoracic Surgery
ing.41 Target areas for axillary sweating also include T4 and (AATS) formed a joint committee to establish standards
T5. In addition, an accessory sympathetic nerve fiber that and guidelines for training and certification in VATS.46 As
runs lateral to the sympathetic chain (known as the nerve of a result of the educational efforts of this committee, many
Kuntz) should be sought and, if identified, divided. Compen- surgeons were trained within a short time, and VATS was
satory hyperhidrosis of the inner thighs is a common compli- quickly incorporated into thoracic surgical practice and resi-
cation. Neuralgia is frequent after VATS sympathectomy. dency training. The important considerations with respect
Some authors advocate a 2-day postoperative course of to the training and practice of VATS have been well
dexamethasone to reduce the incidence of this problem.42 articulated.46,47
VATS is not minor surgery: it is a minimally invasive, com-
plex intrathoracic procedure that should be performed only
Miscellaneous VATS Procedures by persons who are familiar with intrathoracic anatomy and
Several other procedures have been performed by VATS, pathology and are fully competent to manage complications
including ligation of the thoracic duct43 and resection of the and make intraoperative decisions in such a way as to ensure
adrenal gland.44 For adrenal resection, three incisions are safe outcomes for thoracic surgical patients. The complica-
placed at the ninth or 10th ICS, extending from the anterior tions encountered during thoracoscopic operations are
axillary line to the posterior axillary line. A fan retractor is potentially immediately life-threatening, whereas those
inserted through a radial incision in the diaphragm and used encountered during other endoscopic procedures usually are
to retract the perirenal fat. The adrenal gland is dissected not. For that reason, VATS procedures should not be per-
free and removed, and the associated vessels are clipped or formed by anyone—surgeon or nonsurgeon—who lacks the
cauterized. training and experience to perform immediate thoracotomy
and repair of intrathoracic injuries.
Cost Considerations
Conclusion
It is hard to estimate the cost-effectiveness of VATS pro-
cedures because the instrumentation, the types of procedures Since its reintroduction into clinical practice in the early
performed, and the surgical expertise with these operations 1990s, VATS has been investigated in a scholarly and aca-
are all still evolving. Initially, VATS procedures proved demically rigorous manner. It represents a paradigm for the
expensive for several reasons (e.g., the cost of purchasing evaluation of surgical innovation, leading to safe and effective
video and endoscopic equipment, the cost of disposable application in patients. This chapter describes the most
instrumentation, and the need for long operating times as common video-assisted thoracic procedures performed in the
surgeons and nursing staff gained experience with the pro- current practice of thoracic surgery.
cedures). Soon after VATS was introduced, a study from
the Mayo Clinic compared the cost of performing VATS Financial Disclosures: None Reported
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1550–9. 486–95. Assisted Thoracic Surgery. J Thorac Cardio-
20. Allen MS, Trastek VF, Daly RC, et al. Equip- 34. Demmy TL, Krasna MJ, Detterbeck FC, vasc Surg 1992;104:1.
ment for thoracoscopy. Ann Thorac Surg et al. Multicenter VATS experience with 47. Thoracoscopy forum, continuing dialogue.
1993;56:620–3. mediastinal tumors. Ann Thorac Surg 1998; Chest 1992;102:1915.
21. Yim APC, Ho JKS. Malfunctioning of 66:187.
vascular staple cutter during thoracoscopic 35. Lang-Lazdunski L, Mouroux J, Pons F, et al.
lobectomy. J Thorac Cardiovasc Surg 1995; Role of videothoracoscopy in chest trauma.
109:1252. Ann Thorac Surg 1997;63:327.
Acknowledgments
22. Nicastri DG, Yun J, Swanson SJ. VATS 36. Spann JC, Nwariaku FE, Wait M. Evaluation
lobectomy. In: Sugarbaker SJ, Bueno R, of video-assisted thoracoscopic surgery in Figures 8–19 Christine Kenney
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4 THORAX 11 MEDIASTINAL PROCEDURES — 1
11 MEDIASTINAL PROCEDURES
Joseph B. Shrager, MD, FACS, and Vivek Patel, MBBS
Procedures for Lesions of the Anterior Mediastinum remote adenopathy or an elevated serum lactate dehydrogenase
More than half of all mediastinal masses arise from the level is also suggestive.3 When peripheral nodes are palpable, the
anterior compartment. Most primary malignancies of the diagnosis may be most easily obtained by excising one of them.
mediastinum also develop in the anterior mediastinum. Patients with suspected lymphoma who have an isolated anterior
Because of the narrowness of the space that makes up the mediastinal mass should undergo core-needle biopsy or a
thoracic inlet, as well as the presence of the trachea and Chamberlain procedure (anterior mediastinotomy), depending
esophagus traversing this region, anterior mediastinal masses on the pathologists’ level of comfort with classifying lymphoma
become symptomatic earlier than their counterparts in other on the basis of small specimens at one’s institution. Resection
anatomic spaces of the mediastinum. Whereas adults with of lymphoma is not indicated; it may be avoided by performing
masses of the middle or posterior mediastinum usually report a diagnostic biopsy whenever lymphoma is suspected.
no significant symptoms, more than 50% of patients with Unlike lymphomas, thymic neoplasms are uncommon before
anterior mediastinal masses present with chest pain, fever, the fourth decade of life. Thymoma [see Figure 1a] may be asso-
cough, dyspnea, dysphagia, or vascular obstruction. Thymic ciated with any of several paraneoplastic syndromes. MG occurs
neoplasms and lymphoma, the two most common masses in conjunction with a pathologic condition of the thymus—either
in the anterior mediastinum, may have systemic manifesta- thymoma or thymic hyperplasia—in 80 to 90% of cases.
Thymoma may also be associated with pure red cell aplasia,
tions (e.g., weakness associated with myasthenia gravis
agammaglobulinemia, systemic lupus erythematosus, and vari-
[MG] or symptoms associated with International Working
ous autoimmune disorders. The presence of any of these associ-
Formulation [IWF] group B lymphoma).
ated syndromes essentially clinches the diagnosis of thymoma.
In what follows, we focus on surgical approaches to the
Autoantibodies to the acetylcholine receptor (anti-AChR anti-
diagnosis and treatment of the more common neoplasms
bodies) should be measured: their presence is diagnostic of MG,
of the anterior mediastinum, including thymic tumors,
and they are found in nearly 60% of patients who have thymoma
lymphomas, and germ cell tumors. Embryologic anomalies
without neurologic symptoms.4 Once the diagnosis of thymoma
and neoplasms arising from normal structures in this region
has been made, the goal is to proceed to direct resection without
broaden the differential diagnosis [see Table 1]. Finally, we
preliminary biopsy; these tumors have a predilection for local
address thymectomy for MG, a procedure that is frequently
recurrence once the capsule has been violated.
performed even in the absence of neoplastic disease.
The majority of germ cell tumors, whether malignant or
preoperative evaluation benign, are diagnosed in the second or third decade of life.
Benign teratomas are usually well encapsulated, with frequent
In a patient with an anterior mediastinal mass, it is frequently
recapitulation of one or more tissue elements seen on radiogra-
possible to make a strong provisional diagnosis of the tumor type
phy.5 The appearance of the lesions on CT is often diagnostic
on the basis of clinical evaluation and diagnostic imaging.1
[see Figure 1b]. Surgical extirpation is the mainstay of treatment
As noted (see above), the presence of systemic manifestations
for these mature germ cell tumors, and biopsy is not indicated.
may be helpful. Physical examination must include examination
Malignant germ cell tumors, on the other hand, are treated with
of peripheral lymph node groups and testes. Computed tomog-
primary chemotherapy, radiotherapy, or both; when suspected,
raphy (CT) yields valuable information about the anatomic
these patients should undergo biopsy rather than being taken
location of the tumor, its characteristics (i.e., fatty, solid, or
directly to resection. Characteristic serum tumor markers,
cystic), and its degree of invasiveness (if any) [see Figure 1].
including b–human chorionic gonadotropin (b-hCG) and a-
Occasionally, magnetic resonance imaging (MRI) provides
fetoprotein (AFP), are elaborated by most malignant germ
useful additional information about the obliteration of normal
cell neoplasms but are not found in benign germ cell tumors.6
tissue planes. Positron emission tomography (PET) generally
Elevation of the AFP level beyond 500 ng/mL is considered
demonstrates strong fluorodeoxyglucose (FDG) uptake in lym-
diagnostic of a nonseminomatous component in a malignant
phoma; thus, PET and CT may be useful in guiding sites for
germ cell tumor and is usually associated with a concomitant
biopsy in that disease. Several small trials have been conducted
increase in serum b-hCG levels.7 In the absence of any marked
evaluating the utility of PET in the evaluation of thymoma.2
elevation in the AFP or b-hCG level, percutaneous needle
Uptake of FDG appears to be greater in thymoma than in
biopsy usually suffices to establish the diagnosis.
thymic hyperplasia, and thymic carcinomas appear to have the
highest FDG uptake. The reproducibility and thus diagnostic operative planning
utility of this finding, though, have yet to be clearly elucidated.
Lymphoma is the most likely diagnosis in persons younger Biopsy versus Resection
than 40 years, and the presence of IWF group B symptoms Clearly, the decision whether to perform a biopsy of an
further raises the level of suspicion. The presence of palpable anterior mediastinal mass is not a simple one. Routine biopsy
DOI 10.2310/7800.S04C11
02/10
Table 1 Differential Diagnosis of Anterior

Mediastinal Mass
Neoplastic conditions
Thyroid
Substernal goiter
Ectopic thyroid tissue
Thymus
Thymic hyperplasia
Thymoma
Thymic carcinoma
Thymic carcinoid
Thymic small cell carcinoma
Thymic cyst
Thymolipoma
Teratoma
Mature teratoma
Immature teratoma
Teratoma with malignant component
Lymphoma
Ectopic parathyroid with adenoma
Germ cell tumors
Seminoma
Nonseminoma
Yolk sac tumor
Embryonal carcinoma
Choriocarcinoma
Hemangioma
Lipoma
Liposarcoma
Fibroma
Fibrosarcoma
Cervicomediastinal hygroma
Infectious conditions
Acute descending necrotizing mediastinitis
Subacute mediastinitis
Figure 1 (a) Computed tomography (CT) scan shows a
Vascular conditions well-encapsulated anterior mediastinal mass—a thymoma.
Aneurysm of aortic arch with projection in anterior mediastinum (b) CT scan shows a benign teratoma of the anterior
Innominate vein aneurysm
mediastinum; calcification and varying tissue densities may
Superior vena cava aneurysm
Dilation of superior vena cava (with anomalous pulmonary be seen.
venous return)
Persistent left superior vena cava
lymphoma, biopsy is also preferable to immediate attempt
at resection. Such lesions may represent aggressive thymomas
that may benefit from neoadjuvant treatment, malignant
should be avoided, not only because of the cost and the
germ cell tumors, or other rare disease processes. Once
unnecessary morbidity but also because of the risk that biopsy
the decision has been made to proceed with biopsy rather
may spread thymoma. The choice to proceed with biopsy
than resection, selection of a biopsy approach is based on
should be made according to which tumor type is believed to
anatomic considerations and patient factors.
be most likely on the basis of the diagnostic workup.
Well-encapsulated lesions that are believed not to represent biopsy of anterior mediastinal mass
lymphoma are resected, without a preceding biopsy, for both
diagnosis and treatment. Neoplasms that commonly fall into Chamberlain Approach
this category include noninvasive thymomas, mature terato- Anterior parasternal mediastinotomy (the Chamberlain
mas, mesenchymal tumors, and, occasionally, benign cysts. procedure) is favored by most surgeons for biopsy of lesions
Most patients with MG should be offered thymectomy in the anterior mediastinum and the aortopulmonary window.
whether they have a thymic mass or not. It is usually done under general anesthesia, although local
When lymphoma is suspected, biopsy is required. The anesthesia may be used instead, and it does not require single-
technique employed should be minimally invasive while still lung ventilation. This operation affords good exposure and
permitting the acquisition of a sufficient tissue sample. CT- allows generous biopsy specimens to be taken, and it can be
guided core-needle biopsy may be attempted, but, frequently, performed as an outpatient procedure.
this technique does not provide enough tissue for the analyses
required to classify the tumor.8,9 Thus, the Chamberlain Operative technique Step 1: initial incision A 5 cm
procedure (anterior mediastinotomy) is recommended in transverse incision is made over the second costal cartilage on
these situations. the side to be operated on (the second cartilage is identified
For locally invasive or frankly unresectable anterior by its continuity with the sternal angle). The pectoralis major
mediastinal masses other than those felt likely to represent is separated in a direction parallel to the direction of its fibers,
02/10
R2
Figure 2 Biopsy of anterior mediastinal mass: Chamberlain approach. Depicted are incision and subperichondrial resection of
the second costal cartilage.
and the cartilage is resected in a subperichondrial plane be controlled with electrocauterization. We often leave an
[see Figure 2]. Leaving perichondrium behind facilitates absorbable hemostatic agent in place as well.
postoperative regrowth of the cartilage.
Step 2: dissection and exposure The posterior perichon- Transcervical Approach
drium is incised, and the parietal pleura is bluntly dissected As an alternative to the Chamberlain procedure, a mass of
laterally with a peanut sponge; this affords entry into the the anterior mediastinum may be approached for biopsy
mediastinal fat and direct access to the tumor mass. Almost through a cervical incision, exactly as in a transcervical thy-
invariably, the internal mammary vessels can be mobilized mectomy [see Resection of Anterior Mediastinal Mass, Tran-
medially and preserved, but, if necessary, they may be ligated scervical Approach, below]. The use of a Cooper thymectomy
to improve exposure. retractor (Pilling Company, Fort Washington, Pennsylvania),
Step 3: biopsy A generous wedge-shaped portion of the which elevates the sternum, affords excellent exposure of the
mass is excised with a scalpel. Frozen-section examination is anterior mediastinum and sometimes allows direct examina-
then performed to confirm that diagnostic tissue has been tion to ascertain the invasiveness of an otherwise uncertain
obtained. It is important to remember to request that flow mass. In most cases, general anesthesia is required, but
cytometry be performed on the specimen. transcervical biopsy can be performed as an outpatient pro-
Step 4: closure The posterior perichondrium is reapproxi- cedure. We have used this technique occasionally and have
mated, followed by the pectoralis major, the subcutaneous achieved results comparable to those of anterior mediasti-
fat, and the skin. notomy.10 Proper performance of this procedure does,
however, require a level of experience with the technique that
Troubleshooting If the pleura was entered, a red rubber is not widely available.
catheter is used to evacuate the pleural space as the lung is
inflated with a large positive pressure breath, and the catheter Video-Assisted Thoracic Surgery
is withdrawn through the layers of closure. A small post- Video-assisted thoracic surgery (VATS) has been applied
operative pneumothorax is almost always attributable to to diagnostic biopsy of anterior mediastinal masses, but VATS
residual air rather than to an ongoing air leak. biopsy procedures are not widely employed for this purpose.
Sometimes the tumors are fairly vascular and bleed moder- The necessity of single-lung ventilation adds a level of
ately after biopsy is performed. This bleeding can always complexity to the procedure beyond what is required for the
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Chamberlain procedure or the transcervical approach. Further- is not uncommon, and resection of the great vessels has been
more, intercostal incisions are frequently more painful than performed with both technical success and good long-term
transcervical incisions or the incision for an anterior mediasti- survival. All great vessels resected must be reconstructed,
notomy. VATS does have certain advantages that may be of with the exception of the innominate vein, which may be
value in individual cases, such as the capacity to provide simul- ligated with little deleterious effect. Every effort should be
taneous access to other compartments of the mediastinum and made to preserve the phrenic nerves: damage to even one of
the ability to evaluate the pleural space for evidence of tumor these nerves can be disastrous in an already weakened myas-
dissemination. Robot-assisted thoracoscopic procedures for thenia patient. In a patient with a malignancy, however, one
anterior mediastinal masses have also been described,11 but their phrenic nerve may be sacrificed if tumor invasion necessitates
availability does not eliminate the major objection to transpleu- this step, provided that the patient’s preoperative respiratory
ral approaches to mediastinal masses—namely, the possibility status is acceptable and curative resection is likely.
of spreading a disease that had been contained within the In cases of thymectomy for advanced MG, every effort
mediastinum into the pleural space. must be made to optimize the patient’s condition preopera-
tively. To this end, a multidisciplinary approach that includes
resection of anterior mediastinal mass a neurologist and, possibly, a pulmonologist is necessary. If
Operative Planning the disease does not stabilize with medication (e.g., pyr-
idostigmine, low-dose steroids, or intravenous c-globulin),
The most frequent indications for resection (as opposed to preoperative plasmapheresis may be required. Patients with
biopsy) of an anterior mediastinal mass are (1) thymoma and moderate or greater generalized weakness despite optimiza-
(2) thymectomy for MG. The principles underlying thymoma tion of medication should certainly undergo plasmapheresis.
resection can be applied to resection of other, rarer anterior The question of which MG patients should be offered thy-
mediastinal masses such as thymic carcinoma, thymolipoma, mectomy is, at best, difficult to answer. Most studies have
and germ cell tumors. The first successful resection of a found the impact of thymectomy to be greater if it is per-
thymic mass for MG was described in 1939.12 Since the intro- formed in patients with less severe and shorter-duration
duction of transcervical thymectomy (TCT), there has been disease. Accordingly, our practice is to offer TCT sooner in
ongoing debate regarding the optimal method for thymec- the course of the disease rather than later; however, we will
tomy in patients with nonthymomatous MG. There is little perform the procedure at any stage, from ocular-only disease
debate, however, regarding the optimal approach to resection to severe, generalized weakness. Because TCT is associated
of anterior mediastinal malignancies. with minimal morbidity, requires only a small incision, and
For all primary invasive masses of the anterior mediasti- can generally be done as an outpatient procedure, it is a very
num—including invasive thymomas, malignant germ cell attractive option for patients with milder disease. At the same
tumors (after systemic treatment), thymic carcinomas, and time, it is also more easily tolerated by patients with severe
other, less common malignancies—the most important prog- disease than is a median sternotomy.
nostic factor is complete resection. Accordingly, the operative An approach to thymectomy for MG that is favored by a
approach must be selected with an eye to providing optimal few surgeons is so-called maximal transsternal-transcervical
exposure. There is little doubt that a full median sternotomy thymic resection, which combines a median sternotomy with
is ideal in this regard. However, a less than full sternotomy is an additional neck incision to provide wide access to all areas
a reasonable choice for small (< 3 cm) noninvasive thymomas where thymic tissue has been identified. The rationale for
or other noninvasive mediastinal tumors (e.g., mature terato- such extensive exposure is the observation that thymic tissue
mas), particularly when the diagnosis of thymoma is in doubt may reside in several extrathymic locations. Proponents of
before operation. In such situations, we usually begin with the maximal approach argue that if thymectomy for MG is to
TCT,13,14 but we do not hesitate to convert to a sternotomy provide optimal benefit, it should include removal of all of
if unexpected invasion is identified. Some surgeons have this extraglandular thymic tissue. This approach has never
employed a partial upper sternotomy in these settings; how- been compared to TCT in a randomized trial, but, in our
ever, this approach limits exposure, and we do not believe view, most of the available data suggest that remission rates
that it actually reduces morbidity in comparison with a full after maximal transsternal-transcervical thymic resection are
sternotomy. Video thoracoscopic (VATS) and even robotic not remarkably different from those after TCT, which is
thymectomy have now been described by a number of groups much less invasive. Because we do not personally perform the
employing several technical variations and with apparently maximally invasive procedure, we do not describe it in this
good results. These approaches have, like TCT, been applied chapter.
generally to patients with MG without thymoma or those
with small, noninvasive thymomas. Studies with longer Median Sternotomy Approach
follow-up reporting myasthenia remission rates and thymoma As noted (see above), the standard approach to masses
cure rates will be required before these VATS and robotic of the anterior mediastinum is via a median sternotomy.
approaches can be considered to have a proven role in the Resection of a thymoma of the anterior mediastinum is
management of these diseases. performed as follows.
En bloc resection of malignancies is mandatory, and resec-
tion of adjacent serosal membranes (including pleura or peri- Operative technique Step 1: initial incision and exposure
cardium) is required if there is any suggestion of attachment The patient is placed in the supine position and intubated
during the operation. Resection of adjacent lung parenchyma with a double-lumen endotracheal tube. The skin incision
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typically extends from 2 cm below the jugular notch to the The small arteries supplying the thymus, which are most
xiphisternal junction; however, depending on the extent of often not even clearly seen arising laterally via branches from
the expected pathologic condition, the incision may be short- the internal mammary vessels, are coagulated or ligated and
ened further and the full sternum divided by reaching beneath divided as they are encountered. Care must be taken to stay
skin flaps. Finger dissection is performed beneath the ster- away from the phrenic nerves while controlling the arterial
num to rule out tumor invasion into the posterior sternal blood supply.
table. If the posterior sternal table is clear, the sternum is Step 5: mobilization of superior poles of thymus Dissection is
divided, hemostasis is achieved, and the edges are separated then continued in the neck, where the two cervical extensions
with a sternal retractor. are isolated by means of gentle traction and blunt dissection
Step 2: determination of resectability The anterior mediasti- and followed until they trail off into the thyrothymic liga-
num is inspected, the mass is visually identified, and an initial ment. This ligament is clamped, divided, and ligated superi-
assessment of resectability is undertaken. orly at a point where only a small blood vessel is present and
Step 3: mobilization of inferior poles of thymus Dissection of no visible glandular tissue remains.
the thymus begins at the caudad aspect, with the inferior Step 6: dissection of thymus from innominate vein The cervi-
poles and surrounding mediastinal fat mobilized first from cal poles are followed down over the innominate vein. Sharp
the underlying pericardium and diaphragm by electrocautery
dissection is continued onto the surface of the vein, and the
dissection. It is difficult to determine by visual means pre-
two to five veins draining the gland into the innominate vein
cisely where thymic tissue merges into simple mediastinal fat;
are ligated and divided [see Figure 4].
accordingly, to ensure complete resection of the thymus, all
Step 7: removal of specimen Once the body of the thymus
fatty tissue between the phrenic nerves and down to the level
has been freed from the innominate vein, the H-shaped gland
of the diaphragm is removed with the specimen. The medi-
and the associated mass are removed [see Figure 5]. If the
astinal pleura, to which this fatty and thymic tissue tends to
be adherent, is also taken with the specimen [see Figure 3].
This is done by first opening the mediastinal pleura along the
entire length of the chest, approximately 1 cm posterior to the
sternum.
Step 4: continuation of dissection cephalad From within the
pleural space, the phrenic nerves are identified and followed
along their entire path up to the point where they course
beneath the innominate vein. Sharp dissection is carried close
to the nerves, dividing the mediastinal pleura again along this
more posterior line, to secure an adequate tumor margin and
ensure removal of all thymic tissue that is progressively mobi-
lized medially. It is advisable to clip small vessels near the
nerves before dividing them so as to prevent irritating bleed-
ing, which can be difficult to control without compromising
the nerve.
Figure 4 Resection of anterior mediastinal mass: median

Figure 3 Resection of anterior mediastinal mass: median sternotomy approach. View from feet shows the thymus and
sternotomy approach. Intraoperative photograph shows tumor mobilized off the innominate vein. The entire right
dissection of the right inferior thymic pole and associated thymus (both the upper and the lower pole) has been fully
mediastinal fat. mobilized.
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Figure 5 Resection of anterior mediastinal mass: median

sternotomy approach. Shown is the resected thymoma
specimen. Figure 6 Resection of anterior mediastinal mass: median
sternotomy approach. Hemiclamshell incision provides
exposure to masses located at the thoracic apex.
clean plane between the mass and the underlying pericar-

dium—a plane normally composed of fine, filmy adhesions—
is at all compromised, one should not hesitate to resect a TCT should be employed very cautiously in cases in which
portion of the pericardium en bloc with the specimen, with a neoplasm is suspected or proved on the basis of preopera-
care taken to maintain a gross margin of at least 2 cm at all tive studies or is identified during the course of intraoperative
times. exploration. Because thymoma is often an indolent tumor,
Step 8: closure Two pleural drains that traverse the medi- with recurrence developing many years after resection, long-
astinum and reach the apex of each hemithorax are placed, term follow-up studies are required before TCT can be firmly
and the sternum and the soft tissues are reapproximated in recommended for treatment of even small thymomas. On
layers. the other hand, it is likely that surgeons who have extensive
experience with TCT can safely resect small (< 3 cm) thymo-
Troubleshooting If invasion of great vessels is consid- mas via this approach without risking tumor spillage or
ered a possibility before the start of the operation, the groin incomplete resection.
should be prepared and draped into the field to provide access
for cardiopulmonary bypass if needed. Giant anterior medi- Operative technique Step 1: initial incision and exposure
astinal masses may necessitate extension of a partial median The patient is placed on the operating table in the supine
sternotomy incision into an ipsilateral intercostal space (usu-
position, with the head supported by a foam doughnut and
ally the fourth space). Such extension may be achieved by
an inflatable bag placed horizontally beneath the scapulae.
making an ipsilateral incision in the neck along the anterior
The bag is inflated until the cervical spine is maximally
border of the sternocleidomastoid muscle and making a
extended. It is important that the top of the patient’s head
submammary skin incision continuous with the incision over
be all the way up to the edge of the table so that the surgeon
the sternum (a hemiclamshell incision) [see Figure 6].
can easily reach all areas of the mediastinum from a seated
Transcervical Approach position at the head.
Although the transcervical approach to thymic resection A 5 to 6 cm curvilinear incision is made about 2 cm supe-
was the first one used in the early 1900s, it fell into disuse rior to the jugular notch and extending about 1 cm above
during the middle of the 20th century, when the median each clavicular head [see Figure 7]. Electrocautery dissection
sternotomy approach became feasible. During the past 20 is continued through the platysma, and subplatysmal flaps
years, however, there has been a resurgence of interest in are elevated. The strap muscles are separated in the midline,
TCT. Today, TCT is used primarily for thymectomy in the and the interclavicular ligament is divided. Separating a small
setting of MG, although, as noted (see above), a transcervical portion of the attachment of each sternocleidomastoid muscle
approach can be useful for biopsy or resection of other ante- from the corresponding clavicular head allows the sternum to
rior mediastinal processes as well. Proponents of TCT have be elevated somewhat higher, thereby improving exposure.
published data establishing that complete remission rates Step 2: mobilization of superior poles of thymus The superior
from MG after so-called extended TCT using the sternum- poles of the thymus are located (usually on the left side first)
lifting Cooper retractor15 are very similar to remission rates by means of gentle blunt dissection beneath the strap mus-
after the more invasive approaches.14,16,17 Because TCT is cles. After one pole is identified, it is divided between ties at
an outpatient procedure, hospital stay and operative recovery its superior extent. Its medial edge is then followed down to
are certainly dramatically shorter than after thymectomy by where it meets the medial edge of the opposite superior pole,
sternotomy. and this opposite pole can then be similarly traced upward
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Figure 7 Resection of anterior mediastinal mass:

transcervical approach. Shown is the location of the skin
incision for transcervical thymectomy in relation to the
sternal notch and the heads of the clavicles.
into the neck, ligated, and divided. A very important part

Figure 8 Resection of anterior mediastinal mass:
of the procedure is the placement of 0 silk ligatures around transcervical approach. A Cooper thymectomy retractor is
an area containing strong tissue within each superior pole. placed beneath the sternum, and retraction on the upper
These ligatures are left long and clamped. The surgeon or an poles of the thymus is maintained with silk sutures.
assistant places traction on them during the remaining course
of the dissection to manipulate and progressively mobilize the
gland [see Figure 8].
Step 3: continuation of dissection downward into superior Step 6: dissection of posterior aspect of thymus Once the
mediastinum As traction is being placed on the upper poles, thymus is freed from the innominate vein, dissection of
sharp and blunt dissection, staying outside the well-defined the posterior aspect of the gland must be continued directly
capsule of the gland, is extended downward into the superior on the surface of the pericardium. This posterior dissection is
carried as far down as possible, primarily in a blunt fashion.
mediastinum to the level of the innominate vein. The
Most of the time, the surgeon holds one ring clamp contain-
procedure becomes much more difficult if the capsule is
ing a sponge dissector in each hand while an assistant holds
violated.
the upper poles. Occasionally, the surgeon holds the sutures
Step 4: elevation of sternum Finger dissection is performed
attached to the upper poles in one hand while employing the
in the substernal plane, and the arm of a Cooper thymectomy
sponge dissector in the other hand.
retractor is placed into the retromanubrial space to elevate
Step 7: removal of specimen When the posterior dissection
the sternum. The retracting arm is placed under upward ten-
has been extended as far as possible toward the diaphragm,
sion as the inflatable bag beneath the shoulders is deflated.
further mobilization of the thymus is typically accomplished
This step leaves most patients actually hanging from the
by working the glandular tissue laterally, first off the pleura
retractor, thereby opening up a sizable space that allows good
on one side, then off the sternum anteriorly, and finally off
visualization and ready passage of dissecting instruments into
the pleura on the opposite side. In this way, the entire gland
the anterior mediastinum. Army-Navy retractors are placed is ultimately removed between the phrenic nerves and down
in each of the two upper corners of the incision, and their to the diaphragm. During this final mobilization, the surgeon
distal ends are tied to the siderails of the table with Penrose periodically asks to have ventilation held temporarily so that
drains to provide countertraction and to hold the skin the pleura can fall back and thus permit improved visualiza-
incision open. tion. Small feeding vessels from the mammary are doubly
Step 5: dissection of venous tributaries to innominate vein With clipped and divided as they are encountered.
the superior poles gently pulled upward by an assistant (and Often the final stages of blunt dissection may be facilitated
at times looped over the Cooper retractor), the inferior by placing a ring clamp on the body of the gland to allow
surface of the gland is dissected until the innominate vein is slightly more vigorous retraction than can be achieved by
encountered. The venous tributaries draining the thymus into using the upper poles alone. If any suspicious residual tissue
the innominate vein are isolated sharply, ligated with fine silk is seen in the mediastinum at this point, it can be removed
sutures, and divided. piecemeal; however, this is an unusual occurrence.
02/10
Step 8: closure After inspection of the surgical field for increased awareness of minimally invasive strategies. Pro-
hemostasis, the strap muscles and the platysma are closed ponents of VATS thymectomy cite decreased postoperative
over a red rubber catheter, to which suction may be applied. pain, decreased length of stay, improved cosmesis, and less
The catheter is subsequently removed, and the skin is morbidity than sternotomy as reasons in support of VATS
closed. thymectomy. Most case series report complete stable remis-
sion rates from MG18,19 comparable to transsternal and trans-
Troubleshooting In the course of preoperative evalua- cervical approaches. The data in this area, however, are not
tion before TCT, it is important to be sure that the patient nearly as mature as those in support of TCT or sternotomy
is able to extend the neck to a reasonable degree. TCT is for thymectomy.
simplest in young persons who are capable of good extension; The drawbacks of VATS thymectomy depend on the
it can be difficult or impossible in persons with cervical spine particular technical approach that is chosen, which include
disease that hinders extension. unilateral, bilateral, and substernal approaches. As with any
During the procedure itself, it is important that the branches minimally invasive technique, detractors have pointed out
of the innominate vein be tied rather than clipped; the space that there may be an inability to provide complete clearance
anterior to the vein becomes the avenue through which dis- of all thymic tissue. It has been suggested that a unilateral
secting instruments are passed into and out of the mediasti- VATS approach may provide inadequate access to the por-
num, and these instruments often rub against the vein fairly tion of the gland approaching the contralateral phrenic nerve.
vigorously. Aside from the question of the completeness of thymectomy,
When working laterally, one must take care not to injure any transthoracic, minimally invasive approach may create a
the phrenic nerves, and one certainly should not use the small risk of transpleural seeding in patients with thymoma.
electrocautery while working at the lateral extremes of the Given that “drop metastasis” to the pleural surfaces is the
dissection. If the pleural space is entered while one is working typical mode of spread of thymoma, there is substantial
laterally, a red rubber catheter [see Operative Technique, concern that a transpleural, thoracoscopic approach may
Step 8, above] is advanced well into that pleural space, and facilitate this mode of spread.
suction in the form of several large positive-pressure breaths
is applied before the catheter is removed.
Procedures for Lesions of the Middle Mediastinum
If a thymoma is encountered during TCT, continuation via
this approach may be considered. In our view, most noninva- The majority of masses found in the middle mediastinum in
sive thymic lesions less than 3 cm in diameter can be safely adults are malignant, representing either lymphoma or lymph
and completely resected via the transcervical approach. node metastases from primary lung carcinoma. Accordingly, the
In addition, it generally is not difficult to resect a portion of procedures performed in this anatomic area primarily involve
the anterior pericardium as well if a tumor or the thymus is biopsy for staging or diagnosis rather than curative or palliative
adherent to it. However, because the evidence currently avail- resection. On infrequent occasions, however, benign or primary
able does not conclusively establish that TCT is equivalent to malignant lesions of the middle mediastinum occur for which
resection via sternotomy for thymoma, some surgeons prefer resection is appropriate. In what follows, we briefly discuss
to convert to a sternotomy if a suspicious mass is discovered resection of such lesions; for the most part, the principles are the
during transcervical exploration. Certainly, if any difficulty is same as those underlying resection of masses in the posterior
encountered that might lead to an incomplete thymectomy mediastinum [see Procedures for Lesions of the Posterior
or incomplete removal of a thymoma, the incision should be Mediastinum, below].
extended. Of particular surgical interest in the middle mediastinum are
Approximately 90% of patients are able to go home on benign cysts, which may arise from the pleura, the pericardium,
the same day as their procedure. The most common cause the airways, or the esophagus. Bronchogenic cysts, which typi-
for hospital admission is a pneumothorax that must be cally develop in proximity to the carina, are probably the middle
monitored or drained. Occasionally, a seroma develops at the mediastinal cysts most commonly encountered in clinical
site of the incision, but it almost always resolves either spon- practice, with pericardial cysts running a close second. On rare
taneously or after a single percutaneous drainage procedure occasions, ectopic remnants from cervical structures (e.g.,
in the office. the parathyroid and thyroid glands) are encountered in this
compartment.20
VATS/Robotic Thymectomy preoperative evaluation

Although we do not have personal experience with VATS CT generally provides an accurate preoperative diagnosis
or robotic thymectomy and will therefore not include a of a benign middle mediastinal cyst, as well as information
discussion on its technique, an increasing number of pub- regarding abutment of adjacent structures, the consistency of
lished reports suggest that these are safe and effective alter- the mass, and potential invasiveness. MRI may be helpful if
natives to transsternal and transcervical approaches. Since there is concern that a cyst might actually represent an aber-
the first sporadic case reports of VATS thymectomy in the rant vascular structure or an aneurysm, if the simple nature
early 1990s, the popularity of this procedure has increased, of the cyst is in doubt, or if clearer delineation of suspected
likely because of the increased availability of VATS instru- invasion of surrounding structures is required. Radionuclide
mentation, surgeon familiarity with VATS techniques, and scans (e.g., with technetium-99m or radioactive iodine) may
02/10
be useful if the differential diagnosis includes a parathyroid portion of cyst wall is excised. Typically, approximately
or thyroid mass. Cystic structures adjacent to the airways and 50% of the cyst wall can be removed in this fashion. Some of
the esophagus are evaluated by means of bronchoscopy, the remaining cyst wall may be cauterized; this too must be
esophagoscopy, barium esophagography, or some combina- done with caution, given the proximity of the adjacent vital
tion of these imaging modalities to rule out communication structures.
with the lumina.
operative planning Procedures for Lesions of the Posterior Mediastinum

Middle mediastinal cysts that are symptomatic should The majority of posterior mediastinal masses occurring
be treated surgically. However, simple cysts of the middle in adults are benign. These lesions may be usefully classified
mediastinum that are asymptomatic and meet all radiographic according to their radiologic appearance—that is, as either
criteria for benignity may be followed. This conservative cystic or solid. Cystic masses in this region typically are bron-
approach is often more appropriate for asymptomatic middle chogenic cysts or esophageal duplication cysts, whereas solid
mediastinal cysts than for asymptomatic posterior mediastinal masses most frequently are benign neurogenic tumors (e.g.,
cysts in that complete cyst resection (at least for broncho- schwannomas, neurofibromas, or ganglioneuromas). Esopha-
genic cysts) tends to be more complex in the middle medias- geal leiomyomas (benign intramuscular tumors within the
tinum than in the posterior mediastinum, given the closer esophageal wall) are often grouped with these posterior medi-
proximity to vital structures and the deeper placement astinal lesions and are managed in a similar fashion. In many
within soft tissue. Complete resection of pericardial cysts, on cases, posterior mediastinal masses come to light as asymp-
the other hand, typically is easily accomplished by means of tomatic radiographic abnormalities; however, they may also
VATS; therefore, such cysts are probably best resected when be associated with signs of infection (in the case of infected
discovered, even if they are asymptomatic. VATS resection cysts), dysphagia, chest pain, or respiratory complaints.
of subcarinal bronchogenic cysts is feasible and has been At present, because of the growing availability of less morbid,
described in published reports.21 It is our experience, how- minimally invasive approaches to posterior mediastinal
ever, that larger and more chronic cysts in this location may masses, most authors recommend resection even when the
be difficult to remove completely by a VATS approach. lesion is asymptomatic. Although this recommendation
Thus, for a symptomatic, large, or chronic subcarinal remains somewhat controversial, we agree with it.
bronchogenic cyst (a not uncommon occurrence), one is left
operative planning
to choose between (1) thoracotomy for complete resection
and (2) some other approach for incomplete resection. VATS versus Thoracotomy
Because this area is easily accessible by means of mediastinos-
Resection of posterior mediastinal masses may be accom-
copy, and because we believe that mediastinoscopy is simpler
plished by means of either VATS or thoracotomy. The
and causes less morbidity than VATS, we prefer partial
procedure is essentially the same with either approach, and
resection via mediastinoscopy as the initial approach to these
the goal is complete resection. With some exceptions, VATS
lesions.22 If cysts treated in this manner recur with associated
is considered preferable to thoracotomy in this setting; gener-
symptoms, one can always perform thoracotomy for complete
ally, VATS results in less postoperative pain and quicker
resection at that time, and little will have been lost in the
functional recovery.23,24 Some surgeons argue that a VATS
meantime.
approach may be more likely to leave a patient with micro-
mediastinoscopic partial resection of subcarinal scopic residual disease. In our experience and that of others,
bronchogenic cyst however, recurrences of these lesions are very rare after VATS
excision.25,26 Given the low recurrence rate and the fact that
Operative Technique these masses are almost always benign, we believe that the
Step 1: mediastinoscopy and pretracheal dissection risk-benefit ratio favors VATS in most cases.
A standard cervical mediastinoscopy is performed, with dis- There are, however, several circumstances in which thora-
section in the pretracheal plane down to the level of the cotomy is indicated from the outset [see Table 2]. A sugges-
carina. tion of malignancy (in particular, invasion of surrounding
structures) on preoperative radiography mandates explora-
Step 2: freeing of cyst from surrounding tissues With tion and resection by thoracotomy; in this situation, the
the cyst wall kept intact, as much of the wall as can safely be potential consequences of positive margins justify the more
exposed is visualized by bluntly dissecting it away from the aggressive approach. The presence of active infection within
undersurface of the carina and the mainstem bronchi. Next, a cyst is a relative indication for thoracotomy in that it can
the mass is dissected away from the soft tissues anterior and cause disruption of normal tissue planes and thereby render
posterior to it; obviously, this must be done with caution, VATS dissection more hazardous. Masses larger than approx-
given that the right main pulmonary artery and the esophagus imately 6 cm also call for an open approach: such lesions are
are located nearby (anteriorly and posteriorly, respectively). typically more difficult to mobilize safely from underlying
structures than smaller lesions are, they are more likely to
Step 3: aspiration of cyst contents and excision of be malignant, and their removal between the ribs is likely
exposed cyst wall The contents of the cyst are aspirated to necessitate rib spreading, which may negate some of the
for cytologic and microbiologic examination, and the exposed benefit of true VATS.
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Table 2 Indications for Planned Thoracotomy Approach vats resection of neurogenic tumor of posterior
to Middle or Posterior Mediastinal Mass mediastinum
Suggestion of malignancy on preoperative radiography Operative Technique
Presence of inflammation or infection, blurring tissue planes
Large mass (> 5–6 cm) Resection of a solid neurogenic tumor of the posterior
Esophageal duplication cyst believed to communicate with mediastinum that does not invade the neural foramen [see
esophageal lumen on the basis of preoperative computed Figure 9] proceeds as follows.
tomography, barium esophagography, or esophagoscopy
Esophageal lesions without evidence of overlying normal
esophageal mucosa on preoperative esophagoscopy or Step 1: intubation and endoscopy The patient is
endoscopic ultrasonography intubated with a double-lumen endotracheal tube to allow
Previous ipsilateral thoracotomy with adhesions single-lung ventilation. Preoperative bronchoscopy (for
Tumor located at apex of the chest, which may necessitate
thoracosternotomy cystic lesions) or esophagoscopy (for lesions abutting the
esophagus) is performed as indicated (see above).
Step 2: patient positioning and placement of ports

When a cyst is arising from or abutting the esophagus, The patient is placed in the lateral thoracotomy position and
the possibility of a communication between the cyst and the stabilized with bean bags so that the operating table can safely
esophageal lumen should be investigated preoperatively. be tilted as much as 45° to either side. With this degree of
Such a communication may be suggested on CT scans by the tilt, the lung tends to fall away from the field of vision; thus,
presence of an air-fluid level. To rule out this phenomenon, there usually is no need to place an additional port for a lung
we perform barium esophagography during the preoperative retractor.
workup, followed by intraoperative esophagoscopy at the The port for the scope is placed through an incision in the
commencement of the operation. If a communication is midaxillary line at the level of the mass; if it is placed much
identified or cannot be ruled out, thoracotomy is performed. more anteriorly than the midaxillary line, the surgeon’s view
After excision of an esophageal duplication cyst with a com- of posterior lesions may be obscured by the lung. The two
munication, reapproximation of the esophageal mucosa is a working ports are placed through separate incisions in the
paramount consideration; in our view, this is best done posterior axillary line, made as far cephalad and caudad
through an open approach. as possible. Sometimes placement of an alternative upper
In cases of suspected leiomyoma of the esophagus, pre- working port posterior to the scapula is advantageous [see
operative investigation should be done to confirm the Figure 10]. The main working instruments are an endoscopic
presence of intact overlying mucosa, which is virtually pathog- scissors-cautery, a ring clamp, an endoscopic peanut dissec-
nomonic of this disease. Esophagoscopy is done to assess the tor, a Maryland dissector, a long right-angle clamp, and an
mucosa; if the mucosa is intact, the possibility of malignancy endoscopic clip applier.
is essentially ruled out. Simultaneously, endoscopic ultraso-
nography may be performed to establish the depth to which Step 3: incision of pleura The parietal pleura is incised
the esophageal wall is involved. With a preoperative diagnosis around the mass, with a margin of approximately 2 cm
of probable leiomyoma, VATS is the approach of choice in circumferentially. The pleura is tented up with the aid of
our practice.
So-called dumbbell neurogenic tumors (tumors that invade
the neural foramen) are special cases. Any solid mass in the
costovertebral sulcus should be evaluated by means of MRI
to determine whether it is invading the neural foramen if
the absence of invasion was not clearly established by CT.
Although invasion of the neural foramen by tumor is not
in itself an indication for thoracotomy, it does necessitate a
combined anterior-posterior approach with neurosurgical
involvement for the intraspinal portion of the procedure. Sev-
eral versions of such an approach have been described.27–29
We prefer to perform the posterior neurosurgical resection of
the intraspinal component (laminectomy and intervertebral
foraminotomy) first and then to reposition the patient
and carry out the remainder of the procedure (generally via
VATS).30
Although VATS is often an excellent approach to posterior
mediastinal lesions, it must be emphasized that one should
never hesitate to convert a VATS procedure to a thoracotomy
if required. Accordingly, informed consent to undergo thora-
cotomy should be sought before operation from all patients Figure 9 Resection of neurogenic tumor of posterior
being treated for posterior mediastinal lesions, even when mediastinum. Intraoperative photograph shows a solid
VATS is the intended approach. neurogenic tumor of the costovertebral sulcus.
02/10
hemostasis while protecting the underlying esophagus, vagus

and intercostal nerves, and azygos vein. This dissection and
all subsequent work are facilitated by placing gentle traction
on the mass with a sponge stick or, for smaller masses, by
grasping the entire mass within a ring clamp.
Step 4: dissection of soft tissue attachments Once

Alternative Upper the pleura has been incised circumferentially, the soft tissue
Working Ports attachments are further dissected bluntly with the endoscopic
peanut dissector. Attachments that are relatively thick or
vascular are best controlled by double-clipping and division.
If the tumor originates from an intercostal nerve, gentle dis-
Tumor section is done beneath the tumor to identify the intercostal
bundle that is the source of the lesion.
Camera Step 5: division of source intercostal bundle The

Port source intercostal bundle lateral to the tumor is mobilized,
doubly clipped, and divided. Once this has been accom-
plished, blunt dissection is performed until the nerve root
Lower emerging from the neural foramen and the associated inter-
Working Port
costal vessels are the last remaining attachments. If the tumor
Figure 10 Resection of neurogenic tumor of posterior originates from the sympathetic chain, the chain is clipped
mediastinum. Shown is typical port placement for video above and below the tumor, and the intercostal bundle is
thorascopic resection of a posterior mediastinal mass. spared if possible.
the right-angle clamp or the Maryland dissector to separate Step 6: removal of specimen The remaining stalk is
it from the underlying structures [see Figure 11]. This separa- doubly clipped and divided [see Figure 12], and the mass is
tion allows the use of the electrocautery, which provides removed in an endoscopic bagging device.
Step 7: drainage A 24 French chest tube is positioned

posteriorly at the apex.
Troubleshooting
Care must be taken to ensure that only very gentle traction
is exerted on a mass adjacent to the neural foramen. Over-
zealous traction can cause tearing of the nerve root proximal
to the extraspinal extent of the dura, and this tearing can lead
to a cerebrospinal fluid (CSF) leak, which most often becomes
evident only postoperatively (in the form of persistent clear
Figure 11 Resection of neurogenic tumor of posterior

mediastinum. Shown is circumferential incision of the pleura Figure 12 Resection of neurogenic tumor of posterior
around a neurogenic mass. mediastinum. The final remaining intercostal stalk is divided.
02/10
chest tube output). The diagnosis of CSF leakage can be the cyst wall that directly abuts the mediastinum is found to be
confirmed by measuring the b2-transferrin level in the fluid. too adherent to underlying structures to be removed safely, we
If CSF leakage is confirmed, reoperation with a neurosurgeon intentionally rupture the cyst and then remove as much of the
is mandatory; the leak is repaired and buttressed with cyst wall as possible. As much as 35% of the cyst wall may be
vascularized tissue. left in place. In such cases, we ablate the residual intact cyst wall
After resection of a tumor at the costoverterbral sulcus, with the electrocautery to destroy any potential secretory tissue.
regular neurologic examinations of the lower extremities are In our estimation, if more than approximately 35% of the
indicated. Tamponade with hemostatic agents should never cyst must be left in place, conversion to thoracotomy should be
be employed for bleeding at the neural foramen: doing so can considered.
result in an intraspinal hematoma with subsequent cord
compression. Careful use of the electrocautery at the bony resection of esophageal leiomyoma
margins of the foramen or watchful waiting is preferable. Operative Technique
If hemostasis cannot be achieved with these measures, a
neurosurgical consultation should be obtained. In the event In addition to the steps described for resection of a
of oozing from the vicinity of a foramen that is not easily neurogenic mass, there are several special maneuvers that
controlled, there should be no hesitation in converting a facilitate resection of esophageal intramural masses, such as
VATS procedure to an open procedure. leiomyomata [see Figure 14a] and duplication cysts:
In a minority of patients, clipping and division of an inter- 1. The pleura is incised longitudinally with the electrocautery
costal nerve result in intercostal neuralgia after the procedure; after it is tented up away from the esophagus, the vagus
the possibility that this may occur must be discussed with the nerve, and the azygos vein with a right-angle clamp or a
patient preoperatively. Many patients who undergo division Maryland dissector [see Figure 14b].
of a lower thoracic intercostal nerve that supplies an upper 2. In some cases, exposure is facilitated by dividing the azygos
abdominal dermatome notice postoperative bulging of the vein with an endoscopic stapler [see Figure 14c].
ipsilateral abdomen in the area supplied by that nerve. 3. The longitudinal esophageal muscle fibers that overlie
the mass are separated bluntly or with the electrocautery
resection of benign cyst of posterior mediastinum
in the line of the fibers. These fibers are often markedly
Resection of a benign cystic mass of the posterior medias- attenuated as a result of the expansion of the mass [see
tinum closely resembles resection of a neurogenic tumor Figure 14d].
[see Resection of Neurogenic Tumor of Posterior 4. Blunt dissection with an endoscopic peanut dissector
Mediastinum, above]; the differences are relatively minor [see allows careful, progressive mobilization of the mass, first
Troubleshooting, below]. from the muscle layer and then from the underlying
mucosa. Gentle traction on the mass facilitates exposure at
Troubleshooting
this point in the procedure [see Figure 14e]. A suture may
In the initial stages of dissection of a benign cyst of the poste- be placed into the tumor to facilitate this retraction. Having
rior mediastinum, care should be taken not to rupture the cyst; an assistant place the endoscope within the esophageal
initial mobilization from surrounding structures is easier when lumen to distend and illuminate the mucosa also may
the cyst wall is under tension [see Figure 13]. If the area of be helpful at this stage. Once the mass has been com-
pletely resected, it is sent for pathologic examination [see
Figure 14f].
5. The esophagus is distended by insufflating air from above
while the distal esophagus is occluded with a sponge stick.
The air-filled esophagus is then submerged in saline, and
the area of the resection is examined for air leakage.
Troubleshooting
The muscular defect in the esophageal wall must be closed
after resection to ensure that an esophageal diverticulum will
not develop. Such closure may be accomplished by means of
thoracoscopic suturing.
Frequently, duplication cysts are more adherent to the
underlying esophageal mucosa than leiomyomata are, and
transillumination of the esophageal wall helps define the
plane at which blunt dissection should be performed. Where
the cyst wall becomes difficult to separate from the mucosa,
a small amount of the wall may be left in place if, in the
surgeon’s judgment, attempting to remove all of it might lead
Figure 13 Resection of benign cyst of posterior
mediastinum. Intraoperative photograph shows a fluid-filled to a breach in the mucosa.
posterior mediastinal cyst. The tenseness of the cyst wall
facilitates initial dissection. Financial Disclosures: None Reported.
02/10
a b
c d
e f
Figure 14 Resection of esophageal leiomyoma. (a) Shown is an esophageal leiomyoma beneath the azygos vein. (b) The
mediastinal pleura overlying the leiomyoma is incised. (c) The azygos vein is divided with an endoscopic stapler. (d) The muscle
fibers overlying the mass are divided. (e) Gentle traction is applied to facilitate blunt dissection. (f) Shown is a completely
resected horseshoe-shaped esophageal leiomyoma.
02/10
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mediastinal masses. Ann Thorac Surg 2003; Surg 1939;110:544. the diagnosis of the intermediate solitary
75:1086. 13. Shrager JB, Deeb ME, Mick R, et al. Trans- pulmonary nodule. Ann Thorac Surg 1995;
2. Kumar A, Regmi SK, Dutta R, et al. Charac- cervical thymectomy for myasthenia gravis 59:868.
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PET CT. Ann Nucl Med 2009 July 8. [Epub by sternotomy. Ann Thorac Surg 2002; nary function, postoperative pain, and serum
ahead of print] 74:320. cytokine level after lobectomy: a comparison
3. Koduri P. The diagnostic approach to medi- 14. Shrager JB, Nathan D, Brinster CJ, et al. of VATS and conventional procedure. Ann
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1888. cal thymectomies for myasthenia gravis. Ann 25. Martinod E, Pons F, Azorin J, et al. Thoraco-
4. Vernino S, Lennon VA. Autoantibody Thorac Surg 2006;82:1863–9. scopic excision of mediastinal bronchogenic
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27. Shadmehr MB, Gaissert HA, Wain JC, et al.
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J Clin Oncol 2000;18:832. myasthenia gravis in 100 consecutive patients. 28. Osada H, Aoki H, Yokote K, et al. Dumbbell
7. Wood DE. Mediastinal germ cell tumors. Ann Surg 1999;230:555. neurogenic tumor of the mediastinum: a
Semin Thorac Cardiovasc Surg 2000;12: 18. Meyer DM, Herbert MA, Sobhani NC, et al. report of three cases undergoing single-staged
278. Comparative clinical outcomes of thymec- complete removal without thoracotomy. Jpn
8. Watanabe M, Takagi K, Aoki T. A compari- tomy for myasthenia gravis performed by J Surg 1991;21:224.
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11. Savitt MA, Gao G, Furnary AP, et al. Appli- mediastinal tumors. Ann Thorac Surg 1998; Figure 1b Photo courtesy of Wallace T. Miller
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surgical evaluation and treatment of the ante- 22. Smythe WR, Bavaria JE, Kaiser LR. Medias- Medicine
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4 THORAX 12 PERICARDIAL PROCEDURES — 1
12 PERICARDIAL PROCEDURES
Dawn Emick, MD, and Thomas A. D’Amico, MD
Surgical procedures are performed on the pericardium either relative noncompliance, the pericardium exerts an influence
for diagnostic purposes or for relief of the hemodynamic on cardiac hemodynamics. This influence can easily be seen
consequences of pericardial disease. The pericardial processes in the normal inspiratory variation in systemic arterial pres-
for which surgical intervention is required can be divided sure. Under normal circumstances, intrapericardial pressure
into two broad categories: pericardial effusion and constric- is slightly less than 0 mm Hg, becoming more negative during
tive pericarditis. Pericardial effusion can either be acute or inspiration and less negative during expiration. Negative
chronic, and the management of effusion depends largely intrathoracic pressure during inspiration augments right
on the rapidity of fluid accumulation and the risk of cardiac ventricular filling. Because the pericardium does not allow
tamponade. The decisions that must be made regarding significant acute right ventricular dilation, the ventricular
the selection of patients, the timing of surgery, and the choice cavity enlarges by shifting the septum toward the left ventri-
of technique or approach often pose substantial challenges cle. In addition, the noncompliance of the pericardium
to the surgeon. Accordingly, a thorough knowledge of the prevents the free wall of the left ventricle from distending to
anatomy, physiology, and pathophysiology of the pericardium recapture its normal cavitary volume. Thus, the volume
is essential for successful management of pericardial disease ejected from the left ventricle is slightly decreased, resulting
processes. in lower systemic arterial pressure. Normally, this effect is
exceedingly small. However, it becomes more pronounced
Anatomic and Physiologic Considerations when the pericardium is filled with fluid: ventricular disten-
tion is restricted even further, and paradoxical pulse becomes
anatomy clinically apparent.
Like the pleura, the pericardium consists of two layers. The pathophysiology
inner layer, the visceral pericardium (or epicardium), is a
monolayer of mesothelial cells that is adherent to the heart. Although the pericardium is resistant to rapid distention, it
The outer layer, the parietal pericardium, is a tough fibrous is capable of distending over time. If filled slowly, it can
structure composed of dense bundles of collagen fibers with expand to contain significant amounts of fluid (sometimes
occasional elastic fibers. The fibrous structure of this layer more than 1 L) before hemodynamic consequences develop.
renders the pericardial sac relatively noncompliant, and this In the setting of an acute pericardial effusion (e.g., from
noncompliance plays a significant role in pericardial function trauma), however, devastating hemodynamic consequences
and pathophysiology. may occur with only 100 to 200 mL of blood in the pericar-
The pericardium surrounds the heart and the great vessels dium. When the elastic capacity of the pericardium is
[see Figure 1]. Its parietal and visceral surfaces meet superiorly exceeded, even small increases in volume cause large increases
at the ascending aorta and the superior vena cava. From that in intrapericardial pressure and, if untreated, can lead to
point, the pericardium continues down the right border of the rapidly fatal cardiac tamponade. Although large, chronic
heart and over the anterior surface of the pulmonary veins to effusions accumulate slowly over time, there is still a point at
the inferior vena cava. After crossing the inferior vena cava, which the pericardium can no longer accommodate more
the inferior pericardium is densely adherent to the diaphragm. volume, and tamponade can develop quickly. In a series of
Just past the apex of the heart, it turns superiorly again and 28 patients with large idiopathic pericardial effusions, nearly
runs over the pulmonary veins back to the aorta. 30% developed cardiac tamponade unexpectedly.1 Thus,
Anteriorly, there are normally no connections between the drainage of large effusions even without signs of tamponade
visceral and parietal layers of the pericardium. Posteriorly, may be appropriate, particularly if there is evidence of
the pattern of pericardial reflections around the pulmonary right-sided diastolic collapse. A number of different processes
veins and the venae cavae creates two sinuses. The oblique can result in the accumulation of fluid in the pericardial space
pericardial sinus is the space in the center of the pulmonary [see Table 1].
veins, directly behind the left atrium. The transverse pericar- Constrictive pericarditis is defined as a chronic fibrous
dial sinus is bordered anteriorly by the aorta and the main thickening of the pericardium that causes cardiac compres-
pulmonary artery and posteriorly by the dome of the left sion sufficient to prevent normal diastolic filling. It can best
atrium and the superior vena cava. be thought of as the chronic sequela of acute pericarditis or
of any situation resulting in pericardial irritation and adhesion
normal physiology formation. Almost any cause of acute pericarditis can result
The pericardium is normally filled with 15 to 50 mL of in pericardial constriction [see Table 2]. In many patients,
serous fluid, which serves as lubrication to facilitate the there is no clear antecedent event, and the cause of the con-
motion of the heart within this structure. By virtue of its strictive pericarditis cannot be determined with certainty.
DOI 10.2310/7800.S04C12
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Figure 1 Shown is a view of the pericardium with the heart removed.
Pathologic examination typically demonstrates end-stage Table 2 Causes of Constrictive Pericarditis

fibrosis, and these cases are presumed to be viral in origin.
Historically, mycobacterial tuberculosis has been the most Common Causes
Unknown
common infectious cause of constrictive pericarditis, and it Infection
is still the dominant infectious cause in many developing Tuberculosis
countries today.2,3 In the United States, tuberculosis is the Viral infection (coxsackievirus B)
cause of constrictive pericarditis in approximately 6% of Bacterial infection
Fungal infection (histoplasmosis, coccidioidomycosis)
patients who undergo pericardiectomy.4 Constrictive pericar-
Parasitic infection (amebiasis, echinococcosis)
ditis also occurs after instrumentation of the pericardium Cardiac surgery or pacemaker insertion
and is seen occasionally (in 0.2 to 0.3% of cases) after Penetrating, nonpenetrating, or iatrogenic trauma
cardiac surgery.5,6 It also may develop after iatrogenic cardiac Radiation therapy
perforation in the course of catheterization or pacemaker Connective tissue disorders (rheumatoid arthritis, systemic lu-
pus erythematosus, scleroderma)
Renal failure
Neoplasm
Metastatic disease (breast, lung, lymphatic system, skin)
Table 1 Common Causes of Pericardial Effusion Primary mesothelioma
Drugs (procainamide, methysergide, hydralazine)
Malignancy
Trauma Uncommon Causes
Uremia Myocardial infarction
Infection (viral, bacterial, fungal, tubercular) Asbestosis
Autoimmune processes Amyloidosis
Cardiac surgery (postoperative complication) Sarcoidosis
Myocardial infarction Dermatomyositis
Iatrogenesis (intracardiac procedures) Actinomycosis
Aortic dissection Lassa fever
Radiation Whipple disease
Idiopathic origin Mulibrey nanism
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placement and after blunt or penetrating trauma—essentially, Pericardial Drainage Procedures for Pericardial
after any process resulting in an incompletely drained Effusion
hemopericardium.7,8 Pericardial effusion fluid may be transudate, exudate, pyo-
The pericardium may harbor metastatic disease or locally pericardium, or hemopericardium. Regardless of the origin
advanced disease (e.g., mesothelioma), which may lead to of the fluid accumulation, once the pericardium has reached
pericardial constriction.9,10 Connective tissue disorders (e.g., the limits of its elasticity, the only way in which it can increase
rheumatoid arthritis and lupus) can cause recurrent acute its volume is by reducing the volume occupied by the heart
pericarditis and pericardial effusions, eventually resulting in within it. Increases in pericardial pressure result in progressive
constrictive pericarditis. A similar situation may arise in cardiac compression and reductions in intracardiac volumes
patients receiving radiation therapy and patients with renal and myocardial diastolic compliance. This effect is most pro-
failure. nounced in the chambers with the lowest normal intracavitary
The stiffening and thickening of the pericardium have pressures—namely, the right atrium and the right ventricle.14
three major physiologic effects. First, the thicker pericardium Changes in systemic cardiac output occur as a result of right
isolates the heart from changes in intrathoracic pressure. heart compression, which leads to diminished right ventri-
Normally, the pulmonary veins (which are intrathoracic cular stroke volume, reduced pulmonary blood flow, and
structures) and the cardiac chambers experience the same decreased left ventricular filling. In the early stages of pericar-
changes in intrathoracic pressure. In the presence of pericardial effusion, various compensatory changes act to preserve
dial constriction, however, the negative intrathoracic pressure cardiac output. Such changes include an increased ejection
generated during inspiration cannot be transmitted to the fraction, tachycardia, increased intravascular volume via renal
heart. This isolation of the heart results in decreased flow conservation of salt and water, increased peripheral vascular
through the pulmonary veins during inspiration and reduced resistance, and time-dependent pericardial stretch.15,16
left-side filling.
Second, the ventricles become interdependent. Because preoperative evaluation
total pericardial volume does not change, the inspiratory The presenting symptoms of pericardial effusion may
decrease in left ventricular filling seen with constriction must be nonspecific and related to the underlying disorder (e.g.,
be accompanied by an increase in right ventricular filling, fever, chest pressure, and fatigue). Fluid accumulation that is
with a resultant septal shift toward the left ventricle. During substantial enough to have hemodynamic consequences is
expiration, the opposite occurs: left ventricular filling increases defined as cardiac tamponade. Patients with early tamponade
and right ventricular filling decreases, and there is a septal may have dyspnea, tachycardia, mild hypotension, decreased
shift toward the right ventricle. urine output, and paradoxical pulse. As tamponade pro-
Third, the encasement of the heart impairs the diastolic gresses, patients may manifest signs of end-organ hypoper-
filling of all cardiac chambers. Elevated atrial pressure causes fusion (e.g., mental status changes, renal insufficiency, and
rapid initial filling of the ventricle (with as much as 75% shock). The classic physical findings known as the Beck triad
of the ventricle filled during the first 25% of diastole), but by (i.e., jugular venous distention, systemic hypotension, and
the middle of diastole, filling abruptly decreases as a result of distant heart sounds) are more common with acute tampon-
the rigid pericardium. Because of this limit to diastolic filling, ade (such as results from trauma) than with slow-developing
increasing the heart rate becomes the most effective method tamponade (such as results from medical processes). In
of increasing cardiac output.11 patients with slow-developing tamponade, systemic fluid
Other uncommon but potentially significant pericardial retention is observed, often manifested by peripheral edema
diseases include congenital defects and cysts. In one study, or ascites.
congenital defects of the pericardium were found in 1 of Most commonly, pericardial effusion is diagnosed when a
10,000 autopsies.12 Most commonly, these included partial patient exhibits new symptoms in the context of an underly-
or total absence of pericardium on the left (70%), right ing disorder associated with pericardial effusion (e.g., renal
(17%), or total bilateral (rare), and 30% had other associated failure or malignancy). Chest x-rays may reveal a globular
anatomic anomalies. Most patients with complete absence heart or an increasing cardiac silhouette on serial films. Cur-
or large defects are asymptomatic; partial left-sided defects rently, echocardiography is the most commonly employed
can be complicated by herniation of the heart through the and most useful modality for the diagnosis of pericardial
defect and possible strangulation leading to chest pain, effusion: it reliably determines the presence, location, and
shortness of breath, syncope, or sudden death. Surgical peri- relative volume of fluid accumulations. The size of effusions
cardioplasty may be indicated in patients with imminent can be graded based on echocardiographic findings. Grade I
strangulation. Pericardial cysts may be congenital, inflamma- effusions are small (echo-free space in diastole <10 mm),
tory, or echinococcal in origin. Regardless of origin, most grade II effusions are moderate (10 to 20 mm), grade III are
cysts are asymptomatic and detected incidentally. Patients large (g20 mm), and grade IV are very large (g20 mm and
with symptoms from compression on the heart are candidates compression of the heart).17 In many cases, echocardiography
for percutaneous aspiration and ethanol sclerosis, with the can identify early tamponade, often before symptoms develop.
addition of pretreatment with albendazole for echinococcal A variety of echocardiographic findings are helpful in diag-
cysts.13 Patients with symptomatic inflammatory or congeni- nosing hemodynamically significant effusions, the most useful
tal cysts who do not respond to aspiration and sclerosis being right atrial collapse and right ventricular collapse. Right
may be candidates for video-assisted thoracotomy or surgical atrial collapse during late diastole tends to occur early in the
excision. development of tamponade because of the normally low right
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atrial filling pressures. Right ventricular free wall collapse

during early diastole suggests progression of tamponade.
Other useful signs are loss of the normal inspiratory collapse
of the inferior vena cava and an increase in right ventricular
diameter with a reciprocal decrease in left ventricular
diameter during inspiration.
In patients who are undergoing invasive hemodynamic
monitoring (e.g., those who have just undergone cardiac sur-
gery), hemodynamic findings suggestive of tamponade include
elevation of right atrial pressure and equalization of right
atrial pressure and pulmonary capillary wedge pressure. It is
important to remember, however, that localized tamponade
can occur (especially in the postoperative period) without
these changes. A common cause is localized clot in the oblique
pericardial sinus behind the left atrium, which causes reduced
left atrial compliance. Transesophageal echocardiography
here may be particularly useful, but it is important to have a
high degree of suspicion in these cases as thrombosis does not
have the typical echolucent area on echocardiography. Figure 2 Computed tomography demonstrates right pleural
and pericardial effusions, for which a right thoracoscopic
operative planning approach is ideal.
Choice of Procedure
improve the diagnostic yield and reduce the likelihood of
Three procedures are commonly performed for surgical
recurrent effusion. The major limitation of thoracoscopic
diagnosis and treatment of pericardial effusion: pericardio-
pericardiostomy is the need for lung isolation and lateral
centesis, subxiphoid pericardiostomy (pericardial window),
positioning, which should not be attempted in patients with
and thoracoscopic pericardiostomy (via either the right or
evidence of tamponade. By weighing the relative risks and
the left pleural space). The choice of a surgical approach to
benefits of these three procedures, the surgeon can choose the
the pericardial space depends on the clinical condition of the
optimal approach for each patient.
patient, the presence or absence of associated pleural effusion
or other thoracic process, and the underlying diagnosis (if pericardiocentesis
known). Patients with tamponade may decompensate rapidly
during the vasodilatation and positive pressure ventilation Operative Technique
associated with general anesthesia. Accordingly, careful con- Pericardiocentesis is performed either at the bedside in an
sideration must be given to the type of anesthesia employed urgent situation or, preferably, under echocardiographic or
for pericardial drainage procedures. fluoroscopic guidance in a catheterization laboratory. The
Pericardiocentesis is routinely done with local anesthesia basic technique is simple.
only and may be the best choice in an acutely unstable patient
with tamponade. If this option is chosen, however, the choice Step 1: placement of needle A local anesthetic is infil-
must be made with the understanding that pericardiocentesis, trated along the left side of the xiphoid. An 18-gauge spinal
because of its high recurrence rate and its limited diagnostic needle attached to a three-way stopcock and syringe is then
capacity, is unlikely to constitute definitive therapy. Subxi- advanced into the pericardial space and directed cephalad
phoid pericardiostomy is generally done with initial local toward the left shoulder at a 45° angle until fluid is aspirated
anesthesia followed by induction of general anesthesia, and [see Figure 3]; if air is aspirated, the needle is withdrawn and
most patients with tamponade can undergo this procedure. redirected more medially. Once fluid is aspirated freely, it is
The subxiphoid approach provides the hemodynamic benefits inspected. If the fluid is bloody, 5 mL is withdrawn and
of pericardiocentesis, offers the enhanced diagnostic capabil- placed on a sponge. If the fluid on the sponge clots, it is fresh
ity of pericardial biopsy, and has a low recurrence rate. blood, probably from a cardiac injury occurring during the
Consequently, it is the procedure of choice for patients with procedure or from intracardiac positioning of the needle;
tamponade who are stable enough to be transported to the blood that has been in the pericardium for even a short time
operating suite. Thoracoscopic pericardiostomy has the becomes defibrinated and will not clot.18
advantage of enabling simultaneous treatment of pleural
processes, which are commonly present in these patients [see Troubleshooting The inherent danger of cardiac injury
Figure 2]. Ipsilateral pleural and pericardial spaces can be during pericardiocentesis should be obvious. The risk is
fully explored, pleural effusions can be drained, loculations highest with small or loculated effusions and patients with
can be divided, and biopsy specimens can be obtained as coagulation abnormalities. The possibility of cardiac aspira-
needed. The thoracoscopic approach can be especially useful tion or injury can be minimized, although not eliminated,
in the case of a known loculated effusion that is limited to one by means of various safety measures. Of historical interest,
area of the pericardium, in that a pericardial window can be the simplest of these measures was to attach an electrocardio-
created via either pleural space. This approach also allows graphic (ECG) lead to the needle and employ continuous
resection of a larger segment of pericardium, which may ECG monitoring. If the needle contacts the epicardium, ST
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Although a diagnosis can be confirmed by positive results

from fluid culture or cytology, negative results from cytology
do not rule out malignant effusion. Cytologic analysis of
pericardial fluid is diagnostic in only 55 to 85% of patients.20
Further diagnostic maneuvers often must be undertaken,
usually involving subxiphoid or thoracoscopic approaches
with pericardial biopsy. Recurrence of pericardial effusion
after pericardiocentesis is extremely common. In a review
that included 139 patients with malignant pericardial effu-
sions who were treated with pericardiocentesis, successful
fluid removal with symptomatic relief was achieved in 97.1%
of cases.21 Of the 139 patients, 2.9% experienced complica-
tions (e.g., pneumothorax and ventricular laceration) and
one (0.7%) died. In all, 45 of the patients received no further
therapy, and in 25 (55%) of the 45, recurrent effusions
developed that necessitated reintervention.
Several techniques for preventing recurrent pericardial
effusion have been tried. Instillation of a sclerosing agent
(e.g., tetracycline, thiotepa, or bleomycin) into the pericar-
dium to promote fusion of the two layers of the pericardium
Figure 3 Pericardiocentesis. The needle is angled toward the has been shown to increase the success rate of pericardiocen-
left shoulder at an angle of 45°. tesis by as much as 85%.22–24 Placement of an indwelling
catheter (see above) also has been shown to improve the
success rate.21,25 Several authors have described creating a
segment elevation will be observed, in which case, the needle pericardial window percutaneously by means of balloon
is withdrawn until the ST elevation disappears. This is not dilation of the tract created by pericardiocentesis, which
considered to be an adequate safeguard anymore, and most theoretically allows fluid to drain into the pleural space or the
experts recommend direct visualization using fluoroscopic subcutaneous tissues, where it can be absorbed.26,27 However,
or echocardiographic guidance. Fluoroscopy or echocardio- it is unclear how long a window created in this fashion will
graphy is essential in cases of loculated effusions to help remain patent. Although pericardiocentesis provides initial
direct aspiration. Simultaneous cardiac catheterization has symptomatic relief in most patients, the observation that 15
also been used to locate the right coronary artery and the to 45% of patients require a further procedure for diagnosis
atrioventricular groove. and as many as 55% require reintervention for recurrence has
led some authorities to question its benefit.
Step 2: placement of drainage catheter and aspiration
of fluid Once the needle is within the pericardial space, a subxiphoid pericardiostomy ⁽pericardial window⁾
guide wire is placed through it, and a small-bore drainage
catheter is advanced into the effusion by means of a modified Operative Technique
Seldinger technique. Fluid is aspirated and sent for labora- Subxiphoid pericardiostomy may be performed either
tory evaluation (including cell count, chemistry, culture, to diagnose pericardial effusion or to manage tamponade.
and cytology). The catheter is then connected to a closed For diagnosis, the procedure is usually done with general
drainage system for 24 to 72 hours; this may help reduce anesthesia. In an unstable patient with significant tamponade,
recurrence. who would be at risk for hemodynamic collapse with general
anesthesia, the procedure may be performed with the patient
Complications under local anesthesia and mild sedation and breathing spon-
The most serious complications of pericardiocentesis are taneously. If there is any question of tamponade, the patient
laceration and/or rupture of the myocardium and coronary is prepared and draped while awake, and anesthesia is induced
vessels. Thankfully, these are rare (<1% when fluoroscopy is only when the surgeon is ready to begin. In all patients, the
used).19 More common complications of pericardiocentesis entire chest should be prepared in case a left anterior thora-
include arrhythmias, pneumothorax, air embolism, puncture cotomy or median sternotomy is required. Ideally, the patient
of the abdominal cavity or abdominal organs, misdiagnosis, is sedated and the airway controlled while spontaneous
and recurrence of pericardial effusion. In every patient under- respiration is maintained to minimize hemodynamic effects.
going pericardiocentesis, pneumothorax must be ruled out If necessary, a local anesthetic may be infiltrated and the
by means of chest x-ray at the completion of the procedure incision made before induction of anesthesia.
or, if respiratory or hemodynamic changes develop intra-
operatively, during the procedure. Cardiac injuries range Step 1: initial incision and exposure of pericardium
from minor needle lacerations to the epicardium, which are A small vertical incision is made from the xiphisternal junc-
self-limited in patients with normal coagulation parameters, tion downward to a point slightly below the tip of the xiphoid
to potentially fatal injuries to the myocardium or coronary process [see Figure 4a]. The upper extent of the linea alba
vessels that can lead to acute cardiac tamponade. Incorrect is divided, with care taken not to enter the peritoneum.
diagnoses based on pericardiocentesis are not uncommon. Peritoneal openings are easily repaired but can make the
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a b
Figure 4 Subxiphoid pericardiostomy. (a) A small vertical incision is made from the xiphisternal junction down to a point just
below the tip of the xiphoid, the upper extent of the linea alba is divided, and the xiphoid is removed. (b) The pericardium is
opened, and the edge of the opening is grasped and elevated. A pericardial specimen several square centimeters in size is then
resected to create the pericardial window.
procedure technically more difficult in that abdominal con- cardiac injury; therefore, the patient’s hemodynamics should
tents tend to impede visualization, especially in spontane- be carefully monitored during this time. When the pressure
ously breathing patients. Positioning patients with feet down placed on the heart by an effusion is released, blood pressure
in a reverse Trendelenburg position prior to the procedure will usually rise and heart rate fall; however, if the heart
may allow the abdominal organs to fall toward the pelvis and has been accidentally injured, the opposite will occur. Once
out of the way. The soft tissue attachments to the xiphoid hemodynamic stability is achieved, administration of a diuretic
are divided, the veins running along either side of the xiphoid (e.g., furosemide) should be considered to reduce the risk of
are controlled, and the xiphoid process is removed. pulmonary edema developing as a result of systemic fluid
The tissue plane behind the lower sternum is developed by retention.
means of blunt dissection. This maneuver exposes the
retrosternal space to allow visualization of the pericardium. Step 3: creation of pericardial window Pericardial
To enhance exposure, the sternum is retracted upward by an fluid is collected for microbiologic and cytologic analysis and
assistant. The anterior pericardial surface is then exposed by for any additional testing suggested by the clinical scenario.
sweeping away the remaining mediastinal fat. If necessary, The pericardial space is gently explored with the fingers, and
the confluence of the pericardium and the diaphragm may be all remaining fluid is evacuated. The edge of the pericardial
retracted caudally to improve exposure. opening is grasped with a clamp and elevated [see Figure 4b].
A pericardial specimen several square centimeters in size—or
Step 2: opening of pericardium The location of the as large as can safely be managed—is resected and sent for
pericardial incision can be confirmed by palpating cardiac pathologic and microbiologic analysis.
motion through the exposed pericardium. The pericardium
is then opened with a scalpel; shallow strokes should be Step 4: drainage and closure A separate stab incision
employed to reduce the chances of injuring underlying for drain placement is made below and to one side of the
myocardium that may be adherent to the pericardium. Upon lowermost aspect of the skin incision. Bringing the drainage
entry into the pericardium, there is an initial outrush of fluid. tube out through a separate incision helps prevent incisional
A sanguineous effusion can be difficult to differentiate from complications (e.g., infection and hernia). A 24 to 28 French
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chest tube (either straight or right-angle) is tunneled through have questioned whether pericardial drainage should even be
the fascia at the entry site so that it lies beneath the divided offered to these patients.32
linea alba in the preperitoneal space. The tube is then directed
through the pericardial window and into the pericardial space thoracoscopic pericardiostomy
and secured at skin level. The fascia at the linea alba is closed Operative Technique
with interrupted sutures to provide secure closure and pre-
Thoracoscopic pericardiostomy is a safe and effective
vent late hernia; the skin and subcutaneous tissue are closed
approach to the diagnosis and management of pericardial
in the standard fashion. The chest tube is connected to a
effusion, especially in patients with a unilateral pleural disease
drainage system with a water seal. Pericardial drainage is
process that can be simultaneously addressed in the course
maintained for several days postoperatively until the output
falls below 100 mL/day. This period allows time for apposi- of the procedure. Thoracoscopic pericardial drainage neces-
tion and adhesion formation between the visceral pericardium sitates single-lung ventilation and thus is unsuitable for
and the parietal pericardium. unstable patients, especially those with tamponade. Such
Although some fluid may initially drain into the subcutane- ventilation can be accomplished by means of either a dual-
ous tissues and be absorbed, the name pericardial window is lumen endotracheal tube or a bronchial blocker placed
something of a misnomer. The surgically created window in through a standard endotracheal tube.
the pericardium is unlikely to remain patent over the long Once the tube is in place, the patient is turned to the
term, and, in fact, obliteration of the pericardial space has appropriate lateral decubitus position. The side of approach
been shown to be the mechanism responsible for the success is chosen on the basis of the location of a loculated effusion
of this procedure.28,29 or the site of any coexisting pathologic condition (e.g., a
pleural effusion, pleural nodules or thickening, or pulmonary
Complications nodule). If the disease process or processes present do not
Complications from subxiphoid pericardiostomy are rare; dictate a particular side of approach, the right side is pre-
bleeding, infection, incisional hernia, anesthetic complica- ferred. It is often easier to operate on the right side because
tions, and cardiac injury have been reported. In a study that there is more working room within the pleural space;
included 155 patients who underwent subxiphoid pericardi- however, operating on the left side usually allows the surgeon
ostomy over a 5-year period, not a single death was attribut- to create a larger pericardial window. If tamponade is present
able to the operative procedure itself.23 The 30-day mortality in a patient for whom the thoracoscopic approach is desired,
was high but was related to the underlying disease process: pericardiocentesis may be performed before induction of
33% in patients with malignant effusions and 5% in those general anesthesia.33
with benign effusions. Recurrent pericardial effusion neces-
sitating additional procedures occurred in four patients Step 1: placement of ports and entry into pleural
(2.5%). In a study that compared 94 patients who underwent space An initial camera port is placed in the posterior
subxiphoid pericardiostomy with 23 patients who underwent axillary line at the eighth intercostal space [see Figure 5]. The
pericardiocentesis, the rate of recurrent effusion that neces- pleural space is entered and explored, and any effusion pres-
sitated reintervention was 1.1% after the subxiphoid window ent is drained. Pleural fluid is sent separately for culture
procedure but 30.4% after pericardiocentesis.30 In this series, and cytologic analysis. To prevent inadvertent entry into the
the rate of major complications after the pericardial window pericardium, which is often distended, a second incision is
procedure was 1.1% (one patient with bleeding that necessi- created anteriorly at the fifth intercostal space under camera
tated reexploration), compared with a major complication visualization.
rate of 17% after pericardiocentesis (including a mortality of
4%). Step 2: opening of pericardium On the left side, the
Several studies have shown that the most important predic- phrenic nerve, which runs midway between the hilum and
tor of long-term outcome is the underlying disease process. the anterior chest wall, is carefully identified, and an initial
In one, the median survival time was 800 days for patients pericardial incision is made approximately 1 cm anterior to
with benign disease, 105 days for patients with known cancer this nerve. Care must be taken to place this first incision in
but negative results from pericardial cytology and pathology, an area that is free of cardiac adhesions. When grasped,
and only 56 days for patients with malignant effusions.28 the pericardium should tent outward slightly. Often cardiac
It appears, however, that cancer patients with hematologic motion is visible through the pericardium.
malignancies and pericardial effusion survive significantly
longer than patients with other malignancies. In another Step 3: creation of pericardial window A pericardial
study, the mean survival time after drainage of pericardial window several square centimeters in area is removed. A
effusion was 20 months for patients with hematologic malig- similar window may be created posterior to the phrenic
nancies, compared with 5 months for patients with any other nerve—again, with care taken to stay at least 1 cm away from
malignancies.31 The investigators suggested that this finding the nerve. The pericardial space is inspected, and any locula-
may be related to the relative responsiveness of hematologic tions are opened. The procedure is similar when performed
cancers to systemic chemotherapy. Patients with HIV disease on the right side, except that the phrenic nerve on the right
have been shown to have universally dismal outcomes after runs much closer to the hilum; accordingly, instead of two
they present with pericardial effusion. In this population, pericardial windows (anterior and posterior to the nerve),
surgical pericardial drainage generally is not diagnostically only a single, larger pericardial window is created (anterior to
revealing and is of little therapeutic value. Several authors the nerve).
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4–5 cm Incision in
1.5 cm Incision in Fifth Intercostal Space
Eighth Intercostal Space for Instruments
for Camera Port
Assistant
behind Patient
Surgeon in Front of Patient
Figure 5 Thoracoscopic pericardiostomy. Shown are the appropriate patient positioning and the proper placement of ports and
instruments.
In patients who can tolerate general anesthesia, a pericar- thoracoscopic procedures (67%) and only 18 of 56 (32%) of
dial window can be created thoracoscopically with excellent the subxiphoid approach. Anesthesia time (117P32 vs
diagnostic yield and relief of symptoms.34 The thoracoscopic 81P26 minutes) and minor procedural morbidity (27%
approach allows directed access and can be useful in treating versus 2%) were higher for the thoracoscopic approach, but
effusions that recur after subxiphoid pericardiostomy.35 long-term control of the effusion seemed to be improved in
the thoracoscopic approach. Equal percentages of patients
Complications had recurrence of their effusions (≈ 10%), but time to recur-
Complications from thoracoscopic pericardiostomy occur rence was much longer for the thoracoscopic procedures
more frequently than from the subxiphoid approach. Reported (36 versus 11 months).
complications include bleeding, infection, and cardiac injury
similar to the subxiphoid approach, but compared to the
subxiphoid approach, patients who undergo thoracoscopic Pericardiectomy for Constrictive Pericarditis
procedures have longer anesthesia times and require single- Constrictive pericarditis appears to be about three times
lung ventilation, which increases the incidence of anesthesia- as common in males as in females, and it may occur at
related complications. Patients who undergo thoracoscopic any point in life from childhood to the ninth decade.37 The
procedures require pleural tubes in the immediate postopera- symptoms of constrictive pericarditis usually develop pro-
tive period, and various complications related to chest tubes gressively over a period of years but may develop within
(e.g., recurrent pneumothorax, trapped lung) may occur. weeks to months after a defined inciting event (e.g., media-
One recent study compared subxiphoid to videothoracoscopic stinal irradiation or cardiac surgery). Signs and symptoms
pericardial window procedures in 71 patients.36 In this retro- are related to pulmonary venous congestion (e.g., exertional
spective review, 56 patients underwent subxiphoid pericar- dyspnea) and systemic venous congestion (e.g., elevated jugu-
diostomy and 15 underwent the procedure thoracoscopically. lar venous pressure, hepatomegaly, ascites, and peripheral
Nonpericardial procedures were performed in 10 of 15 edema).
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preoperative evaluation should be performed with an oscillating saw. Access to the

The physiologic effects of the thickened pericardium form femoral vessels should be available within the sterile field;
the basis for the diagnosis of constrictive pericarditis and, placement of a femoral arterial line will facilitate percutane-
more important, for the differentiation of constrictive pericar- ous cannulation in the event that the heart is injured during
ditis from restrictive cardiomyopathy, which often presents sternal reentry.
a similar picture. Echocardiography can be employed to After the sternum is opened, all adhesions are dissected
rule out other causes of right-side failure. Specific findings away from the sternum, with care taken to stay as close to the
that suggest pericardial constriction include septal bounce posterior surface of the sternum as possible. Both pleural
(a respiratory phase–related septal shift) and decreased trans- spaces are opened, and the left and right phrenic nerves are
mitral flow velocity during inspiration. Computed tomo- identified.
graphy and magnetic resonance imaging may demonstrate
thickened, often calcified, pericardium; however, the degree Step 2: dissection and resection of pericardium The
of pericardial thickening does not necessarily correlate with phrenic nerves define the limits of pericardial resection bilat-
the presence of hemodynamic effects. erally. Small loculated spaces are often present within the
Cardiac catheterization may demonstrate increases in and pericardium, especially near the great vessels and the dia-
equalization of end-diastolic pressure in all four cardiac phragm, and provide good starting places for pericardiec-
chambers, a dip-and-plateau pattern (the square-root sign) in tomy. Once an initial flap is raised, it is used to provide
the ventricular pressure curves as a result of rapid early filling retraction to facilitate further dissection. Careful attention
and limited late filling, and rapid x and y descents in the atrial must be paid to the coronary artery anatomy: coronary arter-
pressure curves. The most useful information obtainable ies and bypass grafts are vulnerable to injury. If the pericar-
through cardiac catheterization has to do with the respiratory dium is densely adherent in the region of a coronary artery,
variation of ventricular pressure. In a patient with a normal small islands of pericardium may be left on the heart. Areas
heart or a patient with restrictive cardiomyopathy, inspiration of calcification can be addressed with the use of bone-cutting
causes a decrease in both right ventricular pressure and left instruments; however, if an island of calcification appears to
ventricular pressure as a consequence of decreased intratho- extend into the myocardium, it should not be removed.
racic pressure. In a patient with constrictive pericarditis,
because of the interdependence of the ventricles, inspiration
causes a decrease in left ventricular pressure but an increase
in right ventricular pressure.38
operative planning
Choice of Approach
Pericardiectomy may be performed via either a median
sternotomy or a left anterolateral thoracotomy, with equiva-
lent results. Median sternotomy provides better access to
the right atrium and the great vessels, as well as easier access
for cannulation if cardiopulmonary bypass is required; left
anterolateral thoracotomy allows more complete release of
the left ventricle. With either approach, the patient should
undergo full monitoring, including radial artery catheteriza-
tion and central venous catheterization, with consideration
given to placement of a pulmonary arterial catheter if there is
significant hemodynamic compromise. Because significant
blood loss can occur when densely adherent pericardium is
resected, large-bore intravenous access should be available as
well.
operative technique
Median Sternotomy
Step 1: initial incision and exposure The patient is
placed in the supine position, and the skin incision is carried
down to the level of the sternum. If there is no history of
previous pericardial procedures and it is possible to develop
the plane behind the sternum bluntly at the superior and
inferior aspects, a standard sternotomy saw can be used for
the median sternotomy. If, however, there are likely to be
adhesions between the sternum and the pericardium or the Figure 6 Pericardiectomy: median sternotomy approach.
heart (as in the case of constrictive pericarditis after coronary The pericardium is resected from the left phrenic nerve to the
artery bypass grafting), a careful reoperative sternotomy right phrenic nerve.
01/10
Epicardium can also be involved in the disease process For improved exposure, the internal thoracic vessels may be
and should be resected or scored until no further restriction divided and the intercostal muscles divided posteriorly. The
to ventricular filling remains. The heart should be dissected left phrenic nerve is carefully identified.
free of the left pulmonary veins all the way over to the right
pulmonary veins (including the origins of the venae cavae). Step 2: dissection and resection of pericardium As
The pericardium is resected from the left phrenic nerve to the with the median sternotomy approach, loculated spaces are
right phrenic nerve [see Figure 6]. often present near the great vessels and the diaphragm, and
Cardiopulmonary bypass can make dissection easier, but these vessels provide good starting places for dissection. The
in view of the greater risk of bleeding and the increased trans- entire pericardium is dissected free over the left ventricle, and
fusion requirements, it is best avoided if possible. Cardiopul- an island of pericardium is left attached to the phrenic nerve
monary bypass does facilitate repair of cardiac injuries during along its length [see Figure 7]. The pericardium is resected
sternal reentry or dissection and should be used if cardiac from the pulmonary veins to a point just posterior to the
procedures are to be performed concomitantly. phrenic nerve. Resection resumes anterior to the nerve and
continues across the anterior aspect of the heart as far as
Step 3: drainage and closure After completion of the possible, ideally to the right atrioventricular groove. The
pericardiectomy, mediastinal and pleural drains are placed, same precautions should be taken around the coronary
and the sternum is closed in the usual fashion. vessels as are taken with the median sternotomy approach.
Left Anterolateral Thoracotomy Step 3: drainage and closure After completion of the
Step 1: initial incision and exposure The patient is pericardiectomy, mediastinal and pleural drains are placed,
placed in the supine position, with a roll under the left side and the thoracotomy is closed in the usual fashion.
of the torso to elevate the left side 45°. It is often difficult to
outcome evaluation
establish cardiopulmonary bypass through the chest via this
approach; therefore, the femoral vessels should be available There is no proven difference between the two approaches
within the sterile field so that femorofemoral bypass can be to pericardiectomy with respect to outcome. Accordingly, the
instituted if necessary. A curvilinear submammary incision choice between them is based on whether one option affords
is created, and the chest is entered at the fifth interspace. better access to the areas believed to be most involved
a b
Figure 7 Pericardiectomy: left anterolateral thoracotomy approach. (a) The left phrenic nerve is identified. (b) The entire
pericardium is dissected free over the left ventricle, with an island of pericardium left attached to the phrenic nerve along its
length. Care must be taken to avoid injuring coronary vessels.
01/10
(e.g., a median sternotomy is more effective for releasing pericardiectomy for radiation-induced constriction indicate
the right side of the heart) and whether the surgeon is more that constriction is not the sole factor responsible for cardiac
comfortable with one approach or the other. failure in this situation. Although cardiac failure has been
The underlying cause of constrictive pericarditis is a attributed to myocardial atrophy caused by prolonged con-
significant predictor of long-term survival. In a study of striction, the excellent outcomes reported after pericardiec-
163 patients who underwent pericardiectomy, 7-year survival tomy for idiopathic constrictive pericarditis suggest that
rates were highest in patients with idiopathic constrictive constriction is rarely the only cause of cardiac failure.
Another study reported similar findings, with radiation-
pericarditis (88%), somewhat lower in patients with post-
induced constriction leading to significantly decreased 10-
operative constriction (66%), and lowest in patients with
year survival after pericardiectomy.37 The authors also noted
radiation-induced constriction (27%).39 Predictors of decreased that patients who underwent pericardiectomy for radiation-
survival included previous radiation therapy, renal dysfunc- induced constriction had demonstrably worse late functional
tion, pulmonary hypertension, and abnormal left ventricular status. Fifteen of 17 long-term survivors with a history of
systolic function. Perioperative mortality was 6% overall but previous radiation therapy showed New York Heart Associa-
21% in patients who had received radiation therapy and tion class III or IV symptoms, whereas only 31 of 112 patients
8% in postsurgical patients. The slightly higher mortality without a history of radiation therapy had major symptoms of
recorded in postoperative patients may reflect underlying heart failure.
cardiac dysfunction, as well as the vulnerability of previous
bypass grafts to injury. The poor outcomes after Financial Disclosures: None Reported.
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pericardial tetracycline sclerosis in the treat-
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13. Simeunovic D, Seferovic PM, Ristic AD, et al. 1986;58:633. specific survival after pericardiectomy. J Am
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sentations and treatment. In: Seferovic PM, Percutaneous balloon pericardial window
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14. Fowler NO, Gabel M. The hemodynamic 27. DiSegni E, Lavee J, Kaplinsky E, et al. Percu- The authors wish to acknowledge Shari L. Meyerson,
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result of atrial, not ventricular, compression. ment of cardiac tamponade. Eur Heart J chapter on which we have based this update.
Circulation 1985;71:154. 1995;16:184. Figures 1 and 3 through 7 Alice Y. Chen.
01/10
4 THORAX 13 Decortication and Pleurectomy — 1
13 DECORTICATION AND
PLEURECTOMY
Eric S. Lambright, M.D.
In normal circumstances, the pleural space is a potential cavity HISTORY AND PHYSICAL EXAMINATION
between the lung and the chest wall—more specifically, between The physiologic consequences of a fibrothorax culminate in pul-
the visceral pleura and the parietal pleura. In the average healthy monary restriction, manifested by decreased lung volumes, reduced
patient, this space is less than 1 mm thick. There are a number of diffusion capacity, and lower expiratory flow rates. Movement of
pathologic processes that can alter the transport of cells and fluid the chest is impaired.4 The initial clinicial presentation of a fibro-
within this space and thus give rise to clinically significant sequelae. thorax depends on its cause and severity, as well as on the pres-
One such process is fibrothorax, which is defined as the presence ence or absence of underlying parenchymal disease.Typically, dys-
of abnormal fibrous tissue within the pleural space, resulting in pnea on exertion is the most common presenting symptom, though
entrapment of the underlying pulmonary parenchyma (a state var- cough, fever, pleuritic chest discomfort, malaise, night sweats, weight
iously referred to as trapped lung, restrictive pleurisy, or encased loss, or chest pressure may also be present. In obtaining the clinical
lung). Decortication is the surgical procedure by which this history, it is important to determine whether the condition is chron-
restrictive fibrous layer is peeled away from the lung; the literal ic and whether there are any other underlying disease processes that
meaning of the term is the stripping away of a rind (from the Latin may be complicating the pulmonary disease process. Physical ex-
word cortex “bark, rind, shell”). The technical goals of the opera- amination yields relatively nonspecific findings; typically, de-
tion are to reexpand the lung and resolve the pathologic process creased breath sounds and decreased chest wall excursion are noted.
affecting the pleural space so that pulmonary function and chest
wall mechanics will improve and the patient’s symptoms will be DIAGNOSTIC IMAGING AND PHYSIOLOGIC TESTING
relieved. Radiographic evaluation is the mainstay of diagnosis [see Figures
Successful management of a patient with fibrothorax depends 1, 2, and 3]. Computed tomography (CT) of the chest is the imag-
on close adherence to basic surgical tenets: appropriate selection of ing modality of choice for delineating abnormalities of the pleural
patients for surgical treatment, preoperative optimization of the space and defining the character of the pleural disease process. CT
patient’s physiologic status, exacting attention to the technical scanning can assess the extent and thickness of pleural involve-
aspects of the procedure, and timely intervention to address peri- ment and characterize associated parenchymal disease. It readily
operative complications. If insufficient attention is paid to any of identifies parenchymal abnormalities such as fibrosis, bronchiec-
these important tenets, decortication may fail to achieve any signif- tasis, and malignancy. Such factors play a role in surgical decision
icant improvement in the patient’s symptoms or physiologic status, making. In particular, malignancy must be included in the differ-
potentially leaving him or her in an even more debilitated state. ential diagnosis of fibrothorax and ruled out; the management
options for malignant disease are quite different from those for
Preoperative Evaluation benign disease.
Physiologic testing with spirometry and evaluation of diffusing
PATHOPHYSIOLOGY OF FIBROTHORAX
capacity helps define the degree of pulmonary dysfunction and
facilitates risk stratification. The results of pulmonary function
Although any insult to the pleura can result in an inflammato- testing may be quite abnormal preoperatively and are often worse
ry response with fibrin deposition,1 hemothorax and infection than would have been expected from the radiographic evaluation.
(bacterial and mycobacterial) remain the most common causes of Marked abnormalities in physiologic testing should not be consid-
fibrothorax [see Table 1].Typically, empyemas evolve over a 4- to 6- ered absolute contraindications to surgical intervention, because
week period as the infection progresses throughout the pleural some degree of improvement may be anticipated. The improve-
space.The first (exudative) phase is characterized by a thin, fibrin- ment in dyspnea, pulmonary reexpansion, and parenchymal func-
containing fluid exudate. The second (fibropurulent) phase is tion that can realistically be expected after decortication may be
characterized by a heavy fibrin deposit over the pleural surface
with the development of loculations and fibrous debris in the tho-
racic cavity. The third (organizational) phase, which begins at
about 3 to 5 weeks, is characterized by the formation of a thick
fibrous peel that imprisons the lung and prevents expansion.When Table 1 Common Causes of Fibrothorax
fully developed, this peel has three distinct layers: (1) an outer Chronic empyema
layer consisting of loosely organized vascular tissue, (2) a middle Retained hemothorax (traumatic or iatrogenic)
layer consisting of fibrous connective tissue that is relatively avas- Pleural effusive disease
cular and acellular, and (3) an inner layer consisting of necrotic tis- Transudative
sue and fibrinoid masses.2 Generally, if a hemothorax is small, it Chylous
will be reabsorbed, provided that the lymphatic system is intact. Pancreatic
However, if the hemothorax is relatively large, if there is continued Sequelae of Mycobacterium tuberculosis infection
bleeding, or if bacteria are present, there is a high likelihood that a Chronic pneumothorax
fibrous peel will eventually form.3
a b
Figure 1 (a) Shown is a chest x-ray from a patient with a 2-month history of dyspnea and cough associated with
intermittent fever and night sweats. Treatments included three courses of antibiotics and bronchodilator therapy.
(b) A chest CT scan from the same patient shows a large pleural collection containing air and demonstrates pleural
thickening (arrow). The findings are consistent with empyema. Thoracentesis was performed, demonstrating white,
creamy purulence but failing to achieve reexpansion of the lung. Decortication was performed.
estimated on the basis of the preoperative diagnostic imaging and ment of the pleura (usually by adenocarcinoma) is far more com-
physiologic testing. Ultimately, the surgeon’s judgment plays the mon than malignant pleural mesothelioma, which is a primary
key role in deciding for or against surgical intervention. malignancy of the pleural space. Cytologic evaluation of the pleur-
al fluid will establish the diagnosis of metastatic pleural involve-
EXCLUSION OF MALIGNANCY
ment in most cases; however, it tends to be less effective in estab-
In the evaluation of a patient with a fibrothorax, it is essential to lishing the diagnosis of malignant mesothelioma. If the presenta-
keep in mind the possibility of a malignant pleural process. If tion of a chronic pleural process is atypical and the etiology is poor-
malignancy is a concern, this possibility should be excluded before ly defined, a degree of suspicion for malignancy must be main-
a decision is made to proceed with decortication. Decortication of tained. Appropriate initial pleural biopsies can be useful for ruling
a malignant fibrous peel is difficult, and the outcome is not partic- out underlying malignancy before decortication. Currently, pleur-
ularly satisfying from the standpoint of lung expansion; according- al biopsy is usually performed by means of video thoracoscopy, but
ly, for a pleural malignancy, a lesser, palliative intervention is gen- closed pleural biopsy is still done occasionally (though it is fast
erally more appropriate than decortication. Metastatic involve- becoming a lost art). If a malignancy is identified, therapeutic alter-
a b
Figure 2 (a) Shown is a preoperative chest CT scan from a patient with a 6-week history of malaise and
weight loss who ultimately presented with hypotension and respiratory insufficiency necessitating mechanical
ventilatory support. (b) A chest CT scan obtained from the same patient after decortication shows complete
reexpansion of the lung.
ease or airway stenosis.9,10 In this setting, decortication is destined

to fail: the lung parenchyma will not reexpand to fill the pleural
space completely, and any surgical intervention carried out on the
diseased lung will only aggravate the underlying disease process.
Pleuropneumonectomy may be the only option, though it should
be considered a last resort, to be used only if there is significant
parenchymal destruction. Decortication may be precluded by
invasive uncontrolled pulmonary infection, contralateral pul-
monary disease, or a chronically debilitated state that results in a
significant or even prohibitive level of operative risk. Medical opti-
mization may be required as an initial step. Often, however, the
underlying pleural infection process remains unresolved despite
optimal medical management, and surgical intervention becomes
necessary in a patient who remains medically fragile. Optimally,
the patient’s nutritional status should be normalized (with forced
feedings, if necessary), and sepsis, if present, should be controlled
with appropriate antibiotic therapy.
TECHNICAL CONSIDERATIONS
Figure 3 Shown is a chest CT scan from a patient with a pul- Essentially, pleural cavity infection and fibrosis are problems of
monary abscess (arrow) complicated by pleural space infection.
residual intrapleural space.The lung cannot expand sufficiently to
The pleural space was drained via a chest tube thoracostomy. The
lung did not completely reexpand. Sepsis was controlled with
fill the hemithorax, and as a consequence, the residual space
antibiotics. Decortication was not considered, because of the becomes or remains infected.These problems often prove difficult
extensiveness of the underlying pulmonary parenchymal process. for the thoracic surgeon to address; good surgical judgment is cru-
cial for ensuring optimal outcomes. In planning for decortication,
there are a number of technical issues that must be considered,
natives such as pleurodesis or use of the Pleurx pleural catheter including the timing of intervention (taking into account whether
(Denver Biomedical, Golden, Colorado) may be indicated. the disease process is chronic or subacute), the quality of the
underlying pulmonary parenchyma, the expected ability of the
lung to reexpand, the possible need to address residual space
Operative Planning issues, and the physiologic status of the patient. The goal of the
procedure is to remove the peel from the visceral pleura so as to
INDICATIONS FOR SURGICAL INTERVENTION allow the lung to reexpand and, equally important, to ensure that
Fibrothorax is a potentially preventable complication. As noted any potential residual space is obliterated.11
(see above), it is a manifestation of a chronic disease process; thus, There are few absolute contraindications to pulmonary decorti-
the earlier a therapeutic intervention is initiated, the better the cation, other than a patient who is unfit to undergo surgery or the
chances that fibrothorax can be prevented. In patients with a trau- presence of underlying parenchymal or bronchial disease that
matic hemothorax, early and complete drainage often serves to would prevent lung reexpansion. There are, however, some situa-
prevent fibrothorax.5 Observational studies have consistently de- tions in which a lesser intervention (e.g., chest tube thoracostomy,
monstrated that early evacuation of a clotted hemothorax reduces rib resection, or open window thoracostomy) might yield a better
morbidity and mortality and prevents empyema.6,7 When para- outcome than decortication would from the patient’s perspective.
pneumonic effusions are thin, simple aspiration or chest tube drain- In general, decortication is not required for a small, well-defined
age may suffice. Often, the fibropurulent stage characterized by loc- residual cavity; it is usually reserved for a diffuse pleural process.
ulated empyema or clotted hemothorax can be successfully man- Whether the disease process is chronic or subacute will also influ-
aged by means of thoracoscopic intervention with debridement of ence the surgeon’s choice of approach. For example, in the earlier
the intrathoracic debris and irrigation; this approach allows the stages of pleural space infection, when the peel is less organized, a
parenchyma to reexpand before a restrictive peel can be formed.8 thoracoscopic approach that includes cleansing of the pleural
The primary indication for decortication in a patient with fibro- space, removal of the pleural debris, and breaking up of loculations
thorax is symptomatic pulmonary restriction resulting from the may prove adequate. With a chronic process, however, an attempt
development of a fibrinous peel. The timing of the operation is an at thoracoscopic decortication may do more harm than good.
important consideration. In many cases, pleuropulmonary process-
es are self-limiting, and the symptoms resolve over time. As a rule,
Operative Technique
decortication should be considered (1) if pleural thickening has
been present for a substantial period (> 4 to 6 weeks), (2) if respi- The first step in open decortication (which at times includes
ratory symptoms remain disabling, and (3) if there is radiographic parietal pleurectomy in addition to decortication) is bronchoscop-
evidence of reversible entrapment of the lung. Decortication is ic evaluation aimed at identifying any endobronchial obstructions
often necessary when lesser interventions have not achieved control that might prevent satisfactory lung expansion. Such evaluation
of a pleural space infection or have not enabled the lung to reex- sometimes yields unexpected findings, such as malignancy,
pand. For tuberculous empyema, drug therapy remains the treat- bronchial stenosis, or a broncholith.
ment of choice. Decortication may also be performed to treat The chest is entered at the appropriate predetermined inter-
pleural effusions that persist despite long-term medical therapy. space (usually the fifth or sixth) via a standard posterolateral tho-
A condition that poses a major challenge to the thoracic sur- racotomy [see Figure 4]; alternatively, a vertical axillary thoracoto-
geon is pleural space infection with underlying parenchymal dis- my may be employed. With either approach, the latissimus dorsi
Figure 4 Decortication. The chest

is entered through a posterolateral
thoracotomy at the fifth or sixth
interspace.
Skin Incision
and the serratus anterior should be spared because either or both operated on, coupled with continuous positive airway pressure
might subsequently be required for a transposition muscle flap. (CPAP), should provide appropriate countertraction from the
Because the chest is often rigid and contracted as a result of the underlying lung parenchyma.
underlying inflammatory process, it may be helpful to resect a rib An incision is made in the pleural peel, and the appropriate
in a subperiosteal fashion. This measure facilitates exposure and decortication plane is identified [see Figure 6a].The pleural peel is
helps define the extrapleural plane for the initiation of parietal then grasped with hemostats, and blunt and sharp dissection is
pleurectomy. carried out over a broad area to separate the peel from the viscer-
When the disease process is chronic (i.e., has lasted longer than al pleura [see Figure 6b]; a sponge-ball or peanut dissector may be
6 weeks), the parietal pleura and the visceral pleura are often useful for this purpose. Care must be taken to keep from injuring
fused. In this situation, one would proceed with pleurectomy. the underlying pulmonary parenchyma, which is fragile; inadver-
When adhesions are present between the pleural layers but the vis- tent injury may result in prolonged and unnecessary air leaks.
ceral pleura has not fused with the parietal pleura [see Figure 5], Some degree of patience is required, in that this operation often
the adhesions may be lysed with a combination of sharp dissection becomes tedious. For an optimal surgical outcome, all portions of
and electrocauterization. the lung encased by the peel should be addressed.To this end, it is
The key to a technically successful decortication is to define the often necessary to follow the peel into the fissure, down onto the
correct plane between the pleural peel and the visceral pleura. If diaphragm, and into the posterior and anterior sulci. At times, a
the pleural resection is inadequate, lung expansion will be com- second entry point into the chest through another interspace may
promised. If the pleurectomy is too deep, parenchymal injury will be required to achieve an optimal technical result. Should better
result, bleeding and air leakage will occur, and postoperative exposure be deemed necessary, one should not hesitate to proceed
recovery will be prolonged. Gentle manual ventilation of the lung with this counterincision.
Figure 5 Decortication. Any

adhesions between the visceral pleura
and the parietal pleura are lysed with
a combination of sharp dissection and
electrocauterization.
Adhesions between
Visceral and Parietal
Pleura
a Pleural Peel
Incision into
Pleural Peel
Visceral Pleura
Pleural Peel
Figure 6 Decortication. (a) With

the lung expanded, the pleural
peel is sharply incised, and the
appropriate decortication plane is
identified. (b) The peel is separat-
ed from the visceral pleura with
blunt and sharp dissection.
Visceral Pleura
Once resected, the peel is sent for pathologic and microbiolog- tus. Concerns related to residual space may be managed by means
ic evaluation. The lung is tested to confirm that it is capable of of open tube thoracostomy, open window thoracostomy, or place-
complete reexpansion. Any large parenchymal air leaks that are ment of a muscle flap. On rare occasions, thoracoplasty with mul-
noted may be oversewn, but this step often is not necessary. The tiple rib resection may be considered to obliterate any infection in
various pulmonary parenchymal sealants now commercially avail- the residual space by bringing the chest wall down to fill the space.
able may reasonably be considered for control of parenchymal air-
leaks. Chest tubes are placed—typically, one along the diaphragm,
a second anteriorly, and a third posteriorly, toward the apex. Outcome Evaluation
Provided that the lung is satisfactorily reexpanded, air leaks will The morbidity and mortality to be expected after decortication
seal promptly. Hemostasis must be ensured: a residual hemotho- depend on the severity of the underlying illness and on the occur-
rax in a patient with a pleural space infection will serve as a nidus rence of perioperative complications. In a review from 1985, mor-
for ongoing infection. tality was less than 8%.13 Complications tend to be either infec-
The role of parietal pleurectomy in this setting remains unclear. tion related (e.g., perioperative sepsis syndrome) or technique
Opinions differ, but objective data are sparse. Parietal pleurectomy related (e.g., bronchopleural fistula, hemorrhage, and persistent
does result in some improvement of the mechanics of the thoracic air leakage); some of them may necessitate additional surgical
cage12; however, it also increases the risk of bleeding, prolongs the intervention. As with all operations in the chest, close attention to
procedure, and places vital intrathoracic structures (e.g., the detail and meticulous surgical technique are critical for minimiz-
phrenic and vagus nerves, the esophagus, the brachial plexus, and ing the incidence of postoperative complications.
certain blood vessels) at risk for injury. In addition, it is often pos- The degree of functional improvement attained after decortica-
sible that the pleural process will resolve without parietal pleurec- tion depends primarily on the presence and extent of disease in
tomy once the underlying issues are addressed. The technically the underlying lung parenchyma.14-16 If the parenchyma of the
optimal strategy may be to adopt a compromise approach—that is, lung is normal, complete reexpansion of the lung and obliteration
to perform a partial parietal pleurectomy and to take extra care of the pleural space should be achievable. Lung volumes usually
when dissecting near the vital mediastinal structures. improve measurably after decortication, but they generally do not
Postoperative management of the chest tube is dictated by cul- return to normal.14,17 Changes within the chest (i.e., mediastinal
ture results, intraoperative findings, and the patient’s clinical sta- shift and elevation of the diaphragm, with a resultant decrease in
Table 2 Causes of Failed Decortication Inability to define the plane of dissection between the peel and
the visceral pleura is an especially troublesome technical chal-
Active tuberculosis or invasive pulmonary infection lenge that can adversely affect results. If visceral pleurectomy is
Underlying
parenchymal disease
Bronchial stenosis performed, air leakage and postoperative hemorrhage may com-
Chronic lung collapse promise pulmonary function. Care must be taken throughout
Residual space the operation to protect the phrenic nerve from injury; fortu-
Inadequate lung expansion nately, this usually is not an issue, because the mediastinal pleu-
Technical considerations
Air leakage ra is rarely involved in the inflammatory process. Incomplete
Postoperative hemothorax parietal pleurectomy or inability to free the diaphragm may also
compromise results.
If patients are appropriately selected, complete reexpansion of
the lung after decortication can usually be achieved. Occasionally,
the size of the thorax) may account for this finding. It is unclear to however, an issue related to residual pleural space may arise after
what extent the expected functional improvement is influenced by an otherwise technically satisfactory decortication. If this space is
whether the pleural process is acute or chronic. Some authors have not obliterated, failure is inevitable. Options for addressing the
observed an association between shorter durations of pleural dis- residual space problem include thoracoplasty and tissue transpo-
ease before treatment and improved outcomes18,19; others have not sition. Either the latissimus dorsi or the abdominal omentum will
observed such an association.14 Failure to achieve improvement provide sufficient bulk for obliteration of the residual space.20,21
after decortication appears to be most strongly related to errors of The omentum is preferable when the space is in the inferior
surgical judgment (in particular, poor patient selection) and to hemithorax, whereas the latissimus dorsi is preferable when the
insufficiently meticulous surgical technique (leading to periopera- space is in the superior hemithorax. At the time of the initial inci-
tive complications). sion, the surgeon should keep in mind the possibility that tissue
Although to date, no studies have dealt specifically with fail- transposition may eventually prove necessary and should therefore
ure after decortication, it is likely that technical difficulties are opt for a muscle-sparing thoracotomy if possible.
the most common cause of such failure, with the main problem At present, the use of thoracoscopy to address fibrothorax
being inadequate obliteration of the pleural space [see Table 2]. definitively cannot be recommended.
References
1. Samson PC, Merrill DL, Dugan DJ, et al:Technical 9. Savage T, Flemin JA: Decortication of the lung in improvement following decortication in pulmonary
considerations in decortication for the pleural com- tuberculous disease. Thorax 10:293, 1955 tuberculosis. Ann Thor Surg 1:532, 1965
plications of pulmonary tuberculosis. J Thorac Surg 10. Magdeleinat P, Icard P, Pouzet B, et al: Indications 17. LeMense GF, Strange CH, Sahn S: Empyema tho-
Cardiovasc 36:431, 1958 actuelles et resultats des decortications pulmonaries racis: therapeutic management and outcome. Chest
2. Wachsmuth W, Schautz R: Untersuchungen uber die pour pleurisies purulentes non tuberculeuses. Ann 107:1532, 1994
Lungen-Pleura-Grenzschicht beider extrapleuralen Chir 53:41, 1999
18. Carroll D, McClement J, Himmelstein A, et al:
Dekortikation. Chirurg 22:237, 1961 11. Kaiser LR: Pleurectomy and decortication. Atlas of Pulmonary function following decortication of the
3. Drummond DS, Craig RH:Traumatic hemothorax: General Thoracic Surgery. Philadelphia, Mosby- lung. Am Rev Tuberc 63:231, 1951
complications and management. Am Surg 33:404, Year Book, 1997
19. Morton JR, Boushy SF, Guinn GA: Physiological
1967 12. Waterman DH, Domm SE, Roger WK: A clinical evaluation of results of pulmonary decortication. Ann
evaluation of decortication. J Thorac Cardiovasc Surg Thorac Surg 4:321, 1970
4. Bollinger CT, de Kock MA: Influence of a fibrotho-
33:1, 1957
rax on the flow volume curve. Respiration 54:197, 20. Marshall MD, Kaiser LR, Kucharczuk JC: Simple
1988 13. Mayo P: Early thoracotomy and decortication for technique for maximal thoracic muscle harvest. Ann
nontuberculous empyema in adults with and with- Thorac Surg 4:1465, 2004
5. Wilson JM, et al: Traumatic hemothorax: is decorti-
out underlying disease: a twenty-five year review. Am
cation necessary? J Thorac Cardiovasc Surg 77:494, Surg 51:230, 1985 21. Shrager JB, Wain JC, Wright CD, et al: Omentum is
1979 highly effective in the management of complex car-
14. Patton WE, Watson TR, Gaensler EA: Pulmonary
6. Milfield DJ, Mattox KL, Beall AC: Early evacuation diothoracic surgical problems. J Thorac Cardiovasc
function before and at intervals after surgical decor-
of clotted hemothorax. Am J Surg 136:686, 1978 Surg 125:526, 2003
tication of the lung. Surg Gynecol Obstet 95:477,
7. Beall AC, Crawford HW, DeBakey ME: Consider- 1952
ations in the management of acute traumatic hemo- 15. Siebens AA, Storey CF, Newman MM, et al: The
thorax. J Thorac Cardiovasc Surg 52:353, 1966 physiological effects of fibrothorax and the function-
8. Deslauriers J, Mehran RJ: Role of thoracoscopy in al results of surgical treatment. J Thorac Surg 32:53, Acknowledgment
the diagnosis and management of pleural disease. 1956
Semin Thorac Cardiovasc Surg 5:284, 1993 16. Barker WL, Neuhaus H, Langston HT: Ventilatory Figures 4 through 6 Alice Y. Chen.
4 THORAX 14 PULMONARY RESECTION — 1
14 PULMONARY RESECTION
Min P. Kim, MD, and Ara Vaporciyan, MD, FACS
Anatomic resections of the lung (including pneumonectomy function. When wedge resection was compared with lobec-
and lobectomy) are the standard operative techniques tomy for tumors smaller than 3 cm there was a higher local
employed to treat both neoplastic and nonneoplastic diseases recurrence rate after a wedge resection compared with a lobec-
of the lung. In neoplastic disease of the lung the disease pro- tomy. Based on these data the current recommendation is to
cess can be divided between primary and metastatic lung can- perform a lobectomy if the patient’s pulmonary status will tol-
cers. In patients with primary lung cancer, the staging of the erate that volume of resection. A minimally invasive lobectomy
patient is critical to provide best therapy for the patient. can be substituted for an open lobectomy although the pres-
There is no role of pulmonary resection for patients with ence of hilar nodal involvement by tumor or granulomatous
metastatic disease or stage IV disease. In terms of the nodal disease is a relative contraindication to this procedure. For
stations, pulmonary resection maybe offered in patients with metastatic tumors and diagnostic resections of pulmonary
N1 disease or metastatic cancer to ipsilateral hilar lymph nodules a wedge resection, if feasible, is considered adequate.
nodes (level 10, 11, 12, 13, 14). There is controversy about In addition, it is essential to carry out a thorough evaluation of
the role of pulmonary resection in patients with N2 disease all other systems, especially the cardiac system. In patients
or metastatic cancer to ipsilateral mediastinal lymph nodes who have received preoperative chemotherapy, the hemato-
(on right: level 2R, 4R, 7 and on left: level 2L, 4L, 5, 6, 7). logic and renal systems should receive particular attention.
The options include either induction chemotherapy followed
by surgery then consolidative radiation to the mediastinum,
induction chemoradiotherapy followed by surgery, or chemo- Operative Planning
radiation therapy without surgery. The final option is most anes thes ia
commonly chosen when multiple N2 lymph nodes are
involved, the nodal disease is bulky and deemed unresectable, Although pulmonary resections can be performed with bilat-
or when the surgical risk is felt to be too high (for example eral lung ventilation, careful hilar dissection is greatly facilitated
when a right pneumonectomy is required). Finally, there is by using unilateral lung ventilation. The advent of double-
no role for pulmonary resection in patients with N3 disease lumen endotracheal tubes and bronchial blockers has made it
or metastatic cancer to contralateral mediastinal lymph nodes. possible to isolate the ipsilateral lung and has made it easier for
In patients with no nodal or metastatic disease, pulmonary surgeons to carry out complex hilar dissections with the required
resection is a primary therapy. Any surgeon who intends to precision. In patients with centrally located tumors, care must
operate on the pulmonary system must be keenly aware of the be taken with tube placement: inadvertent trauma to an endo-
anatomy of the pulmonary vasculature and the bronchi and bronchial tumor during placement of a double-lumen tube can
the relation between the two. There is no substitute for this lead to significant bleeding and compromise of the airway.
degree of familiarity. Detailed discussions are available in Bronchoscopic confirmation of tube position is recommended
existing anatomy textbooks. In what follows, we describe sev- after the patient has been positioned.
eral of the more common techniques employed for anatomic Requirements for monitoring and intravenous access are
resections of the lung. determined by the patient’s preoperative status and by the
complexity of the resection. In most cases, the standard prac-
tice is to place a radial arterial catheter, two large-bore periph-
Preoperative Evaluation eral intravenous catheters, and a Foley catheter, with more
Detailed discussion of the physiologic evaluation of the invasive monitoring employed if mandated by the patient’s
patient and of the indications for lobectomy or pneumonec- clinical condition. Thoracic epidural catheters are also com-
tomy is beyond the scope of this chapter. In general, the patient monly employed for postoperative pain control. If carefully
must have sufficient pulmonary reserve to tolerate the planned placed by an experienced anesthesiologist, these catheters can
resection. A common contraindication for surgery is an esti- remain in place for as long as 7 days or until the chest tubes
mated postresectional forced expiratory volume in 1 second are removed.
(FEV1) and carbon monoxide diffusion capacity (DLCO) of
less than 35 to 40%. The choice of what volume of lung to p atient p os itioning
resect for lung cancer should be a balance between achieving Patients are routinely placed in the lateral decubitus posi-
an adequate oncologic outcome and preservation of pulmonary tion, with the table flexed just cephalad to the superior iliac
DOI 10.2310/7800.S04C14
10/09
crest. This positioning allows sufficient access for most inci- inspected and palpated. In patients with malignant disease,
sions. If an anterior thoracotomy or a sternotomy is planned, biopsies of any suspicious nodules are performed. The pres-
the patient may be placed in the supine position, with a pillow ence or absence of pleural fluid should be noted; if fluid is
placed in such a way as to elevate the area of the thorax that present, it should be aspirated and sent for immediate cyto-
will be operated on. logic analysis.
When the patient is in the lateral decubitus position, sev- Frequently, the fissures are incomplete as a consequence of
eral measures should be adopted to guard against injury. congenital absence, inflammatory disease, or a neoplasm. If
Adequate padding should be employed to prevent the devel- the adhesions within the fissure are filmy, they may be divided
opment of pressure points on the contralateral lower extrem- sharply or with the electrocautery while the lung is being
ity. A low axillary roll should be used to prevent injury to the ventilated. If the adhesions are more densely adherent, the
contralateral brachial plexus and shoulder girdle. Finally, fissures may have to be completed with staplers. During
adequate padding should be placed beneath the head to keep resection for malignancy, any evidence of tumor extension
the cervical spine in a neutral position. across a fissure or of hilar nodal involvement should be noted.
A decision is then made regarding the extent of the required
g e n e ral t e chn ica l c o n si d e r a t i o n s resection. If there is only minor extension, wedge resection of
Incisions a portion of the additional lobe is indicated. If, however, the
involvement is significant, segmentectomy, bilobectomy, or
Posterior lateral thoracotomy remains the standard incision
pneumonectomy may be indicated. Often we develop the fis-
for anatomic pulmonary resections; however, safe and com-
sures during ventilation until a dense or incomplete region is
plete resections can also be performed through a variety of
encountered, at which point we complete the remainder of
smaller incisions, including posterior muscle-sparing, anterior
the fissure with staples. For this approach to work, the vascu-
muscle-sparing, and axillary thoracotomies. In most cases, the
lar and bronchial anatomy must already have been completely
thorax is entered at the fifth intercostal space, an approach
delineated. If the vascular structures cannot be identified in
that affords excellent exposure of the hilar structures. The
the fissure because the fissure is fused, the pulmonary artery
anterior muscle-sparing thoracotomy is generally placed at the
branches will have to be approached from the anterior and
fourth intercostal space because of the more caudal position-
posterior hilum.
ing of the anterior aspects of the ribs. Although a sternotomy
Traditionally, during a lobectomy, the arterial branches are
may be employed to gain access to the upper lobes, it does not
divided first, followed by the venous branches. However, if
provide good exposure of the lower lobes and the bronchi.
conditions exist that limit exposure (e.g., a centrally placed
Thoracoscopic lobectomy [see 4:10 Video-Assisted Thoracic
tumor or significant inflammation and scarring), the surgeon
Surgery] is being performed with increasing frequency, espe-
should start with the structures that provide the most acces-
cially for early-stage lesions. This procedure employs two or
sible targets. Veins may be ligated first. Proponents of this
three 1 cm ports and a utility thoracotomy (frequently in the
approach believe that it may limit the escape of circulating
axillary position) for instrumentation and removal of the
tumor cells (an event that rarely, if ever, occurs); opponents
specimen. Rib spreading is not necessary, because visualiza-
claim that initial vein ligation may lead to venous congestion
tion is achieved via the thoracoscope. The various thoraco-
and retention of blood that is subsequently lost with the spec-
scopic lobar resections are generally similar with regard to
imen, although peribronchial venous channels will frequently
isolation and division of the hilar vessels and bronchi. Com-
prevent this result. The bronchus may also be ligated first.
plete nodal dissections are also performed thoracoscopically.
However, two points should be kept in mind if this is done.
The main advantages of this approach seem to be reduced
First, the distal limb of the bronchus (the specimen side)
postoperative pain and earlier return to normal activity, but
should be oversewn to prevent drainage of mucus into the
to date, no randomized trials have shown these advantages to
chest. Second, after division of the bronchus, the lobe is
be significant. Because of the technical challenges posed by
much more mobile; therefore, to prevent avulsion of the pul-
thoracoscopic pulmonary resections, surgeons should have a
monary artery branches, care should be taken not to employ
complete mastery of the hilar anatomy before attempting
excessive torsion or traction.
these procedures.
The techniques used for dissection, ligation, and division
of pulmonary arteries and their branches differ from those
Special Intraoperative Issues used for other vessels. Pulmonary vessels are low-pressure,
Upon entry into the thoracic cavity, all benign-appearing high-flow, thin-walled, fragile structures. Accordingly, for
filmy adhesions should be mobilized. Any malignant-appearing, rapid and safe dissection, a perivascular plane, known as the
broad-based, or dense adhesions should be noted, and a plane of Leriche, should be sought. This plane may be absent
decision whether to perform an extrapleural dissection or a in the presence of long-standing granulomatous or tubercu-
chest wall resection should be made on the basis of the depth lous disease, after major chemotherapy, after thoracic radio-
of involvement and the preoperative imaging studies. If there is therapy, and in cases of reoperation. In these situations,
reason to believe that the chest wall or the parietal pleura may proximal control of the main pulmonary artery and the two
be involved, a more aggressive approach may be required to pulmonary veins may be necessary before the more periph-
achieve a complete resection. These techniques are beyond the eral arterial dissection can be started. Before any pulmonary
scope of this chapter. vessel is divided, it should be controlled either with two sep-
Once the lung is freed of all adhesions, the inferior pulmo- arate suture ligatures proximal to the line of division or with
nary ligament is divided and the lung rendered completely vascular staples; stapling devices are especially useful for
atelectatic. The entire lung and the parietal pleura are larger vessels.
10/09
Exposure of the bronchus should not involve stripping the resections (i.e., lobectomy, segmentectomy, and wedge resec-
bronchial surface of its adventitia. Aggressive dissection may tion); however, careful use of water seal in selected patients
compromise the vascular supply and lead to impaired healing (i.e., those with small air leaks whose lungs do not collapse
and bronchial dehiscence. Overlying nodal tissues should be while on water seal) may allow earlier withdrawal of the
cleared, and major bronchial arteries should be clipped just tube.
proximal to the point of division. Bronchial closure has been
greatly facilitated by the use of automatic staplers. Because
the bronchus is frequently the last structure to be divided Operative Technique
before removal of the specimen, we often apply staples only initial s tep s
to the proximal side of the bronchus and divide the bronchus
After making a posterior lateral thoracotomy and exposing
distal to the staple line. Once the stapler is applied, every
the chest cavity through the fifth intercostal space, the inferior
effort should be made to minimize its movement during firing
pulmonary ligament is taken down and the hilum is mobi-
so as to prevent injury to the remaining proximal bronchial
lized. A lung grasper is used to provide tension on the lower
segment. With the stapler applied but not yet fired, the
lobe, and the inferior pulmonary ligament is taken down
remaining lung should be ventilated to determine whether
using a cautery or bluntly to the inferior pulmonary vein. One
there is any impairment of ventilation secondary to placement
needs to be very careful not to injure the pulmonary vein.
of the stapler too close to a proximal lobar bronchus. Only
After this is done, the lung is freed of any filmy pleural attach-
when the absence of ventilatory impairment has been con-
ments. Dense attachments may indicate chest wall involve-
firmed should the stapler be fired. When bronchial length is
ment and should be approached as such.
limited, one may perform suture closure of the bronchial
stump rather than attempt to force a stapler around the right lu ng
bronchus. Whenever there is a high risk of bronchial stump
dehiscence (e.g., after chemotherapy, radiotherapy, or chemo- Right Hilar Dissection
radiotherapy; in patients for whom adjuvant therapy is In the right thoracic cavity, it is important to identify the
planned; or after right pneumonectomy), a vascularized rota- inferior pulmonary vein draining the right lower lobe, supe-
tional tissue flap (e.g., from the pericardium, the pericardial rior pulmonary vein draining the right upper and right middle
fat pad, or intercostal muscle) should be used to reinforce the lobe, the main pulmonary artery, and the truncus anterior
bronchial closure. branch of the pulmonary artery. In addition, the right main
bronchus and the right upper-lobe takeoff and the right bron-
chus intermedius should be identified. Then the lung is
Closure and Drainage rotated posteriorly, and the pleura is incised posterior to the
Once the bronchial closure is complete, the next step is to course of the phrenic nerve, which usually passes close to the
test its adequacy. The bronchial stump is submerged under base of the superior pulmonary vein. The phrenic nerve is
normal saline, and the lung is inflated to a tracheal pressure carefully and gently mobilized anteriorly, avoiding the use of
of 45 cm H2O. Any area of hilar dissection and divided fis- cautery. This will expose the superior pulmonary vein and
sures should be evaluated in a similar fashion. Significant inferior pulmonary vein. The right upper lobe is then rotated
parenchymal air leaks should be repaired with interrupted more inferiorly to provide a better view of the superior aspect
fine sutures (e.g., 4-0 polypropylene). If the air leak is from a of the hilum. This step allows complete exposure of the trun-
diffuse raw surface, especially after upper lobectomy, con- cus anterior branch of the pulmonary artery. Finally, the lung
struction of a pleural tent should be considered. Any air leak is rotated anteriorly, and the right main bronchus as well as
from the bronchial stump should be assessed very carefully. the right upper-lobe bronchus and the bronchus intermedius
A simple repair with fine absorbable sutures may suffice, or are exposed.
the entire closure may have to be redone. Strong consider-
ation should be given to reinforcing the stump with vascular- Right Upper Lobectomy
ized tissue (see above). Pulmonary arteries: truncus anterior and posterior
The chest is usually drained with two chest tubes that are ascending Two branches of the pulmonary artery go into
positioned anteriorly and posteriorly and exit through sepa- the right upper lobe: the truncus anterior and posterior ascend-
rate stab incisions in the chest wall. If an epidural or a para- ing arteries. The truncus anterior is the first branch coming off
vertebral catheter is being employed for postoperative pain the main pulmonary artery and, most of the time, is a large
management, the chest tubes should exit through an intercos- branch that immediately bifurcates to two arteries; however,
tal space that is no more than two spaces below the intercos- at times two truncus anterior arteries may be coming off the
tal space used for entry into the chest. Failure to follow this pulmonary artery. It is imperative that dissection be performed
recommendation is likely to result in pain originating from the with care. Once the vessel is exposed, it is either suture-ligated
chest tube site that will not be adequately addressed postop- and divided or transected with an endovascular stapler.
eratively and will lead to a significant increase in discomfort. It is very important to accurately identify all the vessels to
After a pneumonectomy, the chest tubes can be omitted. If prevent inadvertent ligation of the wrong artery. To expose the
this option is chosen, a needle should be used to aspirate posterior ascending pulmonary artery, the dissection begins
1,000 to 1,200 mL of air from the hemithorax operated on within the interlobar fissure, and the pulmonary artery is
after closure of the skin. If a chest tube is used, a balanced exposed at the junction of the major and minor fissures [see
drainage system is employed without suction. At most institu- Figure 1]. In many cases, the artery is partially obscured by a
tions, suction is employed postoperatively for all other level 11 interlobar lymph node, which should be removed. Also
10/09
Right ing the pleura in the posterior hilum along the lateral edge of
Middle the bronchus intermedius. A level 11 lymph node will be
Interlobar Lobe encountered between the right upper-lobe bronchus and the
Pulmonary bronchus intermedius. Removal of this interlobar node (some-
Posterior Artery Right Middle-
Lobe Artery times referred to as the “sump node”) will expose the poste-
Segmental
Branch of Basilar Segmental rior ascending branch of the pulmonary artery. A right-angle
Right Superior Arteries to Right clamp can be passed from the interlobar fissure between the
Pulmonary Vein Lower Lobe superior segmental branch of the pulmonary artery and the
Right posterior ascending pulmonary artery to the opening between
Lower the right upper-lobe bronchus and the bronchus intermedius.
Lobe A silk can be placed through this opening, which will guide in
separation of the right upper lobe and the right lower lobe.
The fissure can be completed with gastrointestinal anastomo-
sis (GIA) staplers. The posterior ascending artery can be
ligated and divided after completion of the fissure.
Pulmonary vein: right upper-lobe branch of the supe-
rior pulmonary vein The superior pulmonary vein is dis-
sected, and the apical, anterior, and posterior branches are
encircled [see Figure 2]. Care is taken to preserve the middle-
lobe branches. Both the right upper lobe and the middle lobe
often drain into the superior pulmonary vein. However, at
Right times the right middle lobe may drain into the inferior pulmo-
Upper nary vein or into both the superior and the inferior pulmonary
Lobe
vein. The right middle-lobe pulmonary vein branch has to be
Superior
Posterior Ascending clearly identified prior to taking the right upper-lobe pulmonary
Segmental
Branch to Right vein branches. The branches draining the upper lobe are then
Branch to Right
Upper Lobe ligated and divided or controlled with a vascular stapler. Divi-
Lower Lobe
sion of the veins before division of the arterial supply will not
Figure 1 Right upper lobectomy. Shown is the surgeon’s cause the lobe to become engorged. Instead, through collateral
view of the right interlobar fissure. The fissures have been venous drainage to the middle lobe or via bronchial venous
completed, and the segmental arteries to the upper, middle, channels, blood will be shunted away from the upper lobe.
and lower lobes have been identified. The posterior ascending Fissure between the right upper lobe and the right
branch to the upper lobe most commonly varies with respect middle lobe After the division of the right upper-lobe pul-
to size and origin. This vessel may be absent or diminutive
monary veins, the interlobar (or truncus posterior) branch of
and may arise from the superior segmental branch to the
the right pulmonary artery will be visible as it courses poste-
lower lobe. The posterior segmental vein draining into the
superior pulmonary vein (not seen) is clearly visualized in the rior to the superior pulmonary vein branches. Dissection con-
right upper lobe, lateral to the pulmonary artery branches. tinues along the lateral surface of the interlobar artery. Once
the branches to the middle-lobe artery are identified, the dis-
section should reach the region previously dissected within
the fissure. A right-angle clamp can be used to pass a silk
present is the posterior segmental branch of the superior along this opening and keep the right middle pulmonary
pulmonary vein, which traverses the fissure in a posterior-to- artery and vein with the right middle lobe. The fissure between
anterior direction. The pulmonary artery lies medial and the middle lobe and the upper lobe can now be completed
inferior to this venous branch. Once the pulmonary artery is through serial application of GIA staplers.
identified, the branches within the fissure are exposed, includ- Right upper-lobe bronchus The upper lobe is retracted
ing the posterior ascending artery to the right upper lobe. The superiorly and posteriorly, and the interlobar artery is gently
posterior ascending artery typically comes off the main pulmo- retracted anteriorly. The bronchus to the right upper lobe is
nary artery opposite to the right middle-lobe pulmonary artery. circumferentially exposed, and all nodal tissue surrounding
However, at times there may be no posterior ascending artery the right upper-lobe bronchus is swept distally so that it can
or there may be two posterior ascending arteries, or the poste- be included with the specimen. Every effort is made to avoid
rior ascending artery may originate as a branch of the superior devascularizing the bronchus. Once an adequate length of the
segment artery to the right lower lobe. Distal to the posterior right upper-lobe bronchus is exposed, the lung is rotated
ascending artery is the superior segmental artery to the right anteriorly to allow visualization of the course of the bronchus
lower lobe and the basilar branches to the right lower lobe. If intermedius. The bronchus is ligated with a transverse anas-
the exposure is adequate, the posterior ascending branch can tomosis (TA)–30 stapler loaded with 4.8 mm staples. Care is
be ligated and divided. taken to achieve close apposition of the anterior wall to the
Fissure between the right lower lobe and the right posterior membranous wall of the bronchus. With the stapler
upper lobe If additional length is required to expose the applied but not fired, the right lung is ventilated to confirm
posterior ascending artery, the fissure between the superior that the bronchus intermedius has not been compromised.
segment of the lower lobe and the posterior segment of the The stapler is fired, the bronchus is divided, and the speci-
upper lobe can be completed. This is accomplished by open- men is removed.
10/09
To prevent middle-lobe syndrome resulting from torsion of posteriorly to expose the superior pulmonary vein [see
the narrow hilum of the middle lobe after an upper lobectomy, Figure 2]. The branches to the middle lobe are carefully iden-
the middle lobe should be secured to the lower lobe. Once the tified, doubly ligated, and divided. The posterior segmental
lungs are reexpanded, a small portion of the lower lobe and a branch of the superior pulmonary vein should now be easily
comparable portion of the middle lobe are grasped along the identifiable, originating just cephalad to the middle-lobe vein
major fissure. A single application (or, at most, two applica- and coursing posteriorly (lateral to the interlobar artery) to
tions) of a TA stapler should suffice to secure the lobes to each drain the posterior segment of the right upper lobe. As noted
other at this site and thus prevent middle-lobe torsion. (see above), this venous branch is easily identified during dis-
section of the interlobar artery within the fissure.
Right Middle Lobectomy Fissure between the right upper and middle lobes and
Pulmonary arteries: one or two right middle-lobe fissure between the right middle and lower lobes To
pulmonary arteries The initial steps in a right middle complete the fissure between the upper and middle lobes,
lobectomy are similar to those in a right upper lobectomy. dissection continues along the caudal and lateral surface of
The pulmonary artery and its branches are identified within the posterior segmental venous branch until the previously
the fissure. The middle-lobe artery is identified [see Figure 1]. performed dissection of the interlobar artery within the fissure
Not infrequently, there are two middle-lobe arteries. When is reached. The fissure is then completed through serial appli-
this is the case, the most proximal branch is commonly cation of GIA staplers. When the fissure is complete, the sur-
located across from the posterior ascending branch to the geon has a clear view of the posterior segmental branch of the
right upper lobe. Once the anatomy has been confirmed, the superior pulmonary vein and the interlobar branch of the pul-
arterial branches to the middle lobe can be individually ligated monary artery coursing posterior and medial to the veins. If
and divided. If additional exposure is needed before ligation, the proximal arterial branch to the middle lobe could not be
the fissures can be completed to yield added exposure of a safely ligated from the fissure before, it should be easily acces-
proximal middle-lobe artery. sible now. The fissure between the right middle and lower
Pulmonary vein: right middle-lobe branch of the lobes can be completed using serial application of the GIA
superior pulmonary vein Once the arteries are divided staplers by keeping the right middle lobe and the right
(or if additional exposure is required), the lung is rotated middle-lobe bronchus to one side and the right lower lobe
Phrenic Right Mainstem Pericardium

Nerve Bronchus
Right
Pulmonary Artery
Superior
Vena Cava
Trachea Right Superior

Pulmonary Vein
Azygos
Vein
Middle-Lobe
Vein
Vagus
Nerve Pulmonary
Ligament
Posterior Segmental
Right Vein to Right Upper Lobe
Upper Lobe
Truncus Interlobar Artery
Anterior Branch
Figure 2 Right upper lobectomy. Shown is the surgeon’s view of the anterior right hilum. The apical venous branches of the
superior pulmonary vein obscure the interlobar pulmonary artery and, to a lesser degree, the truncus anterior branch. Division
of these venous branches during upper lobectomy improves exposure of the truncus anterior. The splitting of the main pulmo-
nary artery into its two main branches may occur more proximally, and care should be taken to identify both branches before
either one is divided. Another significant possible variation is a branch of the middle-lobe vein that arises from the intrapericar-
dial portion of the superior pulmonary vein.
10/09
with the basilar branches of the pulmonary artery and the segmental artery is encircled and doubly ligated, with care
right lower-lobe bronchus to the other side. taken not to injure the posterior ascending branch if it arises
Right middle-lobe bronchus The middle lobe is then from or close to the origin of the superior segmental branch.
rotated superiorly and posteriorly to expose the right middle- The basilar segmental branches are then encircled and doubly
lobe bronchus [see Figure 3], which usually arises anterior and ligated, with the same care taken not to injure the middle-
inferior to the right middle-lobe branches of the pulmonary lobe branch. Both vessels are then divided.
artery. The basilar artery branches to the right lower lobe are Fissure between the right upper lobe and right lower
gently mobilized posteriorly to expose the bronchus interme- lobe The fissure between the superior segment of the
dius and the origin of the right middle-lobe bronchus. lower lobe and the posterior segment of the upper lobe is
Peribronchial lymph nodes located in this region should be frequently incomplete. If necessary, it is completed as
dissected and removed, with care taken not to injure the previously described [see Right Upper Lobectomy, above].
bronchial arterial branches. Once the bronchus is free, it is The pleura is incised along the bronchus intermedius, and
either divided and ligated with an automatic stapler or the lymph node (sump node) just distal to the takeoff of the
transected and oversewn as previously described (see above). right upper-lobe bronchus is removed so that the previously
dissected pulmonary artery is exposed. Serial application of
Right Lower Lobectomy GIA staplers is employed to complete the fissure.
Fissure between the right middle lobe and right lower
Pulmonary artery: superior segmental branch and
lobe The fissure between the middle and lower lobes may also
basilar branches Once again, the pulmonary artery is
have to be completed (although, in many cases, it is congenitally
exposed within the oblique fissure. The pulmonary branches
complete). The pleura is incised within the anterior hilum to
to the superior segment and the basilar segments of the right
allow identification of the superior and inferior pulmonary
lower lobe are identified [see Figure 1]. Most of the time, there
veins. The basilar segmental bronchi and the middle-lobe bron-
is one branch to the superior segment of the right lower lobe;
chus should be exposed. Removal of lymphoid tissue allows
however, at times there are two branches, and, rarely, there
easy application of a GIA stapler to complete the fissure.
is a common branch that gives rise to the posterior ascending
Pulmonary vein: inferior pulmonary vein The infe-
branch of the right upper lobe and the superior segmental
rior pulmonary vein is then encircled as it exits the pericar-
branch of the right lower lobe. Careful identification of the
dium [see Figure 4]. This step is facilitated by dissecting the
pulmonary artery is important. All branches within the fissure
superior edge of the inferior pulmonary vein with the lung
are identified, including the middle-lobe artery and the pos-
rotated first anteriorly and then posteriorly. Once encircled,
terior ascending branch to the right upper lobe. The superior
the pulmonary vein can easily be ligated and divided with a
vascular stapler. An infrequent anatomic variant is a vein
Ligated Stump
Middle- draining the posterior segment of the right upper lobe into
of Right Middle-
Lobe Artery Lobe the inferior pulmonary vein. Although an effort can be made
Right Bronchus to save this branch, there is adequate collateral venous drain-
Middle Lobe age within the right upper lobe to allow this branch to be
Right sacrificed without consequences.
Upper Lobe
Right Mainstem Inferior

Right Lower Bronchus Pulmonary Vein
Lobe
Figure 4 Right lower lobectomy. Shown is the surgeon’s view
Figure 3 Right middle lobectomy. Shown is the surgeon’s of the right inferior pulmonary vein. For encirclement of this
view of the right middle-lobe bronchus. Gentle retraction of the vein, dissection may also have to be performed on its anterior
basilar segmental artery to the lower lobe posteriorly allows surface. The branch to the superior segment can be seen
clear visualization of the origin of the middle-lobe bronchus. overlying the origin of the superior segmental bronchus.
10/09
Right lower-lobe bronchus Division of the lower-lobe the right pulmonary artery is exposed as it exits the pericar-
bronchus is best accomplished through the fissure; this dium posterior to the vena cava. Care is taken not to dissect
approach facilitates identification of the middle-lobe bron- distally on the vessel and not to encircle only the truncus
chus and helps prevent inadvertent damage to or compromise anterior branch by mistake. Ligation and division of the right
of the origin of this structure. Level 11 and 12 lymph nodes pulmonary artery can be accomplished in several different
are cleared distally along the bronchi to expose the origin of ways; either dividing the vessel between clamps and oversew-
the superior segmental bronchus [see Figure 5 ]. In some ing it with 3-0 nonabsorbable suture material or using vascu-
patients, there is adequate length to permit oblique place- lar staplers is acceptable.
ment of a stapler for control of all of the lower-lobe segmen- Pulmonary vein: superior and inferior pulmonary
tal bronchi without compromise of the middle-lobe bronchus. vein Next, attention is directed toward the superior pulmo-
If this step is not possible, separate ligation and division of nary vein. The vessel is mobilized on its superior and inferior
the superior segmental bronchus and of all the basilar bronchi aspects with blunt and sharp dissection, encircled with blunt
as a unit should be performed. dissection, and ligated and divided with either clamps or a
The lung is rotated anteriorly, and the bronchus interme- vascular stapler. With the lung retracted superiorly, the infe-
dius is dissected distally until the origin of the superior seg- rior pulmonary vein is dissected as in a right lower lobectomy
mental bronchus is identified from this side. The branch of [see Figure 4]. Once isolated, this vein is also ligated and
the inferior pulmonary vein draining the superior segment divided as previously described (see above).
will be encountered and should be mobilized distally to allow Right mainstem bronchus With the lung retracted
adequate exposure of the superior segmental bronchus origin. anteriorly, attention is directed toward the right mainstem
This bronchus can now be encircled, ligated, and divided bronchus. The subcarinal lymph nodes are mobilized, and
with a stapler or divided and oversewn. the bronchial artery on the posterior medial aspect of the
Next, the basilar segmental bronchi are encircled at a point right mainstem bronchus is controlled. The remaining peri-
where closure will not affect airflow to the middle-lobe bron- bronchial tissues are then mobilized distally with blunt and
chus. Appropriate placement is confirmed by asking the anes- sharp dissection. To avoid leaving a long bronchial stump,
thesiologist to ventilate the right lung while the stapler or exposure of the bronchus to within 1 cm of the carina is
clamp is applied to the base of the basilar bronchi. If place- advisable.
ment is adequate, the basilar segmental bronchi are ligated The bronchus can be closed with a TA stapler loaded with
and divided. 4.8 mm staples. The staples should be oriented so as to allow
good approximation of the anterior and posterior membranous
Right Pneumonectomy walls. If suture closure is selected instead, the bronchus is
Pulmonary artery: right main trunk With the pleura divided with the clamp placed on the distal bronchus to prevent
incised circumferentially around the hilum, the lung is rotated spillage. The open end of the bronchus is then closed with
inferiorly and posteriorly [see Figure 2]. The main trunk of nonabsorbable simple sutures, with the cartilaginous wall
Posterior Segmental Branch of Right Middle-

Superior Pulmonary Vein Lobe Artery
Right
Middle Lobe
Posterior
Ascending Artery
to Right Upper
Lobe
Divided
Lower-Lobe Inferior
Bronchus Pulmonary Vein
Esophagus
Figure 5 Right lower lobectomy. Shown is the surgeon’s view of the right fissure after division of the lower-lobe vessels. The
decision whether to divide the bronchi separately or to transect them with a single oblique application of the stapler depends on
the proximity of the middle-lobe bronchus to the superior segmental and basilar bronchi.
10/09
approximated to the membranous wall. To guard against necro- more distally situated lingular branch. These vessels should
sis of the bronchus, care should be taken not to tie the sutures be identified, individually ligated, and divided.
too tightly. Coverage of the pneumonectomy stump with viable Next, the whole lung is retracted inferiorly to expose the
tissue is preferred, especially if the patient has received or will aortic arch. A large arterial branch supplying the apicoposterior
receive chemotherapy, radiation therapy, or both. The ideal aspect of the upper lobe is usually encountered. Although the
choice for this purpose is either a rotated intercostal muscle flap superior and posterior aspects of this artery are easily dissected,
or a pericardial fat pad rotational flap. The flap is secured with the anterior aspect is frequently obscured by an apical branch
carefully placed 4-0 polypropylene sutures. of the superior pulmonary vein; division of this venous branch
In the preceding description, the artery is divided first, may improve exposure and facilitate control of the artery. Once
followed by the individual veins and, finally, by the bronchus; the artery is encircled, it is ligated and divided. To prevent
however, the steps of this operation can be carried out in any avulsion of this vessel from the main pulmonary artery, care
order. The position of the tumor may make the approach we must be taken not to exert excessive traction on the lung.
describe difficult. For example, an anteriorly placed tumor may Pulmonary vein: superior pulmonary vein The supe-
hinder exposure of the anterior hilum. In this situation, the rior pulmonary vein can then be identified easily. If the apical
bronchus can be divided first, and the pulmonary artery can be branch was not previously ligated, the surgeon should make
approached from the posterior hilum. As another example, if every effort not to damage the pulmonary artery branches that
the tumor is very proximal, the pericardium can be entered via lie posterior to this portion of the vein. The majority of the
a U-shaped incision along the anterior, caudal, and posterior superior pulmonary vein lies anterior to the left upper-lobe
hilum. The pulmonary veins can then be divided en masse as bronchus. Once this vein is encircled, it is ligated and divided.
they originate from the left atrium, and the pulmonary artery Left upper-lobe bronchus Attention is then redirected
can be divided as it courses posterior to the ascending aorta. toward the fissure, and the peribronchial nodal tissue surround-
ing the left upper-lobe bronchus is swept distally with blunt and
le f t l u n g sharp dissection. The fissure between the lingula and the lower
lobe is completed with serial application of GIA staplers [see
Left Hilar Dissection Figure 8]. The left upper-lobe bronchus is encircled and either
In the left chest cavity, it is important to identify the inferior clamped or controlled with a TA stapler. To prevent inadver-
pulmonary vein, pulmonary artery, bronchus, and superior
pulmonary artery. Retract the lung anteriorly and take down
Phrenic Nerve
the mediastinal pleura to expose the inferior pulmonary vein Superior
and continue superiorly to expose the left main bronchus and Pulmonary Left Pulmonary
the pulmonary artery. With the lung retracted inferiorly, dissec- Vein Artery
tion continues proximally along the pulmonary artery. The
pleura is incised under the arch of the aorta to expose the left Aorta
main pulmonary artery. A variable number of small vessels and Apical Left Upper
Branch Lobe
vagal branches to the lung are encountered that must be ligated
and divided. Care is taken not to injure the recurrent laryngeal
nerve as it branches from the vagus and travels under the arch
just distal to the ligamentum arteriosum. With the lung now
retracted posteriorly, the mediastinal pleura is opened parallel
to and posterior to the course of the phrenic nerve [see Figure 6 ].
This will expose the main trunk of the left pulmonary artery
and the superior pulmonary vein.
Left Upper Lobectomy
Pulmonary artery: apicoanterior, posterior, and
lingular The interlobar fissure is developed with a combi-
nation of sharp and electrocautery dissection. The posterior
aspect of the fissure, between the apicoposterior segment of
the left upper lobe and the superior segment of the left lower
lobe, is completed (with a linear stapler if necessary) to expose
the proximal portion of the pulmonary artery. The left upper Left Lower
lobe is then retracted anteriorly and superiorly to expose the Lobe
pulmonary arteries supplying the lobe [see Figure 7]. The left
upper-lobe pulmonary artery anatomy is most variable among
the lobes. The most common anatomy is three branches from
Figure 6 Left upper lobectomy. Shown is the surgeon’s view
the pulmonary artery: apicoanterior, posterior, and lingular
of the anterior left hilum. The apical branches of the superior
branches. However, not infrequently, multiple posterior apical
pulmonary vein course anterior to the apicoposterior branch-
branches are encountered; in fact, as many as seven vessels es of the pulmonary artery. If additional vessel length is
supplying the left upper lobe may be identified. Typically, the needed because of the presence of a central tumor, the
posterior segmental branch frequently arises directly opposite pericardium may be entered and the vein divided at that
the superior segmental branch to the lower lobe, as well as a location.
10/09
Anterior Left Pulmonary Left Recurrent

Segmental Artery Laryngeal Nerve
Apicoposterior Artery
Segmental Artery
Left Vagus
Nerve
Lingular
Segmental
Artery
Left Aorta
Upper
Lobe
Left Lower
Lobe
Superior
Basilar Segmental Artery
Segmental Arteries
Figure 7 Left upper lobectomy. Shown is the surgeon’s view of the left interlobar fissure. The recurrent laryngeal nerve can be
seen coursing lateral to the ligamentum arteriosum. The arterial branches supplying the left upper lobe between the apicoposte-
rior segmental branch and the lingular branch can vary substantially in number and size. Another frequently encountered
variation is a distal lingular branch that arises from a basilar segmental branch.
tent injury, the pulmonary artery branches to the lower lobe

Upper-Lobe Left Pulmonary
should be gently retracted posteriorly during stapler placement.
Bronchus Artery
With the stapler applied (or the clamp in place), the anesthesi-
ologist ventilates the left lung to verify that air is flowing freely
to the entire left lower lobe. Once unobstructed airflow is con-
firmed, the stapler is fired and the bronchus is divided.
Left Lower Lobectomy

Pulmonary artery: superior segmental and basilar
As in a left upper lobectomy, dissection begins within the
interlobar fissure. The pulmonary artery is identified, and the
branches to the upper and lower lobes are dissected [see
Figure 7]. The superior segmental artery is encircled first and
is ligated and divided; not uncommonly, there are actually
two separate superior segmental arteries. The basilar segmen-
tal arteries are then encircled distal to the origin of the lingu-
lar artery. These vessels are also ligated and divided, with
care taken not to encroach on the blood flow to the lingula.
Pulmonary vein: inferior pulmonary vein The lung is
rotated superiorly to expose the inferior pulmonary vein. As in a
right lower lobectomy, the vein is encircled by dissecting first on
its anterior surface with the lung rotated posteriorly, then on its
Figure 8 Left upper lobectomy. Shown is the surgeon’s view posterior surface with the lung rotated anteriorly [see Figure 9].
of the left fissure after division of the upper-lobe arteries. Once the vein is encircled, it is ligated and divided.
Care should be taken not to injure the pulmonary artery Left lower-lobe bronchus Attention is then redirected
inadvertently when applying a stapler. toward the interlobar fissure, and the left lower-lobe bronchus
10/09
Upper-Lobe Left Upper Left Mainstem

Bronchus Lobe Bronchus
Left Pulmonary
Artery
Lower-Lobe
Bronchus
Inferior
Pulmonary
Esophagus
Vein
Figure 9 Left lower lobectomy. Shown is the surgeon’s view

of the left inferior pulmonary vein. The left side, unlike the
right side, affords only limited access to the subcarinal space.
Figure 10 Left lower lobectomy. Shown is the surgeon’s view
However, the length of the inferior pulmonary vein outside
of the left fissure after division of the lower-lobe vessels. In
the pericardium is greater on the left side than on the right.
this procedure, a single oblique transection of the entire left
lower-lobe bronchus can be employed without any concern
that a proximal bronchus will be compromised; this step
is identified [see Figure 10]. The origin of the bronchus is would not be feasible in a right lower lobectomy, in that the
cleared by sweeping nodal tissue distally with blunt and sharp right middle-lobe bronchus arises from the bronchus
dissection. The upper-lobe branches of the pulmonary artery intermedius.
are gently retracted superiorly to allow placement of a TA
stapler on the bronchus. With the stapler applied, the anes- to the ligamentum arteriosum, care should be taken not to
thesiologist ventilates the left lung to confirm the adequacy of narrow the main pulmonary artery and thereby reduce right-
airflow to the upper lobe. The stapler is fired, and the bron- side blood flow. For maximal safety, systemic blood pressures
chus is divided distal to the staple line. and oxygenation should be evaluated for 15 to 20 seconds
after application of the clamp or stapler but before ligation.
Left Pneumonectomy Pulmonary vein: superior and inferior pulmonary
Pulmonary artery: left main pulmonary artery The vein With the lung retracted posteriorly, the pleura is
initial steps of a left pneumonectomy are similar to those of incised posterior to the course of the phrenic nerve, and the
a left upper lobectomy. The lung is retracted caudally, and superior pulmonary vein is identified [see Figure 6]. The vein
the pleura is incised along the course of the aortic arch [see is encircled with blunt dissection, then ligated and divided.
Figure 7]. The superior and posterior surfaces of the pulmo- As noted (see above), the apical branch usually travels across
nary artery are dissected as it enters the thorax under the the apical branch of the pulmonary artery, and care should
aortic arch. Once the perivascular space is entered, the entire be taken not to injure this vessel during dissection.
vessel can usually be encircled with blunt dissection. If The lung is then retracted superiorly to expose the inferior
the superior pulmonary vein’s apical branch limits access to pulmonary vein. Dissection is performed on the anterior and
the anterior surface of the pulmonary artery, the branch may posterior aspects of the inferior pulmonary vein, and blunt
be ligated and divided first to improve exposure of the artery; dissection is used to achieve complete encirclement of the
alternatively, the superior pulmonary vein itself may be vein [see Figure 9], which is ligated and divided.
ligated and divided first to facilitate arterial exposure (see Left main bronchus Next, the lung is retracted anteri-
below). orly and superiorly. Complete dissection of the subcarinal
Once the pulmonary artery is encircled, the vessel can be lymph nodes is performed, facilitated by division of one or
ligated and divided. Our preferred method is to use an two pulmonary branches of the left vagus nerve and both
endovascular GIA stapler, the advantages of which include its bronchial arteries. Gentle traction is applied in conjunction
rapidity of use, its consistently reproducible results, and its with blunt dissection to allow encirclement of the proximal
ability to control the vessel along a broad surface. Mass liga- left mainstem bronchus [see Figure 11]. An effort should be
tion is not advisable, because the risk of dislocation of the tie made to encircle the bronchus within 1 cm of the carina.
is too great. When the length of exposed artery is too short or A TA stapler is then passed around the left mainstem bron-
a stapler cannot be placed safely, the surgeon may apply vas- chus and applied at this point. If excessive traction is required
cular clamps to the proximal and distal portions of the vessel to achieve this placement, the bronchial stump can be
instead. Once the vessel is divided, the proximal end may be left slightly longer: 1 to 1.5 cm, as measured from the carina.
oversewn with a continuous polypropylene suture. The stapler is fired, and the bronchus is divided distal to the
If additional vessel length is required because of the presence staple line.
of a proximal tumor, the ligamentum arteriosum may be Frequently, the position of the bronchial stump under the
divided. The recurrent laryngeal nerve should be identified aortic arch and deep within the mediastinum renders coverage
and preserved. In dividing the left pulmonary artery proximal of the stump unnecessary. If the surgeon is concerned about
10/09
Stumps of Left
Pulmonary Artery
Left Inferior
Pulmonary
Vein
Aorta
Stump of
Left Mainstem
Pericardium Bronchus
Left Vagus
Nerve Left Superior
Pulmonary Vein
Figure 11 Left pneumonectomy. Shown is the surgeon’s view of the posterior left hilum. The carina is located deep under the
aortic arch. A left-side double-lumen tube or bronchial blocker may have to be withdrawn to afford better exposure of the proximal
left mainstem bronchus. The orientation of the superior pulmonary vein and the pulmonary artery (anterior and superior to the
bronchus, respectively) should be noted.
possible stump dehiscence (e.g., in a patient who has under- remove the tube when the air leak has resolved and the output
gone high-dose preoperative radiotherapy), coverage with a is less then 300–400 cc in 24 hours. Patients are then transi-
flap from the pericardial fat pad or intercostal muscle is tioned to oral pain medication and discharged home.
appropriate.
Postoperative Management Min P. Kim, MD, owns stock, stock options, or bonds in ATSI,
General Electric, and Johnson & Johnson Inc.
A key to successful postoperative management after pul-
monary resection is pain control, pulmonary toilet and chest
tube management. Thoracic epidural can provide great pain Selected Reading
relief after the operation. If this modality is not available or
not efficacious, patient controlled analgesia with or without Fell SC, Kirby TJ. Technical aspects of lobectomy. In: Shields TW, LoCicero J,
Ponn RB, et al, editors. General thoracic surgery. 6th ed. Philadelphia: Lippin-
continuous local anesthetic to the thoracotomy incision can cott Williams & Wilkins; 2005. p. 433.
be a good alternative. Although adequate pain control is one Hood RM. Techniques in general thoracic surgery. 2nd ed. Philadelphia: Lea &
of the key elements of good pulmonary toilet it is not suffi- Febiger; 1993.
Kirby TJ, Fell SC. Pneumonectomy and its modifications. In: Shields TW,
cient by itself. Patient education should begin preoperatively LoCicero J, Ponn RB, et al, editors. General thoracic surgery. 6th ed. Philadel-
with clear explanation of the goals of pulmonary toilet and phia: Lippincott Williams & Wilkins; 2005. p. 470.
the methods used to achieve this. This includes coughing, Martini N, Ginsberg RJ. Lobectomy. In: Pearson FG, Cooper JD, Deslauriers J,
et al, editors. Thoracic surgery. 2nd ed. Philadelphia: Churchill Livingstone;
deep breathing, usually assisted with an incentive spirometer, 2002. p. 981.
ambulation, bronchodilators, and, if necessary, nasotracheal Nesbitt JC, Wind GG. Thoracic surgical oncology. In: Exposures and tech-
niques. 1st ed. Philadelphia: Lippincott Williams & Wilkins; 2003. p. 320.
suctioning or even flexible bronchoscopy. An x-ray is obtained Waters PF. Pneumonectomy. In: Pearson FG, Cooper JD, Deslauriers J, et al,
after the operation to evaluate for appropriate lung expan- editors. Thoracic surgery. 2nd ed. Philadelphia: Churchill Livingstone; 2002.
sion, shift of the mediastinum and the diaphragm. After a p. 974.
lobectomy or any lesser resection, the chest tube is usually
placed on suction at ⫺20 cm H2O then transitioned to a Acknowledgment
water seal once there is a minimal air leak. Although there are
wide variations in chest tube management most surgeons will Figures 1, 2, and 3 through 11 Alice Y. Chen.
10/09
4 THORAX 15 DIAPHRAGMATIC PROCEDURES — 1
15 DIAPHRAGMATIC PROCEDURES
Ayesha S. Bryant, MSPH, MD, and Robert James Cerfolio, MD, FACS, FCCP
Although the diaphragm is sometimes thought of as little branches of the internal thoracic arteries. Some blood is
more than a partition between the thoracic organs and the supplied by small branches of the pericardiophrenic arteries
abdominal organs, it is, in fact, a dynamic anatomic structure that run with the phrenic nerve, mainly where the nerves
that plays a pivotal role in the physiology of respiratory penetrate the diaphragm. Venous drainage occurs via the
mechanics. For example, paralysis of just one hemidiaphragm inferior vena cava and the azygos vein on the right and via
can lead to the loss of 50% of a patient’s vital capacity.1 Like the suprarenal and renal veins and the hemiazygos vein on the
any other anatomic structure, the diaphragm may be affected left.
by either benign or malignant conditions. Overall, benign dis-
eases of the diaphragm (e.g., paralysis) are far more common innervation
than malignant ones. With either type of condition, however, The diaphragm receives its muscular neurologic impulse
the development of a safe surgical treatment strategy depends
from the phrenic nerve, which arises primarily from the fourth
on a solid knowledge of diaphragmatic anatomy and physiol-
cervical ramus but also has contributions from the third and
ogy. Accordingly, we begin with a brief review of the embry-
fifth rami. The phrenic nerve originates around the level of
ology and anatomy of the diaphragm. We then describe the
main procedures performed to treat the more common the scalenus anterior and runs inferiorly through the neck and
congenital diseases (e.g., congenital diaphragmatic hernia thorax before reaching its terminal point, the diaphragm.
[CDH]) and acquired pathologic conditions (e.g., paralysis Because the phrenic nerve follows such a long course before
and tumor) that affect this structure. reaching its final destination, a number of processes can dis-
rupt the transmission of neurologic impulses through the
nerve at various points and thereby cause diaphragmatic
Anatomic Considerations paralysis.
developmental anatomy
The diaphragm is a modified half-dome of musculofibrous
tissue that lies between the chest and the abdomen and serves
to separate these two compartments. It is formed from four
embryologic components: (1) the septum transversum, (2) Sternal Portion Esophagus
Inferior
two pleuroperitoneal folds, (3) cervical myotomes, and (4) Vena Cava
the dorsal mesentery. Development of the diaphragm begins
Costal Rib
during week 3 of gestation and is complete by week 8. Failure Portion
of the pleuroperitoneal folds to develop, with subsequent
muscle migration, results in congenital defects.
classical anatomy
The diaphragmatic musculature originates from the lower
six ribs on each side, from the posterior xiphoid process, and
from the external and internal arcuate ligaments. A number
of different structures traverse the diaphragm, including three
distinct apertures (foramina) that allow the passage of the
vena cava, the esophagus, and the aorta [see Figure 1]. The
aortic aperture is the lowest and most posterior of the dia-
phragmatic foramina, lying at the level of the 12th thoracic
vertebra. Besides the aorta, the thoracic duct and, sometimes,
the azygos and hemiazygos veins also pass through this
aperture. The esophageal aperture is the middle foramen; it
is surrounded by diaphragmatic muscle and lies at the level Lumbar Tendon
of the 10th thoracic vertebra. The vena caval aperture is the Portion
highest of the three foramina, lying level with the disk space
between T8 and T9.
vascular supply
Spine Aorta
The diaphragm is supplied by the right and left phrenic
arteries, the intercostal arteries, and the musculophrenic Figure 1 Shown is an inferior view of the diaphragm.
DOI 10.2310/7800.S04C15
03/10
Procedures for CDH repair of morgagni hernia
repair of bochdalek hernia Morgagni hernias, named after the Italian anatomist and
pathologist Giovanni Battista Morgagni, are related to malde-
Bochdalek hernia, named after the Czech anatomist velopment of the embryologic septum transversum and to
Vincent Alexander Bochdalek, is the most common form failed fusion of the sternal and costal fibrotendinous elements
of CDH and is also the most common surgical emergency of the diaphragm.6 The Morgagni hernia involves an opening
in neonates.1 It involves an opening on the left side of the on the right side of the diaphragm. The liver and intestines
diaphragm. The stomach and intestines usually herniate into usually herniate into the thoracic cavity. These hernias are
the thoracic cavity. The usual presenting symptoms are severe generally asymptomatic7 and are usually detected as inciden-
respiratory distress and a scaphoid abdomen. The primary tal findings on radiographs. Accordingly, the average age at
pathologic condition is the presence of posterolateral defects diagnosis is typically greater for Morgagni hernia than for
of the diaphragm, which result either in maldevelopment of Bochdalek hernia: in one report, the mean age at which the
the pleuroperitoneal folds or in improper or absent migration former was diagnosed was 45 years.8 Morgagni hernias are
of the diaphragmatic musculature. most commonly seen on the right side. The hernia sac usually
Bochdalek hernias occur in approximately one of every contains omentum, but it may also contain part of the trans-
2,500 live births and are twice as common in male neonates verse colon or, less commonly, parts of the stomach, the liver,
as in female neonates. Mortality ranges from 45 to 50%. or the small bowel; almost any upper abdominal structure
The bulk of the morbidity and mortality of CDH is attri- may herniate in this setting.
butable to the resultant hypoplasia of the lung on the affected
side and to various associated abnormalities (e.g., malro- Preoperative Evaluation
tation of the gut, neural tube defects, and cardiovascular On chest radiography, a Morgagni hernia appears as a mass
anomalies). at the right cardiophrenic angle [see Figure 2]. Computed
tomography (CT) of the chest and abdomen, liver scintigra-
phy, and multiplanar magnetic resonance imaging (MRI) are
Prenatal ultrasound examination accurately diagnoses occasionally helpful in the diagnostic process.
CDH in 40 to 90% of cases.2 In most instances, the examina-
tion is performed to rule out polyhydramnios. It is notewor- Operative Technique
thy that polyhydramnios is present in as many as 80% of Morgagni hernias can be repaired via a subcostal, a para-
pregnant women whose fetuses have CDH.3 In neonates median, or a midline incision. We prefer to use an upper
with CDH, besides the upper gastrointestinal tract, parts midline abdominal incision. Once the peritoneal cavity is
of the colon, the spleen, the kidneys, and the pancreas may entered, the hernia sac is identified just posterior to the
herniate, and the abnormal position of these organs can xiphoid and the posterior sternal border and then opened.
be identified by means of ultrasonography. Malrotation and The herniated abdominal viscera are restored to their normal
malfixation of the small bowel should be ruled out. Once the abdominal anatomic positions, and the sac is ligated. The
diagnosis is confirmed, additional radiographic, echocardio- entire hernia sac is defined, resected, and closed. The dia-
graphic, and ultrasonographic studies should be performed to phragmatic defect may be repaired in several different ways,
rule out associated anomalies. depending on its size and position. Because there is weak
tissue in the area of the defect, we generally use a prosthetic
Operative Technique patch for the repair. Either polypropylene mesh (e.g., Marlex;
As a rule, neonates with Bochdalek hernias are taken to the C. R. Bard, Inc., Murray Hill, New Jersey) or polytetrafluo-
operating room immediately after birth. Some studies, how- roethylene (PTFE) mesh (e.g., Gore-Tex; W. L. Gore and
ever, have shown that delayed surgical repair yields improved Associates, Newark, Delaware) may be used for this purpose.
survival rates.4 We prefer PTFE because it may cause fewer adhesions to the
For left-side hernias, a transabdominal subcostal approach underlying abdominal structure, which may be an important
is generally preferred, whereas for right-side hernias, a trans- consideration if further abdominal surgery subsequently
thoracic approach may be more useful. The herniated organs proves necessary. The prosthetic patch is sewn to the midline
are returned to the peritoneal cavity. The lung is inspected, abdominal fascia, with wide bites taken to prevent an abdom-
but no attempt to expand the hypoplastic lung should be inal incisional hernia. The rest of the patch is sewn to the
made. If any extralobar pulmonary sequestration is present thickened investing fascia that made up the edges of the
(as is occasionally the case), it should be excised. Most of the hernia sac. As noted, the frequently marginal quality of this
defects may be closed primarily with interrupted nonabsorb- tissue is the reason why a patch repair is almost always
able sutures; particularly large defects may be closed with a required.
prosthetic patch. The left pleural space is drained with a chest Repair of a Morgagni hernia via a thoracic incision follows
tube, which should be placed on water seal. the same basic principles. The hernia sac is entered, the vis-
Some surgeons have attempted surgical correction of severe ceral contents are mobilized and reduced into the abdomen,
Bochdalek hernias in the prenatal period. The safety and fea- the sac is resected, and the diaphragm is repaired. Again,
sibility of this therapeutic approach continue to be debated. the closure should be completed without tension. If the
Prenatal correction of these hernias poses a risk to both the defect cannot be closed with horizontal mattress sutures, a
mother and the fetus, with possibly fatal results for both.5 prosthetic patch should be used.
03/10
Figure 2 Repair of Morgagni hernia. The differential diagnosis of a cardiophrenic-angle mass includes pericardial fat, a
lipoma, a pericardial cyst, a Morgagni hernia, and a thymoma. Shown are (a) chest x-rays and (b) chest computed tomographic
scans from a 33-year-old man with an incidental finding of a Morgagni hernia.
Complications necessitates conversion to an open procedure. Laparotomy

has been associated with postoperative pleural effusion,9
The potential complications of surgical treatment of wound infection,10 deep vein thrombosis,11 and pulmonary
Morgagni hernia depend to an extent on the type of proce- embolism.12 Thoracotomy has been associated with pneumo-
dure undertaken to repair the defect. Laparoscopy may result nia, sepsis, and bowel obstruction in the postoperative
in failure to reduce the contents of the hernia sac, which period.13
03/10
Outcome Evaluation Physical examination may reveal dullness to percussion and

Most patients do not have any significant postoperative an absence of breath sounds over the lower chest on the
limitations after repair of a Morgagni hernia, nor are such involved side.
hernias likely to recur. In one study, 16 patients who In most cases, the diagnosis of hemidiaphragmatic paralysis
underwent transthoracic repair of a Morgagni hernia were is suspected on the basis of incidental findings on a chest
followed for 5.7 years; no recurrences or symptoms related to x-ray. Typically, the roentgenogram reveals an elevated hemi-
the operation were reported.14 diaphragm, diminished lung volume, and basilar atelectasis.
Fluoroscopy may also be performed. The diagnosis is con-
firmed by performing a fluoroscopic sniff test, in which para-
Procedures for Diaphragmatic Paralysis doxical elevation of the paralyzed diaphragm is observed with
The diaphragm is the most important of the respiratory sniffing.15 The sniff test is the gold standard for the diagnosis
muscles: diaphragmatic contraction decreases intrapleural of this condition. In certain patients, a chest CT scan may be
pressure during inspiration, expands the rib cage, and thereby indicated for evaluating the potential cause of the paralysis.
facilitates the movement of gases into the lungs. Accordingly, If an obvious cause is not apparent from the history or a
paralysis of the diaphragm can have a major adverse effect on previous evaluation, CT scanning of the chest should be
respiratory function. Diaphragmatic paralysis may involve performed to ensure that no pathologic process is compress-
either the whole diaphragm (bilateral paralysis) or only one ing or invading the phrenic nerve. Similarly, MRI of the neck
leaflet or hemidiaphragm (unilateral paralysis). The possible or the spine may be indicated in certain patients to look
causes of diaphragmatic paralysis are numerous [see Table 1]; for conditions that might be causing the diaphragmatic
the most common causes are phrenic nerve trauma related paralysis.
to a surgical procedure (e.g., stretching, crushing, or Two other tests that are also (albeit less commonly) used
transection) and invasion by a malignant neoplasm. for the diagnosis of unilateral diaphragmatic paralysis are
electromyography and transdiaphragmatic pressure assess-
diaphragmatic plication for unilateral paralysis
ment. In the first, the phrenic nerve is electrically stimulated
Preoperative Evaluation in the neck in an effort to distinguish between neuropathic
With unilateral diaphragmatic paralysis, the paralyzed and myopathic causes of paralysis. In the second, transdia-
hemidiaphragm paradoxically moves upward on inspiration phragmatic pressures are measured by placing a thin-walled
and downward on expiration, passively following changes in balloon transnasally at the lower end of the esophagus in such
intrapleural and intra-abdominal pressure. Patients with a a way as to reflect changes in pleural pressure; a second
paralyzed hemidiaphragm who are otherwise healthy usually balloon manometer is then placed in the stomach in such a
have no symptoms at rest but experience dyspnea during way as to reflect changes in intra-abdominal pressure. The
exertion and show a decrease in exercise performance. difference between the two pressures is the transdiaphrag-
matic pressure. Measurement of transdiaphragmatic pressure
can help differentiate diaphragmatic paralysis from other
Table 1 Common Causes of Diaphragmatic Paralysis causes of respiratory failure.
Yet another test involves measurement of maximal inspira-
Neurologic conditions
tory pressures. Patients with diaphragmatic dysfunction and
Spinal cord transection
Multiple sclerosis paralysis show a decrease in their maximal inspiratory
Amyotrophic lateral sclerosis pressures. These patients cannot generate high negative inspi-
Cervical spondylosis ratory pressures; thus, their maximal inspiratory pressures
Poliomyelitis will be less negative than −60 cm H2O.
Guillain-Barré syndrome
Phrenic nerve dysfunction
Operative Planning
Compression by tumor
Cardiac surgery cold injury Surgical treatment of hemidiaphragmatic paralysis is
Blunt trauma reserved for symptomatic patients who, after a follow-up
Idiopathic phrenic neuropathy
Diabetes mellitus
period of at least 6 months, have persistent shortness of
Postviral phrenic neuropathy (herpes zoster) breath with exertion that is sufficiently pronounced to
Radiation therapy interfere with lifestyle. For a patient to be considered for
Cervical chiropractic manipulation operation, the sniff test should show significant paradoxical
Myopathic conditions motion.
Limb-girdle dystrophy The basic principle of the surgical procedure is to “reef”
Hyperthyroidism/hypothyroidism (i.e., reduce the surface area of) the redundant floppy dia-
Malnutrition
Acid maltase deficiency phragm by plicating it. This measure lowers the resting
Connective tissue disease position of the hemidiaphragm and thus affords the lung the
Systemic lupus erythematosus opportunity to expand fully. The effective result is an increase
Dermatomyositis in the functional vital capacity of the ipsilateral lung. The
Mixed connective tissue disease
Amyloidosis results of plication have been shown to be better in children
Idiopathic myopathy compared to adults. Plication is of limited benefit in weaning
Muscular dystrophy ventilated adults; however, it still results in lifetime improve-
Multiple siclerosis ment in nonventilated adults.16 A couple of studies have found
03/10
that plication of the diaphragm led to long-term improve- diaphragmatic pacing for bilateral paralysis
ments in pulmonary function test results, as well as reduced
dyspnea.17,18
In patients with bilateral diaphragmatic paralysis, the respi-
Operative Technique ratory accessory muscles assume all the work of breathing by
Diaphragmatic plication may be performed with either contracting more intensely. Both hemidiaphragms move
sutures or staples; we prefer sutures for this procedure. upward on inspiration, concomitant with inward (rather than
The chest is entered through a thoracotomy in the seventh the normal outward) movement of the abdominal wall.20
or eighth intercostal space. Horizontal mattress sutures Patients typically present with severe respiratory failure or
buttressed with Teflon pledgets are then placed in a lateral- with dyspnea (sometimes misinterpreted as a sign of heart
to-medial direction [see Figure 3]. We typically use monofila- failure) that worsens in the supine position, and they gener-
ment nonabsorbable sutures that pass easily through the ally exhibit tachypnea and rapid, shallow breathing when in
muscle and can be tightened without dragging through tissue. the recumbent position. Increased expenditure of effort in
the struggle to breathe may fatigue the accessory muscles
To distribute the tension, multiple sutures must be placed;
and lead to ventilatory failure. Patients also report anxiety,
this is especially important on the right side, where the dia-
insomnia, morning headache, excessive daytime somnolence,
phragm must be pulled down against the upward force
confusion, fatigue, poor sleep habits, and signs of cor
exerted by the presence of the right hemiliver. When the
pulmonale.21
sutures are tied, the hemidiaphragm should be almost back
During physical examination, auscultation of the chest
to its normal anatomic location. Care must be taken to ensure reveals limitation of diaphragmatic excursion and bilateral
that the repair is not under undue tension: excessive tension lower-chest dullness with absent breath sounds. The finding
is likely to result in early dehiscence. Occasionally, a that establishes the diagnosis is a paradoxical inward move-
prosthetic patch may be used to buttress the repair further, ment of the abdomen with inspiration. As with unilateral
but in the majority of cases, this measure should be unneces- diaphragmatic paralysis, however, it is more common for
sary. If the choice is made to use staples rather than sutures, the diagnosis to be suspected on the basis of a chest roent-
care must be taken to ensure that the underlying abdominal genogram that shows bilateral diaphragmatic elevation and
contents are not caught in the staple line. then confirmed by means of the sniff test.
Diaphragmatic plication can also be performed via video-
assisted thoracoscopic approach. Some studies have shown Operative Planning
that the minimally invasive approach reduces the risk and the Treatment depends on the cause and severity of the dia-
recovery time when compared to a thoracotomy.19 phragmatic paralysis. Most patients are treated with ventila-
tory support, but some are treated with bilateral plication
or with pacing (as shown in Figure 4). Plication for bilateral
paralysis is performed in the same way as plication for unilat-
eral paralysis [see Diaphragmatic Plication for Unilateral
Paralysis, above], except that both hemidiaphragms are
lowered.
There are patients who have suffered high cervical injuries
and are either quadriplegic or have loss of the C3, C4, and
C5 anterior horn cells in the nerve roots. These patients are
on ventilators for life and usually nonambulatory. To date,
two pacing devices have been approved by the Food and
Drug Administration: the Mark IV Breathing Pacemaker
System (Avery Biomedical Devices, Commack, New York)
uses an electrode that is placed on the skeletonized phrenic
nerve, and the NeuRx (Synapse Biomedical, Cleveland,
Ohio) uses electrodes placed directly in the diaphragm fibers
either video-assisted thoracoscopically or laparoscopically.
Both are connected to a small receiving electrode unit placed
under the skin. A battery-powered external transmitting box
connected to an antenna is taped over the surface of the skin,
just above the subcutaneous receiver. This transmitting box
permits adjustment of pulse duration, pulse train duration,
respiratory rate, pulse frequency, and current amplitude. In
most patients, the only parameters that the clinician adjusts
are current amplitude and respiratory rate.
Implantation of a diaphragmatic pacer requires experience
on the part of the surgeon—not so much because of any
Figure 3 Diaphragmatic plication. Shown is suture plication particular technical demands imposed by the implantation
of the right hemidiaphragm. Placement of sutures buttressed itself but because of the procedures for diaphragm training
with pledgets extends anteriorly to the level of the vena cava. that must be carried out in the postoperative period.
03/10
External Internal than the cervical approach would. The disadvantage of the
Receiver and thoracic approach is the preconceived notion that entry into
Antenna Electrode
the chest is associated with a higher morbidity than entry into
Phrenic the neck.
Nerve
Operative Technique
Cervical placement In the neck, the phrenic nerve runs
between the scalenus anterior and the scalenus medius. A
transverse skin incision is made in the midportion of the
neck, just lateral to the sternocleidomastoid muscle, and the
borders of the two scalene muscles are dissected. The scalene
muscles are then divided, and the phrenic nerve is identified
lying in a layer of fascia just anterior to the anterior surface
of the scalenus medius. Identification of this nerve is often
facilitated by the use of a handheld nerve stimulator. Intra-
operative fluoroscopy allows observation of diaphragmatic
contraction in response to phrenic nerve stimulation, which
confirms that pacing is successful.
Diaphragm Once the phrenic nerve is identified, it is carefully dissected
Mark IV free of its investing fascia, and the Y-shaped electrode is
placed under it and secured with sutures. Care must be taken
to ensure that the nerve is not injured during this step. The
connecting wire from the electrode is then tunneled subcuta-
neously to a subcutaneous pocket that is created just below
the ipsilateral clavicle. The connections are made and sealed,
and the small incisions are closed.
Thoracic placement In the thoracic approach, the chest

is entered through a high thoracotomy (usually over the
fourth interspace), and the proximal phrenic nerve is identi-
Figure 4 Diaphragmatic pacing. Shown are internal and fied. On the right side, the nerve lies along the mediastinum,
external pacer connections. situated just anterior to the vena cava and coursing along the
pericardial surface. On the left side, it lies on the pericardium
for most of its length. The proximal nerve is freed of its
fibrous investments, and the electrode is placed under it and
Surgical implantation of a diaphragmatic pacer can be secured with sutures. The electrode is connected to the
done via either a cervical approach or a thoracic approach. receiver, which is placed in a subcutaneous pocket.
The primary advantage of the cervical approach is that it As noted (see above), there are alternative approaches to
avoids the morbidity associated with bilateral thoracotomies, pacer implantation that avoid the cervical approach but also
which may not be well tolerated in patients who have mar- do not involve standard thoracotomies. For example, there
ginal pulmonary function or a history of severe pulmonary is limited (but growing) experience with thoracoscopic place-
contusions. However, there are other ways of avoiding this ment of phrenic nerve pacing leads.23 In addition, laparo-
morbidity, either laparoscopically, by video-assisted thoracoscopic implantation of intramuscular pacing electrodes onto
scopic surgery (VATS), or with a small muscle-sparing, rib- the inferior aspect of the diaphragm has been reported.24
sparing, nerve-sparing thoracotomy.22 One disadvantage of Taking into account all the advantages and disadvantages
the cervical approach is that in a small percentage of patients, of each approach to pacer implantation, we generally prefer
the current amplitude necessary to stimulate the phrenic the thoracic approach, either via VATS or via a thoracot-
nerve results in transmission of the current through the soft omy.23,25 The evolution of less invasive surgical techniques
tissues. The transmitted current stimulates the functioning may allow the thoracic approach to be employed in patients
portions of the brachial plexus, causing rhythmic jerking who are unable to tolerate thoracotomy.
motions of the upper extremities. Another disadvantage is
that a number of accessory nerve branches arise distal to the Complications
neck. Besides the usual complications associated with any
One advantage of the thoracic approach is that inadvertent thoracic procedure (i.e., infection, bleeding, atrial fibrillation,
stimulation of portions of the brachial plexus (as sometimes and pneumonia), several specific complications are associated
occurs with the cervical approach) may be avoided. Another with diaphragmatic pacing. The most common of these are
advantage is that there is some neuroanatomic evidence that dislodgment of the pacer electrode, transmission of pacer
a small branch of the phrenic nerve joins the main nerve impulses to the brachial plexus with resultant rhythmic jerk-
trunk only after it enters the chest cavity; thus, the thoracic ing of the upper extremity (seen with cervical placement of
approach may stimulate a larger portion of the phrenic nerve the electrode), and hardware malfunction.
03/10
Outcome Evaluation calcification, sharp margins, and flattened contours are indic-
Retrospective analysis of the collective experience at a ative of a malignant process, such as pleural metastases,
single center between 1981 and 1987 suggested that long- mesothelioma, or a primary diaphragmatic tumor.
term pacing did not lead to progressive diaphragmatic The most common indication for diaphragmatic resection
dysfunction.26 Six of the 12 patients in this cohort continued is mesothelioma. This remains true even though mesotheli-
to undergo diaphragmatic pacing on a full-time basis for a oma is relatively uncommon in comparison with broncho-
median period of more than 14 years. Pacing was well toler- genic malignancy and even though few patients with
ated in this group; the reasons for discontinuance included mesothelioma are actually candidates for resection. Again,
intercurrent medical illness and lack of social support. Con- resection of a mesothelioma is not addressed here. The
cerns have been raised that prolonged diaphragmatic pacing ensuing operative description focuses on diaphragmatic
might damage the phrenic nerve. In the series cited, however, resection to treat either a lung cancer invading the diaphragm
the ability to pace the phrenic nerve was not lost in any of the or a primary diaphragmatic tumor [see Figure 5].
patients, and the mean threshold currents for pacing did not
operative technique
change significantly over time.
Once the decision is made to resect a tumor involving the
diaphragm, the key considerations are (1) the surgical
Resection of Diaphragmatic Tumors approach to be taken and (2) the placement of the incision
Primary tumors of the diaphragm are extremely rare. in the diaphragm. We prefer a skin incision that is lower
Benign tumors (e.g., lipomas and cystic masses) are more and slightly more anterior than a normal posterolateral
common than malignant tumors, which mostly are sarcomas thoracotomy; such an incision allows easy entry over the top
of fibrous or muscular origin. Thoracic and abdominal tumors of the seventh rib. After entry into the chest, the lung, the
(e.g., bronchogenic carcinomas, pleural malignancies, and pericardium, and the pleural surface are carefully visualized
chest wall malignancies) may involve the diaphragm second- and palpated to search for any signs of metastatic disease.
arily through direct extension. Malignant pleural mesotheli- Next, the incision in the diaphragm is planned. Ideally, the
oma represents a different scenario and is not discussed incision should be made anterior or lateral to the tumor so
here. Schwannomas, chondromas, pheochromocytomas, and that a hand can be placed easily into the peritoneal cavity [see
endometriomas have all been reported. Bilateral occurrence, Figure 5a]. Intra-abdominal palpation confirms that the tumor
a b
Right Lower-Lobe
Tumor Invading Gore-Tex Patch
Diaphragm
Figure 5 Resection of diaphragmatic tumor. The patient has a right lower-lobe bronchogenic malignancy with erosion into the
right hemidiaphragm. (a) The tumor is resected en bloc with the diaphragmatic fibers; the electrocautery is used to achieve
clear surgical margins and hemostasis. (b) The defect in the right hemidiaphragm is closed with a mesh patch.
03/10
has not extended into underlying structures. This informa- under tension. Accordingly, repair with a prosthetic patch is
tion is almost always gleaned from the preoperative CT scan, the usual choice. Infection of such a patch is exceedingly rare,
but if any uncertainty remains after the scan, diagnostic and with the exception of the cost, there is little downside to
laparoscopy may be performed before the thoracotomy to the use of prosthetic material in this setting. As in the repair
look for possible tumor extension. of a CDH, we prefer PTFE mesh [see Figure 5b] to polypro-
The tumor is then resected with 2 to 4 cm margins. The pylene mesh because it is less likely to adhere to underlying
large arteries that course through the diaphragmatic fibers are abdominal structures.
ligated. It is our practice also to place a few silk sutures (stay The mesh patch is sewn to the edges of the defect (prefer-
stitches) in the edges of the defect; this prevents the edges ably with nonabsorbable suture material, such as 0 polypro-
from retracting, helps keep the defect as small as possible, pylene), starting at the most anterior and inferior portions of
and keeps abdominal contents from interfering with the resec- the opening and continuing toward the surgeon [see Figure 5].
tion. In addition, we place clips on the edges for guidance The inferior half of the repair is done with a continuous
purposes in case adjuvant radiotherapy is delivered after the suture. The repair is completed with two or three sutures,
operation. If adequate margins are obtained, which is usually which are tied circumferentially. To prevent paradoxical
relatively easy in a diaphragmatic resection, postoperative motion, the diaphragm must not be too redundant or floppy.
radiotherapy should be unnecessary. If, however, the tumor It should remain in the normal anatomic position so that the
abuts vital structures (e.g., the suprahepatic vena cava), remaining lung can expand completely. In general, however,
postoperative radiotherapy may have a useful role to play. it is best to keep the repair taut so as to optimize pulmonary
Once the entire tumor has been resected and clear margins mechanics after the procedure.
have been confirmed by frozen-section examination, the
diaphragm is reconstructed. Primary repair is rarely indicated Financial Disclosures: Dr. Cerfolio is a speaker and consultant for
because in most cases, the defect is too large and the tension Ethicon, Millicore, Medela, and Atrium. He is a consultant for
on the repair would be too great. Moreover, the tissue in the Neomend, and Closure (J&J). He is a speaker for E Plus Health
anterior aspect of the diaphragm is thin and is likely to tear Care, OSI Pharmaceuticals, Oncotech, Covidien, and Precision.
References
1. Kirks DR, Caron KH. Gastrointestinal tract. hernias in a patient presenting with the clini- adult patients with unilateral diaphragm
In: Kirs DR, editor. Practical pediatric imag- cal features of restrictive pulmonary disease: paralysis. Ann Thorac Surg 2006;81:1853–7.
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1991; p. 709–904. 11. Missen AJB. Foramen of Morgagni hernia. Abdominal wall movement in normals and
2. Lewis DA, Reickert C, Bowerman R, Hirschi Proc R Soc Med 1973;66:654. patients with hemidiaphragmatic and bilateral
RB. Prenatal ultrasonography frequently fails 12. Dawson RE, Jansing CW. Case report: diaphragmatic palsy. Thorax 1977;32:589.
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J Pediatr Surg 1997;32:352–6. Med Assoc 1997;75:325. Unexplained diaphragmatic paralysis: a
3. Adzick NS, Harrison MR, Glick PL, et al. 13. Lev-Chelouche D, Ravid A, Michowitz M, harbinger of malignant disease? J Thorac
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diagnosis and outcome in 94 cases. J Pediatr in elderly patients. J Clin Gastroenterol 1999; 22. Cerfolio RJ, Bryant AS, Patel B, et al.
Surg 1985;20:357. 28:81. Intercostal muscle flap decreases the pain of
4. Breaux CW Jr, Rouse TM, Cain WS, et al. 14. Kiliç D, Nadir A, Döner E, et al. Transtho- thoracotomy: a prospective randomized trial.
Improvement in survival of patients with racic approach in surgical management of
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congenital diaphragmatic hernia utilizing a Morgagni hernia. Eur J Cardiothorac Surg
23. Morgan JA, Morales DL, John R, et al. Endo-
strategy of delayed repair after medical and/ 2001;20:1016.
scopic, robotically assisted implantation
or extracorporeal membrane oxygenation 15. Miller JM, Moxham J, Green M. The maxi-
of phrenic pacemakers. J Thorac Cardiovasc
stabilization. J Pediatr Surg 1991;26:333. mal sniff in the assessment of diaphragm
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1991;165:838. Diaphragm plication following phrenic nerve via intramuscular diaphragm electrodes. Am J
6. Panicek DM, Benson CB, Gottlieb RH, et al. injury: a comparison of paediatric and adult Respir Crit Care Med 2002;166:1604.
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1988;8:385. Long term results of diaphragmatic plication thoracotomy. Ann Thorac Surg 2003;76:
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Acknowledgment
10. Ngaage DL, Young RA, Cowen ME. An Functional and physiologic results of video-
unusual combination of diaphragmatic assisted thoracoscopic diaphragm plication in Figures 1 and 3 through 5 Tom Moore
03/10
4 THORAX 16 THORACIC DIAGNOSTIC AND STAGING PROCEDURES — 1
16 THORACIC DIAGNOSTIC AND

STAGING PROCEDURES
Farzaneh Banki, MD and Larry R. Kaiser, MD, FACS
Thoracic diagnostic and staging procedures can be divided (CT) scans of the chest most commonly performed following
into those that involve the lungs, pleural space, mediastinum, the injection of intravenous contrast are the mainstay of tho-
and esophagus. Surgeons must be familiar with the TNM racic imaging procedures. These scans are the most sensitive
staging system for each major thoracic disease to decide on for defining parenchymal lung lesions and can detect lesions
appropriate treatment. A general principle is to proceed with down to a size of several millimeters.
the diagnostic modality that will potentially yield or rule out The appearance of a parenchymal lung nodule does not
the highest stage. As an example, in a patient with presumed necessarily indicate malignancy. The only definitive informa-
non–small cell lung cancer and a pleural effusion, there is tion that can be obtained regarding a lung nodule seen on
no reason to proceed with mediastinoscopy to assess lymph a CT scan is its size. There are no specific defining charac-
node involvement prior to interrogating the pleural space teristics that are accurate in delineating a benign from a
with video-assisted thoracoscopy (VATS). In this chapter, malignant nodule. If previous CT scans are available for
we review the diagnostic and staging procedures that relate comparison, an increase in the size of a nodule points toward
to the most common thoracic malignancies that occur in the malignancy but, again, is not definitive. The presence of a
thoracic cavity that have relevance to the general surgeon. new nodule on a CT scan may mandate nothing more than
a repeat scan in 3 months to assess whether the nodule is
changing in size. An increase in the size of a nodule should
Clinical Diagnosis and Staging mandate further diagnostic procedures to define the nodule.
The diagnosis and staging of intrathoracic disease have The size increase alone may be an indication for resection
major implications for treatment planning, especially in light or, depending on the clinical setting, may mandate a needle
of recent advances in both neoadjuvant and adjuvant treat- aspiration biopsy to obtain material for cytologic analysis.
ment regimens in both lung cancer and esophageal cancer. However, one must be aware that only a positive result is
These two malignancies account for the majority of the helpful, as with any diagnostic test. A “negative” biopsy is of
pathology seen within the chest cavity and treated by thoracic no use because a sampling error may account for the negative
result and we are still faced with a nodule that has increased
surgeons. TNM staging for both lung cancer and esophageal
in size. Thus, prior to obtaining a needle aspiration biopsy,
cancer recently has undergone revision as noted in the
the surgeon should know how the information will be used.
seventh edition of the American Joint Committee on Cancer
One recognizes intuitively that if the biopsy is positive for
(AJCC) cancer staging manual, effective since January 2010.1
malignancy and there is no evidence of locally advanced or
It is mandatory for every surgeon who treats these diseases
distant disease, the patient is a candidate for resection unless
to be intimately familiar with the staging classification as
that option is precluded because of other underlying medical
mentioned in the latest edition of this manual. The surgeon
problems. But if operation is also indicated in the presence of
needs to be familiar with clinical staging based on preoperative
a negative result on biopsy, one has to think seriously as to
imaging studies and pathologic staging that result from either whether the risk of a needle biopsy is warranted.
preoperative invasive staging techniques or the findings that CT scans are also excellent for demonstrating enlargement
are generated by the pathologist who reviews the histology of mediastinal and hilar lymph nodes, but, once again, an
of the material obtained at the time of definitive resection. increase in size alone does not necessarily translate into
Optimal surgical resection that results in definitive informa- malignancy. By convention, we define mediastinal lymph
tion detailing the final clinical stage includes complete removal nodes larger than 1 cm on short axis as pathologic, although
of the primary tumor as well as, ideally, a systematic dis- some prefer to use 1.5 cm as the definition for pathologic.2
section or, at minimum, sampling of the regional lymph Many surgeons have used CT scans to identify those patients
nodes. Any procedure that is not this inclusive results in par- without pathologic lymph nodes as defined by size criteria so
tial information that makes a decision regarding postoperative that certain patients may proceed to resection without the
treatment significantly more difficult and may result in a need for invasive mediastinal staging. It has been reported
poorer outcome for the patient. that only 3 to 16% of patients with mediastinal lymph nodes
Clinical staging of intrathoracic disease, specifically intra- less than 1 cm in size on a CT scan are found to have tumor
thoracic malignancies, relies on imaging modalities that involvement at mediastinoscopy.3,4 Sensitivity and specificity
range from plain chest radiography to positron emission will vary depending on what size criteria for positivity one
tomography (PET). Most commonly, patients with intratho- chooses to use. A meta-analysis looking at CT scans in assess-
racic complaints obtain a chest radiograph that may or may ing mediastinal lymph node involvement in bronchogenic
not delineate the relevant pathology. Computed tomographic carcinoma found an overall sensitivity and specificity of
DOI 10.2310/7800.2206
09/11
79% and 78%, respectively.5 McLoud and colleagues reported Diagnostic and Staging Procedures for the Lungs,
even lower sensitivity and specificity of 64% and 62%, Pleura, and Mediastinum
respectively.6 The bottom line here is that the presence of
enlarged lymph nodes should prompt additional staging bronchoscopy
studies, including 18F-fluorodeoxyglucose (18F-FDG) PET Bronchoscopy is the standard diagnostic modality used for
and most likely mediastinoscopy to document the presence the assessment of disease that involves the airway, lungs, and
or absence of malignancy before deciding that a patient is pleura. The use of the fiberoptic bronchoscope has, for the
not an operative candidate.7 most part, supplanted the use of rigid bronchoscopy for
PET is highly sensitive in the detection of mediastinal all but lesions thought to involve the trachea or proximal
lymph node involvement in patients with bronchogenic mainstem bronchi. It is safe, although sad, to say that rigid
carcinoma, with a lower limit of detection reported at 4 mm.8 bronchoscopy is a dying art except for the few thoracic
It has been estimated to have a sensitivity as high as 91 to surgeons and interventional bronchoscopists who continue to
96% and a specificity as high as 86 to 93% in staging of use it for certain indications. Flexible bronchoscopes allow
mediastinal lymph nodes.9–13 PET has also been found to be for visualization of the entire tracheobronchial tree out to the
quite useful in differentiating benign from malignant paren- level of subsegmental bronchi, and lesions may be sampled
chymal lung nodules. A nodule with positive 18F-FDG uptake via the working channel of the instrument. Techniques for
on PET has a better than 90% likelihood of being malignant. sampling include brushings, washings, and use of a flexible
Figure 1a demonstrates a right upper lobe nodule seen on biopsy forceps to obtain tissue samples. The procedure may
a CT scan, whereas Figure 1b shows the same nodule on easily be performed with the patient awake and lightly sedated
a PET scan. Increased metabolic activity is suggestive of with the instrument passed either via the nares or through
malignancy, as seen in the hilar lymph node. The use of the mouth using topical anesthetic to attenuate the gag
combined PET-CT is growing, and several studies suggest reflex. Use of an endotracheal tube is not required to place
that the use of integrated PET-CT improves anatomic the bronchoscope but may be used to secure the airway if
localization of lymph nodes compared with PET alone.11 necessary.
This study provides both the anatomic localization and size Once the instrument is passed, the vocal cords are visual-
information when looking at the mediastinal lymph nodes, ized and traversed, with inspection then carried out of the
as well as the metabolic information obtained from the entire airway. Topical anesthetic may be injected through the
PET scan, which provides additional information useful in instrument as needed to prevent the patient from coughing.
determining benign from malignant tumors. The same applies Orientation is secured by visualizing the origin of the right
to parenchymal lesions. upper lobe bronchus, which is the most proximal orifice
Figure 1 (a) Right upper lobe non–small cell lung cancer on a computed tomographic scan. (b) Positron emission tomographic
scan. The blue arrows indicate the primary tumor, and the red arrow indicates the hilar lymph node.
09/11
visualized when one proceeds beyond the carina and takes off bronchoscope. Occasionally, epinephrine in saline is used to
at an acute angle [see Figure 2]. Proceeding down the right control bleeding after a transbronchial lung biopsy.
mainstem bronchus, the bronchus intermedius is entered
Transbronchial Needle Aspiration
distal to the right upper lobe takeoff, and the origin of
the middle lobe and lower lobe bronchus can be seen. The Transbronchial needle aspiration (TBNA) is another
takeoff of the superior segment of the lower lobe is visualized diagnostic technique that may be used to assess regional
lymph nodes and is performed via the flexible bronchoscope.
heading posteriorly. Next, the left main bronchus is entered
A needle catheter is passed through the working channel of
and both upper and lower lobe bronchi are interrogated.
the instrument and guided to the area of the tracheobronchial
Any endobronchial lesions seen may be sampled with the tree adjacent to the mediastinal lymph node of interest. The
cup biopsy forceps. Parenchymal lesions may also be sampled needle catheter is advanced through the tracheal or carinal
via a transbronchial approach using fluoroscopy for precise wall into the mediastinal lymph node, and a syringe is con-
localization of the biopsy forceps. Special alligator forceps are nected to aspirate cellular material. Several passes may be
passed distally into the airway via the appropriate segmental necessary until an adequate specimen is confirmed by the
bronchus, and either a discrete lesion or diffusely involved cytopathologist, who, ideally, is present. On-site cytopatho-
parenchyma may be sampled. Bleeding, if encountered, logic examination of needle aspiration specimens significantly
usually only requires saline lavage and tamponade with the improves the yield of TBNA.
Figure 2 Diagrammatic representation of the right mainstem bronchus and the origin of the right upper lobe bronchus.
Note the position of the upper lobe takeoff. This is the point of orientation for bronchoscopy. Reproduced with permission from
Kaiser LR et al.25
09/11
TBNA is used most frequently to assess subcarinal lymph instrument is turned so as to facilitate passage into the airway.
nodes. Paratracheal lymph nodes may also be sampled with The rigid instrument cannot be passed beyond the lobar level
TBNA, but these are somewhat more difficult to access and is directed by turning the head. Rigid forceps may be
mainly because of the technical difficulty of sufficiently angu- used for sampling proximal lesions, and larger specimens may
lating the bronchoscope containing the needle catheter.14 be obtained than can be using the flexible instrument. The
It has been reported that it is feasible to obtain adequate rigid bronchoscope may also be used as a therapeutic tool to
specimens via TBNA in approximately 80 to 90% of cases.15 remove foreign bodies, dilate strictures, or debulk tumor that
Results achieved for lymph nodes less than 1 to 1.5 cm may may be occluding proximal airways. It remains a very useful
be substantially reduced but may improve up to 90% for tool for those who have the expertise to use it.
nodes of greater than 1.5 cm.16–18
mediastinoscopy
Endobronchial Ultrasound-Guided Needle Aspiration
This procedure remains the gold standard for assessing the
Endobronchial ultrasound-guided needle aspiration status of the mediastinal lymph nodes whether for patients
(EBUS-NA) is a procedure similar to conventional TBNA with a parenchymal lung lesion or for those who simply pres-
that also uses local anesthesia and sedation. However, the ent with mediastinal adenopathy of unknown etiology. The
patient is intubated because of the larger external diameter CT scan of the chest is used to identify enlarged mediastinal
of the EBUS-NA bronchoscope. EBUS-NA is a relatively lymph nodes, and the PET scan may be highly suggestive or
new technique for mediastinal staging and employs a bron- even “definitive” that these nodes may harbor malignancy,
choscope with a convex ultrasound probe that allows for but until there is histologic proof from tissue obtained, some
real-time ultrasound-guided TBNA [see Figure 3]. EBUS-NA doubt remains. Even with a positive PET scan, at least a 10
can be used to sample the highest mediastinal, upper and to 20% chance of a false positive result attributable mainly to
lower paratracheal, and subcarinal lymph nodes, as well as inflammatory disease remains.
hilar lymph nodes. The overall reported sensitivity is 90%, In 2007, Detterbeck and colleagues published evidence-
with values ranging from 79 to 95%. The average reported based clinical practice guidelines for invasive mediastinal
false negative rate is 24% but varies significantly among staging of lung cancer that concluded the following14:
reported series.19–21
1. In patients with discrete mediastinal nodal enlargement,
Rigid Bronchoscopy staging by CT or PET scan is not sufficiently accurate.
Rigid bronchoscopy, when indicated, is performed with the The sensitivity of various techniques is similar in this set-
patient anesthetized and in the supine position. The head ting, although the false negative rate of needle techniques
should be placed in the “sniffing” position, and using the is higher than that for mediastinoscopy.
operator’s thumb as a fulcrum, the instrument tip is used to 2. In patients with a stage II or central tumor, invasive
elevate the epiglottis. Once the vocal cords are visualized, the staging of the mediastinal nodes is necessary.
a b
Figure 3 (a) Endobronchial ultrasound probe with the inflated balloon. (b) Ultrasound image with the tip of the needle in the
mediastinal lymph node. Reproduced with permission from Yasufuku K et al.20
09/11
3. Mediastinoscopy is generally preferable because of the a single sample from the most easily accessible location suf-
higher false negative rates of needle techniques in the fices, but adequate tissue for diagnosis must be confirmed by
setting of normal-sized lymph nodes. the pathologist on frozen section at the time of the procedure
4. Patients with a peripheral clinical stage I non–small cell prior to terminating the operation.
lung cancer do not usually need invasive confirmation of The possibility of a major injury to the azygos vein, innom-
mediastinal nodes unless a PET scan finding is positive in inate artery, or pulmonary artery is very real if the surgeon
the nodes. should inadvertently attempt to obtain a specimen from what
5. The staging of patients with left upper lobe tumors should appears to be a lymph node but is actually a vessel. Often the
include an assessment of the aortopulmonary window azygos vein looks very much like an enlarged lymph node, but
lymph nodes. palpation with the suction or cautery gives the tactile sense of
something other than a solid structure. The development of
Mediastinoscopy is performed with the patient under
this tactile sense often comes only with significant experience
general anesthesia and positioned supine with the neck hyper-
with this procedure. Injury to a vessel may also occur if a
extended. A small cervical incision is made approximately
lymph node is adherent, unbeknownst to the surgeon, who
2 cm above the sternal notch, and the strap muscles are
separated in the midline. The pretracheal fascia is incised, encounters significant bleeding after sampling a node.
and the me

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FOR IMMEDIATE RELEASE

New Editor, New Vision for ACS Surgery

Dr. Ashley is the Frank Sawyer Professor and Vice Chairman

As the new Editor-in-Chief, Dr. Ashley brings his estimable

About Stanley W. Ashley, MD, FACS

About BC Decker Inc

About the American College of Surgeons

For more information, please contact:

ACS Surgery: Principles and Practice

Table 1 American College of Surgeons’ Code of Professional Conduct27

ACS Surgery: Principles and Practice

ACS Surgery: Principles and Practice

environment, the practice of surgery will never again be science-education.nih.gov/snapshots.nsf/story?openform

ACS Surgery: Principles and Practice

ACS Surgery: Principles and Practice

ACS Surgery: Principles and Practice

disadvantages of structural variables Process of Care Measures

ACS Surgery: Principles and Practice

ACS Surgery: Principles and Practice

ACS Surgery: Principles and Practice

ACS Surgery: Principles and Practice

ACS Surgery: Principles and Practice

Risk-Adjusted Mortality (%)

ACS Surgery: Principles and Practice

ACS Surgery: Principles and Practice

3 STRATEGIES FOR IMPROVING SURGICAL

ACS Surgery: Principles and Practice

Table 1 Characteristics of Different Strategies for Improving Surgical Quality

surgical care improvement project (scip)

ACS Surgery: Principles and Practice

Nicholas et al, 2000 US hospitals/ 6 high-risk procedures SCIP INF/VTE- No No No

Lehtinen, 201041 1 ACS-NSQIP hospital Gastrointestinal surgery SCIP INF-10 No

Pastor, 201042 1 US hospital (2006–2008) Colorectal surgery (491) SCIP INF-Composite No

Berenguer, 201029 1 ACS-NSQIP hospital Colorectal surgery (197) SCIP INF-Composite

ACS Surgery: Principles and Practice

Outcomes Measurement and Feedback Regional Collaborative Quality Improvement

ACS Surgery: Principles and Practice

participating in ACS-NSQIP improvement by having the ability to rapidly identify and

ACS Surgery: Principles and Practice

ACS Surgery: Principles and Practice

ACS Surgery: Principles and Practice

Table 1 Levels of Evidence, as Stratified by the chance

“THE REAL WORLD”

Ask the question &

Conduct Measure the results Analyze & interpret

the observed difference that would be expected if the same

5 PATIENT SAFETY IN SURGICAL

Precursors of Latent Unsafe Active

6 PREOPERATIVE TESTING, PLANNING,

ACS Surgery: Principles and Practice

ACS Surgery: Principles and Practice

ACS Surgery: Principles and Practice

ACS Surgery: Principles and Practice

ASA/Surgery CXR ECG CBC Lytes BUN/Cr Glucose LFTs PT/PTT UA

ACS Surgery: Principles and Practice

Frailty Medical Cardiology Resting 2–3 ETT MUGA PFTs Beta

ACS Surgery: Principles and Practice

ACS Surgery: Principles and Practice

but only if the results might change management. Patients

ACS Surgery: Principles and Practice