REVIEW

Diagnosis and Treatment of Peptic Ulcer Disease

Robert T. Kavitt, MD, MPH,a Anna M. Lipowska, MD,b Adjoa Anyane-Yeboa, MD,a Ian M. Gralnek, MD, MSHS, FASGEc,d
a
Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Ill; bDivision of Gastroenterology and Hepatology, Uni-
versity of Illinois at Chicago; cInstitute of Gastroenterology, Hepatology, and Nutrition, Emek Medical Center, Afula, Israel; dRappaport
Faculty of Medicine, Technion−Israel Institute of Technology, Haifa, Israel.

ABSTRACT

Peptic ulcer disease continues to be a source of significant morbidity and mortality worldwide. Approximately
two-thirds of patients found to have peptic ulcer disease are asymptomatic. In symptomatic patients, the most
common presenting symptom of peptic ulcer disease is epigastric pain, which may be associated with dyspep-
sia, bloating, abdominal fullness, nausea, or early satiety. Most cases of peptic ulcer disease are associated
with Helicobacter pylori infection or the use of nonsteroidal anti-inflammatory drugs (NSAIDs), or both. In
this review, we discuss the role of proton pump inhibitors in the management of peptic ulcer disease, highlight
the latest guidelines about the diagnosis and management of H. pylori, and discuss the latest evidence in the
management of complications related to peptic ulcer disease, including endoscopic intervention for peptic
ulcer-related bleeding. Timely diagnosis and treatment of peptic ulcer disease and its sequelae are crucial in
order to minimize associated morbidity and mortality, as is prevention of peptic ulcer disease among patients
at high risk, including those infected with H. pylori and users of NSAIDs.
Ó 2019 Elsevier Inc. All rights reserved.  The American Journal of Medicine (2019) 132:447−456

KEYWORDS: Helicobacter pylori; Peptic ulcer disease

INTRODUCTION treatment of patients with peptic ulcer disease attributed to H.

It was previously accepted as dogma that stress was the etiol- pylori.4 By the end of the 20th century, a decrease in the
ogy of peptic ulcer disease, mediated via increased gastric occurrence of peptic ulcer disease was observed.5 The
acid production.1 Until the late 1970s, peptic ulcers in the decrease in H. pylori infection rate in the population is
United States were treated with antacids and anticholinergics, assumed to have resulted from increasing hygiene standards.5
and surgery was frequently necessary for the treatment of In this review we focus on an update about the diagnosis
ulcer disease.1 Histamine-2-receptor antagonists (H2RAs) of peptic ulcer disease and highlight advances in treatment
were introduced in 1976. Dr. J. Robin Warren had observed strategies in recent years.
Helicobacter pylori (originally named Campylobacter pylo-
ridis) in gastric biopsies,2 and in 1982 Dr. Barry Marshall cul-
tured H. pylori from patients with ulcers and gastritis.3 EPIDEMIOLOGY AND ETIOLOGIC FACTORS
However, it was not until 1994 that National Institutes of Peptic ulcer disease is a source of significant morbidity and
Health guidelines recommended the use of antibiotics in the mortality worldwide. Sequelae may range from abdominal
pain and gastrointestinal bleeding to gastric outlet obstruc-
tion and perforation.
Funding: None. The prevalence of peptic ulcer disease in the United
Conflict of Interest: None.
Authorship: RTK proposed the review topic, collated and reviewed States is estimated to be 8.4%.6 Higher peptic ulcer disease
relevant literature, co-wrote the manuscript, and reviewed each version of incidence has been found to be associated with male sex,
the manuscript; AL and AA collated and reviewed relevant literature and smoking, and chronic medical conditions.6,7 Peptic ulcer
co-wrote the manuscript; IG collated and reviewed relevant literature, co- disease has also been found to be associated with increasing
wrote the manuscript, and reviewed each version of the manuscript. age.8 Over time, a significant decrease in peptic ulcer dis-
Requests for reprints should be addressed to Ian M. Gralnek, MD,
MSHS, Institute of Gastroenterology, Hepatology, and Nutrition, Emek
ease diagnoses, as well as its associated complications, has
Medical Center, 21 Izhak Rabin Blvd., Afula 1834111, Israel. been observed in both the United States and elsewhere in
E-mail address: ian_gr@clalit.org.il the world.9-12

0002-9343/© 2019 Elsevier Inc. All rights reserved.

https://doi.org/10.1016/j.amjmed.2018.12.009
448 The American Journal of Medicine, Vol 132, No 4, April 2019

The majority of peptic ulcer disease cases are now with biopsy of peptic ulcers allows for characterization of a
known to be associated with H. pylori infection or the use benign vs malignant etiology (Figure 2).
of nonsteroidal antiinflammatory drugs (NSAIDs), or Diagnostic testing for H. pylori infection includes urea
both.13 H. pylori is a Gram-negative bacterium that colo- breath testing, stool antigen testing, rapid urease testing or
nizes the gastric mucosa, progressing to gastritis and poten- histology of gastric biopsies taken at the time of upper
tially peptic ulcer disease and gastric cancer.14,15 H. pylori endoscopy, and serologic testing (Table 2). In most circum-
affects a large segment of the stances, tests for active infection
population; however, only a small (urea breath testing, stool antigen
subset will develop clinical dis- CLINICAL SIGNIFICANCE testing, rapid urease testing, or his-
ease.15 NSAID use, including aspi- tology) are preferable compared
rin, is common and leads to an  Two-thirds of patients with peptic with serologic antibody testing due
increased risk of gastrointestinal ulcer disease are asymptomatic; those to low pretest probability of infec-
24
adverse events, including peptic with symptoms most commonly experi- tion. In those with documented
ulcer disease. The relative risk of ence epigastric pain. peptic ulcer disease, serologic test-
developing a symptomatic ulcer is ing for H. pylori immunoglobulin G
4.0 for nonaspirin NSAID users  Most cases of peptic ulcer disease antibody is appropriate due to a
and 2.9 for patients taking aspirin.16 are associated with Helicobacter pylori higher pretest probability.24 Those
While H. pylori and NSAID use infection or nonsteroidal antiinflam- with a peptic ulcer disease history
are the cause of the vast majority of matory drug use. who have been treated for H. pylori
peptic ulcers, other less common in the past are advised to undergo
causes have been identified, includ-  Timely diagnosis and treatment of pep- testing for eradication with either
ing gastrinoma (eg, Zollinger- tic ulcer disease is crucial. stool antigen testing or urea breath
Ellison syndrome), other medica- testing.24 Due to the possibility of
tions, and other etiologies, as false negative testing, testing to
detailed in Table 1.17-19 confirm eradication of H. pylori infection should be per-
formed no sooner than 1 month after completing antibiotic
treatment.24
CLINICAL MANIFESTATIONS AND DIAGNOSIS
A prospective study of patients in Taiwan undergoing a
screening upper endoscopy as part of routine health mainte- ADVANCES IN TREATMENT
nance determined that approximately two-thirds of those
found to have peptic ulcer disease are asymptomatic.20 Role of Proton Pump Inhibitors in the
Among symptomatic patients with peptic ulcer disease, Treatment of Peptic Ulcer Disease
the most common presenting symptom is epigastric pain, Since their introduction into medical practice in the late
which may be associated with dyspepsia, bloating, abdomi- 1980s, proton pump inhibitors (PPIs) have substantially
nal fullness, nausea, and early satiety.21 In many patients, changed the approach to peptic ulcer disease management.
symptoms may be intermittent in nature. PPIs remain the mainstay of medical therapy for peptic
It is imperative to obtain a detailed clinical history about ulcer-related gastrointestinal bleeding. Well-performed sys-
NSAID use and any documented prior H. pylori infection. tematic reviews support the initiation of PPIs prior to endo-
Upper endoscopy can be used to diagnose peptic ulcer dis- scopic evaluation for acute upper gastrointestinal bleeding,
ease and is of particular urgency in those with dyspepsia although a clear mortality benefit has not been demon-
and concurrent alarm symptoms (eg, age >60 years, family strated.25,26 The length of PPI administration following the
history of upper gastrointestinal tract malignancy, weight diagnosis of a peptic ulcer depends on the underlying ulcer
loss, early satiety, dysphagia, gastrointestinal bleeding, iron etiology, location, and associated complications. The ulti-
deficiency anemia, or vomiting) (Figure 1).22,23 Endoscopy mate goal of PPI therapy is to promote ulcer healing

Table 1 Risk Factors for Peptic Ulcer Disease

Helicobacter pylori infection Significantly more common in developing nations
May lead to both gastric and duodenal ulcers
Nonsteroidal antiinflammatory drugs Includes acetylsalicylic acid (ASA)
More commonly associated with gastric ulcers
Other medications Co-administration of corticosteroids and bisphosphonates with NSAIDs;
Sirolimus, selective serotonin reuptake inhibitors (SSRIs), 5-fluorouracil (5-FU)
Smoking Synergistic effect between tobacco use and H. pylori infection
Neoplasms Gastrinoma, gastric adenocarcinoma, carcinoid syndrome
Idiopathic No cause identified despite thorough investigation
NSAID = nonsteroidal antiinflammatory drug.
Kavitt et al Diagnosis and Treatment of Peptic Ulcer Disease 449

History
Epigastric abdominal pain, postprandial
pain, weight loss, nausea, vomiting,
history of NSAID use

For patients <60 without alarm Other patients, patients

features, in regions with H. >60, patients with
Pylori prevalence > 20% alarm features

Test and Endoscopy

treat for H. with ulcer
Pylori biopsy
Figure 1 Diagnosis of peptic ulcer disease.

through acid suppression, while the underlying etiology of bleeding from peptic ulcers in patients with a history of
the ulcer(s) is addressed. Positive H. pylori testing prompts both atherosclerotic and peptic ulcer disease and who take
treatment of the infection, while patients with NSAID- a thienopyridine.39
induced ulcers are counseled to avoid the aggravating When patients who are found to have an H. pylori-
agents.27 Patients with peptic ulcer disease who require related ulcer undergo testing after antibiotic treatment to
ongoing NSAID therapy are recommended to remain on confirm H. pylori eradication, PPI use can lead to false neg-
PPI co-therapy while on treatment.28-30 ative test results. Therefore, it is recommended that patients
Concern over the long-term safety profile of PPI use has switch to treatment with an H2RA rather than a PPI for the
triggered changes in prescribing patterns and patient reluc- 2 weeks prior to H. pylori eradication testing.
tance to pursue treatment.31,32 Long-term PPI use inducing
gastric hypochlorhydria and hypergastrinemia may have an H. Pylori Treatment
adverse effect on absorption of calcium, iron, magnesium, The Maastricht V/Florence Consensus Report, released in
and vitamin B12, and may predispose to infection.33,34 2017, presented evidence-based, consensus guidelines on
Some studies have suggested an association between PPI the diagnosis and management of H. pylori infection.40
use and community-acquired pneumonia, Clostridium diffi- This consensus report cites several meta-analyses illustrat-
cile infection, and chronic kidney disease, among other ing increased H. pylori cure rates for 14-day triple therapy
conditions.35-37 However, causality remains unclear, with over 10-day triple therapy.40 The authors advocate a 14-day
low quality of evidence to date.34 Physicians are advised to H. pylori treatment course for bismuth- and non-bismuth-
evaluate each patient individually, confirming the appropri- containing quadruple therapy as well as clarithromycin-
ate treatment indication and the lowest appropriate PPI based triple therapy (unless 10-day therapies are proven
dose for an appropriate duration of therapy. effective locally). Data supporting extending quadruple
therapy from 10 to 14 days is not as robust, however, the
Role of H2 Receptor Antagonists in Peptic Ulcer guideline recommends a longer duration of antibiotic ther-
Disease apy, particularly in known areas of high resistance to metro-
In the era of PPI therapy, there is only a limited role for nidazole.
H2RAs in the treatment of peptic ulcer disease. As early as The American College of Gastroenterology (ACG) also
the 1980s, as compared with H2RAs, PPIs were demon- published guidelines in 2017 about the diagnosis and treat-
strated to improve rates of peptic ulcer healing.38 A recent ment of H. pylori infection.24 These guidelines also note
randomized controlled trial showed that famotidine failed that prior antibiotic exposure should be taken into account
to significantly reduce the incidence of peptic ulcers or when choosing an H. pylori treatment regimen. The
450 The American Journal of Medicine, Vol 132, No 4, April 2019

Figure 2 Endoscopic images of peptic ulcer disease. (A) Clean-based ulcer of gastric antrum. (B) Ulcer of incisura with adherent
clot. (C) Large ulcer of incisura. (D) Gastric ulcer with adherent clot. (E) Gastric ulcer with nonbleeding visible vessel. (F) Gastric
ulcer with nonbleeding visible vessel after thermal coagulation therapy.
Kavitt et al Diagnosis and Treatment of Peptic Ulcer Disease 451

ing, recommended that biopsies are taken

Stays positive for years after successful cure
guidelines recommend clarithromycin triple therapy with a

Decreased sensitivity by acute ulcer bleed-

sensitivity with the use of bismuth-con-

Most expensive test, not widely available,

decreased sensitivity in bleeding peptic

from 2 sites in the stomach, decreased

PPI, clarithromycin, and amoxicillin or metronidazole for

taining compounds, antibiotics, PPIs

can be used to test for eradication
14 days in areas of low (<15%) clarithromycin resistance

Can be used to test for eradication,

and in those patients with no prior history of macrolide
exposure. The guidelines further suggest bismuth quadruple
therapy (PPI, bismuth, tetracycline, and a nitroimidazole)
for 10-14 days as an additional first-line treatment option,

of the infection
particularly among patients with any prior macrolide expo-
ulcer disease

sure or those with a penicillin allergy.24 Tables 3 and 4

highlight common first-line and salvage therapies for
the treatment of H. pylori recommended by the ACG
Notes

guidelines.24
Only limited data about modern H. pylori treatment regi-
men efficacy and H. pylori antibiotic resistance rates are
85% sensitivity, 79% specificity (if no prior
91%-96% sensitivity, 93%-97% specificity

available in the United States; thus, the majority of guide-

line recommendations are based on data from studies per-
>90% sensitivity, >95% specificity

formed elsewhere in the world. First-line therapies offer the

>95% sensitivity and specificity

>95% sensitivity and specificity

greatest likelihood of treatment success; however, it is

unlikely that most regimens ever achieve >90% eradication
success.24 There are no organized efforts in the United
exposure to H. pylori)

States to track H. pylori antibiotic resistance patterns.24

Management of Complications of Peptic Ulcer

Efficacy

Disease
Complications of peptic ulcer disease include bleeding, per-
foration, penetration, and gastric outlet obstruction.41,42
Gastric biopsies are placed in medium containing urea with
a pH-sensitive indicator. In the presence of H. pylori ure-
Helicobacter pylori antigen detected in the stool by enzyme
Ingestion of urea in presence of isotope C13 or C14 causes

Patient-specific risk factors associated with complicated

ase, urea is metabolized and there is an increase in pH
Detects H. pylori immunoglobulin G antibodies in serum,
CO2 production, which is detected in expired breath

peptic ulcer disease include use of NSAIDs including aspi-

Detects pathologic changes associated with H. pylori

rin, H. pylori infection, smoking, and acid hypersecretory

states (eg, Zollinger-Ellison syndrome). In addition, ulcer-
immunoassay using anti-H. pylori antibody

specific characteristics such as chronicity/refractory type

ulcers, large size (≥1 cm), and location (eg, pyloric chan-
nel) are associated with an increased risk of developing an
ulcer complication. Factors associated with poor outcome
in patients with complicated peptic ulcer disease include
concomitant comorbid disease, older age, poor physiologi-
cal status at the time of presentation (eg, hypotensive shock,
blood, or urine

metabolic acidosis, acute renal failure, hypoalbuminemia),

and delayed treatment.41
Mechanism

Acute upper gastrointestinal hemorrhage is the most

common complication of peptic ulcer disease and is associ-
ated with morbidity (mortality up to 10%) and high medical
Helicobacter Pylori Diagnostic Tests

costs.41,42 Upper endoscopy is the best initial test in sus-

Rapid urease test
Antibody testing
Urea breath test

pected peptic ulcer bleeding because it is both diagnostic

Stool antigen

and, if required, therapeutic. Table 524 highlights the treat-

Histology
testing

ment of peptic ulcer disease prior to, during, and after

Test

endoscopy. Modern-day endoscopic hemostasis therapies

PPI = proton pump inhibitor.

include injection, thermal, mechanical, or a combination of

these modalities.43-45 Endoscopic hemostasis has been
Nonendoscopic diagnostic

Endoscopic biopsy-based

shown to be effective in achieving primary hemostasis and

to significantly reduce ulcer re-bleeding, need for blood
transfusion, urgent surgery, length of hospitalization, and
mortality.46 High-dose intravenous PPIs should be used
Table 2

for 72 hours post endoscopic hemostasis followed by oral

tests

tests

PPI therapy.43-45 Patients with recurrent bleeding should

undergo repeat endoscopy with repeat endoscopic
452 The American Journal of Medicine, Vol 132, No 4, April 2019

Table 3 Common First-Line Therapies for Treating Helicobacter Pylori Infection

Treatment Regimen Medication (Dose) Dosing Frequency Duration of Treatment
Clarithromycin-based triple PPI (standard or double dose) Twice daily 14 days
(if clarithromycin resistance Clarithromycin (500 mg) Twice daily
<15%) Amoxicillin (1 gm) Twice daily
Clarithromycin-based triple (if PPI (standard or double dose) Twice daily 14 days
clarithromycin resistance Clarithromycin (500 mg) Twice daily
<15%, penicillin allergy) Metronidazole (500 mg) Three times daily
Bismuth-based quadruple PPI (standard dose) Twice daily 10-14 days
Bismuth subcitrate (120−300 mg) Four times daily
or subsalicylate (300 mg)
Tetracycline (50 0mg) Four times daily
Metronidazole (250 mg-500 mg) 250 mg 4 times
daily or 500 mg 3
times daily
Concomitant (non-bismuth- PPI (standard dose) Twice daily 10-14 days
based quadruple) Clarithromycin (500 mg) Twice daily
Amoxicillin (1 gm) Twice daily
Metronidazole (500 mg) or Tinidazole (500 mg) Twice daily
Sequential PPI (standard dose) + Amoxicillin (1 gm) Twice daily 5-7 days
PPI (standard dose) + Clarithromycin (500 mg) + Twice daily 5-7 days
Metronidazole (500 mg) or Tinidazole (500 mg)
PPI = proton pump inhibitor.
Note: Adapted from the American College of Gastroenterology Clinical Guideline: Treatment of Helicobacter pylori Infection.24 Note that the only FDA-
approved regimens are clarithromycin triple-therapy with amoxicillin and Pylera (Allergan USA, Inc, Madison, NJ), a combination product containing bis-
muth-based quadruple therapy.

hemostasis.43-45 Those patients who again fail endoscopic used when interventional radiology services are unavailable
hemostasis should be referred for interventional radiology or other therapeutic interventions have failed. Comprehen-
evaluation (eg, multi-detector computed tomography angi- sive, evidence-based guidelines for the evaluation and treat-
ography § transcatheter angiography) and treatment.47 The ment of peptic ulcer bleeding are widely available.43-45
role of surgery in the treatment of peptic ulcer bleeding has Perforated peptic ulcer is a medical emergency with
significantly diminished over the past 2 decades and is now associated mortality of up to 30%.48-50 Perforated peptic

Table 4 Common Salvage Therapies for Treating Helicobacter Pylori Infection

Treatment Regimen Medication (Dose) Dosing Frequency Duration of Treatment
Bismuth-based quadruple PPI (standard dose) Twice daily 14 days
Bismuth subcitrate Four times daily
(120−300 mg) or
subsalicylate (300 mg)
Tetracycline (500 mg) Four times daily
Metronidazole (500 mg) Three times daily or
4 times daily
Fluoroquinolone-based triple PPI (standard dose) Twice daily 14 days
Levofloxacin (500 mg) Once daily
Amoxicillin (1 gm) Twice daily
Concomitant (non-bismuth- PPI (standard dose) Twice daily 10-14 days
based quadruple) Clarithromycin (500 mg) Twice daily
Amoxicillin (1 gm) Twice daily
Metronidazole (500 mg) Twice daily or
or tinidazole (500 mg) 3 times daily
Rifabutin-based triple PPI (standard dose) Twice daily 10 days
Rifabutin (300 mg) Once daily
Amoxicillin (1 gm) Twice daily
PPI = proton pump inhibitor.
Note: Adapted from American College of Gastroenterology Clinical Guideline: Treatment of Helicobacter pylori Infection.24 After failure of second-line
treatment, culture with susceptibility testing to guide treatment. Note that the only US Food and Drug Administration-approved regimen is Pylera (Allergan
USA, Inc, Madison, NJ), a combination product containing bismuth-based quadruple therapy.
Kavitt et al Diagnosis and Treatment of Peptic Ulcer Disease 453

Table 5 Treatment for Peptic Ulcer Disease

Treatment for Peptic Ulcer Disease
Prior to Endoscopy During Endoscopy After Endoscopy
Assess hemodynamic stability and provide Perform endoscopic procedure within If high-risk stigmata is present on endos-
resuscitation 24 hours of presentation following copy, treat with high-dose intravenous
resuscitation and optimization of PPI for 72 hours
other medical problems
Administer blood transfusion to target hemo- Assess for high-risk peptic ulcer stig- Repeat endoscopy if there is evidence of
globin ≥7 g/dL mata including active bleeding, visi- recurrent bleeding
ble vessel, or adherent clot
Utilize the Glasgow-Blatchford Score for risk Carry out endoscopic therapy if active Avoid routine second-look endoscopy
stratification. If the score is zero, consider bleeding or visible vessel are after initial endoscopic therapy
early discharge without intervention identified
Evaluate for coagulopathy and consider dis- Add a second modality of treatment, Refer to surgery or interventional radiol-
continuation of blood-thinning medications such as thermal therapy or clipping, ogy if there is rebleeding after second
if evidence of bleeding is present to epinephrine injection endoscopic therapy
Stop NSAID drugs Closely assess need for NSAIDs in those
with NSAID-associated ulcers
Consider use of prokinetic drugs to aid in visu- Treat for Helicobacter pylori infection if
alization and decrease need for repeat applicable
endoscopy
Initiate PPI intravenous therapy prior to Continue long-term PPI therapy in those
endoscopic intervention to decrease likeli- with idiopathic peptic ulcers
hood of high-risk stigmata presence during
endoscopy
NSAID = nonsteroidal antiinflammatory drugs; PPI = proton pump inhibitor.
From Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017;112
(2):212-239.

ulcer should be suspected in patients presenting with aorto-enteric fistula), and the colon. Pyloric channel or
acute, diffuse, severe, abdominal pain.48,49 The classic prepyloric peptic ulcers may penetrate directly into the
triad of sudden onset of abdominal pain, tachycardia, duodenal bulb, creating a gastroduodenal fistula, creating
and abdominal rigidity is the hallmark of peptic ulcer an acquired “double” pylorus.51 Complications of ulcer
perforation.48 Physical examination can demonstrate penetration into adjacent anatomic structures include
abdominal distension, tenderness to palpation, guarding, abscess formation, exsanguinating hemorrhage, hemobilia,
and rebound when peritonitis is present. Leukocytosis hyperamylasemia, and rarely, pancreatitis.
and fever may be present. Plain film chest x-ray studies Gastric outlet obstruction is the least common complica-
(upright) may miss sub-diaphragmatic free air in up to tion of peptic ulcer disease, yet when it does occur, is most
15% of cases in patients with bowel perforation.49 often associated with a duodenal or pyloric channel ulcer.
Abdominal computed tomography is more sensitive However, with the decreasing incidence of peptic ulcer dis-
(98% sensitivity) in detecting small amounts of free air ease, upper gastrointestinal tract malignancy may now be a
and has thus become the imaging modality of choice in more common cause of gastric outlet obstruction. Clinical
suspected perforated peptic ulcer.48 Initial management manifestations include bloating, nausea, vomiting, early
includes nil per os status, nasogastric suction, fluid satiety, anorexia, epigastric distress, and weight loss.52,53
resuscitation, PPI, broad-spectrum antibiotics, and The diagnosis is usually made with upper endoscopy and
immediate surgical consultation. Early diagnosis, prompt biopsy, especially to exclude malignancy.52 In selected
hemodynamic resuscitation, and urgent surgical inter- cases, computed tomography or surgical evaluation may be
vention are imperative to improve patient outcomes. necessary to obtain a definitive diagnosis when malignancy
Delay to surgery has consistently been shown to be is suspected and endoscopic biopsies are unrevealing.
associated with increased mortality.48-50 Treatment of patients with gastric outlet obstruction due to
Peptic ulcer penetration is defined as the penetration of a benign cause, and who are thought to have reversible fac-
an ulcer through the bowel wall into an adjacent organ or tors, may be achieved with medical therapy (eg, intensive
anatomic structure without free air perforation or leakage antisecretory therapy initially using high-dose intravenous
of bowel contents into the peritoneal cavity. Penetration PPI, and then oral PPI if responsive). Patients not respond-
occurs most commonly with gastric antral ulcers and ing to medical therapy should be considered for endoscopic
duodenal ulcers. Penetration may occur into the pancreas, therapy (eg, balloon dilatation or biodegradable stent).52,53
biliary tract, omentum, liver, vascular structures (eg, However, in patients with fibrosis and scarring, endoscopic
454 The American Journal of Medicine, Vol 132, No 4, April 2019

therapy may be inadequate and thus, elective surgery (eg, clear. The relative risk of rebleeding and mortality is higher
pyloroplasty or gastrojejunostomy drainage procedures) in patients with H. pylori-negative idiopathic ulcers than in
may be preferred. H. pylori-positive controls.62 The ACG guidelines condi-
tionally recommend daily PPI therapy for these patients,
however, data are quite limited.44
Prevention of Peptic Ulcer Disease
NSAID use increases the risk of rebleeding in patients with
prior peptic ulcer disease. The ACG 2012 guideline about CONCLUSIONS
the management of patients with ulcer bleeding advises Timely diagnosis and management of peptic ulcer disease
careful assessment of the need for ongoing NSAID use in and its sequelae are crucial, as is prevention of peptic ulcer
patients with a history of peptic ulcer and permanent disease among patients at high risk. Prompt diagnosis of
NSAID discontinuation if possible.44 If a patient is unable H. pylori and initiation of appropriate therapy is important,
to discontinue NSAIDs, it is recommended that a cyclooxy- as is cautious use of NSAIDs.
genase (COX)-2 selective NSAID be used at the lowest
effective dose in conjunction with a PPI.44 The risk of
rebleeding is decreased by the use of a COX-2 selective ACKNOWLEDGMENT
NSAID in conjunction with a proton pump inhibitor, and We thank Debra Werner, library services at the University
this is thought to be due to decreased effects of COX-1 on of Chicago, who diligently assisted in the comprehensive
the gastrointestinal mucosa.54,55 literature search. Ms. Werner received no extra compensa-
Furthermore, the risk of rebleeding with concomitant tion for her contributions.
NSAID use and H. pylori infection is higher than the risk of
bleeding with NSAID use alone.56 For patients with H.
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