WJGEv 4 I 6

ISSN 1948-5190 (online)
World Journal of
Gastrointestinal Endoscopy
World J Gastrointest Endosc 2012 June 16; 4(6): 201-268
www.wjgnet.com
Editorial Board
2009-2013
The World Journal of Gastrointestinal Endoscopy Editorial Board consists of 400 members, representing a team of
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June 16, 2012
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June 16, 2012
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June 16, 2012
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June 16, 2012
Contents
EDITORIAL
Monthly Volume 4 Number 6 June 16, 2012

201
Endoscopy in inflammatory bowel disease when and why

Rameshshanker R, Arebi N
212
NOTES, MANOS, SILS and other new laparoendoscopic techniques

Noguera JF, Cuadrado A
TOPIC HIGHLIGHT
218 Endoscopic ultrasound using ultrasound probes for the diagnosis of early
esophageal and gastric cancers
Yoshinaga S, Oda I, Nonaka S, Kushima R, Saito Y
OBSERVATION
227
Informed consent for digestive endoscopy

Kopacova M, Bures J
231
Supportive techniques and devices for endoscopic submucosal dissection of gastric

cancer
Sakurazawa N, Kato S, Fujita I, Kanazawa Y, Onodera H, Uchida E
GUIDELINES FOR
236
BASIC SCIENCE
GUIDELINES FOR
Outcomes research in gastroenterology and endoscopy

Gupta P, Buscagli JM
241
CLINICAL PRACTICE
Post-endoscopic retrograde cholangiopancreatography complications: How can they

be avoided?
Vila JJ, Artifon ELA, Otoch JP
REVIEW
247
Pancreatic cystic lesions: How endoscopic ultrasound morphology and

endoscopic ultrasound fine needle aspiration help unlock the diagnostic puzzle
Barresi L, Tarantino I, Granata A, Curcio G, Traina M
BRIEF ARTICLE
260
Sedation practices for routine diagnostic upper gastrointestinal endoscopy in

Nigeria
Nwokediuko SC, Obienu O
CASE REPORT
266
Unusual penetration of plastic biliary stent in a large ampullary carcinoma: A case

report
Tolan HK, Sriprayoon T, Akaraviputh T
WJGE|www.wjgnet.com
June 16, 2012|Volume 4|Issue 6|
World Journal of Gastrointestinal Endoscopy
Contents
Volume 4 Number 6 June 16, 2012
ACKNOWLEDGMENTS
Acknowledgments to reviewers of World Journal of Gastrointestinal Endoscopy
APPENDIX
Meetings
I-V
Instructions to authors
ABOUT COVER
Yoshinaga S, Oda I, Nonaka S, Kushima R, Saito Y. Endoscopic ultrasound

using ultrasound probes for the diagnosis of early esophageal and gastric
cancers.
World J Gastrointest Endosc 2012; 4(6): 218-226

http://www.wjgnet.com/1948-5190/full/v4/i6/218.htm
World Journal of Gastrointestinal Endoscopy (World J Gastrointest Endosc, WJGE, online ISSN
1948-5190, DOI: 10.4253), is a monthly, open-access, peer-reviewed journal supported
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FLYLEAF
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doi:10.4253/wjge.v4.i6.201
EDITORIAL
Endoscopy in inflammatory bowel disease when and why

Rajaratnam Rameshshanker, Naila Arebi
Rajaratnam Rameshshanker, Naila Arebi, Department of
Gastroenterology, St Marks Hospital, Watford Road, London,
HA1 3UJ, United Kingdom.
Author contributions: Rameshshanker R and Arebi N both
equally contributed to this paper.
Correspondence to: Dr. Rajaratnam Rameshshanker, MB,
MRCP, Department of Gastroenterology, St Marks Hospital,
Watford Road, London, HA1 3UJ,
United Kingdom. rameshshan777@yahoo.co.uk
Telephone: +44-2082354084 Fax: +44-2082354093
Received: August 25, 2011
Revised: November 21, 2011
Accepted: May 27, 2012
Published online: June 16, 2012
Associate Professor, Department of Medicine, Faculty of

Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia
Rameshshanker R, Arebi N. Endoscopy in inflammatory
bowel disease when and why. World J Gastrointest Endosc
2012; 4(6): 201-211 Available from: URL: http://www.wjgnet.
com/1948-5190/full/v4/i6/20.htm DOI: http://dx.doi.
org/10.4253/wjge.v4.i6.20
INTRODUCTION
Endoscopy is a crucial tool in the management of inflammatory bowel disease (IBD). There is a spectrum
of situations when an endoscopy may be of value in
IBD, extending from initial diagnosis to differentiating
between Crohns disease (CD) and ulcerative colitis (UC)
to long term management of both conditions.
Of the several endoscopic tools, colonoscopy remains the prime diagnostic tool. Gastroscopy, enteroscopy and endoanal ultrasound scan may be useful in the
assessment of specific organ involvement in CD and to
differentiate between UC and CD. Novel tools such as
capsule endoscopy and double balloon enteroscopy have
been playing an increasing role for small bowel Crohn
s disease assessments. Both CD and UC can be complicated by primary sclerosing cholangitis (PSC): ERCP
previously the gold standard to diagnose PSC has broadly been superseded by magnetic resonance cholangio
pancreatography[1]. This article will focus on the role of
colonoscopy in IBD as this is by far the most important
tool. A brief overview of other endoscopic tools will
follow.
Abstract
Endoscopy plays an important role in the diagnosis and
management of inflammatory bowel disease (IBD). It
is useful to exclude other aetiologies, differentiate between ulcerative colitis (UC) and Crohns disease (CD),
and define the extent and activity of inflammation.
Ileocolonoscopy is used for monitoring of the disease,
which in turn helps to optimize the management. It
plays a key role in the surveillance of UC for dysplasia
or neoplasia and assessment of post operative CD.
Capsule endoscopy and double balloon enteroscopy
are increasingly used in patients with CD. Therapeutic
applications relate to stricture dilatation and dysplasia
resection. The endoscopists role is vital in the overall
management of IBD.
Key words: Colonoscopy; Oesophagogastroduodenoscopy; Capsule endoscopy; Enteroscopy; Ulcerative colitis; Crohns disease; Dysplasia; Endoscopist
COLONOSCOPY
Peer reviewers: Sherman M Chamberlain, Associate Professor
Over the years, improvements in colonoscope technology have led to more comfortable procedures with better
quality image definition (namely narrow band imaging,
chromo endoscopy, endomicroscopy and high definition
screens)[2]. Training in colonoscopy has optimised the
of Medicine, Section of Gastroenterology, BBR-2538, Medical

College of Georgia, Augusta, GA 30912, United States; Oscar
Tatsuya Teramoto-Matsubara, Med Center, Av. Paseo de las
Palmas 745-102, Lomas de Chapultepec, Mxico, 11000,
Mxico; Sanjiv Mahadeva, MBBS, MRCP, CCST, MD,
WJGE|www.wjgnet.com
201
Rameshshanker R et al . Endoscopy in IBD

Table 2 Non infective causes of diarrhoea
Table 1 Infective causes of inflammation which mimic inflammatory bowel disease
Inflammatory
Behcets disease
Drugs
Non streroidal anti inflammatory drugs
Erythema and ulcers in colon
Iatrogenic
Gold
Penicillamine
Radiation colitis
Mild to moderately severe colitis
Vascular
Infective cause
Salmonella
Endoscopic appearance
Friable mucosa with haemorrhages in ileum and colon
Shigella
Patchy intense erythema in ileum and colon
Campylobacter
E.coli 0157:H7
Yersinia
Patchy colitis with ileal aphthoid ulcers
C.difficile
Pseudo membranes and predominantly left side colitis
Klebsiella
Haemorrhagic colitis
Mycobacterium
Transverse or circumferential ulcers ileum
Neisseria
Proctitis with ulcers and peri anal disease
Chlamydia
Peri anal abscess, ulcer and fistula
Treponema
Proctitis with ulcers and peri anal disease
Schistosoma
Extensive colitis, may be segmental with polyps
Entamoeba
Acute colitis and ulcers
Herpes
Proctitis with rectal ulcers and perianal disease
Neoplastic
ulcers, which may coalescence to large ulceration extending circumferentially. By virtue of the continuous
inflammatory nature of UC, ulcers always surrounded by
inflamed mucosa (Figure 3).
Distribution of the inflammation may be helpful in
differentiating between UC and other causes of colitis
particularly Crohns colitis. Rectal involvement is invariable with continuous disease extending proximally. Recognised variations to this pattern include rectal sparing,
particularly if patients have been using topical therapy,
and peri-appendiceal inflammation. Small bowel involvement may occasionally be present in the form of
backwash ileitis. This appearance differs from CD: diffuse continuous erythema with no ulceration compared
to typical Crohns appearance [9]. Endoscopic mucosal
appearance alone might underestimate the extent when
compared to the histological involvement.
Chronic UC may display quiescent disease but changes
of previous activity such as post-inflammatory polyps
(Figure 4) scarring (Figure 5) and a shortened tubular colon (Figure 6) may be evident. Strictures are rare in UC; its
presence heralds a fivefold risk of colorectal cancer (CRC)
and such patients should be followed up with care[10].
Disease extent and activity influence medical management: this is reflected in the choice of medical
therapy and the route of administration as well as risk
stratification of colonic cancer[11]. Hence the importance
of recording these finding in endoscopic report cannot
be underestimated. Disease extent is recorded as the
extent of inflammation from the anal verge; mucosal
involvement is not static it can progress or regress over
time[12]. Disease activity is recorded as mild, moderate or
severe with more than 12 disease activity scoring systems
reported in the literature[13]. Commonly used endoscopic
indices[14-18] are summarised in Table 3. The score used in
most drug studies is the Mayo endoscopic score of activity. The Mayo score ranges from 0 to 12, with higher
scores corresponding with more severe disease[19]. An
optimal scoring instrument for UC is still to be developed and will require validation before extensive use in
clinical trials can be promoted13].
Cytomegalovirus Colitis with punched out shallow ulcers

Aspergillus
Ulcers with bleeding
Histoplasma
Predominantly right side colitis
use of this instrument for various diagnostic purposes.

Colonoscopy remains the first line endoscopic investigation for suspected CD. Flexible sigmoidoscopy offers a
diagnostic option for UC, with colonoscopy reserved to
define the disease limit in some cases. The role of colonoscopy in the management of IBD can be summarised
as follows[3,4]: (1) to establish a diagnosis; (2) to assess
the disease extent and activity; (3) to monitor disease
activity; (4) for surveillance of dysplasia or neoplasia; (5)
to evaluate ileal pouch and ileorectal anastomosis; (6) to
provide endoscopic treatment, such as stricture dilation/
stent placement.
COLONOSCOPY AS A DIAGNOSTIC TOOL

One of the pitfalls in diagnosing IBD is the failure to
consider other diseases, which may give terminal ileal
and colonic inflammation. By far the commonest cause
of inflammation is infection. Infective causes[5] are outlined in Table 1; the typical features to assist diagnosis
are also described. Other conditions that may mimic
IBD[6] with colonic and terminal ileum (TI) inflammation are summarised in Table 2.
Once these conditions have been excluded there
remains the challenge of differentiating between CD
and UC. This activity has important implications for disease management and prognosis. Whilst most cases are
straightforward, around 5% of cases particularly with
colitis, final diagnosis is evasive and the disease is defined
as unclassified IBD[7].
Features of UC
The endoscopic findings of active UC range from erythema, loss of the usual vascular pattern due to oedema,
granularity of the mucosa and friability/spontaneous
bleeding to erosions/ulceration[8] (Figures 1 and 2).
The ulceration in UC has typical features: superficial
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Vasculitis
Ischaemic colitis
Colorectal cancer
Features of Crohns disease

Inflammation in CD can involve the entire gastrointestinal tract; 40%-55% of cases show inflammation
in the terminal ileum and colon, 15%-25% colonic inflammation alone and in 25%-40% ileum is exclusively
202

Screening colonoscopy at 10 years
(preferably in remission, pancolonic dye-spray)
Intermediate risk
Extensive colitis with mild active
endoscopic/histological inflammation
or post-inflammatory polyps
or family history CRC in FDR aged
50+
Lower risk
Extensive colitis with no
active endoscopic/histological
inflammation
or left-sided colitis
or Crohn's colitis of < 50%
colon
3 years
5 years
Higher risk
Extensive colitis with moderate/severe active
endoscopic/histological inflammation
or stricture in past 5 years
or dysplasia in past 5 years declining surgery
or PSC/transplant for PSC
or family history CRC in FDR aged < 50 years
1 year
Figure 1 British Society of Gastroenterology guidelines on surveillance of colitis. PSC: Primary sclerosing cholangitis; CRC: Colorectal cancer.
Post-colectomy surveillance of
puch/rectal mucosa
Lower risk
None of the higher
rish factors
Consider 5 years
Higher risk
Any of:
Previous rectal dysplasia
Dysplasia/cancer at time of pouch
surgery
PSC
Type C mucos a puch (persistent
atrophy and severe inflammation)
Figure 3 Severe colitis (Sutherland score 3). Friable, granular mucosa with
exudates overlying the surface, ulcers and sub mucosal oedema of rectum.
Consider 1 year
Figure 2 British Society of Gastroenterology surveillance recommandations post colectomy. PSC: Primary sclerosing cholangitis.
Several activity indices for CD are in use. Most of

them are complicated and time consuming. A simple
scoring system suitable for clinicians is the simple endoscopic score of CD (SES-CD) which came into use
recently. Table 4 summarises the features of SES-CD[24].
Biopsy specimens should be taken from ulcerated
mucosa as well as from normal mucosa adjacent to
inflammatory areas, in order to demonstrate the skip
phenomenon. Biopsy specimens taken from the edges
of ulcers and aphthous erosions maximize the yield of
identifying granulomas. The practice of collecting biopsies from macroscopically normal rectal mucosa allows
the differentiation between a diagnosis of UC in suspected colonic CD[21,22,25]. Table 5 summarises the prime
endoscopic differences between UC and CD[26].
involved[20]. Involvement of oesophagus, stomach and

proximal small bowel occurs in up to 10% of CD patients. The rectum is spared in up to 50% patients with
colonic disease[6].
The endoscopic hallmark of CD is the heterogeneous
patchy nature of inflammation or skip lesions (areas of
inflammation interposed between normal mucosa). Ulceration in CD commonly occurs on a background of
minimal inflammation[5].
CD ulcers tend to be longitudinal, polycyclic ulcers
(snail track) associated with cobblestone appearance of
ileum, fistulous tract and strictures either in the colonic
or ileum. Circumferential inflammation is rare in CD. The
ulcers are deep when compared to superficial ulcers in
UC[6] (Figure 7).
The presence of small ulcerations on the ileocaecal valve or within the TI in a symptomatic individual
is highly suggestive of CD (Figure 8); the possibility of
tuberculosis and nonsteroidal antiinflammatory drug induced ileal ulcers should be considered[21,22]. Young people
may have benign aphthous ulceration related to lymphoid
hyperplasia which should not be diagnosed as CD[23].
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MONITORING DISEASE ACTIVITY

The use of colonoscopy as a diagnostic tool is non-contentious. Its value in disease monitoring is an evolving
indication for the procedure. The thrust in this direction
comes from the more recent focus on mucosal healing
or reducing inflammatory activity in IBD. The prognostic implications of mucosal healing include reduced sur-
203

Table 3 Endoscopic indices used in ulcerative colitis
0
3
Exudates and spontaneous haemorrhages
4
-
Mild (erythema, decreased Moderate (marked erythema, absent Severe (spontaneous

vascular pattern)
vascular pattern)
bleeding, ulceration)
Baron
Normal: matt mucosa, ramify- Abnormal, but non-haemor- Moderately haemorrhagic: bleeding Severely haemorrhagic:
ing vascular pattern, no sponta- rhagic: appearances between to light touch, but no spontaneous spontaneous bleeding
neous bleeding/to light touch 0-2
bleeding
and bleeds to light touch
Feagan
Normal, smooth, glistening Granular mucosa; vascular As 1, with a friable mucosa, but not As 2, but mucosa spon- As 3, but clear
mucosa, with normal vascu- pattern not visible; not fri- spontaneously bleeding
taneously bleeding
ulceration; delar pattern
able; hyperaemia
nuded mucosa
Sutherland
Normal
Schroeder
Normal or inactive disease
1
Mild friability
2
Moderate friability
Powel- Tuck Non haemorrhagic, no spon- Haemorrhagic, no spontane- Haemorrhagic, spontaneous bleedtaneous bleeding or bleeding ous bleeding, but bleeding ing ahead of instrument at initial into light touch
to light touch
spection with bleeding to light touch
Lemann,
Hanauer
Normal mucosa
Oedema, +/- loss of vascular Friability, petechiae

pattern, granularity
Spontaneous haemorrhage, visible ulcers
Figure 4 Post inflammatory polyp in transverse colon in a patient with

ulcerative colitis.
Figure 5 Extensive scarring of sigmoid colon in a patient with long history of colitis.
gical intervention[27], prolonged remission[27], and reduced

risk of colorectal cancer[10].
Patients with quiescent disease may have a relatively
normal appearing mucosa with a distorted vascular pattern but without friability. Mild disease might appear
oedematous and granular with distortion of the vascular
markings, moderate activity is defined by the presence of
a coarse granular pattern, erosions and friability of the
mucosa. Severe disease displays gross ulcerations and areas bleed spontaneously[5]. The presence of severe ulceration is usually associated with refractory disease and increased frequency of complications such as perforation[5].
pan-colitis[30]. Risk assessment of CRC also critically relies on endoscopic appearance of the severity of disease
activity: both endoscopic and histological inflammation
was shown to be associated with increased risk[10,31]. Conversely, in a macroscopically normal colonoscopy the associated cancer risk was observed to be similar to age and
sex-matched controls[10]. PSC is an independent risk factor for cancer with an odd ratio for developing cancer of
4.49 (95% CI: 3.58-6.41) compared to patients without
PSC[32].
As a consequence of the above observations, colonoscopic surveillance for neoplasia is recommended by
most gastroenterology and endoscopic societies. The
purpose of surveillance colonoscopy is to identify early
pre-malignant lesions indicative of an enhanced risk
of CRC. The original literature focused on dysplasiaassociated lesions/masse (DALM), however we now have
evidence that neoplasia may be flat and subtle. The endoscopic techniques for improving dysplasia detection are
discussed here in the later section.
SURVEILLANCE FOR DYSPLASIA OR

NEOPLASIA
Several studies have reported an increased risk for colorectal cancer in UC and Crohns colitis. This risk has been
examined with respect to disease duration and extent[28,29].
The cumulative risk for colorectal cancer was estimated
as 1.6%, 8.3% and 18.4% after 10, 20 and 30 years of
disease respectively[28]. The associated risk for extent was
reported in a population based study as standardised
incidence ratio of 2.8 for left sided colitis and 14.8 for
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FLEXIBLE SIGMOIDOSCOPY
One of the limitations of colonoscopy is the need for
204
Figure 6 Shortened tubular colon in a patient with pan colitis.
Figure 8 Multiple linear, deep ulcers with normal islands of intervening

mucosa in the terminal ileum indicates severe Crohns disease.
Table 4 Simple endoscopic score for Crohns disease

Variable
Size of ulcers
Figure 7 Deep ulcers, sub mucosal oedema and haemorrhages in the sigmoid colon in a patient with Crohns colitis.
Ulcerated
surface
Affected
surface
None
Presence of
narrowing
None
Unaffected
segment
1
Aphthous
ulcers
< 10%
2
Large ulcers
10%-30%
3
Very large
ulcers
> 30%
< 50%
50%-75%
> 75%
Single, scope Multiple, scope

Scope
passable
passable
impassable
Table 5 Differences in the macroscopic appearance between

Crohns disease and ulcerative colitis
oral bowel preparation to enhance adequate mucosal

views. In some situations a limited examination of the
left colon with flexible sigmoidoscopy may suffice. The
procedure may be undertaken following an enema or
sometimes-unprepared procedure. Sigmoidoscopy provides useful information in many situations particularly:
(1) when colonoscopy is considered high risk or contraindicated e.g., acute severe colitis or fulminant colitis[13]; (2) to define the severity of the disease in established colitis; (3) to exclude superimposed infection with
cytomegalovirus (CMV) and C.Difficile; (4) to exclude
other causes for symptoms when there is poor response
to therapy e.g., ischaemic colitis.
Macroscopic features
UC
CD
Erythema
+++
++
Loss of vascular pattern
+++
Granularity of mucosa
+++
++
Cobble stone appearance

Pseudo polyps
+++
+++
Aphthous ulcers
+++
Deep ulcers
+++
Patchy inflammation
+++
++++
+++
++
Ileal ulcers
Rectal involvement
UC: Ulcerative colitis; CD: Crohns disease.
sions, and thickened mucosal folds[35]. OGD with small

bowel biopsy in patients with IBD include evaluation of
concomitant coeliac disease and small bowel adenocarcinoma[36]. There are therapeutic applications of OGD
in patients suffering from CD; symptomatic duodenal or
pyloric strictures (Figure 9) can be successfully treated
with endoscopic balloon dilation[37] (Figure 10).
OESOPHAGO-GASTRODUODENOSCOPY
Oesophagogastroduodenoscopy (OGD) in suspected
IBD are recommended in paediatric population where
differentiating between UC and CD can be challenging[33]. In adult IBD, there are no specific recommendations. Symptoms of dyspepsia, abdominal pain, vomiting
or findings of nutritional deficiency in CD warrant an
OGD. Upper gastrointestinal (GI) tract involvement
occurs in up to 13% of patients with CD[34]. Moreover a minority of UC patients may also have upper GI
tract inflammation, manifesting as diffuse duodenitis
or gastritis, characterised by oedema, erythema, ero-
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Simple endoscopic score

0
None
CAPSULE ENDOSCOPY
Small bowel capsule endoscopy (SBCE) was first introduced in 2001. Over the last decade it has evolved as
a sensitive modality for the detection of small bowel
205
Figure 9 Linear pyloric ulcer and surrounding sub mucosal oedemapyloric Crohns disease.
Figure 10 Balloon dilatation of Crohns stricture.
lesions including CD. The main advantage of SBCE is

the potential to visualise the entire length of the small
bowel. It is less invasive and better tolerated. When compared to radiological investigations (CT or MR enterography) it is very sensitive to detect early mucosal lesions.
Recent study showed the sensitivity for diagnosis of CD
of the terminal ileum 100% by SBCE, 81% MR enterography, and 76% by CT enterography, respectively[38,39].
Recent meta-analysis suggested that SBCE has the
highest diagnostic yield in non-stricturing CD (69%
SBCE vs 30% small bowel Barium follow through) and is
significantly superior to the conventional endoscopy or
CT/MR enterography for lesion detection. It is particularly useful in patients with established CD to detect disease recurrence[40]. There are drawbacks of SBCE. The
main disadvantage is the lack of tissue sampling option.
Non-diagnostic mucosal abnormalities may thereafter
need to be followed by more invasive (enteroscopy) procedures for histological sampling. Additional drawbacks
include obscured view due to debris, non-suitability for
patients with delayed transit and the risk of capsule retention in severe stricturing disease[40].
Despite the limitations experts propose capsule endoscopy for monitoring of patients with known diagnosis of Crohns disease and in detecting post surgical disease recurrence[41,42]. Costs and availability may however
mitigate its value in repetitive testing.
gical decisions on 20 of the 33 occasions reducing the

length of planned resection in 14 cases.
ROLE OF ENDOSCOPY IN SPECIAL

SITUATIONS
Endoscopic surveillance
Surveillance for CRC is indicated for patients with IBD:
the risks for UC are similar to Crohns colitis of equal
colonic extent and disease duration. Endoscopic appearances are a valuable predictor of future dysplasia and
CRC[2]. Rutter et al[10] showed that post-inflammatory
polyps, strictures, shortened colons and tubular colons
were associated with increased risk for future neoplasia
with respective odds ratios of 2.14 (95% confidence
interval 1.24-3.70), 4.22 (1.08-15.54), 10 (1.17-85.6) and
2.03 (1.00-4.08). No significant association was found
with the presence of backwash ileitis, scarring, or a featureless colon.
The British Society of Gastroenterology (BSG) guidelines propose that patients with UC or Crohns colitis
should have a colonoscopy 10 years after the initial diagnosis to define the extent and activity of the disease[7].
Surveillance colonoscopy should be undertaken preferably
in remission. The following risk factors dictated the risk
and frequency of future surveillance procedures: disease
duration and extent associated primary sclerosing cholangitis, family history of sporadic colorectal cancer, young
age at diagnosis and endoscopic and histological appearance during colonoscopy[5,9,10]. Screening interval depends
on the above risk factors and according to the national
and international guidance. Figures 1 and 2 illustrates the
summary of current BSG guidelines[7].
Several studies have shown improved detection rates
for dysplasia and cancer if targeted biopsies are taken
rather than random biopsies[10]. This approach may serve
to mitigate the poor clinician compliance to endoscopic
protocols for random biopsies every 10 cm [47]. Narrow band imaging has been shown to be no better than
standard white light colonoscopy and hence cannot be
recommended as an alternative to chromo endoscopy[7].
Although confocal endomicroscopy may enhance the
ENTEROSCOPY
Double balloon enteroscopy allows a more complete
evaluation of the small intestine than single balloon
enteroscopy [43-45]. It complements capsule endoscopy
particularly when the diagnosis of IBD is uncertain and
biopsies are required and for therapeutic interventions
namely dilation of small bowel strictures[43,44].
A recent study examined the value of intra-operative
enteroscopy to define mucosal inflammation extent as a
means of minimising resection length[46]. Intra operative
small bowel endoscopy was performed on 33 occasions
in 31 patients with CD to compare intraluminal to external inflammation. Endoscopic findings influenced sur-
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206
Figure 11 Dysplasia-associated lesions/masse in caecal pole in a patient

with a long history of pancolitis.
Figure 12 Dysplasia-associated lesions/masse in caecal pole after dye

spray.
in vivo characterisation of lesions, it requires prior lesion

detection by other means before confocal endomicroscopy can be deployed[2]. Therefore pan colonic dye spray
(either with methylene blue or indigo carmine) with
targeted biopsies is now recommended[7]. Intuitively
such an approach may be expected to be time consuming however the colonoscopy duration was not shown
to differ to standard colonoscopy[10]. A recent study by
Saunders et al[48] described a time-saving technique using
a washer pump for dye spray application: indigo carmine
was successfully applied to the entire mucosal surface
and reduced the procedural time by several minutes
while optimising mucosal views and biopsy access.
Most cancers arise with pan colitis; there is little or
no increased risk associated with proctitis and left-sided
colitis carries an intermediate cancer risk[13]. There is
evidence to indicate that colorectal cancer is also more
likely to develop with persistent colonic inflammation
even in microscopic level[2]. Hence, active inflammation
noted at surveillance colonoscopy, is an indication for
escalation of medical treatment.
When a dysplastic polyp is detected, it is essential
to biopsy the adjacent flat mucosa at the base of the
dysplastic polyp to assess the extent of disease and also
to detect dysplasia in the surrounding (macroscopically
normal) flat mucosa. This may help to differentiate between adenoma-like lesions (ALM) or the traditionally
described DALMs[49] (Figures 11 and 12). The swathe of
literature pertaining to the management of dysplastic lesions has been summarised in several review articles and
lies beyond the scope of this article.
histological assessment is needed to make the diagnosis

of pouchitis[51,52].
Pouch endoscopy (pouchoscopy) provides crucial information with respect to the severity and extent of mucosal inflammation, pre-pouch ileitis and CD of pouch
and cuffitis. It also demonstrates other abnormalities
such as polyps, strictures, sinuses and fistula. Supplemental information from histology may reveal granulomas,
CMV inclusion bodies and dysplasia[51,53-59]. Several diagnostic criteria are available and the commonest in clinical
use is the pouch disease activity index[60].
Postsurgical crohns disease
Ileal or ileocolonic CD (Montreal L1 or L3) affects 75%
of the Crohns population[6,20]. In this selected group of
patients remission may be achieved by medical or surgical means with a right hemi-colectomy. The latter procedure may also be required for complications particularly
strictures and penetrating disease with fistula formation.
Disease recurrence in the neo-terminal ileum is invariable. Rutgeerts group reported endoscopic, clinical
and surgical recurrence rates of 73%, 20% and 5% at
1 year respectively[12]. We reported similar rates at our
centre for clinical and surgical recurrence in a retrospective series of 99 patients following surgery (28% clinical
and 5% surgical recurrence at 1 year)[61]. The Rutgeerts
scoring system is proposed as a means to predict postsurgical recurrence risk[62] (Table 6). The predictability of
future clinical recurrence was based on neo-terminal ileal
endoscopic appearances (Figure 13) at one year, with a
greater risk for scores > i2[12].
Other clinical and histological risk factors for disease
recurrence have been identified. The evidence for smoking is the most compelling[63]. Additional clinical factors
are disease behaviour with perforating disease and previous resection for CD. Plexitis in the proximal margin of
resection specimens implies more aggressive disease and
greater recurrence risk[64].
Post-surgical colonoscopic examination of ileocolonic anastomosis (Figure 14) is a valuable predictor
for risk of recurrence and may identify patients in need
of medical therapy escalation. The optimal time interval
Endoscopic assessment of pouchitis

Pouchitis has been reported as a complication of restorative proctocolectomy for UC in as many as 40%-50%
of patients[50]. There are no specific symptoms and signs
for pouchitis, which may be similar to other pouch complications such as cuffitis, irritable pouch and CD of the
pouch. Furthermore, severity of symptoms does not
always correlate with the endoscopic or histological findings and the disease activity is variable with time. Therefore a cumulative assessment of clinical, endoscopic and
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207

Table 6 Rutgeerts scoring system to monitor post surgery
Crohns disease activity
Score
Endoscopic features
i0
Absence of any lesions at anastomosis and in

the neo terminal ileum
Less than 5 aphthous ulcers (< 5 mm)
i1
i2
i3
i4
Figure 13 Aphthous ulcer in the neo terminal ileum in a patient who had
ileorectal anastomosis( indicates recurrence of Crohns disease). Note
healthy surrounding mucosa.
More than 5 ulcers with normal intervening

mucosa or large patchy lesions, or lesions
confined to anastomosis (< 1 cm)
Diffuse aphthous ileitis with diffuse inflammation of the ileal mucosa
Diffuse ileitis with large ulcers, nodularity
and stenosis.
Mucosal appearance
Appearance should be described in detail focusing on
loss of vascular pattern, ulcers size, depth and extent of
circumference, haemorrhages and fistula. Distribution
of abnormal mucosa should include description of continuous or patchy inflammation, rectal and non-rectal involvement, peri-appendiceal involvement and TI changes.
Disease extent
Describe the extent of disease involvement for instance
in UC it is expressed as inflammation distance from the
anal verge and in CD length of inflamed segments.
Image labelling
Capture appropriate images of abnormal mucosa and
label correctly.
Figure 14 Pin hole stricture in the neo terminal ileum (Crohns disease).
Specimen collection
Collect and correctly label histology specimen. Ensure
adequate number of biopsies are taken to increase the
yield of histological diagnosis: current consensus is at
least two biopsies from five sites including ileum and
rectum[7]. Biopsies should be taken from areas of inflammation and the adjacent mucosa proximal to the area of
inflammation.
When colonoscopy is undertaken for refractory or
acute severe disease the following points must be considered: Alternative diagnosis (ischemia, drug induced,
vasculitis, un-related infection); Complications of CD or
UC (CMV or Clostridium difficile colitis or neoplasia or
fistula formation).
Finally, good communication between endoscopist
and histopathologist is mandatory for final decision
on diagnosis. This may be achieved through regular
multidisciplinary team meeting or attaching the detailed
colonoscopy report to all pathology requests.
between surgery and colonoscopy is not known. At our

centre we undertake the first colonoscopy at 6 mo. We
also proposed a risk stratification of patients based on
their risk, with prophylactic medical therapy directed at
the risk[65-70]. Figure 3 illustrates the proposed postoperative surveillance strategy.
ROLE OF THE ENDOSCOPIST

Ultimately, it is the endoscopists interpretation of endoscopic findings that underpins clinical decisions and not
endoscopic technological advances. Other than the appropriate choice of endoscopic test to answer the relevant clinical questions, there is an additional responsibility on the endoscopist to recognise and comprehensively
record mucosal abnormalities. By assimilating these findings with the clinical presentation a diagnosis is often
achieved and a management plan generated. Emphasis
on clear, accurate and systematic reporting is paramount
particularly when the endoscopist is not the treating physician. Therefore to ensure accurate communication of
findings, a simple check list for reporting diagnostic or
prognostic colonoscopies should include the following
descriptions.
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CONCLUSION
Colonoscopy is one of the most important diagnostic
and prognostic tools in the diagnosis and management
of IBD. Other endoscopic procedures usually supple-
208
ment colonoscopy for additional information or treatment of the disease. Management relies on interpretation of endoscopic findings, therefore good knowledge
of the various mucosal appearances, descriptions and
the implication of each finding, with careful attention
to recording each finding is crucial to the optimal management of patients. Surveillance roles for colonoscopy
involve optimising the procedure particularly in cancer
surveillance and post-operative CD. Therapeutic applications of endoscopy are related to excision of dysplastic
lesions and dilatation of strictures.
16
17
18
19
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L- Editor A E- Editor Yang XC


wjge@wjgnet.com
doi:10.4253/wjge.v4.i6.212
EDITORIAL
NOTES, MANOS, SILS and other new laparoendoscopic

techniques
Jos F Noguera, Angel Cuadrado
Key words: Laparoscopy; Endoscopy; Natural orifice
translumenal endoscopic surgery; Single incision laparoscopic surgery; Minilaparoscopy-assisted natural orifice surgery; Flexible endoscopy
Jos F Noguera, Angel Cuadrado, Consorcio Hospital General Universitario, Instituto de Investigacin en Ciencias de la
Salud, 46014 Valencia, Spain
Author contributions: Noguera JF and Cuadrado A contributed
to this paper; Noguera JF provided direction of the paper and
redaction of chapters Notes: allies and enemies and Invisible surgery in the laboratory; Cuadrado A made redaction of
chapters Beginning of a surgical revolution: endoscopic and
laparoscopic surgery and Appearance and development of
NOTES.
Correspondence to: Jos F Noguera, MD, PhD, Department
of Surgery, Consorcio Hospital General Universitario, 46014
Valencia, Spain. drjfnoguera@hotmail.com
Telephone: +34-961-972000 Fax: +34-961-972015
Received: December 17, 2011 Revised: May 6, 2012
Peer reviewers: Gianpiero Gravante, MD, BSC, MBBS,

PhD, Department of Upper Gastrointestinal Surgery, Frenchay
Hospital-North Bristol NHS Trust, Flat 8 Room 25, Clark
Hall-Frenchay Hospital, Frenchay Park Road, Bristol-BS16
1LE, United Kingdom; Kenneth Kak Yuen Wong, MD, PhD,
Assistant Professor, Department of Surgery, The University
of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong
Kong, China
Noguera JF, Cuadrado A. NOTES, MANOS, SILS and other
new laparoendoscopic techniques. World J Gastrointest Endosc
2012; 4(6): 212-217 Available from: URL: http://www.wjgnet.com/1948-5190/full/v4/i6/212.htm DOI: http://dx.doi.
org/10.4253/wjge.v4.i6.212
Abstract
A new way of opening a body cavity can be a revolution in surgery. In 1980s, laparoscopy changed how
surgeons had been working for years. Natural orifice
translumenal endoscopic surgery (NOTES), minilaparoscopy-assisted natural orifice surgery (MANOS),
single incision laparoscopic surgery (SILS) and other
new techniques are the new paradigm in our way
st
of operating in the 21 century. The development of
these techniques began in the late 90s but they have
not had enough impact to develop and evolve. Parallels
between the first years of laparoscopy and NOTES can
be made. Working for an invisible surgery, not only for
cosmesis but for a less invasive surgery, is the target
of NOTES, MANOS and SILS performed by surgeons
and endoscopists over the last 10 years. The future
flexible endoscopic platforms and the fusion between
laparoscopic instruments and devices and robotic surgery will be a great advance for scarless surgery.
BEGINNING OF A SURGICAL
REVOLUTION: ENDOSCOPIC AND
LAPAROSCOPIC SURGERY
Modern endoscopy began in 1805, when Phillip Bozzini
first used a system to visualize the inside of the rectum
and bladder through a mirror, a candle and a double-lumen ureteral catheter. The first source of inner light was
invented by Bruck[1] in 1867 for examining the mouth
using an electrical resistance with a platinum filament as
a light source.
In 1878, Maximilian Carl-Friedrich Nitze introduced
the first working cystoscope that contained a prismatic
lens system and a channel through which you could insert a ureteral catheter, conducted in collaboration with
Joseph Leiter. After the invention of the incandescent
light lamp by Thomas A Edison in 1880, the endoscope
became more practical. With the arrival of the twentieth
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212
Noguera JF et al . Invisible surgery
century, cystoscopy and other studies of open cavities

such as esophagoscopy, laryngoscopy and proctoscopy
were well established.
In 1909, Hans C Jacobeus conducted the first human laparoscopies and thoracoscopies. In 1918, the
importance of pneumoperitoneum was recognized after
Goetzes works of his inflating needle. In 1938, Janos
Veress developed a needle with a safety tip for the practice of therapeutic pneumothorax in tuberculosis. The
cold light was a term used for several years before the
fiber optic and light cables were in use. In 1953, Hopkins[2] led the invention of the cylindrical lenses system,
which provided images with a greater clarity, brightness
and color. The real advances in instrumentation and
techniques of laparoscopic surgery were made by Kurt
Semm in the mid 60s to the 80s when developing an automatic insufflator with a pressure monitor and a lot of
devices for laparoscopy[3]. Familiar with Semms works,
Erich Mhe took interest in surgery of the gallbladder
and designs a new laparoscope, called the Galloscope.
The tube diameter was larger and had a system for indirect vision and valves that prevent the loss of gas. On
September 12th, 1985, Mhe performed the first laparoscopic cholecystectomy in the world.
Throughout this time, laparoscopic visualization was
restricted exclusively to the surgeon. The greatest advance in this field was the development and coupling of
the mini video-camera in 1987, which allowed assistants
to observe surgeries and help more efficiently. Thus, in
1987, Philippe Mouret performed the first video-laparoscopic cholecystectomy. In subsequent years, Dubois
published the first series of laparoscopic cholecystectomies and performed a great laparoscopic activity, developing new techniques such as vagotomy in the treatment
of ulcer in 1989[4]. Other pioneers of video-laparoscopic
surgery are John B McKernan, WB Saye, Eddie Joe
Reddick and Douglas Olsen (United States), Sir Alfred
Cuschieri and Leslie K Nathanson (United Kingdom)
and Jackes Perrisat (France)[5,6].
Parallel to the development of the clinical implementation of the laparoscopic approach to organs like the
spleen, adrenals and stomach, mini-laparoscopy or acuscopic surgery was developed. This form of minimally
invasive surgery attempts to make the least number of
hits on the abdominal cavity using smaller diameter
instrumentation. Instruments and 2.8 mm and 3 mm
optics, which allow the same actions with an acceptable
view, reproduce conventional laparoscopy with minimal
parietal hits. Nowadays, these instruments have awakened interest as a support to hybrid approaches in translumenal surgery.
in 2004, communicating their successes on a porcine

model to which a peritoneoscopy and liver biopsy by
the transgastric route had been made. Rao and Reddy[8]
performed a peritoneoscopy, hepatic procedures and
on genitals with flexible peroral endoscopes with laparoscopic support. In 2006, Reddy and Rao reported the
first human appendectomy by the transgastric route: this
intervention aroused wide interest in the clinical application of NOTES.
In the following year, several groups described various techniques in animal models that awakened interest
in the feasibility and reproducibility of NOTES. Kaloo
s group[9,10] reports its satisfactory results performing
tubal ligation and transgastric gastrojejunostomies and
Thompsons group[11] does the same with their abdominal exploration transgastric experiences and the resection of gynecological organs. In connection with the
transgastric cholecystectomy, also in 2005, the groups of
Swanstrom and Park[12,13] successfully performed cholecystectomies and transgastric cholecystogastrostomies
with flexible endoscopes.
It took 2 years to awaken the interest for clinical application and, during that period of time, the difficulty
of safely performing transgastric cholecystectomy was
found in experimental animals and access through the
vagina was considered and experimented with. The
safety of clinical transvaginal NOTES approach was endorsed by its widespread use in the field of gynecology
with culdoscopy and with the use of the vaginal route
for the extraction of surgical specimens[14-18].
In early March 2007, Zorrons group[19,20] made the
first series of transvaginal NOTES cholecystectomies in
4 patients, based on previous experimental studies. Shortly afterwards in the same month, Bessler carried out a
successful hybrid transvaginal cholecystectomy with 3
laparoscopic abdominal ports[21]. Marescaux[22], in April
2007, conducted the purest NOTES cholecystectomy in
a patient using only an abdominal port through which
he introduced a Veress needle for pneumoperitoneum
control and a gripper for the vesicular traction. Branco
s[23,24] group reported their experience with hybrid cholecystectomy, performing a case with a single abdominal
access trocar and then a transvaginal nephrectomy with
two 5 mm abdominal trocars. At this time, new applications and a series of cases performed by NOTES take
place[25-29].
Transcolonic and transvesical access have been advocated by some researchers as more appropriate for
the abdominal approach of supramesocolic structures
that are often more difficult to achieve through a transgastric route. Limas group used combined transgastric
and transvesical approaches to increase the feasibility of
moderate complexity procedures, such as nephrectomy
and cholecystectomy in experimental animals[30]. Feussner[31] published his results on the transcolonic approach
in experimental animals, creating potentially safe access
to the peritoneal cavity replicable model through access
via the sigmoid and upper rectum.
To minimize the access and transparietal support,
APPEARANCE AND DEVELOPMENT OF

NOTES
Defined as an acronym for Natural orifice translumenal endoscopic surgery (NOTES), the first description
of NOTES in animals was made by the Kalloo[7] group
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213
can also find some developments that may be considered

as enemies to NOTES. Techniques of single incision
and single port involve a major breakthrough for minimally invasive surgery, but they are a step backwards for
the development of surgery without scars on the abdomen. It is a conceptual paradigm shift, a radical change
in philosophy: from the desire to surgery without scars
on the abdomen, to making a single incision but of considerable size and in an area such as the umbilical, with
a high risk of incisional hernia[37]. With NOTES, we try
to minimize incisions in the abdomen to the point where
we can make them disappear. With single-incision surgery we try to hide a minilaparotomy in an area such as
the navel. With NOTES, we aim to fight against wound
infection and against the generation of hernias and postsurgical adhesions, avoiding trauma to the abdominal
wall. With the single-incision surgery, we tend to minimize the importance of these aspects but we do not
minimize the risk of their occurrence. Using the flexible
endoscope through a transvaginal, transgastric or transumbilical approach is an interesting topic today because
in the future, with new endoscopes and flexible endoscopic platforms, we will be able to perform a surgical
procedure with them with a single abdominal access. In
the meantime, as illustrated in Figure 1, we are evolving
from a conventional laparoscopy to other more minimalist approaches.
Many studies are needed so that we can ascertain
whether it is better to group trocars into a single incision or keep them separate under a better triangulation
in surgery and patient safety. In surgeries where a minilaparotomy for the removal of the piece is not needed, it
is difficult to justify the use of this modality; however, in
surgeries such as colectomy, splenectomy and other similar surgeries with the extraction of limited size pieces,
the use of this access seems very appealing.
new techniques and tools have been developed to perform maneuvres of traction and suspension of the target organ, such as magnets and tissue retractors attached
to the parietal peritoneum. Scott's[32] group maintained
the traction of the vesicular background with magnets
in animals, avoiding the placement of a gateway in the
abdominal wall. All these developments are being validated in animal and pilot clinical experiences, with the
intention to perform pure NOTES procedures as soon
as possible, equipped with the necessary clinical safety.
NOTES: ALLIES AND ENEMIES

Since the clinical application of NOTES began in 2007,
we soon realized it would be impossible at that time to
perform pure techniques and that laparoscopic support
was needed. The development of endoscopes was not
progressing quickly and it was necessary to triangulate
to maneuvre correctly and safely into the abdomen and
tools for hemostasis and sealing of structures that could
not be used through the flexible endoscope were also
needed. It was necessary to resign from pure NOTES
and develop a hybrid NOTES, with more or less support
through laparoscopic ports in the abdomen.
Thus, we have seen the techniques using natural orifices as forced allies of NOTES, although rigid material
is introduced through them, and to Minilaparoscopy
Assisted Natural Orifice Surgery (MANOS) techniques,
which use natural orifices for some surgical gestures and
the removal of the piece, with support from minilaparoscopy. Both modalities should not be considered as
NOTES techniques as long as they do not use the flexible endoscope to perform surgical maneuvres, but their
similarity in relationship to the use of natural orifices
and the use of minilaparoscopy on the access of the
abdomen make this kind of surgery progress together
through natural orifices, preferably through the vagina.
Access to the abdomen with rigid instruments from
a natural orifice can only be done from a pelvic access.
The vagina is the easiest access for its short canal, lack
of complications in its access and ease of closing. This
kind of rigid NOTES surgery developed by the German
group Zornig et al[28] has the possibility of using laparoscopic instrumentation and requires no training in handling the flexible endoscope. By contrast, with the MANOS technique, the access through the natural orifices
can be done from any entry, not just the vagina, with the
possibility of using the endoscope as an instrument that
provides light, camera and the ability to help surgery,
which is actually performed through minilaparoscopy
with parietal abdominal ports. The first description was
by Tsin in 2001 under the name of culdolaparoscopy but
went unnoticed until the advent of NOTES surgery[33].
Recently, this surgical approach has been applied to the
realization of colorectal, splenic and bariatric surgery[34-36].
If these two types of minimally invasive approaches
can be considered as allies to NOTES for the contribution to the development of natural orifice surgery, we
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INVISIBLE SURGERY IN THE

LABORATORY
NOTES surgery has slowed its development for several
reasons, among which we can refer to the appearance
of single-incision surgery and the fateful economical period of time in which it has been developed. It is a new
type of therapeutic procedure with a high dependence
on technology that requires a significant investment to
develop new platforms, vision systems and instrumentation. The appearance of the single-incision surgery,
which manages to reach a wide range of surgical procedures and seems to be more accessible to the entire
surgical community with little investment in technology,
is going to make us wait for its development and implementation to re-awaken the growing interest in NOTES.
Despite all this, transluminal surgery should be further
developed. It is necessary that the groups that first began
its development carry on with the technique, establishing
the needs and specifying the target diseases. Thus, when
we are ready to re-address the technological develop-
214
CL
5-11
5
5
SIS
CML
11
5
11
25-30
TU
TV
FSIS
5
5
12
12
15
Figure 1 Distribution of the entry-ports by approach to perform cholecystectomy. CL: Conventional laparoscopy. CML: Conventional minilaparoscopy; SIS:
Single incision surgery; TV: Flexible or rigid transvaginal endoscopy; TU: Transumbilical flexible endoscopy; FSIS: Flexible single incision surgery.
mental working channel to implement elements of coagulation, washing and vacuuming. These new endoscopes
can control the pneumoperitoneum and enable joint
working tools, getting the necessary triangulation, even
in limited space[38,39]. The new miniaturized terminals for
bipolar coagulation, tissue sealing, ultrasounds and radiofrequency are shown as very promising elements to facilitate dissection, hemostasis and sealing. Possible future
application energies, such as lasers and microwaves, may
also have their place through the flexible endoscope.
On the other hand, flexible endoscopes are progressing and the classical concept of a long flexible tube is
being substituted by a concept of a translumenal surgery
platform which seeks to overcome the difficulties of
navigation by stabilizing the transporter of the instruments and allowing a greater skill in movements, endowing a more accurate triangulation and precision[40,41].
These new platforms try to allow the surgeon to make
gestures of great similarity to those made in laparoscopic
surgery, supported largely by the application of robotics
to facilitate accuracy of movements.
Finally, robotics seems to be the technology that will
achieve the breakthrough for this type of intracavitary
surgery in the not too distant future. The miniature robots are intended to give a step further, putting our vision in intracavitary or intraluminal situation, as well as
our tools and the conveyor platform. The simplest ones
incorporate the light source and the camera, but the
more advanced ones are configured with two arms that
even allow surgical maneuvres to be performed[42].
Figure 2 Cholecystectomy by flexible single incision surgery. Umbilical single incision and direct approach with the flexible endoscope without complementary device. Two parallel 5 mm ports are needed to perform a secure procedure.
ment of NOTES, there will be groups who are willing

to put the technologies in use which are now sleeping
in the labs. While we wait for this new technology, the
combination of the flexible endoscopy and minimally
invasive access can give us some benefits with a low cost,
as can be seen in Figure 2.
Among these new instruments and equipment that
are in preclinical research, those which seem to have
more interest are the new scopes, the platforms for
NOTES and minirobots. The new endoscopes have in
common the development of several working channels,
up to four, with the intention to give input to instruments in two of them, and at least, to another instru-
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215
While all these developments come into our hands,

it is necessary to promote the combined use of all minimally invasive techniques available to us, as well as team
collaboration, which is a fast way of exchanging information and brings the chance to quickly transfer new
indications to techniques and specific equipment. The
knowledge of the advantages and limitations of each
approach allows the development of hybrid techniques
where the process cannot be performed without involving both techniques.
18
19
20
21
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S- Editor Yang XC L- Editor Roemmele A E- Editor Yang XC
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wjge@wjgnet.com
doi:10.4253/wjge.v4.i6.218
TOPIC HIGHLIGHT
Shigetaka Yoshinaga, MD, PhD, Series Editor
Endoscopic ultrasound using ultrasound probes for the

diagnosis of early esophageal and gastric cancers
Shigetaka Yoshinaga, Ichiro Oda, Satoru Nonaka, Ryoji Kushima, Yutaka Saito
conventional EUS, although the accuracy of EUS using
high-frequency ultrasound probes relatively decreases
for those patients with depressed-type lesions, undifferentiated cancer, concomitant ulceration, expanded
indications, type 0-lesions, and lesions located in the
upper-third of the stomach. A 92% overall accuracy
rate was achieved when both the endoscopic appearance and the findings from EUS using high-frequency
ultrasound probes were considered together for tumor
classification. Although EUS using high-frequency ultrasound probes has limitations, it has a high depth of
invasion accuracy and is a useful procedure to distinguish lesions in the esophagus and stomach that are
indicated for endoscopic resection.
Shigetaka Yoshinaga, Ichiro Oda, Satoru Nonaka, Yutaka

Saito, Endoscopy Division, National Cancer Center Hospital,
5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Ryoji Kushima, Pathology Division, National Cancer Center
Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Author contributions: Yoshinaga S performed endoscopic examinations and therapies, and also wrote this manuscript mainly;
Oda I, Nonaka S and Saito Y performed endoscopic examinations
and therapies; Kushima R evaluated resected specimens pathologically and took pictures of resected specimens.
Correspondence to: Dr. Shigetaka Yoshinaga, MD, PhD,
Endoscopy Division, National Cancer Center Hospital, 5-1-1
Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. shiyoshi@ncc.go.jp
Telephone: +81-3-35422511 Fax: +81-3-35423815
Received: October 13, 2011 Revised: April 27, 2012
Key words: Endoscopic ultrasound; High-frequency ultra

sound probe; Esophageal cancer; Gastric cancer; Depth
diagnosis
Abstract
Endoscopic ultrasound (EUS) devices were first designed and manufactured more than 30 years ago, and
since then investigators have reported EUS is effective
for determining both the staging and the depth of invasion of esophageal and gastric cancers. We review the
present status, the methods, and the findings of EUS
when used to diagnose and stage early esophageal and
gastric cancer. EUS using high-frequency ultrasound
probes is more accurate than conventional EUS for the
evaluation of the depth of invasion of superficial esophageal carcinoma. The rates of accurate evaluation of
the depth of invasion by EUS using high-frequency ultrasound probes were 70%-88% for intramucosal cancer, and 83%-94% for submucosal invasive cancer. But
the sensitivity of EUS using high-frequency ultrasound
probes for the diagnosis of submucosal invasive cancer
was relatively low, making it difficult to confirm minute
submucosal invasion. The accuracy of EUS using highfrequency ultrasound probes for early gastric tumor
classification can be up to 80% compared with 63% for
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Peer reviewer: Istvn Rcz, MD, PhD, Professor, Head of In-
ternal Medicine Department and Gastroenterology, Petz Aladr

County and Teaching Hospital, Gyr, Hungary
Yoshinaga S, Oda I, Nonaka S, Kushima R, Saito Y. Endoscopic ultrasound using ultrasound probes for the diagnosis
of early esophageal and gastric cancers. World J Gastrointest
Endosc 2012; 4(6): 218-226 Available from: URL: http://www.
wjgnet.com/1948-5190/full/v4/i6/218.htm DOI: http://dx.doi.
org/10.4253/wjge.v4.i6.218
INTRODUCTION
Endoscopic ultrasound (EUS) devices were first designed
and manufactured in the early 1980s. Since then, EUS has
been adapted not only for pancreatic lesions but also for
gastrointestinal and perigastrointestinal lesions, such as
gastrointestinal cancers, gastrointestinal stromal tumors,
218
Yoshinaga S et al . EUS for esophageal and gastric cancers
and abdominal and mediastinal lymphadenopathy. Some

investigators have reported EUS is effective for the staging of esophageal and gastric cancers[1,2], and EUS is also
useful for determining the depth of invasion of early
esophageal and gastric cancers. Ever since Gotoda et al[3]
described the incidence of lymph node metastasis from
early gastric cancer, and with the development of endoscopic submucosal dissection (ESD), many early gastric
cancer lesions have been resected endoscopically. In addition, ESD has recently been adapted for excision of
esophageal lesions. It is important to accurately estimate
the depth of the lesion before endoscopic resection of
early esophageal and gastric cancers; a vague estimation
of lesion depth may allow residual cancer to remain, leading to recurrences and additional resections.
We review the present status of, the methods used
for, and the findings of EUS using high-frequency ultrasound probes for diagnosing and staging early esophageal
and gastric cancer.
Epithelium
200 mm
m2
m3
sm1 sm2 sm3

Mucosa
Muscularis mucosae
Submucosa
Muscularis propria
Adventitia
Figure 1 Scheme of the depth of esophageal cancer invasion.
differentiate submucosal invasive cancers from intramucosal cancers were 74%, 62%, and 77%, respectively[10].
Especially, May et al[9] reported the diagnostic accuracy
was not yet satisfactory with submucosal invasive cancers
located at the esophagogastric junction (EGJ) or with infiltration of the first third of the submucosa. In addition,
it is difficult to distinguish between cancer invasion and
inflammatory cell infiltration[4]. Thus, although EUS can
distinguish between definite intramucosal cancers and
definite submucosal invasive cancers, it is relatively difficult to confirm minute submucosal invasion even when
using high-frequency probes.
Although water introduced normally into the esophagus can provide acoustic coupling for EUS, it is difficult
to submerge the target lesion because the water flows off
easily. To solve this problem, some investigators developed EUS devices utilizing either a water-filled balloon
method[11], a device for continuous irrigation of water[12],
or a jelly-filled method[13]. However, the balloon interferes
with the diagnosis of m1 and m2 cancer, so the water
or the jelly-filled methods may be preferred[4,13,14]. In our
institute, we use an endoscope with a water-jet system to
provide irrigation.
EUS FOR EARLY ESOPHAGEAL CANCERS

Present status
The depth of early esophageal squamous cell cancer invasion is classified according to six categories that range
from only penetrating the epithelium to reaching the
proper muscle layer: cancer limited to the epithelium is
described as m1; cancer limited to the lamina propria is
m2; invasion reaching the muscularis mucosa or invading
the muscularis mucosa is m3; invasion of the submucosa
less than 200 m in the endoscopically resected specimen
or invasion of the first third of submucosa is sm1; invasion of the submucosa by more than 200 m in the endoscopically resected specimen or invasion of the second
third of submucosa is sm2; and that reaching the proper
muscle layer is classed as sm3[4] (Figure 1). The rates of
lymph node metastasis in m1 and m2 cancers are estimated at less than 5%, while those of m3 and sm1 cancers
are 12%-27%, and those of sm2 and sm3 cancers are
36%-46%[5]. This evidence suggests that invasion depth
confined to m1 or m2 regions is a good indication for
excision using a procedure such as endoscopic mucosal
resection (EMR) or ESD. Therefore, an accurate determination of invasion depth will help distinguish indicated
lesions from contra-indicated lesions.
Because EUS using high-frequency ultrasound probes
is more accurate than conventional EUS in the evaluation of the depth of invasion of early esophageal carcinoma[6], usually EUS using high-frequency ultrasound
probes is performed to evaluate tissue penetration. In
previous reports, the accuracies of the depth of invasion measurements by ultrasound probes were 70%-88%
for intramucosal cancer, and 83%-94% for submucosal
invasive cancer[6-8]. Murata et al[4] reported the extent of
cancer invasion had been correctly determined in 81% of
m1 and m2 lesions, in 60% of m3 and sm1 lesions, and
in 87% of sm2 and sm3 lesions. But in another report,
the sensitivity for submucosal invasive cancer was only
48%[9], and overall accuracy, sensitivity, and specificity to
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m1
EUS methods in our institute

Our EUS procedure is performed using a 20 MHz ultrasound probe (UM-3R; Olympus Optical Co, Ltd, Tokyo,
Japan) with an endoscopic ultrasound system (EU-M2000;
Olympus) through a forward-viewing endoscope with a
water-jet system (GIF-Q260J; Olympus). Deaerated water
is boiled at least one day before the procedure and then
allowed to rest to remove any bubbles. This preparation
is necessary to achieve accurate data from the EUS procedure (Figure 2A and B).
For premedication, scopolamine butylbromide as
an antispasmodic and midazolam as a sedative, and, occasionally, pethidine hydrochloride as an analgesic, are
administered to the patients. After the patients have received the premedication, their blood pressure, heart rate,
and arterial oxygen saturations are monitored until an
hour after the procedure is finished.
With patients lying in a left lateral decubitus position,
we insert an endoscope into the esophagus and attempt
to visualize a lesion; if one is discovered, mucus and saliva on the lesion are washed away gently (Figure 3A). An
ultrasound probe is inserted through an instrument channel and we begin irrigating with deaerated water through
a water jet channel operated by an assistant, while we
watch the lesion directly. After sufficient deaerated water
is present to act as an acoustic coupling medium, ultra-
19
Figure 2 Differences in endoscopic ultrasound features

with quality of water used for irrigation. A: Water from a
faucet ; B: Deaerated water.
Figure 3 Endoscopic ultrasound procedure for early esophageal cancer as performed at the National Cancer Center Hospital. A: Endoscopic features after
washing mucus and saliva from the lesion; B: Endoscopic features after region is filled with deaerated water. Endoscopic ultrasound (EUS) can be performed under
direct vision of the lesion; C: EUS features.
fifth layer is the submucosa. The sixth to eighth layers are

the proper muscle layers, with the sixth layer corresponding to the circular muscle, the seventh to the connective
tissue and interface, and the eighth layer to the longitudinal muscle. The ninth layer is the adventitia (Figure 4).
Cancers are visualized as hypoechoic lesions, and
it should be recognized which layers are destroyed and
which layers are normal. An m1 cancer is located in the
first and second layers[4], and sometimes it is difficult
to recognize the lesion (Figure 5A-D). An m2 cancer
invades the third layer, but the fourth layer under the lesion is preserved (Figure 6A-D). Cancers with m3 to sm1
invasion penetrate the fourth layer, but the fifth layer
is intact[4] (Figure 7A-D). In some cases of sm1 cancer,
the fifth layer under the lesions appears slightly irregular
(Figure 8A-D). An sm2 cancer invades the fifth layer, but
there is a hyperechoic layer between the cancer and the
sixth layer[4] (Figure 9A-D).
Figure 4 Endoscopic ultrasound features of normal esophageal wall. Each

numbered circle, 1-9, with a white arrow, indicates the corresponding numbered
tissue layer, first through ninth.
sound scanning is begun (Figure 3B and C). Technically,

it is difficult to scan lesions which are located near EGJ
precisely because the lower esophagus is sometimes spastic or not distended.
EUS FOR EARLY GASTRIC CANCERS

Present status
According to the report by Gotoda et al[3], the expanded
indications of endoscopic resection for gastric cancer are
defined as follows: (1) differentiated type, no lymphatic or
venous invasion, intramucosal cancer without ulceration,
regardless of tumor size; (2) intramucosal cancer with ulceration, less than 3 cm diameter; (3) minute submucosal
cancer that invades less than 500 m in the submucosa,
EUS findings for early esophageal cancers

When we use high-frequency ultrasound probes, the
esophageal wall is delineated as nine alternating high- and
low-echo layers[4]. The first to the fourth layers represent
the mucosa, with the first and second layers corresponding to the epithelium, the third layer to the lamina propria, and the fourth layer to the muscularis mucosa. The
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220
Figure 5 Findings for an m1 cancer of the esophagus. A: Endoscopic features. A reddish depressed lesion was located on the anterior and left wall of the middle
esophagus; B: Endoscopic features after iodine dye. Biopsy specimens showed squamous cell carcinoma; C: Endoscopic ultrasound (EUS) features. The white dotted
line indicates the extent of the lesion. EUS revealed an irregularity of the first layer and a slight thickness of the second layer; D: Pathological findings. The tumor was
confined to the epithelium. (Hematoxylin and eosin stain, 40).
Figure 6 Findings for an m2 cancer of the esophagus. A: Endoscopic features. A reddish flat lesion was located on the anterior wall of the middle esophagus; B:
Endoscopic features after iodine dye. Biopsy specimens showed squamous cell carcinoma; C: Endoscopic ultrasound (EUS) features. The white dotted line indicates
the extent of the lesion. EUS revealed a thickness in the second layer and a disappearance of the third layer. The yellow line with an arrow indicates the intact fourth
layer; D: Pathological findings. The tumor was confined to the lamina propria. (Hematoxylin and eosin stain, 100).
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221
Figure 7 Findings for an m3 cancer of the esophagus. A: Endoscopic features. A reddish flat and partially elevated lesion was located on the posterior wall of the
middle esophagus; B: Endoscopic features after iodine dye. Biopsy specimens showed squamous cell carcinoma; C: Endoscopic ultrasound (EUS) features. The
white dotted line indicates the extent of the lesion. EUS revealed a thickness of the second layer and a disappearance of the third and fourth layer. The fifth layer
seemed to be intact; D: Pathological findings. The tumor was reaching and partially invading the muscularis mucosae. (Hematoxylin and eosin stain, 40).
Figure 8 Findings for an sm1 cancer of the esophagus. A: Endoscopic features. A depressed, white, flat lesion was located on the posterior wall of the middle
esophagus; B: Endoscopic features after iodine dye. Biopsy specimens showed squamous cell carcinoma; C: Endoscopic ultrasound (EUS) features. The white dotted line indicates the extent of the lesion. EUS revealed a thickness of the second layer and a disappearance of the third and fourth layer. The fifth layer seemed to be
slightly irregular; D: The tumor was invading the submucosal layer to about 170 m in depth. (Hematoxylin and eosin stain, 40).
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222
Figure 9 Findings for an sm2 cancer of the esophagus. A: Endoscopic features. A depressed lesion was located on the posterior and right wall of the middle
esophagus; B: Endoscopic features after iodine dye. Biopsy specimens showed squamous cell carcinoma; C: Endoscopic ultrasound (EUS) features. The white dotted
line indicates the extent of the lesion. EUS revealed a thickness of the second layer and a disappearance of the third and fourth layer. The fifth layer had become thin,
but the sixth layer was intact; D: Pathological findings. The tumor was invading the submucosal layer to a 320 m depth. (Hematoxylin and eosin stain, 40).
Figure 10 Endoscopic ultrasound procedure as performed at the National Cancer Center Hospital when it is difficult to approach lesions horizontally. A:
Elevated lesion with central depression was located on the greater curvature of the angle; B: The lesion could be approached horizontally when using a multi-bending
endoscope; C: Endoscopic ultrasound features after region is filled with deaerated water.
less than 3 cm diameter; and (4) undifferentiated type, no

lymphatic or venous invasion, intramucosal cancer without ulceration, less than 2 cm diameter. Therefore, we
should distinguish intramucosal (m) cancer, minute submucosal invasive (sm1) cancer, and massive submucosal
invasive (sm2) cancer.
The accuracies of EUS using high-frequency ultrasound probes for the staging of early gastric cancer have
been described as up to 80% compared with 63% for
conventional EUS[15]. Rodriguez et al[16] mentioned that
many endosonographers now feel that catheter-based
miniprobes scanning at 20 MHz may be better suited to
staging early gastric cancers. In previous reports, the over-
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all accuracies of the depth of invasion by the ultrasound

probes were 65%-86%[17-20]. In those reports, the accuracy of EUS relatively decreased for those patients with
lesions of depressed type, undifferentiated cancer[18,19],
concomitant ulceration, the expanded indications that
we described[19], type 0-I lesions, and lesions located in
the upper-third of the stomach[20]. Also, Akahoshi et al[18]
mentioned that the accuracy decreased as tumor size increased. In addition, over staging of early gastric cancers
with the 20 MHz probe occurs in 19%-24% of patients
due to peritumoral fibrosis mimicking deeper invasion[16,17,21]. But when both the endoscopic appearance and
EUS findings were applied together for tumor classifica-
223
1
2
Figure 11 Endoscopic ultrasound features of normal gastric wall. Each

numbered circle, 1-5, with a white arrow, indicates the corresponding numbered
tissue layer, first through fifth.
tion, a 92% overall accuracy rate was achieved[17]. Though

Mouri et al[22] reported both high-frequency ultrasound
probes and conventional EUS are useful for accurately
determining the depth of invasion of gastric cancer without ulcerous change, they did not distinguish between intramucosal cancers and minute submucosal invasive cancers in terms of the expanded indication of endoscopic
resection, and they also excluded the lesions that EUS
could not sufficiently evaluate. In other words, it is still
difficult to distinguish those cancers, especially with ulcerous change, and EUS cannot evaluate all gastric lesions.
EUS methods in our institute

Our preparations and patient premedications are the
same for both gastric and esophageal EUS procedures.
Usually, we use a conventional endoscope that can be
bent more than 180 degrees, both because we dont need
to use a water jet system for gastric EUS and because
sometimes we need to scan at the retroflex position.
After washing the lesion and removing water collected
in the stomach, we start irrigating with deaerated water
introduced through an instrument channel. After the area
to be imaged is filled with deaerated water, an ultrasound
probe is inserted through an instrument channel and
ultrasound scanning is begun. When it is difficult to approach lesions horizontally (Figure 10A) it is sometimes
impossible to scan. In such cases we use a multi-bending
endoscope (GIF-2TQ260M; Olympus) to approach lesions horizontally (Figure 10B and C). Technically, it is
sometimes difficult to scan lesions which are located in
the angle and the antrum because lesions are located on
the curve or not submerged under water.
Figure 12 Findings for an m cancer of the stomach. A: Endoscopic features. A

depressed lesion with surrounding elevation was located on the greater curvature
of the antrum; B: Endoscopic figure after indigo carmine dye. Biopsy specimens
showed adenocarcinoma; C: Endoscopic ultrasound (EUS) features. The white
dotted line indicates the extent of the lesion. EUS revealed an irregularity of the
first layer and a slight thickness of the second layer; D: Pathological findings. The
tumor was confined to the lamina propria. (Hematoxylin and eosin stain, 40).
second and third layers is considered to correspond to

the muscularis mucosae.
The EUS images were interpreted with regard to tumor invasion according to the five layer architecture of
the gastric wall, and lesions were classified as m cancers
(Figure 12A-D) and submucosal invasive (sm) cancers[17]
(Figure 13A-D). Although the fifth layer under the lesions seems to be slightly irregular in some cases of sm1
cancer (Figure 14A-D), it is difficult to distinguish m and
sm1 definitively.
EUS findings for early gastric cancer

When we use high-frequency ultrasound probes, the normal gastric wall is visualized as the mucosa (combination
of the first hyperechoic and second hypoechoic layers)
and the submucosa (the third hyperechoic layer). The
muscularis propria is visualized as the fourth hypoechoic
layer, and the fifth hyperechoic layer is the serosa including the subserosa (Figure 11)[17]. According to the report
by Yanai et al[23] the fine hypoechoic layer between the
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224
Figure 13 Findings for an sm2 cancer of the stomach. A: Endoscopic features. An elevated lesion was located on the posterior wall of the upper gastric body; B:
Endoscopic features after indigo carmine dye. Biopsy specimens showed adenocarcinoma; C: Endoscopic ultrasound (EUS) features. The white dotted line indicates
the extent of the lesion. EUS revealed a thickness of the second layer and a thin third layer, but the fourth layer was intact; D: Pathological findings. The tumor was
invading the submucosa massively. (Hematoxylin and eosin stain, 12.5).
Figure 14 Findings for an sm1 cancer of the stomach. A: Endoscopic features. A white, flat lesion with central elevation was located on the greater curvature of
the angle; B: Endoscopic features after indigo carmine dye. Biopsy specimens showed adenocarcinoma; C: Endoscopic ultrasound (EUS) features. The white dotted
line indicates the extent of the lesion. EUS revealed a thickness of the second layer and a slightly irregular third layer; D: Pathological findings. The tumor was invading the submucosal layer to a 400 m depth. (Hematoxylin and eosin stain, 40).
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225

9
COMPLICATIONS OF EUS
Fortunately, no severe complications of EUS have been
reported so far, but aspiration of water occurs occasionally. There is a larger risk for this when patients have a
hiatal hernia, as water collected in the stomach runs back
easily. Therefore, conscious sedation, rather than deep
sedation, is more suitable for EUS. If possible, a balloon
should be fixed oral to the tips of an endoscope to prevent water reflex[4] for esophageal lesion procedures.
10
11
12
CONCLUSION
We reviewed the present status of, the methods used for,
and the findings of, EUS using high-frequency ultrasound
probes to diagnose and stage early esophageal and gastric
cancer. Although EUS using high-frequency ultrasound
probes still has some limitations, such as low accuracy
for minute submucosal invasion cancers and lesions with
ulcerous change, it still has good accuracy for determining the depth of invasion of early esophageal and gastric
cancers. Because determining the depth of malignant
invasion is essential to distinguish lesions indicated for
endoscopic resection, EUS is a useful clinical procedure.
When both the endoscopic and EUS diagnoses are considered, clinicians can achieve a high accuracy of staging
of early esophageal and gastric cancers.
13
14
15
16
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1
2
3
17
Puli SR, Reddy JB, Bechtold ML, Antillon D, Ibdah JA, Antillon MR. Staging accuracy of esophageal cancer by endoscopic ultrasound: a meta-analysis and systematic review.
World J Gastroenterol 2008; 14: 1479-1490
Tsendsuren T, Jun SM, Mian XH. Usefulness of endoscopic
ultrasonography in preoperative TNM staging of gastric
cancer. World J Gastroenterol 2006; 12: 43-47
Gotoda T, Yanagisawa A, Sasako M, Ono H, Nakanishi Y,
Shimoda T, Kato Y. Incidence of lymph node metastasis
from early gastric cancer: estimation with a large number of
cases at two large centers. Gastric Cancer 2000; 3: 219-225
Murata Y, Napoleon B, Odegaard S. High-frequency endoscopic ultrasonography in the evaluation of superficial
esophageal cancer. Endoscopy 2003; 35: 429-435; discussion
436
Kodama M, Kakegawa T. Treatment of superficial cancer of
the esophagus: a summary of responses to a questionnaire
on superficial cancer of the esophagus in Japan. Surgery 1998;
123: 432-439
Hasegawa N, Niwa Y, Arisawa T, Hase S, Goto H, Hayakawa T. Preoperative staging of superficial esophageal
carcinoma: comparison of an ultrasound probe and standard
endoscopic ultrasonography. Gastrointest Endosc 1996; 44:
388-393
Murata Y, Suzuki S, Ohta M, Mitsunaga A, Hayashi K, Yoshida K, Ide H. Small ultrasonic probes for determination of
the depth of superficial esophageal cancer. Gastrointest Endosc 1996; 44: 23-28
Fukuda M, Hirata K, Natori H. Endoscopic ultrasonography
of the esophagus. World J Surg 2000; 24: 216-226
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May A, Gnter E, Roth F, Gossner L, Stolte M, Vieth M, Ell C.

Accuracy of staging in early oesophageal cancer using high
resolution endoscopy and high resolution endosonography:
a comparative, prospective, and blinded trial. Gut 2004; 53:
634-640
Chemaly M, Scalone O, Durivage G, Napoleon B, Pujol B,
Lefort C, Hervieux V, Scoazec JY, Souquet JC, Ponchon T.
Miniprobe EUS in the pretherapeutic assessment of early
esophageal neoplasia. Endoscopy 2008; 40: 2-6
Inoue H, Kawano T, Takeshita K, Iwai T. Modified softballoon methods during ultrasonic probe examination for
superficial esophageal cancer. Endoscopy 1998; 30 Suppl 1:
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Chak A, Canto M, Stevens PD, Lightdale CJ, Van de Mierop
F, Cooper G, Pollack BJ, Sivak MV. Clinical applications of a
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Esaki M, Matsumoto T, Moriyama T, Hizawa K, Ohji Y, Nakamura S, Hirakawa K, Hirahashi M, Yao T, Iida M. Probe
EUS for the diagnosis of invasion depth in superficial esophageal cancer: a comparison between a jelly-filled method and
a water-filled balloon method. Gastrointest Endosc 2006; 63:
389-395
Odegaard S, Kimmey MB, Martin RW, Yee HC, Cheung
AH, Silverstein FE. The effects of applied pressure on the
thickness, layers, and echogenicity of gastrointestinal wall
ultrasound images. Gastrointest Endosc 1992; 38: 351-356
Singh N, Herreros-Tejada A, Waxman I. High-frequency ultrasound probes. In: Gress FG, Savides TJ. Endoscopic Ultrasonography. 2nd ed. Hoboken: Wiley-Blackwell, 2009: 63-69
Rodriguez SA, Faigel DO. EUS of the stomach and duodenum. In: Gress FG, Savides TJ. Endoscopic Ultrasonography.
2nd ed. Hoboken: Wiley-Blackwell, 2009: 83-97
Yanai H, Matsumoto Y, Harada T, Nishiaki M, Tokiyama H,
Shigemitsu T, Tada M, Okita K. Endoscopic ultrasonography
and endoscopy for staging depth of invasion in early gastric
cancer: a pilot study. Gastrointest Endosc 1997; 46: 212-216
Akahoshi K, Chijiwa Y, Hamada S, Sasaki I, Nawata H,
Kabemura T, Yasuda D, Okabe H. Pretreatment staging of
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Kim GH, Park do Y, Kida M, Kim DH, Jeon TY, Kang HJ,
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according to the indications for endoscopic treatment of
early gastric cancer. J Gastroenterol Hepatol 2010; 25: 506-511
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20-megahertz linear endoscopic ultrasonography in early
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doi:10.4253/wjge.v4.i6.227
OBSERVATION
Informed consent for digestive endoscopy

Marcela Kopacova, Jan Bures
Marcela Kopacova, Jan Bures, 2nd Department of Medicine,
Faculty of Medicine at Hradec Krlov, University Teaching
Hospital, Sokolsk 581, 500 05 Hradec Krlov, Czech Republic
Author contributions: Kopacova M and Bures J contributed
equally to this work.
Supported by The research project, No. MZO 00179906 from
the Ministry of Health, Czech Republic
Correspondence to: Marcela Kopov, MD, PhD, 2nd Department of Medicine, Faculty of Medicine at Hradec Krlov,
University Teaching Hospital, Sokolsk 581, 500 05 Hradec
Krlov, Czech Republic. kopacmar@fnhk.cz
Telephone: +420-49-5834240 Fax: +420-49-5834785
Received: October 20, 2011
Revised: May 7, 2012
htm DOI: http://dx.doi.org/10.4253/wjge.v4.i6.227
INTRODUCTION
There is a general consensus that every patient coming for digestive endoscopy has the right and should be
informed in an adequate, appropriate and understandable way about the procedure. This information should
be given in a timely fashion before the endoscopy and
should provide a description of the test comprehensibly, explain the reason for investigation, the alternatives,
possible risks and benefits, and main implications. It is
mandatory to have time and the opportunity to ask additional questions. The decision to undergo endoscopy
should not be made under duress and confirmed by the
patients signature on a written form of informed consent. Thus, everything is clear. However, daily routine
practice is a little bit more complicated.
Abstract
Informed consent is necessary in good clinical practice.
It is based on the patients ability to understand the
information about the proposed procedure, the potential consequences and complications, and alternative
options. The information is written in understandable
language and is fortified by verbal discussion between
physician and patient. The aim is to explain the problem, answer all questions and to ensure that the patient understands the problems and is able to make a
decision. The theory is clear but what happens in daily
practice?
PATIENTS AND METHODS

According to a survey of the European Society of
Gastrointestinal Endoscopy (ESGE) in 2002 [1], the
procedure for obtaining informed consent for digestive
endoscopy varies considerably. A structured questionnaire regarding the quality of informed consent was sent
to particular endoscopic societies that are members of
the ESGE. The response rate was 59% (26/44). The
required information is given prior to written consent
in only 23% (6/26) of the countries. Information about
the procedure is given to the patients in 96% of the responding countries and in only 77% is there sufficient
time for patients to ask questions about the nature of
the test. In 15% (4/26) of the countries, neither diagnostic nor therapeutic alternatives to endoscopy or the potential complication rate are discussed[1]. Other published
data available is rather controversial. Several studies had
different experiences. For instance, in one survey, 92%
of patients were properly informed[2], while according
to others, 51% felt dissatisfied because they would have
Key words: Informed consent; Endoscopy; Written consent; Uninformed consent

Peer reviewer: Mauro Manno, MD, Nuovo Ospedale Civile
S.Agostino-Estense, Gastroenterology and Digestive Endoscopy
Unit, Via Giardini, 1355, 41126 Baggiovara di Modena (Mo),
Italy
Kopacova M, Bures J. Informed consent for digestive endoscopy. World J Gastrointest Endosc 2012; 4(6): 227-230 Available
from: URL: http://www.wjgnet.com/1948-5190/full/v4/i6/227.
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227
Kopacove M et al . Informed consent for digestive endoscopy
wanted more information (before diagnostic endoscopy)

and 25% to 76% had not been adequately informed
about the potential risks (of diagnostic endoscopy or
endoscopic retrograde cholangiopancreatography ) and
alternative methods (to percutaneous endoscopic gastrostomy)[3-5]. In a Veterans Administration study[6], all
patients signed the consent form before sigmoidoscopy
but only 14% of patients actually read all of it (most
thought that they had enough information to proceed
with the endoscopy). Most patients (93%) were given
the opportunity to ask questions but only 22% actually
did so[6]. Some gastroenterologists are afraid that patients
undergoing open access endoscopy are less likely to be
properly informed about their endoscopic procedure
than the group of patients referred from specialized
clinics[7]. Others propose to send information booklets
or leaflets on endoscopy procedures in advance by post[8]
or provide patients with information by means of computer-based visualization[9]. Despite all non-homogenous
data, it is quite clear that informed consent is only one
of the items of information needed by patients before
digestive endoscopy.
However, some demands are difficult to meet. Mayberry[10] studied levels of information required by patients
(516 persons contacted) and solicitors specializing in clinical negligence (79 subjects addressed) before gastroscopy
and flexible sigmoidoscopy. Of the solicitors, 86% felt
that patients needed to be informed about the procedure
on at least two occasions and favored booklets and videos.
Both 75% of solicitors and 44% of patients thought that
informed consent for endoscopy should be obtained 2
wk before the test. Forty-eight percent of solicitors and
38% of patients felt that patients should be told of very
uncommon risks (16% of solicitors even expected information about risks of 1 in 1000000)[10]. According to the
British Society of Gastroenterology Guidelines for Informed Consent[3], the patient should be fully informed by
the endoscopist ideally at least 24 h before the procedure;
however, for busy units these are impossible standards[3].
A significant number of patients (41%) signing informed consent were worried by the explanation of the
risks (before laparoscopy)[11].
Another study was carried out at the Inverclyde
Royal Hospital, Greenock, Scotland. Demosthenous et
al[12] used validated tests of memory on 59 patients undergoing lower limb arthroplasty to assess how well they
learned and recalled information about their planned
procedure. Neuropsychological tests were administered
to measure the patient's ability to receive, store and recall
information delivered verbally. All patients showed an
ability to learn new material; however, younger age and
higher educational achievement correlated with better
performance (patients were excluded if they had any
condition impairing memory or communication: dementia, cerebrovascular disease, epilepsy, head injury, dysphasia or aphasia). These results have serious implications
for orthopedic surgeons discussing planned procedures.
They identified groups of patients who may require en-
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hanced methods of communicating the objectives, risks

and alternatives to surgery.
One third of patients were distressed or surprised to
be given oral or written information in a French study,
obtaining informed consent for digestive endoscopy
was distressing for 20% of those subjects[13]. In another
French study[14], 10% of patients considered that the
written consent for gastrointestinal endoscopy altered
their trust in their endoscopist. Discussions of risk must
especially be made in a friendly manner[15] and should
not frighten the patient or even discourage him/her
from undergoing the endoscopy.
Informed consent has been set within the framework
of medical ethics. Whenever possible, patients should
remain responsible for themselves. Where a choice of
investigation/treatment might be reasonably offered,
the physician may always advise the patient of his/her
recommendation (together with reasons for such a suggestion). Clinicians must respect the need to maintain
the autonomy and self-determination of patients [16].
Nevertheless, the question of protecting physicians from
malpractice claims is a major aspect of the guidelines for
informed consent of the British Society of Gastroenterology[16] and the American Society for Gastrointestinal
Endoscopy[17].
It is questionable whether all endoscopy units working within particular societies of gastrointestinal endoscopy should use identical protocols of informed consent.
For instance, the British Society of Gastroenterology[16]
recommends that each unit should develop its own code
of practice suitable to its mode of operation. However,
some elements are universal and should always be included. The clinician proposing an endoscopic procedure
should explain the reasons for the test and describe its
essential elements[16,18]. Prior to the endoscopy, patients
should be provided with written information in a timely
fashion and in a form understandable to the patient[12,15].
The written information describes the principles of
investigation and the reasons it is performed. It must list
diagnostic/therapeutic alternatives to the test and explain
possible major complications (in terms that the patient
will understand). It is important to mention in writing
that findings within endoscopy and/or possible complications may extend the investigation and/or change the
treatment. It is mandatory to inform the patient about
who has overall responsibility for the procedure and
reassure him/her that the endoscopist and all the staff
will do their best for the patients benefit. A special part
of informed consent should provide information about
conscious sedation and its consequences (the patient
will not be able to drive a vehicle, operate apparatus
requiring full vigilance and must refrain from alcohol
consumption for 24 h after the test). The patient must
have an opportunity to ask additional questions. He/she
must be also advised whom to contact in case of any
complaint or complication after his/her discharge from
the unit (including telephone number for consultation).
A psychological approach to the patient is essential, in-
228
cluding further clarification, reassurance and calming of

any possible fears. Naturally, the form (appended with
date, time and place) identifies not only the patient but
also the unit and the responsible physician. After a full
explanation and comprehension, the informed consent
is signed by the patient and responsible physician. The
form for informed consent should be prepared in duplicate, one for patient and one for medical records.
There are some special situations that should also
be mentioned. The first one is uninformed consent.
Some patients agree with endoscopy but state that they
do not wish to receive any information about the procedure and this should be respected. Ethically, information
cannot be forced on them but their uninformed consent
would still be valid if they are offered detailed information and if they understand that such information is
available for them[18]. Parents (or guardians) will give (and
sign) informed consent on behalf of their children and
guardians (or first-degree relatives) on behalf of mentally disabled patients[18]. Special endoscopic procedures
(insertion of esophageal or biliary stents and percutaneous endoscopic gastrostomy placement) should also be
discussed in detail, including matters of long-term management and potential problems. Some of these patients
are in a serious condition and their capacity to give consent may vary due to cerebral dysfunction. Consent may
be possible orally or by gesture alone but since gastrostomy placement is an invasive procedure, a reasonable
degree of certainty that the patient has consented plus
discussion with relatives is needed in every case[16]. Since
informed consent is a process and not a single event,
post procedural follow-up of patients is obligatory[18]. In
cases of an emergency (when the situation is life threatening or it is necessary to relieve severe pain and suffering), no consent is necessary, the endoscopist takes full
responsibility and acts in the patients best interest[16,18].
The understanding of the risks of endoscopy is insufficient, especially in the cases of older, poorly educated
patients and outpatients[19]. It is also very important to
respect a language barrier[20].
Technological progress has recently brought a lot of
new endoscopic methods and devices. The 21th century
especially has enriched gastroenterology with new great
possibilities: balloon or deep enteroscopy, capsule enteroscopy, confocal laser endomicroscopy, biodegradable
stents etc. Some of new endoscopic methods are still
under evaluation and their yield and safety aspects must
be further determined. These facts must be taken into
account in the informed consent.
Lastly but not least, it is necessary to emphasize that
the patient has a right to withdraw his/her previous consent at any time before or during the endoscopy. If the
patient is under conscious sedation when requesting to
end the procedure, the physician should make a judgement based on the best interests of the patient[18]. The
Latin saying salus aegroti suprema lex (the patients benefit is the highest law) must not be forgotten at any time.
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CONCLUSION
Informed consent is only one of the items of information needed by patients before digestive endoscopy. It is
mandatory to give the patient time and the opportunity
to ask additional questions. The clinician proposing an
endoscopic procedure should explain the reasons for
the test and describe its essential elements. Prior to the
endoscopy, patients should be provided with written information in a timely fashion and in a form understandable to the patient. It is necessary to emphasize that the
patient has a right to withdraw his/her previous consent
at any time before or during the endoscopy.
Movement away from informed consent towards
an informed decision would be the target we should
reach in the near future.
REFERENCES
1
Triantafyllou K, Stanciu C, Kruse A, Malfertheiner P, Axon

A, Ladas SD. European Society of Gastrointestinal Endoscopy. Informed consent for gastrointestinal endoscopy: a
2002 ESGE survey. Dig Dis 2002; 20: 280-283
2 Manthous CA, DeGirolamo A, Haddad C, Amoateng-Adjepong Y. Informed consent for medical procedures: local and
national practices. Chest 2003; 124: 1978-1984
3 Bassi A, Brown E, Kapoor N, Bodger K. Dissatisfaction with
consent for diagnostic gastrointestinal endoscopy. Dig Dis
2002; 20: 275-279
Ladas SD, Triantafyllou K, Liappas I, Hatziargyriou M,
4
Tzavellas E, Barbatzas C, Christodoulou G, Raptis SA. Percutaneous endoscopic gastrostomy: adequacy and quality
of information given to decision makers. Dig Dis 2002; 20:
289-292
OSullivan S, Crippen C, Ponich T. Are patients informed
5
when they consent to ERCP? Can J Gastroenterol 2002; 16:
154-158
Basson MD, Gomez R, Fishman L, Panzini L. Informed con6
sent for screening sigmoidoscopy in a Veterans Administration population. Dis Colon Rectum 2004; 47: 1939-1946
7 Staff DM, Saeian K, Rochling F, Narayanan S, Kern M,
Shaker R, Hogan WJ. Does open access endoscopy close the
door to an adequately informed patient? Gastrointest Endosc
2000; 52: 212-217
Shepherd HA, Bowman D, Hancock B, Anglin J, Hewett D.
8
Postal consent for upper gastrointestinal endoscopy. Gut
2000; 46: 37-39
Enzenhofer M, Bludau HB, Komm N, Wild B, Mueller K,
9
Herzog W, Hochlehnert A. Improvement of the educational
process by computer-based visualization of procedures:
randomized controlled trial. J Med Internet Res 2004; 6: e16
10 Mayberry MK, Mayberry JF. Towards better informed
consent in endoscopy: a study of information and consent
processes in gastroscopy and flexible sigmoidoscopy. Eur J
Gastroenterol Hepatol 2001; 13: 1467-1476
11 Wijtenburg E, Navez B, Cambier E, Guiot P. Patients opinion about written information before laparoscopy: a consecutive series of 100 cases. Acta Chir Belg 2002; 102: 17-19
12 Demosthenous N, St Mart JP, Jenkins P, Chappel A, Cheng
K. Cognitive function in patients undergoing arthroplasty:
the implications for informed consent. Adv Orthop 2011;
2011: 346161
13 Roque I, Hochain P, Merle V, Lerebours E, Hecketsweiler P,
Ducrotte P. Assessment of the quality and psychological impact of information delivered using official consent forms in
229

digestive endoscopy (in French). Gastroenterol Clin Biol 2003;
27: 17-21
14 Denis B, Bottlaender J, Goineau J, Peter A, Weiss AM. Informed consent for gastrointestinal endoscopy. A patientopinion survey (in French). Gastroenterol Clin Biol 2002; 26:
675-679
15 Isaacs PE. What information should be given to patients undergoing therapeutic endoscopy? Dig Dis 2002; 20: 226-229
16 Guidelines for informed consent for endoscopic procedures.
British Society of Gastroenterology, 1999. Available from:
URL: http://www.bsg.org.uk/clinical_prac/guidelines/
consent.htm
17 American Society for Gastrointestinal Endoscopy. Informed consent for gastrointestinal endoscopy. Gastrointest
Endosc 1988; 34: 26S-27S
18
Stanciu C, Novis B, Ladas S, Sommerville A, Zabovowski

P, Isaacs P, Papatheodoridis G, James T. Recommendations
of the ESGE workshop on Informed Consent for Digestive
Endoscopy. First European Symposium on Ethics in Gastroenterology and Digestive Endoscopy, Kos, Greece, June
2003. Endoscopy 2003; 35: 772-774
19 Song JH, Yoon HS, Min BH, Lee JH, Kim YH, Chang DK,
Son HJ, Rhee PL, Rhee JC, Kim JJ. Acceptance and Understanding of the Informed Consent Procedure Prior to Gastrointestinal Endoscopy by Patients: A Single-Center Experience in Korea. Korean J Intern Med 2010; 25: 36-43
20 Clark S, Mangram A, Ernest D, Lebron R, Peralta L. The informed consent: a study of the efficacy of informed consents
and the associated role of language barriers. J Surg Educ
2011; 68: 143-147
S- Editor Yang XC L- Editor Roemmele A E- Editor Yang XC
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doi:10.4253/wjge.v4.i6.231
OBSERVATION
Supportive techniques and devices for endoscopic submucosal

dissection of gastric cancer
Nobuyuki Sakurazawa, Shunji Kato, Itsuo Fujita, Yoshikazu Kanazawa, Hiroyuki Onodera, Eiji Uchida
Key words: Countertraction; Endoscopic submucosal
dissection; Gastric cancer
Nobuyuki Sakurazawa, Shunji Kato, Itsuo Fujita, Yoshikazu

Kanazawa, Hiroyuki Onodera, Eiji Uchida, Department of
Surgery, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku,
Tokyo 113-8603, Japan
Author contributions: Sakurazawa N drafted the manuscript;
Kato S, Fujita I, Kanazawa Y, Onodera H and Uchida E critically
revised the paper; and all the authors read and approved the final
manuscript.
Correspondence to: Nobuyuki Sakurazawa, MD, PhD, Department of Surgery, Nippon Medical School, 1-1-5, Sendagi,
Bunkyo-ku, Tokyo 113-8603, Japan. nsakuraz@nms.ac.jp
Telephone: +81-3-38222131 Fax: +81-3-56850989
Received: August 30, 2011 Revised: February 26, 2012
Peer reviewers: Hiroto Kita, MD, PhD, Professor and Chair,
Department of Gastroenterology, International Medical Center,

Saitama Medical University, 1397-1, Yamane, Hidaka, Saitama
350-1298, Japan; Naoki Muguruma, MD, PhD, Department of
Gastroenterology and Oncology, The University of Tokushima
Graduate School, 3-18-15, Kuramoto-cho, Tokushima 770-8503,
Japan
Sakurazawa N, Kato S, Fujita I, Kanazawa Y, Onodera H,
Uchida E. Supportive techniques and devices for endoscopic
submucosal dissection of gastric cancer. World J Gastrointest
Endosc 2012; 4(6): 231-235 Available from: URL: http://www.
wjgnet.com/1948-5190/full/v4/i6/231.htm DOI: http://dx.doi.
org/10.4253/wjge.v4.i6.231
Abstract
The indications for endoscopic treatment have expanded in recent years, and relatively intestinal-type
mucosal stomach carcinomas with a low potential
for metastasis are now often resected en bloc by endoscopic submucosal dissection (ESD), even if they
measure over 20 mm in size. However, ESD requires
complex maneuvers, which entails a long operation
time, and is often accompanied by complications such
as bleeding and perforation. Many technical developments have been implemented to overcome these
complications. The scope, cutting device, hemostasis
device, and other supportive devices have been improved. However, even with these innovations, ESD
remains a potentially complex procedure. One of the
major difficulties is poor visualization of the submucosal layer resulting from the poor countertraction
afforded during submucosal dissection. Recently,
countertraction devices have been developed. In this
paper, we introduce countertraction techniques and
devices mainly for gastric cancer.
INTRODUCTION
The incidence of gastric cancer is high in East Asia, Eastern Europe and South America. In Japan, 50000 people a
year die from gastric cancer, so countering gastric cancer
is an important mission. Early detection and early treatment are regarded as the most important factors in the
treatment strategy. In patients with early gastric cancer
(mucosal stomach cancer), endoscopic submucosal dissection (ESD) enables en-bloc dissection of larger lesions
than that by endoscopic mucosal resection (EMR)[1-3]. Enbloc resection allows more accurate pathological diagnosis
and reduces the risk of recurrence[3-6].
However, ESD requires complex technical maneuvers and a long operation time. Moreover, complications
such as bleeding and perforation occur more frequently
with ESD than with EMR[2,3,7]. To overcome these complications, many supportive techniques and devices have
been developed.
We classify supportive techniques and devices under the following 3 categories: (1) improvements to the
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231
Sakurazawa N et al . Development of countertraction devices
scope [magnifying endoscopy[8-10], the narrow band imaging system[11-13] and the flexible spectral imaging color
(FICE) system[14], scopes with a built-in forced irrigation channel[15], and so on]; (2) cutting and hemostasis
devices (high frequency generator[16], various knives[17-19],
various hemostasis forceps[20], various hemostasis clips
and so on); and (3) other supportive devices (local injection agents[21]) and CO2 insufflations to the alimentary
tract[22]). Even with these innovations in place, ESD is
still not easy. One of the major difficulties is poor visualization of the submucosal layer resulting from the poor
countertraction afforded during submucosal dissection,
therefore countertraction devices have been developed
in recent years[23-39]. These countertraction devices could
be placed in the 4th category in addition to the three
outlined above. The focus of this article will be countertraction devices (Table 1).
Double-channel therapeutic endoscope (the R-scope) Yonezawa et al[29] 2006
SUPPORTIVE TECHNIQUES AND DEVICES

FOR ESD
Table 1 Classification of countertraction devices and methods

Double endoscope methods
Authors
Year
Double endoscopic intralumenal operation (DEILO) Kuwano et al[23] 2004
Uraoka et al[25]
2010
Transnasal endoscope-assisted ESD
Ahn et al[24]
2010
Yamamoto[26]
2003
Countertraction tool attached to the endoscope

Small-caliber-tip transparent hood
Multipurpose treatment hood (TxHood)
Kawano et al[28]
Angler fish-type countertraction system

Sheath-assisted countertraction ESD
Sakurazawa et al[30] 2009

Hijikata et al[27] 2010
2008
Countertraction tool independent of the endoscope
Improvements to the scope

Zoom endoscopy magnifies the surface structure of tumors and allows the operator to detect the precise border of the tumor[8-10]. The narrow band imaging system
(NBI) selects a spectrum of the emitted illumination
to enhance the structure of the blood vessels and the
tumor border. By using these systems, a more accurate
diagnosis is obtained to avoid unnecessary resection of
the lesion to reduce the risk of bleeding and perforation[11-13]. The FICE system is different from the NBI
system in that it allows selection of the limited spectrum
of the light being reflected from the lesion to enhance
detection of the border between the tumor and normal
mucosa[14]. The water-jet scope can immediately wash
away bleeding during an ESD procedure. With this facility, bleeding points can be precisely identified, and we
can stop bleeding more easily[15].
Percutaneous traction-assisted EMR

Magnetic anchor system
Kondo et al[31] 2004

Kobayashi et al[33] 2004
External grasping type of forceps
Imaeda et al[34]
2006
Internal traction using a nylon loop
Chen et al[36]
2007
Percutaneously-assisted endoscopic surgery using

a new PEG-minitrocar
Peroral traction-assisted ESD
Spring-assisted ESD
von Delius et 2008

al[32]
Jeon et al[39]
2009
Sakurazawa et al[40] 2009
The pulley method ESD
Li et al[38]
Medical ring system
Matsumoto et al[35] 2011
Clip-band technique
Parra-Blanco et al[36] 2011
2010
ESD: Endoscopic submucosal dissection; EMR: Endoscopic mucosal

resection.
flation has been used for ESD. Because, CO2 is more

quickly absorbed in water than air, even in the event of
a perforation-related pneumoperitoneum occurring, the
CO2 is absorbed immediately[22]. This helps to prevent
perforation-related pneumoperitoneum compartment
syndrome.
Countertraction devices
Various countertraction devices have been developed.
We have classified these devices under the following
three types: double endoscope methods, countertraction
tool attached to the endoscope, countertraction tool independent of the endoscope.
Cutting and hemostasis devices

The new high frequency generator calculates the electrical resistance of the tissue instantly, and changes the current flowing though the electric knife depending on the
electrical resistance of the tissue to enhance coagulation
thus decreasing bleeding from the area of incision[16].
Various knives (IT knife, Hook knife, and Flex knife)
have been developed[17-19], in addition to various hemostasis forceps and hemostasis clips[20]. These innovations
now allow us to use the most appropriate knife, hemostasis forceps and hemostasis clips in each scene of ESD.
Double endoscope method: This method involves the

use of two scopes as two endoscopists are sometimes
required, one scope lifts the lesion and the other resects
it. The merit of this technique is that the direction and
strength of countertraction can be obtained by manipulating the lifting scope. The demerit is that their movements are slightly affected by friction between the two
scopes. Kuwano et al[23] reported a double endoscopic
intralumenal operation. This novel technique is characterized by the use of two endoscopes. One scope lifts
the lesion in any desired direction to give clear visualization of the submucosal layer. Because two scopes were
inserted together into the stomach via the oral cavity,
ESD was undertaken under general anesthesia. Ahn et
al[24] reported transnasal endoscope-assisted ESD, which
is a traction method using two scopes. The nasal scope is
used as the traction scope. This method reduces friction
between the two scopes in the oral cavity. The disadvan-
Other supportive devices and techniques

As a substitute for saline which is used conventionally,
a new local injection agent was developed based on hyaluronic acid. Following the use of hyaluronic acid, the
mucosal elevation time improved markedly[21]. Because
mucosal elevation was stable for a long time, the risk
of perforation was reduced. In recent years, CO2 insuf-
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Thin endoscope-assisted ESD
232
Kondo et al[31] reported percutaneous traction-assisted

EMR which uses a type of forceps which penetrates the
abdominal and gastric walls to provide countertraction.
With this method it is easy to coordinate the strength
and direction of the countertraction. However, there is
a risk of pneumoperitoneum and peritonitis. von Delius et al[32] reported percutaneously-assisted endoscopic
surgery using a new PEG-minitrocar for advanced endoscopic submucosal dissection. The device is inserted
using a PEG technique through the skin and stomach
wall, and pulls on the lesion. This system seems similar
to the above mentioned percutaneous traction-assisted
EMR. The magnetic anchor system was reported by Kobayashi et al[33]. It requires the use of a magnetic control
system. This uses magnetic force and it is able to change
the direction and strength of countertraction. However,
this system is large and because it depends on the use
of magnetic force, it is not appropriate in patients fitted
with a pacemaker. The external grasping-type forceps
were reported by Imaeda et al[34]. These forceps pull the
specimen to obtain countertraction. The direction of
countertraction is limited, because the countertraction
tool can only be used to pull and push the tissue of interest. This type of forceps is used from the outside so it
is unlikely to be affected by the movement of the scope.
The medical ring system was reported by Matsumoto
et al[35]. It uses a ring and makes countertraction. This
tool is compact and can pass the forceps channel of the
scope, and achieves countertraction during local traction
of a tumor. The clip-band technique was reported by
Parra-Blanco et al[36]. This method uses a rubber band to
make countertraction. This rubber band was originally
used for orthodontic treatment. The author carefully
determined the size of the ring in accordance with ESD.
This system is easy to prepare and inexpensive. Chen et
al[37] reported internal traction using a nylon loop that
was attached to the tumor edges with hemoclips. The
loop anchored by the 2 hemoclips was tightened by
pulling the smaller loop with the hot biopsy forceps,
and local countertraction is provided by rolling up the
tumor. Li[38] reported the pulley method of ESD which
can change the direction of the traction by using a pulley
in the stomach. The pulley method with standard clips
and dental floss was used to provide traction to improve
visualization of the dissection plane during ESD. Jeon[39]
reported peroral traction-assisted ESD. A thread is inserted orally to pull a lesion to make countertraction.
After circumferential mucosal cutting, one hemostatic
clip, tied with a white silk suture, was applied at a site of
the lesion suitable for oral traction. During submucosal
dissection, the applied suture material was pulled to the
oral side.
We have introduced and performed spring-assisted
ESD in which countertraction is applied with a spring[40].
A spring is introduced into the stomach through the
forceps channel. One end of the spring loop is fixed to
the tumor with a clip. The loop at the other end of the
spring is fixed with a clip to the intact mucosa on the
tages of the procedure include nasal bleeding due to the

transnasal access and the requirement for two endoscopists. Uraoka et al[25] reported thin endoscope-assisted
ESD. The traction was obtained by using a thin endoscope in the large intestine. This system uses the thin
endoscope as lifting forceps to obtain traction in the desired direction. Thin endoscope-assisted ESD has been
limited to the rectum and rectosigmoid colon due to
difficulty in intubating the second endoscope to the oral
side of the distal sigmoid colon. The thin endoscope is
not stiff enough for deep intubation. Another limitation
is the need for a second endoscopist to operate the traction system.
Countertraction tool attached to the endoscope: An
advantage of this method is that it uses a single scope,
thus the preparations for the device are comparatively
simple. Furthermore, it is not difficult for the operator
to achieve countertraction, because the countertraction
tool is attached to the endoscope. One disadvantage is
that the direction and strength of countertraction is affected by the movement of the scope.
Yamamoto et al[26] developed an ST hood which is
clear and placed on the tip of the scope. The ST hood
prevents tissue from adhering to the scope lens to allow
clear observation of the cutting line. At the same time,
the ST hood opens the cutting line and exerts countertraction in the local area. However, the field of view is
limited to a small area. Endoscopic submucosal dissection with sheath-assisted countertraction was reported by
Hijikata et al[27]. This method uses 2 channel scopes and
a sheath which lifts the lesion and exerts countertraction
in the cutting area. The sheath uses one channel and the
knife uses the other channel. A TxHood was developed
by Kawano et al[28]. It can include various therapeutic and
treatment tools such as an electric needleknife, a snare
wire, an injection needle, and a water jet line, and the
lines can be selected freely before insertion of an endoscope covered with the TxHood. Using the grasping forceps from the TxHood, the lesion is lifted to make the
cutting line clear.
The therapeutic endoscope we use (the R-scope)
was developed by Yonezawa et al[29]. This instrument is
equipped with a multibending system and has two movable instrument channels: one moves a grasping forceps
vertically for lesion countertraction; the other swings a
knife horizontally for dissection. We have also employed
the angler fish-type countertraction system[30]. This device has a fine spring grasper which works as the fishing
rod to lift up the desired lesion.
Countertraction tool independent of the endoscope:
The benefit of this approach is that the direction and
strength of countertraction is not affected by the movement of the scope because the countertraction tool
is independent of the endoscope. Preparations differ
greatly for each method, and are associated with both
advantages and disadvantages.
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233
opposite side. The submucosal layer is dissected under

adequate countertraction force. Our newly introduced
countertraction device can be easily handled by one
endoscopist, and shows sufficient effective traction distance in any desired direction without interference by the
gastroscope movements. The device was helpful for dissection of the submucosal layer without complications
and hemostatic treatment.
14
15
16
CONCLUSION
17
ESD is a very effective treatment for early gastric cancer,

but there are many complications. It is thought that we
can reduce complications and treatment time through
the use of various innovative devices. We think that the
countertraction device will become an important device
in the future.
18
19
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L- Editor Webster JR
E- Editor Yang XC


wjge@wjgnet.com
doi:10.4253/wjge.v4.i6.236
GUIDELINES FOR BASIC SCIENCE
Outcomes research in gastroenterology and endoscopy

Parantap Gupta, Jonathan M Buscaglia
Parantap Gupta, Jonathan M Buscaglia, Department of
Medicine, Division of Gastroenterology, Stony Brook University Medical Center, State University of New York, Stony Brook,
NY 11794, United States
Author contributions: Gupta P and Buscaglia JM contributed
equally to this work.
Correspondence to: Jonathan M Buscaglia, MD, Department of Medicine, Division of Gastroenterology, Stony Brook
University Medical Center, 100 Nicolls Road, HSC Level 17,
Room 060, Stony Brook, NY 11794,
United States. jonathan.buscaglia@sbumed.org
Telephone: +1-631-4442117 Fax: +1-631-4448886
Received: October 7, 2011 Revised: November 16, 2011
Gupta P, Buscagli JM. Outcomes research in gastroenterology

and endoscopy. World J Gastrointest Endosc 2012; 4(6): 236-240
Available from: URL: http://www.wjgnet.com/1948-5190/full/
v4/i6/236.htm DOI: http://dx.doi.org/10.4253/wjge.v4.i6.236
INTRODUCTION
The contemporary outcomes research movement in the
United States began about three decades ago when an
increasing emphasis on cost reduction led to interest in
determining and obviating unnecessary procedures. The
movement was induced by the discovery of substantial
variation in medical practice based on geography and
race, with no observable differences in health outcomes[1].
This movement was further propagated by the evidence
of inconsistent use of diagnostics, rising healthcare costs
and concerns about adverse effects on quality of care
from changes in healthcare reimbursement models[2].
These discoveries lead us to realize that there were deficits in our understanding of the safety, indications, and
efficacy of medications and diagnostics, as well as therapeutic procedures. It can be assumed that some interventions produce better outcomes than others given these
variations in practice and differences in results.
Outcomes research has been defined as the scientific
study of the result of diverse therapies used for particular
diseases, conditions, or illnesses. The specific goals of
this type of research are to create treatment guidelines,
document treatment effectiveness and to study the effect
of reimbursement policies on outcomes[3]. In addition
to measuring clinical and physiological endpoints, outcomes studies may assess the effects of an intervention
on health-related quality of life, functional status, patient
satisfaction, and cost[4].
Although overlap clearly exists, outcomes research is
different from traditional clinical research in its focus and
methods. Outcomes research tends to be observational
rather than experimental, and it is patient-centered as
compared to clinical research which is more disease-centered. Outcome measures concentrate more on processes
Abstract
Although the field of outcomes research has received
increased attention in recent years, there is still considerable uncertainty and confusion about what is outcomes research. The following editorial is designed
to provide an overview on this topic, illustrate specific
examples of outcomes research in clinical gastroenterology and endoscopy, and discuss its importance as
a whole. In this article, we review the definition and
specific goals of outcomes research. We outline the
difference between traditional clinical research and
outcomes research and discuss the benefits and limitations of outcomes research. We summarize the types
of outcomes studies and methods utilized for outcomes
assessment, and give specific examples of the impact
of outcomes studies in the field of gastroenterology
and endoscopy.
Key words: Clinical research; Outcomes; Outcomes research

Peer reviewer: Varut Lohsiriwat, MD, Department of Surgery,
Faculty of Medicine Siriraj Hospital, Mahidol University,

Bangkok 10700, Thailand
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236
Gupta P et al . Outcomes research in gastroenterology and endoscopy
standards of care or shifts in practice patterns may also

be evaluated. In short, outcomes research uses a variety
of methods and the following paragraphs provide a general summary of the extent of research embraced by this
field of interest.
Table 1 Differences in focus between outcomes research and

traditional clinical research
Focus
Outcomes research
Observational
Traditional clinical research

Experimental
Example Retrospective analysis assessing the factors associated with

mortality in patients with severe acute pancreatitis
Randomized placebo-controlled
trial of drug X administered to
patients presenting with severe
acute pancreatitis
Focus
Patient-centered
Example Long-term outcomes in patients with dysplastic Barretts
esophagus treated with radiofrequency ablation
Disease-centered
Detection of subsquamous intestinal metaplasia (buried Barretts)
on repeat surveillance esophageal
biopsies
Focus
Physiological factors
Socioeconomic factors
Example Survey study assessing the impact on quality of life in teenaged

patients diagnosed with ulcerative colitis (UC)
OUTCOMES ASSESSMENT USING LARGE

ADMINISTRATIVE DATABASES
Data collected for billing and coding or management
purposes might contain valuable objective data such as
cost, length of hospital stay, outpatient visits, resource
use or mortality. These data can be analyzed promptly
and cheaply without requiring patient consent or interfering with the doctor-patient relationship. Medicare,
Medicaid and large private databases have been extensively used to investigate a variety of outcomes such as
the risk of re-hospitalization for patients using clopidogrel with a proton pump inhibitor[8], or the disparities in
demographics among hospitalized patients with pancreatitis-related mortality[9].
The surveillance, epidemiology, and end results
(SEER) program of the National Cancer Institute provides considerable information on cancer statistics not
available for other digestive conditions. For example,
in 2004 approximately 233000 people were diagnosed
with digestive system cancers, representing 18% of all
malignancies[10]. A recent analysis of the SEER database
revealed that patients with early esophageal cancer managed with endoscopic therapy have equivalent longterm survival compared to those treated with surgical
resection[11]. These types of data are generally limited by
quality and completeness of the available information.
Detailed clinical information is lacking as it is collected
for administrative purposes. Nonetheless, when exercised
cautiously by seasoned researchers, analysis of such data
can provide important evidence-based information to
supplement randomized controlled trials, or provide the
framework for other clinical studies.
Retrospective analysis on postoperative complications in patients with UC undergoing total

proctocolectomy
and delivery of care rather than on drugs and instruments. It aims to study the impact of diseases on patients
rather than the mechanisms of disease, and it measures
the effects of socioeconomic factors, not the effect of
biochemical and physiological factors (Table 1).
Outcomes studies can help physicians in advising
patients about what works, what doesnt, when in the
course of illness does it begin working, and what it costs
to actually work in the real world of clinical practice.
These data can help physicians, payers and patients
make rational, insightful choices on medical care-related
issues[5]. The outcomes research movement is gaining
momentum with the recognition of its importance by
physicians, specialty medical societies and managed care
organizations. This movement towards assessment and
accountability has been termed the third revolution in
medical care[6].
Outcomes research, however, has its own limitations [7]. Applying outcomes research data is difficult
when making complex and individualized patient care
decisions. In addition, very few of the commonly used
and continuously evolving procedures and devices used
in medicine are supported by evidence from randomized controlled trials, given that these trials often cost
millions of dollars and frequently last years in duration.
Finally, compliance with practice guidelines (put forth as
a result of outcomes research) is extremely difficult to
assess throughout the medical community as a whole.
Outcome measurements in outcomes research may
be evaluated based on the categories of clinical measures,
economic measures or humanistic indices. Clinical measures include data for clinical events (e.g., need for repeat
hospitalization following an upper GI bleed), physiological measures (e.g., assessing acid reflux by esophageal pH
measurement studies) or mortality. Economic measures
include direct and indirect medical costs (e.g., outpatient
visits, work loss, etc.), and analyses of resource use. Humanistic indices evaluate symptoms, functional status (e.g.,
health-related quality of life) and patient satisfaction. Appropriateness of medical interventions, conformance to
WJGE|www.wjgnet.com
DECISION ANALYSIS
Decision analysis is the methodology of using mathematical computation for the evaluation of clinical decisions. It is used to ascertain best strategies when there
are several different courses of action, and an indefinite
or hazardous pattern of outcomes. A decision-tree is
created after identifying all accessible choices and likely
outcomes. The tree is used to symbolize the available
strategies and the likelihood of occurrence of each outcome if a particular strategy is selected. Decision analysis is used to identify the crucial factors in the decisionmaking exercise and can be used to make healthcare
policy recommendations and develop clinical management guidelines. For example, decision analysis played
an important role in the development of the current
American College of Gastroenterology guidelines[12] for
the management of dyspepsia[13].
237
META-ANALYSIS
CLINICAL GUIDELINE DEVELOPMENT
A meta-analysis combines the results of several clinical

studies which address a set of related research hypotheses that meet pre-determined standards of quality. An
expertly conducted meta-analysis can improve statistical
power if the sample size of individual studies is small.
Meta-analyses are becoming increasingly important in
the determination of clinical efficacy and harm, to plan
future studies and to make clinical recommendations for
therapy. It is an important source of outcomes data for
the practice of evidence-based medicine. For example, a
meta-analysis of the role of endoscopic variceal ligation
in the primary prophylaxis of esophageal variceal bleeding[14] was instrumental in formulating the American Association for Study of Liver Diseases guidelines for the
prevention and management of gastroesophageal varices
and variceal hemorrhage in cirrhosis[15].
Due to wide-spread cost containment measures, clinical

guidelines detailing healthcare recommendations have
become abundant, however, these guidelines have been
based on varying degree of scientific evidence. The
Agency for Healthcare Research and Quality (AHRQ)
has defined strict criteria for the development of guidelines. Guidelines should be based on robust scientific
evidence rather than on expert opinion. It has not been
shown conclusively that guidelines change physician
behavior. Reasons for this finding may be because some
guidelines may not be designed for community physicians, the practicing physicians may disagree with the
expert opinion of the guideline author or they may elect
not to follow the guidelines because of fear of litigation.
RANDOMIZED CLINICAL TRIALS

Randomized clinical trials (RCTs) are generally considered the gold standard in clinical research. For example,
the National Polyp Study was the landmark randomized
clinical trial to evaluate effective surveillance of patients
discovered to have one or more colorectal adenomas[22].
Traditional RCTs encompass efficacy studies which
generally have a strict code of conduct and require predefined hypotheses, randomization of carefully selected
subjects to pre-specified intervention arms, largely similar populations, experienced investigators, a specific protocol, a comparable intervention and intense follow-up.
Results from these types of studies are robust. However,
because of the restrictive design, the results may not be
valid in community practice.
On the other hand, outcomes research focuses on effectiveness studies which are designed to evaluate interventions in community settings with unselected patients,
typical care providers and usually-performed procedures.
Effectiveness studies are often observational and retrospective, without randomized allocation of patient population. Selection bias may be a problem in such studies
and adjustment for severity of illness and case mix is an
important aspect to retain validity.
COST-EFFECTIVENESS ANALYSES
Cost-effectiveness analysis is a form of economic analysis that compares the relative costs and outcomes of two
or more courses of action to determine the most productive use of limited resources. The cost-effectiveness
ratio evaluates alternative patient management strategies,
programs or services. The most commonly used outcome measure is quality-adjusted life years. This type of
analysis is a measure to critically evaluate clinical practices and weigh outcomes against their costs. These data
can be used for the distribution of limited funds. Such
studies have also been used to compare the cost-effectiveness of practices in gastroenterology with the costeffectiveness of other medical practices. For example,
colonoscopy has been compared with computed tomographic colonography in cost-effectiveness studies[16].
HEALTH SERVICES RESEARCH

The measurement of health status, patient preferences,
and quality of care are a part of health services research[17]. Health services research examines how people
gain access to health care[18], how much care costs, and
what happens to patients as a result of this care. The
main goals of health services research are to identify the
most effective ways to organize, manage, finance, and
deliver high quality care, as well as to reduce medical errors and improve patient safety[19].
The measurement of quality of life is also an important topic of research under health services research.
General and specific quality of life measures have been
developed for research purposes. The Crohns disease
activity index[20], the Harvey-Bradshaw index and the Inflammatory Bowel Disease Questionnaire are examples
of such measures. Health services research also encompasses measurement of healthcare use. For example,
does early endoscopy alter healthcare use patterns or
satisfaction in patients with dyspepsia [21]?
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CLINICAL EPIDEMIOLOGY
Clinical epidemiology employs rigorous epidemiological
methods to study diagnoses, effective management, and
natural progression or prognosis of diseases. Clinical
epidemiologic studies such as observational studies help
in the development of guidelines in the absence of randomized clinical trials[23,24].
IMPORTANCE OF OUTCOMES RESEARCH

TO GASTROENTEROLOGY
Digestive diseases have a heavy medical, social, political
and economic burden in the United States. In 2004, the
238
are becoming part of the report cards that purchasers

and consumers can use to assess the quality of care in
health plans[29]. For public programs such as Medicaid
and Medicare, outcomes research provides policymakers
with the tools to monitor and improve quality both in
traditional settings and under managed care. Outcomes
research in this regard can be the key to knowing how
we better achieve and deliver quality healthcare.
direct health care costs of digestive diseases were more

than $97 billion, up from $40 billion in 1985. The total
cost of digestive diseases, including direct and indirect,
in the United States in 2004 was estimated to be $141.8
billion. More than 72 million ambulatory care visits with
patients with a first-listed diagnosis of a digestive disease
were reported in 2004. Digestive diseases were also common diagnoses at hospital discharge with approximately
4.6 million discharges of patients with a first-listed diagnosis of a digestive disease and 13.5 million discharges
with a digestive disease as a primary or secondary diagnosis. In 2004, there were > 236000 deaths in the United States with a digestive disease as an underlying cause,
which represented 9.8% of all deaths[25].
It is estimated that > 20 million upper and lower endoscopies are performed yearly in the United States[26].
There is no single national database that can provide
accurate, population-based information on the absolute
number of gastrointestinal (GI) endoscopies and their
indications and diagnostic outcomes. To bridge this important gap in knowledge on the burden of GI disease, a
National Endoscopic Database (NED) has been started
by the Clinical Outcomes Research Initiative (CORI).
CORI was developed to study outcomes of GI
endoscopic procedures in real life settings with the
primary goal to use the NED to acquire information
that will improve the quality of clinical practice in gastroenterology. Physicians participating in the CORI consortium produce GI endoscopy reports using a specialty
electronic health record. Data from the reports are sent
electronically to a central data repository where they are
pooled with data from other consortium participants in
the NED. The CORI project began in 1995 under the
auspices of the American Society for Gastrointestinal
Endoscopy. In 2007, the NED received over 250 000
reports from 70 practice sites in 24 states with approximately 400 participating endoscopists. Practice sites
include hospitals, ambulatory care centers, private practices, universities, and Veterans Affairs hospitals. The
NED now contains close to 2 million reports[27]. These
data have been analyzed to examine endoscopic practice
patterns, to develop research hypotheses, to support
quality measure reporting, and as a resource for prospective research on topics such as colon polyp surveillance.
Although the participating sites are over-represented by
veteran and military facilities, the patterns of endoscopy
in NED have been shown to be quite similar to that of
a national sample of the Medicare population and may
well be applicable to the United States as a whole[28].
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S- Editor Yang XC
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E- Editor Yang XC


wjge@wjgnet.com
doi:10.4253/wjge.v4.i6.241
GUIDELINES FOR CLINICAL PRACTICE
Post-endoscopic retrograde cholangiopancreatography

complications: How can they be avoided?
Juan J Vila, Everson LA Artifon, Jose Pinhata Otoch
Juan J Vila, Endoscopy Unit, Gastroenterology Department,
Complejo Hospitalario de Navarra, Pamplona 31008, Spain
Everson LA Artifon, Associate Professor of Surgery, University
of Sao Paulo, Sao Paulo 04304-030, Brazil
Jose Pinhata Otoch, Associate Professor of Surgery, University
of Sao Paulo, Sao Paulo 04304-030, Brazil
Author contributions: Vila JJ drafted the article; Artifon ELA
and Otoch JP critically reviewed the article.
Correspondence to: Juan J Vila, MD, Endoscopy Unit,
Gastroenterology Department, Complejo Hospitalario de
Navarra, Pamplona 31008, Spain. juanjvila@gmail.com
Telephone: +34-848-422114 Fax: +34-848-422303
Received: September 16, 2011 Revised: February 23, 2012
cholangiopancreatography complications: How can they be

avoided? World J Gastrointest Endosc 2012; 4(6): 24-246
Available from: URL: http://www.wjgnet.com/1948-5190/full/v4/
i6/24.htm DOI: http://dx.doi.org/10.4253/wjge.v4.i6.24
INTRODUCTION
Endoscopic retrograde cholangiopancreatography
(ERCP) is an endoscopic procedure which has a high
complication rate ranging from 5%-40% in different
series depending on the difficulty of the examination,
previous diagnosis and patient comorbidities. These
complications develop mainly as a consequence of papillary maneuvers to achieve deep biliary or pancreatic duct
cannulation.
Nowadays, ERCP has entered a new era in which
related procedures only fit therapeutic intention. It is not
ethically justified to offer such risky exploration to patients intended only as a diagnostic procedure. Thus, patients may be exposed to these risks when the intention
of the procedure is to offer a minimally invasive exam
with excellent results, thus avoiding surgery or radiologic
interventions.
However, in recent years this morbidity has declined
due to the benefits of different maneuvers which have
allowed this technique to be performed with greater security. This article presents and discusses factors which
can help to reduce the morbidity of ERCP, including
both non-technical factors, and therefore, endoscopistindependent, and technical factors, and therefore,
endoscopist-dependent. In the latter we will include the
role of the different cannulation techniques and their
influence on post-ERCP morbidity. With regard to nontechnical factors, we will review the role of two methods
which have accumulated scientific evidence in the prevention of post-ERCP pancreatitis such as pancreatic
stent placement and administration of non-steroidal
anti-inflammatory drugs (NSAIDs).
Abstract
Endoscopic retrograde cholangiopancreatography
(ERCP) has a significant complication rate which can
be lowered by adopting technical variations of proven
beneficial effect and prophylactic maneuvers such as
pancreatic stenting during ERCP or periprocedural
non-steroidal anti-inflammatory drug administration.
However, adoption of these prophylactic maneuvers by
endoscopists is not uniform. In this editorial we discuss
the beneficial effects of the aforementioned maneuvers.
Key words: Acute necrotizing; Anti-inflammatory

Agents; Catheterization; Cholangiopancreatography;
Complications; Endoscopic retrograde; Non-steroidal;
Pancreatitis; Stents
Peer reviewer: Ka Ho Lok, MBChB, MRCP, FHKCP,
FHKAM, Associate Consultant, Department of Medicine and
Geriatrics, Tuen Mun Hospital, Tsing Chung Koon Road, Tuen
Mun, Hong Kong, China
Vila JJ, Artifon ELA, Otoch JP. Post-endoscopic retrograde
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241
Vila JJ et al . ERCP complications
the rectal administration of 100 mg of diclofenac immediately after ERCP, or 100 mg of indomethacin immediately prior to ERCP, significantly decrease the risk of
post-ERCP pancreatitis from 12.5% to 4.4%, with a risk
reduction of 0.33 and an NNT of 15 patients. Furthermore, in published studies no adverse effects attributable
to NSAIDs have been described.
The use of NSAIDs peri-ERCP is indicated in lowrisk cases to prevent the development of post-ERCP
pancreatitis[4] and probably, although this has not been
assessed, in patients at high risk in whom a prophylactic
pancreatic stent could not be inserted.
The prophylactic use of antibiotics before or after
ERCP to prevent the development of post-ERCP cholangitis or other infectious complications has been extensively evaluated in numerous studies. The British Society
of Gastroenterology guide for antibiotic prophylaxis in
gastrointestinal endoscopy has recently been published
and recommends the prophylactic administration of antibiotics during ERCP in patients who are in the following situations: patients who are not expected to obtain
full patency of the bile duct by one ERCP, patients with
advanced hematologic cancer, patients with a history of
liver transplantation, patients with pancreatic pseudocysts and patients with severe neutropenia[10].
Quinolones are the recommended antibiotics, although the antibiotic and regimen should be tailored to
the antimicrobial resistance profile of each hospital.
Confirmation that the best predictor of the development of post-ERCP infectious complications is
incomplete resolution of biliary obstruction was subsequently confirmed in a meta-analysis which included
nine prospective randomized studies with a total of
1573 patients[11]. According to this meta-analysis, prophylactic antibiotic therapy halved the risk of bacteremia
(RR: 050, 95% CI: 0.33-0.78) after ERCP, but did not
show any effect on overall mortality (RR: 1.33, 95% CI:
0.32-5.44). In the subgroup of patients in whom ERCP
completely resolved the biliary obstruction, the protective effect of antibiotics had no impact. In contrast, the
subgroup of patients in whom biliary obstruction could
not be resolved completely with ERCP benefitted from
antibiotic prophylaxis.
REDUCING MORBIDITY BY MEANS OF

NON-TECHNICAL FACTORS
We consider endoscopist-independent prophylactic factors as those factors which have proven prophylactic
benefit, such as pancreatic stent placement and administration of NSAIDs and antibiotics. The first two factors
are used in the prophylaxis of post-ERCP pancreatitis
and the latter in the prophylaxis of post-ERCP cholangitis and other infectious complications.
Pancreatic stent placement in various studies was
proved to be effective in preventing the development of
post-ERCP pancreatitis. Several meta-analyses have also
been published, the first in 2004 which included 5 studies and 481 patients[1]. This meta-analysis showed that
the incidence of post-ERCP pancreatitis was significantly lower in the stented group (5.8%) versus the control
group (15.5%), with an odds ratio (OR) of 3.2 and the
number of patients needed to treat (NNT) to prevent
pancreatitis was 10. A subsequent meta-analysis included
a sixth randomized controlled trial, with similar results[2].
In the stented group the incidence of acute pancreatitis
was 12% vs 24% in the control group, with a protective
OR of 0.44 for the stented group and a NNT of only
8. The final meta-analysis was published recently and included 8 randomized controlled trials which demonstrated a reduction in the OR to 0.22 (95% CI: 0.12-0.38, P
< 0.01) in the stented group and a NNT of 8 patients[3].
These results have not gone unnoticed in scientific
societies, and the European Society of Gastrointestinal
Endoscopy includes the recommendation to place prophylactic pancreatic stents in high-risk patients undergoing ERCP[4]. This group of high-risk patients is not well
defined, although there is a consensus to consider the
following high-risk patients: patients undergoing ERCP
for sphincter of Oddi dysfunction, young women, patients with previous history of pancreatitis, patients in
whom a high number of pancreatic duct cannulations
and injections have been made during cannulation or
ampullectomy, and many authors advocate the introduction of a prophylactic pancreatic stent when using the
double-wire technique.
The recommended stent is currently a short ( 5
cm) 5F plastic stent, and preferably with only an external
flange, although some authors prefer to introduce double flanged stents[5,6]. Up to 10 d after stenting, observations for spontaneous migration should be made and if
present, the stent should be endoscopically extracted.
However, it is not always easy to insert a pancreatic
stent and complications related to pancreatic duct cannulation to insert the stent can occur. Therefore, prophylactic pancreatic stenting is recommended when the
endoscopists success rate for this maneuver is higher
than 75%[4].
Currently, there are four prospective studies evaluating the utility of prophylactic administration of NSAIDs
for post-ERCP pancreatitis, which have been evaluated
in three meta-analyses[7-9]. These data have shown that
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REDUCING MORBIDITY BY MEANS OF

TECHNICAL FACTORS
Of the endoscopist-dependent protective factors we can
include all the described cannulation variations which
have proved beneficial in the incidence of post-ERCP
complications. The first factor is undoubtedly the guidewire cannulation technique. This technique was introduced by Siegel and Pullano in 1987[12]. Cannulation with
a guide-wire consists of the introduction of a guide-wire
into the bile or pancreatic duct instead of contrast injection as the first maneuver. There are several variations of
this technique, and the tip of the catheter or sphincterotome is inserted initially with which we will cannulate a
242
Figure 1 The guide-wire technique has been used in this patient to cannulate the minor papilla. The minor papilla is cannulated with the guide-wire
tip protruding a few millimeters over the cannula.
few millimeters through the papillary orifice and then

introduce the guide-wire to the target. Another variation
is direct cannulation with the guide-wire hovering a few
millimeters or even one or two inches through the catheter or sphincterotome. This latter option is especially
useful in pancreatic cannulation through the minor papilla (Figure 1).
The benefit of this technique compared with classic
contrast cannulation has been demonstrated in several
studies which show similar results and have been jointly
analyzed in a recent meta-analysis[13,14]. This meta-analysis
included 5 studies and 1762 patients, and demonstrated
that the use of the guide-wire technique significantly
improved the primary cannulation rate from 74.9% to
85.3% (OR: 2.05, 95% CI: 1.27-3.31) and more importantly, significantly reduced the incidence of post-ERCP
pancreatitis from 8.6% to 1.6% (OR: 0.23, 95% CI:
0.13-0.41). Consequently, the authors concluded that the
guide-wire technique should be considered the standard
cannulation technique.
The double-wire cannulation technique was first
described by Dumonceau et al[15] in 1998. It can be used
when access to the pancreatic duct can only be achieved
during a biliary ERCP. A guide-wire is placed into the
pancreatic duct and parallel to this guide-wire a catheter
or sphincterotome is inserted to cannulate the bile duct
(Figure 2). The functions and benefits attributed to this
technique are that the guide-wire in the pancreatic duct
could open a stenotic papillary orifice, stabilize the papilla, raise the papilla towards the working channel of
the endoscope, rectify the pancreatic and common duct,
drain the pancreatic duct and minimize the injections
into the pancreatic duct.
One of the first studies evaluating this technique
compared a group of 27 patients with difficult cannulation who underwent this technique with another group
of 26 patients in whom the endoscopist persisted in trying the classical contrast injection technique. The doublewire technique significantly improved the rate of cannulation to 93% vs 58% achieved with the classic technique (P
= 0.0085), showing no significant differences in the inci-
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Figure 2 Image of the double guide-wire technique. A guide-wire is inserted

in the pancreatic duct and left in situ. The cannula is then inserted parallel to the
pancreatic guide-wire (A) in order to cannulate the bile duct (B).
dence of post-ERCP pancreatitis[16]. However, Ito et al[17]

did not obtain such good results with this technique and
described a cannulation rate of 73% with an incidence of
post-ERCP pancreatitis of 12%.
A randomized prospective trial comparing a group
of 97 patients with difficult cannulation in whom the
double-wire technique was used with another group of
91 patients in whom persistence of classical cannulation was attempted has been published recently[18]. The
double-wire technique resulted in a poorer outcome
compared with the classical technique regarding the incidence of post-ERCP pancreatitis (17% vs 8%, P > 0.05),
and the cannulation rate was significantly worse with the
double-wire technique (OR: 0.66, 95% CI: 0.64-1.12).
The authors concluded that the double-wire technique
offers no advantage over the classical technique in
achieving biliary cannulation, and did not decrease the
incidence of post-ERCP pancreatitis.
Therefore, the data available in the literature on
this technique are contradictory and at present it is not
recommended for achieving cannulation or decreasing
post-ERCP pancreatitis. This technique may be useful
for achieving biliary cannulation in patients in whom repeated pancreatic duct injections are performed. If this
technique is used, a prophylactic pancreatic stent should
also be inserted.
A variation of the previous technique is guide-wire
cannulation over a pancreatic stent (Figure 3). This
technique consists of the introduction of a pancreatic
243
Figure 3 In this fluoroscopic image biliary cannulation over a pancreatic

stent technique is shown. The technique resembles the double-wire technique, but a plastic stent (arrow) is inserted in the pancreatic duct instead of the
guide-wire, and the bile duct is cannulated in parallel.
stent over the guide-wire initially left in the pancreatic

duct, and in parallel with a sphincterotome or catheter
to cannulate the bile duct. In a first study, Fogel et al[19]
reported a significantly lower incidence of post-ERCP
pancreatitis in patients with sphincter of Oddi dysfunction in whom a pancreatic stent was placed followed by
needle knife sphincterotomy compared with the doublewire technique (10.7% vs 28.3%, P < 0.05). In a similar
group of patients Madacsy et al[20] also showed a significant benefit using a pancreatic stent and had no cases
of post-ERCP pancreatitis compared with a post-ERCP
incidence of 43% in the group of patients in whom the
needle knife was performed with a guide-wire into the
pancreatic duct (P < 0.05).
More recently, Ito et al[21] did not find significant differences using the cannulation over a pancreatic stent
technique compared with the double-wire cannulation
technique regarding primary cannulation (80% vs 94%, P
= 0.15) in a group of patients with difficult cannulation,
however, there was a significant benefit in the incidence
of post-ERCP pancreatitis (2.9% vs 23%, P < 0.05).
Therefore, this technique offers a clear protective effect against the development of post-ERCP pancreatitis,
and would be recommended when we have access to the
pancreatic duct and needle knife sphincterotomy is decided.
Finally, needle knife sphincterotomy (Figure 4) is a
well known and validated technique which has different variants: cephalad incision from papillary orifice,
pancreatic precut and fistulotomy. Although there are
no studies comparing the outcomes of these variants,
optimal results with the pancreatic precut technique and
fistulotomy technique have been described recently.
The appropriate timing of this technique has been
studied. In a recently published meta-analysis including
6 prospective, randomized, controlled trials comparing
the rate of cannulation and the incidence of post-ERCP
pancreatitis in a group of patients with difficult cannulation in whom early pre-cut was performed (442 patients)
with another group in whom persistence in cannulation
was performed with late pre-cut if cannulation was un-
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Figure 4 Needle knife sphincterotomy technique. A superficial mucosal

cut is performed showing the duodenal portion of the common bile duct as a
reddish rounded protrusion (asterisk) (A). A deeper cut is made on this nodule
going into the bile duct (B).
successful (524 patients)[22]. There were no differences

in the success rate of cannulation (90.2% vs 89.6%, OR:
1.20, 95% CI: 0.54-2.69), however, significant differences
were seen in the incidence of post-ERCP pancreatitis
(2.48% vs 5.34%, OR: 0.47, (95% CI: 0.24-0.91) favoring
early pre-cut.
Therefore, performing early pre-cut has a similar rate
of primary cannulation but is associated with a lower incidence of post-ERCP pancreatitis.
Other endoscopist-dependent factors no less important in our opinion when it comes to reducing the incidence of post-ERCP complications are subjective and
difficult to evaluate. These include knowledge update,
the progression of more complicated cases and techniques, and cautious attitude of the endoscopist. These
factors are extremely important and help to identify not
only an appropriate indication for ERCP, but also the
different therapeutic techniques performed during this
procedure, hopefully contributing to a reduction in the
incidence of complications.
CONCLUSION
The acceptance of the aforementioned maneuvers
by endoscopists is not uniform. An American survey
showed that expert endoscopists are aware of the protective effect of pancreatic stents in patients at high risk,
but the indications for stent placement and the type
of stent chosen varies widely among endoscopists[23].
244
A recently published survey showed that up to 21.3%

of endoscopists in Europe never perform prophylactic
pancreatic stenting despite favorable scientific evidence,
mainly because of lack of experience[24]. In this survey
it was shown that the vast majority of endoscopists did
not regularly attempt prophylactic pancreatic stenting
when procedure-related risk factors for post-ERCP pancreatitis were present, and slightly more frequently when
patient-related risk factors were present. Moreover,
83.7% of endoscopists do not use NSAIDS for postERCP pancreatitis prophylaxis[24].
Expert endoscopists with greater experience in
ERCP are more reluctant to adopt changes to their usual
technique, probably because they have favorable rates
of outcomes and complications, and because they think
that introducing an alternative technique into their working methods might lead to a temporary decrease in successful cannulation rates and an increase in complication
rates. However, a recent study from Japan has shown
that wire-guided cannulation is useful immediately after
its introduction in a specialized center with expertise in
contrast cannulation, and in this context wire-guided
cannulation has a higher rate of primary cannulation, a
shorter procedural time and a lower rate of hyperamylasemia[25]. On the other hand, endoscopists with less
experience and those in training should know these techniques and adopt them as standard practice given the
scientific evidence of benefit.
The question is whether an endoscopists personal
preference is enough reason to maintain a technique?
In our opinion it is not, since there is scientific evidence
supporting a different policy. Endoscopists in training
should adopt the technique proven to be the best. On
the other hand, expert endoscopists who reject changes
in their technique could argue that they already achieve
favorable outcomes. But even good outcomes can be
improved and expert ERCPists should be the first to
adopt proven variations in technique to obtain clinical
improvement.
To conclude, although recommendations in endoscopy should not be rigid and cannot replace clinical
judgment[4], it is the duty of both expert and non-expert
endoscopists to know their results and complication
rates and if these are unfavorable, evaluate which of the
previously described variations should be performed to
improve their outcomes.
8
9
10
11
12
13
14
15
16
17
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246
E- Editor Yang XC


wjge@wjgnet.com
doi:10.4253/wjge.v4.i6.247
REVIEW
Pancreatic cystic lesions: How endoscopic ultrasound

morphology and endoscopic ultrasound fine needle
aspiration help unlock the diagnostic puzzle
Luca Barresi, Ilaria Tarantino, Antonino Granata, Gabriele Curcio, Mario Traina
creatic cystic lesions: How endoscopic ultrasound morphology and endoscopic ultrasound fine needle aspiration help
unlock the diagnostic puzzle. World J Gastrointest Endosc
2012; 4(6): 247-259 Available from: URL: http://www.wjgnet.com/1948-5190/full/v4/i6/247.htm DOI: http://dx.doi.
org/10.4253/wjge.v4.i6.247
Luca Barresi, Ilaria Tarantino, Antonino Granata, Gabriele

Curcio, Mario Traina, Unit of Gastroenterology and Digestive
Endoscopy, Mediterranean Institute for Transplantation and Advanced Specialized Therapies, 90146 Palermo, Italy
Author contributions: Barresi L wrote the paper; Granata A
and Curcio G researched the literature; Tarantino I and Traina
M revised the final version.
Correspondence to: Luca Barresi, PhD, Mediterranean Institute for Transplantation and Advanced Specialized Therapies,
Via Tricomi n1, 90146 Palermo, Italy. lbarresi@ismett.edu
Telephone: +39-331-1718159 Fax: +39-0912192400
Received: October 14, 2011
Revised: May 8, 2012
INTRODUCTION
A search on Medline with the key-words pancreatic
cyst would find 7074 results, at the time of writing.
Why so much interest? There are three answers to this
question.
Firstly, there has been an increase in the diagnosis
of these lesions, itself a result of improvements in
imaging techniques, such as multidetector computerized tomography (MDCT), magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS). From an
autoptic point of view, these lesions are very common.
About a quarter of examined pancreases show cystic lesions, 16% of which contain atypical epithelium and 3%
high grade dysplasia[1]. Currently, about 1% of patients
in hospitals receive, often accidentally, a diagnosis of a
pancreatic cystic lesion[2,3]. During imaging tests (MDCT,
MRI, EUS) for other reasons, between 13% and 20% of
exams will show a pancreatic cystic lesion (PCL)[4] and,
more importantly, most of these lesions (90%) are neoplasms with premalignant or malignant features and not
pancreatic pseudocysts[5].
Secondly, pancreatic cystic lesions are a large group of
varying entities, with a wide variability of biological behavior, from benign to borderline to malignant (Table 1).
Thirdly, and most importantly, until now there has
not been a unique test accurate enough to make a differential diagnosis in all of these lesions.
This last point is the focus of this review. We cannot, in fact, make the right decision for our patients if
Abstract
Cystic lesions of the pancreas are being diagnosed with
increasing frequency, covering a vast spectrum from
benign to malignant and invasive lesions. Numerous
investigations can be done to discriminate between benign and non-evolutive lesions from those that require
surgery. At the moment, there is no single test that
will allow a correct diagnosis in all cases. Endoscopic
ultrasound (EUS) morphology, cyst fluid analysis and
cytohistology with EUS-guidedfine needle aspiration
can aid in this difficult diagnosis.
Key words: Pancreatic cystic lesions; Endoscopic ultrasound; Endoscopic ultrasound fine needle aspiration
Peer reviewers: Sylvain Manfredi, MD, PhD, SMAD, CHU
Pontchaillou, 2 rue H le Guilloux, 35000 Rennes, France;

Kazuichi Okazaki, Chairman and Professor, Department of
Gastroenterology and Hepatology, Kansai Medical University,
2-3-1, Shinmachi, Hirakata, Osaka 573-1191, Japan
Barresi L, Tarantino I, Granata A, Curcio G, Traina M. Pan-
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247
Barresi L et al . Endoscopic ultrasound in pancreatic cystic lesions
we are not able to determine exactly what kind of lesion

we are studying and so predict the likelihood of developing a malignancy. In the last 10 years we have seen
enormous improvements in our diagnostic arsenal. Radiological diagnostic modalities have seen the advent of
new CT scans, the emergence of MRI with the help of
cholangio-pancreato-RM and, last but not least, the diffusion of EUS, with the possibility of fine needle aspiration (FNA) and analysis of the intracystic fluid. In this
review, we will analyze these diagnostic modalities, with
particular attention on the EUS aspect of pancreatic cystic lesions, in order to draw some possible and plausible
conclusions on the state of the art.
Table 1 Cystic lesions of the pancreas

mission of Dr. Parra-Herran CE)
(reprinted with per-
Cystic lesions of the pancreas

Non-neoplastic cysts (30%-40%)
No lining
Inflammatory pseudocyst
Paraduodenal wall cyst
Infection-related cyst
True lining
Mucinous non-neoplastic cysts (mucoceles, retention cysts)
Cystic hamartoma
Enterogenous (congenital, duplication) cyst
Endometriotic cyst
Lymphoepithelial cyst
Squamoid cyst of pancreatic ducts
Others (unclassified)
Neoplastic cysts (60%-70%)
True lining
Mucinous lining (30%)
Intraductal papillary mucinous neoplasm (20%)
Mucinous cystic neoplasm (10%)
Serous lining (20%)
Serous cystadenoma (microcystic, oligocystic)
Von Hippel-Lindau-associated pancreatic cyst
Serous cystadenocarcinoma
Squamous lining (< 1%)
Epidermoid cyst within intrapancreatic accessory spleen
Dermoid cyst
Acinar cell lining (< 1%)
Acinar cell cystadenoma
Acinar cell cystadenocarcinoma
Endothelial lining (< 1%)
Lymphangioma
Solid tumors with cystic change (5%)
Solid pseudopapillary tumor
Ductal adenocarcinoma with cystic change
Neuroendocrine tumor with cystic change
Other invasive carcinomas with cystic change
No lining (< 1%)
Mesenchymal neoplasms with cystic change
Others (unclassified)
DIAGNOSIS OF PANCREATIC CYSTIC

LESIONS
Epidemiological and clinical aspects
Firstly we focus on the prevalence of the different PCLs.
Serous cystoadenoma neoplasm (SCN), intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic
neoplasm (MCN) represent about 90% of all pancreatic
cystic neoplasms. These lesions, together with pancreatic
pseudocysts (PP), are responsible for 90% of all pancreatic cystic lesions[5-8]. Knowing this, we focus more on
these lesions in our diagnostic reasoning.
As in every diagnostic work up in medicine, we start
with epidemiological and clinical aspects that in the case
of PCLs offer several important indications (Table 2).
SCN represents 32%-39% of all cystic neoplasms[2,9],
with a peak of incidence at 62 years of age (although
the range is quite wide), a slight prevalence in females
(3-4:1)[10] and a slight preference for the pancreatic head
(50%)[11]. It is usually asymptomatic unless it is larger
than 4 cm, in which case the symptoms are caused by
the mass effect. Of the thousands of reported cases in
the literature, there are only 26 reported cases of malignancy[12], so it can often be considered a benign lesion.
IPMN represents 21%-33%[2] of all pancreatic cystic neoplasms, although it is likely that its prevalence is
greater because of an increase in the diagnosis of small
branch duct lesions, particularly in elderly patients. IPMN
can involve the main pancreatic duct (MD-IPMN), the
branch pancreatic duct (BD-IPMN) or both (MIXIPMN), although in about 20% of cases such a distinction is not possible[13-15]. In the differential diagnosis of
other pancreatic cystic lesions, however, we have to take
BD-IPMN into consideration because the classic aspects
of MD-IPMN do not require a differential diagnosis with
other pancreatic cysts but rather with chronic pancreatitis.
There is a slight prevalence in males (60%), with a mean
age 65 years, although it can also affect young patients.
The most common localizations are the head of pancreas, most often in the uncinate process[15]. Most patients
are asymptomatic[16]. When associated with symptoms,
IPMN can present with pain similar to chronic pancreatitis, weight loss, jaundice, steatorrhea, diabetes or intermittent acute pancreatitis, which is the sentinel symptom
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[19]
in 15% of cases, both in MD and BD-IPMN[17], due to

obstruction of the pancreatic duct with mucin.
The risk of malignancy is very high (mean 70%) in
MD-IPMN but low in BD-IPMN (mean 25%) and virtually nonexistent in the absence of risk factors, which are
clinical symptoms, mural nodes, cyst size > 3 cm, main
pancreatic duct dilation over 6 mm and negative cytology[18].
With these first two kinds of pancreatic cystic lesions, there are essentially no clinical and demographic
aspects that are of real use for diagnosis.
The frequency of MCNs is reported to range from
10% to 45%[2], although the real incidence is likely less
than that of serous cystoadenoma and IPMN[8,19]. MCNs
present almost exclusively in females (95%), with a mean
age of 53 years (range 19-82 years) and located in 95%
of cases in the body-tail of the pancreas[17,18,20,21]. Gender
and localization are very important characteristics in the
differential diagnosis of pancreatic cystic lesions because
they have a high negative predictive value for MCNs.
Regarding potential malignancy, these lesions cer-
248
cysts, such as septa, cyst contents such as debris, as well

as the pancreatic ductal system and its connection to the
cyst[26,28-31] .
A classification system of cyst morphology[32] has
been proposed for narrowing the differential diagnosis
and improving the diagnostic yield. Pancreatic cysts can
be classified into four subtypes: (1) unilocular cysts; (2)
microcystic lesions; (3) macrocystic lesions; and (4) cysts
with a solid component. Although this classification is
useful, it cannot by itself be used as a final solution for
differential diagnoses because of the overlap of morphological aspects of different lesions, especially in small
cysts (< 3 cm).
Accuracy of CT and MRI in characterizing cystic
pancreatic masses for malignancy has been proven but
they have only limited accuracy for the diagnosis of specific lesions (less than 50%)[33,34].
A study of 136 resected patients with incidental
pancreatic cysts showed that, on cross sectional imaging
(CT, MRI or both), diagnosis was correct in only 63% of
cases[14].
Regarding the indications of 18-fluorodeoxyglucose
positron emission tomography (PET) in PCLs, a study
showed that it is more accurate than the International
Consensus Guidelines in distinguishing benign from malignant (invasive and non-invasive) IPMNs[35] but it has
no role in determining specific diagnosis of PCLs and
there are no studies comparing PET with other diagnostic tools (such as EUS-FNA).
In conclusion, both CT and MRCP are helpful in
characterizing cystic pancreatic lesions, with an acceptable accuracy in determining malignancy but low accuracy in determining a specific diagnosis.
More studies are needed in order to determine the
role of PET in the management of PCLs.
Table 2 Major features of four most common cystic lesions

Feature
SCN
MCN
IPMN
Prevalent age Middle aged

Middle aged
Elderly
Sex
F>M
F1
M>F
Alcohol abuse
No
No
No
History of
No
No
Frequent
pancreatitis
Location
Evenly
Body-tail1
Head
Malignant
Very rare Moderate to high Low to high
potential
Pseudocyst
Variable
M>F
Yes
Yes1
Evenly
None
Mark the most useful epidemiological and clinical information (printed

with permission of Dr. M Raimondi). SCN: Serous cystoadenoma neoplasm; MCN: Mucinous cystic neoplasm; IPMN: Intraductal papillary
mucinous neoplasm.
tainly have to be considered potentially evolutive. The

Sendai International Guidelines[18] recommend resection
of all these lesions, although a recent report[21] on 163
resected MCNs showed only 5.5% in situ carcinoma and
12% truly invasive carcinoma, less than previously reported, and all malignant lesions were at least 40 mm in
size or with nodules.
Pancreatic pseudocysts are quite common, with some
reports[22] indicating that they comprise up to 70% of
all cystic lesions. However, there are now a number of
non-inflammatory small cystic lesions diagnosed with
the widespread use of imaging. PPs are slightly more
prevalent in males and age is variable. They are evenly
distributed in the gland, although the important point is
that they are rarely asymptomatic. To formulate a suspicion of pseudocyst, there will almost always be a history
of acute or chronic pancreatitis, or at least there will be
imaging from CT, MRI or EUS compatible with chronic
pancreatitis and a history of alcohol abuse, trauma, recent surgery or family history of pancreatitis. It is now
accepted that in patients with no history of acute or
chronic pancreatitis, a strong work-up should be done to
exclude possible neoplastic cystic lesions before suspecting PPs[22,23].
Finally, although some demographic and clinical
characteristics are suggestive of specific lesions and have
to be taken into account in the diagnostic evaluation,
these characteristics are not sufficient by themselves for
a definitive diagnosis in all such lesions.
EUS in cystic lesions

EUS has many features that make it, hypothetically, the
ideal tool for evaluating pancreatic cystic lesions. The
strict proximity between the transducer and the lesions
allows for a very precise definition of the structural
component of the cysts and some components of pancreatic cysts, such as the honeycomb pattern or small
mural nodules, are better visualized with EUS than with
other modalities.
With EUS, it is possible to define cystic localization,
size, locularity, internal structural features, mural nodules, contours, cystic wall, pancreatic duct and calcification. One of the problems with this technique related to
the morphological aspects of pancreatic cystic lesions is
the plurality of terms used by different authors to define
them.
Locularity is determined by the presence of septa
and can be classified as unilocular (or monolocular) or
multilocular (or multicystic). The cystic component can
be classified with microcystic area or without microcystic area. The microcystic area is defined as an area
where small (less than 2-3 mm each) cysts aggregate
(usually more than 6 cysts) separated by thin-walled
Imaging characteristics
CT and MRI are the two radiological techniques used
for the diagnosis of pancreatic cystic lesions. CT is often the first modality in the diagnosis of these lesions,
which are usually detected during exams done for other
reasons. The multidetector row CT gives a very good
image of the lesions, clearly showing the lesions and the
rest of pancreatic parenchyma[24-26]. Some characteristics,
such as calcification, can be seen only with this modality.
However, a recent review of diagnostic accuracy of CT
showed a range of between 20% and 90%[27].
MRI with cholangiopancreatography (MRCP) allows
optimal depiction of the internal features of pancreatic
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249
85% of SCNs and is highly accurate in the specific

diagnosis of these lesions[36]. A central stellate scar (sunburst)[38], sometimes calcified, is pathognomonic but is
seen in 20%-30% of cases on MDCT but only in 11%
of cases with EUS[39].
The capsule is usually poor developed and there is
often a poor distinction between the tumor and the surrounding pancreatic parenchyma[37,39,41].
These lesions usually have lobulated contours [36]
(Figure 1C).
In lesions in which the cysts are a few millimeters in
size, the tumor can have a solid appearance due to innumerable interfaces[40], the so called pseudosolid form
(Figure 1D). A third morphological pattern is also known
as the oligocystic variant with few cystic spaces[40].
Unilocular SCNs with no microcystic component
account for about 10% of all these lesions. The only
characteristics that can help in identifying these is the
absence of a discernible cystic wall[39] and lobulated contour[36,37], although in this case a more reliable diagnostic
tool is analysis of cystic fluid.
In SCN, communication with the pancreatic duct is
never seen[41].
EUS aspects of MCNs are variable[38]. They are a well
defined, single, round[36] (orange like)[18] cyst that can be
unilocular[36,37] but more typically present with multiple
macrocystic locules (usually less than 6[36], which are usually > 1-2 cm in diameter[39,42,43]) divided by septa[20,36,40,44]
(Figure 2A and B) and with no macroscopic communication with the pancreatic duct[18,44]. The aspect is of a cysts
in cyst[18]. MCNs commonly have a visible cystic wall
(< 2 mm)[7,37-39]. Thick mucoid cyst content can appear
granulated on EUS[38].
Focally thickened cystic wall or internal septa, clear
intramural nodules or solid component, and dilation of
the pancreatic duct are associated with invasive malignancy[20,21,45-48]. Goh et al[45] reported that none of the 40
malignant (carcinoma in situ or invasive) MCNs in his
study were < 3 cm; only one was < 4.5 cm (3 cm). In a
study by Crippa et al[21], all MCNs with cancer were either
40 mm in size or had nodules.
Peripheral wall curvilinear calcifications (egg shell
calcification) are characteristic of these lesions, although
present in less than 10%-25% of cases[49], and are considered predictive of malignancy[47].
BD-IPMNs (and sometimes MIX-IPMNs) need a
differential diagnosis with the other pancreatic cystic
lesions. MD-IPMNs most need a differential diagnosis
with chronic pancreatitis. The typical aspect of BDIPMNs is mutiloculated lesion[28,50], with a bunch of
grapes[18,50] aspect (Figure 3A), produced by multiple
secondary pancreatic ducts dilated by mucin. So these
aspects produce two important image characteristics
of these lesions: firstly, the lesions have cysts in cyst
aspect[18] different from MCNs, which have a cyst in
cyst aspect[18]. In addition, these lesions do not have a
round shape but do have an irregular contour. A study
by Kubo et al[36] showed that all MCNs had a round appearance and only 7% of BD-IPMNs appeared round.
Table 3 Endoscopic ultrasound morphology and cystic fluid

analysis in pancreatic cystic lesions
Serous
Mucinous cystic
cystoadenoma neoplasm
Localization
Head
+++
Body-tail
++
Locularity
Unilocular
+
Multilocular
+++
Internal structural features
Microcystic aspect +++
Bunch of grape aspect +
Countors
Round
+
Lobulated
+++
Irregular
+/Central scar
+
Visible cystic wall
Multifocality
Debris
Visible comunication with pancreatic duct
Calcification
Central
+
Periphery
Solid lesion
CEA
+/ 192 mg/mL
+
5 mg/mL
+++
5 mg/mL
Amylase
> 250 U/L
+
K-RAS mutation
Mucin
Cytology
Glycogen
BDPseudocyst
IPMN
+/+++
+++
++
++
++
+
+++
+
+++
+++
+
+
+++
+++
+/++
-
+
+
+++
+
++
++
+++
+/+/++
+/++
+
+
+
+/-
++
+++
+/-
++
+++
+/-
+/++
+
+/++
++
+
Mucinous
++/+++
++
+
Mucinous
+++
Inflammatory
+++: Very frequent; ++: Moderately frequent; +: Infrequent; +/-: Possible

but very infequent. BD-IPMN: Branch duct intraductal papillary mucinous
neoplasm; CEA: Carcinoembryonic antigen.
septa, producing a honeycomb-like appearance[36].

The contour can be round (or ovoid), lobulated or irregular. Lobulated is defined as the presence of rounded
contours that cannot be described as the borders of the
same circle[37]. Irregular is defined as the presence of
high irregularity in the contours.
The wall cyst is considered thin if it is 2 mm or less
and thick if more than 2 mm for at least 25% of the lesion circumference[37].
Specific EUS aspects of a single cystic lesion can be
observed (Table 3).
In SCNs, there is controversy over the site of the
pancreas most frequently affected[38] but probably these
cysts are evenly distributed.
Visualization of the microcystic area within the cyst,
located either at the centre of the cyst (Figure 1A) or
next to a macrocystic area[36] (Figure 1B) or in the internal septa of the lesions[39] (Figure 1C), is very typical of
these lesions. The thin internal septa are hypervascular
on Doppler[40]. The best modality for depicting this aspect is EUS. The microcystic area is present in about
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250
Figure 1 Serous cystoadenoma. A: Microcystic area, centrally located; B: Beside microcystic area; C: Peripheral and
internal septa microcystic area, lobulate contour; D: Pseudosolid form.
Figure 2 Mucinous cystic neoplasm. A-B: Round

lesions with septa (aspects of cysts in cyst with round
contour).
Figure 3 Branch duct intraductal papillary mucinous neoplasm. A: Bunch of grapes lesion (cysts by cyst aspects with irregular contour); B: Finger-like aspect; C:
Clubbed-like aspect.
Another typical aspect of a BD-IPMN is a cystic lesion

composed of finger (Figure 3B), tubular or clubbed-like
dilation (Figure 3C) of secondary pancreatic ducts.
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All the aspects of BD-IPMNs described above can

be seen in the same lesions, so radiologists have called
the aspect of BD-IPMNs a pleomorphic cystic shape,
251
change of the decubitus of the patient or during aspiration of intracystic fluid. It is important to look for this
characteristic because it is highly specific to pseudocysts.
Macari et al[55] reported that on MRI, 13 of 14 (93%)
pseudocysts had debris but only 1 (4%) of 22 cystic neoplasms had debris. Debris is very easily seen with EUS.
Sometimes, MCNs with very viscous mucin can have
an intracystic fluid with a granular aspect that looks like
debris[38]. Gonzalez Obeso et al[23] reported a 22% rate of
pseudocysts with internal debris seen on EUS and in this
study, a diagnosis of pseudocyst either was suggested or
made definitively by the endosonographer for the majority of patients (69%).
Despite the fact that pseudocysts typically communicate with the pancreatic duct, this is often not identifiable on cross-sectional or EUS imaging[52].
A characteristic to be taken into account is that pseudocysts, different from cystic neoplasms, can show rapid
changes in the arc in just a few weeks, either rapidly increasing or decreasing, until spontaneous resolution[47,52] .
The EUS aspect of chronic pancreatitis (CP) should
always be taken in to serious account and, despite some
limits, EUS is the most useful single test for evaluating
CP[56]. A pancreatic cystic lesion without a history of
acute or chronic pancreatitis, or without the presence of
a risk factor and imaging clearly diagnostic of chronic
pancreatitis, regardless of the EUS aspects, should be
considered a pancreatic cystic neoplasm until other tests
can definitively exclude it.
A review by Oh et al[27] of seven studies[42,57-62] of the
diagnostic accuracy of EUS morphology in differentiating
cystic lesions of the pancreas, reported results of between
51% and 90%. Furthermore, in one study of videotapes
of EUS procedures from 31 consecutive cases[63], there
was little more than chance inter-observer agreement
among experienced endosonographers on a diagnosis of
neoplastic vs non-neoplastic lesions, specific type and the
EUS features of pancreatic cystic lesions.
The differences result from the intrinsic differences
among these studies. Some studies were done to identify whether EUS was able to detect the occurrence of
overtly malignant change [42,58], others to differentiate
benign from premalignant lesions[60-62], and another to
differentiate all subtypes of lesions[59]. All but one[61]
were retrospective. Some studies were done of EUS
imaging[60] or videotape[63] that may not have completely
reproduced the findings as compared with an actual
real-time examination and endosonographers were not
aware of the history or prior imaging studies. The combination of clinical history and cross-sectional imaging,
along with real-time EUS, may increase the contribution
of EUS to the characterization of cystic lesions of the
pancreas. Definitions of EUS criteria for specific lesions
and malignancy were sometimes different among these
studies and reflect the lack of a uniform nomenclature
for describing the EUS features of cystic lesions.
On the other hand, OTool et al[39] found EUS to be
better in delineating the internal structures of cysts, such
Figure 4 Pancreatic pseudocyst. Round lesion without septa and with visible
hyperechoic debris inside.
which is defined as one containing three or more cysts,

including oval, tubular or clubbed-finger-like cysts[28,51].
However, these lesions are sometimes formed by only
one large ectatic pancreatic secondary duct and in this
case the lesions will be unilocular[50,52], round and impossible to distinguish from other unilocular pancreatic cystic
lesions by EUS aspect only. One of the most important
diagnostic tools for BD-IPMNs is identifying whether
there is communication between the lesion and the pancreatic duct. MRI was significantly more accurate than
MDCT in identifying this characteristic in one study[13].
However, EUS, although operator dependent, can be
very useful, particularly when CT or RMN are equivocal.
Kim et al[53] demonstrated that there is no difference between MRI and EUS in showing communication between
pancreatic cystic lesions and the pancreatic duct.
Another specific sign for diagnosis of IPMNs is the
presence of cystic dilation of the small branches of the
pancreatic ductal system in two or more areas within the
pancreatic parenchyma. Multifocality has been reported
in about 30% of IPMN[18] and is quite specific to these
lesions because only rarely do other lesions have this
characteristic (simple cyst or serous cystoadenoma in
Von Hippel-Lindau syndrome, multiple neuroendocrine
tumor with cystic aspects, metastasis with cystic pattern).
During EUS exams, an endoscopic view of the papilla
should be always done to exclude mucin extruding from
the patulous papilla (fish mouth papilla), which is diagnostic of IPMN[38], although this phenomenon is present
in only 30% of cases, almost all of which with MD or
MIX IPMN[15].
Pais et al[54] showed that in 74 operated patients, EUS
features of a solid lesion, a dilated main pancreatic duct,
ductal filling defects and thickened septa were predictive
of malignancy in IPMNs.
The most frequent aspect of PPs is a round, unilocular cyst without internal septation or mural nodules, with
less than 10%-20% appearing multilocular[23,36]. The appearance of the cystic wall can vary, from imperceptible
or minimally visible to that of a uniform thickness[37,47].
Internal debris visible at EUS as hyperechoic material inside the cyst (Figure 4) can be seen floating with
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252
is little data on this technique. A recently published prospective study by Hong et al[69] described techniques for
obtaining more cellularity for cytological diagnosis. This
technique consists of attempting to obtain a cystic wall
biopsy (CWB) by puncturing the far wall of the cyst and
moving the needle back and forth through the wall, after
aspiration of fluid from the cyst. The author reports that
81% of the specimens had cellular material adequate for
cytological assessment, which was higher than has previously been reported for standard FNA.
A new device, the Echobrush (Cook Medical), was
tested in several studies [70-72]. Although better results
than those for standard needles have been[70] reported,
some limitations have to be considered. The brush takes
only a 19 G needle, so stiffness limits its use, especially
for lesions in the pancreatic head and uncinate process.
In addition, it can only be used for lesions that are at
least 2 cm in diameter and a high rate of complications
(8%-10%) and one death have been reported[71]. More
studies are needed.
A meta-analysis[73] comparing EUS-FNA-based cytology with surgical biopsy or histology and including
376 patients from eleven[42,58,59,61,74-80] studies showed a
low sensitivity (63%), but good specificity (88%) in differentiating mucinous cystic lesions from non-mucinous
lesions, with a diagnostic accuracy of 89%. However, the
authors concluded that review literature on diagnostic
accuracy of EUS-FNA-based cytology for pancreatic
cystic lesions is limited and heterogeneous, and that welldesigned randomized trials are needed in this field.
The largest study of FNA cytology is a prospective
cooperative pancreatic cyst study[61] of 112 surgically
proven lesions that showed a sensitivity, specificity and
accuracy of 34.5%, 83% and 51%, respectively. A prospective two center study to investigate the technical success of EUS-FNA in pancreatic cysts in 143 patients was
recently published[81]. de Jong et al[81] reported that EUSFNA was possible in 90% of patients but that cytological diagnosis was obtained in only 31%, due to insufficient cellularity of aspirate liquid, and that biochemical
analysis was possible in only 49%, due to insufficient
amount of fluid or high viscosity. These numbers are
much lower than those reported in another prospective
study by Frossard et al[59]. In that study, cytological analysis was done in 127 patients with pancreatic cysts and a
classifying diagnosis was provided in 98 cases (77%). The
authors used the FNA needle to obtain fluid and a mini
biopsy, while the cytologist used a liquid-based cytology,
the ThinPrep 2000 (Cytyc Corp., Marlborough, MA), a
cell preparation processor that provided a monolayered
cell population. Both mini biopsy and cyst fluid process
may have made the difference in this study, although not
all authors agree with the use of liquid-based cytology to
process cyst fluid[48].
Greater agreement among cytopathologists and in
general among physicians involved in PCL treatment is
needed on processing of cyst fluid for cytology.
Looking for the presence of extracellular mucin in
as septa, thick content and mural nodule. The combination of a cystic wall that is thickened and the absence of
microcysts had a sensitivity of 100% and specificity of
78% for a diagnosis of MCN compared with macrocystic SCN. Song et al[44] showed that absence of septa and
mural nodules and the presence of parenchymal change
are indicators of a pseudocyst rather than a cystic neoplasm, with 88% accuracy.
More recently, Kubo et al[36] observed that 8 of 11
monolocular cystic lesions in his study were non-neoplastic and that 11 of 12 SCNs included microcystic areas.
All MCNs were round, while 93% of IPMNs were not.
In a multivariate analysis, he concluded that locularity
(presence of septa) and a cystic component (presence of
microcystic area) were important for a differential diagnosis of potentially malignant cystic pancreatic tumors
and that the characteristics of cystic tumors revealed by
EUS are useful for differential diagnoses.
There are few studies comparing radiological and
EUS accuracy in pancreatic cystic lesions[53,62,64]. Gerke et
al[62] found an accuracy in classification into benign and
malignant or potentially malignant cystic lesions of 66%
for EUS and 71% for CT scan, with very poor agreement between them. More recently, Kim et al[53] found
that there was no difference between the ability of MRI
and EUS to correctly classify lesions as cystic or solid
(accuracy, 90%-98% vs 88%; P > 0.05) for the characterization of septa, mural nodule, main pancreatic duct
dilatation, communication with the main pancreatic duct
and a prediction of malignancy.
EUS-FNA
Linear array echoendoscopy allows for EUS-FNA of
solid and cystic lesions. In PCLs, EUS-FNA allows
evaluation of extracellular mucin, cytological and sometimes histological analysis, biochemical, tumor markers
and molecular analysis[65] and the complication rate for
EUS-FNA of cystic pancreatic lesions from a systematic
review[66] was slightly more than that for solid ones (2.75%
vs 0.82%), with pancreatitis being the most frequent. The
others were pain and bleeding that were self-limiting,
and infection, which has become very rare since the introduction of antibiotic prophylaxis.
The risk of seeding is very low, with only one published case of peritoneal seeding after EUS-FNA of a
PCLs[67]. The EUS-FNA techniques for pancreatic cystic
lesions are quite simple. The needles normally used are
the same as those for solid lesions, 19, 22 and 25 G.
Doppler is recommended to avoid puncture of intervening vessels, as is crossing the normal pancreatic parenchyma as little as possible to help avoid pancreatitis.
Other recommendations include complete drainage of
the cyst in a single needle passage, antibiotic prophylaxis
with intravenous antibiotics just before the procedure,
followed by the oral route for 3-5 d to reduce the risk of
infection.
Only one study with ten patients was done on the use
of Trucut biopsy in pancreatic cystic lesions[68], so there
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253
with serous cystoadenomas, they do have significantly

higher levels of cyst fluid CEA[23].
For practical purposes, we can summarize the information on CEA dosage in cystic fluid from different
studies: values above 192 ng/mL support the interpretation of mucinous cyst, with increasing specificity mirroring an increase in CEA concentrations. Values lower
than 5 ng/mL strongly support a diagnosis of nonmucinous cyst, particularly of serous cystoadenoma.
Pseudocysts rarely have values above 197 ng/mL and
the median value to be expected is about 40 ng/mL (Table
3). A few reports have suggested that CEA can predict
malignancy if it is found to exceed some value (ranging
between 200 ng/mL and 5000 ng/mL), with varied specificity and sensitivity, although many large studies[61,82,83,85]
have shown that CEA is not useful in differentiating benign from malignant cyst.
Although CEA is not the solution to all diagnostic
problems in pancreatic cystic lesions, the 2007 American
College of Gastroenterologists Guidelines recommend it
as the first test to do if minimal fluid is acquired during
aspiration[86].
Amylase levels in pancreatic cystic fluid are used to
investigate the possibility that the cyst is communicating
with the pancreatic duct. There is no definitive value to
demonstrate communication with the pancreatic duct.
Values between 250 U/L and 5000 U/L can be found in
different studies[82,84].
Amylase values in pseudocysts are usually in the
thousands and almost never under 250 U/L[82,83,87]. Amylase values are over 5000 U/L in 3/4 of IPMN[83,84]. In
serous cystoadenoma, the amylase value is usually less
than 250 U/L[16,82,83], although there are a number of
exceptions. MCN very rarely have macroscopic communication with the pancreatic duct, so the expected
level of amylase is low in pancreatic cystic fluid[20]. There
are several studies[16,83,87] that have shown that amylase
intracystic fluid levels in MCN can be elevated, with no
differences between IPMN and pseudocysts, perhaps
because of diminutive connections between the cyst and
the ductal system.
There are some reports that speculate on the presence of malignancy in IPMN and MCN with low levels
of amylase in intracystic fluid, assuming that rapid uncontrolled cellular growth could occlude any macroscopic or microscopic ductal connections[83-87]. At present,
there are insufficient data for investigating this suspicion.
In summary, we can say that pseudocysts rarely have
intracystic fluid values of less than 250 U/L, IPMN have
elevated values in 75% of cases, and serous cystoadenomas usually, but not always, have values below 250 U/L.
MCN can have widely variable values (Table 3).
Molecular analyses have been done on intracystic fluid. The largest study in this field is the PANDA study[88],
which was a prospective, multicenter study to evaluate
the role of cystic fluid DNA analysis in differentiating
mucinous from nonmucinous cysts. It showed that, in
113 patients with pancreatic cysts, elevated amounts of
aspirate from PCLs may aid in making a diagnosis, at

least in distinguishing mucinous from non mucinous lesions, although it is not present in approximately 50% of
mucinous cysts. Although mucin may be visible at aspiration, thick sheets of colloidal-like mucin that cover much
of the slides need to be watched for. This type of mucin
is sufficient for a diagnosis of mucinous cyst, even if
acellular[48]. Mucin stain (alcian blue, mucicarmine) may
lead to an erroneous interpretation of wisp mucin from
gastrointestinal contaminants as indicative of mucinous
cyst. Liquid-based cytology attenuates the appearance
of mucin and Pitman et al[48] do not recommended it for
processing cyst fluid.
Correct execution of sampling[69], an experienced
cytopathologist and correct treatment of smears and
aspirated fluid[59,73,81] can improve the sensitivity of these
tests, although new methods for improving the yield of
FNA are needed. The Echobrush or CWB could conceivably improve results, although larger randomized trials are needed to confirm results and safety.
To enhance the diagnostic capability of cytology, cyst
fluid can be analyzed for tumor markers and amylase.
The overall cystic fluid amount for dosage of tumor
markers and amylase is about 0.5 mL for each, so with
just 1 mL it is possible to do both tests. Several tumor
markers in aspirate from PCLs have been considered:
Carcinoembryonic antigen (CEA), CA 19-9, CA 72-4
and CA-125. CEA is considered the most accurate
marker in differentiating mucinous from non-mucinous
cysts. There is continual debate in the literature over the
best cut-off of CEA levels for discriminating mucinous
from non-mucinous cysts The value of cut-off ranges
from 20 ng/mL to 800 ng/mL in different studies, obviously with greater sensitivity for a low cut-off value
and greater specificity for higher ones[27,49]. However,
the most frequently utilized cut-off derives from a large
prospective study by Brugge et al[61] on 112 patients who
underwent surgery. It established that a level of 192 ng/
mL has a diagnostic sensitivity of 75%, a specificity of
84% and an accuracy of 79% in differential diagnosis of
mucinous and non-mucinous cysts. In another pooled
analysis from 12 studies, a value of > 800 ng/mL arrived
at a specificity of 98%, but a sensitivity of only 48%[82].
Very low values of CEA are extremely useful. CEA
levels of less than 5 ng/mL have been found in the
pooled analysis of published studies[82] to be highly diagnostic for serous cystoadenomas or pseudocysts (sensitivity 50%, specificity 95%). A retrospective analysis[83]
of patients with histologically confirmed cysts showed
that cyst fluid CEA of less than 5 ng/mL for a diagnosis
of non-mucinous lesions had a sensitivity of 44%, specificity of 96% and diagnostic accuracy of 78%. Very few
mucinous cysts have values below 5 ng/mL[83,84].
For pseudocysts there are more widespread values.
Rarely do they have a value above 192 ng/mL (5%-14%)[23,83]
and only 25% have a value of less than 5 ng/mL[23,83]. In
a paper on 21 pseudocysts, the median of intracystic fluid
CEA was 41 ng/mL (mean 129 ng/mL) so, compared
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254
Figure 5 Unilocular aspects in cystic pancreatic lesions. A: Sixty year old female, no symptoms. Lesion in pancreatic head, no visible communication with pancreatic duct. Carcinoembryonic antigen (CEA) 1.5 ng/mL, Amylase 125 U/L, K-RAS mutations negative. Cytology: Cuboidal cell periodic acid-Schiff positive, no mucus.
Diagnosis: Unilocular serous cystoadenoma; B: Seventy-nine year old female, no symptoms. Multiple cystic lesion in pancreatic head and tail. Lesion in pancreatic tail
with visible communication with pancreatic duct. CEA 12000 ng/mL, amylase 12870 U/L, K-RAS mutation positive. Cytology: Mucin and cuboidal cell with mild atypia
and papillary arrangement. Diagnosis: Multifocal branch ducts-intraductal papillary mucinous neoplasm; C: Fifty year old female. Lesion in pancreatic body, no visible
communication with pancreatic duct. CEA 280 ng/mL, amylase > 15000 U/L, K-RAS mutation positive. Cytology: Acellular without mucin. Surgical histology: Mucinous
cystoadenoma; D: Forty-five year old male, history of alcoholism and recurrent acute pancreatitis. Lesion in pancreatic body. CEA 61 ng/mL, amylase > 15000 U/L,
K-RAS mutations negative. Cytology: Inflammatory cells and pigmented histocytes. Diagnosis: Pancreatic pseudocyst.
pancreatic cyst fluid DNA, high-amplitude mutations

and specific mutation acquisition sequences were indicators of malignancy and the presence of a k-ras mutation
was indicative of a mucinous cyst.
Another study[89], however, showed a poor correlation
between CEA levels and molecular analysis, although the
combination of CEA and molecular analysis achieved
100% sensitivity for the diagnosis of mucinous cyst. Molecular analysis needs very small quantities of intracystic
fluid (0.4 mL) and is surely a promising test. However,
high cost and availability pose some limits. Accuracy of
molecular analysis needs to be tested before drawing any
definitive conclusions. In addition, reproducibility has to
be tested in other laboratories and a cost-benefit analysis
for comparison with current tests has to be done.
Glycosylation variants of mucins[90], proteomic analy[91]
sis and microRNA expression profile[92,93] are among
the emerging tests under investigation that could potentially become biomarkers in cyst fluid samples.
mation deriving from demographic, clinical, radiological,

EUS morphological and intracystic fluid analyses.
EUS morphology alone cannot provide for a sure
diagnosis in all cases and a recently published paper on
inter observer agreement confirms that such agreement
is generally low[94]. This same paper also showed that the
more expert the endosonographers, the higher the rate
of agreement, probably because they speak the same
language. So it is likely that having greater agreement
on what to look for and the meaning assigned to specific
morphological aspects of pancreatic cystic lesions would
improve the weight of EUS morphology. Palazzo et al[95]
underlines this concept, proposing the creation of an
international expert educational image bank for CPLs
that could help to standardize image analysis. However,
there are some studies that have clearly shown that
EUS shows clearer images of some cystic aspects, such
as diffuse or localized microcystic aspects, lobulated
contours for serous cystoadenomas, debris for pseudocysts, connections with the pancreatic duct, grape-like,
finger- or clubber-like aspects for IPMNs, and rounded
contour and internal septa for MCN. Moreover, some
EUS aspects, such as intracystic nodules, pericystic solid
mass, localized thickening of the parietal wall or of the
intracystic septa, and dilation of the pancreatic duct, are
CONCLUSION
There is no single test accurate enough to make a sure
diagnosis in every pancreatic cystic lesion and so the
diagnosis of such lesions is a puzzle, with bits of infor-
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18 Tanaka M, Chari S, Adsay V, Fernandez-del Castillo C,
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19 Parra-Herran CE, Garcia MT, Herrera L, Bejarano PA. Cys-
Table 4 Accurancy of endoscopic ultrasound morphology in

differentiating pancreatic cystic lesions (printed with permission of Dr M. Raimondi
Author
No. of patients Study design
Koito et al[57]
Cellier et al[64]
Pais et al[54]
Ahmad et al[60]
Sedlack et al[42]
Hernandez et al[58]
Frossard et al[59]
Brugge et al[61]
Gerke et al[62]
Total
52
21
51
38
34
9
67
112
66
450
Retrospective
Retrospective
Retrospective
Retrospective
Retrospective
Retrospective
Retrospective
Prospective
Retrospective
Accuracy (%)
94
76
86
66
82
89
73
51
67
Median 72.5 (mean 77)
predictive of malignancy and some of these aspects are

frequently better seen with EUS.
Analyses of data from nine studies[42,54,57-62,64] (Table 4),
with a total of 450 patients, of accuracy of EUS morphology in differentiating CPLs showed a median of
72.5% (mean 77%). This is better than the 50%-60%
accuracy of radiology[33-35] and slight different from the
accuracy of CEA (79%)[61]. Compared with cytology, the
accuracy of EUS morphology varies a great deal because
of the significant heterogeneity in the results of the cytology studies, with an accuracy ranging between 51%
and 93%[73] but with a median of 73%, which is quite
close to the accuracy of EUS morphology. Moreover,
EUS allows for the execution of FNA for cytological examination and intracystic fluid analysis, especially in such
doubtful lesions as unilocular cystic pancreatic lesions,
which do not have specific EUS aspects (Figure 5).
In general, cytology in every study showed low sensitivity and high specificity, allowing, when positive, to predict the type of lesion. CEA showed good accuracy for
mucinous lesions when the cut-off was 192 ng/mL and a
high specificity for serous cystoadenomas when using the
low cut-off of 5 ng/mL. Amylase levels are undoubtedly
useful for excluding pseudocyst. There are other diagnostic tests beyond intracystic fluid that are very promising,
such as molecular analysis, variants of mucins, proteomic
analysis and mRNA analysis, although larger studies than
those done to date are needed for validation.
Several case reports and case series have shown the
utility of EUS-FNA in diagnosing much rarer PCLs,
such as cystic change of pancreatic neuroendocrine
tumors[96], solid papillary neoplasm[97], lymphoepithelial
cyst[98], pancreatic schwannoma[99] and pancreatic cystic
lymphangioma[100].
We can conclude by saying that diagnosis of pancreatic cystic lesions is composed of different bits of
information, derived from a number of different sources.
EUS morphology and EUS-FNA are important diagnostic tools and can useful in solving this difficult diagnostic
puzzle.
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S- Editor Yang XC
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L- Editor Roemmele A E- Editor Li JY


wjge@wjgnet.com
doi:10.4253/wjge.v4.i6.260
BRIEF ARTICLE
Sedation practices for routine diagnostic upper gastrointestinal

endoscopy in Nigeria
Sylvester Chuks Nwokediuko, Olive Obienu
endoscopists. Monitoring of oxygen saturation during
sedation was practiced by only 57.1% of respondents.
Over half of the respondents (18/35 or 51.4%) never
used supplemental oxygen for diagnostic upper gastrointestinal endoscopy.
Sylvester Chuks Nwokediuko, Olive Obienu, Gastroenterology Unit, Department of Medicine, University of Nigeria
Teaching Hospital Ituku/Ozalla, 01129 Enugu, Nigeria
Author contributions: Both authors participated actively in the
conception, design, data acquisition, analysis and interpretation
of data; they also worked together to draft the manuscript and
revise it for intellectual content.
Correspondence to: Dr. Sylvester Chuks Nwokediuko,
Gastroenterology Unit, Department of Medicine, University of
Nigeria Teaching Hospital Ituku/Ozalla, 01129 Enugu, Nigeria.
sylvester.nwokediuko@unn.edu.ng
Telephone: +23-4-8033218181 Fax: +23-4-42553210
Received: September 1, 2011
Revised: November 14, 2011
CONCLUSION: Sedation for routine diagnostic upper

gastrointestinal endoscopy in Nigeria is characterized
by lack of guidelines, and differs markedly from that in
developed countries.
Key words: Gastrointestinal endoscopy; Nigeria; Sedation

Peer reviewers: Somchai Amornyotin, Associate Professor,
Department of Anesthesiology, Siriraj Gastrointestinal
Endoscopy Center, Faculty of Medicine Siriraj Hospital, Mahdol
University, Bangkok 10700, Thailand; Perminder Phull, MD,
FRCP, FRCPE, Gastrointestinal and Liver Service, Room
2.58, Ashgrove House, Aberdeen Royal Infirmary, Foresterhill,
Aberdeen AB25 2ZN, United Kingdom
Abstract
AIM: To determine the sedation practices and preferences of Nigerian endoscopists for routine diagnostic
upper gastrointestinal endoscopy.
Nwokediuko SC, Obienu O. Sedation practices for routine

diagnostic upper gastrointestinal endoscopy in Nigeria. World J
Gastrointest Endosc 2012; 4(6): 260-265 Available from: URL:
http://www.wjgnet.com/1948-5190/full/v4/i6/260.htm DOI:
http://dx.doi.org/10.4253/wjge.v4.i6.260
METHODS: A structured questionnaire containing

questions related to sedation practices and safety procedures was administered to Nigerian gastrointestinal
endoscopists at the 2011 annual conference of the
Society for Gastroenterology and Hepatology in Nigeria
which was held at Ibadan, June 23-35, 2011.
RESULTS: Of 35 endoscopists who responded, 17
(48.6%) used sedation for less than 25% of procedures, while 14 (40.0%) used sedation for more than
75% of upper gastrointestinal endoscopies. The majority of respondents (22/35 or 62.9%) had less than
5 years experience in gastrointestinal endoscopy. The
sedative of choice was benzodiazepine alone in the
majority of respondents (85.7%). Opioid use (alone or
in combination with benzodiazepines) was reported by
only 5 respondents (14.3%). None of the respondents
had had any experience with propofol. Non-anaesthesiologist-directed sedation was practiced by 91.4% of
WJGE|www.wjgnet.com
INTRODUCTION
Routine diagnostic upper gastrointestinal (GI) endoscopy is the standard practice for diagnosing esophageal,
gastric and duodenal diseases. It has very low complication and mortality rates[1] and may be performed with or
without sedation. The use of sedation improves the tolerance and acceptance of the examination[2], but increases the cost of the procedure and is responsible for about
50% of complications associated with the procedure[3].
Sedation practices differ from one country to anoth-
260
Nwokediuko SC et al . Sedation for upper gastrointestinal endoscopy
er and even vary within the same country. These differences may reflect many different factors, which include
the personal differences and training of the endoscopist,
the availability of anesthetic services, the need to train
colleagues in endoscopic techniques, the cost and availability of monitoring equipment, differences in the availability and use of common drugs, and particularly, the
expectations of the patient[4]. In the United Kingdom
and United States, sedation is widely used in endoscopies. In France, 80% of colonoscopies are performed
under general anesthesia, while in Germany and Finland
most examinations are conducted without any form of
anesthesia[4].
Unsedated upper GI endoscopy is effective in selected patients, but causes reduced operator satisfaction.
A meta-analysis showed that sedation achieved better
patient cooperation and satisfaction and a willingness to
have it repeated[5].
Successful endoscopic procedures can be achieved
with patients in either moderate or deep sedation or
general anesthesia; however, moderate sedation is generally considered adequate to control the pain and anxiety
of routine endoscopic examinations and to achieve adequate amnesia[6].
Sedation is a continuum of progressive impairment
of consciousness ranging from minimal sedation to general anesthesia. Although clinicians may target a specific
level of sedation, it is not always possible to predict how
each patient will respond to sedative or analgesic medications. Patients can move in a fluid manner between these
extremes[7]. Targeting moderate sedation is the goal, but
in clinical practice some patients will transiently be in
lighter or deeper levels of sedation. Targeting conscious
levels results in an overall safer profile than targeting
deeper levels and should result in a substantial safety
margin for non-anesthesiologists.
Since the 1980s, the use of benzodiazepines, often
in combination with an analgesic has become standard practice in the United States and many parts of
Europe[8,9]. Time consuming and technically complex
endoscopies of the GI tract such as endoscopic retrograde cholangio-pancreatography and endoscopic
ultrasonography require deep sedation and propofol is a
popular choice for induction and maintenance of deep
sedation[10]. Propofol has also been adjudged a very safe
sedative for endoscopist-directed sedation[11].
In Nigeria, there are currently no guidelines for sedation in GI endoscopy. This study was carried out to determine the sedation practices of Nigerian endoscopists
for routine diagnostic upper GI endoscopy. Information
obtained from this study would be useful not only in the
audit of the practice of gastroenterology in a resourcepoor setting such as Nigeria, but also in formulating
guidelines and further research.
tered to all GI endoscopists who attended the annual scientific conference and general meeting of the Society for
Gastroenterology and Hepatology in Nigeria (SOGHIN)
which was held in Ibadan, Oyo State, Nigeria between
June 23 and 25, 2011.
The questionnaire included 12 multiple choice questions focusing on the practices of routine diagnostic
upper GI endoscopy. Such practices included sedation
preference and administration, sedative drugs used,
monitoring during sedation, use of supplemental oxygen, use of antispasmodic drugs and use of patient
consent form. The data were expressed as percentages.
Where appropriate, the difference between proportions
was determined using 2. P value of < 0.05 was considered statistically significant.
RESULTS
Of 41 questionnaires handed out, 35 were completed and
returned, giving a response rate of 85.4%. There were
31 males (88.6%) and 4 females (11.4%). The majority
of endoscopists were physicians (82.9% or 29/35), while
14.3% (5/35) were surgeons. One respondent did not indicate whether he was a physician or a surgeon (2.8%).
Twenty two respondents (62.9%) had less than 5
years experience in GI endoscopy, while only 4 (11.4%)
had up to 15 years experience (Table 1). Seventeen respondents (48.6%) performed less than 25% of routine
diagnostic upper GI endoscopies with sedation, while
14 (40.0%) performed 75% or more of the procedures
with sedation (Table 2). The difference between the proportions was not statistically significant ( 2 = 0.2014, P
= 0.6536). With regard to the criteria for deciding who
receives sedation (Table 3), 24 respondents (71.4%)
used sedation for uncooperative patients, 14 (40%) for
children, 9 (25.7%) for patients who requested it, and 12
(34.3%) for patients less than 60 years of age.
Regarding the question Do you routinely ask for the
preference of your patient for sedated or unsedated examination, 27 (77%) responded in the negative. Thirty
endoscopists (85.7%) used benzodiazepine alone as the
sedative drug. Only 5 respondents (14.3%) had used
opioids alone or in combination with benzodiazepines.
None of the respondents reported ever using propofol
(Table 4).
Concerning the administration of the sedative; 20 endoscopists (57.1%) administered it themselves while 14
(40%) employed other non-anesthesiologist staff. Only 3
endoscopists (8.6%) answered that anesthesiologists administered the sedation (Table 5). Bolus administration
was practiced by 26 endoscopists (74.3%), while only 9
(25.7%) administered it in titrated fashion. For sedated
patients, 30 respondents (85.7%) monitored vital signs.
However, 18 respondents (51.4%) monitored unsedated
patients. Oxygen saturation and electrocardiogram
(ECG) were monitored by only 20 respondents (57.1%)
and 5 respondents (14.3%), respectively. Eighteen respondents (51.4%) never used supplemental oxygen
MATERIALS AND METHODS

In this study, a structured questionnaire was adminis-
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261

Table 3 Reasons for using sedation
Table 1 Distribution of gastrointestinal endoscopists according to years of experience

Years of practice
< 5 yr
No. of endoscopists (n = 35)

22

24
Percentage
71.4
Children
Patients < 60 yr
14
12
40
34.3
Reason
Uncooperative patients
Percentage
62.9
5 yr to 10 yr
8.5
> 10 yr to 15 yr
14.3
Patients request
25.7
> 15 yr
11.4
Patients > 60 yr
14.3
1
35
2.9
100
Not stated
Total
Table 4 Frequency of use of different sedative drugs

Table 2 Frequency of using sedation in upper gastrointestinal
endoscopy
Upper gastrointestinal
endoscopies with sedation
< 25%
25%-49%
50%-74%
75%
Total
17
0
4
14
35
Drug(s)
Benzodiazepine alone
Percentage
48.6
0
11.4
40.0
100
Percentage
85.7
Opioid alone
2.9
Benzodiazepine + opioid
11.4
Propofol
Total
35
100
for endoscopy do not exist. Therefore the 35 endoscopists who responded to the questionnaire are representative of the total number on the ground.
The majority of the GI endoscopists in Nigeria are
physicians (82.8%). This is because in most training
institutions it was the physicians that first introduced endoscopy into their practice in the early 1980s. In recent
times, more surgeons have become interested and are
making efforts to be trained.
In this study, the majority of respondents had less
than five years practice experience in GI endoscopy. This
again reflects the fact that endoscopy practice in Nigeria
is still at a very early stage of development[18]. Some of
the pioneer endoscopists were lost to the brain drain in
the 1980s and 1990s[19,20], with the result that the training
of future endoscopists suffered a tremendous setback.
Most of the practicing gastroenterologists in Nigeria
are products of the two postgraduate medical colleges
(West African College of Physicians/Surgeons and the
National Postgraduate Medical College of Nigeria).
With regard to use of sedation for routine upper GI
endoscopy, 48.6% use sedation in less than 25% of procedures, while 40% use sedation in more than 75% of
procedures (P = 0.6536). This means that among Nigerian digestive endoscopists, sedated and unsedated procedures are practiced. The use of sedation is said to be
on the increase in some developed societies[12]. However,
the present study is unable to make any inference in that
regard as this is the first study in Nigeria on this subject.
The majority of respondents (77%) did not give
patients the privilege of choosing between sedated and
unsedated procedures. This is not right as medical practice has moved sharply from the traditional paternalistic
fashion to a model where patients actually participate
in taking decisions regarding their care[21]. With regard
to the reasons for using sedation in some patients and
not others, 71.4% answered that they sedate patients
who are uncooperative. This suggests that such sedation
(Table 6).
With regard to use of antispasmodics, the responses
were always, in most cases, occasionally and never by 9
(25.7%), 3 (14.3%), 17 (48.6%) and 4 (11.4%) respondents,
respectively. Informed consent prior to endoscopic examination was routinely obtained by 29 respondents (82.9%),
while 6 (17.1%) did not obtain informed consent.
DISCUSSION
The practice of endoscopic sedation varies from country
to country due to social, cultural, economic and regulatory influences[2-4,6]. Although the medical literature is
replete with guidelines and recommendations for the
practice of sedation in developed nations, principally the
United States and Western Europe[12-15], minimal data exist about sedation practices in resource-poor countries
including Nigeria. In this study, the questionnaire was
administered directly to the endoscopists rather than
studying one or two individuals adjudged to be experts
in the field and accepting their views as representative of
whole nations[16]. The problem with the latter approach
is that responses to questions could reflect preconceived
beliefs about practice patterns internationally rather than
actual practice.
The response rate in this study was 85.4%. This is
considered satisfactory for a study of this nature. There
were only 35 respondents. This clearly reflects a doctor
to population ratio of 3 per 10000 in Nigeria, compared to US which stands at 26 per 10000. The gap is
even wider when one considers the gastroenterologist to
population ratio. Nigeria has a population of over 150
million[17] but has less than 60 gastroenterologists (registered with the national society, SOGHIN). Of these
gastroenterologists, close to a third do not practice GI
endoscopy because they work in centres where facilities
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30
262

Table 6 Frequency of use of supplemental oxygen
Table 5 Personnel responsible for administering sedation

No. of endoscopists (n = 35) Percentage
Personnel
Endoscopist
Nurse
Doctor (resident doctors,
medical officers, house officers)
Anesthesiologist
20
57.1
7
7
20.0
20.0
Type of patient
None
High risk patients
8.6
may only be administered after the procedure has commenced and the patient is judged to be uncooperative.
The decision to sedate is supposed to precede the actual
procedure and must be based on evidence.
Benzodiazepine alone is employed by most respondents (85.7%), while only 14.3% use opioids either
alone or in combination with a benzodiazepine. Patients
undergoing GI endoscopy may be anxious, as the procedure may be uncomfortable or painful. Effective sedation throughout the procedure is an important aspect of
patient management and it should meet the anxiolytic
and analgesic needs of the individual patient[22]. The fact
that most Nigerian endoscopists use benzodiazepine
alone means that the concept of balanced sedation is
not observed and many patients may actually be undersedated. Granted that both the pharmacological effects
and the side effects of benzodiazepines and opioids are
synergistic and must be used with caution[23], observations from Western Europe[12,13] and the United States[24]
indicate that a benzodiazepine/opioid combination is
the preferred method of endoscopic sedation worldwide.
The 2 drug classes have a long history of safety, efficacy
and widespread acceptance by non-anesthesiologists[25].
They also have pharmacological antagonists which is an
added advantage.
None of the respondents had any experience with
propofol. The use of this sedative has been expanding
in most developed countries of the world. It has a good
safety profile[11]. However, its use is highly regulated in
America and Europe [26,27]. The observed low rate of
opioid use and non-use of propofol for routine diagnostic upper GI endoscopy in this study may be partly
explained by the physician-dominated digestive endoscopy. Traditionally, surgeons work with anesthesiologists
and anesthesiology is part of the standard training of
surgeons. It is therefore likely that an endoscopy service
that is dominated by surgeons may employ opioids and
propofol more than that observed in this study.
Bolus rather than titrated injection is practiced by
74.3% of respondents. Although clinicians may target a
specific level of sedation, it is not always possible to predict how each patient will respond to sedative or analgesic medications. Clinicians commencing sedation/analgesia intending to produce a given level of sedation should
be able to rescue patients whose level of sedation has
become deeper than initially intended. A key principle in
the administration of sedation is to titrate medications
in incremental doses to the desired sedative effect[28].
Sedatives and analgesics must be titrated based upon the
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18
9
Percentage
51.4
25.7
Oxygen desaturation
22.9
All
No response
0
1
0
2.9
condition of the patient, information from monitoring

equipment and the needs of a procedure[15].
The person who administers the sedation may be an
anesthesiologist or a non-anesthesiologist. In this study,
the sedation is administered by a non-anesthesiologist in
97% of respondents. It is common knowledge that the
endoscopists, nurses and other doctors who administer
these sedatives have not received any formal training for
that purpose. There is uniform agreement in the literature and all relevant societal guidelines agree that specific
training is needed for both the endoscopic procedure
and any sedation associated with that procedure[26,28-32].
Some even specify a certain number of supervised procedures required before competency can be assessed[32].
The time has come for similar guidelines to be developed for resource-poor countries including Nigeria.
With regard to monitoring, 85.7% of respondents
monitor sedated patients with vital sign measurements.
Oxygen saturation and ECG are monitored by 57.1%
and 14.3% of respondents, respectively. This is clearly
unsatisfactory. Since sedation occurs along a continuum,
all sedated patients should have their level of consciousness determined periodically during the examination and
recovery periods using a standardized sedation scale. The
risk of an unplanned cardiopulmonary event is directly
related to the level of sedation. As the depth of sedation increases, so too does the likelihood that a patient
will develop loss of the airway reflex, hypoventilation
and/or apnea, or cardiovascular instability [15]. Direct
observation of a patients ventilation and airway status
by a trained individual may detect potential problems
prior to any automated monitoring device. Monitoring
of the patients heart rate, arterial oxygen saturation, and
blood pressure must be performed in patients receiving
sedation. This recommendation is common to several
societal guidelines[15,26]. The American Society of Anesthesiologists guidelines recommend continuous monitoring of patients with significant cardiovascular disease
or arrhythmia during moderate sedation. For Nigeria, a
home-grown guideline will be able to address these issues taking cognizance of the personnel and resources
available.
Over half of the respondents (51.4%) said they never
used supplemental oxygen. Less than half of the respondents admitted using supplemental oxygen for specific
indications. This is at variance with what occurs in many
developed countries. Supplemental oxygen improves
oxygenation and in the event of hypoventilation or apnea, extends the time that a patient remains adequately
263

using a questionnaire which was administered to all Nigerian gastrointestinal
endoscopists who attended their annual conference. In this way, the actual
practitioners were reached rather than studying a few individuals and using
their views, perceptions and preferences to make generalizations.
oxygenated. It has become standard practice throughout

many areas of the world to administer supplemental
oxygen during endoscopy to all patients receiving moderate sedation[15,30,33,34]. The low rate of administration of
supplemental oxygen among Nigerian endoscopists may
be related to the low rate of utilization of moderate/
deep sedation as well as non availability of oxygen in the
endoscopy suites.
The majority of respondents (82.9%) said they routinely obtained informed consent from patients prior to
sedation. That is good clinical practice. However, 17.1%
did not obtain consent. The concept of informed consent is a process that must take place between physician
and patient, prior to the procedure or treatment, and
should include discussion of pertinent risks, benefits and
alternatives[2,35,36]. Besides, properly informed patients
seldom sue. Busy endoscopy units and long waiting lists
for gastroscopy are not an excuse for omitting proper
patient information[37,38] and not asking their preference
for sedation.
Over a quarter of the respondents used antispasmodic injection (hyoscine) in all diagnostic upper GI endoscopies. This is a very important finding because the
role of antispasmodic agents in GI endoscopy remains
controversial[39]. There are fears about anticholinergics
initiating glaucoma. There is also an unproven suspicion
that the stomach is rendered atonic and more difficult to
distend with air thereby making the procedure more difficult and heightening the risk of perforation. There have
also been reports of adverse reactions to hyscine[40-42].
Recommendations based on evidence are needed in this
area of upper GI endoscopy.
In conclusion, the sedation practices of Nigerian GI
endoscopists for routine upper GI endoscopy differ significantly from what is recommended by many national
professional societies in the developed world. There is
also considerable disparity between the sedation practices of different endoscopists. This state of affairs has
been brought about by a complete absence of guidelines
for sedation practices in Nigeria. There is therefore an
urgent need for all the stakeholders, particularly gastroenterologists and anesthesiologists, to come up with
guidelines appropriate to the existing human and material resources.
Innovations and breakthroughs
Both sedated and unsedated upper gastrointestinal endoscopy were common

as 48.6% used sedation for less than 25% of procedures, while 40.0% used
sedation in more than 75% of endoscopies. The most commonly used sedative
is benzodiazepine (85.7%), while opioid use is limited to 14.3%. None of the
endoscopists had any experience with propofol. Other findings were lack of
guidelines, lack of proper monitoring of sedated patients and lack of nonanesthesiologist staff trained in the use of propofol.
Applications
The results from this study would provide the necessary framework for the
eventual development of a guideline for sedation in gastrointestinal endoscopy
in Nigeria. Similarly, the training and retraining needs of practicing endoscopists
would be better addressed.
Terminology
Endoscopy means looking inside and gastrointestinal endoscopy means looking

inside the gastrointestinal tract using an instrument called an endoscope.
Because the procedure is uncomfortable and may actually be painful, the
standard practice is to carry out the procedure with sedation. Sedation is the
reduction of irritability or agitation by administration of a drug (sedative).
Peer review
This is an interesting survey of sedation practice for upper gastrointestinal

endoscopy in Nigeria. Clearly sedation practice varies between countries and
it is important to develop local guidelines and safety standards, and this survey
would be an important first step in this direction. The paper is generally well
written.
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S- Editor Yang XC
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E- Editor Yang XC


wjge@wjgnet.com
doi:10.4253/wjge.v4.i6.266
CASE REPORT
Unusual penetration of plastic biliary stent in a large ampullary

carcinoma: A case report
H Kerem Tolan, Tassanee Sriprayoon, Thawatchai Akaraviputh
H Kerem Tolan, Tassanee Sriprayoon, Thawatchai Akaraviputh, Department of Surgery, Division of General Surgery,
Minimally Invasive Surgery Unit, Siriraj Gastrointestinal Endoscopy Center, Mahidol University, Bangkok 10700, Thailand
Author contributions: Tolan HK wrote the manuscript; Sriprayoon T read and provided critical comment on the manuscript;
Akaraviputh T performed the procedure and revised the manuscript.
Supported by Faculty of Medicine Siriraj Hospital, Mahidol
University
Correspondence to: Thawatchai Akaraviputh, MD, Siriraj
Gastrointestinal Endoscopy Center, Minimally Invasive Surgery
Unit, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700,
Thailand. sitak@mahidol.ac.th
Telephone: +662-419-8006 Fax: +662-412-1370
Received: October 16, 2011 Revised: April 13, 2012
Accepted: April 27, 2012
Key words: Complication; Endoscopic retrograde chola

ngiopancreatography; Penetration; Perforation
Peer reviewer: Praveen Roy, MD, Health Partners, 2nd Floor,
Gastroenterology, 5400 Gibson Blvd SE, PO Box 92485,
Albuquerque, NM 87199, United States
Tolan HK, Sriprayoon T, Akaraviputh T. Unusual penetration of

plastic biliary stent in a large ampullary carcinoma: A case report. World J Gastrointest Endosc 2012; 4(6): 266-268 Available
from: URL: http://www.wjgnet.com/1948-5190/full/v4/i6/266.
htm DOI: http://dx.doi.org/10.4253/wjge.v4.i6.266
INTRODUCTION
Over the last two decades; after reporting the first use
of a plastic stent in 1980 for a malignant biliary obstruction of the distal common bile duct[1], endoscopic biliary
drainage is now a well-established treatment of choice
for many biliary disorders. Today, a variety of plastic
stents of different shapes, sizes and length are available
in the market[2,3]. Commonly used plastic endoprostheses
are less expensive, but have a higher risk of clogging and
dislocation[4].
The main problem with plastic stents is stent malfunction leading to recurrent jaundice and cholangitis after weeks or months requiring stent exchange in 30% to
60% of patients[5]. To avoid stent migration, the biliary
stent should be placed across the sphincter of Oddi[6].
Distal stent migration is an infrequent late complication, but occurs in up to 6% of cases[7,8]. The majority
of stents pass through the intestinal system without any
problems. However, if the stent gets stuck in the bowel
then it should be removed; endoscopic retrieval is often
possible and surgical intervention is rarely necessary[9,10].
The duodenum is the most common site of a migrated
Abstract
Endoscopic biliary stenting is a well-established treatment of choice for many obstructive biliary disorders.
Commonly used plastic endoprostheses have a higher
risk of clogging and dislocation. Distal stent migration
is an infrequent complication. Duodenum is the most
common site of a migrated biliary stent. Intestinal
perforation can occur during the initial insertion or
endoscopic or percutaneous manipulation, or as a late
consequence of stent placement. A 52-year-old male
who presented with obstructive jaundice underwent
endoscopic retrograde cholangiopancreatography
(ERCP) with plastic stent placement. However, jaundice
did not improve and he then underwent ERCP which
revealed the plastic stent penetrating the ampullary tumor into the duodenal wall causing malfunction of the
stent. A new plastic stent was inserted and the patient
underwent Whipples operation. He is currently doing
well after the operation.
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266
Tolan HK et al . Unusual penetration of plastic biliary stent in a large ampullary carcinoma
10 Fr
7 Fr
Figure 1 Fluoroscopic image after placement of a new 10 Fr plastic stent

in the common bile duct with the previous 7 Fr plastic stent penetrating
the duodenum.
Figure 2 Operative specimen (Whipples operation) showed the plastic

stent was not inside the common bile duct (white arrow). It penetrated the
ampullary mass into the duodenum.
biliary stent[11-14]. However, complications such as perforations and fistulisations in the rest of the small intestine[15] and colon are also seen.
In the recent literature, most (92%) cases of intestinal perforation were in the duodenum after endoscopic
or percutaneous placement of a biliary stent[16-19]. These
were due to various mechanisms; firstly, the stent may
have been placed incorrectly, and the mechanical force
exerted by the tip of the plastic stent against the duodenal mucosa can lead to necrosis of the wall over time.
Secondly, inflexibility or a stent of incorrect length may
lead to pressure necrosis[20,21].
post-operative complications. He was discharged from

the hospital two weeks after surgery. He is currently doing well.
DISCUSSION
Plastic stent occlusion due to tumor overgrowth or bile
clogging the lumen is the most common (54%) problem
seen with endoprostheses following ERCP[18]. Although
it is seen in about 6% of cases; migration of the stent
is one of the most important problems[2,7]. When distal
migration occurs, the majority of stents pass through
the intestinal system without any problem. However, if a
stent gets stuck in the bowel then it should be removed.
Generally, removal is done endoscopically and surgical
intervention is rarely necessary[8,9].
Intestinal perforation can occur during initial insertion, manipulation or as a late consequence of biliary
stent placement. In the recent literature, most cases of
intestinal perforation (92%) were in the duodenum after endoscopic or percutaneous placement of a biliary
stent[4,15-17]. The incidence of small bowel perforation
following ERCP is 0.08%-0.57%[19,20]. In 1999, Howard
et al[21] classified perforations after ERCP into 3 groups;
guidewire-related, periampullary- or postsphincterotomy-related and scope-induced perforations in which
periampullary-related were the most common. In 2000,
Stapfer et al[22] classified ERCP-related perforations, in
descending order of severity, into four types: Type : lateral or medial wall duodenal perforation, Type : periVaterian injuries, Type : distal bile duct injuries related
to wire/basket instrumentation and Type : retroperitoneal air alone.
In our patient, following insertion of the first plastic
stent into the CBD there was lateral penetration of the
stent just proximal to the ampulla; which was due, in our
opinion, to the tumor mass effect on the stent pushing
it into the second part of the duodenum. During the
second ERCP after accessing the first portion of the
duodenum we noted the previous stent, and thought
that distal migration had occurred. When we proceeded
CASE REPORT
We report here on a 52-year-old male who presented
with fever and jaundice. His liver function tests were
TB/DB: 7.3/6.2, Albumin/Globulin: 3.6/3.6, SGOT/
SGPT: 119/214, Alkaline phosphatase: 621. An abdominal computed tomography scan showed marked dilatation of the common bile duct (CBD) with gallstone. He
underwent endoscopic retrograde cholangiopancreatography (ERCP) which revealed a large ulceroproliferative
mass at the ampulla. A plastic stent (7 Fr. 10 cm: Amsterdam type) was placed over the guidewire. Multiple
biopsies were performed at the ampulla and histopathological results showed adenocarcinoma. Two weeks later,
his jaundice had not improved. ERCP was performed
again. After the duodenal scope was introduced, penetration of the previous stent in the ampullary mass into
the duodenal lumen was seen. Cannulation of the CBD
through the ampulla opening where the tip of the previous plastic stent was found was attempted, but failed.
Precut sphincterotomy using a needle knife at the duodenal wall (fistulotomy technique) was performed. Finally the guidewire could be passed into the CBD over the
sphincterotome catheter. A new plastic stent (10 Fr. 10
cm: Amsterdam type) was placed into the CBD (Figure 1).
Good run off of infected bile and contrast media was
seen. One month later, the patient underwent Roboticassisted Whipples operation (Figure 2). There were no
WJGE|www.wjgnet.com
267
Tolan HK et al . Unusual penetration of plastic biliary stent in a large ampullary carcinoma
towards the ampulla we observed the distal part of the

stent coming out of the ampulla. We failed to cannulate
the CBD using a standard technique. Therefore, using
the precut fistulotomy technique a new 10 Fr. plastic
stent was placed and good bile flow was observed. In
this case report we wanted to share this atypical complication of ERCP and plastic stent placement.
peritoneal perforation of the duodenum from biliary stent

erosion. Curr Surg 2005; 62: 512-515
11 Bui BT, Oliva VL, Ghattas G, Daloze P, Bourdon F, Carignan L. Percutaneous removal of a biliary stent after acute
spontaneous duodenal perforation. Cardiovasc Intervent Radiol 1995; 18: 200-202
12 Elder J, Stevenson G. Delayed perforation of a duodenal
diverticulum by a biliary endoprosthesis. Can Assoc Radiol J
1993; 44: 45-48
13 Gould J, Train JS, Dan SJ, Mitty HA. Duodenal perforation
as a delayed complication of placement of a biliary endoprosthesis. Radiology 1988; 167: 467-469
14 Diller R, Senninger N, Kautz G, Tbergen D. Stent migration necessitating surgical intervention. Surg Endosc 2003;
17: 1803-1807
15 Frakes JT, Johanson JF, Stake JJ. Optimal timing for stent replacement in malignant biliary tract obstruction. Gastrointest
Endosc 1993; 39: 164-167
16 Klein U, Weiss F, Wittkugel O. [Migration of a biliary Tannenbaum stent with perforation of sigmoid diverticulum].
Rofo 2001; 173: 1057
17 Blake AM, Monga N, Dunn EM. Biliary stent causing colovaginal fistula: case report. JSLS 2004; 8: 73-75
18 Akimboye F, Lloyd T, Hobson S, Garcea G. Migration of
endoscopic biliary stent and small bowel perforation within
an incisional hernia. Surg Laparosc Endosc Percutan Tech 2006;
16: 39-40
19 Vandervoort J, Soetikno RM, Tham TC, Wong RC, Ferrari AP, Montes H, Roston AD, Slivka A, Lichtenstein DR,
Ruymann FW, Van Dam J, Hughes M, Carr-Locke DL. Risk
factors for complications after performance of ERCP. Gastrointest Endosc 2002; 56: 652-656
20 Masci E, Toti G, Mariani A, Curioni S, Lomazzi A, Dinelli M,
Minoli G, Crosta C, Comin U, Fertitta A, Prada A, Passoni
GR, Testoni PA. Complications of diagnostic and therapeutic ERCP: a prospective multicenter study. Am J Gastroenterol 2001; 96: 417-423
21 Howard TJ, Tan T, Lehman GA, Sherman S, Madura JA,
Fogel E, Swack ML, Kopecky KK. Classification and management of perforations complicating endoscopic sphincterotomy. Surgery 1999; 126: 658-63; discussion 664-5
22 Stapfer M, Selby RR, Stain SC, Katkhouda N, Parekh D,
Jabbour N, Garry D. Management of duodenal perforation
after endoscopic retrograde cholangiopancreatography and
sphincterotomy. Ann Surg 2000; 232: 191-198
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Haskin PH, Butch RJ, Papanicolaou N. Biliary stent endoprosthesis: analysis of complications in 113 patients. Radiology 1985; 156: 637-639
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S- Editor Yang XC
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E- Editor Yang XC
World J Gastrointest Endosc 2012 June 16; 4(6): I


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ACKNOWLEDGMENTS
Acknowledgments to reviewers of World Journal of

Gastrointestinal Endoscopy
Many reviewers have contributed their expertise and
time to the peer review, a critical process to ensure
the quality of World Journal of Gastrointestinal Endoscopy.
The editors and authors of the articles submitted to
the journal are grateful to the following reviewers for
evaluating the articles (including those published in this
issue and those rejected for this issue) during the last
editing time period.
Nevin Oruc, MD, Associate Professor, Ege University,

Gastroenterology Department, Ege University Hospital, Bornova,
zmir 35100, Turkey
Hongchun Bao, PhD, Research Fellow, The Center for Micro-Photonics,

Faculty of Engineering and Industrial Sciences, Swinburne University of
Technology, PO Box 218, Hawthorn, Victoria 3122, Australia
Sema Zer Toros, MD, Department of Otorhinolaryngology/Head

and Neck Surgery, Haydarpaa Numune Education and Research
Hospital, M.Saadettin Sk. Mecidiye Mh. Saadet Apt. No:3 D:4
Ortaky/Beikta, Istanbul, Turkey
Krish Ra gunath, Associate Professor, Consultant

Gastroenterologist, Nottingham Digestive Diseases Centre and
Biomedical Research Unit, Queens Medical Centre campus,
Nottingham University Hospitals NHS Trust, Nottingham NG7
2UH, United Kingdom
Simon Bar-Meir, Professor, Director, Department of

Gastroenterology, Chaim Sheba Medical Center, Tel Hashomer, Ramat
Gan 52621, Israel
Antonio Tucci, Dr. Gastrointestinal Unit, Castel S. Pietro Terme

Hospital, University of Bologna, Bologna, Italy
Jochen Wedemeyer, MD, Department of Gastroenterology,
Hepatology and Endocrinology, Medical School Hannover, Carl
Neuberg Str. 1, 30625 Hannover, Germany
Hajime Isomoto, MD, PhD, Associate Professor, Department of

endoscopy, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki
852-8501, Japan
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www.wjgnet.com
Meetings
Events Calendar 2012
January 19-21, 2012

American Society of Clinical
Oncology 2012 Gastrointestinal
Cancers Symposium
San Francisco, CA 3000,
United States
January 19-21, 2012
2012 Gastrointestinal Cancers
Symposium
San Francisco, CA 94103,
United States
January 20-21, 2012
American Gastroenterological
Association Clinical Congress of
Gastroenterology and Hepatology
Miami Beach, FL 33141,
United States
February 2-4, 2012
14th Dusseldorf International
Endoscopy Symposium 2012
Dusseldorf, Germany
February 24-27, 2012
Canadian Digestive Diseases Week
2012
Montreal, Canada
March 1-3, 2012
International Conference on
Nutrition and Growth 2012
Paris, France
March 7-10, 2012
Society of American Gastrointestinal
and Endoscopic Surgeons Annual
MEETING
Meeting
San Diego, CA 92121, United States
Diseases
Melbourne, Australia
March 12-14, 2012

World Congress on
Gastroenterology and Urology
Omaha, NE 68197, United States
April 22-24, 2012

EUROSON 2012 EFSUMB Annual
Meeting
Madrid, Spain
March 30-April 2, 2012

Mayo Clinic Gastroenterology and
Hepatology
San Antonio, TX 78249,
United States
April 28, 2012

Issues in Pediatric Oncology
Kiev, Ukraine
September 8-9, 2012

New Advances in Inflammatory
Bowel Disease
La Jolla, CA 92093, United States
September 8-9, 2012
Florida Gastroenterologic Society
2012 Annual Meeting
Boca Raton, FL 33498, United States
May 3-5, 2012

9th Congress of The Jordanian
Society of Gastroenterology
Amman, Jordan
March 31-April 1, 2012

5th Annual Endoscopy Directors
Meeting Endoscopy Unit
Management in the 21st Century:
Issues, Solutions, and Plans for the
Future
Washington, DC 20057, United
States
September 15-16, 2012

Current Problems of
Gastroenterology and Abdominal
Surgery
Kiev, Ukraine
May 7-10, 2012

Digestive Diseases Week
Chicago, IL 60601, United States
October 4-6, 2012

EURO-NOTES 2012: NOTES and
Advanced Interventional Endoscopy
Prague, Czech Republic
May 17-21, 2012

2012 ASCRS Annual MeetingAmerican Society of Colon and
Rectal Surgeons
Hollywood, FL 1300, United States
April 8-10, 2012

9th International Symposium on
Functional GI Disorders
Milwaukee, WI 53202, United States
May 18-23, 2012

SGNA: Society of Gastroenterology
Nurses and Associates Annual
Course
Phoenix, AZ 85001, United States
April 15-17, 2012

European Multidisciplinary
Colorectal Cancer Congress 2012
Prague, Czech
May 19-22, 2012

2012-Digestive Disease Week
San Diego, CA 92121, United States
April 19-21, 2012

Internal Medicine 2012
New Orleans, LA 70166,
United States
June 18-21, 2012

Pancreatic Cancer: Progress and
Challenges
April 20-22, 2012

Diffuse Small Bowel and Liver
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Lake Tahoe, NV 89101, United States
October 19-24, 2012

American College of
Gastroenterology 77th Annual
Scientific Meeting and Postgraduate
Course
Las Vegas, NV 89085, United States
November 3-4, 2012
Modern Technologies in
Diagnosis and Treatment of
Gastroenterological Patients
Dnepropetrovsk, Ukraine
December 1-4, 2012
Advances in Inflammatory Bowel
Diseases
Hollywood, FL 33028, United States
World J Gastrointest Endosc 2012 June 16; 4(6): I-V


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INSTRUCTIONS TO AUTHORS
Aims and scope
The major task of WJGE is to report rapidly the most recent re
sults in basic and clinical research on gastrointestinal endoscopy
including: gastroscopy, intestinal endoscopy, colonoscopy, capsule
endoscopy, laparoscopy, interventional diagnosis and therapy, as
well as advances in technology. Emphasis is placed on the clini
cal practice of treating gastrointestinal diseases with or under
endoscopy. Papers on advances and application of endoscopy-asso
ciated techniques, such as endoscopic ultrasonography, endoscopic
retrograde cholangiopancreatography, endoscopic submucosal
dissection and endoscopic balloon dilation are also welcome.
GENERAL INFORMATION
World Journal of Gastrointestinal Endoscopy (World J Gastrointest Endosc,

WJGE, online ISSN 1948-5190, DOI: 10.4253), is a monthly,
open-access (OA), peer-reviewed online journal supported by an
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The biggest advantage of the OA model is that it provides free,
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Editor-in-chief
Nadeem Ahmad Afzal, MD, MBBS, MRCP, MRCPCH,
Consultant Paediatric Gastroenterologist and Honorary Senior
Clinical Lecturer, Room EG244D, Mailpoint 44, Floor G,
Southampton General Hospital, Tremona Road, Southampton,
Hampshire SO16 6YD, United Kingdom
Spiros D Ladas, MD, Professor of Medicine and Gastroenterology,
Medical School, University of Athens, Chairman, 1st Department
of Internal Medicine-Propaedeutic, Director, Medical Section,
Laiko General Hospital of Athens, 17 Agiou Thoma Street,
11527 Athens, Greece
Juan Manuel-Herreras, MD, PhD, AGAF, Professor, Gastroenterology Service, Hospital Universitario Virgen Macarena, Aparato
Digestivo, Avda. Dr. Fedriani, s/n, 41071 Sevilla, Spain
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of the World Medical Association (Declaration of Helsinki, 1964,
as revised in 2004).
Till Wehrmann, MD, PhD, Professor, FB Gastroenterologie

Gastro-enterologie, Deutsche Klinik fuer Diagnostik, Aukammallee
33, 65191 Wiesbaden, Germany
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accompanying the printed article. For example, reviewers: Professor

Jing-Yuan Fang, Shanghai Institute of Digestive Disease, Shanghai,
Affiliated Renji Hospital, Medical Faculty, Shanghai Jiaotong
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An informative, structured abstracts of no more than 480
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(no more than 20 words): Only the purpose should be included.
Please write the aim as the form of To investigate/study/;
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RESULTS (no more than 294 words): You should present P values
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designed the research; Wang CL, Zou CC, Hong F and Wu XM
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1
F, 2F, 3F; or sometimes as other symbols with a superscript (Arabic
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effect of Jianpi Yishen decoction in treatment of Pixu-diar

rhoea. Shijie Huaren Xiaohua Zazhi 1999; 7: 285-287
In press
3 Tian D, Araki H, Stahl E, Bergelson J, Kreitman M. Signature
of balancing selection in Arabidopsis. Proc Natl Acad Sci USA
2006; In press
Organization as author
4 Diabetes Prevention Program Research Group. Hyperten
sion, insulin, and proinsulin in participants with impaired
glucose tolerance. Hypertension 2002; 40: 679-686 [PMID:
12411462 PMCID:2516377 DOI:10.1161/01.
HYP.0000035706.28494.09]
Both personal authors and an organization as author
5 Vallancien G, Emberton M, Harving N, van Moorselaar RJ;
Alf-One Study Group. Sexual dysfunction in 1, 274 European
men suffering from lower urinary tract symptoms. J Urol
2003; 169: 2257-2261 [PMID: 12771764 DOI:10.1097/01.
ju.0000067940.76090.73]
No author given
6 21st century heart solution may have a sting in the tail. BMJ
2002; 325: 184 [PMID: 12142303 DOI:10.1136/
bmj.325.7357.184]
Volume with supplement
7 Geraud G, Spierings EL, Keywood C. Tolerability and safety
of frovatriptan with short- and long-term use for treatment
of migraine and in comparison with sumatriptan. Headache
2002; 42 Suppl 2: S93-99 [PMID: 12028325 DOI:10.1046/
j.1526-4610.42.s2.7.x]
Issue with no volume
8 Banit DM, Kaufer H, Hartford JM. Intraoperative frozen
section analysis in revision total joint arthroplasty. Clin Orthop
Relat Res 2002; (401): 230-238 [PMID: 12151900 DOI:10.109
7/00003086-200208000-00026]
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9 Outreach: Bringing HIV-positive individuals into care. HRSA
Careaction 2002; 1-6 [PMID: 12154804]
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Personal author(s)
10 Sherlock S, Dooley J. Diseases of the liver and billiary system.
9th ed. Oxford: Blackwell Sci Pub, 1993: 258-296
Chapter in a book (list all authors)
11 Lam SK. Academic investigators perspectives of medical
treatment for peptic ulcer. In: Swabb EA, Azabo S. Ulcer dis
ease: investigation and basis for therapy. New York: Marcel
Dekker, 1991: 431-450
Author(s) and editor(s)
12 Breedlove GK, Schorfheide AM. Adolescent pregnancy. 2nd
ed. Wieczorek RR, editor. White Plains (NY): March of Dimes
Education Services, 2001: 20-34
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Proceedings of the 5th Germ cell tumours Conference; 2001
Sep 13-15; Leeds, UK. New York: Springer, 2002: 30-56
Conference paper
14 Christensen S, Oppacher F. An analysis of Koza's comput
ational effort statistic for genetic programming. In: Foster JA,
Lutton E, Miller J, Ryan C, Tettamanzi AG, editors. Genetic
programming. EuroGP 2002: Proceedings of the 5th Euro
pean Conference on Genetic Programming; 2002 Apr 3-5;
Kinsdale, Ireland. Berlin: Springer, 2002: 182-191
Electronic journal (list all authors)
15 Morse SS. Factors in the emergence of infectious diseases.
Emerg Infect Dis serial online, 1995-01-03, cited 1996-06-05;
1(1): 24 screens. Available from: URL: http://www.cdc.gov/
ncidod/eid/index.htm
Patent (list all authors)
16 Pagedas AC, inventor; Ancel Surgical R&D Inc., assignee.
Flexible endoscopic grasping and cutting device and pos
itioning tool assembly. United States patent US 20020103498.
2002 Aug 1
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tumors: A prospective controlled two-center study. World J
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10.3748/wjg.13.6356]
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ISSN 1948-5190 (online)

Michael J Bourke, Sydney

F Douglas Bair, Ontario

Paul Richard Harris, Marcoleta

June 16, 2012

Jens Tischendorf, Aachen

Georgios K Anagnostopoulos, Athens

Paulina Salminen, Turku

Tiberiu Hershcovici, Jerusalem

Ramanathan S Bharathi, Uttar Pradesh

Paola De Angelis, Rome

June 16, 2012

Hirofumi Kawamoto, Okayama

Vasileios Panteris, Rotterdam

Jaekyu Sung, Daejeon

Mihai Ciocirlan, Bucharest

Kassem A Barada, Beirut

Zhiwei Huang, Singapore

United Arab Emirates

Young-Tae Bak, Seoul

June 16, 2012

Krish Ragunath, Nottingham

John C Deutsch, Duluth

Abraham Mathew, Hershey

June 16, 2012

Monthly Volume 4 Number 6 June 16, 2012

Endoscopy in inflammatory bowel disease when and why

NOTES, MANOS, SILS and other new laparoendoscopic techniques

Informed consent for digestive endoscopy

Supportive techniques and devices for endoscopic submucosal dissection of gastric

Outcomes research in gastroenterology and endoscopy

Post-endoscopic retrograde cholangiopancreatography complications: How can they

Pancreatic cystic lesions: How endoscopic ultrasound morphology and

Sedation practices for routine diagnostic upper gastrointestinal endoscopy in

Unusual penetration of plastic biliary stent in a large ampullary carcinoma: A case

June 16, 2012|Volume 4|Issue 6|

World Journal of Gastrointestinal Endoscopy

Volume 4 Number 6 June 16, 2012

Acknowledgments to reviewers of World Journal of Gastrointestinal Endoscopy

Yoshinaga S, Oda I, Nonaka S, Kushima R, Saito Y. Endoscopic ultrasound

World J Gastrointest Endosc 2012; 4(6): 218-226

AIM AND SCOPE

Responsible Assistant Editor: Xiao-Cui Yang

Responsible Science Editor: Xing Wu

Proofing Editorial Office Director: Xiao-Cui Yang

and Gas-troenterology, Medical School, University

No.90 Jaffe Road, Wanchai,

June 16, 2012|Volume 4|Issue 6|

World J Gastrointest Endosc 2012 June 16; 4(6): 201-211

Online Submissions: http://www.wjgnet.com/1948-5190office

Endoscopy in inflammatory bowel disease when and why

Associate Professor, Department of Medicine, Faculty of

Peer reviewers: Sherman M Chamberlain, Associate Professor

of Medicine, Section of Gastroenterology, BBR-2538, Medical

June 16, 2012|Volume 4|Issue 6|

Rameshshanker R et al . Endoscopy in IBD

Table 1 Infective causes of inflammation which mimic inflammatory bowel disease

Non streroidal anti inflammatory drugs

Erythema and ulcers in colon