Imaging and Endoscopy: Original Paper
Dig Dis
DOI: 10.1159/000489394
Absence of Complications after
Endoscopic Mucosal Biopsy
Brian Johnson Marc D. Basson
Department of Surgery, School of Medicine and the Health Sciences, University of North Dakota, Grand Forks, ND, USA
Keywords
Endoscopy · Biopsy · Safety · Risk · Complications
Abstract
Background: There is no clarity with regard to the occur-
rence of serious complications from EGD-driven mucosal bi-
opsy. This is important for considering both clinically indi-
cated procedures and mucosal sampling for research. Meth-
ods: We sought to quantify rates of serious complications
from esophagogastroduodenoscopy (EGD) with biopsy. We
studied 13,233 patients undergoing outpatient EGD with bi-
opsy over 5 years in 2 North Dakota community hospitals,
based on the reasoning that serious complications would
cause hospitalization within 30 days. We reviewed the re-
cords of all patients with a diagnostic or procedure code or
admission within 30 days after the outpatient EGD with bi-
opsy. Results: Of the 13,233 patients who underwent outpa-
tient EGD with biopsy, 411 were admitted within 30 days,
most of them because of their underlying diagnosis. Two
patients were admitted due to complications that resulted
because of additional simultaneous procedures. No patient
was admitted because of complications that could be as-
cribed to conscious sedation, upper GI endoscopic access,
or mucosal biopsy. Conclusions: These data confirm that
© 2018 S. Karger AG, Basel
E-Mail karger@karger.com
www.karger.com/ddi
Received: January 12, 2018
Accepted: April 18, 2018
Published online: May 15, 2018
EGD biopsy is safe within community settings and suggest
that the risk/benefit ratio for performing EGD biopsy for re-
search is likely to be favorable if the research has scientific
merit. Serious complications or perforation following EGD
biopsy did not occur in 13,233 patients in community hos-
pitals in North Dakota. © 2018 S. Karger AG, Basel
Introduction
Esophagogastroduodenoscopy (EGD) is a common
procedure. Over 6.9 million upper endoscopies are per-
formed annually in the United States alone, of which 1.2
million include obtaining biopsies [1]. Much has been
written about the complications of advanced upper endo-
scopic procedures such as dilation, stenting, and endo-
scopic surgery [2–8]. In contrast, esophagogastroduode-
noscopy with mucosal biopsy is generally considered to
be safe and relatively of low risk. However, there is little
evidence in the modern literature to substantiate this im-
pression.
It is important to ascertain the complication rate of
esophagogastroduodenoscopy with biopsy in order to be
able to share this information with patients as they make
141.216.78.40 - 5/19/2018 11:47:54 AM
Univ. of Michigan, Taubman Med.Lib.
Marc D. Basson, MD, PhD, MBA
Professor of Surgery, Pathology, and Biomedical Science, Senior Associate Dean for
Medicine and Research, University of North Dakota School of Medicine and Health
Sciences, 1301 North Columbia Road, Stop 9037, Grand Forks, ND 58202-9037 (USA)
Downloaded by:
E-Mail Marc.basson @ med.und.edu
decisions about whether to undergo this procedure. Mod-
ern doctrines of informed consent suggest that patients
have a right to know the risks of a procedure as well as its
benefits [9]. Even more importantly, there is increasing
interest in sampling the mucosa of the upper gastrointes-
tinal GI tract for research purposes, as scientists attempt
to assess the expression of the genome or kinome or sam-
ple the microbiome of normal humans or patients with
various diseases. There is an extra burden to be accurate
when informing potential research subjects about the
risks of a proposed procedure, and indeed Institutional
Review Boards will typically ask for such information
even before approving a proposed study.
We therefore sought to assess the risk of serious com-
plications in a large cohort of patients undergoing esoph-
agogastroduodenoscopy with mucosal biopsy in the “re-
al-world” community hospital setting. Based on the as-
sumption that any serious complication would lead to
hospital admission, we screened a 5-year consecutive se-
ries of patients undergoing outpatient esophagogastro-
duodenoscopy and biopsy in 2 community hospitals in
North Dakota for subsequent hospitalizations within
30  days. We reviewed the medical records for all such
hospitalized patients to determine the indication for hos-
pitalization and characterized each hospitalization as re-
lated to a complication of the endoscopy and biopsy, re-
lated to some other procedure beyond biopsy done at the
time of the endoscopy, or unrelated to a complication of
the procedure. Our results remarkably demonstrated an
absence of any serious complications that could be as-
cribed to the endoscopic access to the GI tract or to the
mucosal biopsy in this entire series of patients, providing
information that should be profoundly reassuring to pa-
tients and Institutional Review Boards considering this
procedure.
Methods
This study was approved by the Institutional Review Boards of
the University of North Dakota, Altru Hospital, and the Sanford
Hospital system. We used administrative procedure codes to iden-
tify patients who underwent outpatient esophagogastroduodenos-
copy and biopsy at the Sanford Medical Center in Fargo, North
Dakota and at Altru Hospital in Grand Forks North Dakota be-
tween 2011 and 2016. The records of these patients were then re-
viewed and reasons for admission recorded.
All admissions were discussed by both authors and agreement
reached on whether to code the admission as related to a complica-
tion of endoscopic access or mucosal biopsy, related to a simultane-
ous procedure (such as an esophageal dilation done at the time of
esophagogastroduodenoscopy and biopsy), or unrelated to either.
2 Dig Dis
DOI: 10.1159/000489394
We initially analyzed the procedures done at each hospital sep-
arately. However, since there did not appear to be any substantial
differences in the results obtained at each institution, we pooled
the data from both hospitals for presentation here. Because no se-
rious complications could be attributed to the endoscopic access
to the GI tract and subsequent mucosal biopsy, we used the “rule
of three” to estimate a 95% CI for the frequency of such complica-
tions [10].
Results
We identified 13,233 patients who underwent out-
patient EGD with biopsy at the 2 hospitals over the
5-year study period. Of these patients, 411 were admit-
ted to the hospital within 30 days of their procedure.
Of these 411 patients, after careful chart review, we
could ascribe 2 admissions to complications related to
other procedures done at the time of the endoscopy.
One patient was admitted for prolonged hypoxia after
a very long endoscopic procedure involving attempts to
clip a Mallory-Weiss tear and one patient was admitted
for observation for potential bleeding after a superficial
mucosal tear during an endoscopic mucosal resection
of an esophageal tumor. In neither case could we attri-
bute the hospitalization to a mucosal biopsy. Indeed,
we identified no patients who were perforated or ad-
mitted for complications secondary to the endoscopic
biopsy. Instead, these patients were admitted for other
reasons, typically reflecting their underlying diagnosis
(Table 1).
The “rule of three” [10] suggests that we can state with
95% confidence based upon our results that less than one
in 4,411 patients will experience a serious complication
from upper endoscopy and biopsy, with the actual inci-
dence of such a complication being between 0 and
0.0227%.
Discussion
Patients are increasingly being submitted for diagnos-
tic upper endoscopy, while researchers want to sample
the upper GI mucosa to study its biology. Although diag-
nostic colonoscopy has a very real perforation rate [11,
12], upper endoscopy is widely assumed to be a safer pro-
cedure because the scope must traverse a shorter distance
with far less angulation or looping [13–15]. Conscious
sedation for any procedure may entail its own set of risks
including oversedation, aspiration, and medication reac-
tion [16, 17]. It therefore becomes important for clini-
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Univ. of Michigan, Taubman Med.Lib.
Johnson/Basson
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 Table 1. Hospitalizations after outpatient EGD and biopsy

Total number of patients who underwent EGD with biopsy n =13,233

Hospitalization within 30 days of EGD biopsy 411

Hospitalizations due to perforations secondary to EGD biopsy, n 0
Hospitalizations requiring EGD therapy to control upper GI bleeding, n 406
Underlying diagnosis for these patients
Angiodysplasia 104
Dieulafoy lesion 19
Gastric ulcer 91
Duodenal ulcer 88
Mallory-Weiss tear 39
Gastric varices 5
Gastritis 5
Esophagitis 3
Esophageal varices 8
AV malformation 10
GAVE 27
Post Sphincterotomy Bleeding 3
Gastric polyp 3
GIST 1
Hospitalizations secondary to workup of abdominal pain (gastric cancer), n 3
Hospitalizations secondary to prolonged hypoxia (s/p clipping of Mallory-Weiss tear), n 1
Hospitalizations to monitor for bleeding of superficial mucosal tear s/p EMR, n 1

GAVE, gastric antral vascular ectasia; GIST, gastrointestinal stromal tumor; AV, arteriovenous; EMR, en-
doscopic mucosal resection.

cians and research scientists to have actual quantitative
data to provide to patients, research subjects, and regula-
tory bodies such as Institutional Review Boards about the
risk of upper endoscopy and biopsy. Surprisingly, this is
poorly addressed in modern literature.
Our results validate the clinical intuition that upper
endoscopy and biopsy are remarkably safe procedures. It
might be objectionable to accept that patients who devel-
oped complications might have travelled to be admitted
to other institutions and therefore might have been
missed in our study, but the geography of eastern North
Dakota makes this very unlikely. The fact that we did
identify 2 patients who were admitted because of compli-
cations of more aggressive endoscopic manipulations
suggests that we could have found such admitted patients
if they existed. It must be acknowledged, however, that by
choosing to study only outpatient procedures, we may
have selected for healthier patients. For instance, Behrens
and Ell [17] found no serious complications attributable
to conscious sedation for upper endoscopy or colonos-
copy in 177,994 patients who were American Society of
Anesthesiology (ASA) class 1 or 2. Although gastroenter-
ologists’ estimation of ASA classification has been report-
ed of limited reproducibility [18] and bariatric patients
[19] and patients with sleep apnea [20] have been report-
ed to still be at low risk for conscious sedation, sick or
unstable patients could be at higher risk for sedation. We
did not study minor complications such as the use of a
reversal agent after sedation that did not require subse-
quent hospitalization, and this has been reported to occur
more frequently in higher ASA class patients [21]. These
results should therefore be interpreted cautiously while
assessing the potential risk for such patients.
Although not the primary goal for this study, our re-
sults also offer an interesting picture of the reasons for
admission after outpatient upper endoscopy in the com-
munity setting. Most such patients were admitted be-
cause of their underlying diagnoses, being observed ei-
ther for rebleeding after hemostasis had been achieved or
for being managed further for continued bleeding from
their underlying diagnosis. We reviewed data regarding
upper GI bleeding etiology in the published literature for
comparison to our patients. Although peptic ulcer disease
is still the most common underlying cause for substantial
upper GI bleeding, it is becoming less so [22]. This is re-
flected in our study, as 44.1% of study patients presented
with upper GI bleeding secondary to peptic ulcer disease.
Mallory Weiss tears was the reason for 9.6% of the pa-
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Absence of Complications after Dig Dis 3

Endoscopic Mucosal Biopsy DOI: 10.1159/000489394
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tients being admitted for upper GI bleeding cases in our
study, and this finding is comparable with that of the lit-
erature [23]. Variceal bleeding accounted for 3.2% of up-
per GI bleeding admissions in our study, only slightly less
than the reported 5–15% in literature [24]. Angiodyspla-
sias was found in 25.6% of the patients in our study who
were admitted for observation or management of upper
GI bleeding. In contrast, published literature generally at-
tributes only 4–7% of upper GI bleeding to angiodyspla-
sia [25]. These lesions are increasingly being diagnosed
with improved endoscopy. However, this could also re-
flect difficulty in controlling angiodysplastic bleeding or
feeling comfortable with such control, since the 25.6%
figure in our study represents only patients who were ad-
mitted. It is possible that our endoscopists disproportion-
ately admitted such patients rather than sending them
home. Geographic differences in Helicobacter pylori colo-
nization and susceptibility have previously been de-
scribed [26]. In addition, there is clearly a variation in the
way in which endoscopists manage upper gastrointestinal
bleeding [27].
Schulman et al. [28] recently reported a meta-analysis
of upper endoscopic sham procedures done as controls
for research purposes with a disturbingly high serious
complication rate, including an 11.8% perforation rate.
Our results present a stark contrast with those of Schul-
man. However, careful reading of that analysis suggests
that many patients having “sham” endoscopies received
not only either conscious sedation or general anesthesia
and an upper endoscopy but also other procedures such
as “mucosal fluid injection, installation of large fluid bo-
luses into the stomach, overtube placement, and Bougie
advancement with frequent rotation.” These additional
procedures may have created the additional risk described
in that analysis, as a nearly 12% perforation rate is consis-
tent with neither our results nor the general clinical expe-
rience with upper endoscopy.
These data confirm that EGD biopsy is very safe with-
in community settings and suggest that the risk/benefit
ratio for performing EGD biopsy for research purposes is
likely to be favorable if a research proposal has scientific
merit. Serious complications or perforation following
EGD biopsy did not occur in 13,233 patients in commu-
nity hospitals in North Dakota, and are not likely to occur
more than once in every 4,411 patients.
Disclosure Statement
The authors have no conflicts of interest to declare.

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