GUIDELINE

American Society for Gastrointestinal Endoscopy guideline on

the role of endoscopy in the management of acute colonic
pseudo-obstruction and colonic volvulus
Mariam Naveed, MD,1,* Laith H. Jamil, MD, FASGE,2,* Larissa L. Fujii-Lau, MD,3 Mohammad Al-Haddad, MD,4
James L. Buxbaum, MD, FASGE,5 Douglas S. Fishman, MD, FASGE,6 Terry L. Jue, MD, FASGE,7
Joanna K. Law, MD,8 Jeffrey K. Lee, MD,9 Bashar J. Qumseya, MD, MPH,10
Mandeep S. Sawhney, MD, FASGE,11 Nirav Thosani, MD,12 Andrew C. Storm, MD,13
Audrey H. Calderwood, MD, FASGE,14 Mouen A. Khashab, MD,15 Sachin B. Wani, MD, FASGE,16
ASGE Standards of Practice Committee Chair

This document was reviewed and approved by the Governing Board of the American Society for Gastrointestinal
Endoscopy.

Colonic volvulus and acute colonic pseudo-obstruction (ACPO) are 2 causes of benign large-bowel obstruction. Colonic
volvulus occurs most commonly in the sigmoid colon as a result of bowel twisting along its mesenteric axis. In contrast,
the exact pathophysiology of ACPO is poorly understood, with the prevailing hypothesis being altered regulation of
colonic function by the autonomic nervous system resulting in colonic distention in the absence of mechanical
blockage. Prompt diagnosis and intervention leads to improved outcomes for both diagnoses. Endoscopy may play
a role in the evaluation and management of both entities. The purpose of this document from the American Society
for Gastrointestinal Endoscopy’s Standards of Practice Committee is to provide an update on the evaluation and
endoscopic management of sigmoid volvulus and ACPO. (Gastrointest Endosc 2020;91:228-35.)

This document is a focused update on the role of endos- references. Pertinent studies published in English were
copy in the management of colonic volvulus and acute reviewed. Additional references were obtained from the
colonic pseudo-obstruction (ACPO) prepared by the Stan- bibliographies of the identified articles and from
dards of Practice Committee of the American Society for recommendations of expert consultants. When little or no
Gastrointestinal Endoscopy. For guidelines on the role of data existed from well-designed prospective trials, emphasis
endoscopy in the management of malignant colon obstruc- was given to results from large series and recommendations
tion and benign colonic strictures, please refer to the 2010 from recognized experts. Guidelines for appropriate use of
guideline, “The role of endoscopy in the management of pa- endoscopy are based on a critical review of the available
tients with known and suspected colonic obstruction and data and expert consensus at the time the guidelines were
pseudo-obstruction.”1 In preparing this document, a drafted. Further controlled clinical studies may be needed
comprehensive search of the medical literature was to clarify aspects of this guideline. This guideline may be
performed by using EMBASE, PubMed, and Web of Science revised as necessary to account for changes in technology,
from 2009 through March 2019 that related to the topic of new data, or other aspects of clinical practice.
“endoscopic management of colon volvulus and acute
colonic pseudo-obstruction” by using the keyword(s)
endoscopy, colon volvulus, gastrointestinal endoscopy, INTRODUCTION
acute colonic pseudo-obstruction, sigmoid volvulus,
endoscopic procedures, and procedures. The search was Large-bowel obstruction accounts for approximately
supplemented by accessing the “related articles” feature of 25% of all intestinal obstructions.2 Obstruction can be
PubMed, with articles identified on PubMed as the either functional or mechanical in origin. Colonic
volvulus is the most common cause of benign
mechanical obstruction and accounts for approximately
Copyright ª 2020 by the American Society for Gastrointestinal Endoscopy 3.5% of all cases of large-bowel obstruction in the United
0016-5107/$36.00 States and up to 50% in areas such as Africa and the Middle
https://doi.org/10.1016/j.gie.2019.09.007 East.3 Functional bowel obstruction, an example of which

228 GASTROINTESTINAL ENDOSCOPY Volume 91, No. 2 : 2020 www.giejournal.org

 Endoscopic management of ACPO and colonic volvulus

is ACPO, occurs as a result of alterations in GI motility and over colonoscopy in patients with cecal volvulus because
can be characterized by a clinical picture suggestive of endoscopic reduction is rarely effective and is associated
mechanical obstruction with no demonstrable cause of with a higher risk of perforation.13,14
obstruction noted on imaging.4 The endoscopic appearance of sigmoid volvulus is char-
Given that patients with both colon volvulus and ACPO acterized by 2 points of abruptly twisted or converging co-
may present with abdominal pain and distention, demo- lon mucosa. Between the distal and proximal points of
graphic factors and abdominal cross-sectional imaging torsion, the colon is dilated as a result of closed-loop
with CT are used to differentiate between the 2 etiologies obstruction. Endoscopic treatment involves inserting the
and mechanical obstruction other than volvulus. Typically, endoscope to the point of obstruction and gently attempt-
patients at risk for either colon volvulus or ACPO are ing to pass the endoscope through the twisted segment. If
elderly, debilitated, and hospitalized, with multiple medical this is successful, aggressive decompression of the dilated
comorbidities. Abdominal CT findings of ACPO include colon segment should be performed and will often result
colonic dilatation with possible transition zone and no in spontaneous detorsion. In addition to being a therapeu-
obvious mechanical cause of obstruction, whereas patients tic modality, endoscopy allows for assessment of colon
with volvulus may present with dilated colon and mesen- viability.15 The success rate of endoscopic detorsion of
teric whirl sign. Early recognition and management are sigmoid volvulus ranges from 55% to 94%.9,16-18 In a
essential in both clinical entities because a delay in diag- single-center retrospective study of 21 patients with sig-
nosis is associated with substantial morbidity and mortal- moid volvulus, the success rate of endoscopic detorsion
ity.5 For this focused update, a literature review from the was 61.9%, whereas the rest required emergency surgical
date of the latest reference in the previous guideline was treatment. Absence of abdominal tenderness, use of laxa-
performed specifically on the role of endoscopy in the tives, and history of open abdominal surgery were identi-
management of colon volvulus and ACPO. fied as factors predictive of successful endoscopic
detorsion.19 Although randomized controlled data are
lacking, placement of a decompression tube proximal to
COLON VOLVULUS the point of torsion after successful detorsion is
advocated in efforts to maintain the reduction and allow
Etiology and clinical presentation for continued colonic decompression.6,9,11,13,20,21
Acute colonic volvulus, resulting from torsion of a In pediatric patients, endoscopic detorsion is also the
redundant segment of colon along its mesenteric axis, preferred method for sigmoid volvulus reduction.22 One
most commonly occurs in the sigmoid colon or cecum.6 of the initial series in children demonstrated efficacy of
Risk factors for colonic volvulus include anatomic factors only 47%.23 However, a more recent series of 13 cases
such as a long redundant colon with a narrow mesenteric demonstrated that decompression was effective in all
attachment, constipation, colonic dysmotility, and prior cases.22 It is also common practice to place a rectal tube
abdominal surgery.7 Although sigmoid volvulus is more while awaiting surgery. Recurrence of volvulus is
common in adult men >70 years old, African Americans, reported in up to 100% of pediatric cases.22-24
and patients with diabetes and neuropsychiatric
disorders, cecal volvulus is more prevalent in younger Recurrence
females.3 Common presenting symptoms include nausea, Recurrence rates of up to 86% have been reported after
vomiting, abdominal pain, distention, and obstipation. successful endoscopic decompression.6,25 In a recent
Contrast-enhanced CT has replaced abdominal radio- single-center cohort study of 168 patients with sigmoid
graphs and water-soluble contrast enemas as the preferred volvulus, recurrence was observed in 84% of successful
diagnostic study for both cecal and sigmoid volvulus.8 nonoperative decompression cases within a median of 58
Abdominal radiographs are diagnostic in 60% of patients days, with a median of 2 recurrences.26 In a retrospective
with sigmoid volvulus, whereas CT has been shown to study,16 a recurrence rate of 46.2% was noted, with 6 of 13
confirm diagnosis of sigmoid volvulus with near 100% patients experiencing recurrent volvulus. Because the
sensitivity and >90% specificity.9-11 mortality rate of patients presenting with recurrent sigmoid
volvulus is high, elective surgical treatment, specifically
Endoscopic treatment sigmoid colectomy, is generally recommended in candidate
Patients with signs of peritonitis, perforation, or with patients during the index admission or shortly thereafter.13
recurrent or unsuccessful nonoperative decompression
should be referred immediately for surgical management.12 Advanced endoscopic therapy
In the absence of these aforementioned adverse events, In patients who are not candidates for surgery,
nonoperative detorsion with flexible sigmoidoscopy with advanced endoscopic techniques such as percutaneous
or without placement of a decompression tube is endoscopic colostomy (PEC) and percutaneous endo-
considered first-line therapy in the management of sigmoid scopic sigmoidopexy have been suggested as management
volvulus.13 In contrast, surgical management is preferred options. Both techniques aim to fix the involved colon

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Endoscopic management of ACPO and colonic volvulus

segment to the anterior abdominal wall, restricting its first-line therapy. This includes identification and discon-
mobility and thus preventing recurrent volvulus. Although tinuation of predisposing factors (eg, narcotic use), correc-
case series exist with patients successfully undergoing tion of fluid and electrolyte disorders, maintaining patient
these procedures for recurrent sigmoid volvulus, it is with nothing by mouth, ambulation, treatment of infec-
important to note that both modalities are associated tions, and decompression of the proximal gut with a
with a relatively high incidence of immediate and delayed nasogastric tube. Overall success rate of this approach is
serious adverse events, including infection, tube migration, variable, with rates ranging from 77% to 96%.39,40 Serial
perforation, obstruction, abdominal wall bleeding, and assessment of the cecal diameter is prudent given the
death.27-29 Frank et al30 reported a 21% risk of morbidity risk of perforation with cecal diameters greater than 12
and 5% risk of mortality associated with PEC placement cm.33 For patients who are not candidates for
in patients with recurrent sigmoid volvulus. conservative management or in whom symptoms persist
beyond 48 to 72 hours, either pharmacologic therapy
or endoscopic decompression should be considered as
ACUTE COLONIC PSEUDO-OBSTRUCTION the next step in the treatment algorithm (Fig. 1). One
retrospective study found colonic decompression
Etiology and clinical presentation performed by experienced endoscopists to be a more
ACPO, synonymous with Ogilvie’s syndrome, is character- effective initial therapy compared with neostigmine.
ized by an acute presentation of massive dilation of the large However, there was no decrease in length of hospital
intestine in the absence of a mechanical etiology.4 Most stay, intensive care unit stay, or need for colostomy.41
patients are hospitalized at onset. The exact pathogenesis
remains to be elucidated, but current evidence suggests an Pharmacologic therapy
alteration in the autonomic nervous system resulting in Neostigmine, a short-acting anticholinesterase parasym-
colonic atony and pseudo-obstruction.31,32 Several risk fac- pathomimetic agent, remains the pharmacologic agent of
tors have been identified in the development of ACPO, choice in the management of ACPO. Continuous moni-
including critical illness, recent surgical procedure, metabolic toring of cardiac rhythm and respiratory status and imme-
imbalance, and nonoperative trauma.33 Although the true diate access to atropine in the event of bradycardia are
incidence remains unknown, in a retrospective cohort required during drug administration. Coadministration
study using a national admissions database, the annual of glycopyrrolate may be useful in preventing side
incidence of ACPO was approximately 100 cases of 100,000 effects of the medication, including hypersalivation and
inpatient admissions per year.34 bronchospasm.42 Other common adverse events include
nausea, vomiting, diarrhea, abdominal pain, and sweating.
Adverse events Neostigmine is contraindicated in patients with evidence of
The most serious adverse events of ACPO are ischemia intestinal or urinary obstruction and known hypersensitivity
and perforation, with an increased risk for these adverse reaction. Relative contraindications include bradycardia,
events in patients with cecal diameters greater than 10 to asthma, renal insufficiency, peptic ulcer disease, recent
12 cm and in those with duration of distention exceeding myocardial infarction, and acidosis.43
6 days.33,35 At the time of colonoscopy, approximately Three placebo-controlled, double-blind randomized tri-
10% of patients have some degree of ischemia in the als have demonstrated neostigmine to be effective in
right-sided colon. Risk of spontaneous perforation is esti- 85% to 94% of cases.44-46 In a meta-analysis by Valle and
mated to be between 3% and 25%, with up to 50% risk Godoy,47 resolution of ACPO was significantly higher in
of mortality in the event of a perforation.33,36,37 patients who received 1 dose of neostigmine (2-5 mg) as
Imaging is crucial in establishing a diagnosis because me- compared with placebo (89.2% [range, 84.6%-95.2%] vs
chanical obstruction must be excluded. Plain-film abdominal 14.8%). A systematic review reported that neostigmine
radiography is usually sufficient in making a diagnosis, was associated with improvement in clinical symptoms,
although it cannot always reliably distinguish mechanical reduction in time to resolution, and reduction of
from functional causes of obstruction.38 Water-soluble recurrence in patients who failed conservative
contrast enema of the rectum and distal colon is another management.48 Reduced duration of ACPO in patients
diagnostic option, although CT has largely replaced contrast who received neostigmine versus placebo alone has been
enema studies. It is worth noting that mechanical obstruc- demonstrated in other studies.49 In patients who fail an
tion rarely occurs in a patient admitted for unrelated ill- initial dose of neostigmine, are partial responders, or
nesses (eg, pneumonia, elective non-GI surgery). have recurrence, a second dose has been associated with
clinical response in 40% to 100%.40,50,51 Male gender,
Conservative therapy younger age, postsurgical status, and having electrolyte
In patients with uncomplicated ACPO (absence of imbalance are risk factors for nonresponse to neostigmine.
ischemia, peritonitis, cecal diameter >12 cm, and/or signif- Daily administration of polyethylene glycol via nasogastric
icant abdominal pain), conservative management remains tube has also been shown to decrease recurrence.51

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 Endoscopic management of ACPO and colonic volvulus

Acute colonic distention

Yes
Surgery Ischemia or Perforation or
Cecal Volvulus

No
Appropriate Therapy Yes No Acute colonic pseudo-
(e.g. surgery, endoscopic detorsion Mechanical obstruction obstruction
of volvulus, palliative stenting)

Conservative management x 48 to 72 hours

(NPO, nasogastric tube, avoid offending medications, correct fluids and electrolytes, mobilize and treat
reversible casuses)

Partial or No Response

Neostigmine
Success
(if no contraindications)

Consider low-dose daily Colonoscopic

Success
PEG administration Decompression**

Surgery or PEC Partial or No Response

Figure 1. Management of acute colonic pseudo-obstruction. **Limited recent data suggest that colonic decompression may be superior to neostigmine
as first-line therapy for acute colonic pseudo-obstruction refractory to conservative management; however, these study results need to be supported
further before definitive clinical recommendations can be made.

Although neostigmine has traditionally been adminis- 81.6%, P Z .6). Continuous-infusion neostigmine, howev-
tered intravenously in bolus dosing for treatment of er, was associated with greater bowel diameter reduction
ACPO, studies have noted success with alternative routes at 24 hours.54 Ilban et al55 noted no significant difference
of administration. In a recent, multicenter, retrospective, between patients who received bolus dosing (2 mg in 15
observational study of 182 patients with ileus, ACPO, or re- minutes) versus those who received continuous
fractory constipation, subcutaneous neostigmine resulted intravenous infusion (.4 mg neostigmine/h); however, the
in passage of stool within a median time of 29 hours.52 mean time to treatment response was shorter in the
Increasing evidence also supports the role for continuous bolus dosing group compared with the infusion group
infusion of neostigmine in patients who are refractory (165 minutes vs 510 minutes, P Z .001). Continuous
to bolus dosing. White and Sandhu53 described the intravenous infusion may be associated with decreased
successful use of continuous infusion of .4 mg/h side effects compared with bolus dosing.48,54
neostigmine (5 mg neostigmine in 50 mL of .9% normal Several additional pharmacologic agents have been used
saline solution) in a patient with ACPO refractory to 3 for patients who have not responded to treatment with
slow bolus doses of neostigmine. This protocol was first neostigmine, including oral pyridostigmine, a long-acting
described by van der Spoel et al45 in patients with critical acetylcholinesterase inhibitor; peripherally acting u-opioid
illness–related colonic ileus. A continuous neostigmine receptor antagonists such as methylnaltrexone; and
infusion of .4 to .8 mg/h over 24 hours resulted in passage traditional prokinetics such as metoclopramide and eryth-
of stool and flatus in 19 of 24 patients in comparison with romycin. Pyridostigmine, used routinely in the manage-
0 patients in the placebo arm.45 A recent retrospective ment of myasthenia gravis, has been shown to
study comparing clinical response of intermittent bolus successfully treat ACPO refractory to neostigmine and
versus continuous infusion noted that the initial clinical endoscopic decompression.56 Weinstock and Chang57
response was similar between both groups (62.2% vs noted resolution of opioid-induced ACPO using

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Endoscopic management of ACPO and colonic volvulus

methylnaltrexone in 1 patient who failed treatment with decompression to be superior to neostigmine. In a retro-
neostigmine. Prucalopride, a second generation 5-HT4 re- spective 10-year review of 100 patients with ACPO, Tsirline
ceptor partial agonist, has been shown to successfully treat et al63 found colonoscopic decompression to be superior
a patient with acute refractory pseudo-obstruction.58 to neostigmine both after 1 (75% vs 35.5%, P Z .0002)
Further research into the safety and efficacy of these and 2 interventions (84.6 vs 55.6%, P Z .0031). The risk
agents is warranted before their routine use can be of perforation was equivalent in both groups.63 In a
recommended in the management of ACPO. retrospective, nonrandomized, clinical study of sequential
patients with ACPO, Peker et al41 demonstrated colonic
decompression was more effective than neostigmine as
Endoscopic decompression an initial therapy and was more effective at avoiding a
Colonoscopic decompression is an important method second treatment modality. Further, no significant
for managing patients with ACPO. Traditionally, colonic difference in outcome was noted in either group of
decompression has been reserved for patients with persis- patients who eventually required surgery. Other reviews
tent and marked colonic dilatation who have failed to have found the 2 treatment modalities to be equivalent.66
respond to conservative measures, those refractory to The evidence supporting first-line colonoscopic therapy
medical management, or in whom neostigmine is contrain- in managing ACPO is limited, and these study results
dicated.34 Younger age at the time of diagnosis, abdominal need to be further supported before definitive clinical rec-
distention as a chief complaint, and greater cecal diameter ommendations can be made.
have been identified as independently associated with
poor response to medical treatment.59 Endoscopic and percutaneous colostomy of the
The efficacy of colonoscopic decompression has not cecum
been established in randomized trials. However, based An alternate method of decompression includes percuta-
on available data, initial and sustained colonic decompres- neous endoscopic colostomy of the cecum (PEC-cecum),
sion from colonoscopy has been noted in up to 95% of pa- which can be used in the treatment of cecal volvulus and
tients.36,37 The procedure should be performed by an ACPO. PEC-cecum tubes, placed radiographically or via
experienced endoscopist using water infusion and minimal endoscopy, have reported success rates of up to 100%.67,68
to no insufflation of carbon dioxide rather than air. Seda- Nevertheless, this procedure is invasive, and serious adverse
tion with benzodiazepines or other non-narcotic medica- events have been noted including wound infection, bleeding
tion is preferred, because narcotics potentiate colonic or hematoma formation, perforation, granuloma, and buried
atony. The colon should also be unprepped, and an bumper.69 PEC-cecum tubes can be placed through a
attempt should be made to reach at least the distal trans- combined endoscopic and radiologic approach in a manner
verse colon, after which extensive suctioning of air is rec- analogous to percutaneous endoscopic gastrostomy tube
ommended.60 There is an approximately 2% risk of placement or via the “introducer” method, which uses T-
perforation with endoscopic decompression and 1% risk fasteners to secure the colon to the abdominal wall.70
of mortality.5,61 Repeat colonoscopy is fairly commonplace Studies comparing efficacy of PEC tubes with other
given 40% risk of recurrence, especially in patients in methods of decompression are lacking.
whom a decompression tube is not placed.62
Randomized controlled trial data are lacking in support Surgical therapy
of decompression tubes. Cohort studies provide For patients in whom conservative, pharmacologic, and
contradictory data on whether decompression tubes endoscopic treatment options fail, surgical intervention is
provide additional benefit.37,61,63-65 Evidence supports the next appropriate step in management. Patients pre-
that polyethylene glycol solution after endoscopy can senting with peritonitis, ischemia, perforation, clinical
lower recurrence rate.51 As previously noted, benefits of deterioration, or cecal diameter greater than 12 cm should
endoscopic decompression extend beyond treatment also be referred for surgery. Because mortality rates are
because it also allows for simultaneous evaluation of the substantial in patients with ACPO who require surgical
colonic mucosa. It is important to exclude perforation intervention, all efforts should be made to manage these
before performing endoscopic decompression with a patients nonoperatively. In patients with ischemic or perfo-
plain abdominal x-ray performed within several hours rated bowel, surgical mortality as high as 44% has been re-
before the procedure, especially in those patients with ported.33 Surgical treatment options include surgically
fever, leukocytosis, or worsening abdominal pain. placed cecostomy tube, percutaneous cecostomy, or
subtotal colectomy. Surgically placed cecostomy tubes,
Comparison of medical and endoscopic however, are associated with substantial morbidity and
therapy mortality.67 Female gender, emergent admission, and
Although no prospective randomized studies compare increased comorbidities (specifically chronic obstructive
endoscopic decompression and pharmacologic treatment, pulmonary disease and metastatic cancer) have been
2 retrospective studies independently found colonoscopic identified as independent risk factors of colonoscopy failure.

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 Endoscopic management of ACPO and colonic volvulus

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Surg 2012;10:453-7. to this publication: M. Al-Haddad: Teaching and research support from Bos-
50. Mehta R, John A, Nair P, et al. Factors predicting successful outcome ton Scientific. M.A. Khashab: Consultant for BSCI, Olympus, and Medtronic. S.
following neostigmine therapy in acute colonic pseudo-obstruction: B. Wani: Consultant to Boston Scientific and Medtronic. All other authors dis-
a prospective study. J Gastroenterol Hepatol 2006;21:459-61. closed no financial relationships relevant to this publication.
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Received September 4, 2019. Accepted September 4, 2019.
ylene glycol electrolyte balanced solution on patients with acute
colonic pseudo obstruction after resolution of colonic dilation: a pro-
*Drs Naveed and Jamil contributed equally to this article.
spective, randomised, placebo controlled trial. Gut 2006;55:638-42.
52. Kram B, Greenland M, Grant M, et al. Efficacy and safety of subcutane- Current affiliations: Advent Health Medical Group, Gastroenterology/Hep-
ous neostigmine for ileus, acute colonic pseudo-obstruction, or refrac- atology, Advent Health Hospital Altamonte Springs, Altamonte Springs,
tory constipation. Ann Pharmacother 2018;52:505-12. Florida, USA (1), Division of Gastroenterology and Hepatology, Beaumont,
53. White L, Sandhu G. Continuous neostigmine infusion versus bolus Royal Oak, Royal Oak, Michigan, USA (2), Gastroenterology Service, The
neostigmine in refractory Ogilvie syndrome. Am J Emerg Med Queen’s Medical Center, Honolulu, Hawaii, USA (3), Division of Gastroen-
2011;29:576. terology/Hepatology, Indiana University School of Medicine, Indianapolis,
54. Smedley LW, Foster DB, Barthol CA, et al. Safety and Efficacy of Inter- Indiana, USA (4), Division of Gastrointestinal and Liver Diseases, Keck
mittent Bolus and Continuous Infusion Neostigmine for Acute Colonic School of Medicine, University of Southern California, Los Angeles, Califor-
Pseudo-Obstruction. J Intensive Care Med 2018:885066618809010. nia, USA (5), Department of Gastroenterology, Baylor College of Medicine/

234 GASTROINTESTINAL ENDOSCOPY Volume 91, No. 2 : 2020 www.giejournal.org

 Endoscopic management of ACPO and colonic volvulus

Texas Children’s Hospital, Houston, Texas, USA (6), The Permanente Med- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota,
ical Group (7), Department of Gastroenterology (9), Kaiser Permanente San USA (13), Department of Gastroenterology and Hepatology, Dartmouth
Francisco Medical Center, San Francisco, California, USA; Digestive Disease Hitchcock Medical Center, Geisel School of Medicine, Lebanon, New
Institute, Virginia Mason Medical Center, Seattle, Washington, USA (8), Hampshire, USA (14), Division of Gastroenterology and Hepatology, Johns
Department of Gastroenterology, Archbold Medical Group, Thomasville, Hopkins University, Baltimore, Maryland, USA (15), Division of Gastroenter-
Georgia, USA (10), Division of Gastroenterology, Beth Israel Deaconess ology and Hepatology, University of Colorado Anschutz Medical Center,
Medical Center/Harvard Medical School, Boston, Massachusetts, USA Aurora, Colorado, USA (16).
(11), Division of Gastroenterology, Hepatology and Nutrition, McGovern
Medical School, UTHealth, Houston, Texas, USA (12), Department of

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