The role of endoscopy in the management of patients with diarrhea

Abstract

This is one of a series of statements discussing the use of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy (ASGE) prepared this text. In preparing this guideline, a search of the medical literature was performed by using PubMed. Studies or reports that described fewer than 10 patients were excluded from analysis if multiple series with more than 10 patients addressing the same issue were available. Additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants. Guidelines for appropriate use of endoscopy are based on a critical review of the available data and expert consensus at the time the guidelines are drafted. Further controlled clinical studies may be needed to clarify aspects of this guideline. This guideline may be revised as necessary to account for changes in technology, new data, or other aspects of clinical practice. The recommendations are based on reviewed studies and are graded on the strength of the supporting evidence (Table 1).1Guyatt G.H. Oxman A.D. Vist G.E. et al.GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.BMJ. 2008; 336: 924-926Crossref PubMed Google Scholar The strength of individual recommendations is based on both the aggregate evidence quality and an assessment of the anticipated benefits and harms. Weaker recommendations are indicated by phrases such as “we suggest,” whereas stronger recommendations are typically stated as “we recommend.”Table 1GRADE system for rating the quality of evidence for guidelinesAdapted from Guyatt et al.1Guyatt G.H. Oxman A.D. Vist G.E. et al.GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.BMJ. 2008; 336: 924-926Crossref PubMed Google ScholarQuality of evidenceDefinitionSymbolHigh qualityFurther research is very unlikely to change our confidence in the estimate of effect⊕⊕⊕⊕Moderate qualityFurther research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate⊕⊕⊕○Low qualityFurther research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate⊕⊕○○Very low qualityAny estimate of effect is very uncertain⊕○○○ Open table in a new tab This guideline is intended to be an educational device to provide information that may assist endoscopists in providing care to patients. This guideline is not a rule and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment. Clinical decisions in any particular case involve a complex analysis of the patient's condition and available courses of action. Therefore, clinical considerations may lead an endoscopist to take a course of action that varies from this guideline.Diarrheal illnesses can be associated with significant morbidity and mortality, especially in high-risk populations such as the very young, the elderly, and those with comorbid medical illnesses. Diarrhea is defined in adults by abnormal stool weight (>200 g/day), consistency (loose or liquid), and/or frequency (>3 times/day).2Thomas P.D. Forbes A. Green J. et al.Guidelines for the investigation of chronic diarrhoea, 2nd edition.Gut. 2003; 52: 1-15Crossref PubMed Google Scholar, 3Fine K.D. Schiller L.R. AGA Technical review on the evaluation and management of chronic diarrhea.Gastroenterology. 1999; 116: 1464-1486Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar A 4-week symptom duration is generally considered as a cutoff point to distinguish acute (≤4 weeks) from chronic (>4 weeks) diarrhea.2Thomas P.D. Forbes A. Green J. et al.Guidelines for the investigation of chronic diarrhoea, 2nd edition.Gut. 2003; 52: 1-15Crossref PubMed Google Scholar, 3Fine K.D. Schiller L.R. AGA Technical review on the evaluation and management of chronic diarrhea.Gastroenterology. 1999; 116: 1464-1486Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar Because the causes of acute and chronic diarrhea are often different, the need, threshold, and timing of endoscopic evaluation for acute versus chronic diarrhea are different. This document describes the role of endoscopy in the management of patients with diarrhea, with separate discussions for immunocompetent and immunocompromised patients, and is an update of a previous ASGE guideline.4Eisen G.M. Dominitz J.A. Faigel D.O. et al.American Society for Gastrointestinal Endoscopy. Use of endoscopy in diarrheal illnesses.Gastrointest Endosc. 2001; 54: 821-823Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar There are few indications for endoscopy in the management of acute diarrhea, and, although these are briefly discussed, the document primarily focuses on the evaluation on chronic diarrhea.Immunocompetent HOSTInfectious diarrheal illnesses in otherwise healthy individuals are common and short-lived and rarely require specific therapy.5Garthright W.E. Archer D.L. Kvenberg J.E. Estimates of incidence and costs of intestinal infectious disease in the United States.Public Health Rep. 1988; 103: 107-115PubMed Google Scholar Therefore, endoscopy is not warranted for the initial evaluation of acute diarrhea.6Barbut F. Beaugerie L. Delas N. et al.Comparative value of colonic biopsy and intraluminal fluid culture for diagnosis of bacterial acute colitis in immunocompetent patients. Infectious Colitis Study Group.Clin Infect Dis. 1999; 29: 356-360Crossref PubMed Scopus (39) Google Scholar However, an endoscopic evaluation should be considered for patients with persistent symptoms, inconclusive diagnosis after routine blood and stool tests, or failure to respond to empirical therapy.7Lasson A. Kilander A. Stotzer P.O. Diagnostic yield of colonoscopy based on symptoms.Scand J Gastroenterol. 2008; 43: 356-362Crossref PubMed Scopus (48) Google ScholarFlexible sigmoidoscopyFlexible sigmoidoscopy may be a suitable initial investigation for the evaluation of acute diarrhea in patients with suspected diffuse colitis (eg, suspected Clostridium difficile colitis) or chronic diarrhea in patients who are pregnant, have significant comorbidities, or when symptoms characteristic of left-sided colonic disease predominate (eg, tenesmus and urgency). In many situations, flexible sigmoidoscopy may be sufficient as the initial endoscopic test in patients with chronic diarrhea. Biopsies should be performed to obtain specimens for histologic evaluation, even when the mucosa appears normal, to exclude microscopic colitis and other etiologies, as discussed in the next section. Colonoscopy should be considered if the findings at flexible sigmoidoscopy are inconclusive, the symptoms persist, there is large-volume blood loss, or inflammatory bowel disease (IBD) or colorectal cancer is suspected.ColonoscopyIn patients with chronic diarrhea, colonoscopy with biopsy is valuable for the diagnosis of IBD, microscopic inflammatory disorders, and colorectal neoplasia.8Giardiello F.M. Lazenby A.J. Bayless T.M. et al.Lymphocytic (microscopic) colitis. Clinicopathologic study of 18 patients and comparison to collagenous colitis.Dig Dis Sci. 1989; 34: 1730-1738Crossref PubMed Scopus (144) Google Scholar, 9Yusoff I.F. Ormonde D.G. Hoffman N. Routine colonic mucosal biopsy and ileoscopy increases diagnostic yield in patients undergoing colonoscopy for diarrhea.J Gastroenterol Hepatol. 2002; 17: 276-280Crossref PubMed Scopus (66) Google Scholar The role of colonoscopy in the diagnosis, surveillance, and endoscopic therapy of IBD was reported in a separate ASGE guideline.10Leighton J.A. Shen B. Baron T.H. et al.ASGE guideline: endoscopy in the diagnosis and treatment of inflammatory bowel disease.Gastrointest Endosc. 2006; 63: 558-565Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar For those patients with diarrhea who are candidates for routine colorectal cancer screening or surveillance, a diagnostic colonoscopy can be performed to both evaluate the diarrhea and satisfy their cancer screening or surveillance needs.The type of bowel preparation for colonoscopy in the evaluation of diarrhea should be determined on an individual basis. It is recognized that sodium phosphate–based bowel preparations may cause mucosal changes that can be confused with the macroscopic appearance of IBD, most commonly in the distal colon.11Zwas F.R. Cirillo N.W. El-Serag H.B. et al.Colonic mucosal abnormalities associated with oral sodium phosphate solution.Gastrointest Endosc. 1996; 43: 463-466Abstract Full Text Full Text PDF PubMed Scopus (116) Google Scholar, 12Rejchrt S. Bures J. Siroky M. et al.A prospective, observational study of colonic mucosal abnormalities associated with orally administered sodium phosphate for colon cleansing before colonoscopy.Gastrointest Endosc. 2004; 59: 651-654Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar While these changes may be problematic to differentiate endoscopically, they usually can be differentiated on histology.13Watts D.A. Lessells A.M. Penman I.D. et al.Endoscopic and histologic features of sodium phosphate bowel preparation-induced colonic ulceration: case report and review.Gastrointest Endosc. 2002; 55: 584-587Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause terminal ileal mucosal changes that mimic IBD.14Lengeling R.W. Mitros F.A. Brennan J.A. et al.Ulcerative ileitis encountered at ileocolonoscopy: likely role of nonsteroidal agents.Clin Gastroenterol Hepatol. 2003; 1: 160-169Abstract Full Text Full Text PDF PubMed Scopus (78) Google ScholarHistology is essential in the evaluation of chronic diarrhea because of the fact that many etiologies are not macroscopically evident (eg, quiescent IBD, microscopic colitis, eosinophilic colitis, and amyloidosis). The diagnostic yield of colonoscopy in patients with chronic diarrhea ranges from 7% to 32%, with IBD and microscopic colitis being most common.15Marshall J.B. Singh R. Diaz-Arias A.A. Chronic, unexplained diarrhea: are biopsies necessary if colonoscopy is normal?.Am J Gastroenterol. 1995; 90: 372-376PubMed Google Scholar, 16Patel Y. Pettigrew N.M. Grahame G.R. et al.The diagnostic yield of lower endoscopy plus biopsy in nonbloody diarrhea.Gastrointest Endosc. 1997; 46: 338-343Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 17Lee J.H. Rhee P.L. Kim J.J. et al.The role of mucosal biopsy in the diagnosis of chronic diarrhea: value of multiple biopsies when colonoscopic finding is normal or nonspecific.Korean J Intern Med. 1997; 12: 182-187PubMed Google Scholar, 18Shah R.J. Fenoglio-Preiser C. Bleau B.L. et al.Usefulness of colonoscopy with biopsy in the evaluation of patients with chronic diarrhea.Am J Gastroenterol. 2001; 96: 1091-1095Crossref PubMed Google Scholar, 19Fine K.D. Seidel R.H. Do K. The prevalence, anatomic distribution, and diagnosis of colonic causes of chronic diarrhea.Gastrointest Endosc. 2000; 51: 318-326Abstract Full Text Full Text PDF PubMed Scopus (142) Google Scholar, 20da Silva J.G. De Brito T. Cintra Damião A.O. et al.Histologic study of colonic mucosa in patients with chronic diarrhea and normal colonoscopic findings.J Clin Gastroenterol. 2006; 40: 44-48Crossref PubMed Scopus (48) Google Scholar There are 2 forms of microscopic colitis: lymphocytic colitis and collagenous colitis. It is characterized by watery diarrhea in the absence of obvious endoscopic abnormalities. In referral centers, microscopic colitis accounts for approximately 10% of patients seen for chronic diarrhea.19Fine K.D. Seidel R.H. Do K. The prevalence, anatomic distribution, and diagnosis of colonic causes of chronic diarrhea.Gastrointest Endosc. 2000; 51: 318-326Abstract Full Text Full Text PDF PubMed Scopus (142) Google Scholar In a retrospective study of 809 patients with chronic diarrhea who had undergone colonoscopy and biopsy, more than 99% of 122 abnormal pathologic findings were identifiable on distal colonic biopsy samples.19Fine K.D. Seidel R.H. Do K. The prevalence, anatomic distribution, and diagnosis of colonic causes of chronic diarrhea.Gastrointest Endosc. 2000; 51: 318-326Abstract Full Text Full Text PDF PubMed Scopus (142) Google Scholar The majority (80 of 122) showed microscopic colitis. The authors calculated sigmoidoscopy to be a more cost-effective method of investigation than colonoscopy. However, multiple other studies have shown that the disease distribution of microscopic colitis can be patchy, and when biopsy specimens are taken only from the left side of the colon, the diagnosis may be missed.8Giardiello F.M. Lazenby A.J. Bayless T.M. et al.Lymphocytic (microscopic) colitis. Clinicopathologic study of 18 patients and comparison to collagenous colitis.Dig Dis Sci. 1989; 34: 1730-1738Crossref PubMed Scopus (144) Google Scholar, 21Pardi D.S. Microscopic colitis.Mayo Clin Proc. 2003; 78: 614-617Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar, 22Thijs W.J. van Baarlen J. Kleibeuker J.H. et al.Microscopic colitis: prevalence and distribution throughout the colon in patients with chronic diarrhea.Netherlands J Med. 2005; 63: 137-140PubMed Google Scholar, 23Offner F.A. Jao R.V. Lewin K.J. et al.Collagenous colitis: a study of the distribution of morphological abnormalities and their histological detection.Hum Pathol. 1999; 30: 451-457Abstract Full Text PDF PubMed Scopus (104) Google Scholar, 24Fernandez-Banares F. Salas A. Forné M. et al.Incidence of collagenous and lymphocytic colitis: a 5-year population-based study.Am J Gastroenterol. 1999; 94: 418-423Crossref PubMed Scopus (260) Google Scholar, 25Tanaka M. Mazzoleni G. Riddell R.H. Distribution of collagenous colitis: utility of flexible sigmoidoscopy.Gut. 1992; 33: 65-70Crossref PubMed Scopus (158) Google Scholar Therefore, in patients with chronic diarrhea and normal findings on colonoscopic examination, it is recommended that multiple biopsy samples should be taken from both the right and left sides of the colon.Retrograde ileoscopy with biopsy in the diagnostic evaluation of diarrheal illness can be helpful.26Geboes K. The strategy for biopsies of the terminal ileum should be evidence based.Am J Gastroenterol. 2007; 102: 1090-1092Crossref PubMed Scopus (26) Google Scholar The differential diagnosis for abnormal endoscopic and histologic findings in the terminal ileum of patients with acute or chronic diarrhea includes Crohn's disease, NSAID-induced enteropathy, carcinoid, tuberculosis, lymphoma, and adenocarcinoma.14Lengeling R.W. Mitros F.A. Brennan J.A. et al.Ulcerative ileitis encountered at ileocolonoscopy: likely role of nonsteroidal agents.Clin Gastroenterol Hepatol. 2003; 1: 160-169Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar, 27Yoong K.K. Heymann T. It is not worthwhile to perform ileoscopy on all patients.Surg Endosc. 2006; 20: 809-811Crossref PubMed Scopus (27) Google Scholar, 28Morini S. Lorenzetti R. Stella F. et al.Retrograde ileoscopy in chronic nonbloody diarrhea: a prospective, case-control study.Am J Gastroenterol. 2003; 98: 1512-1515Crossref PubMed Scopus (31) Google Scholar In a prospective evaluation of 138 patients, ileoscopy provided additional information leading to an incidental, conclusive diagnosis in 2.7% of asymptomatic patients undergoing colonoscopy for polyp surveillance; the rate increased to 18% in 22 non–human immunodeficiency virus (HIV) patients with diarrhea.29Zwas F.R. Bonheim N.A. Berken C.A. et al.Diagnostic yield of routine ileoscopy.Am J Gastroenterol. 1995; 90: 1441-1443PubMed Google Scholar Terminal ileal biopsy is most helpful in patients with or suspected of having inflammatory diarrhea.26Geboes K. The strategy for biopsies of the terminal ileum should be evidence based.Am J Gastroenterol. 2007; 102: 1090-1092Crossref PubMed Scopus (26) Google Scholar, 30Batres L.A. Maller E.S. Ruchelli E. et al.Terminal ileum intubation in pediatric colonoscopy and diagnostic value of conventional small bowel contrast radiography in pediatric inflammatory bowel disease.J Pediatr Gastroenterol Nutr. 2002; 35: 320-323Crossref PubMed Scopus (32) Google Scholar Biopsy may be of the greatest value in patients undergoing endoscopy for known or strongly suspected Crohn's disease, with abnormal findings on an imaging study of the terminal ileum, or when abnormal terminal ileal mucosa is identified endoscopically.31McHugh J.B. Appelman H.D. McKenna B.J. The diagnostic value of endoscopic terminal ileum Biopsies.Am J Gastroenterol. 2007; 102: 1084-1089Crossref PubMed Scopus (72) Google Scholar, 32Geboes K. Ectors N. D'Haens G. et al.Is ileoscopy with biopsy worthwhile in patients presenting with symptoms of inflammatory bowel disease?.Am J Gastroenterol. 1998; 93: 201-206Crossref PubMed Scopus (168) Google Scholar In 1 report, microscopic lesions of the terminal ileum were found in 125 (49%) of 257 patients with diarrhea and suspected IBD.32Geboes K. Ectors N. D'Haens G. et al.Is ileoscopy with biopsy worthwhile in patients presenting with symptoms of inflammatory bowel disease?.Am J Gastroenterol. 1998; 93: 201-206Crossref PubMed Scopus (168) Google Scholar Ileal biopsies were essential for the diagnosis in 15 (6%) patients and contributed to the diagnosis in 53 (21%). The diagnostic yield of ileal biopsy of normal-appearing mucosa is not well studied, with reports of significant findings ranging from 0% to 4.2% of patients.9Yusoff I.F. Ormonde D.G. Hoffman N. Routine colonic mucosal biopsy and ileoscopy increases diagnostic yield in patients undergoing colonoscopy for diarrhea.J Gastroenterol Hepatol. 2002; 17: 276-280Crossref PubMed Scopus (66) Google Scholar, 18Shah R.J. Fenoglio-Preiser C. Bleau B.L. et al.Usefulness of colonoscopy with biopsy in the evaluation of patients with chronic diarrhea.Am J Gastroenterol. 2001; 96: 1091-1095Crossref PubMed Google Scholar, 31McHugh J.B. Appelman H.D. McKenna B.J. The diagnostic value of endoscopic terminal ileum Biopsies.Am J Gastroenterol. 2007; 102: 1084-1089Crossref PubMed Scopus (72) Google Scholar, 32Geboes K. Ectors N. D'Haens G. et al.Is ileoscopy with biopsy worthwhile in patients presenting with symptoms of inflammatory bowel disease?.Am J Gastroenterol. 1998; 93: 201-206Crossref PubMed Scopus (168) Google Scholar Therefore, the value of routine ileal biopsy of normal-appearing mucosa is controversial but overall is probably of low yield.EsophagogastroduodenoscopyAcute diarrheal illnesses are generally caused by infectious agents involving the lower part of the GI tract. Routine use of esophagogastroduodenoscopy (EGD) in these self-limited disorders is therefore not indicated. In the absence of significant findings on laboratory studies and lower endoscopy, an upper GI evaluation for small-bowel disease should be considered in patients with chronic diarrhea. The differential diagnosis in these patients includes celiac disease, Giardia infection, Crohn's disease, eosinophilic gastroenteropathy, Whipple's disease, intestinal amyloid, and pancreatic insufficiency.Mucosal biopsies of the small intestine should be performed even when the endoscopic appearance is normal. It is important to include the clinical suspicion in the pathology request form so that special histochemical and immunohistochemical stains of biopsy specimens can be performed, as indicated.33Akram S. Murray J.A. Pardi D.S. et al.Adult autoimmune enteropathy: Mayo Clinic Rochester experience.Clin Gastroenterol Hepatol. 2007; 5: 1282-1290Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar Some studies have shown that orientation of biopsy specimens is important for accurate histologic evaluation.34Ravelli A. Bolognini S. Gambarotti M. et al.Variability of histologic lesions in relation to biopsy site in gluten-sensitive enteropathy.Am J Gastroenterol. 2005; 100: 177-185Crossref PubMed Scopus (161) Google Scholar, 35Brocchi E. Bonora M. Epifanio G. et al.Routine duodenal biopsies: is it time to change our minds?.Gastrointest Endosc. 2004; 59: 331-332Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar, 36Serra S. Jani P.A. An approach to duodenal biopsies.J Clin Pathol. 2006; 59: 1133-1150Crossref PubMed Scopus (66) Google ScholarCeliac serology should be considered as the first-line diagnostic modality in patients suspected of having celiac disease.2Thomas P.D. Forbes A. Green J. et al.Guidelines for the investigation of chronic diarrhoea, 2nd edition.Gut. 2003; 52: 1-15Crossref PubMed Google Scholar The tissue transglutaminase assay has demonstrated the highest performance characteristics for the serologic diagnosis of celiac disease in the absence of IgA deficiency.37Hill I.D. Dirks M.H. Liptak G.S. et al.North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.J Pediatr Gastroenterol Nutr. 2005; 40: 1-19Crossref PubMed Scopus (957) Google Scholar Most experts recommend that a positive serologic test result for celiac disease should be confirmed with a tissue biopsy.38Freeman H.J. Small intestinal mucosal biopsy for investigation of diarrhea and malabsorption in adults.Gastrointest Endosc Clin North Am. 2000; 10: 739-754PubMed Google Scholar, 39AGA Institute Medical Position Statement on the Diagnosis and Management of Celiac Disease.Gastroenterology. 2006; 131: 1977-1980Abstract Full Text Full Text PDF PubMed Scopus (237) Google Scholar Although a diagnosis of celiac disease cannot be definitively made based on the endoscopic appearance of the small bowel (eg, scalloped mucosal folds), magnification endoscopy may enhance the diagnostic yield and may be helpful in highlighting the diseased area for targeted biopsy.40Lo A. Guelrud M. Essenfeld H. et al.Classification of villous atrophy with enhanced magnification endoscopy in patients with celiac disease and tropical sprue.Gastrointest Endosc. 2007; 66: 377-382Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar, 41Badreldin R. Barrett P. Wooff D.A. et al.How good is zoom endoscopy for assessment of villous atrophy in coeliac disease?.Endoscopy. 2005; 37: 994-998Crossref PubMed Scopus (44) Google Scholar Biopsy specimens obtained from the second or third portion of the duodenum with standard forceps are usually sufficient.39AGA Institute Medical Position Statement on the Diagnosis and Management of Celiac Disease.Gastroenterology. 2006; 131: 1977-1980Abstract Full Text Full Text PDF PubMed Scopus (237) Google Scholar, 42Dandalides S.M. Carey W.D. Petras R. et al.Endoscopic small bowel mucosal biopsy: a controlled trial evaluating forceps size and biopsy location in the diagnosis of normal and abnormal mucosal architecture.Gastrointest Endosc. 1989; 35: 197-200Abstract Full Text PDF PubMed Scopus (83) Google Scholar, 43Pais W.P. Duerksen D.R. Pettigrew N.M. et al.How many duodenal biopsy specimens are required to make a diagnosis of celiac disease?.Gastrointest Endosc. 2008; 67: 1082-1087Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar A study of 102 patients showed that if 2, 3, and 4 biopsy specimens were obtained, celiac disease was confirmed in 90%, 95%, and 100% of the cases, respectively.43Pais W.P. Duerksen D.R. Pettigrew N.M. et al.How many duodenal biopsy specimens are required to make a diagnosis of celiac disease?.Gastrointest Endosc. 2008; 67: 1082-1087Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar Therefore, we recommend obtaining a minimum of 4 biopsy specimens. The distribution of celiac disease may be patchy, particularly in pediatric patients,44Bonamico M. Mariani P. Thanasi E. et al.Patchy villous atrophy of the duodenum in childhood celiac disease.J Pediatr Gastroenterol Nutr. 2004; 38: 204-207Crossref PubMed Scopus (161) Google Scholar and isolated jejunal involvement by celiac disease can occur.45Murray J.A. Rubio-Tapia A. van Dyke C.T. et al.Mucosal atrophy in celiac disease: extent of involvement, correlation with clinical presentation, and response to treatment.Clin Gastroenterol Hepatol. 2008; 6: 186-193Abstract Full Text Full Text PDF PubMed Scopus (160) Google Scholar Evaluation of the more distal small bowel may be of benefit in selected patients (eg, those with persistent symptoms in suspected celiac disease and those with suspected small-bowel lymphoma). Because concurrent celiac disease and microscopic colitis are common,46Williams J.J. Kaplan G.G. Makhija S. et al.Microscopic colitis-defining incidence rates and risk factors: a population-based study.Clin Gastroenterol Hepatol. 2008; 6: 35-40Abstract Full Text Full Text PDF PubMed Scopus (121) Google Scholar, 47Matteoni C.A. Goldblum J.R. Wang N. et al.Celiac disease is highly prevalent in lymphocytic colitis.J Clin Gastroenterol. 2001; 32: 225-227Crossref PubMed Scopus (95) Google Scholar celiac serology and/or upper endoscopy with proximal small-bowel biopsy may be considered to rule out celiac disease in patients with a diagnosis of microscopic colitis who do not respond to treatment.Patients at high risk of Giardia infection with negative findings on stool studies may benefit from upper endoscopy with duodenal biopsies for touch preparation and/or duodenal aspirates to identify trophozoites.48Oberhuber G. Stolte M. Symptoms in patients with giardiasis undergoing upper gastrointestinal endoscopy.Endoscopy. 1997; 29: 716-720Crossref PubMed Scopus (17) Google Scholar, 49Bown J.W. Savides T.J. Mathews C. et al.Diagnostic yield of duodenal biopsy and aspirate in AIDS-associated diarrhea.Am J Gastroenterol. 1996; 91: 2289-2292PubMed Google Scholar Upper endoscopy with quantitative culture of small-bowel biopsies or aspirate is useful for the diagnosis of small-bowel bacterial overgrowth.50Stotzer P.O. Brandberg A. Kilander A.F. Diagnosis of small intestinal bacterial overgrowth in clinical praxis: a comparison of the culture of small bowel aspirate, duodenal biopsies and gastric aspirate.Hepatogastroenterology. 1998; 45: 1018-1022PubMed Google Scholar, 51Riordan S.M. McIver C.J. Duncombe V.M. et al.Bacteriologic analysis of mucosal biopsy specimens for detecting small-intestinal bacterial overgrowth.Scand J Gastroenterol. 1995; 30: 681-685Crossref PubMed Scopus (27) Google Scholar Endoscopy-assisted pancreatic function tests may be useful for the diagnosis of pancreatic insufficiency in chronic pancreatitis.52Conwell D.L. Zuccaro Jr., G. Vargo J.J. et al.An endoscopic pancreatic function test with synthetic porcine secretin for the evaluation of chronic abdominal pain and suspected chronic pancreatitis.Gastrointest Endosc. 2003; 57: 37-40Abstract Full Text Full Text PDF PubMed Scopus (94) Google ScholarVideo capsule endoscopyVideo capsule endoscopy (VCE) has been studied in patients with chronic diarrhea with concurrent abdominal pain and other abdominal symptoms.53Fry L.C. Carey E.J. Shiff A.D. et al.The yield of capsule endoscopy in patients with abdominal pain or diarrhea.Endoscopy. 2006; 38: 498-502Crossref PubMed Scopus (66) Google Scholar, 54May A. Manner H. Schneider M. et al.Prospective multicenter trial of capsule endoscopy in patients with chronic abdominal pain, diarrhea and other signs and symptoms (CEDAP−Plus Study).Endoscopy. 2007; 39: 606-612Crossref PubMed Scopus (83) Google Scholar Diagnostic yield ranged from 13% to 24%, with findings consistent with Crohn's disease, NSAID-induced enteropathy, celiac disease, and submucosal masses.53Fry L.C. Carey E.J. Shiff A.D. et al.The yield of capsule endoscopy in patients with abdominal pain or diarrhea.Endoscopy. 2006; 38: 498-502Crossref PubMed Scopus (66) Google Scholar, 54May A. Manner H. Schneider M. et al.Prospective multicenter trial of capsule endoscopy in patients with chronic abdominal pain, diarrhea and other signs and symptoms (CEDAP−Plus Study).Endoscopy. 2007; 39: 606-612Crossref PubMed Scopus (83) Google Scholar, 55Petroniene R. Dubcenco E. Baker J.P. et al.Given capsule endoscopy in celiac disease: evaluation of diagnostic accuracy and interobserver agreement.Am J Gastroenterol. 2005; 100: 685-694Crossref PubMed Scopus (145) Google Scholar VCE may be more sensitive for the detection of mucosal changes of celiac disease than EGD with a sensitivity of 70% to 85% and a specificity of 100% in untreated celiac disease.55Petroniene R. Dubcenco E. Baker J.P. et al.Given capsule endoscopy in celiac disease: evaluation of diagnostic accuracy and interobserver agreement.Am J Gastroenterol. 2005; 100: 685-694Crossref PubMed Scopus (145) Google Scholar, 56Hopper A.D. Sidhu R. Hurlstone D.P. et al.Capsule endoscopy: an alternative to duodenal biopsy for the recognition of villous atrophy in celiac disease?.Dig Liver Dis. 2007; 39: 140-145Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar However, because of the modest diagnostic yield, inability to obtain tissue, and risk of capsule retention, VCE is not recommended for the routine evaluation of chronic diarrhea.EnteroscopyThere are limited data on the diagnostic value of enteroscopy solely for the evaluation of diarrhea. Push enteroscopy has been evaluated as a complementary investigation for small-bowel follow-through, EGD, and colonoscopy, with a diagnostic yield of as high as 22% in patients with chronic diarrhea and/or malabsorption.57Bouhnik Y. Bitoun A. Coffin B. et al.Two way push video enteroscopy in investigation of small bowel disease.Gut. 1998; 43: 280-284Crossref PubMed Scopus (47) Google Scholar, 58Landi B. Tkoub M. Gaudric M. et al.Diagnostic yield of push-type enteroscopy in relation to indication.Gu