Terminal ileum ileoscopy and histology in patients undergoing high-definition colonoscopy with virtual chromoendoscopy for chronic nonbloody diarrhea: A prospective, multicenter study.

Background and aims: Ileo-colonoscopy is the procedure of choice for chronic nonbloody diarrhea (CNBD) of unknown origin. Histological evaluation at different colonic sites is mandatory to assess the presence of microscopic colitis. However, the value of routine ileal biopsy on normal-appearing mucosa as assessed by means of standard-resolution white-light ileoscopy is controversial given its reported low diagnostic yield. Hence, we have assessed for the first time the accuracy of retrograde ileoscopy using high-definition and dyeless chromoendoscopy (HD + DLC), thereby calculating the impact and cost of routine ileal biopsy in CNBD. Methods: Patients with CNBD of unknown origin were prospectively enrolled for ileo-colonoscopy with HD + DLC at five referral centers. Multiple biopsies were systematically performed on each colorectal segment and in the terminal ileum for histopathological analysis. Results: Between 2014 and 2017, 546 consecutive patients were recruited. Retrograde ileoscopy success rate was 97.6%. A total of 492 patients (mean age: 53 ± 18 years) fulfilled all the inclusion criteria: Following endoscopic and histopathological work-up, 7% had lymphoid nodular hyperplasia and 3% had isolated ileitis. Compared to the histopathology as the gold standard, retrograde ileoscopy with HD + DLC showed 93% sensitivity, 98% specificity and 99.8% negative predictive value. In patients with normal ileo-colonoscopy, ileum histology had no diagnostic gain and resulted in a cost of US $26.5 per patient. Conclusions: Retrograde ileoscopy with HD + DLC predicts the presence of ileitis in CNBD with excellent performance. The histopathological evaluation of the terminal ileum is the gold standard for the diagnostic assessment of visible lesions but has no added diagnostic value in CNBD patients with negative ileo-colonoscopy inspection using modern endoscopic imaging techniques.

Microscopic colitis: pathophysiology and clinical management.

Microscopic colitis is a chronic inflammatory disease of the colon that frequently causes chronic watery diarrhoea that might be accompanied by abdominal pain, nocturnal diarrhoea, urgency, and faecal incontinence. These symptoms lead to poor quality of life and increased health-care costs. Diagnosis relies on histological examination of multiple biopsy samples from the colonic mucosa, which often show no or only few abnormalities on endoscopy. Two major histological subtypes can be distinguished-collagenous colitis and lymphocytic colitis-but incomplete and variant forms with fewer characteristic features have been reported. Here we summarise the latest evidence on epidemiology, pathogenesis, and risk factors, and discuss established and novel therapeutic options for clinical remission. Finally, we propose an updated treatment algorithm. Further prospective studies are needed to clarify the natural history of microscopic colitis, supported by validated criteria for the assessment of disease activity.

Idiopathic microscopic colitis of rhesus macaques: quantitative assessment of colonic mucosa.

Idiopathic chronic diarrhea (ICD) is a common cause of morbidity and mortality among juvenile rhesus macaques. While lesions may be absent at colonoscopy, the histopathologic evaluation of the biopsy specimens is consistent with human macroscopic colitis (MC). In this study, we developed an isotropic uniform random sampling method to evaluate macroscopic and microscopic changes and applied it on proximal ascending colon in monkeys. Colonic tissue and peripheral blood specimens were collected from six MC and six control juvenile macaques at necropsy. Uniform random samples were collected from the colon using punch biopsy tools. The volume of epithelium and lamina propria were estimated in thick (25 µm) sections using point probes and normalized to the area of muscularis mucosae. Our data suggests a significant increase of the Vs of the lamina propria (1.9-fold, P = 0.02) and epithelium (1.4-fold, P = 0.05) in subjects with MC. The average colonic surface mucosa area in the MC monkeys increased 1.4-fold over the controls (P = 0.02). The volume of the proximal colon in animals with MC showed a 2.4-fold increase over the non-diarrhea control monkeys (P = 0.0001). Cytokine, chemokine, and growth factor levels in peripheral blood were found to be correlated with the volume estimate of the lamina propria and epithelium. We found that ICD in macaques has features which simulates human MC and can be used as a spontaneous animal model for human MC. Furthermore, this developed sampling method can be used for unbiased preclinical evaluation of therapeutics in this animal model.

Diagnostic yield and economic implications of endoscopic colonic biopsies in patients with chronic diarrhoea.

AIMS: Random colonic biopsies are recommended to exclude microscopic colitis in patients with chronic diarrhoea especially when mucosa is macroscopically normal at endoscopy. This study aimed to assess the clinical outcome and economic impact of such a policy in an unselected group of patients with macroscopically normal mucosa. METHODS: All new patients undergoing colonoscopy for investigation of chronic diarrhoea between April and December 2009 were included. Patients were divided into two groups: macroscopically normal mucosa and macroscopically inflamed mucosa. Endoscopic findings were correlated with histology of random biopsies and haematological parameters. Symptom status and any treatment were established from follow-up. The breakdown and overall cost of random biopsies for each patient with a macroscopically normal mucosa were determined, and cost incurred per diagnosis of microscopic colitis was established. RESULTS: Altogether 137 (90.1%) of 152 patients with chronic diarrhoea had macroscopically normal mucosa at colonoscopy. Overall incidence of microscopic colitis in the study was 1.3% (2/152); both patients belonged to the macroscopically normal mucosa group. At follow-up, both these patients had spontaneous symptom resolution without any specific treatment. The policy of undertaking random biopsies in patients with macroscopically normal mucosa incurred an extra cost of £22,057 to diagnose two cases of microscopic colitis but did not alter medical treatment. CONCLUSIONS: In unselected patients with chronic diarrhoea and macroscopically normal mucosa, random colonic biopsies have a low diagnostic yield and incur a high cost. Continued research for predictive markers to improve patient selection for targeted biopsies is needed to develop a cost-effective investigative algorithm in chronic diarrhoea.

Optimal approach to obtaining mucosal biopsies for assessment of inflammatory disorders of the gastrointestinal tract.

Endoscopic evaluation and mucosal biopsy analysis have assumed important roles in the clinical management of patients with symptoms related to the gastrointestinal tract. Several common inflammatory diseases, including eosinophilic esophagitis, Barrett's esophagus, Helicobacter pylori infection, celiac disease, lymphocytic colitis, collagenous colitis, and inflammatory bowel disease, may display a patchy or discontinuous distribution and, thus, multiple mucosal samples may be required to obtain diagnostic tissue in some cases. Not surprisingly, clinicians and pathologists are increasingly challenged to determine the optimum number of procedures and tissue samples necessary to detect, or exclude, the presence of inflammatory disorders of the gastrointestinal tract. Unfortunately, clinical practice varies widely with respect to tissue sample procurement in the evaluation of these disorders, particularly when the endoscopic appearance of the gastrointestinal mucosa is normal or shows only minimal changes. Guidelines concerning the appropriate number of tissue samples are well established for some diseases, such as Barrett's esophagus and chronic gastritis, but are not clear in other instances. The purpose of this review is to discuss the available literature pertaining to appropriate endoscopic sampling in the assessment of medical diseases of the gastrointestinal tract, and to develop recommendations regarding the clinical evaluation of common gastrointestinal disorders.