Determining the optimal treatment target in patients with ulcerative colitis: rationale, design, protocol and interim analysis for the randomised controlled VERDICT trial.

INTRODUCTION: Symptoms, endoscopy and histology have been proposed as therapeutic targets in ulcerative colitis (UC). Observational studies suggest that the achievement of histologic remission may be associated with a lower risk of complications, compared with the achievement of endoscopic remission alone. The actiVE ulcerative colitis, a RanDomIsed Controlled Trial (VERDICT) aims to determine the optimal treatment target in patients with UC. METHODS AND ANALYSIS: In this multicentre, prospective randomised study, 660 patients with moderate to severe UC (Mayo rectal bleeding subscore [RBS] ≥1; Mayo endoscopic score [MES] ≥2) are randomly assigned to three treatment targets: corticosteroid-free symptomatic remission (Mayo RBS=0) (group 1); corticosteroid-free endoscopic remission (MES ≤1) and symptomatic remission (group 2); or corticosteroid-free histologic remission (Geboes score <2B.0), endoscopic remission and symptomatic remission (group 3). Treatment is escalated using vedolizumab according to a treatment algorithm that is dependent on the patient's baseline UC therapy until the target is achieved at weeks 16, 32 or 48. The primary outcome, the time from target achievement to a UC-related complication, will be compared between groups 1 and 3 using a Cox proportional hazards model. ETHICS AND DISSEMINATION: The study was approved by ethics committees at the country level or at individual sites as per individual country requirements. A full list of ethics committees is available on request. Study results will be disseminated in peer-reviewed journals and at scientific meetings. TRIAL REGISTRATION NUMBER: EudraCT: 2019-002485-12; NCT04259138.

Wireless capsule endoscopy for obscure gastrointestinal bleeding: a single-centre, one-year experience.

BACKGROUND: Wireless capsule endoscopy (CE) is increasingly being used in the investigation of obscure gastrointestinal (GI) bleeding, but some studies have found that many of the bleeding lesions recognized by this technique are within the reach of conventional endoscopy. METHODS: The results of CE performed in the authors' centre in a 12 month period for obscure GI bleeding were retrospectively reviewed. RESULTS: Of the 46 patients with obscure GI bleeding, CE found a definite or probable cause in 19 (41%) and a possible cause in another 10 (22%), with an overall diagnostic yield of 63%. One of these lesions was found to be within reach of conventional gastroscopy, two were within reach of push enteroscopy, four were within reach of colonoscopy and one was within reach of retrograde enteroscopy through a stoma. The percentage of patients with a bleeding source within reach of routine endoscopy but missed during pre-CE endoscopy was significantly higher for those patients having endoscopy only in the community (30% [eight of 27]) versus in the authors' centre (0% [zero of 19]). CONCLUSIONS: CE was valuable for diagnosing bleeding lesions not only within the small bowel, but also in the stomach and colon. However, "second-look" endoscopy may be considered before ordering CE for obscure GI bleeding when local expertise is available.

Capsule endoscopy findings in patients with established and suspected small-bowel Crohn's disease: correlation with radiologic, endoscopic, and histologic findings.

BACKGROUND: Little is known about the accuracy of capsule endoscopy (CE) in evaluation of small-bowel Crohn's disease. METHODS: Symptomatic eligible patients had ileocolonoscopy and biopsies from the terminal ileum, followed by small-bowel radiologic studies before CE. Endoscopic, radiologic, CE, and histologic findings were compared. Histology (terminal ileum biopsy specimens or a tissue sample after small-bowel resection) served as a criterion standard. RESULTS: Fifty-four patients were enrolled; 15 of the 54 patients were excluded from data analysis (critical small-bowel strictures, 14, identified on radiology; incomplete CE, 1). Data were analyzed for 39 patients. All patients had histologic evaluation of the small bowel. Final diagnosis of active small-intestine Crohn's disease was made in 29/39 patients (74.4%). When calculated, CE yielded a sensitivity and a specificity of 89.6% and 100.0%, respectively, and a positive predictive value and a negative predictive value of 100.0% and 76.9%, respectively, whereas small-bowel series were 27.6%/100.0% and 100.0%/32.3%. CONCLUSIONS: CE is more accurate in detecting small-bowel inflammatory changes suggestive of Crohn's disease than conventional studies. CE, combined with ileocolonoscopy, may be proposed as a first-line investigation of the small intestine in cases of uncomplicated known or suspected Crohn's disease.

Given capsule endoscopy in celiac disease: evaluation of diagnostic accuracy and interobserver agreement.

BACKGROUND AND AIMS: Capsule endoscopy (CE) has been increasingly used for diagnosing diseases of the small bowel. It is an attractive technique for assessing celiac disease (CD) because it is noninvasive and provides a close and magnified view of the mucosa of the entire small bowel. In this study, we evaluated the accuracy of CE and interobserver agreement in recognizing villous atrophy (VA) using histopathology as the reference. We also explored the extent of small bowel involvement with CD and the relationship between the length of the affected bowel and the clinical presentation. METHODS: Ten CD patients with histologically proven VA and the same number of controls were subjected to CE. Four, blinded to histology findings, investigators (two with and two without prestudy CE experience) were asked to diagnose VA on CE images. RESULTS: Based on assessment of all four investigators, the overall sensitivity, specificity, PPV, and NPV of CE in diagnosing VA were 70%, 100%, 100%, and 77%, respectively. The sensitivity and the specificity of the test was 100% when the reports of experienced capsule endoscopists only were analyzed. The interobserver agreement was perfect (kappa= 1.0) between investigators with prestudy CE experience and poor (kappa= 0.2) between the investigators who had limited prestudy exposure to CE. Celiac patients with extensive small bowel involvement had typical symptoms of malabsorption (diarrhea, weight loss) as opposed to mild and nonspecific symptoms in patients whose disease was limited to the proximal small bowel. CE was tolerated well by all study participants with 95% reporting absence of any discomfort. CONCLUSIONS: Although based on a small sample size, the study suggests that CE may be useful in assessing patients with CD. Familiarity with CE technology appears to be a critical factor affecting the accuracy of the test. Larger studies are warranted to more precisely define the advantages and limitations of CE in CD.