Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease.

OBJECTIVES: Loss of intestinal barrier function plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Shedding of intestinal epithelial cells is a potential cause of barrier loss during inflammation. The objectives of the study were (1) to determine whether cell shedding and barrier loss in humans can be detected by confocal endomicroscopy and (2) whether these parameters predict relapse of IBD. METHODS: Confocal endomicroscopy was performed in IBD and control patients using intravenous fluorescein to determine the relationship between cell shedding and local barrier dysfunction. A grading system based on appearances at confocal endomicroscopy in humans was devised and used to predict relapse in a prospective pilot study of 47 patients with ulcerative colitis and 11 patients with Crohn's disease. RESULTS: Confocal endomicroscopy in humans detected shedding epithelial cells and local barrier defects as plumes of fluorescein effluxing through the epithelium. Mouse experiments demonstrated inward flow through some leakage-associated shedding events, which was increased when luminal osmolarity was decreased. In IBD patients in clinical remission, increased cell shedding with fluorescein leakage was associated with subsequent relapse within 12 months after endomicroscopic examination (p<0.001). The sensitivity, specificity and accuracy for the grading system to predict a flare were 62.5% (95% CI 40.8% to 80.4%), 91.2% (95% CI 75.2 to 97.7) and 79% (95% CI 57.7 to 95.5), respectively. CONCLUSIONS: Cell shedding and barrier loss detected by confocal endomicroscopy predicts relapse of IBD and has potential as a diagnostic tool for the management of the disease.

Urgent endoscopy is associated with lower mortality in high-risk but not low-risk nonvariceal upper gastrointestinal bleeding.

BACKGROUND AND STUDY AIMS: The role of urgent endoscopy in high-risk nonvariceal upper gastrointestinal bleeding (NVUGIB) is unclear. The aim of this study was to determine whether esophagogastroduodenoscopy (EGD) performed sooner than the currently recommended 24 h in high-risk patients presenting with NVUGIB is associated with lower all-cause in-hospital mortality. METHODS: All adult patients undergoing EGD for the indications of coffee-grounds vomitus, hematemesis or melena at a university hospital over an 18-month period were enrolled. Patients with variceal and lower gastrointestinal bleeding were excluded. Data were prospectively collected. RESULTS: A total of 934 patients were included. The area under the receiver operating characteristic curve (AUROC) for the Glasgow-Blatchford score (GBS) was 0.813 for predicting all-cause in-hospital mortality, with a cut-off score of ≥ 12 resulting in 90 % specificity. In low-risk patients with GBS < 12, presentation-to-endoscopy time in those who died and in those who survived was similar. In high-risk patients with GBS of ≥ 12, presentation-to-endoscopy time was significantly longer in those who died than in those who survived. Multivariate analysis of the high-risk cohort showed presentation-to-endoscopy time to be the only factor associated with all-cause in-hospital mortality. For high-risk patients, the AUROC for presentation-to-endoscopy time in predicting all-cause in-hospital mortality was 0.803, with a sensitivity of 100 % at the cut-off time of 13 h. All-cause in-hospital mortality in high-risk patients was significantly higher in those with presentation-to-endoscopy time of > 13 h compared with those undergoing endoscopy in < 13 h from presentation (44 % vs. 0 %; P < 0.001). CONCLUSIONS: Endoscopy within 13 h of presentation was associated with lower mortality in high-risk but not low-risk NVUGIB.

Fluorescein-enhanced autofluorescence imaging for accurate differentiation of neoplastic from non-neoplastic colorectal polyps: a feasibility study.

BACKGROUND: Autofluorescence imaging (AFI) is sensitive but not specific for differentiating neoplastic from non-neoplastic colorectal polyps. We aimed to determine the sensitivity and specificity of fluorescein-enhanced AFI (FAFI) in differentiating neoplastic from non-neoplastic colorectal polyps. METHODS: All patients with colorectal polyps detected during AFI colonoscopy received intravenous fluorescein followed by AFI (FAFI). The video sequences were recorded and divided into a learning group and a test group. AFI and FAFI criteria for neoplastic and non-neoplastic lesions were determined after viewing videos in the learning group unblinded to histology. Videos in the test group were viewed blinded to histology, and diagnoses of neoplastic versus non-neoplastic were made for AFI and FAFI using the predetermined criteria. Still frames were objectively measured for red:green ratio (AFI) and green contrast (FAFI). RESULTS: Eight videos (four neoplastic, four non-neoplastic) were used for the learning group. Criteria for neoplasia when using FAFI were determined as the presence of a patchy or granular pattern which appeared more fluorescent green compared with the background. For AFI, purple or pink represented neoplasia; green represented non-neoplasia. In the test group (13 neoplastic, 12 non-neoplastic), for differentiating between neoplasia and non-neoplasia, subjective analysis of video sequences yielded a sensitivity of 100 % for AFI and 100 % for FAFI ( P = 1.000), and a specificity of 16.7 % for AFI and 91.7 % for FAFI ( P = 0.004). Using objective color analysis, the area under the receiver operating characteristics curve was 0.647 for AFI using the red:green ratio to distinguish between neoplasia and non-neoplasia, and 0.994 for FAFI using green contrast. CONCLUSIONS: FAFI accurately differentiated between neoplastic and non-neoplastic colorectal polyps.

Recurrent lower gastrointestinal bleeding secondary to cytomegalovirus-associated colonic ulcer in a non human immunodeficiency virus infected patient: timely diagnosis and treatment averted surgery.

Mr C, a 68-year-old Chinese male with diabetes mellitus, previous stroke and ischaemic cardiomyopathy on clopidogrel, presented with haematochezia. Colonoscopy showed a sigmoid ulcer, which was treated endoscopically. Histology of the biopsy from the ulcer revealed non-specific changes. However, he presented with recurrent bleeding from this non-healing sigmoid ulcer. A review of the histologic specimen revealed CMV intranuclear inclusion bodies. He was treated with intravenous ganciclovir, with no further hematochezia.