Increased epithelial gaps in the small intestine are predictive of hospitalization and surgery in patients with inflammatory bowel disease

Jean-Francois Turcotte, Karen Wong, Stephanie J Mah, Levinus A Dieleman, Dina Kao, Karen Kroeker, Brian Claggett, John R Saltzman, Eytan Wine, Richard N Fedorak, Julia J Liu, Jean-Francois Turcotte, Karen Wong, Stephanie J Mah, Levinus A Dieleman, Dina Kao, Karen Kroeker, Brian Claggett, John R Saltzman, Eytan Wine, Richard N Fedorak, Julia J Liu

Abstract

Objectives: Epithelial gaps resulting from intestinal cell extrusions can be visualized with confocal laser endomicroscopy (CLE) during colonoscopy and increased in normal-appearing terminal ileum of inflammatory bowel disease (IBD) patients. Cell-shedding events on CLE were found to be predictive of disease relapse. The aim of this study was to assess the prognostic value of epithelial gap densities for major clinical events (hospitalization or surgery) in follow-up.

Methods: We prospectively followed IBD patients undergoing colonoscopy with probe-based CLE (pCLE) for clinical events including symptom flares, medication changes, hospitalization, or surgery. Survival analysis methods were used to compare event times for the composite outcome of hospitalization or surgery using log-rank tests and Cox proportional hazards models. We also examined the relationship of gap density with IBD flares, need for anti-tumor necrosis factor therapy, disease duration, gender and endoscopic disease severity, and location.

Results: A total of 21 Crohn's disease and 20 ulcerative colitis patients with a median follow-up of 14 (11-31) months were studied. Patients with elevated gap density were at significantly higher risk for hospitalization or surgery (log-rank test P=0.02). Gap density was a significant predictor for risk of major events, with a hazard ratio of 1.10 (95% confidence interval=1.01, 1.20) associated with each increase of 1% in gap density. Gap density was also correlated with IBD disease duration (Spearman's correlation coefficient rho=0.44, P=0.004), and was higher in male patients (9.0 vs. 3.6 gaps per 100 cells, P=0.038).

Conclusions: Increased epithelial gaps in the small intestine as determined by pCLE are a predictor for future hospitalization or surgery in IBD patients.

Figures

Figure 1
Figure 1
Kaplan–Meier plot of event-free survival probabilities in inflammatory bowel disease (IBD) patients with normal and elevated gap densities following probe-based confocal laser endomicroscopy.
Figure 2
Figure 2
Hazard ratio associated with epithelial gap density as a continuous predictor from the Cox proportional hazards model (P=0.034).
Figure 3
Figure 3
Distribution of intestinal epithelial gap densities as a function of disease duration for inflammatory bowel disease (IBD) patients. Epithelial gap density is expressed as the number of epithelial gaps per 100 cells counted. P=0.004.
Figure 4
Figure 4
Comparison of epithelial gap density of the small intestine for male and female inflammatory bowel disease (IBD) patients. *P=0.038.

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