Gastroenterology

Gastroenterology

Volume 133, Issue 4, October 2007, Pages 1099-1105
Gastroenterology

Clinical–alimentary tract
Histologic Inflammation Is a Risk Factor for Progression to Colorectal Neoplasia in Ulcerative Colitis: A Cohort Study

https://doi.org/10.1053/j.gastro.2007.08.001Get rights and content

Background & Aims: Although inflammation is presumed to contribute to colonic neoplasia in ulcerative colitis (UC), few studies have directly examined this relationship. Our aim was to determine whether severity of microscopic inflammation over time is an independent risk factor for neoplastic progression in UC. Methods: A cohort of patients with UC undergoing regular endoscopic surveillance for dysplasia was studied. Degree of inflammation at each biopsy site had been graded as part of routine clinical care using a highly reproducible histologic activity index. Progression to neoplasia was analyzed in proportional hazards models with inflammation summarized in 3 different ways and each included as a time-changing covariate: (1) mean inflammatory score (IS-mean), (2) binary inflammatory score (IS-bin), and (3) maximum inflammatory score (IS-max). Potential confounders were analyzed in univariate testing and, when significant, in a multivariable model. Results: Of 418 patients who met inclusion criteria, 15 progressed to advanced neoplasia (high-grade dysplasia or colorectal cancer), and 65 progressed to any neoplasia (low-grade dysplasia, high-grade dysplasia, or colorectal cancer). Univariate analysis demonstrated significant relationships between histologic inflammation over time and progression to advanced neoplasia (hazard ration (HR), 3.0; 95% CI: 1.4–6.3 for IS-mean; HR, 3.4; 95% CI: 1.1–10.4 for IS-bin; and HR, 2.2; 95% CI: 1.2–4.2 for IS-max). This association was maintained in multivariable proportional hazards analysis. Conclusions: The severity of microscopic inflammation over time is an independent risk factor for developing advanced colorectal neoplasia among patients with long-standing UC.

Section snippets

Materials and Methods

Following approval by The Mount Sinai School of Medicine Institutional Review Board and in accordance with Health Insurance Portability and Accountability Act guidelines, our research group established a UC surveillance database. This database contains all patients in the Mount Sinai Hospital gastrointestinal pathology and surgical pathology registries who had undergone at least 1 surveillance colonoscopy between January 1996 and December 1997, a period chosen to allow for long-term follow-up.

Results

Of 543 UC patients who underwent surveillance colonoscopy between 1996 and 1997, 125 patients were excluded for having dysplasia at their first colonoscopy at our institution, lack of histologic follow-up, or prior colorectal surgery, leaving a cohort of 418 patients with no initial dysplasia. The demographic characteristics of the cohort and their surveillance patterns and medication use are provided in Table 2. Over 90% of patients had extensive colitis, and the median duration of UC was 16

Discussion

Few studies have addressed the severity of colonic inflammation over time as an independent risk factor for progression to neoplasia. Two attempts to determine whether the risk of CRC was associated with frequency of clinical exacerbations found no such relationship.19, 20 Rutter et al, however, successfully demonstrated a correlation between histologic inflammation and neoplastic progression in a case-control study involving 68 cases and 136 matched controls.13 They also showed that endoscopic

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    There are no conflicts of interest to disclose in relation to this manuscript.

    Supported by grants from the Doris Duke Foundation (to R.B.G. and S.M.), the American College of Gastroenterology (to T.U.), and the National Institutes of Health (K-08-DK069393; to T.U.)

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