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

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

Roopali Bansal Gupta, Noam Harpaz‡, Itzkowitz§, Sabera Hossain, Sierra Matula¶, Asher Kornbluth§, Carol Bodian and Ullman§, , Department of Biomathematical Sciences, The Mount Sinai School of Medicine, New York, New York‡Department of Pathology, The Mount Sinai School of Medicine, New York, New YorkDepartment of Medicine, The University of Texas Southwestern, Dallas, Texas§The Dr Henry D. Janowitz Division of Gastroenterology, Department of Medicine, The Mount Sinai School of Medicine, New York, New York¶Department of Surgery, The University of California San Francisco, San Francisco, California Received 9 October 2006; accepted 14 June 2007. Available online 2 August 2007.

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.

Abbreviations: HAI, histologic activity index; HGD, high-grade dysplasia; IS, inflammatory score; IS-bin, binary inflammatory score; IS-max, maximum inflammatory score; IS-mean, mean inflammatory score; LGD, low-grade dysplasia; UC, ulcerative colitis

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.)Address requests for reprints to: Ullman, MD, The Dr Henry D. Janowitz Division of Gastroenterology, Box 1069, The Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, New York 10029. fax: .

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