title: Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Medicine, The University of Texas Southwestern, Dallas, Texas, USA.
authors.forename: Roopali Bansal
authors.initials: RB
authors.lastname: Gupta
authors.forename: Noam
authors.initials: N
authors.lastname: Harpaz
authors.forename: Steven
authors.initials: S
authors.lastname: Itzkowitz
authors.forename: Sabera
authors.initials: S
authors.lastname: Hossain
authors.forename: Sierra
authors.initials: S
authors.lastname: Matula
authors.forename: Asher
authors.initials: A
authors.lastname: Kornbluth
authors.forename: Carol
authors.initials: C
authors.lastname: Bodian
authors.forename: Thomas
authors.initials: T
authors.lastname: Ullman
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000150:complications* / Q000473:pathology; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000473:pathology; D019992:Databases as Topic; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000473:pathology; D008297:Male; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors