Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study.
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.
Gupta
Roopali Bansal
RB
Department of Medicine, The University of Texas Southwestern, Dallas, Texas, USA.
Harpaz
Noam
N
Itzkowitz
Steven
S
Hossain
Sabera
S
Matula
Sierra
S
Kornbluth
Asher
A
Bodian
Carol
C
Ullman
Thomas
T
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