Objective Ulcerative colitis (UC) is a dynamic disease with its severity continuously changing over time. We hypothesised that the risk of colorectal neoplasia (CRN) in UC closely follows an actuarial accumulative inflammatory burden, which is inadequately represented by current risk stratification strategies.
Design This was a retrospective single-centre study. Patients with extensive UC who were under colonoscopic surveillance between 2003 and 2012 were studied. Each surveillance episode was scored for a severity of microscopic inflammation (0=no activity; 1=mild; 2=moderate; 3=severe activity). The cumulative inflammatory burden (CIB) was defined as sum of: average score between each pair of surveillance episodes multiplied by the surveillance interval in years. Potential predictors were correlated with CRN outcome using time-dependent Cox regression.
Results A total of 987 patients were followed for a median of 13 years (IQR, 9-18), 97 (9.8%) of whom developed CRN. Multivariate analysis showed that the CIB was significantly associated with CRN development (HR, 2.1 per 10-unit increase in CIB (equivalent of 10, 5 or 3.3 years of continuous mild, moderate or severe active microscopic inflammation); 95% CI 1.4 to 3.0; P<0.001). Reflecting this, while inflammation severity based on the most recent colonoscopy alone was not significant (HR, 0.9 per-1-unit increase in severity; 95% CI 0.7 to 1.2; P=0.5), a mean severity score calculated from all colonoscopies performed in preceding 5 years was significantly associated with CRN risk (HR, 2.2 per-1-unit increase; 95% CI 1.6 to 3.1; P<0.001).
Conclusion The risk of CRN in UC is significantly associated with accumulative inflammatory burden. An accurate CRN risk stratification should involve assessment of multiple surveillance episodes to take this into account.
- colorectal cancer screening
- colorectal neoplasia
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TAG and ALH are co-senior authors.
IAB, N-S(J)D, G-HL and AA contributed equally.
Contributors C-HRC: study concept and design, acquisition of data, analysis and interpretation of data, drafting of manuscript, obtained funding and statistical analysis. IAB, N-SD, AA, G-HL: acquisition of data and statistical analysis. JW, MM, AH, AIW, ST-G, MDR, and BPS: study concept, design and critical revision of manuscript for important intellectual content. TAG: study concept and design, critical revision of manuscript for important intellectual content, statistical analysis, obtained funding and study supervision. ALH: study concept and design, critical revision of manuscript for important intellectual content, analysis and interpretation of data, obtained funding and study supervision.
Funding The authors acknowledge funding from Cancer Research UK (A19771 to TAG), the Wellcome Trust (202778/Z/16/Z to TAG) and the Barts Charity (472/2300 to TAG). C-HRC was funded by a studentship from the Derek Willoughby Fund for Inflammatory Research, and IAB is funded by a studentship from the UK Medical Research Council.
Competing interests None declared.
Ethics approval National Research Ethics Committee and Northwest London Hospitals NHS Trust (reference number, 17/EM/0289); East Midlandsâ€”Derby Research Ethics Committee, UK.
Provenance and peer review Not commissioned; externally peer reviewed.
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