Abstract Background Ulcerative colitis (UC) confers an increased risk of dysplasia and colorectal cancer (CRC), largely driven by sustained mucosal inflammation1,2,3. While inflammatory burden is a known risk factor4, the specific impact of repeated endoscopic inflammation and contemporary therapies exposure warrant further investigation. We aimed to investigate the impact of cumulative inflammation in the risk of dysplasia and CRC development in UC. Methods We performed a retrospective cohort study of adult UC patients diagnosed between 1975 and 2023 at a tertiary inflammatory bowel disease (IBD) center. Repeated colonoscopies were analyzed using the Andersen-Gill extension of the Cox proportional hazards model. Propensity score matching (1:2 ratio) was applied based on age at diagnosis, sex, smoking status, disease duration and extent to adjust for confounding. Results A total of 571 patients and 1614 colonoscopies were included. There were 304 (53.2%) men, with a median age at diagnosis of 39.5 years (IQR 27.3–54.2) and a median follow-up of 7.1 years (IQR 3.7–13.3). At diagnosis, 147 patients (25.7%) had proctitis, 203 (35.6%) had left-sided colitis and 191 (33.5%) had extensive colitis. During follow-up 56 (9.8%) developed dysplasia or CRC. Advanced therapy was used in 152 patients (26.8%). In the propensity-matched cohort (n = 123), repeated higher endoscopic inflammation measured by Mayo endoscopic score (adjusted HR: 1.600; 95% CI: 1.082–2.366; p = 0.019), family history of CRC (adjusted HR 1.518; 95% CI: 1.011-2.290, p = 0.039) and exposure to advanced therapies (adjusted HR 2.048; 95% CI: 1.392-3.013, p 0.001) were associated with higher dysplasia/CRC risk. Conclusion Our findings indicate that repeated endoscopic inflammation, a family history of CRC, and the use of advanced therapy are associated with an elevated risk of dysplasia and CRC in adult UC patients. References: 1. Gros B, Kaplan GG. Ulcerative Colitis in Adults: A Review. JAMA. 2023;330(10):951-965. doi:10.1001/jama.2023.15389 2. Castaño-Milla C, Chaparro M, Gisbert JP. Systematic review with meta-analysis: the declining risk of colorectal cancer in ulcerative colitis. Aliment Pharmacol Ther. 2014;39(7):645-659. doi:10.1111/apt.12651 3. Shah SC, Itzkowitz SH. Colorectal Cancer in Inflammatory Bowel Disease: Mechanisms and Management. Gastroenterology. 2022;162(3):715-730.e3. doi:10.1053/j.gastro.2021.10.035 4. Choi CHR, Al Bakir I, Ding NS (John), et al. Cumulative burden of inflammation predicts colorectal neoplasia risk in ulcerative colitis: a large single-centre study. Gut. 2019;68(3):414-422. doi:10.1136/gutjnl-2017-314190 Conflict of interest: Jiménez Recio, Lucía: I have recieved support for travel for meetings to support study from Lilly and Janssen. Trigo Bonachera, Manuel: No conflict of interest Valdivia Krag, Carlos: No conflict of interest Mirabent Moreno, Carlos: No conflict of interest González Castilla, Lourdes: No conflict of interest Benítez Cantero, José Manuel: José Manuel Benítez has served as an speaker, consultant and advisory member or has recieved grants or honoraria for scientific activities and presentations from Dr Falk Pharma, Faes Farma, Ferring, Shire Pharmaceuticals, Chiesi, Tillots Pharma, MSD, Abbvie, Takeda, Janssen, Gilead, Pfizer, Adacyte, Galápagos, Lilly and Alfasigma. Marin Pedrosa, Sandra: No conflict of interest Soto Escribano, Pilar: No conflict of interest Iglesias Flores, Eva: Eva Iglesias Flores has served as an speaker, consultant and advisory member or has recieved research funding from Abbvie, Janssen, Takeda, Gillead, Celgene, Pfizer, Lilly, Ferring, Faes Farma, Dr Falk Pharma, Chiesi and Adacyte. Gros, Beatriz: Beatriz Gros has served as a speaker for Abbvie, Johnson and Johnson, Takeda, Roche, Gilead, Pfizer and Galapagos and has served as an advisor for Roche, Gilead, Abbvie, Galapagos and Takeda
Recio et al. (Thu,) studied this question.