Cumulative burden of inflammation predicts colorectal neoplasia risk in ulcerative colitis: a large single-centre study

Abstract

ObjectiveUlcerative 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.DesignThis 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.ResultsA 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).ConclusionThe 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.

No Association Between Pseudopolyps and Colorectal Neoplasia in Patients With Inflammatory Bowel Diseases

“…3,5,6 Commonly referred to as "pseudopolyps," PIPs are encountered in 20%-45% of patients with IBD and colonic involvement. [7][8][9][10] Previous case-control studies reported a 1.9-to 2.5-fold increased risk of CRC in patients with PIPs. 8,9,11 More recently, however, in a large retrospective cohort study of patients with ulcerative colitis (UC) undergoing CRN surveillance, PIPs did not independently predict CRN or predict progression from low-grade dysplasia (LGD) to advanced CRN (ACRN; defined as high-grade dysplasia [HGD] or CRC).…”

Systematic review with meta‐analysis: biologics and risk of infection or cancer in elderly patients with inflammatory bowel disease

“…Since old people show an increased baseline risk of infections and cancer, older patients are less likely to receive biologics . Additionally, the risk of infection and cancer is associated with disease activity . For these reasons, collecting and appraising the evidence concerning the potential harms associated with use of biologics in elderly IBD patients is very important .…”

Systematic review with meta‐analysis: high prevalence and cost of continued aminosalicylate use in patients with ulcerative colitis escalated to immunosuppressive and biological therapies

“…While endoscopic surveillance for dysplasia is a key component of chronic UC management, field cancerisation effects secondary to inflammation may be more effectively attenuated by chemoprevention. Recent work suggests that it is cumulative inflammatory burden which contributes to development of CRC, thus in theory any drug preventing inflammation might mediate this risk . Whether there are specific chemopreventive benefits for aminosalicylates is unclear .…”

“…Recent work suggests that it is cumulative inflammatory burden which contributes to development of CRC, thus in theory any drug preventing inflammation might mediate this risk. 66 Whether there are specific chemopreventive benefits for aminosalicylates is unclear. 67 It has been hypothesised that aminosalicylates may specifically reduce colorectal dysplasia risk secondary to activation of peroxisome proliferator-activated receptor-γ, 68 free radical scavenging, 69 or inhibition of the Wnt/β-catenin pathway.…”