Inflammation and disease duration have a cumulative effect on the risk of dysplasia and carcinoma in IBD: A case–control observational study based on registry data

Abstract

Patients with long-standing inflammatory bowel disease (IBD) have an increased risk for colorectal carcinoma (CRC). Earlier studies suggest that the severity of inflammation is an independent risk factor for CRC in ulcerative colitis (UC). We investigated the role of histological inflammation as a risk factor for colorectal dysplasia or CRC to better target dysplasia surveillance in IBD. By combining our hospital patient registry and pathology database between 1996 and 2008, we identified 183 IBD patients with dysplasia or CRC. The control group was collected from our registry of IBD patients. Histological severe inflammation was present in 41.4% of patients with dysplasia and in 24.1% of patients with CRC, but in only 4.3% of controls. Severe inflammation had an odds ratio (OR) of 31.8 [95% confidence interval (CI): 15.6-64.9] for dysplasia or carcinoma compared to patients with no inflammation. Among patients with mild to moderate inflammation, the OR was 2.6 (95% CI: 1.6-4.1). Disease duration increased the annual risk for dysplasia or CRC by 4.5%. Coexisting primary sclerosing cholangitis (PSC) did not elevate the risk, whereas use of thiopurines (OR 5 0.09, 95% CI: 0.02-0.33) and also 5-aminosalicylic acid (OR 0.17, 95% CI: 0.017-1.01) protected against CRC. As conclusion, degree of inflammation and duration of disease cumulatively increase the risk for dysplasia and CRC. PSC was not identified as a risk factor. We demonstrated that use of thiopurines strongly protects against CRC. These results can be applied to better target dysplasia surveillance in IBD patients.

IL-15 suppresses colitis-associated colon carcinogenesis by inducing antitumor immunity

“…23,24 The role of the inflammatory milieu is of particular importance in CRC as the risk of developing dysplasia and CRC positively correlates with the duration and degree of inflammation in patients with irritable bowel disease (IBD). 25 While there is abundant evidence indicating the causal relationship of chronic mucosal inflammation with CRC, 26 the mechanism(s) underlying this correlation, namely the role of IL-15-mediated signaling, remain largely unknown.…”

Radiation therapy in patients with inflammatory bowel disease and colorectal cancer: Risks and benefits

“…The incidence of IBD has been increasing worldwide in both adult and pediatric populations [2,3]. Despite optimal medical treatment, the inflammation inherent in IBD increases the risk for high-grade colorectal dysplasia and colorectal cancers (CRC), with the duration of IBD being a significant risk factor [4][5][6]. In addition to an increased risk of developing colorectal neoplasms, patients with IBD who develop node-positive CRC may have worse outcomes and shorter overall survival when compared to patients without IBD [7].…”

Multiyear Patterns of Serum Inflammatory Biomarkers and Risk of Colorectal Neoplasia in Patients with Ulcerative Colitis

“…4 In a recent study from Finland, patients with UC and severe colonic 18 Similarly, in a study of patients with UC undergoing regular endoscopic surveillance for dysplasia, severity of histologic inflammation was associated with 3-fold increase in risk for progression to advanced CRN (high-grade dysplasia or cancer). 17 Rubin et al 5 were one of the first to report that both maximum and mean histologic disease activities are associated with CRN and that the risk of CRN increases with continuing disease activity over time.…”