P651. Association between Crohn's disease and small bowel cancers: a Danish nationwide population based study
R.D. Bojesen1, L.B. Riis2, O.H. Nielsen3, T. Jess1, 1Statens Serum Institut, Department of Epidemiology Research, Copenhagen, Denmark, 2Herlev Hospital, University of Copenhagen, Department of Pathology, Herlev, Denmark, 3Herlev Hospital, University of Copenhagen, Department of Gastroenterology, Medical Section, Herlev, Denmark
Small bowel cancers (SBC) are rare, with approximately 100 annual cases in Denmark. An association between SBC and Crohn's disease (CD) was first described in 1956, and a meta-analysis of population based studies has suggested a 27-fold increased relative risk of SBC in CD. However, this mentioned analysis was based on only 13 cases worldwide. We assessed the risk of SBC in a nationwide population-based IBD cohort. Cases were further characterized through review of medical records and pathological re-examination of all resection specimens.
By combining the Danish National Patient Registry (NPR) with The Danish Cancer Registry (DCR) and the Danish Pathology Registry (DPR), we initially identified 147 potential cases of SBC in Danish patients with IBD within the period 1978–2010. Medical records where obtained for 146 cases and were evaluated through manual scrutiny, leaving 40 confirmed cases, of which 24 were adenocarcinomas. Available resection specimens of confirmed adenocarcinomas were re-examined with special focus on adjacent inflammation and dysplasia. The risk of SBC in IBD patients was estimated using standardized incidence ratios (SIR), comparing the observed number of SBCs in IBD cases with the expected number based on national rates adjusted for age, sex, and calendar period.
During 131 million person years of observation, 21 CD patients developed small bowel adenocarcinomas in the ileum or jejunum resulting in a 23-fold increased risk (SIR 23.5, 95% CI: 14.6–36.0). Nine CD patients developed carcinoid tumours resulting in a 6-fold increased risk (SIR 6.6, 95% CI: 3.0–12.5). CD patients were not at increased risk of sarcomas, nor were patients with ulcerative colitis at increased risk of SBCs. Of the 21 CD associated adenocarcinomas severe inflammation was found in 13 (62%), moderate inflammation in 3 (14%), mild in 2 (10%), and 1 (5%) case was in remission.
This is the hitherto largest population-based study evaluating the risk of SBC in IBD, and the first to include an additional systematic pathological reevaluation of the material. Our findings show that the risk of small bowel adenocarcinomas in CD is increased 23-fold. Furthermore, the pathological re-evaluation suggests that severity of inflammation is a central part of carcinogenesis in CD associated SBCs, similar to what is known for colorectal cancer in IBD.