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Article 4, 4/2016

ORIGINAL PAPER

Impaired Gastric Cancer Survival in Patients with Inflammatory Bowel Disease

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Loes H.C. Nissen1, Eemke L. Assendorp1, Rachel S. van der Post2, Lauranne A.A.P. Derikx1, Dirk J. de Jong1, Wietske Kievit3, Marieke Pierik4, Tim van den Heuvel4, Rob Verhoeven5, Lucy I.H. Overbeek6, Frank Hoentjen1, Iris D. Nagtegaal2.

1) Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology,
2) Department of Pathology,
3) Department for Health Evidence, Radboud University Medical Center, Nijmegen;
4) Department of Gastroenterology and Hepatology, Maastricht University Medical Center,
5) Netherlands Cancer Registry / Netherlands comprehensive cancer organization,
6) Stichting PALGA, The Netherlands.
** and ***: See appendix A and B

DOI: http://dx.doi.org/10.15403/jgld.2014.1121.254.nis

ABSTRACT
Background & Aims: Both chronic inflammation and reduced immunosurveillance contribute to malignancy development in inflammatory bowel disease (IBD). Previous literature suggests that especially Crohn’s disease patients are at an increased risk for developing gastric cancer (GC). This study aimed to identify risk factors for GC development in IBD and to compare the clinical characteristics of GC in IBD to those in the general population.

Methods: We retrospectively searched the Dutch Pathology Database to identify all Dutch IBD patients with GC between January 2004 and December 2008. Two case-control studies were performed. I: to identify risk factors for GC in IBD, with controls from the IBD South Limburg (IBDSL) population-based cohort; and II: to compare GC disease course in IBD patients with the general population. General population data were obtained from the Eindhoven Cancer Registry (ECR).

Results: We included 59 patients with IBD and GC (cases). Cases were significantly older at IBD diagnosis than IBDSL controls (median age 61 years versus 40; p<0.01), and ulcerative colitis (UC) was more frequent in the case group (69.5% versus 51.4%; p<0.01). We found no difference in age at diagnosis, gender, tumor location and tumor differentiation between IBD GC patients and ECR controls. When corrected for confounders and TNM-stage, IBD patients showed impaired survival (p=0.035; HR 1.385).

Conclusions: Survival is significantly reduced in IBD patients compared to the general population in the multivariate analysis of our study, but age at GC diagnosis and TNM-stage were comparable between IBD cases and controls. Elderly onset IBD emerged as a risk factor for GC development in IBD patients, particularly in UC.

Key words: inflammatory bowel diseases – gastric cancer – immunosuppressive therapy.

Abbreviations: CD: Crohn’s disease; EBV: Epstein-Barr virus; EBER: EBV-encoded RNA; EBER-ISH: EBV-encoded RNA – in situ hybridization; ECCO: European Crohn’s and Colitis Organization; ECR: Eindhoven Cancer Registry; GC: Gastric cancer; IBD: Inflammatory bowel disease; IBDSL cohort: Inflammatory Bowel Diseases South Limburg cohort; MMR proteins: Mismatch repair proteins; RIVM: Dutch National Institute for Public Health and Environment; UC: Ulcerative colitis.