Gastroenterology

Gastroenterology

Volume 145, Issue 1, July 2013, Pages 166-175.e8
Gastroenterology

Original Research
Full Report: Clinical—Alimentary Tract
Risk of Colorectal High-Grade Dysplasia and Cancer in a Prospective Observational Cohort of Patients With Inflammatory Bowel Disease

This work was presented in a plenary session at DDW 2009, Chicago, IL.
https://doi.org/10.1053/j.gastro.2013.03.044Get rights and content

Background & Aims

There is an unclear risk of colonic high-grade dysplasia (HGD) and colorectal cancer (CRC) among patients with inflammatory bowel disease (IBD) treated with immunosuppressants. We analyzed data on CRC development among patients with IBD enrolled in the observational cohort Cancers et Surrisque Associé aux Maladies Inflammatoires Intestinales En France (CESAME).

Methods

We followed and collected data from 19,486 patients with IBD (60.3% with Crohn's disease, 30.1% receiving thiopurine therapy) enrolled in CESAME from May 2004 and June 2005, and followed them until December 2007. When the study began, 2841 patients (14.6%) were characterized as having long-standing extensive colitis (ie, >10 years and involving ≥50% of the colon). Early lesions (HGD and CRC) were defined as those diagnosed within 10 years after diagnosis of IBD.

Results

Thirty-seven patients developed CRC during the follow-up period, and 20 developed colorectal HGD. The standardized incidence ratios of CRC were 2.2 for all IBD patients (95% confidence interval [CI]: 1.5−3.0; P < .0001), 7.0 for patients with long-standing extensive colitis (95% CI: 4.4−10.5; P < .001), and 1.1 for patients without long-standing extensive colitis (95% CI: 0.6−1.8; P = .84). Among patients with long-standing extensive colitis, the multivariate adjusted hazard ratio for colorectal HGD and cancer was 0.28 for those who received thiopurines compared with those who never received thiopurine therapy (95% CI: 0.1−0.9; P = .03). Twenty-two patients developed early lesions; 7 of these were related to IBD, based on histologic analysis.

Conclusions

Patients with IBD and long-standing extensive colitis are at increased risk for CRC, although the risk is lower among patients receiving thiopurine therapy. Patients without long-standing extensive colitis have a risk for CRC similar to that of the general population, but they can develop IBD-related lesions within 10 years after diagnosis of IBD.

Section snippets

CESAME Cohort Design and Population

Details on the design and demographics of the cohort are available elsewhere.23 In brief, from May 2004 to June 2005, six hundred and eighty French gastroenterologists (38.4% with a full-time hospital practice, 24.3% with a mixed public and private practice, and 37.3% with a full-time private practice) enrolled, on an unpaid basis, 19,486 consecutive IBD patients from their individual practices. There were no exclusion criteria.

Data were collected on an electronic case report form. The

Patient Population and Follow-up Time

The patient characteristics, according to IBD subtype and long-standing extensive colitis status are provided in Table 1. At baseline, 2841 (14.6%) IBD patient had long-standing extensive colitis and 16,645 (85.4%) patients did not have long-standing extensive colitis. Compared with patients without long-standing extensive colitis, patients with long-standing extensive colitis tended, as expected, to be older (P < .0001) and to have been younger at the time of IBD onset (P < .0001). Median

Discussion

This is the first prospective study of the epidemiology of colorectal HGD and cancer in IBD in the thiopurine era. The results show that the risk of high-grade dysplasia and CRC is still markedly elevated in IBD patients with long-standing extensive colitis, although to a lesser extent in the subset of patients receiving thiopurines. In contrast, patients without long-standing extensive colitis have a CRC risk similar to that of general population, but they can develop early IBD-related lesions.

Acknowledgments

English editing (Nature Publishing Group Language Editing) was supported by funding of the CESAME cohort.

References (42)

  • G. Van Assche et al.

    Second European evidence-based consensus on the diagnosis and management of ulcerative colitis: special situations

    J Crohns Colitis

    (2013)
  • G.C. Nguyen et al.

    A tale of two cohorts: are we overestimating the risk of colorectal cancer in inflammatory bowel disease?

    Gastroenterology

    (2012)
  • F. Carrat et al.

    Aminosalicylates, thiopurines and the risk of colorecatl cancer in inflammatory bowel diseases: a case-control study nested in the CESAME cohort

    Gastroenterology

    (2010)
  • S. Matula et al.

    Chemoprevention of colorectal neoplasia in ulcerative colitis: the effect of 6-mercaptopurine

    Clin Gastroenterol Hepatol

    (2005)
  • W.R. Connell et al.

    Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis

    Gastroenterology

    (1994)
  • B.A. Lashner et al.

    The effect of folic acid supplementation on the risk for cancer or dysplasia in ulcerative colitis

    Gastroenterology

    (1997)
  • T. Jess et al.

    Increased risk of intestinal cancer in Crohn's disease: a meta-analysis of population-based cohort studies

    Am J Gastroenterol

    (2005)
  • J.A. Eaden et al.

    The risk of colorectal cancer in ulcerative colitis: a meta-analysis

    Gut

    (2001)
  • T.A. Ullman et al.

    Intestinal inflammation and cancer

    Gastroenterology

    (2011)
  • A. Ekbom et al.

    Ulcerative colitis and colorectal cancer. A population-based study

    N Engl J Med

    (1990)
  • J. Torres et al.

    Review article: colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease

    Aliment Pharmacol Ther

    (2011)
  • Cited by (288)

    View all citing articles on Scopus

    Conflicts of interest These authors disclose the following: Laurent Beaugerie has received lecture fees from Abbott, MSD, Ferring Pharmaceuticals, and consulting fees from Abbott. Philippe Seksik has received consulting fees from Biocodex, Ferring Pharmaceutical, MSD, and Abbott. Matthieu Allez has received lecture or consulting fees from MSD, Abbott, Novo Nordisk, Ferring, Pfizer, and GSK. Hedia Brixi has received lecture and consulting fees from Abbott. Bernard Duclos has received lectures fees from Abbott, MSD, and consulting fees from Abbott and MSD. Arnaud Bourreille has received consulting or advisory board fees from Ferring Laboratories, Given Imaging, lecture fees from Abbott Laboratories, Biocodex, Merck, Norgine, Scherring-Plough, Therakos, Vifor, grant support from Abbott, Merck, and Vifor. Laurent Peyrin-Biroulet has received lecture and consulting fees from Abbott, Merck, UCB-Pharma, Tillots, Ferring, Norgine, and Shire. Fabrice Carrat has received consultancy fees from Novartis, GSK, and Laboratoires Boiron. The remaining authors disclose no conflicts.

    Funding The CESAME project was supported by grants from Programme Hospitalier de Recherche Clinique National (AOM05157), Association François Aupetit, Délégation Inter-Régionale de la Recherche Clinique Ile de France-AP-HP, Ligue Contre le Cancer, and Fonds de Recherche de la Société Nationale Française de Gastro-Entérologie.

    View full text