Risk Factors Associated With Small Bowel Adenocarcinoma in Crohn's Disease
Risk Factors Associated With Small Bowel Adenocarcinoma in Crohn's Disease
Background and Aims: It is well established that Crohn's disease (CD) is associated with an increased risk of small bowel adenocarcinoma (SBA). The data concerning SBA risk factors in CD are scanty. The aim of this study was to identify them.
Methods: In 11 French centers affiliated with the GETAID (Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif), we identified 29 patients with CD and SBA. Eighty-seven CD controls without SBA recruited in a single center were matched to the cases for sex, age, duration, and CD site. A conditional logistic regression, taking into account the matching between cases and controls, was performed.
Results: In univariate analysis, the cases had had significantly less small bowel resection and received prolonged treatment with salicylates (more than 2 yr), less often than the controls (odds ratio, OR [95% confidence interval, CI] 0.07 [0.01–0.32] and 0.29 [0.10–0.82], respectively). In multivariate analysis, both associations remained significant (OR 0.04 [0.01–0.28], P = 0.001; OR 0.16 [0.03–0.79], P = 0.02, respectively).
Conclusion: This study suggests that small bowel resection and prolonged salicylates use may protect against SBA in CD patients.
Colorectal cancer (CRC) in ulcerative colitis (UC) has been thoroughly studied. However, there have been relatively few studies dedicated to small bowel adenocarcinoma (SBA) in Crohn's disease (CD). It is well established that there is an increased risk of SBA in patients with CD. A recent meta-analysis of five population-based cohort studies has shown that ratios of observed to expected SBA rates in CD patient cohorts ranged from 3.4 to 66.7, giving a 27-fold increased overall risk of SBA in CD patients (standardized incidence ratio 27.1, 95% confidence interval [CI] 14.9–49.2). In another meta-analysis pooling population-based as well as hospital or specialist center-based series, the overall pooled estimate of relative risk of SBA in CD was found to be 33.2 (95% CI 15.9–60.9). According to one population-based study where the standardized incidence ratio estimate was as high as 200, the SBA risk increase could be even higher in patients with ileal CD (95% CI 54–512). Given the extremely low incidence of SBA in the general population, it is thought that even this large relative risk does not result in a high rate of SBA. However, in a recent study, based upon a hospital cohort of 1,935 patients with small bowel involvement, the cumulative risk of SBA in CD (95% CI) was estimated to be 2 (0–8) and 22 per 1,000 patients (7–64) after 10 and 25 yr of follow-up, respectively. In the same series, SBA accounted for 50% and 66% of the risk of gastrointestinal carcinoma after 10 and 25 yr of small bowel CD, respectively. Similarly, in the Copenhagen county population-based study, 4 out of 7 intestinal cancers observed in 374 patients after a median time of 17 yr were SBA.
In clinical practice, SBA often presents as an ominous surprise, after a median time of 15 yr from CD diagnosis (range 0–37 yr). In most cases, SBA diagnosis is not suspected preoperatively and is made either during laparotomy or by the pathological examination of the ileal resection specimen in a patient with longstanding, but recently aggravated, ileal CD. The median survival is only 24 months and the median age is 46 yr, 21 yr less than the median age of SBA cases in the general population.
Thus, SBA seems to be more common than previously thought, occurs in young patients, and carries a poor prognosis. Considerable progress is needed in the prevention, screening, diagnosis, and therapy of SBA in CD patients. The identification of risk factors is a prerequisite for defining screening and prevention strategies. The aim of the present study was to define SBA risk factors in CD patients. To achieve this goal, we performed a case–control study in which we compared CD patients, with or without SBA, in a ratio of 3 controls (patients without SBA) for one case (patient with SBA).
Abstract and Introduction
Abstract
Background and Aims: It is well established that Crohn's disease (CD) is associated with an increased risk of small bowel adenocarcinoma (SBA). The data concerning SBA risk factors in CD are scanty. The aim of this study was to identify them.
Methods: In 11 French centers affiliated with the GETAID (Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif), we identified 29 patients with CD and SBA. Eighty-seven CD controls without SBA recruited in a single center were matched to the cases for sex, age, duration, and CD site. A conditional logistic regression, taking into account the matching between cases and controls, was performed.
Results: In univariate analysis, the cases had had significantly less small bowel resection and received prolonged treatment with salicylates (more than 2 yr), less often than the controls (odds ratio, OR [95% confidence interval, CI] 0.07 [0.01–0.32] and 0.29 [0.10–0.82], respectively). In multivariate analysis, both associations remained significant (OR 0.04 [0.01–0.28], P = 0.001; OR 0.16 [0.03–0.79], P = 0.02, respectively).
Conclusion: This study suggests that small bowel resection and prolonged salicylates use may protect against SBA in CD patients.
Introduction
Colorectal cancer (CRC) in ulcerative colitis (UC) has been thoroughly studied. However, there have been relatively few studies dedicated to small bowel adenocarcinoma (SBA) in Crohn's disease (CD). It is well established that there is an increased risk of SBA in patients with CD. A recent meta-analysis of five population-based cohort studies has shown that ratios of observed to expected SBA rates in CD patient cohorts ranged from 3.4 to 66.7, giving a 27-fold increased overall risk of SBA in CD patients (standardized incidence ratio 27.1, 95% confidence interval [CI] 14.9–49.2). In another meta-analysis pooling population-based as well as hospital or specialist center-based series, the overall pooled estimate of relative risk of SBA in CD was found to be 33.2 (95% CI 15.9–60.9). According to one population-based study where the standardized incidence ratio estimate was as high as 200, the SBA risk increase could be even higher in patients with ileal CD (95% CI 54–512). Given the extremely low incidence of SBA in the general population, it is thought that even this large relative risk does not result in a high rate of SBA. However, in a recent study, based upon a hospital cohort of 1,935 patients with small bowel involvement, the cumulative risk of SBA in CD (95% CI) was estimated to be 2 (0–8) and 22 per 1,000 patients (7–64) after 10 and 25 yr of follow-up, respectively. In the same series, SBA accounted for 50% and 66% of the risk of gastrointestinal carcinoma after 10 and 25 yr of small bowel CD, respectively. Similarly, in the Copenhagen county population-based study, 4 out of 7 intestinal cancers observed in 374 patients after a median time of 17 yr were SBA.
In clinical practice, SBA often presents as an ominous surprise, after a median time of 15 yr from CD diagnosis (range 0–37 yr). In most cases, SBA diagnosis is not suspected preoperatively and is made either during laparotomy or by the pathological examination of the ileal resection specimen in a patient with longstanding, but recently aggravated, ileal CD. The median survival is only 24 months and the median age is 46 yr, 21 yr less than the median age of SBA cases in the general population.
Thus, SBA seems to be more common than previously thought, occurs in young patients, and carries a poor prognosis. Considerable progress is needed in the prevention, screening, diagnosis, and therapy of SBA in CD patients. The identification of risk factors is a prerequisite for defining screening and prevention strategies. The aim of the present study was to define SBA risk factors in CD patients. To achieve this goal, we performed a case–control study in which we compared CD patients, with or without SBA, in a ratio of 3 controls (patients without SBA) for one case (patient with SBA).
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