Risk of anorectal cancer in patients with Crohn's disease and perianal fistula: a nationwide Danish cohort study.

AIM: Patients with Crohn's disease (CD) often suffer from perianal fistulizing disease. Their risk of anorectal cancer remains uncertain. We aimed to examine the long-term risk of anorectal cancer in a population-based cohort of CD patients with anorectal fistula. METHOD: Our study population covered all individuals (n = 7 987 520) aged 15+ years living in Denmark from 1978 to 2018. We identified all patients with CD and anorectal fistula in the Danish National Patient Register (NPR) and 50 matched noninflammatory bowel disease (IBD) individuals from the general population. Using Cox regression analyses, we examined the risk of anorectal cancer in CD fistula patients versus non-IBD individuals. All patients with CD were identified using codes from the International Classification of Diseases and their data extracted from the NPR. The main outcome measure was cases of anorectal cancer. RESULTS: A total of 2786 CD patients with anorectal fistula and 139 300 non-IBD individuals were followed for 1 553 917 person-years. During follow-up, anorectal cancer was observed in 19 CD patients (0.68%) and 340 non-IBD individuals (0.24%), corresponding to a 2.9-fold increased hazard ratio (HR) of anorectal cancer in CD fistula patients (95% CI 1.80-4.53), with a particularly high risk of anal cancer (HR 15.13, 95% CI 6.88-33.31) and a mean time from CD fistula diagnosis to anorectal cancer of 6.7 (SD 6.5) years. The risk was slightly higher in women than men and had no apparent relation to treatment with tumour necrosis factor-α inhibitors. Sensitivity analyses using CD nonfistula patients for comparison revealed similar results. Individual data on smoking and infection with human papilloma virus were not available. CONCLUSION: Patients with CD and anorectal fistula have a three-fold increased risk of anorectal cancer compared with the general population. The number needed to surveil to detect one case of anorectal cancer in this patient population was 2160 patients per year in patients with long-standing fistula (>6 years).

Risk of cancer in patients with bile acid diarrhoea: a Danish nationwide matched cohort study.

OBJECTIVE: Bile acid diarrhoea is a common cause of chronic diarrhoea. Increased levels of potentially carcinogenic bile acids in faeces, theoretically, may increase the risk of colorectal cancer in particular, but the long-term disease course is unknown. We aimed to investigate the overall and site-specific cancer risk in bile acid diarrhoea. DESIGN: Adult patients with bile acid diarrhoea were identified using nationwide Danish registries from 2003 to 2020 by a diagnostic gold-standard 75-selenium tauroselcholic acid procedure followed within 6 months by sequestrant prescription. The risk of overall and site-specific cancers in cases with bile acid diarrhoea was compared with sex, age and comorbidity-adjusted matched controls. A competing risk model estimated cumulative incidence functions and cause-specific HRs. RESULTS: We identified 2260 patients with bile acid diarrhoea with a mean follow-up of 5.5 years (SD 4.2). The overall cancer risk was increased by an HR of 1.32 (95% CI 1.12 to 1.54). The risk of site-specific cancer was increased in 3 of 10 cancer groups: haematological, HR 2.41 (1.36 to 4.02); skin, HR 1.33 (1.01 to 1.71); and male genital cancers, HR 1.85 (1.11 to 2.92). No increased risk of colorectal cancer was detected in patients with bile acid diarrhoea, HR 0.73 (0.34 to 1.63). CONCLUSIONS: Bile acid diarrhoea was associated with an increased overall risk of cancer, especially haematological cancers, but the risk of colorectal cancer was not increased. The lack of a diagnostic code for bile acid diarrhoea and potential residual confounding are limitations, and the findings should be replicated in other cohorts.

Rectal Cancer Risk After Colectomy in Patients With Inflammatory Bowel Disease-A Population-Based Danish Cohort Study 1978-2018.

Background and Aims: Selected patient groups with ulcerative colitis and Crohn's disease are at increased risk of colorectal cancer. Surveillance guidelines rarely cover patients after colectomy. We performed a nationwide population-based cohort study to estimate the risk of developing rectal cancer in patients with inflammatory bowel disease after subtotal colectomy. Methods: Through the Danish Civil Registration System, a source population of all individuals living in Denmark between 1978 and 2018 was retrieved. The risk of rectal cancer in patients with diverted rectum was assessed using Cox regression analyses with comparison to both the individuals with inflammatory bowel diseases without subtotal colectomy and the background population. Results: Rectal cancer occurred in 42 of 4931 patients (0.9%) after subtotal colectomy and diverted rectum, compared to 209 of 49,251 (0.4%) in the matched inflammatory bowel diseases cohort without colectomy and 941 of 246,550 (0.4%) in the background population. The hazard ratio (HR) for rectal cancer in patients with inflammatory bowel disease and diverted rectum vs patients without colectomy was 0.76 (95% CI, 0.28, 2.07) before 10 years and 7.56 (95% CI, 5.21, 10.86) 10 years after colectomy. The HR for patients with diverted rectum compared to the background population was 0.84 (95% CI, 0.31, 2.24) and 10.01 (95% CI, 7.20, 13.94) respectively. Conclusion: In our nationwide population-based Danish cohort study, we found the risk of rectal cancer in the diverted rectum to be markedly increased 10 years postcolectomy. This calls for better long-term surveillance of colectomized patients with inflammatory bowel diseases.

Reducing BMI below the obesity threshold in adolescents treated with once-weekly subcutaneous semaglutide 2.4 mg.

OBJECTIVE: The aim of this study was to examine how improvement in BMI with the glucagon-like peptide-1 receptor agonist semaglutide translated to changes in BMI category in a post hoc analysis of the double-blind, phase 3a randomized controlled Semaglutide Treatment Effect in People with obesity (STEP) TEENS trial. METHODS: Adolescents with obesity received once-weekly subcutaneous semaglutide 2.4 mg or placebo plus lifestyle intervention, which comprised counseling in healthy nutrition and a goal of 60 minutes of moderate- to high-intensity physical activity per day. Achievement of an improvement in BMI category and attainment of normal-weight or overweight BMI by week 68 were analyzed using logistic regression models. RESULTS: In the overall population, 44.9% of participants receiving semaglutide achieved weight reduction resulting in reclassification to a normal-weight or overweight BMI category versus 12.1% receiving placebo at week 68 (odds ratio: 22.7; 95% CI: 7.6-67.9). The proportion of semaglutide-treated participants in obesity class III decreased from 37.3% to 13.6% but increased with placebo. The odds ratio for achieving an improvement of at least one BMI category was significantly greater with semaglutide versus placebo (23.5; 95% CI: 9.9-55.5); an improvement of at least one BMI category was seen in 73.7% of participants receiving semaglutide compared with 19.0% of participants receiving placebo. CONCLUSIONS: Semaglutide was highly effective in reducing BMI category. While on treatment, most trial participants' BMI improved by at least one category, and >40% reached a category below the obesity threshold.