Spotlight on colorectal neoplasia in IBD

Recent research focused on colorectal neoplasia in patients with inflammatory bowel disease (IBD), identifying both risk factors, including a novel association with cigarette smoke exposure, and protective factors.

Three recent studies focused on the increased risk of colorectal neoplasia due to mucosal inflammation in patients with inflammatory bowel disease (IBD).

First, a retrospective cohort study at a hospital in the Netherlands found that cigarette smoke exposure is associated with an increased risk of colorectal neoplasia in both patients with Crohn's disease and those with ulcerative colitis. The study included 1,386 patients from the hospital's IBD clinic. Patients had previous colorectal biopsies, were screened for development of colorectal neoplasia via a nationwide pathology registry, and were stratified for guideline-based risk of colorectal neoplasia. Cigarette smoke exposure was ascertained at the end of follow-up. Results were published online on Jan. 13 by Clinical Gastroenterology and Hepatology.

One hundred fifty-three patients (11.5%) developed colorectal neoplasia, consisting of 11 diagnoses (7.2%) of colorectal carcinoma, 12 (7.8%) of high-grade dysplasia, and 130 (85.0%) of low-grade dysplasia. Former smoking increased risk of colorectal neoplasia in patients with ulcerative colitis (hazard ratio [HR], 1.73; 95% CI, 1.05 to 2.85), whereas passive smoke exposure yielded no effect. For patients with Crohn's disease, both active smoking (HR, 2.20; 95% CI, 1.02 to 4.76) and passive smoke exposure (HR, 1.87; 95% CI, 1.09 to 3.20) significantly increased colorectal neoplasia risk. Previously described risk factors, such as having a first-degree family member with colorectal neoplasia in Crohn's disease (P=0.001) and the presence of postinflammatory polyps in ulcerative colitis (P=0.005), were replicated. The study was limited by its single-center design and the fact that patients were treated in a tertiary IBD clinic and may have had an increased baseline risk of colorectal neoplasia, the authors noted. “This study is the first to describe the important role of cigarette smoke in [colorectal neoplasia] development in IBD patients,” they wrote. “Adding this risk factor … might allow for better risk stratification and further refinement of guidelines in the near future.”

Next, researchers from the Dutch Initiative on Crohn and Colitis conducted a systematic review and meta-analysis finding 13 risk factors and five protective factors for advanced colorectal neoplasia (high-grade dysplasia or colorectal cancer) in IBD patients. A total of 164 studies (120 cohort studies, 44 case-control studies) were included, allowing pooled analysis of 31 potential prognostic factors for advanced colorectal neoplasia. Eighty-three studies were conducted in Europe, 44 in North America, 29 in Asia, four in Australia or New Zealand, two in Africa, and two in South America. The overall quality of the included studies, assessed using the Quality In Prognosis Studies tool, was graded as low risk of bias in 83 studies, moderate in 32 studies, and high in 49 studies. Results were published online on Dec. 28, 2020, by Gastroenterology.

In univariate analysis, the evidence for extensive disease as a risk factor was classified as strong, while evidence for low-grade dysplasia, strictures, primary sclerosing cholangitis, postinflammatory polyps, family history of colorectal cancer, and ulcerative colitis versus Crohn's disease was considered moderate. Evidence was weak for the following risk factors: any dysplasia, colon segment resection, aneuploidy, male sex, and age. In addition, histologic inflammation was identified as a risk factor in multivariate analysis, with weak evidence. The evidence for the following protective factors was moderate in univariate analysis: colonoscopic surveillance, 5-aminosalicylic acid, thiopurines, and smoking. Multivariate analysis provided weak evidence for statin use as a protective factor. “These findings may aid in the development of an improved [colorectal cancer] risk stratification model in IBD patients,” the authors concluded.

The final study, a case-control study and systematic review with meta-analysis, focused specifically on the risk of neoplasia in patients with ulcerative colitis. The case-control study compared rates of neoplasia between patients with ulcerative colitis with serrated epithelial change (SEC) and those with ulcerative colitis without SEC who were matched for age, disease duration, and disease extent. Researchers then performed a systematic review and meta-analysis, combining the local data with previously published data. Results were published online on Dec. 9, 2020, by Inflammatory Bowel Diseases.

The study included 196 ulcerative colitis patients without prior neoplasia, 98 with SEC and 98 without SEC. Those with SEC had a higher rate of synchronous or metachronous neoplasia than those without SEC (26.5% vs. 3.1%; P<0.001). Synchronous or metachronous high-grade dysplasia and colorectal cancer were found more frequently in ulcerative colitis patients with SEC than in those without SEC (11.2% vs. 2.0%; P=0.02). The meta-analysis, which standardized the inclusion criteria to IBD patients without prior neoplasia, was consistent with these findings, showing a higher rate of neoplasia in patients with SEC compared to those without SEC (16.4% vs. 3.9%; P<0.001). While the study was limited by its retrospective design and some missing data, the authors concluded that ulcerative colitis patients with SEC “are far more likely to develop neoplasia compared with [ulcerative colitis] patients without SEC and deserve yearly surveillance.”