Risk factors for neoplasia in inflammatory bowel disease patients with pancolitis.

OBJECTIVES: Colorectal cancer (CRC), developing from dysplastic lesions, is the main long-term complication of pancolitis. The aims of the present study were to assess the risks for neoplasia and advanced neoplasia (AN), respectively, in ulcerative colitis (UC) and Crohn's disease (CD) patients with pancolitis, and to search for protective and risk factors for colorectal neoplasia. METHODS: A total of 855 inflammatory bowel disease (IBD) patients with longstanding pancolitis (276 UC, 56 IBD unclassified (IBDu), and 523 CD) had pathological examination of a proctocolectomy specimen (n=255) or multiple biopsy samples from a surveillance colonoscopy (n=600) after median disease duration of 115 months. Risk factors for low-grade dysplasia (LGD) and AN, respectively, were searched for in the whole group of patients and in a case-control comparison after matching for IBD phenotype. RESULTS: A total of 75 patients eventually developed colorectal neoplasia: 14 adenomas, 28 nonadenomatous LGD, and 33 ANs. The 25-year cumulative risks for neoplasia and AN, respectively, were 32.8±5.7% and 25.9±5.7% in UC and IBDu vs. 12.1±2.7% and 3.9±2.0% in CD (P<0.0001). In CD, patients with UC-like endoscopic appearance (n=126) had an increased risk for AN compared with those with discrete lesions (at 25 years, 10.6±7.2 vs. 1.5±0.9%). In the case-control comparison, factors associated with an increased risk of AN were primary sclerosing cholangitis (hazard ratio (HR) 4.72 (1.54-14.52)) and family history of CRC (HR 3.37 (1.02-11.14)), whereas previous segmental colectomy was protective (HR 0.25 (0.07-0.88)). CONCLUSIONS: The risk of AN in longstanding pancolitis is higher in UC or IBDu than in CD. In CD, this risk is significantly increased in patients with UC-like endoscopic lesions. The surveillance program should focus on these latter patients.

Current smoking differentially affects blood mononuclear cells from patients with Crohn's disease and ulcerative colitis: relevance to its adverse role in the disease.

BACKGROUND: Epidemiologic data suggest that smoking increases the risk and the severity of Crohn's disease (CD), although it may protect patients with ulcerative colitis (UC). To investigate this paradox, we evaluated the effect of cigarette smoke in the function of blood mononuclear cells from healthy subjects and patients with CD or UC in flare up. METHODS: The production of mediators associated with inflammation but also with protective functions was evaluated by enzyme-linked immunosorbent assay (ELISA) and enzyme immunoassay (EIA), following either in vivo or in vitro exposure to cigarette smoke. RESULTS: We found that mononuclear cells from smokers with CD were functionally impaired. These cells secreted lower levels of chemokines and cytokines as compared with nonsmoker counterparts, whereas healthy smokers or smokers with UC were not affected. Similar findings were noted after in vitro exposure to cigarette smoke extract. In addition, cells from patients with CD who smoke presented a defective sensitivity to antiinflammatory or antioxidant protection, and particularly synthesized lower levels of cytoprotective Hsp70. The effects observed were not due to diminished cell viability. Our experiments suggest that cigarette smoke-related responses were largely dependent on oxidative stress generated, and not on the nicotine component. CONCLUSIONS: Overall, our data point out the presence of biological differences between blood mononuclear cells from patients with CD and UC toward cigarette smoke that might support its opposite role in both diseases.