Mesalazine changes apoptosis and proliferation in normal mucosa of patients with sporadic polyps of the large bowel

Background and Study Aims: Regular intake of nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the occurence of colorectal adenoma and carcinoma, possibly by inducing apoptosis and/or decreasing proliferation in colorectal epithelial cells. Mesalazine is widely used in the treatment of patients with inflammatory bowel disease, and well tolerated. We investigated its effect on apoptosis and proliferation of colorectal mucosa in 21 patients with sporadic polyps of the large bowel, Patients and Methods: In total, 17 patients with sporadic colorectal polyps (greater than or equal to 5 mm) underwent polypectomy and biopsy of uninvolved mucosa before and after treatment with 1g/d mesalazine for 1, 3, 7 or 14 days. Four additional patients served as untreated controls, Apoptotic index (AI) was measured by terminal deoxynucleotidyl transferase-mediated d-uridine triphosphate nick-end labeling (TUNEL) assay; proliferation index (PI) was measured by immunohistochemical examination with anti-Ki67 antibody. Results: Al was significantly increased 1 and 3 days after initiation of treatment with mesalazine compared with controls (P = 0.0107 for the 1-day treatment group and P = 0,0142 for the 3-day treatment group), and seemed to remain largely unchanged after longer treatment duration. Proliferation appeared to be decreased by mesalazine in all treatment groups, while proliferation in controls did not change (P = 0,0107 for the 1-day treatment group and P = 0.0142 for the 3-day treatment group compared with controls. Conclusions: Mesalazine significantly induces apoptosis and decreases proliferation in colorectal mucosa in patients with sporadic polyps of the large bowel, This may be clinically relevant in that it may lower the rate of polyp recurrence after polypectomy, thereby possibly contributing to the chemoprevention of sporadic colorectal carcinoma.