Proliferative instability and experimental carcinogenesis at colonic anastomoses.

The possibility that proliferative instability around a healing anastomosis promotes carcinogenesis was tested in 234 male Sprague-Dawley rats. Animals received the first of five weekly injections of azoxymethane (total dose 50 mg/kg) either immediately after transection of the descending colon or at 2, 4, 8, and 12 weeks later; controls received handling of the bowel alone. Crypt cell proliferation was assessed by autoradiography following 3HTdR injection. An overall increase in tumour yields in all transection groups was due solely to the frequent presence of anastomotic tumours. Changes in crypt morphometry and labelling index were most marked in crypt positions 1-10 away from the anastomosis. Crypts at this site increased in height at 2, 4, and 8 weeks (p less than 0.001) but returned to normal values by 12 weeks. Likewise, labelling index was increased at 2, 4, and 8 weeks (p less than 0.001) and remained higher at 12 weeks (p less than 0.05). Increased crypt cell proliferation in the immediate vicinity of an apparently 'healed' colonic anastomosis may explain its persisting susceptibility to carcinogenesis.