Tomio Narisawa

Preoperative use of 5-fluorouracil suppository for carcinoma of the rectum

A total of 50 patients with carcinoma of the rectum were treated with 5-fluorouracil suppository before operation. The suppository, which was made of Witepsol suppository base containing 5-fluorouracil, yielded high drug concentrations in carcinoma, draining blood and regional lymph nodes. As a clinical response to the suppository, a significant decrease in the size of tumor mass was noted in 8 of 50 carcinomas, but in other cases the gross change was unmeasurable. Thirty-three percent of the surgically resected carcinomas were histologically judged to have responded to the suppository. In such cases, histologic changes correlated well with the total dose of 5-fluorouracil. The adverse effects of the suppository were confined to anal pain, tenesmus and anal bleeding, probably due to the topical effect of 5-fluorouracil on the rectal mucosa.

The correlation between cholecystectomy and fecal bile acids, and large-bowel cancer induced with 1,2-dimethylhydrazine in mice

The relationship between cholecystectomy and large-bowel cancer development was investigated in animal models. Female ICR mice underwent cholecystectomy, and received 15 weekly intragastric administrations (Experiment 1) or 10 weekly subcutaneous injections (Experiment 2) of 15 mg/kg body weight of large-bowel carcinogen 1,2-dimethylhydrazine (DMH). Autopsy at 28 weeks after surgery showed that cholecystectomized mice had a nonsignificantly increased incidence of large-bowel carcinomas, compared to sham-operated and/or unoperated control mice (85 vs. 64 percent in Experiment 1; 31 vs. 16 and 20 percent in Experiment 2). Cholecystectomy alone without DMH treatment did not produce any cancer. Cholecystectomized mice excreted a significantly increased level of primary bile acids but an unchanged level of secondary bile acids in the feces, compared with unoperated control mice. It is obvious that cholecystectomy enhanced the development of DMH-induced, large-bowel carcinomas along with the change of fecal bile acid composition, suggesting that changes of bile acid metabolism after cholecystectomy may enhance or promote large-bowel carcinogenesis in man as well. This association of cholecystectomy and large-bowel cancer is not a strong one however, as presented in epidemiologic as well as experimental studies.