Influence of intraperitoneal 5-fluorouracil plus folinic acid on the healing of colonic anastomoses in rats.

Abstract

We studied the effects of intraperitoneal 5-fluorouracil (5-FU) administration with or without the addition of folinic acid (FA) on the healing of colonic anastomoses in rats immediately after surgery. Sixty-three male Wistar rats were subjected to colonic anastomosis. During surgery, the rats were randomized into one of three groups. Therapy was administered as an intraoperative intraperitoneal injection which was repeated once daily for the first 2 postoperative days. A 0.9% NaCl solution was administered to the rats in the control group. In group 2, we injected 5-FU (20 mg/kg/day) and in group 3 5-FU (20 mg/kg/day) plus FA (2 mg/kg/day). The rats were sacrificed on postoperative days 3, 5 or 8. Rupture of the anastomosis was significantly higher in the rats of groups 2 and 3, compared with the control group (p < 0.05). There were, however, no differences between groups 2 and 3. Formation of adhesions and abscesses was more common in groups 2 and 3 than in the control group for all study days. A significant difference in the anastomotic bursting pressure was measured for the control group in comparison to groups 2 and 3 on days 5 and 8 (p < 0.05). Histologic evaluation also showed a more profound inflammatory reaction and delayed healing of the anastomoses in groups 2 and 3, compared to the control group. Therefore, the perioperative intraperitoneal administration of 5-FU can inhibit the healing of colonic anastomoses in rats. The addition of an intraperitoneal injection of FA does not aggravate this negative effect.