Healing of colonic anastomoses after immediate and delayed administration of 5-fluorouracil plus folinic acid

The purpose of this experimental study was to investigate whether the delayed, postoperative, intraperitoneal administration of 5-fluorouracil plus folinic acid had adverse effects on wound healing, as did their early administration. Seventy male Wistar rats underwent colonic resection followed by anastomosis of the colon. The animals were randomized into four groups. The rats in control group 1 received a 0.9% NaCl solution intraperitoneally and those in group 2 received 5-fluorouracil (20 mg/kg) plus folinic acid (2 mg/kg) immediately after surgery and for the next 3 days. The rats in control group 3 and those in group 4 received intraperitoneally a 0.9% NaCl solution or 5-fluorouracil plus folinic acid, respectively, from postoperative day 4 to day 7. The rats were sacrificed on the 8th postoperative day. The rupture rate of the anastomoses was statistically significantly higher in group 2 with early treatment compared to control group 1 (p < 0.05); no differences were observed between control group 3 and group 4 with delayed treatment (p > 0.05). Adhesion and abscess formation were more marked in group 2 compared to control group 1; no differences were recorded between groups 3 and 4. The anastomotic bursting pressure was statistically significantly lower in group 2 compared to control group 1 (p < 0.05); no differences were measured between groups 3 and 4. Histologic evaluation showed a more profound inflammatory response and less marked fibroblastic activity in group 2 compared to control group 1; new collagen production was more evident in group 1. No such differences were observed between groups 3 and 4. In conclusion, the immediate, postoperative, intraperitoneal administration of 5-fluorouracil plus folinic acid inhibited wound healing, but delaying chemotherapy (beginning on the 4th postoperative day) had no adverse effects on the healing of colonic anastomoses and can be considered safe.