EXPERIMENTAL COLONIC HEALING IN RELATION TO TIMING OF 5-FLUOROURACIL THERAPY

In an experimental study resembling clinical use of adjuvant 5-fluorouracil (5-FU) treatment of colorectal carcinoma, 97 male Wistar rats were operated on with a standardized left colonic resection. Treatment was given as a daily intraperitoneal injection. The animals were randomized to one of four groups: early treatment with 5-FU 20 mg/kg or saline 0.1 mol/l from the day of operation to day 7 after operation, and delayed treatment with 5-FU 20 mg/kg or saline 0.1 mol/l from the third day after operation to the day before killing. The animals were killed in groups on day 7 or 10 after operation. In the group receiving early 5-FU treatment there was an increased rate of anastomotic complications (seven of 26) compared with none in the control or delayed 5-FU groups. The anastomotic breaking strength in animals having early 5-FU treatment (day 7, median 1.45 (range 0.20-2.95) N; day 10, median 1.80 (range 0.95-3.20) N) was significantly lower than that in controls on both day 7 (median 3.20 (range 2.50-3.80) N) and day 10 (median 3.20 (range 2.20-3.60) N). In the delayed 5-FU treatment group anastomotic breaking strength did not differ from that in controls. Colonic healing was not impaired when intraperitoneal 5-FU treatment was started on day 3 after operation, whereas immediate postoperative administration of 5-FU had a detrimental effect on wound healing.