Male Wistar rats were subjected to colonic resection and randomized to one of four groups: control group (intraperitoneal NaCl, intravenous NaCl); 5-fluorouracil (5-FU) group (intraperitoneal 5-FU, intravenous NaCl); folinic acid group (intraperitoneal NaCl, intravenous folinic acid); and 5-FU-folinic acid group (intraperitoneal 5-FU, intravenous folinic acid). Treatment was started immediately after surgery and continued until the animals were killed at 3 or 7 days. Anastomotic complications (abscesses or dehiscence) occurred in four of 33 animals in the control group, 12 of 36 in the 5-FU group, one of 32 in the folinic acid group and nine of 36 in the 5-FU-folinic acid group. Anastomotic and skin breaking strength did not differ between groups on day 3 but by day 7 were significantly reduced in the 5-FU group. In rats given 5-FU-folinic acid, breaking strength was also reduced, but less so than in the 5-FU group. Breaking strength in animals receiving folinic acid was similar to that in the control group. In this model colonic healing was impaired after intraperitoneal 5-FU administration, but when folinic acid was added no further deterioration occurred.

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.

In an experimental study resembling clinical use of adjuvant 5-fluorouracil (5-FU) treatment of colorectal carcinoma 86 male Wistar rats were operated with a standardized left colon resection and anastomosis with interrupted sutures. Treatment was given as daily intraperitoneal (i.p.) injections. The animals were randomized to one of two groups: (A) 5-FU (20 mg/kg) i.p., and (B) NaCl i.p. from the day of operation to sacrifice. Anastomotic complications were registered. In experiment 1 animals were randomized within treatment groups to be tested for anastomotic breaking strength with or without sutures in place when sacrificed 7 days postoperatively. In experiment 2 collagen synthesis was studied by an in vivo incorporation and hydroxylation of ³H-proline in the anastomotic segment during 24 h prior to sacrifice. The animals were sacrificed in groups on the third or seventh postoperative day. A higher number of anastomotic complications was registered when 5-FU was given. The anastomotic breaking strength was only 40% of controls both when tested with and without sutures. A reduced radioactivity of ³H-hydroxyproline in the anastomotic segment after 7 days of 5-FU treatment was found implying a reduction in collagen synthesis. In our model colonic healing was impaired after i.p. 5-FU treatment and this could be attributed to a reduced collagen synthesis in the wound gap as well as in the adjacent tissue responsible for the suture-holding capacity.

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