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.
Weiber
S
S
Department of Surgery, Allmänna sjukhuset, Malmö, Sweden.
Graf
W
W
Glimelius
B
B
Jiborn
H
H
Påhlman
L
L
Zederfeldt
B
B
D000818:Animals; D003106:Colon / Q000601:surgery*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005472:Fluorouracil / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*
D005472:Fluorouracil