S. Weiber et al., EXPERIMENTAL COLONIC HEALING IN RELATION TO TIMING OF 5-FLUOROURACIL THERAPY, British Journal of Surgery, 81(11), 1994, pp. 1677-1680
In an experimental study resembling clinical use of adjuvant 5-fluorou
racil (5-FU) treatment of colorectal carcinoma, 97 male Wistar rats we
re operated on with a standardized left colonic resection. Treatment w
as given as a daily intraperitoneal injection. The animals were random
ized to one of four groups: early treatment with 5-FU 20 mg/kg or sali
ne 0.1 mol/l from the day of operation to day 7 after operation, and d
elayed 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 kille
d in groups on day 7 or 10 after operation. In the group receiving ear
ly 5-FU treatment there was an increased rate of anastomotic complicat
ions (seven of 26) compared with none in the control or delayed 5-FU g
roups. 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 healin
g 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.