The effect of 5-fluorouracil on wound healing and collagen synthesis in left colon anastomoses. An experimental study in the rat.
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.
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
D000714:Anastomosis, Surgical; D000818:Animals; D003094:Collagen / Q000096:biosynthesis* / Q000187:drug effects; D003106:Colon / Q000601:surgery*; D005472:Fluorouracil / Q000008:administration & dosage*; D008297:Male; D011183:Postoperative Complications / Q000139:chemically induced; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014945:Wound Healing / Q000187:drug effects*
D003094:Collagen; D005472:Fluorouracil