The healing of colon anastomosis covered with fibrin glue after early postoperative intraperitoneal chemotherapy.
BACKGROUND
After colon resection for colonic cancer, the administration of antineoplastic agents may prolong survival by killing residual cancer calls and preventing metastasis, but may also slow anastomotic healing. This study was designed to determine the effects of 5-fluorouracil (5-FU) and leucovorin (LEV), injected intraperitoneally, on the healing of colonic anastomoses with or without fibrin glue (FG) covering.


METHODS
Sixty rats were randomized to one of four groups. After resection of a transverse colon segment, an end-to-end sutured anastomosis was performed. Rats in the 5-FU+LEV and the 5- FU+LEV+FG groups received 5-FU+LEV intraperitoneally. The colonic anastomoses of the rats in the FG group and in the 5-FU+LEV+FG group were covered with fibrin glue. All rats were killed on postoperative day 8. Bursting pressure measurements were recorded and the anastomoses were examined macroscopically and histologically.


RESULTS
The leakage rate of the anastomoses was significantly different among groups. Specifically, the leakage rate was significantly higher in the 5-FU+LEV group (40%) than in the FG and in the 5-FU+LEV+FG groups where there were no leakages (p=0.017). The mean adhesion formation score was significantly higher in rats of the 5-FU+LEV group, compared to the control (p=0.023), the FG (p=0.006) and the 5-FU+LEV+FG (p=0.006) groups. Bursting pressures were significantly lower in the 5-FU+LEV group than in the other groups (p<0.001). Also, bursting pressures were significantly lower in the control group compared to the FG and 5-FU+LEV+FG groups (p<0.001). Rats in the 5-FU+LEV+FG group had significantly greater neoangiogenesis and fibroblast activity than those in the 5-FU+LEV group (p=0.025).


CONCLUSIONS
The early intraperitoneal postoperative administration of 5-fluorouracil plus leucovorin impaired colonic wound healing. However, the application of fibrin glue prevented the deleterious effect of chemotherapy.
Kanellos
I
I
4th Surgical Department, G. Papanikolaou Hospital, Aristotle University of Thessaloniki, Greece.
Christoforidis
E
E
Kanellos
D
D
Pramateftakis
M G
MG
Sakkas
L
L
Betsis
D
D
D000714:Anastomosis, Surgical; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D003106:Colon / Q000601:surgery; D015718:Fibrin Tissue Adhesive; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D002955:Leucovorin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
D000964:Antimetabolites, Antineoplastic; D015718:Fibrin Tissue Adhesive; D014803:Vitamin B Complex; D002955:Leucovorin; D005472:Fluorouracil