Combined preoperative irradiation and direct postoperative 5-fluorouracil without negative effects on early anastomotic healing in the rat colon.
OBJECTIVE
Preoperative irradiation with direct postoperative chemotherapy could benefit patients undergoing surgery for colorectal cancer. This study was designed to examine, in an experimental model, if such treatment is feasible without detrimental effects on early anastomotic healing.


METHODS
A colonic segment was irradiated (25 Gy) in 3 groups (n = 10 each) of male Wistar rats. After 5 days, a colonic resection was performed with anastomotic construction; only the distal limb consisted of irradiated bowel. Postoperatively, animals received daily intraperitoneal 5-fluorouracil (5-FU, group I/CH: 17.5 mg/kg; group I/CL: 12.5 mg/kg) or saline (group I). Three additional groups were treated similarly, but with sham-irradiation: CH, CL and C, respectively. All rats were killed 7 days postoperatively. Parameters measured were: weight, serum albumin and protein, and anastomotic bursting pressure, breaking strength and hydroxyproline content.


RESULTS
Body weight was diminished significantly in rats receiving chemotherapy. Serum albumin and protein was significantly lower in irradiated groups. At sacrifice, 40% of I/CH rats had functional rectal stenosis. The average bursting pressure (P = 0.0005) and the average breaking strength (P = 0.012) were only reduced significantly in the CH group. The anastomotic hydroxyproline content was significantly higher in the I/CH and I/CL groups vs. the control group.


CONCLUSIONS
High-dose direct postoperative 5-FU leads to reduced anastomotic strength. Although the combination of preoperative irradiation (25 Gy) and direct postoperative high-dose 5-FU does not reduce early anastomotic strength, some stenosis may occur. The combination of preoperative irradiation and low-dose 5-FU has no such effect.
Biert
J
J
Department of Surgery, University Hospital Nijmegen, The Netherlands.
Wobbes
T
T
Hoogenhout
J
J
de Man
B
B
Hendriks
T
T
D000714:Anastomosis, Surgical; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001835:Body Weight; D003106:Colon / Q000187:drug effects / Q000528:radiation effects / Q000601:surgery*; D015179:Colorectal Neoplasms / Q000628:therapy; D003131:Combined Modality Therapy; D005240:Feasibility Studies; D005472:Fluorouracil / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014945:Wound Healing / Q000187:drug effects / Q000528:radiation effects
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil