COMBINED PREOPERATIVE IRRADIATION AND DIRECT POSTOPERATIVE 5-FLUOROURACIL WITHOUT NEGATIVE EFFECTS ON EARLY ANASTOMOTIC HEALING IN THE RAT COLON

Background and purpose: Preoperative irradiation with direct postopera tive chemotherapy could benefit patients undergoing surgery for colore ctal cancer. This study was designed to examine, in an experimental mo del, if such treatment is feasible without detrimental effects on earl y anastomotic healing. Material and methods: A colonic segment was irr adiated (25 Gy) in 3 groups (n=10 each) of male Wistar rats. After 5 d ays, a colonic resection was performed with anastomotic construction; only the distal limb consisted of irradiated bowel. Postoperatively, a nimals 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 addit ional groups were treated similarly, but with sham-irradiation: CH, CL and C, respectively. All rats were killed 7 days postoperatively. Par ameters measured were: weight, serum albumin and protein, and anastomo tic bursting pressure, breaking strength and hydroxyproline content. R esults: Body weight was diminished significantly in rats receiving che motherapy. Serum albumin and protein was significantly lower in irradi ated groups. At sacrifice, 40% of I/CH rats had functional rectal sten osis. The average bursting pressure (P=0.0005) and the average breakin g 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. Conclusion: High-dose dir ect postoperative 5-FU leads to reduced anastomotic strength. Although the combination of preoperative irradiation (25 Gy) and direct postop erative high-dose 5-FU does not reduce early anastomotic strength, som e stenosis may occur. The combination of preoperative irradiation and low-dose 5-FU has no such effect.