Effect of 5-fluorouracil and leucovorin on the integrity of colonic anastomoses in the rat

PURPOSE: This study was designed to determine the effects of 5-fluorouracil and leucovorin on the healing of colonic anastomoses and assess the safety of conducting a colonic resection and anastomosis during and shortly after a course of this chemotherapy in a rat model. METHODS: Fifty-six male Wistar rats, weighing 200 to 250 gm, were divided into four groups, each consisting of 14 animals. Animals in Group I (control group) underwent colon resection and primary anastomosis. Animals in Group II received 10 mg/kg intravenous 5-fluorouracil and 10 mg/kg leucovorin once a week for four weeks and then underwent the same operation. Animals in Groups III and IV received the same drug dosage for six weeks and were operated at different intervals: Group III at one week and Group IV at two weeks after completion of chemotherapy. Within each group, one-half of the animals were sacrificed on the third postoperative day and one-half on the seventh postoperative day, and anastomotic bursting pressure measurements were performed. RESULTS: At three and seven days, mean bursting pressures of the anastomoses were determined: 98 mmHg and 180.7 mmHg in Group I, 95 and 197.8 in Group II, 85.7 and 189.2 in Group III, and 98.6 and 179.2 in Group IV, respectively. There was no significant difference in bursting pressure between treated animals and controls by the third postoperative day or by the seventh day. The burst occurred at the anastomosis in all specimens tested on the third postoperative day and in the bowel wall adjacent to the anastomosis in all specimens tested on the seventh postoperative day. CONCLUSION: This study demonstrates that the above regimen of chemotherapy has no effect on the healing of colonic anastomoses and that surgery can be performed safely during and shortly after this regimen of chemotherapy.