Effect of early preoperative 5-fluorouracil on the integrity of colonic anastomoses in rats

Abstract

To determine the effect of chemotherapy on wound healing by giving early preoperative 5-fluorouracil (5-FU) to rats with colonic anastomoses. Sixty Albino-Wistar male rats (median weight, 235 g) were used in this study. The rats were fed with standard laboratory food and given tap water ad libitum. The animals were divided into three groups: Group 1: Control group (chemotherapy was not administered), Group 2: Intraperitoneally (i.p.) administered 5-FU group (chemotherapy was administered i.p. to animals at a dose of 20 mg/kg daily during the 5 d preceding surgery), Group 3: Intravenously (i.v.) administered 5-FU group. Chemotherapy was administered via the penil vein, using the same dosing scheme and duration as the second group. After a 3-d rest to minimize the side effects of chemotherapy, both groups underwent surgery. One centimeter of colon was resected 2 cm proximally from the peritoneal reflection, then sutured intermittently and subsequently end-to-end anastomosed. In each group, half the animals were given anaesthesia on the 3rd postoperative (PO) day and the other half on the 7th PO day, for in vivo analytic procedures. The abdominal incisions in the rats were dissected, all the new and old anastomotic segments were clearly seen and bursting pressures of each anastomotic segment, tissue hydroxyproline levels and DNA content were determined to assess the histologic tissue repair process. When the i.v. group was compared with the i.p. group, bursting pressures of the anastomotic segments on the 3rd and 7th PO days, were found to be significantly decreased, hydroxyproline levels at the anastomotic segment on the 7th PO day were significantly decreased (P < 0.01). In this study, we conclude that early preoperative 5-FU, administered i.v., negatively affects wound healing. However, i.p. administered 5-FU does not negatively affect wound healing.