Influence of Intraperitoneal 5-Fluorouracil Plus Folinic Acid on the Healing of Colonic Anastomoses in Rats

Abstract

We studied the effects of intraperitoneal 5-fiuorouracil (5-FU) administration with or without the addition of folinic acid (FA) on the healing of colonic anastomoses in rats immediately after surgery. Sixty-three male Wistar rats were subjected to colonic anastomosis. During surgery, the rats were randomized into one of three groups. Therapy was administered as an intraoperative intraperitoneal injection which was repeated once daily for the first 2 postoperative days. A 0.9% NaCl solution was administered to the rats in the control group. In group 2, we injected 5-FU (20 mg/kg/day) and in group 3 5-FU (20 mg/kg/day) plus FA (2 mg/kg/day). The rats were sacrificed on postoperative days 3, 5 or 8. Rupture of the anastomosis was significantly higher in the rats of groups 2 and 3, compared with the control group (p < 0.05). There were, however, no differences between groups 2 and 3. Formation of adhesions and abscesses was more common in groups 2 and 3 than in the control group for all study days. A significant difference in the anastomotic bursting pressure was measured for the control group in comparison to groups 2 and 3 on days 5 and 8 (p < 0.05). Histologic evaluation also showed a more profound inflammatory reaction and delayed healing of the anastomoses in groups 2 and 3, compared to the control group. Therefore, the perioperative intraperitoneal administration of 5-FU can inhibit the healing of colonic anastomoses in rats. The addition of an intraperitoneal injection of FA does not aggravate this negative effect.

The use of morphometric and fractal parameters to assess the effects of 5-fluorouracil, interferon and dexamethasone treatment on colonic anastomosis healing: an experimental study in rats

“…In concordance with our results, Ersoy et al did not find any significant influence of 5-fluorouracil on the connective tissue remodeling reflected as collagen content changes [39]. The detrimental effects of 5-fluorouracil have also been demonstrated by other researchers [26,40,41]. In the study by Graf et al, it was found to significantly impair anastomosis healing [40].…”

“…The methodology used in most of those studies relied on the analysis of the macroscopic status of the anastomosis. Additionally, bursting strength, intensity of local inflammation, and collagen content have been used by some authors [25,26]. The results of those studies are not completely concordant.…”

“…Most of the studies which have evaluated the influence of chemotherapeutic and steroid agents on colonic anastomosis healing have concentrated on bursting pressures and collagen content analysis with standard histological methods [25,26].…”

Healing of experimental colonic anastomoses: Effects of combined preoperative high‐dose radiotherapy and intraperitoneal 5‐fluorouracil

“…A more pronounced inflammatory response was noted with intraperitoneal administration of 5-FU and with the combined treatment. This inflammatory reaction was also reported when 5-FU was administered intraperitoneally in the rat during surgery or early postoperatively [36,37].…”

The Effect of Iloprost in the Healing of Colonic Anastomosis in Rats under Chemotherapy with Irinotecan

“…On the other hand, the healing process can be significantly inhibited and therefore a rupture in the colon anastomoses may occur (20).…”