The effects of tacrolimus on colonic anastomotic healing in rats.

AIM: The aim of this experimental study is to investigate the effects of tacrolimus on colonic anastomotic healing after subcutaneous administration. MATERIALS AND METHODS: Forty Albino-Wistar male rats were divided into two groups, with two equal subgroups each. They all underwent colonic resection followed by a single-layer, inverted colon anastomosis and were injected subcutaneously with either 1 ml of 0.9% NaCl solution or tacrolimus (0.1 mg/kg body weight) depending on their group. Half of the rats were sacrificed on the fourth postoperative day, while the remaining half were sacrificed on the eighth postoperative day. Macroscopical and histological assessment was performed, while anastomotic bursting pressures and the tissue concentrations in hydroxyproline and collagenase I were evaluated. RESULTS: On the fourth postoperative day, the bursting pressures (217.00 ± 11.12, p < 0.001), the fibroblast activity (2.80 ± 0.42, p = 0.022), the neoangiogenesis (2.10 ± 0.32, p = 0.007) and the tissue hydroxyproline concentration (254.23 ± 67.10, p = 0.001) were significantly higher in the tacrolimus-treated animals. Furthermore, tacrolimus significantly decreased the inflammatory cell infiltration (1.50 ± 0.53, p < 0.001) and the tissue collagenase I concentration (4.16 ± 0.76, p = 0.002). On the eighth day, the bursting pressure (264.00 ± 32.61, p < 0.001) and the hydroxyproline tissue concentration (331.04 ± 55.56, p = 0.002) were significantly higher in the tacrolimus subgroups. The inflammatory cell infiltration (1.20 ± 0.42, p < 0.001) and the collagenase I concentration (1.61 ± 0.83, p < 0.001) were significantly lower. In addition, the adhesion formation score was significantly lower (1.20 ± 0.92, p = 0.065). CONCLUSION: Tacrolimus, when injected subcutaneously, promotes healing of colonic anastomoses in rats. It impairs not only inflammatory response but also collagen degradation, resulting to increased anastomotic strength on the fourth as well as on the eighth postoperative day.

Intraperitoneally administered irinotecan with 5-fluorouracil impair wound healing of colonic anastomoses in a rat model: an experimental study.

AIM: The aim of this experimental study is the assessment of the effects of the immediate post-operative intraperitoneal administration of 5-fluorouracil and irinotecan on the healing process of large bowel anastomoses in rats. MATERIALS AND METHODS: Sixty male Wistar rats were divided into 4 groups of 15 rats each. The rats underwent large bowel resection and anastomosis, followed by the intraperitoneal administration of normal saline (group 1), 5-fluorouracil (group 2), irinotecan (group 3) or the combination of 5-fluorouracil and irinotecan (group 4). All animals were killed on the eighth post-operative day. During post-mortem examination, the anastomoses were assessed macroscopically for a possible anastomotic leak and the extent of adhesion formation. Subsequently, the anastomotic bursting pressure was measured, and the anastomoses were assessed histologically. RESULTS: No anastomotic dehiscence was observed in the rats of group 1. In groups 2 and 3, we observed 3 anastomotic leaks in each group, and in group 4, we observed 5 leaks (P = 0.111). The mean bursting pressure of the anastomoses in group 1 was significantly higher compared to groups 2, 3 and 4 (P < 0.001). The least inflammatory cell infiltration score was observed in group 1 (P < 0.001). The lowest neoangiogenesis score was observed in group 2 and the highest in group 4. The collagen formation in group 1 was significantly higher compared to the other 3 groups (P < 0.001). Similar results were observed for the fibroblast activity, where group 1 revealed significantly higher fibroblast scores compared to groups 2, 3 and 4 (P < 0.001). Finally, groups 2, 3 and 4 showed significantly lower hydroxyproline levels compared to the control group (P < 0.001). CONCLUSION: The immediate, post-operative intraperitoneal administration of 5-fluorouracil or irinotecan had a negative effect on the healing process of the large bowel anastomoses in rats. The negative effects of the combination of 5-fluorouracil and irinotecan were statistically more significant compared to the single use of 5-fluorouracil or irinotecan.

The effects of the intraperitoneal administration of oxaliplatin and 5-FU on the healing of colonic anastomoses: an experimental study.

BACKGROUND: The purpose of this experimental study was to assess the effects of the immediate postoperative intraperitoneal administration of oxaliplatin and 5-FU on the healing of colonic anastomoses in rats. METHODS: Sixty rats were randomized into 4 groups of 15 rats each and were subjected to colonic anastomoses. To the 1st group, saline solution was administered immediately postoperatively, intraperitoneally. To the 2nd group, 5-FU was administered, to the 3rd group oxaliplatin and to the 4th group 5-FU and oxaliplatin were administered immediately postoperatively, intraperitoneally. After killing the rats on the 8th postoperative day, the anastomoses were examined macroscopically and the anastomotic bursting pressures were measured. The anastomoses were also examined histologically and the hydroxyproline contents were determined. RESULTS: Rupture of the anastomosis was observed in no rats of the 1st group, in 3 rats of the 2nd group, in 4 rats of the 3rd group and in 7 rats of the 4th group (P = 0.016). The bursting pressure (P < 0.001), the hydroxyproline content (P < 0.001) and the concentration of collagen (P < 0.001) and fibroblasts (P < 0.001) were significantly lower in the 2nd, 3rd and 4th group in comparison with the 1st group. The formation of adhesions and the leukocytosis on the anastomoses were significantly higher in the 2nd, 3rd and 4th group than in the 1st group (P < 0.001). CONCLUSIONS: The immediate postoperative, intraperitoneal administration of oxaliplatin, 5-FU or the combination of 5-FU and oxaliplatin impairs the healing of colonic anastomoses in rats.