title: Intraperitoneally administered irinotecan with 5-fluorouracil impair wound healing of colonic anastomoses in a rat model: an experimental study.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors: 4th Surgical Department, Aristotle University of Thessaloniki, G Papanikolaou General Hospital, 57010 Exohi, Thessaloniki, Greece. mpramateftakis@hotmail.com
authors: M G
authors: MG
authors: Pramateftakis
authors: D
authors: D
authors: Kanellos
authors: I
authors: I
authors: Mantzoros
authors: K
authors: K
authors: Despoudi
authors: D
authors: D
authors: Raptis
authors: S
authors: S
authors: Angelopoulos
authors: G
authors: G
authors: Koliakos
authors: Th
authors: T
authors: Zaraboukas
authors: Charalambos
authors: C
authors: Lazaridis
mesh_terms: D000714:Anastomosis, Surgical; D057868:Anastomotic Leak / Q000209:etiology; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000494:pharmacology*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D003106:Colon / Q000098:blood supply / Q000737:chemistry / Q000473:pathology / Q000601:surgery*; D005472:Fluorouracil / Q000009:adverse effects / Q000494:pharmacology*; D006909:Hydroxyproline / Q000032:analysis / Q000187:drug effects; D000077146:Irinotecan; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011312:Pressure / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D012421:Rupture / Q000209:etiology; D000267:Tissue Adhesions / Q000209:etiology; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D006909:Hydroxyproline; D005472:Fluorouracil; D002166:Camptothecin