Effects of TachoSil and 5-fluorouracil on colonic anastomotic healing

J Surg Res. 2014 Dec;192(2):375-82. doi: 10.1016/j.jss.2014.05.067. Epub 2014 May 27.

Abstract

Background: The administration of intraperitoneal (IP) 5-fluorouracil (5-FU) during the early postoperative period after cytoreductive surgery can decrease local cancer recurrence but may also cause impairment of the anastomotic healing. This study examined the effects of the use of this therapy and of the anastomotic sealing with TachoSil, a fibrin-thrombin coated sealant (FTCS), on the healing of colon anastomoses.

Materials and methods: Forty male rats were divided into four groups (1-4, 10 rats each) that underwent transection and anastomosis of the left colon. The anastomoses were covered with FTCS in groups 2 and 4. Saline solution (2 mL/d-groups 1 and 2) or 5-FU (20 mg/kg/d; groups 3 and 4) was administered IP once daily for 3 d. Bursting pressure (BP) was recorded, and the anastomoses were examined macroscopically and graded histologically.

Results: The relative weight loss was significantly higher in group 3 than in the other groups (P = 0.0004). Anastomotic dehiscence, postoperative adhesion formation, perianastomotic collections, and preanastomotic dilatation did not differ significantly among groups. BP was significantly lower in group 3 compared with all other groups (P = 0.001). Neoangiogenesis was significantly lower in group 3 compared with groups 1 and 2 (P = 0.05). Fibroblastic activity was significantly higher in group 1 compared with group 3 (P = 0.035). Inflammatory cell infiltration and collagen deposition did not differ significantly among groups.

Conclusions: Our results shown that the early postoperative IP chemotherapy with 5-FU impaired the healing of colon anastomoses. However, anastomotic sealing with FTCS reversed some of the negative effects of this therapy.

Keywords: 5-Fluorouracil; Anastomotic healing; Bursting pressure; Colonic anastomosis; EPIC; Fibrin-thrombin coated sealant; Intraperitoneal chemotherapy; Rats; TachoSil.

MeSH terms

  • Anastomosis, Surgical
  • Animals
  • Antimetabolites / pharmacology
  • Colon / surgery*
  • Colorectal Neoplasms / surgery
  • Drug Combinations
  • Fibrinogen / pharmacology*
  • Fluorouracil / pharmacology*
  • Injections, Intraperitoneal
  • Male
  • Postoperative Period
  • Rats
  • Rats, Wistar
  • Surgical Sponges
  • Thrombin / pharmacology*
  • Tissue Adhesions / etiology
  • Tissue Adhesions / surgery
  • Wound Healing / drug effects*

Substances

  • Antimetabolites
  • Drug Combinations
  • TachoSil
  • Fibrinogen
  • Thrombin
  • Fluorouracil