Effects of TachoSil and 5-fluorouracil on colonic anastomotic healing

• Published in: The Journal of surgical research Vol. 192; no. 2; pp. 375 - 382
• Main Authors: Sabino, Flávio D., MD, MSci, Campos, Carlos Frederico F., MD, Caetano, Carlos Eduardo R., MD, Trotte, Marcele Nogueira S., MD, MSci, Oliveira, Albanita V., MD, PhD, Marques, Ruy G., MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2014
• Subjects: 5-Fluorouracil; Anastomosis, Surgical; Anastomotic healing; Animals; Antimetabolites - pharmacology; Bursting pressure; Colon - surgery; Colonic anastomosis; Colorectal Neoplasms - surgery; Drug Combinations; EPIC; Fibrin-thrombin coated sealant; Fibrinogen - pharmacology; Fluorouracil - pharmacology; Injections, Intraperitoneal; Intraperitoneal chemotherapy; Male; Postoperative Period; Rats; Rats, Wistar; Surgery; Surgical Sponges; TachoSil; Thrombin - pharmacology; Tissue Adhesions - etiology; Tissue Adhesions - surgery; Wound Healing - drug effects; 5-Fluorouracil; TachoSil; EPIC; Intraperitoneal chemotherapy; Bursting pressure; Colonic anastomosis; Rats; Anastomotic healing; Fibrin-thrombin coated sealant
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2014.05.067

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.