September 1995

Retinol May Promote Fluorouracil-Suppressed Healing of Experimental Intestinal Anastomoses

Author Affiliations

From the Department of Surgery, University Hospital Nijmegen (the Netherlands). Dr de Waard is currently affiliated with the Department of Surgery, Westfries Gasthuis, Hoorn, the Netherlands.

Arch Surg. 1995;130(9):959-965. doi:10.1001/archsurg.1995.01430090045017

Objectives:  To examine the effects of perioperative administration of fluorouracil on healing variables of intestinal anastomoses and to explore ways to promote repair under these conditions.

Design:  Seven-day, prospective randomized experimental trial.

Setting:  Animal research laboratory.

Animals:  Male young-adult Wistar rats after resection and anastomosis of both ileum and colon.

Interventions:  Random assignment to groups receiving placebo, daily fluorouracil (20 mg/kg per day, intraperitoneally), daily fluorouracil plus retinol palmitate (5000 lU/kg per day, orally), daily fluorouracil plus interleukin-2 (2×106 IU/kg per day, subcutaneously), or daily fluorouracil plus granulocyte macrophage colonystimulating factor on the first 4 days after operation (20 μ/kg per day, intraperitoneally).

Main Outcome Measures:  Anastomotic bursting pressure, breaking strength, hydroxyproline content, and ex vivo collagen synthetic capacity.

Results:  Administration of fluorouracil decreased anastomotic breaking strength by more than 40% and caused a shift in bursting site from outside to within the suture line. It also lowered anastomotic hydroxyproline content. The capacity for collagen synthesis, which was greatly enhanced in 4-day-old anastomoses from the control group, was significantly (P<.05) and specifically reduced. Concomitant administration of retinol resulted in restoration of strength and hydroxyproline content, particularly in the ileum. Interleukin-2 and granulocyte macrophage colony-stimulating factor did not improve fluorouracil-suppressed repair: both wound strength andcollagen content were similar in the fluorouracil, fluorouracil/interleukin-2, and fluorouracil/granulocyte macrophage colony-stimulating factor groups.

Conclusion:  Intraperitoneal administration of fluorouracil, delivered from the day of operation onward, severely reduces anastomotic strength at the end of the first postoperative week. This negative effect may be prevented by oral administration of retinol.(Arch Surg. 1995;130:959-965)