Is early post-operative treatment with 5-fluorouracil possible without affecting anastomotic strength in the intestine?

• Published in: British journal of cancer 1999-02, Vol.79 (3-4), p.545-550
• Main Authors: van der Kolk, B M, de Man, B M, Wobbes, T, Hendriks, T
• Format: Article
• Language: English
• Subjects: Anastomosis, Surgical; Animals; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - therapeutic use; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Colon - surgery; Drug Resistance; Epidemiology; Fluorouracil - adverse effects; Fluorouracil - therapeutic use; Gastroenterology. Liver. Pancreas. Abdomen; Ileum - surgery; Infusions, Intravenous; Infusions, Parenteral; Intestinal Neoplasms - drug therapy; Intestinal Neoplasms - surgery; Male; Medical sciences; Molecular Medicine; Oncology; Postoperative Complications; Rats; Regular; regular-article; Stomach, duodenum, intestine, rectum, anus; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the digestive system; Tumors; Wound Healing - drug effects
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6690086

Summary Early post-operative local or systemic administration of 5-fluorouracil (5-FU) is under investigation as a means to improve outcome after resection of intestinal malignancies. It is therefore quite important to delineate accurately its potentially negative effects on anastomotic repair. Five groups ( n = 24) of rats underwent resection and anastomosis of both ileum and colon: a control group and four experimental groups receiving daily 5-FU, starting immediately after operation or after 1, 2 or 3 days. Within each group, the drug (or saline) was delivered either intraperitoneally ( n = 12) or intravenously ( n = 12). Animals were killed 7 days after operation and healing was assessed by measurement of anastomotic bursting pressure, breaking strength and hydroxyproline content. In all cases, 5-FU treatment from the day of operation or from day 1 significantly ( P < 0.025) and severely suppressed wound strength; concomitantly, the anastomotic hydroxyproline content was reduced. Depending on the location of the anastomosis and the route of 5-FU administration, even a period of 3 days between operation and first dosage seemed insufficient to prevent weakening of the anastomosis. The effects of intravenous administration, though qualitatively similar, were quantitatively less dramatic than those observed after intraperitoneal delivery. Post-operative treatment with 5-FU, if started within the first 3 days after operation, is detrimental to anastomotic strength and may compromise anastomotic integrity.