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

Abstract

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. © 1999 Cancer Research Campaign

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Carcinomatosis: Higher Complication Rate for Oxaliplatin Compared to Mitomycin C

“…As many series (19), important part of our morbidity is represented by leakages. It has been proved that the use of heated chemotherapy has a detrimental effect on the strength of colonic anastomosis, especially during the early postoperative period (until day 10) (20,21). This may cause anastomotic failure and postoperative morbidity.…”

Effect of early preoperative 5-fluorouracil on the integrity of colonic anastomoses in rats

“…Tissue hydroxyproline levels are important parameters in the tissue repair process [34,35] . Some studies have found that 5-FU decreases the hydroxyproline content of wounds [19,21] . There were significant differences in hydroxyproline levels at the anastomotic segments on both the 3rd and 7th PO days in the IV group compared to the IP group.…”

“…Since its introduction, 5-FU has remained the cornerstone of adjuvant treatment for colorectal cancer. A number of clinical and experimental data are available on the effects of 5-FU, either alone or in combination with other chemotherapeutic agents, on wound healing [19][20][21][22] . In the adjuvant therapy of colorectal cancers, 5-FU was used alone in prolonged systemic regimens or in combination with other agents [22][23][24][25] .…”

Phase II study on early start of chemotherapy after excising primary colorectal cancer with distant metastases (Pearl Star 02)

“…Giving early postoperative 5‐FU has been investigated to improve outcomes after resecting intestinal malignancies 27. Surgeons have been reluctant to prescribe 5‐FU in the immediate postoperative period.…”