Influence of Neo-Adjuvant Chemotherapy with 5-Fluorouracil on Colonic Anastomotic Healing: Experimental Study in Rats

Abstract

Purpose: We studied the effect of neo-adjuvant chemotherapy on the operative outcome and colonic anasto-motic healing in a rat model.

Methods: Firstly, we determined the maximum tolerated dose (MTD) of intraperitoneal 5-flurorouracil (5-FU) in Wistar rats.

Secondly, animals were randomly divided into 3 groups: group CT-H received the MTD of 5-FU, group CT-L received 50% of the MTD and a control group received an equivalent volume of 0.9% saline, intraperitoneally. Colonic anastomosis was performed 4 days after chemotherapy. Animals were sacrificed 10 days after surgery. Evaluations were made of: weight evolution, surgical complications, anastomotic bursting pressure (BP) and histological analysis of the anastomotic site.

Results: A dose of 20 mg/kg 5-FU, intraperitoneally, for 5 consecutive days was found to be the MTD. A significant weight loss occurred in group CT-H in comparison to the control group either during chemotherapy (p < 0.01) or after surgery (p = 0.01). Postoperative complications were seen only in group CT-H (30% versus 0% in CT-L and control groups). More intense adhesion formation was observed in group CT-H in comparison to the control group (p < 0.01). Intraperitoneal 5-FU induced more inflammation and fibrosis in the submucosa, either with the low or the high-dose, compared to the control animals (p < 0.05) and more pronounced vascular sclerosis was noticed with a dose of 20 mg/kg (p = 0.03). No significant differences in BP were found between the chemotherapy groups and the control group. Conclusion: Neoadjuvant chemotherapy with 5-FU does not alter the strength of colon anastomosis in this rat model. A dose of 20 mg/kg induces significantly more intra-abdominal adhesions and histological alterations at the anastomotic site.

Key Words:

• Chemotherapy
• 5-fluorouracil
• animal (rat)
• colon
• surgical anastomosis
• healing

Additional information

Notes on contributors

M. El-Malt

Mohamed El-Malt, M.D. Department of Abdominal Surgery Ghent university Hospital De Pintelaan 185 B-9000 Ghent, Belgium Tel.: [phone] Fax: [phone] E-mail: [email protected]