Effects of intraperitoneal bevacizumab administration on colonic anastomosis and early postoperative adhesion formation

Surg Innov. 2013 Dec;20(6):559-65. doi: 10.1177/1553350613480855. Epub 2013 Mar 13.

Abstract

Aim: The purpose of this study is to investigate the effect of intraperitoneal (IP) bevacizumab on colonic anastomosis and evaluate the effects on early postoperative adhesion formation.

Materials and methods: A total of 24 mature female Sprague-Dawley rats were used for this study. Rats were randomly assigned to a control group that received saline (n = 8) or to experimental groups (n = 8 each) that received bevacizumab at a dose of 2.5 mg/kg (group 1) or 5 mg/kg (group 2). Animals were killed humanely on the seventh day after operation, and measurements of anastomotic strength and biochemical variables were performed.

Results: The mean adhesion grade was 2.63 ± 0.92, and 1 ± 0.93 and 0.75 ± 0.71 for the control and test groups, respectively. Bevacizumab significantly reduced adhesion formation in both low-dose and high-dose IP applications (P < .05). When all groups were compared, it was found that VEGF levels decreased significantly only in the tissue (P = .001), whereas there was no significant difference in the blood and the IP fluid (P = .73 and .08, respectively). We evaluated hydroxyproline levels, anastomosis bursting pressure, and histopathological healing scores. When each of these parameters were examined, there was statistical difference between groups (P = .01, .004, and .01, respectively). It was found that these parameters significantly decreased depending on increasing drug dose.

Conclusion: IP administration of bevacizumab effectively reduced the formation of adhesions and caused significant impairment of anastomotic wound healing when standard doses were administered (5 mg/kg), but the 2.5-mg/kg dosage did not affect the anastomotic wound healing and also effectively reduced the formation of adhesions.

Keywords: anastomoses healing; bevacizumab; intraperitoneal chemotherapy.

MeSH terms

  • Anastomosis, Surgical / adverse effects
  • Anastomosis, Surgical / methods*
  • Animals
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Bevacizumab
  • Biomechanical Phenomena / drug effects
  • Female
  • Injections, Intraperitoneal
  • Postoperative Complications / drug therapy
  • Postoperative Complications / prevention & control
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Adhesions / drug therapy
  • Tissue Adhesions / etiology
  • Tissue Adhesions / prevention & control*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antibodies, Monoclonal, Humanized
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Bevacizumab