The effect of bevacizumab on colon anastomotic healing in rats.
OBJECTIVE
The aim of the study was to investigate the effect of angiogenesis inhibition by bevacizumab, a monoclonal anti-vascular endothelial growth factor (VEGF) antibody, on the healing process of colonic anastomoses in rats, assessing some specific involved factors. This new agent is used mainly in metastatic colorectal cancer. The angiogenesis plays an important role in both wound healing and metastatic invasion and spread of malignant cells. There has not been any evidence assessing the optimal time for its safe use in operated patients.


METHODS
Forty Wistar rats were randomly allocated into four equal groups. A colonic anastomosis was performed in all rats. Half of them received intraoperatively a single dose of bevacizumab 5 mg/body weight and the rest received placebo. The animals were sacrificed on the 7th (Avastin 7th, placebo 7th) and 14th (Avastin 14th, placebo 14th) postoperative day. The anastomosis was resected and sent for histological study and for tissue biochemical assays (VEGF, endothelin-1 (ET-1), C-reactive protein (CRP), pro-oxidant-antioxidant balance (PAB), carbonylated proteins, hydroxyproline) using specific enzyme-linked immunosorbent assay kits. For statistical analysis, the Mann-Whitney U test was used (of statistical significance when P < 0.05).


RESULTS
No complication or anastomotic dehiscence was observed. Histology did not reveal statistically significant differences between groups concerning degree of inflammation, fibroblasts, collagen, and fibrosis. Likewise, hydroxyproline levels did not differ. However, some statistically significant differences were found in VEGF, CRP and carbonyl proteins (Avastin 7th vs placebo 7th, placebo 14th vs placebo 7th), ET-1, and PAB (Avastin 14th vs Avastin 7th), which did not finally affect the collagen synthesis marker hydroxyproline, nor did the anastomotic strength.


CONCLUSIONS
Bevacizumab, when administered intraoperatively, has no significant effect on colon anastomotic healing in rats despite a transient mild ischemia.
Pavlidis
Efstathios T
ET
Second Propedeutical Department of Surgery, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Konstantinoupoleos 49, 546 42, Thessaloniki, Greece.
Ballas
Konstantinos D
KD
Symeonidis
Nikolaos G
NG
Psarras
Kyriakos
K
Koliakos
Georgios
G
Kouzi-Koliakos
Kokona
K
Topouridou
Konstantina
K
Rafailidis
Savas F
SF
Pavlidis
Theodoros E
TE
Marakis
Georgios N
GN
Sakantamis
Athanasios K
AK
D000714:Anastomosis, Surgical / Q000009:adverse effects / Q000379:methods*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D015415:Biomarkers / Q000032:analysis; D003106:Colon; D015179:Colorectal Neoplasms / Q000150:complications / Q000473:pathology / Q000601:surgery*; D013505:Digestive System Surgical Procedures / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D007430:Intraoperative Care; D007511:Ischemia; D011183:Postoperative Complications; D051381:Rats; D017208:Rats, Wistar; D014945:Wound Healing / Q000187:drug effects*
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D000068258:Bevacizumab