The influence of locally applied vascular endothelial growth factor (VEGF) embedded in TachoSil® on esophagogastric anastomotic healing in a rat model

Background: Anastomotic leakage after esophageal surgery develops in 2% to 30% and is a significant cause of morbidity and mortality. To prevent anastomotic leakage and its associated surgical complications, different procedures for anastomotic augmentation have recently been developed, e.g. omentoplasty or collagen-fibrin matrices (TachoSil®).

Aim: i.) to establish a novel model of esophagogastric anastomosis in rats and ii.) to evaluate the effect of the use of TachoSil® – with or without the augmentation of VEGF.

Methods: We developed a novel rat model of gastric tube formation followed by end-to-end esophagogastric anastomosis. Standardized anastomoses were carried out in 69 male Brown-Norway rats. Esophagogastric healing was assessed by measuring anastomotic breaking strength at the fifth postoperative day and tissue was preserved for subsequent molecular and immunohistochemical analyses. Animals were randomly assigned to 3 different groups (n = 23): i.) native-group (control group) ii.) esophagogastric anastomosis supported by a circularly applied TachoSil® matrix (TachoSil® subgroup) and iii.) esophagogastric anastomosis supported by a circularly applied TachoSil® matrix soaked in VEGF solution (T+GF subgroup).

Results: Control animals showed an increased mortality rate of 17.4% (4/23) caused by a higher rate of anastomosis insufficiency in comparison to the T-group with the rate of 8.7% (2/23) and the (T+GF)-group with a rate of 4.3% (1/23). The two latter groups did not differ significant in both mortality and morbidity rates. Moreover, in both T- und (T+GF)- group significantly less adhesions were present compared to control animals, while no significant differences in preoperative weight, time of anaesthesia and operative time were observed. The histopathologic and molecular analyses revealed a mentionable increase in neo-angiogenesis, collagen and fibroblast deposit in both TachoSil® groups in comparison to control animals. Moreover reduced hemorrhage and perianastomotic necrosis was present.

Conclusion: In our study the use of a TachoSil® patch as cover to the esophagogastric anastomosis with or without the augmentation of a growth factor (VEGF) might reduce perioperative complications and improve the outcome after esophagogastric anastomosis.