The anti-adhesive effect of anti-VEGF agents in experimental models: A systematic review

Adhesions constitute a major problem in abdominal-pelvic and thoracic surgery with significant impact in the postoperative quality of life and healthcare services utilization. Adhesiogenesis is the result of increased fibrin formation, impaired fibrinolysis, angiogenesis, and fibrosis. Despite the recent advancements, the ideal anti-adhesive agent remains to be determined. To this end, we performed a comprehensive literature search in PubMed, EMBASE, and Scopus databases to identify studies investigating the antiadhesive role of anti-VEGF agents in peritoneal, pleural, and pericardial experimental adhesion models. Fifteen studies were eligible for inclusion with a total population of 602 animals (334 rats, 180 rabbits, and 88 mice). The majority of included studies (11/15) used bevacizumab, while three studies used other anti-VEGF antibodies and one study used an anti-VEGFR-antibody. A rat model was used in nine studies, while rabbit (n = 3) or mouse (n = 3) models were used less frequently. Eleven studies used peritoneal models, three studies used pleural models, and one study used a pericardial model. The scales (n = 12) and interval (Range: 1-42 days) used for the evaluation of adhesions varied between the studies. All studies demonstrated a significant decrease in adhesion scores between the anti-VEGF and control groups up to 42 days postprocedure. VEGF blockade resulted in decreased fibrosis in four out of five studies that used peritoneal models, while the effect on pleural models depended on the pleurodesis agent and was significant between 7 and 28 days. The effect of anti-VEGF agents on anastomosis integrity depends on the dose and the model that is used (inconclusive results).Current data support the anti-adhesive role of Anti-VEGF agents in all three serosal surfaces up to 6 weeks postprocedure. Further studies are needed to confirm the anti-adhesive role of anti-VEGF agents in pleural and pericardial adhesion experimental models and investigate any effect on anastomosis integrity in peritoneal models.