The role of vascular endothelial growth factors and neovascularization in the development of recurrent varicose veins after surgery

Abstract

Introduction: Varicose disease remains an actual pathology due to high incidence, possible complications and also damage to the quality of life. The basic treatment of varicose veins is surgical one. According to retrospective observations, about 35% of patients over 2-5 years after the surgery develop recurrent varicose veins with pathologic reflux at the sapheno-femural junction (SFJ). Relapsed venous reflux at SFJ can lead to severe venous insufficiency and recurrent venous disease. Materials and methods: The study included 26 patients with venous disease in the basin of great saphenous vein in both legs, taking part to class C2-C3, according to CEAP classification (Clinical- Etiology-Anatomy-Pathophysiology). To the patients with a defect in the SFJ and a great saphenous vein reflux, confirmed by Doppler Duplex scanning, was performed the crossectomy and striping in combination with mini-phlebectomy to remove the dilated veins. In all patients were performed both methods of prevention of the phenomenon of neovascularization: anatomical barrier and selective crossectomy, either on the left or right leg. Vascular endothelial growth factors (VEGF-C/VEGF-D) were determined by immunohistochemical methods through monoclonal antibodies.

Results: One month later after the surgery have been effectuated Duplex scanning to all patients, for the control of performed crossectomy, which demonstrated a lack of residual affluents. One year after the surgery in 15.2% of patients were detected visible varices at the thigh, while the phenomenon of neovascularization, confirmed by Doppler Duplex scanning, was detected in 22.9% patients. After two years the frequency of phenomenon of neovascularization was 34.5% (23% selective crossectomy and anatomical barrier-11.5%). In these patients, plasma levels of VEGF-C/VEGF-D was increased, which confirms the role of these factors in the pathogenesis of the phenomenon of neovascularization and recurrent varicose veins.

Conclusion: In addition to surgical treatment of varicose veins, which includes various methods of prevention of the phenomenon of neovascularization (anatomical barriers, selective crossectomy, endothelial inversion), antiangiogenic therapy gets a new large aspect directed towards receptors VEGFR-3 and its ligands VEGF-C/VEGF-D. They are directly involved in the process of formation of new, tortuous vessels and development of severe venous insufficiency.

Key words: Endothelial growth factors, neovascularization, varices.