Extracorporeal shock wave therapy ameliorates secondary lymphedema by promoting lymphangiogenesis

Objective: Although secondary lymphedema is a common complication after surgical and radiation therapy for cancer, the treatment options for lymphedema remain limited and largely ineffective. We thus studied the effect of extracorporeal shock wave therapy on promoting lymphangiogenesis and improving secondary lymphedema. Methods: A rabbit ear model of lymphedema was created by disruption of lymphatic vessels. Two weeks after surgery, the lymphedematous ear was treated with or without low-energy shock waves (0.09 mJ/mm², 200 shots), three times per week for 4 weeks. Results: Western blot analysis showed that the expression of vascular endothelial growth factor (VEGF)-C (1.23-fold, P < .05) and VEGF receptor 3 (VEGFR3; 1.53-fold, P < .05) was significantly increased in the ears treated with shock wave than in the untreated lymphedematous ears. Compared with the control group, shock wave treatment led to a significant decrease in the thickness of lymphedematous ears (3.80 ± 0.25 mm vs 4.54 ± 0.18 mm, P < .05). Immunohistochemistry for VEGFR3 showed the density of lymphatic vessels was significantly increased by shock wave treatment (P < .05). Conclusion: Extracorporeal shock wave therapy promotes lymphangiogenesis and ameliorates secondary lymphedema, suggesting that extracorporeal shock wave therapy may be a novel, feasible, effective, and noninvasive treatment for lymphedema.