Effects of Tissue Flap on Expression of Vascular Endothelial Growth Factor-C (VEGF-C) as a Marker of Improved Inguinal Lymphatic Circulation on Dissected Mice

Abstract

Background: Radical surgery in cancer patients might result in complications like lymphedema. Tissue transfer procedure and lymphatic reconstruction could be done to manage lymphedema. Few biomarker expressions were identified to be associated with lymphangiogenesis and improved lymphatic system function after dissection. This study aims to evaluate the development of new lymphatic vessels by adding flap tissue after lymphatic dissection, assessed by VEGF-C expression, macrophage infiltration, and fibrotic tissue development. Methods: This is a non-randomized clinical trial at Animal House Skill Laboratory, Faculty of Medicine, Universitas Indonesia, conducted from January to March 2018. Sprague clawley male mice were aged 8-12 weeks were used and divided into control and trial groups. Each mouse underwent inguinal dissection and was randomized to receive additional flap tissue procedures and then evaluated two months after. Methylene blue dye was used to assess the lymphatic flow. Histopathology and immunohistochemistry examination was used to assess the development of fibrotic tissue. Data analysis was done by using SPSS version 20.0 for Windows. Results: 18 mice were included in the analysis and divided into two groups. Eight out of 9 mice (88.9%) in the trial group, which received flap tissue, showed lymphatic flow from the visualization of methylene blue, compared to two mice (22.2%) from the control group (p=0.15) two months after surgery. Histopathology examination showed wider fibrotic tissue of the lymphatic system from the trial group (p=0.05). Immunohistochemistry analysis also showed higher VEGF-C (p=0.01) and CD68 expression in the trial group (p=0.15). Conclusion: The addition of flap tissue might improve lymphatic flow, proven by increased lymphatic circulation and VEGF-C expression.