Abstract
Although physiologic surgeries for lymphedema (i.e., lymphovenous bypass, vascularized lymph node transplantation) are becoming well established, unpredictable outcomes have still been reported in some studies. Therefore, authors have investigated ways to improve these surgery outcomes. The goal of our study was to conduct a comprehensive systematic review of targeted therapy administration in the surgical treatment of lymphedema. We conducted a comprehensive systematic review of the published literature on targeted therapies associated with lymphedema surgery using the PubMed database. Eligibility criteria excluded papers that reported surgical treatment of lymphedema without the use of targeted therapies and also papers describing targeted therapies in nonsurgical treatment of lymphedema. s, presentations, reviews, and meta-analyses were also excluded.Extracted data included the year of study, country, lymphedema model, surgical technique, targeted therapy agent, therapy delivery, findings, and outcomes. From 823 potential papers found in the literature, 10 studies fulfilled the eligibility criteria. All papers were experimental, and most of them on small animal model (7/10). Different targeted therapies were proposed, but all of them were associated with lymph node transplantation. The most common targeted therapy proposed mechanism was growth factor delivery (8/10). However, one paper used adipose-stem cell, and one paper proposed the use of sterile inflammation. The pooled publications assessing targeted therapy administration in the surgical treatment of lymphedema demonstrate encouraging data for positive outcomes. To date, all studies were experimental and related to lymph node transfer.
Highlights
BackgroundLymphedema is a chronic lymphatic condition frequently related to cancer treatment in developed countries
Experimental studies of secondary lymphedema have demonstrated that vascular endothelial growth factor (VEGF) C is an effective promoter of lymphangiogenesis, with potential to reduce tissue edema [8,9]
VEGF-C provided greatest therapeutic results compared to other VEGFs
Summary
Lymphedema is a chronic lymphatic condition frequently related to cancer treatment (i.e., radiation, lymphadenectomy) in developed countries. It is estimated that 5 to 6 million people have lymphedema in the United States, and the incidences described in the literature are high, such as one in every six patients undergoing solid tumor treatment [1]. In spite of mainstream thinking, most patients develop lymphedema only months after the lymphatic injury, demonstrating that the physiopathology behind it involves further inflammatory steps, such as fibrosis (i.e., Th2-inflammatory response), where the parenchyma is replaced by scar tissue [2,3,4]. Experimental studies of secondary lymphedema have demonstrated that vascular endothelial growth factor (VEGF) C is an effective promoter of lymphangiogenesis, with potential to reduce tissue edema [8,9]. Clinical translation of such therapies has been an object of concern, considering the potential risk of metastasis in cancer patients [9]
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