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It is estimated that 140 to 200 million people are affected by lymphedema worldwide. Many studies have proposed targeted therapies that can be delivered systemically or locally to treat lymphedema. Since lymphedema primarily affects the skin and subcutaneous tissues, topical approaches to therapy should be considered as an attractive proposition as they can avoid systemic complications. In light of this, we conducted a systematic review of publications that analyzed the use of topical approaches to delivering targeted therapies in the treatment of lymphedema. We hypothesized that topical approaches resulted in the satisfactory treatment of lymphedema. We conducted a systematic review of publications on PubMed. The main eligibility criterion was that the articles should primarily investigate the use of topical approaches to delivering targeted therapies in the treatment of lymphedema. Consequently, we excluded papers that investigated any other delivery approaches or medical conditions. Of the 174 potential studies found in the literature, six were found to fulfill our eligibility criteria. All these studies were experimental ones on small animals (mice). The authors generally proposed different types of therapies, which could be clustered into two main groups: 1) induction of lymphangiogenesis [vascular endothelial growth factor C (VEGF-C) hydrogel or fibroblast growth factor]; and 2) modulation of inflammation (tacrolimus or topical collagen gel or troxerutin-phosphatidylcholine). All studies presented positive outcomes, demonstrating that topical therapy is a promising route for delivering growth factors and anti-inflammatory agents in the treatment of lymphedema. However, studies were conducted under heterogeneous protocols, and the safe application of these therapies in humans has not been assessed. Further studies are necessary to confirm the benefits and safety of targeted topical therapy on patients with lymphedema.

Different delivery mechanisms have been proposed in the literature for targeted therapies in the treatment of lymphedema. They vary from simple and direct injection to sophisticated induction of gene expression in a targeted tissue. We conducted a systematic review of publications assessing the use of viral vectors for gene transfer in lymphedema treatment. We hypothesized that viral vectors are an effective way to deliver targeted therapy in lymphedema treatment. 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 use of viral vectors for other medical conditions. Abstracts, presentations, reviews, meta-analyses, and non-English language articles were also excluded. From 21 potential articles found in the literature, fourteen fulfilled study eligibility criteria. Positive outcomes in terms of lymphangiogenesis were seen. The viral vectors used included adenovirus and recombinant adeno-associated virus. Most of the genes expressed were growth factors, but expression of dominant-negative transforming growth factor-β1 receptor-II or Prox1 was also proposed. Five studies targeted genetic expression on lymphedema tissue, five on transplanted lymph nodes, two on skeletal muscle, and one on adipose-derived stem cells. Publications assessing use of viral vectors for gene transfer in lymphedema treatment demonstrated that it is an effective mechanism of delivering targeted therapies. However, to date, all studies were experimental and further studies must be performed before translating these therapies into clinical practice.

The main benefit of autologous therapies is its easier obtention and relatively lower concerns regarding ethical implications and patient safety. We conducted a systematic review of publications assessing the potential use of blood components (lymphocytes, red blood cells (RBCs), platelet-rich plasma (PRP)) as targeted therapy in the treatment of lymphedema. We hypothesized that blood components could be used as targeted therapy in the lymphedema treatment. We also conducted a comprehensive, systematic review of the published literature on the use of blood components as targeted therapies in the treatment of lymphedema using the PubMed database. Eligibility criteria excluded papers that aimed to investigate the correlation of inflammatory cells and the physio-pathogenesis of lymphedema. Abstracts, presentations, reviews, and meta-analyses were also excluded. From the 338 potential papers found in the literature, 11 studies fulfilled the eligibility criteria. Different types of targeted therapies were proposed, but the majority of papers investigated the potential use of lymphocytes (9/11). The use of PRP was investigated in two papers and the use of RBCs in one paper. Interestingly, six out of 11 studies were done on patients with lymphedema, but the most recent was published in 1999. The remaining publications were experimental studies on dogs, rats, or in vitro. The publications demonstrated positive outcomes for the delivery of lymphocytes and PRP in lymphedema treatment. Lymphocyte was the most common blood component investigated. Even though more than half of the papers found were conducted on patients, we noticed a scientific gap of more than 20 years on the topic.

Objective Desmoplastic melanoma (DM) is a rare variant of invasive malignancy of the skin pigmented cells. We present a comprehensive study reporting on US demographics, disease characteristics, and survival, to contribute to the current knowledge and raise awareness of this rare disease. Materials and methods The demographics of DM patients diagnosed from January 1, 2004, to December 31, 2015, were obtained by querying the National Cancer Database. The characteristics of DM were compared with common malignant melanoma (CMM) using univariate and multivariate regression models. Five-year overall survival (OS) curves were estimated using Kaplan-Meier analyses and the Cox proportional regression model. Results Our query found 5,895 patients diagnosed with DM and 292,939 patients with CMM. DM tended to present at an older age, a more advanced stage, and with a Breslow depth greater than 4 mm at diagnosis (P