Huayllani, María T.

Background: The incidence of lymphedema may be as high as 65% among breast cancer patients, varying according to the diagnostic method and locoregional treatment. Therefore, investigations of preventive methods are highly welcomed. Our goal was to conduct a systematic review of the literature about the use of axillary reverse mapping to prevent lymphedema during breast cancer treatment. We hypothesized that identification of arm-draining lymph nodes may decrease the incidence of lymphedema. Methods: On October 7, 2019, we conducted a systematic review of studies in PubMed, Cochrane Clinical Answers, and Cochrane Central Register of Controlled Trials, without time frame or language limitations, on the use of axillary reverse mapping to prevent lymphedema during breast cancer treatment. We excluded articles that investigated other uses of lymphoscintigraphy, such as lymphedema diagnosis or treatment evaluation. Results: Of 104 potential articles found in the literature, 5 studies fulfilled the eligibility criteria. A total of 501 patients were included. Reverse mapping was done with radiography or single-photon emission computed tomography/computed tomography. Moreover, the examination was applied with different treatments, such as axillary lymph node dissection or radiotherapy, allowing preservation of noncompromised lymph nodes. Axillary reverse mapping also had prognostic value and was used with sentinel lymph node biopsy to identify patients at higher risk for lymphedema. Only one study compared the incidence of lymphedema between patients who received standard care or reverse mapping, showing significant benefits of its use. Conclusions: Use of axillary reverse mapping to prevent lymphedema is feasible and seems to provide valuable information for breast cancer treatment. Future studies that compare reverse mapping and standard care are still necessary.

Background Demographic characteristics are known to influence the treatment and outcomes of patients with invasive melanoma. Whether these characteristics influence treatment costs is unknown. We aimed to analyze whether patient demographics and tumor characteristics influence treatment costs for patients with invasive cutaneous melanoma in Florida. Methods This was a cross-sectional study in which the Florida Inpatient and Outpatient Dataset of the Agency for Health Care Administration was analyzed for patients with a diagnosis of invasive melanoma between January 1, 2013 and December 31, 2018. Categorical variables were assessed using Pearson χ2 tests, and continuous variables were evaluated using Kruskal-Wallis tests. Logistic regression analysis was conducted to identify the association between patient demographics and total costs. All analyses were done using SAS 9.4 statistical software (SAS Institute, Inc). Results Multivariate analysis showed that sex (P < 0.001), hospital setting (P < 0.001), race/ethnicity (P < 0.01), patient region (P < 0.01), Elixhauser Comorbidity Index score (P < 0.001), presence of metastasis (P < 0.01), total number of procedures (P < 0.001), and length of stay (P < 0.001) were correlated with the cost of treatment of invasive cutaneous melanoma. After stratification, the association between cost and race/ethnicity disappeared for inpatients but remained for Black patients in the outpatient setting (P < 0.001). The association between cost and patient residence regions also differed when the cohort was stratified. Conclusions Strategies addressing disparities in treatment cost of invasive melanoma should differ, depending on the hospital setting where the patient is being treated.

Background: Vascular endothelial growth factor (VEGF) C156S is an engineering variant of VEGF-C that has the potential to promote lymphangiogenesis, activating on VEGF receptor (VEGFR) 3, without promoting angiogenesis (i.e., not acting on VEGFR-2). We conducted a systematic review of publications assessing the use of this growth factor in lymphedema treatment. We hypothesized that VEGF-C156S specificity for VEGFR-3 was an important differential for the lymphangiogenesis promoted by it. Methods and Results: We conducted a comprehensive systematic review of the published literature on PubMed/Medline, Embase, and Cochrane Clinical Answers. Eligibility criteria included articles reporting data on the use of VEGF-C156S in lymphedema treatment. We excluded articles that investigated physiology action of VEGF-C156S and articles that focused on other therapies. From 304 potential articles found in the literature, four studies fulfilled the study eligibility criteria. To date, all studies about this growth factor have been experimental. The effect of VEGF-C156 on lymph node transfer was investigated in half of the experiments. Interestingly, delivery of VEGF-C156S was mostly performed through viral gene transfer, but injection (subcutaneously or intravenously) of it as a protein (liposomal or nonliposomal) was also investigated by one author to assess drug bioavailability. Conclusions: Although authors reported promotion of lymphangiogenesis, VEGF-C156S was correlated with lymphatic hyperplasia or nonstatistically significant lymphangiogenesis compared with controls. Scientific evidence about the use of VEGF-C156S in lymphedema treatment is still limited. However, authors have shown that its lymphangiogenic effect is inferior to VEGF-C.

Abstract Background Posttraumatic lymphedema develops more frequently than expected and reports on its management are scarce in the literature. We aimed to report the clinical outcomes of a case series of posttraumatic lymphedema patients treated with different vascularized lymph node transfers (VLNTs). Patients and Methods Five patients with secondary posttraumatic lower limb lymphedema treated with VLNT were included in this report. The groin-VLNT (n = 1), supraclavicular-VLNT (n = 2), and gastroepiploic-VLNT (n = 2) were implemented. The average flap area was 69.8 cm2. Patients underwent postoperative complex decompressive therapy for an average of 10.0 months. Results The average mean circumference reduction rate was 24.4% (range, 10.2–37.6%). Postsurgical reduction in the number of infection episodes per year was observed in all patients. The mean follow-up was 34.2 months. Conclusions VLNT is a promising surgical treatment for posttraumatic lymphedema patients. In our report, VLNT has demonstrated to reduce the volume and number of infections per year in posttraumatic lymphedema.

Background Radiation-induced skin injuries have been treated with different medical therapies and have shown diverse outcomes. We aim to evaluate the effect of adipose-derived stem cells (ADSCs) therapy on radiation-induced skin injury. Methods We performed a review by querying PubMed, Ovid MEDLINE, and EMBASE databases from inception to April 2020 following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The MeSH terms “adipose-derived stem cells,” “wound healing,” “radiation,” and synonyms in combinations determined our search strategy. Experimental peer-reviewed articles describing the protocol and comparing the results with controls were included. Non-English studies were excluded. Results Our search recorded a total of 137 articles. Only 8 studies met our inclusion criteria and were included in this review. Five studies evaluated the use of ADSC alone, whereas the others evaluated the efficacy of ADSC seeded in scaffolds. Adipose-derived stem cell–based therapies, either alone or seeded in scaffolds, were shown to improve wound healing in most studies when compared with controls. Conclusions There is evidence supporting the positive benefits from ADSC-based therapies in radiation-induced skin injury. However, further studies are needed to standardize the method of ADSC extraction, radiation-induced skin injury experimental model, and increase the time of follow-up to evaluate the results accurately.

Background: Archeological archives report cranioplasty as 1 of the oldest surgical procedures; however, it was not until the last century that true advances have been made. Alternative approaches are necessary to achieve optimal closure of the defect with fewer adverse effects. We aim to evaluate the use of human adipose-derived stem cells (hADSCs) alone or seeded in scaffolds as the main treatment for cranial bone defects and to assess human patient outcomes. Methods: A systematic review was performed by querying PubMed, Ovid MEDLINE, EMBASE, and Cumulative Index to Nursing and Allied Health Literature databases with the MeSH terms: “adipose-derived stem cells,” “cranial bone defect,” “stromal vascular factor,” “fat grafting,” as well as synonyms in combinations determined by our search strategy. We included human models that used hADSCs as primary therapy. We excluded studies in languages other than English. Results: One hundred ninety-four studies were identified after removal of duplicates. Four articles that used hADSCs as the main therapy to treat calvarial defects in humans were included. One article applied the cell therapy alone, and 3 used β-tricalcium phosphate granules as a scaffold to seed the hADSCs. Conclusions: Bone regeneration was reached in a short and intermediate period using autologous hADSCs in humans with no major adverse effects in all 4 articles included. A long-term follow-up study (6 years) exhibited late infections and reabsorption of the β-tricalcium phosphate scaffold seeded with hADSCs.

Bladder acontractility affects several thousand patients in the United States, but the available therapies are limited. Latissimus dorsi detrusor myoplasty (LDDM) is a therapeutic option that allows patients with bladder acontractility to void voluntarily. Our goal was to conduct a systematic review of the literature to determine whether LDDM is a better option than clean intermittent catheterization (CIC) (standard treatment) in patients with bladder acontractility. On January 17, 2020, we conducted a systematic review of the PubMed/MEDLINE, Cochrane Clinical Answers, Cochrane Central Register of Controlled Trials, Embase, and ClinicalTrials.gov databases, without time frame limitations, to identify articles on the use of LDDM for bladder acontractility. Of 75 potential articles, 4 fulfilled the eligibility criteria. The use of LDDM to treat patients with bladder acontractility was reported in four case series by the same group in Europe. Fifty-eight patients were included, and no comparison groups were included. The most common cause of bladder acontractility was spinal cord injury (n=36). The mean (±standard deviation) operative time was 536 (±22) minutes, postoperative length of hospital stay ranged from 10 to 13 days, and follow-up ranged from 9 to 68 months. Most patients had complete response, were able to void voluntarily, and had post-void residual volume less than 100 mL. Although promising outcomes have been obtained, evidence is still weak regarding whether LDDM is better than CIC to avoid impairment of the urinary tract among patients with bladder acontractility. Further prospective studies with control groups are necessary.

The potential to differentiate into different cell lines, added to the easy and cost-effective method of extraction, makes adipose-derived stem cells (ADSCs) an object of interest in lymphedema treatment. Our study’s goal was to conduct a comprehensive systematic review of the use of ADSCs in lymphatic tissue engineering and regeneration. On July 23, 2019, using PubMed/MEDLINE, Cochrane Clinical Answers, Cochrane Central Register of Controlled Trials, and Embase databases, we conducted a systematic review of published literature on the use of ADSCs in lymphatic tissue engineering and regeneration. There were no language or time frame limitations, and the following search strategy was applied: ((Adipose stem cell) OR Adipose-derived stem cell)) AND ((Lymphedema) OR Breast Cancer Lymphedema). Only original research manuscripts were included. Fourteen studies fulfilled the inclusion criteria. Eleven studies were experimental (in vitro or in vivo in animals), and only three were clinical. Publications on the topic demonstrated that ADSCs promote lymphangiogenesis, and its effect could be enhanced by modulation of vascular endothelial growth factor-C, interleukin-7, prospero homeobox protein 1, and transforming growth factor-β1. Pilot clinical studies included 11 patients with breast cancer-related lymphedema, and no significant side effects were present at 12-month follow-up. Literature on the use of ADSCs in lymphatic tissue engineering and regeneration demonstrated promising data. Clinical evidence is still in its infancy, but the scientific community agrees that ADSCs can be useful in regenerative lymphangiogenesis. Data collected in this review indicate that unprecedented advances in lymphedema treatment can be anticipated in the upcoming years.