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International Journal of Molecular... Jul 2022Secondary lymphedema is a common complication of lymph node dissection or radiation therapy for cancer treatment. Conventional therapies such as compression sleeve... (Review)
Review
Secondary lymphedema is a common complication of lymph node dissection or radiation therapy for cancer treatment. Conventional therapies such as compression sleeve therapy, complete decongestive physiotherapy, and surgical therapies decrease edema; however, they are not curative because they cannot modulate the pathophysiology of lymphedema. Recent advances reveal that the activation and accumulation of CD4+ T cells are key in the development of lymphedema. Based on this pathophysiology, the efficacy of pharmacotherapy (tacrolimus, anti-IL-4/IL-13 antibody, or fingolimod) and cell-based therapy for lymphedema has been demonstrated in animal models and pilot studies. In addition, mesenchymal stem/stromal cells (MSCs) have attracted attention as candidates for cell-based lymphedema therapy because they improve symptoms and decrease edema volume in the long term with no serious adverse effects in pilot studies. Furthermore, MSC transplantation promotes functional lymphatic regeneration and improves the microenvironment in animal models. In this review, we focus on inflammatory cells involved in the pathogenesis of lymphedema and discuss the efficacy and challenges of pharmacotherapy and cell-based therapies for lymphedema.
Topics: Animals; Anti-Inflammatory Agents; Lymph Node Excision; Lymphatic System; Lymphatic Vessels; Lymphedema
PubMed: 35886961
DOI: 10.3390/ijms23147614 -
Clinical and Translational Medicine Jun 2022Secondary lymphedema is a common complication of cancer treatment, and previous studies have shown that the expression of transforming growth factor-beta 1 (TGF-β1), a...
BACKGROUND
Secondary lymphedema is a common complication of cancer treatment, and previous studies have shown that the expression of transforming growth factor-beta 1 (TGF-β1), a pro-fibrotic and anti-lymphangiogenic growth factor, is increased in this disease. Inhibition of TGF-β1 decreases the severity of the disease in mouse models; however, the mechanisms that regulate this improvement remain unknown.
METHODS
Expression of TGF-β1 and extracellular matrix molecules (ECM) was assessed in biopsy specimens from patients with unilateral breast cancer-related lymphedema (BCRL). The effects of TGF-β1 inhibition using neutralizing antibodies or a topical formulation of pirfenidone (PFD) were analyzed in mouse models of lymphedema. We also assessed the direct effects of TGF-β1 on lymphatic endothelial cells (LECs) using transgenic mice that expressed a dominant-negative TGF-β receptor selectively on LECs (LEC ).
RESULTS
The expression of TGF-β1 and ECM molecules is significantly increased in BCRL skin biopsies. Inhibition of TGF-β1 in mouse models of lymphedema using neutralizing antibodies or with topical PFD decreased ECM deposition, increased the formation of collateral lymphatics, and inhibited infiltration of T cells. In vitro studies showed that TGF-β1 in lymphedematous tissues increases fibroblast, lymphatic endothelial cell (LEC), and lymphatic smooth muscle cell stiffness. Knockdown of TGF-β1 responsiveness in LEC resulted in increased lymphangiogenesis and collateral lymphatic formation; however, ECM deposition and fibrosis persisted, and the severity of lymphedema was indistinguishable from controls.
CONCLUSIONS
Our results show that TGF-β1 is an essential regulator of ECM deposition in secondary lymphedema and that inhibition of this response is a promising means of treating lymphedema.
Topics: Animals; Antibodies, Neutralizing; Chronic Disease; Endothelial Cells; Fibrosis; Humans; Inflammation; Lymphedema; Mice; Transforming Growth Factor beta1
PubMed: 35652284
DOI: 10.1002/ctm2.758 -
Annals of Vascular Surgery Oct 2022Microsurgery is a new technique for lymphedema treatment. Its advantages and disadvantages remain controversial. This study is sought to collect clinical data from... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Microsurgery is a new technique for lymphedema treatment. Its advantages and disadvantages remain controversial. This study is sought to collect clinical data from patients who underwent lymphovenous bypass and vascularized lymph node transplantation to explore whether surgical procedures can effectively treat lymphedema.
METHODS
We performed a meta-analysis of the effectiveness of lymphatic microsurgery. We searched the databases of literature for articles in Chinese and English. These articles were graded for quality. Report details and outcomes were recorded. Data extraction, systematic review, and meta-analysis were performed.
RESULTS
Thirty-seven studies were included. Patients who underwent microsurgery had a significantly better chance of achieving an excellent result than patients who received conservative treatment (odds ratio = 7.07). The affected limb circumference was reduced by approximately, 44.68% after the microsurgery. After the microsurgery, 63% of the patients did not need physiotherapy, and 96% were free from painful skin infections. Lymphography showed that lymphatic transport capacity was enhanced. Moreover, 12% of the patients reported that edema reappeared in the long-term, 26% required reoperation for unsatisfactory results, and 32% experienced lymphatic leakage.
CONCLUSIONS
A vast majority of patients derive more benefit from lymphatic microsurgery than from conventional treatment. The advantages of lymphatic microsurgery outweigh the disadvantages for patients in the early and middle stages of chronic secondary lymphedema and patients in whom conventional treatment failed.
Topics: Humans; Anastomosis, Surgical; Treatment Outcome; Lymphedema; Lymphography; Lymphatic Vessels
PubMed: 35589027
DOI: 10.1016/j.avsg.2022.04.038 -
International Journal of Molecular... Apr 2023Secondary lymphedema is caused by lymphatic insufficiency (lymphatic drainage failure) following lymph node dissection during the surgical treatment or radiation therapy... (Review)
Review
Secondary lymphedema is caused by lymphatic insufficiency (lymphatic drainage failure) following lymph node dissection during the surgical treatment or radiation therapy of breast or pelvic cancer. The clinical problems associated with lymphedema are reduced quality of life in terms of appearance and function, as well as the development of skin ulcers, recurrent pain, and infection. Currently, countermeasures against lymphedema are mainly physical therapy such as lymphatic massage, elastic stockings, and skin care, and there is no effective and fundamental treatment with a highly recommended grade. Therefore, there is a need for the development of a fundamental novel treatment for intractable lymphedema. Therapeutic lymphangiogenesis, which has been attracting attention in recent years, is a treatment concept that reconstructs the fragmented lymphatic network to recover lymphatic vessel function and is revolutionary to be a fundamental cure. This review focuses on the translational research of therapeutic lymphangiogenesis for lymphedema and outlines the current status and prospects in the development of therapeutic applications.
Topics: Humans; Lymph Node Excision; Lymphangiogenesis; Lymphatic Vessels; Lymphedema; Translational Research, Biomedical; Animals
PubMed: 37175479
DOI: 10.3390/ijms24097774 -
BMJ Open Jul 2023Breast cancer-related lymphoedema (BCRL) is one of the most underestimated and debilitating complications associated with the treatment that women with breast cancer...
Effectiveness of physical exercise programmes in reducing complications associated with secondary lymphoedema to breast cancer: a protocol for an overview of systematic reviews.
INTRODUCTION
Breast cancer-related lymphoedema (BCRL) is one of the most underestimated and debilitating complications associated with the treatment that women with breast cancer receive. Several systematic reviews (SRs) of different physical exercise programmes have been published, presenting disperse and contradictory clinical results. Therefore, there is a need for access to the best available and summarised evidence to capture and evaluate all the physical exercise programmes that focus on reducing BCRL.
OBJECTIVE
To evaluate the effectiveness of different physical exercise programmes in reducing the volume of lymphoedema, pain intensity and improving quality of life.
METHOD AND ANALYSIS
The protocol of this overview is reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols, and its methodology is based on Cochrane Handbook for Systematic Reviews of Interventions. Only those SRs involving physical exercise by patients with BCRL will be included, whether on its own or combined with other exercises or other physical therapy interventions.The outcomes of interest to be considered will be lymphoedema volume, quality of life, pain intensity, grip strength, range of motion, upper limb function and any adverse event. The MEDLINE/PubMed, Lilacs, Cochrane Library, PEDro and Embase databases will be searched for reports published from database inception to April 2023.Two researchers will perform study selection, data extraction and risk of bias assessment independently. Any discrepancy will be resolved by consensus, or ultimately, by a third-party reviewer. We will use Grading of Recommendations Assessment, Development and Evaluation System to assess the overall quality of the body of evidence.
ETHICS AND DISSEMINATION
The results of this overview will be published in peer-reviewed scholarly journals and the scientific dissemination will take place in national or international conferences. This study does not require approval from an ethics committee, as it does not directly collect information from patients.
PROSPERO REGISTRATION NUMBER
CRD42022334433.
Topics: Female; Humans; Breast Cancer Lymphedema; Breast Neoplasms; Chronic Disease; Exercise; Exercise Therapy; Lymphedema; Quality of Life; Systematic Reviews as Topic
PubMed: 37429694
DOI: 10.1136/bmjopen-2023-071630 -
Advances in Wound Care Aug 2022Secondary lymphedema is a debilitating disease caused by lymphatic dysfunction characterized by chronic swelling, dysregulated inflammation, disfigurement, and... (Review)
Review
Secondary lymphedema is a debilitating disease caused by lymphatic dysfunction characterized by chronic swelling, dysregulated inflammation, disfigurement, and compromised wound healing. Since there is no effective cure, animal model systems that support basic science research into the mechanisms of secondary lymphedema are critical to advancing the field. Over the last decade, lymphatic research has led to the improvement of existing animal lymphedema models and the establishment of new models. Although an ideal model does not exist, it is important to consider the strengths and limitations of currently available options. In a systematic review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we present recent developments in the field of animal lymphedema models and provide a concise comparison of ease, cost, reliability, and clinical translatability. The incidence of secondary lymphedema is increasing, and there is no gold standard of treatment or cure for secondary lymphedema. As we iterate and create animal models that more closely characterize human lymphedema, we can achieve a deeper understanding of the pathophysiology and potentially develop effective therapeutics for patients.
Topics: Animals; Disease Models, Animal; Humans; Lymphatic System; Lymphatic Vessels; Lymphedema; Reproducibility of Results
PubMed: 34128396
DOI: 10.1089/wound.2021.0033 -
International Journal of Molecular... Jul 2020The lymphatic vasculature, along with the blood vasculature, is a vascular system in our body that plays important functions in fluid homeostasis, dietary fat uptake,... (Review)
Review
The lymphatic vasculature, along with the blood vasculature, is a vascular system in our body that plays important functions in fluid homeostasis, dietary fat uptake, and immune responses. Defects in the lymphatic system are associated with various diseases such as lymphedema, atherosclerosis, fibrosis, obesity, and inflammation. The first step in lymphangiogenesis is determining the cell fate of lymphatic endothelial cells. Several genes involved in this commitment step have been identified using animal models, including genetically modified mice. This review provides an overview of these genes in the mammalian system and related human diseases.
Topics: Animals; Endothelial Cells; Humans; Lymphangiogenesis; Lymphatic System; Lymphedema; Mice; Neovascularization, Pathologic
PubMed: 32640757
DOI: 10.3390/ijms21134790 -
Missouri Medicine 2021The purpose of this article is to describe the multidisciplinary lymphedema surgery treatment program at Washington University in St. Louis. In this article, we discuss...
The purpose of this article is to describe the multidisciplinary lymphedema surgery treatment program at Washington University in St. Louis. In this article, we discuss our collaboration with colleagues in medicine and therapy for conservative management and lymphedema staging. We describe our preferred imaging modalities for diagnosis, staging, and surgical treatment. Finally, we provide an overview of the surgical procedures we perform and our surgical treatment algorithm.
Topics: Humans; Lymphedema
PubMed: 33840856
DOI: No ID Found -
Journal of Vascular Surgery. Venous and... Sep 2019Lymphedema (LE) has been called the forgotten vascular disease, given such scant knowledge about LE-associated comorbidities or causes. Such knowledge of the...
BACKGROUND
Lymphedema (LE) has been called the forgotten vascular disease, given such scant knowledge about LE-associated comorbidities or causes. Such knowledge of the comorbidities and treatment of LE may assist in diagnostic decisions and health care planning.
METHODS
To determine the proportion of LE patients with various LE-associated comorbidities as well as the rate of associated treatment, deidentified Health Insurance Portability and Accountability Act-compliant commercial administrative claims from the Blue Health Intelligence (BHI) research database (165 million Blue Cross Blue Shield members) were queried. We analyzed a BHI study sample of 26,902 patients with LE who had been enrolled with continuous medical benefits for 12 months before and after the index date for the complete years 2012 through 2016. Patients were first identified by comorbidity and then grouped into those receiving no treatment for LE and those receiving any treatment for LE. Any treatment was defined as receiving manual lymphatic drainage, physical therapy, compression garments, or a pneumatic compression device. The purpose of this study was to determine the proportion of LE patients comorbid with various known LE-associated conditions and the treatment rates of LE patients with each comorbidity.
RESULTS
Among the 84,579,269 BHI patients enrolled during the study window, 81,366 patients were identified with LE. From this LE group, our study focused on the 26,902 patients who were enrolled with continuous medical and pharmacy benefits for 12 months before and after the index date. Among these 26,902 LE patients, breast cancer was the most frequent comorbidity with LE (32.1%), and these patients almost universally received any treatment (94.2%); other cancer types, such as melanoma (2.1%) and prostate cancer (0.7%), were less frequent and received any treatment less often, 75% and 82% of the time, respectively. Venous leg ulcer was the most common non-cancer-linked comorbidity for LE (9.6%), but only 81.7% of venous leg ulcer patients received any treatment for LE.
CONCLUSIONS
To our knowledge, this is the largest study to date detailing the comorbidities associated with LE and LE treatment rates within each. Our findings suggest that a sizable proportion of cancer-related LE patients do not receive appropriate treatment. Furthermore, this study highlights the role of advanced venous disease as an LE comorbidity that is frequently untreated and its associated gap in treatment.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blue Cross Blue Shield Insurance Plans; Child; Child, Preschool; Chronic Disease; Comorbidity; Databases, Factual; Healthcare Disparities; Humans; Infant; Lymphedema; Male; Middle Aged; Neoplasms; Prevalence; Retrospective Studies; Risk Factors; Treatment Outcome; United States; Venous Insufficiency; Young Adult
PubMed: 31248833
DOI: 10.1016/j.jvsv.2019.02.015 -
Anticancer Research Aug 2017Lower body lymphedema is a chronic condition and a significant cause of morbidity following treatment of gynecologic cancer that strongly impacts patients' quality of... (Review)
Review
Lower body lymphedema is a chronic condition and a significant cause of morbidity following treatment of gynecologic cancer that strongly impacts patients' quality of life (QoL). Most studies on secondary lymphedema have been performed on the upper limb after breast cancer treatment and much less is known about lower body lymphedema after gynecologic malignancies. This review focuses on secondary lymphedema due to gynecologic cancer treatment, analyzing its incidence in the different types of gynecologic cancer, diagnosis, risk factors, impact on QoL and treatment. A systematic search of Medline has been performed to track the studies evaluating lower body lymphedema after treatment for endometrial, ovarian, cervical and vulvar cancer. Unfortunately, there is no consensus about a uniform evaluation and, as a consequence, the reported incidence is broadly different among the studies. Standardization in lymphedema evaluation is required to better compare the outcome of different types of treatment.
Topics: Female; Genital Neoplasms, Female; Humans; Lower Extremity; Lymph Node Excision; Lymphedema; Quality of Life; Risk Factors
PubMed: 28739682
DOI: 10.21873/anticanres.11785