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Clinical and Translational Medicine Apr 2022The lymphatic contribution to the circulation is of paramount importance in regulating fluid homeostasis, immune cell trafficking/activation and lipid metabolism. In...
BACKGROUND
The lymphatic contribution to the circulation is of paramount importance in regulating fluid homeostasis, immune cell trafficking/activation and lipid metabolism. In comparison to the blood vasculature, the impact of the lymphatics has been underappreciated, both in health and disease, likely due to a less well-delineated anatomy and function. Emerging data suggest that lymphatic dysfunction can be pivotal in the initiation and development of a variety of diseases across broad organ systems. Understanding the clinical associations between lymphatic dysfunction and non-lymphatic morbidity provides valuable evidence for future investigations and may foster the discovery of novel biomarkers and therapies.
METHODS
We retrospectively analysed the electronic medical records of 724 patients referred to the Stanford Center for Lymphatic and Venous Disorders. Patients with an established lymphatic diagnosis were assigned to groups of secondary lymphoedema, lipoedema or primary lymphovascular disease. Individuals found to have no lymphatic disorder were served as the non-lymphatic controls. The prevalence of comorbid conditions was enumerated. Pairwise co-occurrence pattern analyses, validated by Jaccard similarity tests, was utilised to investigate disease-disease interrelationships.
RESULTS
Comorbidity analyses underscored the expected relationship between the presence of secondary lymphoedema and those diseases that damage the lymphatics. Cardiovascular conditions were common in all lymphatic subgroups. Additionally, statistically significant alteration of disease-disease interrelationships was noted in all three lymphatic categories when compared to the control population.
CONCLUSIONS
The presence or absence of a lymphatic disease significantly influences disease interrelationships in the study cohorts. As a physiologic substrate, the lymphatic circulation may be an underappreciated participant in disease pathogenesis. These relationships warrant further, prospective scrutiny and study.
Topics: Humans; Lipedema; Lymphatic Diseases; Lymphedema; Prospective Studies; Retrospective Studies
PubMed: 35452183
DOI: 10.1002/ctm2.760 -
Physiological Reviews Oct 2021Primary lymphedema is a long-term (chronic) condition characterized by tissue lymph retention and swelling that can affect any part of the body, although it usually... (Review)
Review
Primary lymphedema is a long-term (chronic) condition characterized by tissue lymph retention and swelling that can affect any part of the body, although it usually develops in the arms or legs. Due to the relevant contribution of the lymphatic system to human physiology, while this review mainly focuses on the clinical and physiological aspects related to the regulation of fluid homeostasis and edema, clinicians need to know that the impact of lymphatic dysfunction with a genetic origin can be wide ranging. Lymphatic dysfunction can affect immune function so leading to infection; it can influence cancer development and spread, and it can determine fat transport so impacting on nutrition and obesity. Genetic studies and the development of imaging techniques for the assessment of lymphatic function have enabled the recognition of primary lymphedema as a heterogenic condition in terms of genetic causes and disease mechanisms. In this review, the known biological functions of several genes crucial to the development and function of the lymphatic system are used as a basis for understanding normal lymphatic biology. The disease conditions originating from mutations in these genes are discussed together with a detailed clinical description of the phenotype and the up-to-date knowledge in terms of disease mechanisms acquired from in vitro and in vivo research models.
Topics: Animals; Humans; Lymphangiogenesis; Lymphatic System; Lymphatic Vessels; Lymphedema
PubMed: 33507128
DOI: 10.1152/physrev.00006.2020 -
Cancer Feb 2022
Topics: Breast Cancer Lymphedema; Breast Neoplasms; Female; Humans; Lymphedema
PubMed: 34614203
DOI: 10.1002/cncr.33942 -
Annales de Biologie Clinique Dec 2018The Waldmann's disease is a primitive intestinal lymphangectasia. This exsudative enteropathy initiates a protein leakage by the digestive tract. Clinically, this...
The Waldmann's disease is a primitive intestinal lymphangectasia. This exsudative enteropathy initiates a protein leakage by the digestive tract. Clinically, this syndrome is characterised by oedemas and biologically by hypoprotidemia and loss of lymphocytes T CD4+, which increases a risk for infections. Here, we describe a patient's case for whom the protein loss was aggravated by a nephrotic syndrome.
Topics: Child; Child, Preschool; Edema; Female; Follow-Up Studies; Humans; Infant; Lymphangiectasis, Intestinal; Lymphedema
PubMed: 30543193
DOI: 10.1684/abc.2018.1398 -
Extracellular Vesicles from Adipose-Derived Stem Cells Relieve Extremity Lymphedema in Mouse Models.Plastic and Reconstructive Surgery Nov 2023Transplantation of adipose-derived mesenchymal stem cells (ADSCs) has been reported to improve the severity of chronic lymphedema. Extracellular vesicles (EVs) derived...
BACKGROUND
Transplantation of adipose-derived mesenchymal stem cells (ADSCs) has been reported to improve the severity of chronic lymphedema. Extracellular vesicles (EVs) derived from mesenchymal stem cells have been reported to exert effects such as the promotion of angiogenesis, suppression of inflammation, and regeneration of damaged organs. In this study, the authors show that lymphangiogenesis was induced by EVs derived from ADSCs and reveal the therapeutic potential of these EVs for the treatment of lymphedema.
METHODS
The authors examined the in vitro effects of ADSC-EVs to lymphatic endothelial cells (LECs). Next, they conducted an in vivo analysis of ADSC-EVs to mouse lymphedema models. Bioinformatics analysis was also performed to evaluate the implications of the altered microRNA expression.
RESULTS
The authors showed that ADSC-EVs promoted the proliferation, migration, and tube formation of LECs, and the gene expression of lymphatic markers was elevated in the ADSC-EV-treated group. Notably, a mouse lymphedema model revealed that legs treated with ADSC-EVs had markedly improved edema, with increased numbers of capillary vessels and lymphatic channels. Bioinformatics analysis revealed that ADSC-EV-associated microRNAs, such as miR-199a-3p, miR-145-5p, miR-143-3p, miR-377-3p, miR-100-3p, miR-29a-3p, miR-495-3p, and miR-29c-3p, targeted mouse double minute 2 homolog, which contributed to the stability of hypoxia-inducible factor 1α and resulted in angiogenesis and lymphangiogenesis in LECs.
CONCLUSIONS
The present study showed lymphangiogenic effects of ADSC-EVs, which will lead to new treatment options for chronic lymphedema. Cell-free therapy with EVs has fewer potential risks, such as poor engraftment efficiency and potential tumor formation, than stem cell transplantation and could be a promising tool for patients with lymphedema.
CLINICAL RELEVANCE STATEMENT
This study may open up new possibilities for novel therapies for lymphedema.
Topics: Animals; Mice; Humans; Endothelial Cells; MicroRNAs; Mesenchymal Stem Cells; Extremities; Extracellular Vesicles; Lymphedema
PubMed: 36877751
DOI: 10.1097/PRS.0000000000010388 -
Breast Cancer Research and Treatment Feb 2023Breast cancer-related lymphedema (BCRL) represents a significant concern for patients following breast cancer treatment, and assessment for BCRL represents a key... (Review)
Review
PURPOSE
Breast cancer-related lymphedema (BCRL) represents a significant concern for patients following breast cancer treatment, and assessment for BCRL represents a key component of survivorship efforts. Growing data has demonstrated the benefits of early detection and treatment of BCRL. Traditional diagnostic modalities are less able to detect reversible subclinical BCRL while newer techniques such as bioimpedance spectroscopy (BIS) have shown the ability to detect subclinical BCRL, allowing for early intervention and low rates of chronic BCRL with level I evidence. We present updated clinical practice guidelines for BIS utilization to assess for BCRL.
METHODS AND RESULTS
Review of the literature identified a randomized controlled trial and other published data which form the basis for the recommendations made. The final results of the PREVENT trial, with 3-year follow-up, demonstrated an absolute reduction of 11.3% and relative reduction of 59% in chronic BCRL (through utilization of compression garment therapy) with BIS as compared to tape measurement. This is in keeping with real-world data demonstrating the effectiveness of BIS in a prospective surveillance model. For optimal outcomes patients should receive an initial pre-treatment measurement and subsequently be followed at a minimum quarterly for first 3 years then biannually for years 4-5, then annually as appropriate, consistent with previous guidelines; the target for intervention has been changed from a change in L-Dex of 10 to 6.5. The lack of pre-operative measure does not preclude inclusion in the prospective surveillance model of care.
CONCLUSION
The updated clinical practice guidelines present a standardized approach for a prospective model of care using BIS for BCRL assessment and supported by evidence from a randomized controlled trial as well as real-world data.
Topics: Humans; Female; Breast Neoplasms; Dielectric Spectroscopy; Early Detection of Cancer; Breast Cancer Lymphedema; Lymph Node Excision; Lymphedema; Randomized Controlled Trials as Topic
PubMed: 36566297
DOI: 10.1007/s10549-022-06850-7 -
Integrative Cancer Therapies 2021Lymphedema is a common debilitating late effect among patients post-head and neck cancer (HNC) treatment. Head and neck lymphedema was associated with symptom burden,...
PURPOSE
Lymphedema is a common debilitating late effect among patients post-head and neck cancer (HNC) treatment. Head and neck lymphedema was associated with symptom burden, functional impairment, and decreased quality of life. The objective of this study was to determine the feasibility and potential efficacy of the use of photobiomodulation (PBM) therapy for head and neck lymphedema, symptom burden, and neck range of motion among HNC survivors.
METHODS
This was a single-arm, pre- and post-design clinical trial. Eligible patients included those with lymphedema after completion of complete decongestive therapy (CDT) and 3 to 18 months after completion of cancer therapy. The intervention included PBM therapy 2 times a week for 6 weeks for a total of 12 treatments. Lymphedema, symptom burden, and neck range of motion were measured at baseline, end-of-intervention, and 4-week post-intervention.
RESULTS
Of the 12 patients enrolled in the study, 91.7% (n = 11) completed the study intervention and assessment visits, and no adverse events were reported. When comparing the baseline to 4-week post-intervention, we found statistically significant improvements in the severity of external lymphedema, symptom burden, and neck range of motion (all < .05).
CONCLUSION
PBM therapy was feasible and potentially effective for the treatment of head and neck lymphedema. Future randomized controlled trials are warranted to examine the efficacy of PBM therapy for HNC-related lymphedema.
TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION
ClinicalTrials.gov Identifier: NCT03738332; date of registration: November 13, 2018.
Topics: Feasibility Studies; Head and Neck Neoplasms; Humans; Low-Level Light Therapy; Lymphedema; Quality of Life
PubMed: 34387119
DOI: 10.1177/15347354211037938 -
Asian Journal of Surgery Jan 2021Lymphedema is defined as the abnormal accumulation of interstitial fluid in subcutaneous tissues resulting from cancer, cancer treatment (surgery and/or radiotherapy),... (Review)
Review
Lymphedema is defined as the abnormal accumulation of interstitial fluid in subcutaneous tissues resulting from cancer, cancer treatment (surgery and/or radiotherapy), infection, inflammatory disorders, obesity, and hereditary syndromes. Surgical management of lymphedema can be broadly classified into two categories, reductive surgical techniques such as direct excision, suction assisted protein lipectomy (SAPL) or radical reduction with perforator preservation (RRPP); and physiological surgical procedures such as lymphaticovenous anastomosis (LVA) and vascularised lymph node transfer (VLNT). These techniques and their various combinations were evaluated. The results revealed patients with reversible lymphedema (ISL stage I, mild severity) benefit most from physiological procedures (LVA or VLNT) which can reduce the chance of disease progression to the chronic, solid phase. Reductive techniques such as SAPL, RPPP, or direct excision procedures should be reserved for patients with advanced - severe lymphedema (ISL stages II and especially stage III) as the surgical treatment of choice. In this study, current literature on the surgical treatment of lower extremity lymphedema is reviewed and discussed in conjunction with authors' clinical experiences. An algorithm is presented, based on clinical evidence and experience which aims to provide a structured approach to managing lower limb lymphedema.
Topics: Aged; Algorithms; Anastomosis, Surgical; Female; Humans; Lipectomy; Lower Extremity; Lymph Node Excision; Lymph Nodes; Lymphedema; Male; Middle Aged; Surgical Procedures, Operative
PubMed: 32950353
DOI: 10.1016/j.asjsur.2020.08.010 -
All edema is lymphedema: progressing lymphedema and wound management to an integrated model of care.Wound Management & Prevention Jan 2022Chronic edema affects millions of people in the United States and worldwide. Edema can result from a variety of diseases, trauma, medications, and other contributing... (Review)
Review
BACKGROUND
Chronic edema affects millions of people in the United States and worldwide. Edema can result from a variety of diseases, trauma, medications, and other contributing factors; however, all edema is related to lymphatic fluid dysregulation. Additionally, lymphatic impairment and integumentary dysfunction are interrelated, leading to complex clinical presentations that require an integrated medical model of care to maximize outcomes.
PURPOSE
This narrative review article will highlight the current evidence that details lymphatic physiology, fluid regulation by the endothelial glycocalyx layer, and the interconnectedness of the vascular and integumentary systems leading to a paradigm shift in our understanding of edema, lymphedema, and chronic wounds. Traditional pedagogy remains siloed with respect to the body systems, whereas current evidence indicates a certain interdependence, particularly between and among the venous, lymphatic, and integumentary systems.
METHODS
Comprehensive narrative review of the current and past literature (2010-2021 through PubMed, Google Scholar, MEDLINE Complete, UpToDate) focusing on lymphatic physiology, fluid regulation, the endothelial glycocalyx layer, lymphedema, and venous insufficiency. Review focuses on new evidence supporting the interconnectedness of the systems to support a unified medical management approach.
RESULTS
All edema is related to lymphatic dysfunction, whether transient or permanent, thereby creating a lymphedema continuum. Further, lymphatic impairment creates cutaneous regions of skin barrier failure, rendering the skin more susceptible to breakdown and chronic wounds.
CONCLUSION
A synthesis of the current evidence suggests an interconnected relationship of the lymphatic, venous, and integumentary systems, highlighting the need for a more integrated medical model of care to provide efficient and comprehensive care and improve patient outcomes.
Topics: Edema; Humans; Lymph; Lymphatic System; Lymphatic Vessels; Lymphedema
PubMed: 35263273
DOI: No ID Found -
Systematic Reviews Oct 2022The development of risk prediction models for breast cancer lymphedema is increasing, but few studies focus on the quality of the model and its application. Therefore,... (Review)
Review
PURPOSE
The development of risk prediction models for breast cancer lymphedema is increasing, but few studies focus on the quality of the model and its application. Therefore, this study aimed to systematically review and critically evaluate prediction models developed to predict breast cancer-related lymphedema.
METHODS
PubMed, Web of Science, Embase, MEDLINE, CNKI, Wang Fang DATA, Vip Database, and SinoMed were searched for studies published from 1 January 2000 to 1 June 2021. And it will be re-run before the final analysis. Two independent investigators will undertake the literature search and screening, and discrepancies will be resolved by another investigator. The Prediction model Risk Of Bias Assessment Tool will be used to assess the prediction models' risk of bias and applicability.
RESULTS
Seventeen studies were included in the systematic review, including 7 counties, of which 6 were prospective studies, only 7 models were validation studies, and 4 models were externally validated. The area under the curve of 17 models was 0.680~0.908. All studies had a high risk of bias, primarily due to the participants, outcome, and analysis. The most common predictors included body mass index, radiotherapy, chemotherapy, and axillary lymph node dissection.
CONCLUSIONS
The predictive factors' strength, external validation, and clinical application of the breast cancer lymphedema risk prediction model still need further research. Healthcare workers should choose prediction models in clinical practice judiciously.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021258832.
Topics: Breast Cancer Lymphedema; Breast Neoplasms; Female; Humans; Lymph Node Excision; Lymphedema; Prospective Studies
PubMed: 36229876
DOI: 10.1186/s13643-022-02084-2