Skin mechanical properties measured with skin elasticity measurement device in patients with lymphedema: Scoping review.

BACKGROUND: Skin conditions in patients with lymphedema have been identified according to changes in skin mechanical properties. The skin elasticity meter is a non-invasive tool for measuring the mechanical properties of the skin; however, its potential use in patients with lymphedema has received little attention. This review aimed to provide an overview of studies measuring the skin mechanical properties of patients with lymphedema using a skin elasticity meter. MATERIALS AND METHODS: Search terms and synonyms related to lymphedema and skin mechanical property measurement using a skin elasticity meter were identified, and electronic databases containing articles in English were searched. RESULTS: A total of 621 articles were retrieved, and four articles were analyzed after screening. Despite this research subject receiving increasing attention, no consensus has been reached regarding the best methods. CONCLUSION: Measurement methods are expected to be standardized in the future to elucidate the skin mechanical properties of patients with lymphedema.

Synchronous supraclavicular vascularized lymph node transfer and liposuction for gynecological cancer-related lower extremity lymphedema: A clinical comparative analysis of three different procedures.

OBJECTIVE: Gynecological cancer-related lower extremity lymphedema (GC-LEL), a chronic, progressive condition, lacks a standardized treatment. Currently, supraclavicular vascularized lymph node transfer (SC-VLNT) is a favored approach in the treatment of lymphedema, and there is a trend toward combination technology. This study conducts a comparative analysis of three techniques for treating GC-LEL with simultaneous SC-VLNT and liposuction. METHODS: A cohort of 35 patients with GC-LEL was examined, comprising 13 patients who underwent single lymph nodes flap with a skin paddle (SLNF+P), 12 who received single lymph nodes flap without a skin paddle (SLNF), and 10 who accepted dual lymph nodes flap without a skin paddle (DLNF). Patient demographics and outcomes were meticulously documented, covering intra- and postoperative variables. RESULTS: The median limb volume reduction were 56.4% (SLNF+P), 60.8% (SLNF), and 50.5% (DLNF) in stage II, and 54.0% (SLNF+P), 59.8% (SLNF), and 54.4% (DLNF) in stage III. DLNF group procedures entailed longer flap harvesting and transplantation times. The SLNF+P group, on average, had an 8-day postoperative hospitalization, longer than others. All patients noted subjective improvements in Lymphedema Quality of Life scores, with lymphoscintigraphy revealing enhanced lymphatic flow in 29 of the 35 cases. A notable decrease in cellulitis incidence was observed. Additionally, the occurrence of cellulitis decreased significantly, except for DLNF (Stage Ⅱ). The median follow-up time was 16 months (range, 12-36 months), with no reported severe postoperative complications. CONCLUSIONS: For advanced GC-LEL, SLNF combined with liposuction is a preferred treatment, offering fewer complications, shorter operative time, and hospitalization.

Lower limb lymphedema disrupts both static and dynamic balance.

BACKGROUND: The impact of lower-limb-lymphedema on quality of life of patients regarding balance is unclear due to the scarcity of literature. The aim of this study was to determine the static and dynamic balance of patients with lower-limb-lymphedema in comparison with healthy subjects. METHODS: This case-control designed study included 30 lymphedema patients and 30 healthy individuals, of whom were 52 female and 8 male with a mean age of 50.63 ± 9.72 years. Static balance stability and anterior-posterior with lateral sway parameters on four conditions (eyes-opened-stable-ground, eyes-closed-stable-ground, eyes-opened-unstable-ground, eyes-closed-unstable-ground) and dynamic stability of all participants were evaluated. FINDINGS: The demographic variables were similar between the groups. Majority of the patients had lymphedema due to cancer surgery with a stage of 2. Dynamic stability was significantly disrupted in lymphedema group in comparison with controls (P = 0.049). Static balance parameters were impaired on all conditions except the eyes opened-stable ground in lymphedema patients (P = 0.048,P = 0.043,P = 0.017). The dynamic with static balance and lateral sway parameters were correlated with the duration of lymphedema(P = 0.046,P = 0.002,P = 0.005). Anterior-posterior sway on eyes-closed-unstable-ground condition was correlated with functional status (P = 0.02). Static balance on eyes-opened-unstable-ground condition and anterior-posterior sway parameters were correlated with physical activity level (P = 0.015,P = 0.016,P < 0.05). INTERPRETATION: Closing eyes and the deterioration of ground caused significant alteration of the static and dynamic balance both separately and together in patients with lower-limb-lymphedema compared to healthy subjects. Regarding the static and dynamic imbalance, we suggest the evaluation of balance and inclusion of balance exercises in routine lymphedema rehabilitation program, especially in the early period of disease.

Longitudinal assessment of health-related quality of life and clinical outcomes with at home advanced pneumatic compression treatment of lower extremity lymphedema.

OBJECTIVE: This prospective, longitudinal, pragmatic study describes at home treatment with a proprietary advanced pneumatic compression device (APCD) for patients with lower extremity lymphedema (LED). METHODS: Following institutiona review board approval, four participating Veterans Affairs centers enrolled LED patients from 2016 to 2022. The primary outcome measures were health-related quality of life (HR-QoL) questionnaires (lymphedema quality of life-leg and the generic SF-36v2) obtained at baseline and 12, 24, and 52 weeks. The secondary outcome measures were limb circumference, cellulitis events, skin quality, and compliance with APCD and other compression therapies. RESULTS: Because a portion of the trial was conducted during the coronavirus disease 2019 pandemic, 179 patients had 52 weeks of follow-up, and 143 had complete measurements at all time points. The baseline characteristics were a mean age of 66.9 ± 10.8 years, 91% were men, and the mean body mass index was 33.8 ± 6.9 kg/m2. LED was bilateral in 92.2% of the patients. Chronic venous insufficiency or phlebolymphedema was the most common etiology of LED (112 patients; 62.6%), followed by trauma or surgery (20 patients; 11.2%). Cancer treatment as a cause was low (4 patients; 2.3%). Patients were classified as having International Society for Lymphology (ISL) stage I (68.4%), II (27.6%), or III (4.1%). Of the primary outcome measures, significant improvements were observed in all lymphedema quality of life-leg domains of function, appearance, symptoms, and emotion and the overall score after 12 weeks of treatment (P < .0001) and through 52 weeks of follow-up. The SF-36v2 demonstrated significant improvement in three domains at 12 weeks and in the six domains of physical function, bodily pain, physical component (P < .0001), social functioning (P = .0181), role-physical (P < .0005), and mental health (P < .0334) at 52 weeks. An SF-36v2 score <40 indicates a substantial reduction in HR-QoL in LED patients compared with U.S. norms. Regarding the secondary outcome measures at 52 weeks, compared with baseline, the mean limb girth decreased by 1.4 cm (P < .0001). The maximal reduction in mean limb girth was 1.9 cm (6.0%) at 12 weeks in ISL stage II and III limbs. New episodes of cellulitis in patients with previous episodes (21.4% vs 6.1%, P = .001) were reduced. The 75% of patients with skin hyperpigmentation at baseline decreased to 40% (P < .01) at 52 weeks. At 52 weeks, compliance, defined as use for 5 to 7 days per week, was reported for the APCD by 72% and for elastic stockings by 74%. CONCLUSIONS: This longitudinal study of Veterans Affairs patients with LED demonstrated improved generic and disease-specific HR-QoL through 52 weeks with at home use of an APCD. Limb girth, cellulitis episodes, and skin discoloration were reduced, with excellent compliance.

Comparison of fluid and body composition measures in women with lipoedema, lymphoedema, and control participants.

Lipoedema is the disproportionate accumulation of adipose tissue in the lower body, often associated with hormonal changes in women. Lipoedema is commonly misdiagnosed as lymphoedema or obesity due to similarities in appearance. The aim of this study is to compare body composition and fluid measures of women with lipoedema, lymphoedema, and matched control participants, to determine differences that may help distinguish between each condition. One hundred and eleven participants aged over 18, who presented with the complaint of leg swelling and underwent indocyanine green lymphography were included in this study. Our analysis showed that the individuals with lymphoedema had a significantly higher overall total body water (lymphoedema: 9.6 ± 4.2 L, lipoedema: 7.4 ± 2.3 L, control: 7.5 ± 1.8 L; p < .001) and extracellular fluid (lymphoedema: 4.6 ± 1.6, lipoedema: 3.4 ± 1.0 L, control: 3.5 ± 0.7 L; p < .001) in the legs when compared to individuals with lipoedema and matched control participants. Individuals with lipoedema had a significantly higher overall fat mass as a percentage of body weight when compared to individuals with lymphoedema (lymphoedema: 33.1% ± 9.5%, lipoedema: 39.4% ± 6.5%; p = .003). We are unable to distinguish between individuals with lipoedema and control participants, therefore further research needs to be conducted to help reduce misdiagnosis.

Quality of life evaluation and lack of correlation with volumetric results after lymphovenous anastomoses in lymphedema therapy of the lower extremity.

OBJECTIVE: Chronic primary or secondary lymphedema has huge effects on patients' quality of life (QOL) because of the associated swelling and pain, decreased range of motion, and depression and anxiety and generally requires numerous adaptations. Many studies have shown a positive objective effect of lymphovenous anastomoses (LVAs) on chronic lymphedema. In the present study, we assessed the effect of LVAs on QOL in patients with primary or secondary lymphedema of the lower extremity at 6 months after surgery and examined the correlation between changes in the QOL and volumetric measurements. METHODS: Only patients with either primary or secondary lymphedema of the lower extremity who had undergone LVAs were included in the present study. To assess QOL, a specially designed questionnaire based on the Lymphedema Quality of Life Inventory was used to evaluate the subjective therapeutic results from the patients' perspective. Objective therapy success was assessed using three-dimensional volumetric measurements of the lower leg. The measuring points, for both the subjective and the objective measurements, were the day before and 6 months after therapy. RESULTS: The mean change in volume at 6 months after LVA was -6.5% ± 5.6% (P < .001). Significantly better QOL in terms of physical (37.6% ± 25.2%) and psychosocial (27.0% ± 43.0%) domains and practical restrictions (22.3% ± 24.8%) was found (P < .001 for all). No correlation was found between QOL improvement and volume decrease (P > .05). CONCLUSIONS: For patients with lymphedema of the lower extremity, LVAs can lead to a significant volumetric decrease and QOL improvement at 6 months after treatment with no demonstrable relationship between QOL improvement and volume reduction.

Treatment Outcomes of Manual Lymphatic Drainage in Pediatric Lymphedema.

BACKGROUND: Pediatric lymphedema can result in irreversible, debilitating limb swelling, tissue fibrosis, skin ulcers, infection, and impaired limb function in children at an early age. Manual lymphatic drainage (MLD) is a noninvasive technique, which is a part of intensive decongestive therapy to reroute lymphatic flow to healthy channels used to manage lymphedema. Outcomes of this treatment option in children have not been studied. We evaluated the effect of decongestive therapy involving MLD in pediatric patients with complex lymphatic anomalies by measuring treatment progress and functional outcomes via changes in limb circumference, limb functionality, dexterity, skin quality, and pain. METHODS: A single-institution retrospective study on a cohort of 8 pediatric patients with lymphatic anomalies who completed a course of MLD was conducted from 2015 to 2017 to investigate the role MLD plays in their lymphedema reduction. Pain scores were measured on a scale of 0-10, with 0 being no pain and 10 being the worst pain imaginable. The functional performance was measured by the Canadian Occupational Performance Measurement questionnaire. RESULTS: Among all patients, there were 4 cases affecting the upper extremities, 4 affecting the lower extremities, and 3 affecting the truncal region. Five of 8 patients demonstrated a reduction in lymphedema with an average girth reduction of 8.2% in the lower extremities, 3.0% in the upper extremities, and 7.4% in the truncal regions. In unilateral cases, the difference in limb circumference between the affected and normal extremity decreased by an average of 25.6%. Four patients completed the Canadian Occupational Performance Measurement questionnaire with an average improvement of 30% in daily task performance. Three patients reported complete resolution of pain. CONCLUSIONS: MLD can be used as a reliable noninvasive method for decongestion and analgesia to delay the onset of lymphedema-associated fibrosis and long-term disability in children with complex lymphatic malformations.

Upper Quadrant Edema Patient-Reported Outcome Measure Is Reliable, Valid, and Efficient for Patients With Lymphatic and Venous Disorders.

OBJECTIVE: The main aims of this study were to (1) create a patient-reported outcome measure (PROM) item bank for measuring the impact of upper quadrant edema (UQE) on physical function by calibrating responses to newly developed items; and (2) assess reliability, validity, and administration efficiency of scores based on computerized adaptive test (CAT) and 10-item short-form (SF) administration modes. METHODS: This was a retrospective study including data from patients treated in outpatient rehabilitation clinics for UQE that responded to all 27 candidate items at intake. Item response theory model assumptions of unidimensionality, local item independence, item fit, and presence of differential item functioning were evaluated. UQE-CAT- and UQE-SF-generated scores were assessed for reliability, validity, and administration efficiency. RESULTS: The total cohort included 3486 patients (mean [SD] age = 61 [13] years; range = 14-89 years). After removing 2 items, a 25-item solution was supported for its unidimensionality and fit to the item response theory model with reliability estimates of more than 0.93 for scores based on both CAT and SF administration modes. No items demonstrated differential item functioning. Scores discriminated among multiple patient groups in clinically logical ways and were moderately responsive to change with negligible floor and acceptable ceiling effects. CAT scores were generated using an average of 5.6 items (median = 5). CONCLUSION: Scores on the UQE PROM were reliable, valid, and efficient for assessing perceived physical function of patients with upper quadrant edema; thus, the measure is suitable for research and routine clinical administration. IMPACT: The newly developed UQE PROM is reliable and valid and offers efficient administration modes for assessing perceived physical function of patients with UQE caused by lymphatic and venous disorders, both for research and routine clinical care in busy outpatient rehabilitation settings. As an item response theory-based measure, the UQE PROM allows administration of condition-specific functional questions with low response burden for patients. This study supports a transition to PROMs that are based on modern measurement approaches to achieve high accuracy and efficiency.

The impact of breast cancer-related lymphedema on rural and small-town Survivors' return-to-work and quality of life: A multiple-case study.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a lifelong condition. Millions who develop breast cancer are younger than retirement age and at a lifetime risk for developing BCRL. Rural and small-town survivors may face unique challenges in terms of access to health care and BCRL/survivorship resources. This multiple-case study describes how BCRL influences the work experiences and quality of life (QoL) of survivors living in rural and small towns in Missouri. METHODS AND MATERIALS: Thirteen survivors from rural and small towns in Missouri completed semi-structured interviews and a standardized QoL instrument. Cases were analyzed using in-vivo and open-coding techniques and constant cross-case comparative methods. Twelve of the 13 participants' data are synthesized into themes to represent an illustrative case. The 13th case is presented as a contradictory (rival) case. RESULTS: Four themes are represented within the illustrative case - multiple medical encounters; the development of self-care routines; the reciprocity of work/live activities, triggers, and adjustments; and rural/small-town cultural impact. Upon BCRL diagnosis, survivors received intensive treatments, eventually establishing self-care routines. Survivors identified strategies for working around their BCRL when completing work and home responsibilities. The contradictory (rival) case was more recently diagnosed and, as such, had not established self-care and coping mechanisms in the same way. CONCLUSIONS AND IMPLICATIONS: Survivors alleviate BCRL symptoms and improve their QoL by establishing self-care strategies. This provides guidance for client-centered survivorship care-planning and occupational rehabilitation of rural survivors with BCRL. This study provides the foundation for developing information for rural survivors that supports mental preparation and coping skills for BCRL self-management.

Lipedema: más que un problema de "piernas gordas": actualización en la fisiopatología, diagnóstico y tratamiento quirúrgico / Lipedema: more than a problem of "fat legs": update in the pathophysiology, diagnosis and surgical treatment

Resumen El lipedema es una enfermedad común, frecuentemente subdiagnosticada, crónica y progresiva, que genera un gran deterioro en la calidad de vida. Consiste en el depósito anormal de tejido adiposo subcutáneo principalmente en las extremidades inferiores, afectando casi exclusivamente a mujeres. Sus síntomas principales son el dolor, la sensibilidad y la facilidad para producir equimosis. Desde el punto de vista fisiopatológico, existiría una susceptibilidad poligénica combinada con trastornos hormonales, microvasculares y linfáticos que pueden ser en parte responsables del desarrollo del lipedema. Se clasifica, según la distribución de la grasa en cinco tipos y, según la gravedad de la enfermedad, en cuatro etapas. El diagnóstico es eminentemente clínico y se debe diferenciar de otras patologías que producen aumento de volumen de las extremidades, especialmente el linfedema y obesidad. Es importante realizar un estudio funcional del sistema linfático cuando el diagnóstico es dudoso o para la etapificación del lipedema, por lo que la correcta interpretación de estos resultados es fundamental. El tratamiento está enfocado en disminuir la discapacidad y evitar la progresión, con el fin de mejorar la calidad de vida. Actualmente, la liposucción es un tratamiento efectivo para el lipedema, sin embargo, las técnicas empleadas para la lipectomía en el lipedema son diferentes a las técnicas utilizadas para la liposucción con fines estéticos. Las técnicas selectivas que respetan los vasos linfáticos tienen mejor rendimiento para reducir el volumen de grasa, retrasar la progresión, reducir el dolor, reducir la alteración marcha y mejorar la calidad de vida en estos pacientes.

Lipedema is a common, frequently under-diagnosed, chronic and progressive disease that generates an important detriment in quality of life. It consists in an abnormal deposit of subcutaneous adipose tissue mainly in the lower extremities, almost exclusively affecting women. Its main symptoms are pain, sensitivity and the ease of causing bruising. From the pathophysiological point of view, there would be a polygenic susceptibility combined with hormonal, microvascular and lymphatic disorders that may be partly responsible for the development of lipedema. It is classified according to the distribution of fat into five types and, according to the severity of the disease, in four stages. The diagnosis is eminently clinical and must be differentiated from other diseases that cause an increase in the volume of the extremities, especially lymphedema and obesity. It is important to carry out a study of the lymphatic system functionality when the diagnosis is not clear or for lipedema staging, so the correct interpretation of these results is essential. Treatment is focused on reducing disability and preventing progression, in order to improve quality of life. Liposuction is currently an effective treatment for lipedema, however, the techniques used for lipectomy in lipedema are different from the techniques used for liposuction for cosmetic purposes. Selective techniques that spare the lymphatic vessels have better results reducing fat volume, delaying progression, reducing pain, reducing gait disturbance, and improving quality of life of these patients.

Hypotrichosis-lymphedema-telangiectasia syndrome: Report of ileal atresia associated with a SOX18 de novo pathogenic variant and review of the phenotypic spectrum.

Hypotrichosis-lymphedema-telangiectasia syndrome (HLTS) is a rare condition caused by pathogenic variants in the SOX18 gene. SOX18 plays a key role in angio- and lymphangiogenesis due to its expression in venous endothelial cells from which the lymphatic system develops. It is also expressed in embryonic hair follicles, heart, and vascular smooth muscle cells. The main clinical symptoms of HLTS include sparse hair, alopecia totalis, lymphedema, most often affecting lower limbs, and telangiectatic lesions. Only 10 patients with a SOX18 pathogenic variant have been described that presented with additional features such as hydrocele, renal failure, arterial or pulmonary hypertension, aortic dilatation, and facial dysmorphism. Here, we summarize these phenotypic variations and report an additional HLTS patient, with a 14-nucleotide de novo duplication in SOX18 and congenital ileal atresia, a feature not previously associated with HLTS.

Development and physiological functions of the lymphatic system: insights from human genetic studies of primary lymphedema.

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.

Dysfunction of dermal initial lymphatics of the arm and upper body quadrant causes congenital arm lymphedema.

OBJECTIVE: The objective of this study was to explore the pathologic process underlying primary lymphedema. METHODS: Twenty-seven patients with unilateral congenital arm lymphedema who visited our clinic from January 1, 2014, to May 30, 2019, were enrolled. The patients' clinical signs and the findings of indocyanine green (ICG) lymphography, skin tissue immunohistochemical staining, and whole exome sequencing of tissue and blood were evaluated. RESULTS: Among the 27 patients, 11 were diagnosed with stage II and 16 were diagnosed with stage III lymphedema. No lymphatic vessels were visualized in the affected arm in 25 of 27 (93%) patients who underwent ICG lymphography; likewise, no lymphatics were found in the territories of axillary lymph node drainage in the trunk, irrespective of any anomalies of the axillary lymph nodes. In only two (7%) patients, an unclear lymphatic trunk gradually appeared in the dorsum of the affected hand. The number of initial lymphatics was increased in the skin specimens of all nine patients in whom lymphatics were not demonstrated by ICG lymphography. Among 14 tested patients, we found compound heterozygote variants in the PIEZO1 gene in only one (7%) patient. Two missense variants, c.4072C>T; p.Arg1358Cys and c.5033C>T; p. Ala1678Val, were identified and found to have been inherited from the father and mother, respectively. No other pathogenic or likely pathogenic variants of currently known lymphedema-related genes were identified in the remaining 13 patients. No genetic difference was found between the lymphedematous and nonedematous healthy skin tissue of the same person. CONCLUSIONS: Segmental or regional dysfunction of the dermal initial lymphatics causes congenital arm lymphedema and may have implications for clinical treatment.

The physiological and pathological functions of VEGFR3 in cardiac and lymphatic development and related diseases.

Vascular endothelial growth factor receptors (VEGFRs) are part of the evolutionarily conserved VEGF signalling pathways that regulate the development and maintenance of the body's cardiovascular and lymphovascular systems. VEGFR3, encoded by the FLT4 gene, has an indispensable and well-characterized function in development and establishment of the lymphatic system. Autosomal dominant VEGFR3 mutations, that prevent the receptor functioning as a homodimer, cause one of the major forms of hereditary primary lymphoedema; Milroy disease. Recently, we and others have shown that FLT4 variants, distinct to those observed in Milroy disease cases, predispose individuals to Tetralogy of Fallot, the most common cyanotic congenital heart disease, demonstrating a novel function for VEGFR3 in early cardiac development. Here, we examine the familiar and emerging roles of VEGFR3 in the development of both lymphovascular and cardiovascular systems, respectively, compare how distinct genetic variants in FLT4 lead to two disparate human conditions, and highlight the research still required to fully understand this multifaceted receptor.