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Lipedema is a chronic adipose tissue disorder characterized by the disproportional subcutaneous deposition of fat and is commonly misdiagnosed as lymphedema or obesity. The molecular determinants of the lipedema remain largely unknown and only speculations exist regarding the lymphatic system involvement. The aim of the present study is to characterize the lymphatic vascular involvement in established lipedema. The histological and molecular characterization was conducted on anatomically-matched skin and fat biopsies as well as serum samples from eleven lipedema and ten BMI-matched healthy patients. Increased systemic levels of vascular endothelial growth factor (VEGF)-C (P = 0.02) were identified in the serum of lipedema patients. Surprisingly, despite the increased VEGF-C levels no morphological changes of the lymphatic vessels were observed. Importantly, expression analysis of lymphatic and blood vessel-related genes revealed a marked downregulation of Tie2 (P < 0.0001) and FLT4 (VEGFR-3) (P = 0.02) consistent with an increased macrophage infiltration (P = 0.009), without changes in the expression of other lymphatic markers. Interestingly, a distinct local cytokine milieu, with decreased VEGF-A (P = 0.04) and VEGF-D (P = 0.02) expression was identified. No apparent lymphatic anomaly underlies lipedema, providing evidence for the different disease nature in comparison to lymphedema. The changes in the lymphatic-related cytokine milieu might be related to a modified vascular permeability developed secondarily to lipedema progression.

OBJECTIVE: Lipedema is characterized by pain, fatigue, and excessive adipose tissue and sodium accumulation of the lower extremities. This case-control study aims to determine whether sodium or vascular dysfunction is present in the central nervous system. METHODS: Brain magnetic resonance imaging was performed at 3 T in patients with lipedema (n = 15) and control (n = 18) participants matched for sex, age, race, and BMI. Standard anatomical imaging and intracranial angiography were applied to evaluate brain volume and vasculopathy, respectively; arterial spin labeling and sodium magnetic resonance imaging were applied to quantify cerebral blood flow (CBF) (milliliters per 100 grams of tissue/minute) and brain tissue sodium content (millimoles per liter), respectively. A Mann-Whitney U test (significance criteria P < 0.05) was applied to evaluate group differences. RESULTS: No differences in tissue volume, white matter hyperintensities, intracranial vasculopathy, or tissue sodium content were observed between groups. Gray matter CBF was elevated (P = 0.03) in patients with lipedema (57.2 ± 9.6 mL per 100 g/min) versus control participants (49.8 ± 9.1 mL per 100 g/min). CONCLUSIONS: Findings provide evidence that brain sodium and tissue fractions are similar between patients with lipedema and control participants and that patients with lipedema do not exhibit abnormal radiological indicators of intracranial vasculopathy or ischemic injury. Potential explanations for elevated CBF are discussed in the context of the growing literature on lipedema symptomatology and vascular dysfunction.

BackgroundLong-term results following liposuction in patients with lipedema were available only for an average period of 8?years.ObjectiveTo find out whether the improvements persist for a further 4?years.MethodsIn 60 patients with lipedema a single-centre study with a mail questionnaire ? often in combination with clinical controls ? was performed after an average period of 12?years following liposuction(s). All patients in this group had already been surveyed 4 and 8?years after surgery.ResultsCompared with the earlier results improvement persisted with regard to spontaneous pain, sensitivity to pressure, edema, bruising and restriction of movement; similar outcomes were observed for self-assessment of cosmetic impairment, reduction in quality of life and overall impairment. While in the period from 4 to 8?years postoperatively complaints slightly increased, this was not the case for the period 8 to 12?years postoperatively. In addition a similar reduction of conservative treatment (decongestive therapy, compression garments) was observed as after 4 and 8?years postoperatively. Compared with the body weight before liposuction, 55% of the patients showed a reduction of 6.2?kg on average and 43.3% had a weight increase with an average of 7.9?kg.ConclusionThe results show, that the positive effects of liposuction last 12?years postoperatively without relevant worsening. They imply that liposuction for lipedema leads to a permanent reduction of symptom severity and need for conservative therapy.

Mast cells (MCs) are abundant in almost all vascularized tissues. Furthermore, their anatomical proximity to lymphatic vessels and their ability to synthesize, store and release a large array of inflammatory and vasoactive mediators emphasize their significance in the regulation of the lymphatic vascular functions. As a major secretory cell of the innate immune system, MCs maintain their steady-state granule release under normal physiological conditions; however, the inflammatory response potentiates their ability to synthesize and secrete these mediators. Activation of MCs in response to inflammatory signals can trigger adaptive immune responses by dendritic cell-directed T cell activation. In addition, through the secretion of various mediators, cytokines and growth factors, MCs not only facilitate interaction and migration of immune cells, but also influence lymphatic permeability, contractility, and vascular remodeling as well as immune cell trafficking through the lymphatic vessels. In summary, the consequences of these events directly affect the lymphatic niche, influencing inflammation at multiple levels. In this review, we have summarized the recent advancements in our understanding of the MC biology in the context of the lymphatic vascular system. We have further highlighted the MC-lymphatic interaction axis from the standpoint of the tumor microenvironment.

BACKGROUND: Lipedema is often unrecognized or misdiagnosed; despite an estimated prevalence of 10% in the overall female population, its cause is still unknown. There is increasing awareness of this condition, but its differential diagnosis can still be challenging. In this article, we summarize current hypotheses on its pathogenesis and the recommendations of current guidelines for its diagnosis and treatment. METHODS: This review is based on publications about lipedema that were retrieved by a selective search in the MEDLINE, Web of Science, and Cochrane Library databases. RESULTS: The pathophysiology of lipedema remains unclear. The putative causes that have been proposed include altered adipogenesis, microangiopathy, and disturbed lymphatic microcirculation. No specific biomarker has yet been found, and the diagnosis is currently made on clinical grounds alone. Ancillary tests are used only to rule out competing diagnoses. The state of the evidence on treatment is poor. Treatment generally consists of complex decongestive therapy. In observational studies, liposuction for the permanent reduction of adipose tissue has been found to relieve symptoms to a significant extent, with only rare complications. The statutory healthinsurance carriers in Germany do not yet regularly cover the cost of the procedure; studies of high methodological quality will be needed before this is the case. CONCLUSION: The diagnosis of lipedema remains a challenge because of the hetero - geneous presentation of the condition and the current lack of objective measuring instruments to characterize it. This review provides a guide to its diagnosis and treatment in an interdisciplinary setting. Research in this area should focus on the elucidation of the pathophysiology of lipedema and the development of a specific biomarker for it.

Lipedema is a fat disorder that is often misdiagnosed. It was first identified at the Mayo Clinic in 1940, but medical schools do not include it in their curriculum and is therefore poorly understood. It presents as disproportionate and symmetrical accumulations of fat (bilateral), which is often accompanied by orthostatic edema. Early diagnosis and treatment are crucial, as the disease is progressive and can lead to immobility as well as a significant decrease in the quality of life. Lipedema differs from obesity because it does not respond to diet and exercise. This article gives you a glimpse into what lipedema is about and will help you identify some differences between lipedema and lymphedema. It will also help you identify which surgical procedures have been successful in treating the disease.

Background: Bioimpedance spectroscopy (BIS) demonstrates proficiency in early identification of breast cancer treatment-related lymphedema (BCRL) development. Dual-tab electrodes were designed for consistent and easy electrode placement, however, single-tab electrodes positioned to mimic dual-tab placement on the body may make BIS technology more accessible in community hospitals and outpatient settings. The purpose of this study is to evaluate use of single-tab electrodes for BIS measurements and assess whether single-tab electrodes provide consistent BIS measurements in controls and patients with BCRL. Methods and Results: Upper limb BIS ratios were obtained using ImpediMed L-Dex® U400 in controls (n = 13; age = 23-75 years; 9 repeated measurements) using dual-tab and single-tab electrodes. BCRL patients (n = 17; Stage = 1.65 ± 0.49; number nodes removed = 16.3 ± 7.7; age = 50.9 ± 10.6 years; age range = 33-77 years) and healthy controls (n = 19) were evaluated to determine if single-tab electrodes provided discriminatory capacity for detecting BCRL. Intraclass correlation coefficients (ICC), linear mixed-effects models, Wilcoxon rank-sum tests, and linear regression with two-sided p-values <0.05 required for significance were applied. Single-tab electrodes were found to be statistically interchangeable with dual-tab electrodes (ICC = 0.966; 95% confidence interval = 0.937-0.982). No evidence of differences in single-tab versus dual-tab measurements were found for L-Dex ratios (p = 0.74) from the linear mixed-effects model. Repeated trials involving reuse of the same electrodes revealed a trend toward increases in L-Dex ratio for both styles of electrodes. Single-tab electrodes were significant (p < 0.0001) for discriminating between BCRL and control subjects. Conclusion: Findings expand upon the potential use of BIS in clinic and research settings and suggest that readily available single-tab electrodes provide similar results as dual-tab electrodes for BIS measurements.

Lymphoedema is a well-known concern for cancer survivors. A crucial issue in lymphoedema is that we cannot predict who will be affected, and onset can occur many years after initial cancer treatment. The variability of time between cancer treatment and lymphoedema onset is an unexplained mystery. Retrospective cohort studies have investigated the risk factors for lymphoedema development, with extensive surgery and the combination of radiation and surgery identified as common high-risk factors. However, these studies could not predict lymphoedema risk in each individual patient in the early stages, nor could they explain the timing of onset. The study of anatomy is one promising tool to help shed light on the pathophysiology of lymphoedema. While the lymphatic system is the area least investigated in the field of anatomical science, some studies have described anatomical changes in the lymphatic system after lymph node dissection. Clinical imaging studies in lymphangiography, lymphoscintigraphy and indocyanine green (ICG) fluorescent lymphography have reported post-operative anatomical changes in the lymphatic system, including dermal backflow, lymphangiogenesis and creation of alternative pathways via the deep and torso lymphatics, demonstrating that such dynamic anatomical changes contribute to the maintenance of lymphatic drainage pathways. This article presents a descriptive review of the anatomical and imaging studies of the lymphatic system in the normal and post-operative conditions and attempts to answer the questions of why some people develop lymphoedema after cancer and some do not, and what causes the variability in lymphoedema onset timing.

Lipedematous scalp is an uncommon entity of unknown etiology, rarely described in the pediatric age. It is characterized by boggy thickening of the scalp predominantly located at the vertex and occiput, which acquires a cotton-like consistency. This condition is palpable rather than visible. It is a casual finding because it is usually asymptomatic, although it may involve alopecia, pruritus, or dysesthesia. We report a 10-year-old girl with lipedematous scalp without alopecia. Sonographic and MRI findings confirmed the diagnosis of lipidematous scalp.  El lipedema de cuero cabelludo o cuero cabelludo lipedematoso es una entidad infrecuente y de etiología desconocida, rara vez descrita en la edad pediátrica. Se caracteriza por un engrosamiento difuso y de tacto esponjoso del tejido celular subcutáneo localizado principalmente en vértex y occipucio. Suele ser un hallazgo casual dado que habitualmente cursa de forma asintomática, aunque puede asociar alopecia, prurito o disestesias. Presentamos el caso de una niña de 10 años de edad con lipedema de cuero cabelludo sin alopecia asociada. Los hallazgos ecográficos y de resonancia magnética confirmaron el diagnóstico de lipedema de cuero cabelludo.

OBJECTIVE: The aim of this study is to compare tissue sodium and fat content in the upper and lower extremities of participants with lipedema versus controls using magnetic resonance imaging (MRI). METHODS: MRI was performed at 3.0 T in females with lipedema (n = 15, age = 43.2 ± 10.0 years, BMI = 30.3 ± 4.4 kg/m2 ) and controls without lipedema (n = 14, age = 42.8 ± 13.2 years, BMI = 28.8 ± 4.4 kg/m2 ). Participants were assessed for pain and disease stage. Sodium MRI was performed in the forearm and calf to quantify regional tissue sodium content (TSC, mmol/L). Chemical-shift-encoded water-fat MRI was performed in identical regions for measurement of fat/water (ratio). RESULTS: In the calf, skin TSC (16.3 ± 2.6 vs. 14.4 ± 2.2 mmol/L, P = 0.04), muscle TSC (20.3 ± 3.0 vs. 18.3 ± 1.7 mmol/L, P = 0.03), and fat/water (1.03 ± 0.37 vs. 0.56 ± 0.21 ratio, P < 0.001) were significantly higher in participants with lipedema versus control participants. In the forearm, skin TSC (13.4 ± 3.3 vs. 12.0 ± 2.3 mmol/L, P = 0.2, Cohen's d = 0.50) and fat/water (0.65 ± 0.24 vs. 0.48 ± 0.24 ratio, P = 0.07, Cohen's d = 0.68) demonstrated moderate effect sizes in participants with lipedema versus control participants. Calf skin TSC was significantly correlated with pain (Spearman's rho = 0.55, P = 0.03) and disease stage (Spearman's rho = 0.82, P < 0.001) among participants with lipedema. CONCLUSIONS: MRI-measured tissue sodium and fat content are significantly higher in the lower extremities, but not upper extremities, of patients with lipedema compared with BMI-matched controls.

BACKGROUND: Lymphatic insufficiency might play a significant role in the pathophysiology of lipoedema. Liposuction is up to now the best treatment. As liposuction is invasive, the technique could destruct parts of the lymphatic system and by this aggravate the lymphatic component and/or induce lymphoedema. We investigated the function of the lymphatic system in lipoedema patients before and after tumescent liposuction and thus whether tumescent liposuction can be regarded as a safe treatment. METHODS: Lymphoscintigraphy was performed to quantify the lymph outflow of 117 lipoedema patients. Mean clearance percentages of radioactive protein loaded after 1 min with respect to the total injected dose and corrected for decay of the radiopharmaceutical in the subcutaneous lymphatics were used as functional quantitative parameters as well as the clearance percentages and inguinal uptake 2 h post injection. The results of lymphatic function in lipoedema patients were compared with values obtained from normal healthy volunteers. We also compared 50 lymphoscintigraphies out of the previous 117 lipoedema patients before and six months after tumescent liposuction. RESULTS: In 117 lipoedema patients clearance 2 h post injection in the right and left foot was disturbed in 79.5 and 87.2% respectively. The inguinal uptake 2 h post injection in the right and left groin was disturbed in 60.3 and 64.7% respectively. In 50 lipoedema patients mean clearance and inguinal uptake after tumescent liposuction were slightly improved, 0.01 (p = 0.37) versus 0.02 (p = 0.02), respectively. This is statistically not relevant in clearance. CONCLUSION: Lipoedema legs have a delayed lymph transport. Tumescent liposuction does not diminish the lymphatic function in lipoedema patients, thus tumescent liposuction can be regarded as a safe treatment.

Lipedema is a chronic, progressive disease of adipose tissue with lack of consistent diagnostic criteria. The aim of this study was a thorough comparative characterization of extracellular microRNAs (miRNAs) from the stromal vascular fraction (SVF) of healthy and lipedema adipose tissue. For this, we analyzed 187 extracellular miRNAs in concentrated conditioned medium (cCM) and specifically in small extracellular vesicles (sEVs) enriched thereof by size exclusion chromatography. No significant difference in median particle size and concentration was observed between sEV fractions in healthy and lipedema. We found the majority of miRNAs located predominantly in cCM compared to sEV enriched fraction. Surprisingly, hierarchical clustering of the most variant miRNAs showed that only sEVmiRNA profiles - but not cCMmiRNAs - were impacted by lipedema. Seven sEVmiRNAs (miR-16-5p, miR-29a-3p, miR-24-3p, miR-454-p, miR-144-5p, miR-130a-3p, let-7c-5p) were differently regulated in lipedema and healthy individuals, whereas only one cCMmiRNA (miR-188-5p) was significantly downregulated in lipedema. Comparing SVF from healthy and lipedema patients, we identified sEVs as the lipedema relevant miRNA fraction. This study contributes to identify the potential role of SVF secreted miRNAs in lipedema.

BACKGROUND: Selenium is a trace element, which is utilized by the human body in selenoproteins. Their main function is to reduce oxidative stress, which plays an important role in lymphedema and lipedema. In addition, selenium deficiency is associated with an impaired immune function. The aim of this study was to determine the prevalence of selenium deficiency in these conditions, and if it is associated with disease severity and an associated medical condition such as obesity. METHODS: This cross-sectional study is an anonymized, retrospective analysis of clinical data that was routinely recorded in a clinic specialized in lymphology. The data was comprised from 791 patients during 2012-2019, in which the selenium status was determined as part of their treatment. RESULTS: Selenium deficiency proved common in patients with lymphedema, lipedema, and lipo-lymphedema affecting 47.5% of the study population. Selenium levels were significantly lower in patients with obesity-related lymphedema compared to patients with cancer-related lymphedema (96.6 ± 18.0 μg/L vs. 105.1 ± 20.2 μg/L; p < 0.0001). Obesity was a risk factor for selenium deficiency in lymphedema (OR 2.19; 95% CI 1.49 to 3.21), but not in lipedema. CONCLUSIONS: In countries with low selenium supply, selenium deficiency is common, especially in lymphedema patients. Therefore, it would be sensible to check the selenium status in lymphedema patients, especially those with obesity, as the infection risk of lymphedema is already increased.

The purpose is to determine whether surgical therapy of lipedema (stage I, II or III) using Liposuction the pain in the legs compared to the use of complex decongestive therapy (CDT) relevant improved.

Lipoedema, an adipose tissue disorder, is a poorly visible, often unrecognised condition. To foster a greater understanding of the significant and debilitating impacts faced by women living with lipoedema, the charity Lipoedema UK conducted four focus group interviews, the findings of which were published in a series of reports under the umbrella title 'Women in dire need'. The reports identified the substantial and numerous negative effects of lipoedema on the women's everyday lives, including the patients' experiences with compression garments, the effects of liposuction surgery (many of which were not positive), the everyday impacts ranging from pain and reduced mobility to poor self-esteem and working prospects, and the considerable challenges faced by women with late-stage lipoedema which can render them immobile.

Lipoedema is an incurable chronic disease causing limb deformity, painful skin and excessive ecchymosis. Compression garments are frequently recommended to manage symptoms, but the existing products are not designed specifically for lipoedema, and are for other medical conditions. A structured questionnaire was prepared in Online Surveys in October 2018 to investigate lipoedema symptoms and the use of compression garments to manage them. Some 279 people with lipoedema completed the survey; 70% wore compression garments in all four compression classes, of which class 2 was most common (58% of wearers). The top three reasons for wearing compression garments were to feel supported (73%), reduce lipoedema pain (67%) and improve mobility (54%). Most people with lipoedema who wore compression garments found compression helpful in managing their symptoms, but overall satisfaction was low. Problems with existing compression garments were so severe in some cases that the garments were not worn at all or used less often. The information collected in this survey might be useful for the design and development of compression garments specifically for lipoedema.

<p>Das Lipödem ist eine progrediente Erkrankung, die immer mehr Frauen betrifft und zunehmend bewusster als Krankheit wahrgenommen wird. Sie ist gekennzeichnet durch eine Umfangsvermehrung durch Fettgewebsvermehrung der Extremitäten und kann im Verlauf zu Ödemen führen. Im Gegensatz dazu ist das Lymphödem durch eine umschriebene Lymphabflussstörung definiert, die zur Bindegewebsfibrose des umliegenden Gewebes führen kann. Während das Lipödem als klinische Diagnose gesichert werden kann und eine bildgebende Diagnostik meist nur zum Ausschluss von Begleiterkrankungen eingesetzt werden kann, gibt es bei einem Lymphödem die Möglichkeit zur Darstellung einer Lymphabflussstörung durch bildgebende Verfahren. Eine Ultraschalluntersuchung ist als Basisdiagnostik zur Darstellung der eingelagerten interstitiellen Flüssigkeit sowohl beim Lip- als auch Lymphödem indiziert. Der Goldstandard zur Darstellung einer Lymphabflussstörung ist die Lymphszintigrafie, die auch in Kombination mit einer Computertomografie durchgeführt werden kann. Eine weitere dynamische Untersuchung ist die Indocyaningrün (ICG)-Lymphografie, deren Durchführung immer mehr an Bedeutung gewinnt, weil sie auch intraoperativ genutzt werden kann. Eine Magnetresonanz (MR)-Lymphografie zur 3-dimensionalen Darstellung eines Lymphödems und einer Lymphabflussstörung kann eine sinnvolle Ergänzung zur Therapie eines Lip- bzw. Lymphödems sein. Zur Therapie des Lip- und Lymphödems sollte stets eine Kombination aus konservativen und operativen Maßnahmen angestrebt werden. Während die Liposuktion und andere resezierende Verfahren Möglichkeiten zur Beschwerdelinderung bei bestehendem Lipödem oder fortgeschrittenem Lymphödem bieten, stellen die neuen rekonstruktiven Verfahren, wie beispielsweise die Lymphknotentransplantation und die Schaffung von lymphovenösen Anastomosen, vielversprechende, moderne Methoden zur Behandlung eines Lymphödems dar. Durch die Schaffung neuer Lymphabflusswege können Patienten mit einem Lymphödem auf eine langfristige Volumenreduktion der betroffenen Extremität oder Körperstelle und der damit verbundenen Symptomlinderung und Verbesserung der Lebensqualität hoffen.</p>