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Lymphedema is a complex and burdensome medical problem and requires continuous specific therapy. The aim of this cross-sectional study of community lymphedema care in the metropolitan area of Hamburg, Germany, was to evaluate health-related quality of life (QoL) in lymphedema patients. Generic as well as disease-specific health-related QoL was assessed using EQ-5D and FLQA-LK, respectively. Pain was assessed using a visual analogue scale (VAS). About 301 patients (median age of 60.5 years, 90.8% female) with lymphedema of any origin were included. About 66.4% had lymphedema, 24.1% combined lipolymphedema, and 9.5% lipoedema. Mean disease-specific QoL (FLQA-LK) was 2.4 (range 0 = no to 4 = maximum burden). The highest impairment values were observed in subscales for physical complaints, everyday life, and emotional well-being. Mean EQ-5D VAS was 70.4, mean EQ-5D score 63.3. Lymphedema was associated with major impairments in QoL, which differed for subgroups of pain, clinical severity, and comorbidity. Pain as a common problem for lymphedema patients seemed to be underestimated and undertreated. Early diagnosis and structured treatment strategies are urgently needed.

Background: Breast cancer treatment-related lymphedema (BCRL) arises from a mechanical insufficiency following cancer therapies. Early BCRL detection and personalized intervention require an improved understanding of the physiological processes that initiate lymphatic impairment. Here, internal magnetic resonance imaging (MRI) measures of the tissue microenvironment were paired with clinical measures of tissue structure to test fundamental hypotheses regarding structural tissue and muscle changes after the commonly used therapeutic intervention of manual lymphatic drainage (MLD)., Methods and Results: Measurements to identify lymphatic dysfunction in healthy volunteers (n = 29) and patients with BCRL (n = 16) consisted of (1) limb volume, tissue dielectric constant, and bioelectrical impedance (i.e., non-MRI measures); (2) qualitative 3 Tesla diffusion-weighted, T1-weighted and T2-weighted MRI; and (3) quantitative multi-echo T2 MRI of the axilla. Measurements were repeated in patients immediately following MLD. Normative control and BCRL T2 values were quantified and a signed Wilcoxon Rank-Sum test was applied (significance: two-sided p < 0.05). Non-MRI measures yielded significant capacity for discriminating between arms with versus without clinical signs of BCRL, yet yielded no change in response to MLD. Alternatively, a significant increase in deep tissue T2 on the involved (pre T2 = 0.0371 ± 0.003 seconds; post T2 = 0.0389 ± 0.003; p = 0.029) and contralateral (pre T2 = 0.0365 ± 0.002; post T2 = 0.0395 ± 0.002; p < 0.01) arms was observed. Trends for larger T2 increases on the involved side after MLD in patients with stage 2 BCRL relative to earlier stages 0 and 1 BCRL were observed, consistent with tissue composition changes in later stages of BCRL manifesting as breakdown of fibrotic tissue after MLD in the involved arm. Contrast consistent with relocation of fluid to the contralateral quadrant was observed in all stages., Conclusion: Quantitative deep tissue T2 MRI values yielded significant changes following MLD treatment, whereas non-MRI measurements did not vary. These findings highlight that internal imaging measures of tissue composition may be useful for evaluating how current and emerging therapies impact tissue function.

BACKGROUND: People with lipedema or Dercum's disease (DD) can have a similar distribution of excess painful nodular subcutaneous adipose tissue (SAT), making them difficult to differentiate. METHODS: Case series of 94 patients with DD, 160 with lipedema and 18 with both diagnoses (Lip+DD) from a single clinic in an academic medical center to improve identification and differentiation of these disorders by comparison of clinical findings, prevalence of type 2 diabetes (DM2), hypermobility by the Beighton score and assessment of a marker of inflammation, Total complement activity (CH50). RESULTS: Differences between groups were by Student's t-test with α of 0.05. The Lipedema Group had significantly greater weight, body mass index (BMI), gynoid distributed nodular SAT and fibrotic and heavy tissue than the DD Group. Hypermobility was significantly higher in the Lipedema (58±0.5%) than DD Group (23±0.4%; P<0.0001). DM2 was significantly greater in the DD (16±0.2%; P=0.0007) than the Lipedema Group (6±0.2%). Average pain by an analog scale was significantly higher in the DD (6±2.5%) than the Lipedema Group (4±2.1%; P<0.0001). Fatigue and swelling were common in both groups. Easy bruising was more common in the Lipedema Group, whereas abdominal pain, shortness of breath, fibromyalgia, migraines and lipomas were more prevalent in the DD Group. The percentage of patients with elevated CH50 was significantly positive in both groups. CONCLUSIONS: The significantly lower prevalence of DM2 in people with lipedema compared with DD may be due to the greater amount of gynoid fat known to be protective against metabolic disorders. The high percentage of hypermobility in lipedema patients indicates that it may be a comorbid condition. The location of fat, high average daily pain, presence of lipomas and comorbid painful disorders in DD patients may help differentiate from lipedema.

The lymphatic system regulates tissue fluid homeostasis, intestinal fat absorption, and immune cell trafficing. Lymphedema is soft tissue swelling secondary to lymphatic dysfunction, which results in the accumulation of tissue fluid in the interstitial space. This might occur as a primary disorder of the developing lymphatic system, or alternatively lymphedema might be an acquired disorder secondary to lymphatic injury. For example, secondary lymphedema is a common problem following cancer and cancer treatments such as lymph node surgery and radiotherapy, resulting in significant morbidity. Radiotherapy is an established risk factor for lymphedema, and in addition to causing direct injury to the lymphatic vessel, it is possible that alternative mechanisms might also contribute to radiation-induced lymphatic dysfunction, such as localized ischemia of the lymphatic wall. It is also likely that predisposing genetic risk factors are at play, as not all individuals exposed to the same risk factors will develop secondary lymphedema. Lipoedema is a different form of soft tissue swelling due to the abnormal accumulation of adipose tissue. Lipoedema and lymphatic dysfunction appear to be linked, as individuals frequently develop a degree of lymphedema, particularly as the condition progresses in severity, where it may be decribed as lipo-lymphedema. The cause of lipoedema and the genetic basis of the condition are currently unknown. This thesis aims to discover and define alternative mechanisms for lymphtic dysfunction in the context of secondary lymphedema, particularly focussing on the supply of oxygenated blood to the lymphatic vessel wall. We also aim to describe inheritance patterns and the genetic factors involved in lipoedema and lipo-lymphedema. Such knowledge might uncover therapeutic targets and facilitate the development of treatments for lymphedema and lipoedema, including gene therapy.

BACKGROUND: Long-term results following liposuction in patients with lipoedema are available only for an average period of 4 years. OBJECTIVE: To find out whether the improvement of complaints persists for a further 4 years. METHODS: In a single-centre study, 85 patients with lipoedema had already been examined after 4 years. A mail questionnaire - often in combination with clinical controls - was repeated after another 4 years (8 years after liposuction). RESULTS: Compared with the results after 4 years, the improvement in spontaneous pain, sensitivity to pressure, oedema, bruising and restriction of movement persisted. The same held true for patient self-assessment of cosmetic appearance, quality of life and overall impairment. Eight years after surgery, the reduction in the amount of conservative treatment (combined decongestive therapy, compression garments) was similar to that observed 4 years earlier. CONCLUSION: These results demonstrate for the first time the long-lasting positive effects of liposuction in patients with lipoedema.

Lipedema is a chronic disorder characterized by abnormal distribution of subcutaneous adipose tissue on the proximal extremities, pain and capillary fragility. Its etiology is unknown but in analogy to central obesity, chronic low-level inflammation in adipose tissue has been suggested. There seems to be an increased propagation of pre-adipocytes into mature adipocytes contributing to the massive enlargement of subcutaneous adipose tissue. We investigated whether tyrosine kinases might be involved. Proteins from adipose tissue harvested during microcannular tumescent liposuction in lipedema and in lipomas were subjected to 10% polyacrylamide-gel, transferred to a polyvinylidenfluorid membrane and immunoblotted with indicated P-Tyr-100 antibody followed by enhanced chemiluminescence reaction. A survey of all blots did not reveal tyrosine-phosphorylated proteins with a molecular weight >100 kD in lipedema tissue and controls. These investigations suggest absence of activated growth factor receptors. Some signals indicating unspecific tyrosine-phosphorylation of smaller proteins were detected in tissue of both lipedema patients and controls. The present data suggest that there is no enduring activation of tyrosine kinase pathways of adipogenesis in lipedema as in lipoma controls.

PURPOSE: Lipoedema is a chronic, progressive adipose disorder of unknown etiology, often underdiagnosed or misdiagnosed as obesity. It manifests itself with accumulation of the fat in lower parts of the body and associated edema and, due to numerous physical and psychological consequences, affects the quality of life (QOL) of those who suffer. The aim of this study was to investigate the psychological factors that might have an impact on the QOL of women with lipoedema from the contextual behavioral viewpoint. METHODS: In an Internet-based cross-sectional study, women suffering from lipoedema (N = 120) were asked to fill in questionnaires assessing: symptom severity, QOL (WHOQOL-BREF), satisfaction with life (SWLS), psychological flexibility (Acceptance and Action Questionnaire-II), social connectedness (Social Connectedness Scale-Revised) and other psychological factors. The majority of participants were from the USA, the UK, and Australia. RESULTS: Multiple hierarchical regression analyses showed that a higher level of QOL was predicted by higher levels of psychological flexibility and social connectedness, while controlling for symptom severity. Higher level of SWL was predicted only by higher level of social connectedness. CONCLUSIONS: Acceptance and Commitment Therapy with psychological flexibility as the target of change and Functional Analytic Psychotherapy with social connectedness as the target of change might be useful in treating women with lipoedema; however, further research in this area is needed. The authors conclude that psychological and biomedical interventions for women with lipoedema and their QOL merit more attention from researchers and the medical community than is currently received.

Vascular anomalies and related conditions cause overgrowth of tissues. The purpose of this study was to determine the efficacy and safety of liposuction techniques for pediatric overgrowth diseases. Patients treated between 2007 and 2015 who had follow-up were reviewed. Seventeen patients were included; the median age was 12.7 years. The causes of overgrowth included infiltrating lipomatosis (n = 7), capillary malformation (n = 6), hemihypertrophy (n = 1), infantile hemangioma (n = 1), lipedema (n = 1), and macrocephaly-capillary malformation (n = 1). Forty-seven percent had enlargement of an extremity, 41 percent had facial hypertrophy, and 12 percent had expansion of the trunk. All subjects had a reduction in the size of the overgrown area and improved quality of life. Suction-assisted tissue removal is an effective technique for reducing the volume of the subcutaneous compartment for patients with pediatric overgrowth diseases. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

INTRODUCTION: Liposuction for lymphoedematous limbs is an effective treatment for chronic lymphoedema, with excellent long-term results in well-selected patients. In 2008 NICE produced guidelines 'Liposuction for Chronic lymphoedema', acknowledging this treatment modality. However, there remain very few centers that provide this service in the United Kingdom. We aim to share our experience of our referral system at Ninewells Hospital, Dundee, Scotland. METHODS: A 10 year prospective database from 2005 to 2014 was analysed. Referral sources, patient demographics, diagnosis and treatment offered were examined. RESULTS: There were 221 referrals in total, 190 (86%) female and 31 (14%) male. The mean age was 51 (range 7-86 years). 127 (58%) were referred via their general practitioners, 72 (33%) from a hospital consultant and 22 (10%) from a lymphoedema nurse specialist. 153 (69%) referrals were from Scotland, 61 (28%) from England and 7 (3%) from Northern Ireland. The majority of patients 165 (75%) were referred with lower limb swelling. Following assessment in clinic, 146 (66%) were found to have lymphoedema whilst the rest were deemed to have other non-lymphoedematous diagnoses which include lipoedema (47, 21%), dependent oedema (8, 4%) and obesity (5, 2%). 131 (59%) were offered liposuction- 74 (34%) have received liposuction, 18 (8%) are awaiting their procedure, 3 (1%) have declined surgery, 27 (12%) are awaiting funding approval and 9 (4%) have been declined funding by their primary care trust/clinical commissioning group (PCT/CCG). 4 (2%) are awaiting investigations to further evaluate the cause of their swelling, whilst the remaining 86 (39%) were felt unsuitable for surgery and were treated conservatively. CONCLUSION: Chronic lymphoedema is a challenging condition to treat, with few specialist centers offering surgical treatment. We hereby share our referral process, diagnosis and management.

Methods: Thirty-six legs in 18 patients with secondary lower extremity lymphedema (LEL) and 20 legs in 10 healthy volunteers were examined using elastography. Thirty-six legs in 18 secondary LEL patients were examined using ICG lymphography. Elastography was performed on both legs at the following three sites: medial thigh (MT), medial leg (ML), and anterior ankle (AA). The area of the red region in the subcutaneous tissue demonstrated by elastography was calculated using Image software. ICG lymphography findings were classified into the following four patterns: linear (ICG1), splash (ICG2), stardust (ICG3), and diffuse (ICG4) patterns. Results: As ICG pattern progressed, the red region area was likely to increase. There was a correlation between ICG patterns and red region area according to the severity at bilateral MT (rs Z 0.665), ML (rs Z 0.623), and AA (rs Z 0.668). Significant difference was demonstrated among group means of the red region area by analysis of variance (healthy vs. ICG1 vs. ICG2 vs. ICG3 vs. ICG 4: 14.4 Æ 5.7 vs. 15.1 Æ 10.3 vs. 25.2 Æ 6.2 vs. 30.8 Æ 9.4 vs. 35.0 Æ 2.8; P < 0.001). Conclusions: The area of the red region in the subcutaneous tissue shown using elastography, which represents fluid, increases with the aggravation of lymphedema demonstrated by ICG

Background: Lipedema is a poorly known disorder of painful subcutaneous adipose tissue (SAT) likely affecting millions of women worldwide. Stage 1 lipedema has smooth skin with increased underlying fat, Stage 2 has indentations and nodules, and Stage 3 has large extrusions of skin and SAT. Women with lipedema have more SAT below the waist. As this gynoid fat is known to be cardioprotective, we aimed to determine if health declined with increasing stage and extent of lipedema SAT. Methods and Findings: Chart review from June 2012 to February 2013 at a tertiary academic center. Fifty women and one man were included in consecutive order. Fat was assessed in 29 areas for lipomas, size of the depot, and presence of lipedema fat. Pain was assessed by a numerical pain scale. Average age of patients was 50 ± 13 y; average body mass index was 38 ± 12 kg/m2. Median age of development of lipedema was 20 y. Pain occurred daily in 89.7%. None of the patients with Stage 1 lipedema had diabetes, hypertension or dyslipidemia. The amount of lipedema fat differed significantly between Stages of lipedema (p=0.003), with Stage 3 having significantly more. There was no difference in fat depot size or number of lipomas amongst Stages. Only one of 51 patients had type 2 diabetes. There was an increase in shortness of breath, palpitations, urination, and numbness in Stage 3. Conclusions: Lipedema fat can develop in any SAT location and increases in association with increasing signs and symptoms of systemic illness.

Background: Lipedema is a painful, genetically induced, abnormal deposition of subcutaneous fat in the extremities of women. The pathogenesis is unknown. Also unknown is the number of women affected in Germany. This study presents the epidemiology of the disease. There are currently two treatment options available: Complex physical decongestive therapy and liposuction. Liposuction is the only method that removes fat permanently. An additional study proves its effectiveness and highlights its vital role as part of a comprehensive treatment concept.

AIM: Application of microcurrents of bioresonance may allow protein aggregates lysis and a related enhancement of lymphatic drainage. Combining bioresonance with transcutaneous passage of active principles, by means of skin electroporation, microcirculation and clearance of connective tissues may be theoretically activated. A pilot study on an electro-medical device which includes these two technologies (Transponder(®)), has been performed on patients affected by lymphedema (LYM) and/or lipedema (LIP) of the lower limbs. METHODS: Eight patients affected by primary or secondary unilateral LYM or LIP were submitted to six consecutive daily sessions with the medical device; the first two sessions were performed by a trained physiotherapist, whilst the following four sessions were self-administered by the patients themselves at home (who were educated about the technique). Magnesium silicate was delivered transcutaneously by means of the device at each session. Pre-post-treatment assessment included: 1) limb volumetry by means of tape measurement; 2) segmental multifrequency bioimpedance spectroscopy for fluid changes, with L-DEX measurement; 3) visual analogue scale (VAS) (0-10 score) questionnaire for related symptoms. RESULTS: All the patients completed the scheduled treatment. After the treatment the mean volume of the whole limb decreased from 9462.85 (±3407.02) to 9297.37 cc (±3393.20), which accounts for a 165.48 cc (2%) reduction after six days of treatment. The pre/post-treatment VAS mean score changes were: heaviness from 4.57±3.46 to 2.43±2.57 (-47%), dysesthesias from 1.71±2.63 to 0.71±1.50 (-58%), pain from 1.57±2.57 to 0.57±0.79 (-64%). Diuresis VAS measurement passed from 7.43±1.81 to 8.57±0.98 (15% increase). The average L-DEX percentage reduction was 21%. No side effects were reported and a good patients' compliance was recorded. CONCLUSIONS: The preliminary data of this pilot study show that the combination of microcurrents of bioresonance with transdermal delivery of active principles indicate that it could result in edema decrease and symptom improvement in patients affected by LYM and/or LIP of the lower limbs. Self-administered modality of the electrical device is possible and effective; no side effects have been reported.

BACKGROUND: Distinguishing lymphoedema from lipoedema in women with swollen legs can be difficult. Local tissue water content can be quantified using tissue dielectric constant (TDC) measurements. OBJECTIVES: To examine whether TDC measurements can differentiate untreated lower extremity lymphoedema from lipoedema, and to test interobserver agreement. METHODS: Thirty-nine women participated in the study; 10 patients with lipoedema (LipP), nine patients with untreated lymphoedema (U-LP), 10 patients with lymphoedema treated with compression bandaging for ≥ 4 weeks (T-LP) and 10 healthy controls. All subjects were measured at three predefined sites (foot, ankle and lower leg). All groups except U-LP were measured by three blinded investigators. Using a handheld device, a 300-MHz electromagnetic wave is transmitted into the skin via a 2.5-mm depth probe. TDC calculated from the reflected wave is directly proportional to tissue water content ranging from 1 (vacuum) to 78.5 (pure water). RESULTS: Mean ± SD TDC values for U-LP were 48.8 ± 5.2. TDC values of T-LP, LipP and controls were 34.0 ± 6.6, 29.5 ± 6.2 and 32.3 ± 5.7, respectively. U-LP had significantly higher TDC values in all measurement sites compared with all other groups (P < 0.001). A cut-off value of 40 for ankle and lower-leg measurements correctly differentiated all U-LP from LipP and controls. Intraclass correlation coefficients were 0.94 for the ankle and the lower leg and 0.63 for the foot. CONCLUSIONS: TDC values of U-LP were significantly higher than those of T-LP, LipP and controls and may aid in differentiating lymphoedema from lipoedema. Interobserver agreement was high in ankle and lower-leg measurements but low in foot measurements.