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The purpose of this work was to quantify 3.0 T (i) T(1) and T(2) relaxation times of in vivo human lymph nodes (LNs) and (ii) LN relaxometry differences between healthy LNs and LNs from patients with lymphatic insufficiency secondary to breast cancer treatment-related lymphedema (BCRL). MR relaxometry was performed over bilateral axillary regions at 3.0 T in healthy female controls (105 LNs from 20 participants) and patients with BCRL (108 LNs from 20 participants). Quantitative T(1) maps were calculated using a multi-flip-angle (20, 40, 60°) method with B(1) correction (dual-T(R) method, T(R1) /T(R2)  = 30/130 ms), and T(2) maps using a multi-echo (T(E)  = 9-189 ms; 12 ms intervals) method. T(1) and T(2) were quantified in the LN cortex and hilum. A Mann-Whitney U-test was applied to compare LN relaxometry values between patients and controls (significance, two sided, p < 0.05). Linear regression was applied to evaluate how LN relaxometry varied with age, BMI, and clinical indicators of disease. LN substructure relaxation times (mean ± standard deviation) in healthy controls were T(1) cortex, 1435 ± 391 ms; T(1) hilum, 714 ± 123 ms; T(2) cortex, 102 ± 12 ms, and T(2) hilum, 119 ± 21 ms. T(1) of the LN cortex was significantly reduced in the contralateral axilla of BCRL patients compared with the axilla on the surgical side (p < 0.001) and compared with bilateral control values (p < 0.01). The LN cortex T(1) asymmetry discriminated cases from controls (p = 0.004) in a multiple linear regression, accounting for age and BMI. Human 3.0 T T(1) and T(2) relaxation times in axillary LNs were quantified for the first time in vivo. Measured values are relevant for optimizing acquisition parameters in anatomical lymphatic imaging sequences, and can serve as a reference for novel functional and molecular LN imaging methods that require quantitative knowledge of LN relaxation times.

INTRODUCTION: Lipedema is a syndrome that is characterised by edema, an accumulation of fat, pain and haematomas in the lower limbs that principally affects women. Diagnosis is currently based on clinical criteria, since there is no accurate diagnostic imaging for the condition. The aim of our study was to describe the lymphoscintigraphic findings in patients with lipedema. MATERIAL AND METHOD: A prospective cohort study of women with clinical criteria of lipedema who underwent lymphoscintigraphy. Two independent nuclear physicians described and classified the lymphoscintigraphy findings in different grades of severity, according to the migration and distribution of the radiopharmaceutical. Eighty three patients were included with a median age of 49.7years (range: 18-80) and a mean body mass index (BMI) of 29.9kg/m(2) (95%CI: 28.4-31.3) RESULTS: Lymphoscintigraphy showed alterations in 47% of the patients, most were low (35.9%) or low-moderate grade (48.7%). None of the patients were severely affected (no migration of the radiopharmaceutical). The degree of lymphoscintigraphic involvement bore no relation to age (P=.674), Stemmer's sign (P=.506), or BMI (P=.832). We found lymphoscintigraphy findings in all the clinical stages of lipedema, with no significant differences between the grade of lymphoscintigraphic involvement and the clinical stage of lipedema (P=.142). CONCLUSION: Although lymphoscintigraphy has been used to differentiate lipedema from lymphedema, we found frequent alterations in the patients with lipedema, therefore the presence of findings dues not discount a diagnosis of lip1aedema.

Lipoedema is painful nodular subcutaneous adipose tissue (SAT) on legs and arms of women sparing the trunk. People with Dercum disease (DD) have painful SAT masses. Lipoedema and DD fat resists loss by diet and exercise. Treatments other than surgery are needed. Six women with lipoedema and one with DD underwent twelve 90-min sessions over 4 weeks. Body composition by dual X-ray absorptiometry scan, leg volume, weight, pain, bioimpedance, tissue size by caliper and ultrasound were analysed before and after SAT therapy by paired t-tests. There was a significant decrease from baseline to end of treatment in weight, 87.6 ± 21 to 86.1 ± 20.5 kg (P = 0.03), leg fat mass 17.8 ± 7.7 to 17.4 ± 7.6 kg (P = 0.008), total leg volume 12.9 ± 4 to 12 ± 3.5 L (P = 0.007), six of 20 calliper sites and tissue oedema. Pain scores did not change significantly. By ultrasound, six women had 22 hyperechoic masses in leg fat that resolved after treatment; five women developed seven new masses. Fascia improved by ultrasound after treatment. SAT therapy reduced amount and structure of fat in women with lipoedema and Dercum disease; studies are needed to compare SAT therapy to other therapies.

BACKGROUND: Tape measures continue to be used for the diagnosis and evaluation of lipoedema and lymphoedema in the clinical routine. Extremity volumes are calculated based on standardised circumferential measurements. Other volume measurements such as water displacement are not applied on a regular basis. This study aimed to evaluate a 3D scanner as an alternative and reproducible tool to objectively measure the volumes of the lower extremity. PATIENTS, MATERIALS AND METHOD: We used a commercially available 3D scanner, the Artec Eva(®), to perform 3D scans of the lower extremities on 20 subjects and calculated the volume using the appropriate software. In addition, limb volume was determined with standardised methods using the circumferential method (cone method and disc method) and the water displacement technique. The results and the time taken to perform the three measurement methods were documented and statistically evaluated. RESULTS: There were no significant deviations between the results from 3D volumetry and water displacement (p > 0.05). The cone method significantly overestimated the volume measured by water displacement and 3D volumetry. The disc method revealed no statistically significant differences, but clinically relevant differences with a high variance in the 95 % confidence interval. All methods demonstrated high positive correlations with each other. Water displacement was the most timeconsuming method. CONCLUSION: Our findings obtained from the examination of 40 lower extremities show that 3D scans and software-based volumetric calculations can achieve objective and reproducible measurements in a relatively short time. The deviation from the gold-standard method of water displacement is small. Compared with the cone and disc method, however, we observed clinically relevant deviations with a high variance. We therefore recommend the 3D scan procedure for the objective documentation of conservative and surgical treatments for lipoedema or lymphoedema and have incorporated it into our clinical routine.

Lipedema is a chronic, progressive adipose tissue disorder that may impact the quality of life of women who suffer from it. The main aim of this study was to asses the role of perceived symptom severity, physical and psychological functioning with the disease in predicting quality of life in patients with lipedema. We conducted an online study with 329 participants who responded to five questionnaires measuring quality of life (World Health Organization Quality of Life BREF), lipedema symptom severity, mobility (Lower Extremity Functional Scale), depression (Patients Health Questionnaire-9), and appearance-related distress (Derriford Appearance Scale 24). Multiple hierarchical regression analyses showed that appearance-related distress and depression explained significantly more variance in quality of life when added to the symptom severity and mobility. Lower quality of life was predicted by higher symptom severity, lower mobility, higher appearance-related distress and higher depression severity. Appearance-related distress and depression constitute important aspects of psychological functioning in women with lipedema. Considering their relationship with quality of life, their assessment should be included in lipedema treatment with appropriate interventions aimed at decreasing appearance-related distress, as well as preventing and addressing depression.

BACKGROUND: Implementation of guideline recommendations for the diagnosis and therapy of lipedema and lymphedema seems to be problematic in daily routine. Systematic data for Germany are missing. The aim of the study was data collection regarding diagnosis and therapy of lymphologic diseases in an outpatient setting. METHODS: Monocentric, prospective survey of patients from a lymphologic outpatient clinic using a standardized questionnaire focusing on diagnostics and therapy at the initial diagnosis. RESULTS: In all, 72 patients (83.3% women) with lymphedema (n = 26), lipedema (n = 14) or lipolymphedema (n = 32) were included; 44.4% had symptoms more than 5 years before the initial diagnosis. Main symptoms were swelling of the leg and foot (especially lymphedema) and feeling of heaviness (especially lipedema). In 75%, the initial diagnosis was made by a medical specialist. The basic diagnostics recommended by the guidelines-medical history (73.6%) and clinical examination (84.7%)-were done in most of the patients. After the initial diagnosis, 46% of the patients had decongestion therapy of different intensity and quality. A total of 58.3% of the patients were directly provided a prescription for a medical stocking. Only a few patients received instructions for breathing exercises (22.2%), self-performed lymphatic drainage (6.9%) or muscle exercises (8.3%). DISCUSSION: There are still deficits in the diagnosis and especially in the therapy of patients with lymphologic diseases in an outpatient setting. Further education and training are necessary for physicians, physiotherapists, medical supply businesses, and patients.

INTRODUCTION: Lipoedema is a chronic disorder in which excessive fat distribution occurs predominantly from the waist down, resulting in a disproportion between the lower extremities and upper torso. Lipoedema is often not recognized, while patients experience pain and easy bruising. As a long-term condition, lipoedema has a massive effect on patients' lives and mental health. The aim of this study is to explore patient characteristics, quality of life, physical complaints and comorbidities in patients with lipoedema. METHODS: A survey was conducted by email amongst lipoedema patients, consisting of informed consent and multiple questionnaires. The questionnaires included general patient characteristics, physical complaints, comorbidities, RAND-36 and EQ-5D-3L. Participants who responded to a message on the Dutch Lipoedema Association website were recruited. RESULTS: All lipoedema patients experience physical complaints, with pain (88.3 %) and easy bruising (85.9 %) as primary complaints. The diagnosis was mostly made by a dermatologist after visiting a mean of 2.8 doctors. Furthermore, mean time from onset until diagnosis was 18 years. Quality of life (59.3) was significantly lower than the Dutch female average (74.9; p < 0.001). Additionally, patients with comorbidities had significant lower quality of life (RAND 54.7, p < 0.001). CONCLUSIONS: Lipoedema patients often have severe complaints and experience lower quality of life regarding physical, emotional and social functioning. Additionally, comorbidities have a large impact on quality of life.

Background Lipedema is a chronic disorder presenting in women during puberty or other times of hormonal change such as childbirth or menopause, characterized by symmetric enlargement of nodular, painful subcutaneous adipose tissue (fat) in the limbs, sparing the hands, feet and trunk. Healthcare providers underdiagnose or misdiagnose lipedema as obesity or lymphedema. Materials and methods The benefits (friend) and negative aspects (foe) of lipedema were collected from published literature, discussions with women with lipedema, and institutional review board approved evaluation of medical charts of 46 women with lipedema. Results Lipedema is a foe because lifestyle change does not reduce lipedema fat, the fat is painful, can become obese, causes gait and joint abnormalities, fatigue, lymphedema and psychosocial distress. Hypermobility associated with lipedema can exacerbate joint disease and aortic disease. In contrast, lipedema fat can be a friend as it is associated with relative reductions in obesity-related metabolic dysfunction. In new data collected, lipedema was associated with a low risk of diabetes (2%), dyslipidemia (11.7%) and hypertension (13%) despite an obese average body mass index (BMI) of 35.3 ± 1.7 kg/m2. Conclusion Lipedema is a painful psychologically distressing fat disorder, more foe than friend especially due to associated obesity and lymphedema. More controlled studies are needed to study the mechanisms and treatments for lipedema.

Background Lipedema is a chronic disorder presenting in women during puberty or other times of hormonal change such as childbirth or menopause, characterized by symmetric enlargement of nodular, painful subcutaneous adipose tissue (fat) in the limbs, sparing the hands, feet and trunk. Healthcare providers underdiagnose or misdiagnose lipedema as obesity or lymphedema. Materials and methods The benefits (friend) and negative aspects (foe) of lipedema were collected from published literature, discussions with women with lipedema, and institutional review board approved evaluation of medical charts of 46 women with lipedema. Results Lipedema is a foe because lifestyle change does not reduce lipedema fat, the fat is painful, can become obese, causes gait and joint abnormalities, fatigue, lymphedema and psychosocial distress. Hypermobility associated with lipedema can exacerbate joint disease and aortic disease. In contrast, lipedema fat can be a friend as it is associated with relative reductions in obesity-related metabolic dysfunction. In new data collected, lipedema was associated with a low risk of diabetes (2%), dyslipidemia (11.7%) and hypertension (13%) despite an obese average body mass index (BMI) of 35.3 ± 1.7 kg/m2. Conclusion Lipedema is a painful psychologically distressing fat disorder, more foe than friend especially due to associated obesity and lymphedema. More controlled studies are needed to study the mechanisms and treatments for lipedema.

Das Lipödem ist weit mehr als einfach nur dickere und schmerzhafte Beine! Die Erkrankung Lipödem ist mit zahlreichen Mythen behaftet. Im ersten Teil dieser Übersicht werfen wir einen kritischen Blick auf zwei populäre Statements zum Lipödem; Statements, die vor Jahrzehnten schon Eingang in wissenschaftliche Publikationen gefunden haben und seither unkritisch und stetig wiederholt werden; Statements, die inzwischen zum selbstverständlichen Wissensallgemeingut von Lipödempatientinnen und vor allem auch von Lipödem-Selbsthilfegruppen geworden sind. In unserer Darstellung über die Mythen des Lipödems fokussieren wir uns in diesem Beitrag vor allem auf zwei Aspekte, die aufs Engste mit dem Lipödem verbunden sind: auf die Adipositas sowie auf die psychische Situation von Lipödempatientinnen – die wiederum eng mit der Adipositas in Zusammenhang steht. Dabei überprüfen wir zwei häufig publizierte Statements auf wissenschaftliche Evidenz: 1. „Das Lipödem ist eine progrediente Erkrankung”, 2. „Ein Lipödem macht psychisch krank”. Beide Statements widersprechen in hohem Maße unserer seit Jahren bestehenden täglichen klinischen Erfahrung mit diesem speziellen Patientengut. Gleichzeitig haben wir im Rahmen unserer umfangreichen Literaturrecherche festgestellt, dass es auch keine Evidenz für diese in den „Lipödemsprachgebrauch” eingegangenen Behauptungen gibt. Tatsachlich ist das Lipödem in der Regel keine progrediente Erkrankung! Vielmehr liegt bei Lipödempatientinnen häufig eine Gewichtsprogredienz (meist eine Adipositasprogredienz) vor, in deren Folge sich auch das Lipödem verschlechtern kann. Unsere Pilotstudie zum 2. Statement macht deutlich, dass in der Regel nicht das Lipödem Ursache von psychischen Erkrankungen ist. Hier weisen unsere Ergebnisse in die umgekehrte Richtung: Eine – vorbestehende – psychische Vulnerabilität kann ganz wesentlich zum Krankheitsbild Lipödem beitragen. Um das Lipödem in seiner ganzen Komplexität und Vielfalt zu erfassen, braucht es mehr als nur Medizin. Psychosoziale Therapieansätze sollten integraler Bestandteil eines wirksamen multimodalen Behandlungskonzepts sein. Neben den beiden dargestellten Mythen gibt es weitere, die sich um das Lipödem ranken. Diese werden in weiteren Ausgaben dieser Zeitschrift diskutiert werden.

OBJECTIVE: To test the hypothesis that tissue sodium and adipose content are elevated in patients with lipedema; if confirmed, this could establish precedence for tissue sodium and adipose content representing a discriminatory biomarker for lipedema. METHODS: Participants with lipedema (n = 10) and control (n = 11) volunteers matched for biological sex, age, BMI, and calf circumference were scanned with 3.0-T sodium and conventional proton magnetic resonance imaging (MRI). Standardized tissue sodium content was quantified in the calf skin, subcutaneous adipose tissue (SAT), and muscle. Dixon MRI was employed to quantify tissue fat and water volumes of the calf. Nonparametric statistical tests were applied to compare regional sodium content and fat-to-water volume between groups (significance: two-sided P ≤ 0.05). RESULTS: Skin (P = 0.01) and SAT (P = 0.04) sodium content were elevated in lipedema (skin: 14.9 ± 2.9 mmol/L; SAT: 11.9 ± 3.1 mmol/L) relative to control participants (skin: 11.9 ± 2.0 mmol/L; SAT: 9.4 ± 1.6 mmol/L). Relative fat-to-water volume in the calf was elevated in lipedema (1.2 ± 0.48 ratio) relative to control participants (0.63 ± 0.26 ratio; P < 0.001). Skin sodium content was directly correlated with fat-to-water volume (Spearman's rho = 0.54; P = 0.01). CONCLUSIONS: Internal metrics of tissue sodium and adipose content are elevated in patients with lipedema, potentially providing objective imaging-based biomarkers for differentially diagnosing the under-recognized condition of lipedema from obesity.

Whereas the blood microvasculature constitutes a biological barrier to the action of blood-borne insulin on target tissues, the lymphatic microvasculature might act as a barrier to subcutaneously administrated insulin reaching the circulation. Here, we evaluate the interaction of insulin with primary microvascular endothelial cells of lymphatic [human dermal lymphatic endothelial cells (HDLEC)] and blood [human adipose microvascular endothelial cells (HAMEC)] origin, derived from human dermal and adipose tissues, respectively. HDLEC express higher levels of insulin receptor and signal in response to insulin as low as 2.5 nM, while HAMEC only activate signaling at 100 nM (a dose that blood vessels do not normally encounter). Low insulin acts specifically through the insulin receptor, while supraphysiological insulin acts through both the IR and insulin growth factor-1 receptor. At supraphysiological or injection site-compatible doses pertinent to lymphatic microvessels, insulin enters HAMEC and HDLEC via fluid-phase endocytosis. Conversely, at physiologically circulating doses (0.2 nM) pertinent to blood microvessels, insulin enters HAMEC through a receptor-mediated process requiring IR autophosphorylation but not downstream insulin signaling. At physiological doses, internalized insulin is barely degraded and is instead released intact to the extracellular medium. In conclusion, we document for the first time the mechanism of interaction of insulin with lymphatic endothelial cells, which may be relevant to insulin absorption during therapeutic injections. Furthermore, we describe distinct action and uptake routes for insulin at physiological and supraphysiological doses in blood microvascular endothelial cells, providing a potential explanation for previously conflicting studies on endothelial insulin uptake.

Zusammenfassung Einleitung: Die aktuelle deutsche Leitlinie zur Behandlung des Lipödems empfiehlt neben der Therapie mit flachgestrickten Kompressionsmaterialien und manueller Lymphdrainage auch die Liposuktion. Die Abgrenzung zu Adipositas und asymptomatischer Lipohypertrophie stellt dabei häufig ein differenzialdiagnostisches Problem dar. Eine reproduzierbare und objektivierbare Differenzialdiagnostik ist aber die Grundlage für eine zielführende und wirtschaftliche Behandlung. Material und Methoden: Im Rahmen einer multizentrischen Registerstudie (5 Zentren) wurden im Zeitraum von 01/2016 bis 05/2017 die Beine (n=294) von Patientinnen mit Lipödem (n=136), Lymphödem (n=20), Lipödem mit sekundärem Lymphödem (n=30), Lipohypertrophie (n=42) und Adipositas (n=30) sowie von Gesunden (n=36) sonografisch untersucht. Es wurden Messungen der Dicke von Kutis und Subkutis an den Unter- und Oberschenkeln sowie von deren Komprimierbarkeit durchgeführt. Zusätzlich erfolgte eine Analyse der Sonomorphologie. Ergebnisse: Spezielle sonomorphologische Eigenschaften, die ein Lipödems von den anderen Krankheitsentitäten bzw. vom Gesunden abgrenzen lassen, konnten bislang nicht übereinstimmend und überzeugend herausgearbeitet werden. Die Komprimierbarkeit des Kutis-Subkutis-Komplexes ist vollkommen unspezifisch und lässt keinen Rückschluss auf die Diagnose Lipödem zu. Der Nachweis von Flüssigkeitseinlagerungen bei Patienten mit einer „schmerzhaften Lipohypertrophie” gelingt nicht, sodass die Krankheitsbezeichnung Lipödem irreführend ist und überdacht werden sollte. , Summary Introduction: The current German guidelines on treating lipoedema recommend using flatknitted compression material and manual lymphatic drainage as well as liposuction. Differentiating lipoedema from obesity and asymptomatic lipohypertrophy frequently proves difficult. However, a reproducible and objective differential diagnosis is the foundation of an expedient and cost-effective treatment. Material and Methods: As part of a multi-centre registry study (5 centres) ultrasound scans were performed between 1/2016 and 5/2017 on the legs (n=294) of a total of 147 patients with lipoedema (n=136), lymphoedema (n=20), lipoedema with secondary lymphoedema (n=30), lipohypertrophy (n=42) and obesity (n=30), as well as healthy individuals (n=36). Measurements were performed on the thickness of the cutis and subcutis of the lower and upper leg and on their compressibility. An analysis of the sonomorphology was also conducted. Results: Special sonomorphological properties that allow lipoedema to be differentiated from other disease entities and from healthy individuals have yet to be consistently and conclusively identified. The compressibility of the cutis-subcutis complex is completely unspecific and does not allow for any conclusions to be drawn concerning lipoedema. It has not been possible to detect fluid retention in patients with “painful lipohypertrophy” so that the description of the disease as lipoedema is misleading and should be reconsidered.

The present study aimed to assess LV rotational mechanics by three-dimensional speckle-tracking echocardiography (3DSTE) in lipedema (n=25), lymphedema (n=26) patient groups with age- and gender-matched healthy controls (n=54). 3 lipedema and 4 lymphedema patients were excluded due to insufficient image quality for 3DSTE analysis. LV apical rotation (9.61 ± 4.25 degree vs. 6.40 ± 2.63 degree, p <0.05) and LV twist (13.83 ± 4.89 degree vs. 10.04 ± 3.56 degree, p <0.05) are impaired in lipedema patients as compared to matched controls; similar alterations in lymphedema were not found. Moreover, in some lipedema and lymphedema patients severe LV rotational abnormalities could be detected. Our results suggest that lipedema-associated impaired LV apical rotation and twist assessed by 3DSTE could be a novel differential diagnostic point between lipedema and lymphedema.

Introduction Lipedema (meaning edema in fat) and Dercum Disease (DD) are fat disorders in which accumulation of painful subcutaneous adipose tissue (SAT) affects more females than males, especially at times of female hormone change. Patients with both fat disorders are often misdiagnosed as obese. The purpose of this study was to determine if estrogen (ER) and progesterone receptors (PR) are different in lipedema versus DD in SAT and skin versus controls. These receptors are on mast cells that produce histamine causing leakage from blood vessels inducing hypoxia and angiogenesis. Progesterone is known to activate histamine release from mast cells. We aim to determine levels of ER and PR in SAT and if blood vessels replicate at a higher rate in lipedema and DD versus controls to help further understand these conditions and work towards finding a cure. Materials and Methods Immunohistochemistry (San Diego Pathology, San Diego, CA) was used to test for the presence of PR, ER, Ki67 (marker of replicating cells), and CD117 (marker of mast cells). Results and Discussion Mast cell numbers were similar in control, DD and lipedema SAT (Figure). ER were not different in control, DD and lipedema SAT. PR were significantly lower in lipedema SAT. There was no difference in Ki67 in lipedema or DD blood vessels compared to controls. Conclusion Lower numbers of PR in our data suggest mast cell secretions (histamine and others) could be higher inducing leakage from vessels and fluid collection in SAT. Fluid in the tissue should induce hypoxia and growth of more blood vessels. Despite higher PR on mast cells, lipedema blood vessels did not appear to be replicating at a higher level. With further research and additional samples, the relevance of elevated PR in lipedema tissue may become apparent. Support or Funding Information Research reported in this poster was supported by the National Institute of General Medical Sciences of the National Institutes of Health under linked Award Numbers RL5GM118969, TL4GM118971, and UL1GM118970. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Special acknowledgement to the Minority Health Disparities summer research program at the University of Arizona, the College of Medicine Tucson Treatment, Research, and Education of Adipose Tissue Program. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.