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Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A “multiple-hit” pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data (BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the “imperfect” gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g. , magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention.

Lipedema is an uncommon disorder characterized by localized adiposity of the lower extremities, often occurring in females with a family history of the condition. The adiposity extends from hips to ankles and is typically unresponsive to weight loss. In addition to the aesthetic deformity, women also describe pain in the lower extremities, particularly with pressure, as well as easy bruising. Although the condition is well described, it is relatively rare and often misdiagnosed. The purpose of this review is to describe the initial evaluation and diagnosis of lipedema and discuss treatment options.

Objective: The purpose of this study was to investigate the clinical significance of lymphoscintigraphy imaging in the evaluation of lower extremity lymphedema. Methods: Technetium-99m-labeled nanocolloid was injected subcutaneously in the first web spaces of both feet of 123 patients (M/F: 43/80, mean age 57.5±13.1 years, range 16-78 years) who had clinical evidence of lower extremity swelling with suspicion of lymphedema, and were referred for routine lymphoscintigraphy. Lymphoscintigraphy scan was started as dynamic viewing followed by static whole body imaging at 10 minute, 1 hour and 4 hours after injection. Results: Eighty-seven patients had lymphedema. Patients who had lymphedema were divided into two groups according to their scintigraphy findings: Group I included 58 patients without uptake in the popliteal nodes, and group II included 29 patients with positive popliteal nodes. The rate of popliteal node visualization was higher in patients with dermal backflow as compared to those without dermal backflow (p<0.001). The duration of lymphedema was also longer in patients with dermal backflow and popliteal nodes (p<0.004). Conclusion: Lymphoscintigraphy is a reliable, easily applied and well-tolerated objective method to diagnose lower extremity lymphedema. Uptake by popliteal lymph nodes and the presence of dermal backflow on lymphoscintigraphy, which is performed for evaluation of the lower limb lymphedema, were important signs indicating longer disease duration and higher severity of lymphatic dysfunction.

The increasing prevalence of obesity causes a major interest in white adipose tissue biology. Adipose tissue cells are surrounded by extracellular matrix proteins whose composition and remodeling is of crucial importance for cell function. The expansion ...

Lipedema is a disfiguring disorder with abnormal and progressive deposition of adipose tissue in the hips and lower extremities almost exclusively occurring in women. There is a hereditary tendency and a substantial variability in disease severity. Lipedema is often misdiagnosed as lymphedema or morbid obesity. The etiology and pathogenesis are not understood. Early diagnosis and treatment are critical to minimize physical and psychological morbidity. The diagnosis is usually made by history and clinical examination. Non-invasive imaging techniques such as computed tomography or magnetic resonance can differentiate lipedema from other causes of edematous lower extremities. Lymphoscintigraphy may be helpful in cases which are associated with lymphedema (lipo-lymphedema). Management with manual lymphatic drainage and compression therapy are considered the most appropriate treatment. Use of conventional liposuction is controversial since it may further damage the lymphatic vessels. Newer techniques such as tumescent micro annular laser assisted liposuction and water jet-assisted liposuction have shown some promising results. Variety of other surgical procedures combined with manual lymphatic drainage and tailored post-surgical care are under investigation.

Upper- and lower-body fat depots exhibit opposing associations with obesity-related metabolic disease. We defined the relationship between DEXA-quantified fat depots and diabetes/cardiovascular risk factors in a healthy population-based cohort (n = 3,399). Gynoid fat mass correlated negatively with insulin resistance after total fat mass adjustment, whereas the opposite was seen for abdominal fat. Paired transcriptomic analysis of gluteal subcutaneous adipose tissue (GSAT) and abdominal subcutaneous adipose tissue (ASAT) was performed across the BMI spectrum (n = 49; 21.4-45.5 kg/m(2)). In both depots, energy-generating metabolic genes were negatively associated and inflammatory genes were positively associated with obesity. However, associations were significantly weaker in GSAT. At the systemic level, arteriovenous release of the proinflammatory cytokine interleukin-6 (n = 34) was lower from GSAT than ASAT. Isolated preadipocytes retained a depot-specific transcriptional "memory" of embryonic developmental genes and exhibited differential promoter DNA methylation of selected genes (HOTAIR, TBX5) between GSAT and ASAT. Short hairpin RNA-mediated silencing identified TBX5 as a regulator of preadipocyte proliferation and adipogenic differentiation in ASAT. In conclusion, intrinsic differences in the expression of developmental genes in regional adipocytes provide a mechanistic basis for diversity in adipose tissue (AT) function. The less inflammatory nature of lower-body AT offers insight into the opposing metabolic disease risk associations between upper- and lower-body obesity.

OBJECTIVES: Patient-relevant treatment benefit is traditionally measured with health-related quality of life (HRQoL) instruments. The Patient Benefit Index (PBI) methodology allows for a more direct measurement, with the patients rating both importance and achievement of treatment goals. Here, we developed and validated a PBI version specific for the assessment of benefit in lymphedema and lipedema treatment (PBI-L). METHODS: The development included five steps: (1) open item collection; (2) consensus of items in a multidisciplinary expert panel; (3) application of the German PBI-L in a cross-sectional study (n = 301); (4) translation into English; (5) application of the English PBI-L in a randomized clinical trial (n = 82). Subscales were developed using factor analysis. Construct validity was analyzed by correlating PBI-L and convergent criteria such as HRQoL and quality of care. To test for responsiveness, the association to change in HRQoL measures was computed. RESULTS: Floor and ceiling effects were low. There were few missing values. Two well-interpretable subscales were found with Cronbach's alpha >0.8 each. Global and subscale scores correlated with convergent criteria and with change in disease-specific HRQoL, but not with change in generic HRQoL. CONCLUSIONS: The PBI-L is an internally consistent, valid, and responsive instrument for the assessment of patient-relevant benefit of edema treatment.

Lipedema is a chronic, incurable, often progressive affliction that occasionally causes significant morbidity. Initially, patients develop a disproportionate increase of body fat in the legs, buttocks and/or arms. Dieting and physical exercise have only limited effect on this disproportionate body fat distribution. The legs may be sensitive and are prone to bruising after only mild trauma. This can deteriorate into severe pain and reduced mobility, ultimately leading to a limitation of activity and social participation. As a result, lipedema patients may often be diagnosed with obesity. Dietary measures generally affect the obesity component but have little effect on the disproportionate body fat distribution. Because lipedema contributes to an increased BMI, even in non-­‐obese patients, a connection between lipedema and excessive calorie-­‐intake or obesity is often incorrectly assumed. In addition to physical problems, lipedema can also lead to psychoso-­‐ cial problems. These are often caused by the failure of consulting professionals to recognize or acknowledge the condition, or because (incorrect) recommendations for weight loss and physical exercise do not contribute to improvements in the complaints. Therefore, it is important to recognize lipedema early so that its accompanying symptoms can be acknowl-­‐ edged at an early stage and be incorporated into an integrated treatment. Little consistent information regarding the diagnosis or treatment of lipedema is found in the literature. Therefore, the goal of this directive is to attempt to establish a consensus for the diagnosis of lipedema and to discuss its symptoms and influencing factors, as well as its effects on activity and social limitations, as these negatively influence the life of the patient.

In 2014 250 women with Lipoedema took part in our survey about their experiences with Lipoedema. The results give a clear picture of what living with Lipoedema is like and reveal that along with the pain and discomfort caused by Lipoedema, many simple tasks that other people regard as straightforward become extremely challenging for people with Lipoedema. Lipoedema UK’s Big Survey 2014 led to the development of the Royal College of GPs’ e-learning course, a half hour course, which enables GPs to recognise Lipoedema and diagnose patients Our survey was created by Lipoedema UK, the Lymphoedema Department at St George’s Hospital, London, and the support of the Lymphoedema Support Network.

BACKGROUND: Lipedema is a rare female disorder with a characteristic distribution of adipose tissue hypertrophy on the extremities, with pain and bruising. In advanced stages, reduction of adipose tissue is the only available effective treatment. In elderly patients with advanced lipedema, correction of increased skin laxity has to be considered for an optimal outcome. METHODS: We report on a tailored combined approach to improve advanced lipedema in elderly females with multiple comorbidities. Microcannular laser-assisted liposuction of the upper legs and knees is performed under tumescent anesthesia. Medial thigh lift and partial lower abdominoplasty with minimal undermining are used to correct skin laxity and prevent intertrigo. Postsurgical care with nonelastic flat knitted compression garments and manual lymph drainage are used. RESULTS: We report on three women aged 55-77 years with advanced lipedema of the legs and multiple comorbidities. Using this step-by-step approach, a short operation time and early mobilization were possible. Minor adverse effects were temporary methemoglobinemia after tumescent anesthesia and postsurgical pain. No severe adverse effects were seen. Patient satisfaction was high. CONCLUSION: A tailored approach may be useful in advanced lipedema and is applicable even in elderly patients with multiple comorbidities.

OBJECTIVE: Elephantiasis nostras is a rare complication in advanced lipo-lymphedema. While lipedema can be treated by liposuction and lymphedema by decongestive lymphatic therapy, elephantiasis nostras may need debulking surgery. METHODS: We present 2 cases of advanced lipo-lymphedema complicated by elephantiasis nostras. After tumescent microcannular laser-assisted liposuction both patients underwent a debulking surgery with a modification of Auchincloss-Kim's technique. Histologic examination of the tissue specimen was performed. RESULTS: The surgical treatment was well tolerated and primary healing was uneventful. After primary wound healing and ambulation of the patients, a delayed ulceration with lymphorrhea developed. It was treated by surgical necrectomy and vacuum-assisted closure leading to complete healing. Mobility of the leg was much improved. Histologic examination revealed massive ectatic lymphatic vessels nonreactive for podoplanin. CONCLUSIONS: Debulking surgery can be an adjuvant technique for elephantiasis nostras in advanced lipo-lymphedema. Although delayed postoperative wound healing problems were observed, necrectomy and vacuum-assisted closure achieved a complete healing. Histologic data suggest that the ectatic lymphatic vessels in these patients resemble finding in podoplanin knockout mice. The findings would explain the limitations of decongestive lymphatic therapy and tumescent liposuction in such patients and their predisposition to relapsing erysipelas.

The International Compression Club (ICC) is a partnership between academics, clinicians and industry focused upon understanding the role of compression in the management of different clinical conditions. The ICC meet regularly and from these meetings have produced a series of eight consensus publications upon topics ranging from evidence-based compression to compression trials for arm lymphoedema. All of the current consensus documents can be accessed on the ICC website (http://www.icc-compressionclub.com/index.php). In May 2011, the ICC met in Brussels during the European Wound Management Association (EWMA) annual conference. With almost 50 members in attendance, the day-long ICC meeting challenged a series of dogmas and myths that exist when considering compression therapies. In preparation for a discussion on beliefs surrounding compression, a forum was established on the ICC website where presenters were able to display a summary of their thoughts upon each dogma to be discussed during the meeting. Members of the ICC could then provide comments on each topic thereby widening the discussion to the entire membership of the ICC rather than simply those who were attending the EWMA conference. This article presents an extended report of the issues that were discussed, with each dogma covered in a separate section. The ICC discussed 12 'dogmas' with areas 1 through 7 dedicated to materials and application techniques used to apply compression with the remaining topics (8 through 12) related to the indications for using compression.

A grossly obese woman was wrongly diagnosed throughout her adult life of having lymphoedema. Her condition was subsequently confirmed as lipoedema, an entirely different condition, which is noted in medical text books but is seldom taught to medical students or to general practitioners. The condition is caused by abnormal deposition of adipose tissue in the extremities (usually the lower limbs) and almost exclusively affects women. It often starts at puberty or may occur after pregnancy. The exact aetiology is not yet understood but genetic and hormonal factors may be implicated. The problem is that misdiagnosis leads to inappropriate tests and improper treatment to the patient. When recognised it is often too late to do anything for the patient and they become highly dependent on social care. This case describes how the diagnosis can be confirmed through an ultrasound image and illustrates the need for early recognition to facilitate specialist care.

BACKGROUND: Functional pelvic disorders in patients undergoing conservative surgical approach for rectal cancer are considered a major public health issue and represent one third of cost of colorectal cancer. We investigated the hypothesis that lymphadenectomy, involves the pelvic floor results in a localized hides or silent pelvic lymphedema characterized by symptoms without signs. PATIENTS AND METHODS: We examined 13 colo-rectal cancer patients: five intra-peritoneal adenocarcinoma: 1 sigmoid and 4 upper third rectal cancer (1 male and 3 female) and 9 extra-peritoneal adenocarcinoma: 3 middle and 5 lower third rectal cancer (4 male and 5 female) using 1.5-T magnetic resonance, one week before and twelve months after discharged from hospital. RESULTS: Lymphedema was discovered on post-operative magnetic resonance imaging of all 9 patients with extra-pertitoneal cancer, whereas preoperative magnetic resonance imaging as well as a post-operative examination of 4 intra-peritoneal adenocarcinoma, revealed no evidence of lymphedema. Unlike the common clinical skin signs that typify all other sites of lymphedema, pelvic lymphedema is hides or silent, with no skin changes or any single symptom manifested. Magnetic resonance imaging showed that pelvic illness alone is accompanied by lymphedema related exclusively to venous congestion, and accumulation of liquid in adipose tissue or lipedema. CONCLUSIONS: Alteration of the pelvic lymphatic network during pelvic surgery can lead to lymphedema and, pelvic floor disease. Patients should be routinely examined for the possibility of developing this post-surgical syndrome and further studies are needed to establish diagnosis and to evaluate treatment preferences.

Due to its increased presence in the press and on television, the diagnosis of lipedema is on the way to becoming a trendy diagnosis for those with thick legs. Despite this, one must recognize that lipedema is a very rare disease. It is characterized by disproportional obesity of the extremities, especially in the region of the hip and the legs, hematoma development after minimal trauma, and increased pressure-induced or spontaneous pain. Aids for making the correct diagnosis are (duplex) sonography, the waist-hip index or the waist-height index and lymphoscintigraphy. Important differential diagnoses are constitutional variability of the legs, lipohypertrophy in obesity, edema in immobility, edema in chronic venous insufficiency and rheumatic diseases. The symptom-based therapy of lipedema consists of conservative (compression, manual lymphatic drainage, exercise) and surgical treatments (liposuction). Until now there is no curative therapy. Obesity is an important risk factor for the severity and prognosis of lipedema. Further studies for a better understanding of the pathogenesis of lipedema and in the end possible curative treatments are urgently needed.

Classification, lipoedema, obesity, oedema.