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High-quality three-dimensional (3D) microscopy allows detailed, unrestricted and non-destructive imaging of entire volumetric tissue specimens and can therefore increase the diagnostic accuracy of histopathological tissue analysis. However, commonly used IgG antibodies are oftentimes not applicable to 3D imaging, due to their relatively large size and consequently inadequate tissue penetration and penetration speed. The lack of suitable reagents for 3D histopathology can be overcome by an emerging class of single-domain antibodies, referred to as nanobodies (Nbs), which can facilitate rapid and superior 2D and 3D histological stainings. Here, we report the generation and experimental validation of Nbs directed against the human endothelial cell-selective adhesion molecule (hESAM), which enables spatial visualization of blood vascular networks in whole-mount 3D imaging. After analysis of Nb binding properties and quality, selected Nb clones were validated in 2D and 3D imaging approaches, demonstrating comparable staining qualities to commercially available hESAM antibodies in 2D, as well as rapid and complete staining of entire specimens in 3D. We propose that the presented hESAM-Nbs can serve as novel blood vessel markers in academic research and can potentially improve 3D histopathological diagnostics of entire human tissue specimens, leading to improved treatment and superior patient outcomes.

Lipedema is a multifaceted chronic fat disorder characterized by the bilateral and disproportionate accumulation of fat predominantly in the lower body regions of females. Research strongly supports that estrogen factors likely contribute to the pathophysiology of this disease. We aim to help demonstrate this link by quantifying estrogen factor differences between women with and without lipedema. For time and lipedema adipose tissue conservation, the Protein Simple WES machine will be utilized in place of traditional western blotting. Here, we are interested in evaluating estrogen related factors, such as, but not limited to, estrogen receptors and enzymes involved in the successive conversions of cholesterol and androgens to estrogens in human subcutaneous adipose. Evaluation of these factors within adipose tissue, however, is novel for this instrument. Thus, we optimized tissue lysis and protein extraction for 11 proteins of interest. Antibodies and their working concentrations were determined based upon specific and distinguishable (signal-to-noise) peaks from electropherogram outputs across different tissue lysate concentrations. We found that overnight acetone precipitation proved to be the best procedure for extracting protein from lipid rich adipose tissue samples. Six of the eleven proteins were found to migrate to their expected molecular weights, however, five did not. For proteins that did not migrate as expected, overexpression lysates and empty vector controls were used to validate detection antibodies. Protein extract from subcutaneous adipose tissue and overexpression lysates were then combined to understand if migration was specifically altered by adipose tissue. From these results, we concluded that the lipid rich nature of adipose tissue in combination with the separation matrix designated for use with the WES were preventing the appropriate migration of some proteins rather than non-specific antibody binding or inappropriate preparation methods.

Background: The lymphatic contribution to the circulation is of paramount importance in regulating fluid homeostasis, immune cell trafficking/activation and lipid metabolism. In comparison to the blood vasculature, the impact of the lymphatics has been underappreciated, both in health and disease, likely due to a less well-delineated anatomy and function. Emerging data suggest that lymphatic dysfunction can be pivotal in the initiation and development of a variety of diseases across broad organ systems. Understanding the clinical associations between lymphatic dysfunction and non-lymphatic morbidity provides valuable evidence for future investigations and may foster the discovery of novel biomarkers and therapies. Methods: We retrospectively analysed the electronic medical records of 724 patients referred to the Stanford Center for Lymphatic and Venous Disorders. Patients with an established lymphatic diagnosis were assigned to groups of secondary lymphoedema, lipoedema or primary lymphovascular disease. Individuals found to have no lymphatic disorder were served as the non-lymphatic controls. The prevalence of comorbid conditions was enumerated. Pairwise cooccurrence pattern analyses, validated by Jaccard similarity tests, was utilised to investigate disease–disease interrelationships. Results: Comorbidity analyses underscored the expected relationship between the presence of secondary lymphoedema and those diseases that damage the lymphatics. Cardiovascular conditions were common in all lymphatic subgroups. Additionally, statistically significant alteration of disease–disease interrelationships was noted in all three lymphatic categories when compared to the control population.

The Polycystic ovarian syndrome is a feature of the various menstrual cycles, infertility, hormonal irregularities, and hyperandrogenism. Insulin resistance, lipedema and hyperandrogenism are the most widespread endocrine disorder in PCOS. Most half of women with PCOS suffer from hirsutism, weight gain, metabolic syndrome, insulin resistance, hypothyroidism, and dyslipidemia. The Aim of the Study is to measure thyroid function, especially hypothyroidism in women with the polycystic ovarian syndrome and its association with insulin resistance. It also aims to estimate the effect of hypothyroidism on the level of each of the following biochemical parameters: lipid profile, glucose, insulin, anti mullerain hormones, sex hormone and thyroid disorders frequency (hypothyroidism) in PCOS. Subjects, Materials and Methods: This study was performed on patients in the outpatient clinics of the Obstetrics, Gynecology and Infertility Clinic and at the al-Yarmouk Teaching Hospital in 2020, and it included 30 (control group) and 70 patients, including 35 euthyroid PCOS and 35 hypothyroidism PCOS (PCOS group), in the age group 15-45 years. Thyroid hormone levels Thyroxine (FT3, FT4) and Thyroid Stimulating Hormone (TSH), Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), Prolactin (PRL), Testosterone, Progestogen, Estradiol (E2), Anti Mullerian Hormones (AMH), Thyroperoxidase Anti Bodies (anti TPO), Insulin were measured by using a device cobas e411, and Lipid profile and Glucose by using a device cobas c311. Results: There was an increase in TSH levels, a decrease in thyroxine, an increase in lipid profile levels, an increase in the sex hormones levels, increase glucose and insulin resistance which is a sign of diabetes type 2. However, the reverse is noticed in the relation of hypothyroidism on PCOS with weight gain, lipids, insulin resistance, androgynism and hirsutism. The most frequent thyroid disorders affecting PCOS in this study were found to be autoimmune thyroiditis and hypothyroidism. Conclusions: More than half of the women with PCOS suffer from hypothyroidism, compared to the normal women. As it was observed that dyslipidemia, weight gain, hirsutism, insulin resistance and sex hormones were more in hypothyroidism PCOS women compared to normal control subjects. We also concluded that PCOS and hypothyroidism are interrelated, as the presence of either is a cause of the other and that means the PCOS is more than just oligomenorrhea, amenorrhea, or infertility.

Background: An adequate dietary energy supply is particularly important in patients with lipedema as it promotes weight and fat loss. Accurate estimation of resting metabolic rate (RMR) allows implementing a proper calorie restriction diet in patients with lipedema. Therefore, an accurate assessment of energy demand in patients with lipedema is crucial in clinical practice. Our study aimed to compare actual resting metabolic rate (aRMR) with predicted resting metabolic rate (pRMR) in women with lipedema and to determine the association between individual anthropometric measurements and aRMR.Methods: A total of 108 women diagnosed with lipedema were enrolled in the study. aRMR was measured by indirect calorimetry (IC) using FitMate WM metabolic system (Cosmed, Rome, Italy). pRMR was estimated with predictive equations and BIA. All anthropometric measurements were based on BIA (bioelectric impedance analysis).Results: The mean aRMR in the study group was 1705.2 ± 320.7 kcal/day. Most methods of predicted RMR measurement used in our study significantly underpredicted aRMR in patients with lipedema. We reported statistically significant high correlations between all anthropometric measurements and aRMR/pRMR and a moderate correlation between visceral fat level (VFL) and aRMR. Conclusions: aRMR in patients with lipedema calculated with predictive equations was significantly lower than aRMR measured with other methods. This study found the agreement of predictive equations compared to IC is low (<60%). Fat-free mass (FFM) is a stronger determinant of RMR in patients with lipedema than fat mass.

Attention has been drawn to the role of changes in visceral adipose tissue rather than subcutaneous adipose tissue in the relationship between adipokines and dysfunctional adipose tissue. Especially in lipedema in which subcutaneous adipose tissue is affected, information about adipokines is insufficient. In this study, it was aimed to investigate adiponectin, ghrelin, resistin and visfatin levels and their relationship with adipose tissue thickness in patients with lipedema. For this purpose, subcutaneous adipose tissue thickness was evaluated objectively by ultrasonography. A total of 19 female patients diagnosed with lipedema and 15 healthy women with no age difference were included in the study. Skin and subcutaneous adipose tissue thickness were measured ultrasonographically. Serum levels of adiponectin, ghrein, resistin and visfatin of all subjects were measured using sandwich ELISA protocol. In patients with lipedema, subcutaneous subcutaneous tissue thickness and total skin-subcutaneous thickness were significantly increased in the thigh and calf, excluding skin thickness in the thigh, compared to controls (P0.05). No significant correlation was found between adiponectin, ghrelin, resistin and visfatin and skin, subcutaneous and total thickness measurements by ultrasound in patients with lipedema and controls (P>0.05). Although not statistically significant, when examined in detail, positive or negative correlations were observed between the groups in the relationship between adipokines and ultrasound measurements. According to our findings, although no significant relationship was found between serum levels of adipokines and subcutaneous adipose tissue thickness, it is controversial that they are completely unrelated. Further studies in larger series will shed light on the relationship between adipokines and subcutaneous tissue thickness and the importance of ultrasonography. , Adipokinler ve disfonksiyonel yağ dokusu arasındaki ilişkide subkutan yağ dokusundan ziyade viseral yağ dokusundaki değişikliklerin rolüne dikkat çekilmiştir. Özellikle cilt altı yağ dokusunun etkilendiği lipödemde adipokinler hakkında bilgi yetersizdir. Bu çalışmada lipödemli hastalarda adiponektin, ghrelin, resistin ve visfatin düzeylerinin ve bunların yağ doku kalınlığı ile ilişkisinin araştırılması amaçlandı. Bu amaçla cilt altı yağ dokusu kalınlığı ultrasonografi ile objektif olarak değerlendirildi. Lipödem tanısı almış toplam 19 kadın hasta ve yaş farkı olmayan 15 sağlıklı kadın çalışmaya dahil edildi. Deri ve deri altı yağ dokusu kalınlıkları ultrasonografik olarak ölçüldü. Tüm deneklerin serum adiponektin, ghrein, resistin ve visfatin seviyeleri sandviç ELISA protokolü kullanılarak ölçüldü. Lipödemli hastalarda, uyluk ve baldırda subkutan subkutan doku kalınlığı ve toplam deri-subkutan kalınlığı kontrollere kıyasla, uyluktaki deri kalınlığı dışında önemli ölçüde arttı (P0.05). Lipödemli hastalarda ve kontrollerde ultrason ile adiponektin, ghrelin, resistin ve visfatin ile deri, deri altı ve toplam kalınlık ölçümleri arasında anlamlı bir ilişki bulunmadı (P>0.05). İstatistiksel olarak anlamlı olmasa da detaylı incelendiğinde adipokinler ve ultrason ölçümleri arasındaki ilişkide gruplar arasında pozitif veya negatif korelasyonlar gözlendi. Bulgularımıza göre, serum adipokin düzeyleri ile deri altı yağ dokusu kalınlığı arasında anlamlı bir ilişki bulunmamakla birlikte, tamamen ilgisiz oldukları tartışmalıdır. Daha geniş serilerde yapılacak çalışmalar adipokinlerin cilt altı doku kalınlığı ile ilişkisine ve ultrasonografinin önemine ışık tutacaktır.

The quantitative assessment of lymphatic dermal clearance using NIR fluorescent tracers is particularly important for the early diagnosis of several potential disabling diseases. Currently, half-life values are computed using a mono-exponential mathematical model, neglecting diffusion of the tracer within the dermis after injection. The size and position of the region of interest are subjectively manually selected around the point of injection on the skin surface where the fluorescence signal intensity is averaged, neglecting any spatial information contained in the image. In this study we present and test a novel mathematical model allowing the objective quantification of dermal clearance, taking into consideration potential dermal diffusion. With only two parameters, this "clearance-diffusion" model is simple enough to be applied in a variety of settings and requires almost no prior information about the system. We demonstrate that if dermal diffusion is low, the mono-exponential approach is suitable but still lacking objectivity. However, if dermal diffusion is substantial, the clearance-diffusion model is superior and allows the accurate calculation of half-life values.

OBJECTIVE: Upper extremity lymphedema (UEL) is a burdensome disease with significant impact on quality of life underscoring the importance of quality of life measurements in this patient population. Only recently, the LYMPH Q Upper Extremity Module, a new patient-reported outcome measurement (PROM), has been developed. The aim of the study was to translate the LYMPH Q Upper Extremity Module from English to German and perform a comprehensive validation. METHODS: Translation was performed in accordance with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) best-practice guidelines. To validate the German LYMPH Q, a multicenter study was conducted. Internal consistency was determined by Cronbach's alpha. Reliability was assessed by the intra-class correlation coefficient (ICC). To analyse construct validity, a Pearson correlation coefficient between the LYMPH Q, quickDASH and SF-36 was calculated. Responsiveness was assessed by comparing the pre- and postoperative LYMPH Q scores in five patients receiving lymphatic reconstructive surgery. RESULTS: Validation was performed in a cohort of 65 patients. Internal consistency of the different domains was good to excellent (α: 0.87-0.97). ICC ranged from 0.74 to 0.92. The domains of the LYMPH Q correlated significantly with the corresponding domains of the SF-36 and quick DASH. Construct validity was good with eight of ten hypotheses confirmed. Significant improvements of function (46.4 ± 13.3 vs. 77.8 ± 11.5; p= 0.03), symptoms (42.0 ± 10.7 vs. 70.6 ± 11.6; p= 0.02) and psychological well-being (40.4 ± 14.6 vs. 78.0 ± 17.3; p= 0.03) were observed after lymphatic reconstructive surgery. CONCLUSION: The German version of The LYMPH Q Upper Extremity Module is conceptually equivalent to the original English version. It is a reliable and valid PROM to assess physical and psychological impairments in patients with UEL.

Lipedema is a disabling disease characterized by symmetric enlargement of the lower and/or upper limbs due to deposits of subcutaneous fat, that is easily misdiagnosed. Lipedema can be primary or syndromic, and can be the main feature of phenotypically overlapping disorders. The aim of this study was to design a next-generation sequencing (NGS) panel to help in the diagnosis of lipedema by identifying genes specific for lipedema but also genes for overlapping diseases, and targets for tailored treatments. We developed an NGS gene panel consisting of 305 genes potentially associated with lipedema and putative overlapping diseases relevant to lipedema. The genomes of 162 Italian and American patients with lipedema were sequenced. Twenty-one deleterious variants, according to 3 out of 5 predictors, were detected in PLIN1, LIPE, ALDH18A1, PPARG, GHR, INSR, RYR1, NPC1, POMC, NR0B2, GCKR, PPARA in 17 patients. This extended NGS-based approach has identified a number of gene variants that may be important in the diagnosis of lipedema, that may affect the phenotypic presentation of lipedema or that may cause disorders that could be confused with lipedema. This tool may be important for the diagnosis and treatment of people with pathologic subcutaneous fat tissue accumulation.

Background: There is insufficient clear epidemiological and clinical knowledge about lymphedema patient’s population in Mexico, this limits its investigation. The objective of this study is to present basic lymphedema epidemiological data and its clinical characteristics based on the analysis of lymphedema patients’ data collected from a specialized rehabilitation clinic in Mexico. Methods: This is a cohort study developed between 2015 and 2021. The study was carried ou in a private clinic specialized in oncological and peripheral vascular patients’ rehabilitation. Clinical assessments and interviews were performed to collect each case’s clinical history, considering its medical characteristics, physical activity and functionality and socio-demographic information, classified in a matrix, and later statistically evaluated. Results: Among 446 lymphedema patients, gender distribution was represented by 81% female and 19% male with a mean age of 50.5 years (±44.5). The population was categorized into the following three different study groups according to diagnosis: Cancer-Related Lymphedema (CRL), Non-Cancer-Related Secondary Lymphedema (NCRSL) and Primary Lymphedema. 60.08% of the patients had CRL; 25.11% had NCRSL and 14.79% had Primary Lymphedema. Among the patients with CRL, 81% of them corresponded to breast cancer diagnosis, the rest were associated to 19 different cancer diagnoses. The most prevalent diagnosis was breast CRL 48.6%; phlebolymphedema 19.4%; congenital and praecox lymphedema 14.1%; lipo-lymphedema 4.8%. The BMI of 64% of the patients ranged in overweight and obesity. 37.6% of patients reported that had experienced pain in limbs affected by lymphedema and 45% of all patients reported some disability to perform one or more activities associated to their limb volume or limb discomfort. 82% of patients had no physical activity or performed less physical activity than what is suggested to their population group’s recommendation. Conclusion: This study stablishes a precedent on reporting the broadest available epidemiological and clinical data of lymphedema in Mexico. Further studies are needed to report with a higher precision the epidemiological, clinical, and demographical data about each etiological group for a better understanding of lymphedema in Mexico and Latin America.

BACKGROUND: Lipedema often remains undiagnosed in patients with obesity, leading to mismanagement of treatment. Because of this, despite remarkable weight loss after bariatric surgery and decreases in hip and abdomen circumference, some patients show only small decreases in circumference of the extremities and report persistent limb pain. OBJECTIVE: The goal of this work is to raise awareness of lipedema coincident with obesity, mistakenly diagnosed as obesity alone, in order to ensure the correct diagnosis of the condition and to achieve better treatment outcomes for people with lipedema and coincident obesity. SETTING: CG Lympha Clinic, Cologne, and Ernst von Bergmann Clinic, Potsdam. METHODS: From clinical records, we identified 13 patients who were diagnosed with lipedema only after undergoing bariatric surgery. We describe the course of their pain before and after bariatric surgery, focusing on the long-term progression of symptoms accompanying the disease. RESULTS: Lipedema cannot be cured by bariatric surgery, and although the patients in this study lost an average of more than 50 kg of weight, they displayed no improvement in the pain symptoms typical of lipedema. CONCLUSIONS: Because of the different etiologies of lipedema and obesity, lipedema requires its own specific treatment. Patients suffering from obesity should always be assessed for pain and lipedema. If coincident lipedema is diagnosed, we suggest that bariatric surgery only be performed first if diet and exercise have failed, the patient's body mass index is >40 kg/m2, and the patient has been informed of the possible persistence of pain. Lipedema, like a coincident disease, must be additionally treated conservatively or preferably surgically. This optimized treatment may help to better manage patient expectations after weight loss.

Background: Lipedema is a chronic and progressive adipose tissue disorder that causes significant morbidity and negatively influences mental health and quality of life, and increases the risk of depression, anxiety, and eating disorders. One construct of relevance to better understanding psychological disorders is emotion regulation (ER). Therefore, the aim of this study is to investigate the difficulties in ER among lipedema patients compared to healthy people without lipedema. Methods: This cross-sectional study assessed differences in ER and anxiety between two groups: 26 female patients with lipedema and 26 sex- and age-matched healthy controls. The Difficulties in Emotion Regulation Scale (DERS) assessed emotional regulation across six dimensions: Impulse control, goal-directed behavior, awareness, clarity, non-acceptance, and strategies. Anxiety was assessed by the Hamilton Anxiety Scale (HAM-A). ANOVA assessed differences in measures between lipedema and healthy control groups. Results: Lipedema patients presented with significantly more difficulties in ER and a higher level of anxiety than those without lipedema. Specifically, the lipedema group showed higher and significant differences in total DERS and anxiety scores and all DERS subscales scores compared to those without lipedema. Conclusions: Lipedema patients showed significant difficulties with ER, and were associated with anxiety symptoms, indicating that ER difficulties may play a role in developing emotional disorders, such as anxiety, for patients with lipedema. The health care provider should pay more attention to ER difficulties and psychological status among lipedema patients.

BACKGROUND: Lipedema is characterized as an abnormal deposition of fat in the buttocks and legs bilaterally that may be accompanied by swelling, pain, and tenderness. It is still often confused with more frequent conditions such as obesity and lymphedema. The estimated prevalence in Europe varies between 0.06% and 39%. OBJECTIVES: To evaluate the prevalence of lipedema and identify health factors related to it in the Brazilian population. METHODS: Administration of a previously validated online screening questionnaire to a representative sample of the general population. The questionnaire was distributed and administered to anonymous volunteers representing the general Brazilian population using software designed for population analyses. RESULTS: 253 women answered the questionnaire, 12.3 ± 4% (Confidence Interval [CI] 95%) of whom presented symptoms compatible with a high probability of being diagnosed with lipedema. Furthermore, anxiety, depression, hypertension, and anemia were also correlated with a high probability of the diagnosis. CONCLUSIONS: The estimated prevalence of lipedema in the population of Brazilian women is 12.3%.

Lipohyperplasia dolorosa (LiDo) - commonly referred to as lipedema - is a painful disproportionate but symmetrical fat distribution disorder of the extremities. An accompanying proportional symmetrical adipose tissue proliferation in the sense of coincident obesity can complicate the diagnosis and therapy of LiDo. Surprisingly, no valid anthropometric parameters are used to determine this obesity percentage. The often used parameter body mass index (BMI) lacks construct validity. An alternative is the waist-toheight ratio (WHtR).

Introduction Lipoedema is a chronic feminine disease with disproportional painful fat deposition of the lower body half and occassional arm affection. Aim: The objective of the present study was to assess LA volumetric and functional properties by three-dimensional speckle-tracking...

Objective Lipedema is an inflammatory subcutaneous adipose tissue disease that develops in women and may progress to lipolymphedema, a condition similar to lymphedema, in which lymphatic dysfunction results in irresolvable edema. Because it has been shown that dilated lymphatic vessels, impaired pumping, and dermal backflow are associated with presymptomatic, cancer-acquired lymphedema, this study sought to understand whether these abnormal lymphatic characteristics also characterize early stages of lipedema prior to lipolymphedema development. Methods In a pilot study of 20 individuals with Stage I or II lipedema who had not progressed to lipolymphedema, lymphatic vessel anatomy and function in upper and lower extremities were assessed by near-infrared fluorescence lymphatic imaging and compared with that of a control population of similar age and BMI. Results These studies showed that, although lower extremity lymphatic vessels were dilated and showed intravascular pooling, the propulsion rates significantly exceeded those of control individuals. Upper extremity lymphatics of individuals with lipedema were unremarkable. In contrast to individuals with lymphedema, individuals with Stage I and II lipedema did not exhibit dermal backflow. Conclusions These results suggest that, despite the confusion in the diagnoses between lymphedema and lipedema, their etiologies differ, with lipedema associated with lymphatic vessel dilation but not lymphatic dysfunction.

A Case Series of Lymphatic Injuries After Suction Lipectomy in Women with Lipedema - Article abstract #935016

Background: A detailed quantitative evaluation would be beneficial for management of patients with limb lymphedema. Methods and Results: In 47 patients with lower limb lymphedema at International Society of Lymphology clinical stage 2A (18 limbs), 2B (41 limbs), and 3 (13 limbs), we measured the limb circumference and thickness of epidermis, dermis, and subcutis layers with B-mode ultrasonography and subcutis elastic modulus with ultrafast shear wave velocity (ultrasound elastography) at 5 anatomical levels (M1 to M5) before and after a 3- to 5-day intensive decongestive therapy (IDT) session. Limb circumference and thickness of the epidermis, dermis, and subcutis were greater in the 72 limbs with lymphedema than in the 22 unaffected limbs before and after IDT. The affected limb volume was 10,980 [8458-13,960] mL before and 9607 [7720-11,830] mL after IDT (p < 0.0001). The IDT-induced change in subcutis thickness was -9 [-25 to 13]% (NS), -11 [-26 to 3]% (p = 0.001), -18 [-40 to -1]% (p < 0.0001), -15 [-35 to 3]% (p = 0.0003), and -25 [-45 to -4]% (p < 0.0001) and significantly correlated with the change in elastic modulus, which was 13 [-21 to 90]% (p = 0.004), 33 [-27 to 115]% (p = 0.0002), 40[-13 to 169]% (p < 0.0001), 9 [-36 to 157]% (p = 0.024), and -13 [-40 to 97]% (NS), respectively, at the M1, M2, M3, M4, and M5 levels. Intraobserver reproducibility was satisfactory for skin thickness and fairly good for elastography, but interobserver reproducibility was poor or unacceptable. Conclusions: IDT reduced the circumference and subcutis thickness of lower limbs with lymphedema and increased their elastic modulus, implying greater tissue stiffness probably due to fluid evacuation. Although subcutis thickness measurement proved to be reliable, technological and methodological improvements are required before ultrasonographic elastography can be used in clinical practice.

OBJECTIVE: Lipedema is a chronic and progressive disease associated with lymphatic impairment at later stages. The aim of our study was to describe the functional status and anatomy of lower limb superficial lymphatic system using indocyanine green (ICG) lymphography in patients with lipedema. METHODS: Following ICG injection at the dorsum of the foot, distance (cm) covered by the dye at 10 (T10') and 25 min (T25') was measured and normalized for limb length. If the dye did not reach the groin within 25 min, patients were classified as "drainage-needing" group (DNG). Values of fat and lean distribution assessed by dual-energy X-ray absorptiometry were extracted, and correlation analysis was performed. Furthermore, anatomical patterns of superficial lymphatics were assessed. RESULTS: Overall, 45 women were included, 25 (56%) of whom were classified as DNG. Symptoms duration was significantly associated with DNG status at multivariate analysis (odds ratio 1.07; 95% CI 1.01-1.14; p = 0.047). Moreover, Spearman's analysis showed a negative correlation between symptoms duration and T25' dye migration (r = -0.469; p = 0.037). Overall, no major anatomical lymphatic changes were found. CONCLUSIONS: Present study suggests that lymphatic functioning in patients with lipedema correlates with symptoms duration. Further research on larger cohorts should verify our findings and clarify their potential therapeutic implications. Overall, ICG lymphography may be promising technique to assess both lymphatic anatomy and functioning in patients with lipedema.