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Lipedema is a chronic and progressive disease that may compromise lymphatic function. Although suction-assisted lipectomy (SAL) is considered a safe treatment for lipedema patients, the lymphatic repercussions of this surgical procedure are not fully understood. There is not enough evidence to support the role of SAL in lymphatic function treatment in lipedema. Here, we report a case of lymphatic drainage improvement after lipedema treatment with SAL. Tumescent SAL was performed in the deep subcutaneous layer, preserving the superficial and muscular lymphatic vessels. Pre- and postsurgical lymphoscintigraphy was equally documented under the Genoa protocol. A 34-year-old female patient presented with painful enlargement of the arms and lower limbs caused by lipedema. The patient had undergone conservative treatment with mild improvement in pain and heaviness. Lymphoscintigraphy showed slowed radiotracer progression on the left lower limb, collateral and tortuous lymphatic vessels on the right lower limb, and exuberant radiopharmaceutical concentration on the inguinal chain. Nine months after SAL was performed, the patient underwent another lymphoscintigraphy, which exhibited normalized radiopharmaceutical progression time and normal and symmetrical lymphatic vessel patterns. Collateral lymphatic paths and tortuosity vessels were no longer identified. Furthermore, the patient reported significant improvement in pain and the limb's appearance. Tumescent SAL is not only efficient and safe in treating lipedema, but may also be responsible for improvement in lymphatic drainage in lipedema patients. Additional prospective studies are fundamental to reinforce the current evidence and possibly yield predicting information about the tumescent liposuction eligibility in the improvement of lymphatic drainage.

Background  Untreated lymphedema of an extremity leads to an increase in volume. The therapy of this condition can be conservative or surgical. Methods  "Lymphological liposculpture" is a two-part procedure consisting of resection and conservative follow-up treatment to achieve curative volume adjustment of the extremities in secondary lymphedema. This treatment significantly reduces the need for complex decongestive therapy (CDT). From 2005 to 2020, 3,184 patients with secondary lymphedema after breast cancer and gynecological tumors were treated in our practice and clinic. "Lymphological liposculpture" was applied to 65 patients, and the data were recorded and evaluated by means of perometry and questionnaires. Results  The alignment of the sick to the healthy side was achieved in all patients. In 58.42% ( n  = 38), the CDT treatment could be completely stopped postoperatively; in another 33.82% ( n  = 22) of the patients, a permanent reduction of the CDT was achieved. In 7.69% ( n  = 5) patients, the postoperative CDT could not be reduced. A total of 92.30% ( n  = 60) of the patients described a lasting significant improvement in their quality of life. Conclusion  "Lymphological liposculpture" is a standardized curative sustainable procedure for secondary lymphedema for volume adjustment of the extremities and reduction of postoperative CDT with eminent improvement of the quality of life.

Background: To define the usefulness of three-dimensional (3D) ultrasound diagnostics for lipedema. Methods and Results: In this study, starting in May 2021, it was decided to apply 3D ultrasound diagnostics in the evaluation of the tissue in 40 patients affected with lipedema (stage I-II-III) who arrived at the Pianeta Linfedema Study Centre. Furthermore, subjects with lipohypertrophy were also included in this study to evaluate the structural features of the adipo-fascia and eventual structural similarity with lipedema. With an adequate instrument (SonoScape 20-3D ultrasound) and probe (17 MHz) on bilateral symmetric marker points, the epidermis-dermis complex and subcutaneous tissue were evaluated. In all patients with lipedema, a normal ultrasound representation of the epidermis-dermis complex, the thickness of subcutaneous tissue, due to hypertrophy of the adipose lobules and of interlobular connective septa, the thickness of the fibers that connect the derma to superficial fascia, and the thickness of the superficial fascia itself as well as of the deep fascia have been highlighted; moreover, fibrotic connective areas in the connective septa that correspond to the palpable nodules has been highlighted. The structural feature, present in all the clinical stages, unexpectedly, was the presence along the superficial fascia of anechogenicity due to the presence of fluid. In lipohypertrophy, structural characteristics similar to those in the initial stage of lipedema have been highlighted. Conclusion: 3D ultrasound diagnostics have led to the discovery of important features of adipo-fascia in lipedema not previously highlighted by two-dimensional ultrasound diagnostic studies.

OBJECTIVE: Symmetrical bilateral lower extremity edema (BLEE) needs to be treated effectively. Finding the cause of this condition increases the success of treatment. Fluid increase in the interstitial space (FIIS) is always present as a cause or a result. Subcutaneously administered nanocolloid is transported by uptake by lymphatic pre-collectors, and this uptake takes place in the interstitium. We aimed to evaluate the interstitium with labeled nanocolloid and contribute to the differential diagnosis in cases with BLEE. METHODS: Our retrospective study included 74 female patients who underwent lymphoscintigraphy for bilateral lower extremity edema. Technetium 99m (Tc-99m) albumin colloid (nanocolloid), a marked colloidal suspension, was applied subcutaneously to two different areas on the dorsum of both feet with a 26 gauge needle The dose volume administered intradermally is approximately 0.2-0.3 ml, and each injector has 22-25MBq of activity. Siemens E-Cam dual-headed SPECT gamma camera was used for imaging. Dynamic and scanning images were taken with a high-resolution parallel hole collimator. Ankle images were re-evaluated by two nuclear medicine specialists, independent of physical examination and scintigraphy findings. RESULTS: 74 female patients with bilateral lower extremity edema were divided into two groups based on physical examination and lymphoscintigraphy findings. There were 40 and 34 patients in Groups I and II, respectively. In the physical examination, patients in Group I were evaluated as lymphedema, and patients in Group II were evaluated as lipedema. The main lymphatic channel (MLC) was not observed in any of the patients in Group I in the early images, and the MLC was observed at a low level in the late imaging in 12 patients. The sensitivity of the presence of distal collateral flows (DCF) in the presence of significant MLC in early imaging in demonstrating increased fluid in the interstitial space (FIIS) was calculated as 80%, specificity as 80%, PPV 80%, and NPV 84%. CONCLUSIONS: While MLC is present in early images, concomitant DCF occurs in cases of lipoedema. The transport of increased lymph fluid production in this group of patients can be covered by the existing MLC. Although MLC is evident, the presence of significant DCF supports the presence of lipedema. It can be used as an important parameter in the diagnosis in early cases where physical examination findings are not evident.

A large and growing body of research suggests that the skin plays an important role in regulating total body sodium, challenging traditional models of sodium homeostasis that focused exclusively on blood pressure and the kidney. In addition, skin sodium may help to prevent water loss and facilitate macrophage-driven antimicrobial host defense, but may also trigger immune dysregulation via upregulation of pro-inflammatory markers and downregulation of anti-inflammatory processes. We performed a systematic search of PubMed for published literature on skin sodium and disease outcomes and found that skin sodium concentration is increased in patients with cardiometabolic conditions including hypertension, diabetes, and end-stage renal disease; autoimmune conditions including multiple sclerosis and systemic sclerosis; and dermatologic conditions including atopic dermatitis, psoriasis, and lipedema. Several patient characteristics are associated with increased skin sodium concentration including older age and male sex. While animal evidence suggests that increased salt intake results in higher skin sodium levels, there are conflicting results from small trials in humans. Additionally, limited data suggest that pharmaceuticals such as diuretics and SGLT-2 inhibitors approved for diabetes, as well as hemodialysis may reduce skin sodium levels. In summary, emerging research supports an important role for skin sodium in physiologic processes related to osmoregulation and immunity. With the advent of new non-invasive MRI measurement techniques and continued research on skin sodium, it may emerge as a marker of immune-mediated disease activity or a potential therapeutic target.

Lipedema is still a little-known disease, and the internet and social networks have been increasing the identification of many people with the condition, its characteristics, and diagnostic criteria. It is a disease of the adipose tissue that causes changes in body shape in the regions of the body's extremities, hips, and thighs. Classification of lipedema is based on the distribution of adipose tissue and severity of the disease (stages I, II, III, and IV) [ [1] ]. Lymphedema, venous disease, and hypermobile joints are co-morbidities [ [2] ]. Its overlap with overweight and obesity is common. Also, weight fluctuations and metabolic changes stem from body dissatisfaction commonly affecting women.

Background/Aim: YouTube provides information on several health-conditions including lipedema. The aim of this study was to investigate the properties, quality, and quantity of YouTube videos on lipedema. Methods: We explored YouTube using the key word lipedema and the initial top 50 videos were included to review. The properties comprising informers, target, and domains of videos covering number of views, likes, dislikes, duration, viewing rate (VR), and video power index (VPI) were recorded. A modified DISCERN tool and global quality scale (GQS) were used to assess the reliability and quality of videos, respectively. Results: The top 50 videos had a mean of 35,805 views, 282 likes, 12 dislikes, and 30 comments. The mean VPI (96.4) and VR (63.8%) were high. The videos were generally uploaded by health professionals for patient/public and health professional targets with the same ratio (50%). The majority of video contents was related to general information (68%) followed by surgical treatment (62%). Only a small ratio of their content (22%) was about nonsurgical management. The reliability and quality of the videos were intermediate to low. The median DISCERN and GQS scores were higher in the videos uploaded by health professional group compared with nonhealth professionals, but the number of views, VPI, and VR were similar between the groups with regard to the source. Conclusion: YouTube videos on lipedema are mostly provided by health professionals targeting both public/patients and health care providers but the content is limited and the quality and reliability of them were low to intermediate. Therefore, the lipedema specialists are suggested to work together to create up-to-date, high-quality, accessible online educational content to meet the needs of both patients/public and the health professionals. In addition, control mechanisms and careful peer reviewing of the videos informed by nonhealth professionals are warranted to avoid misleading information.

BACKGROUND: Lipedema is a progressive disease, diagnosed most often in women, which is characterized by the unproportionate and symmetrical distribution of adipose tissue primarily in the extremities. Despite numerous results from in vitro and in vivo studies, many questions regarding the pathology and genetic background of lipedema have remained unanswered. METHODS: Adipose tissue-derived stromal/stem cells (ASCs) were isolated from lipoaspirates derived from non-obese and obese lipedema and non-lipedema donors. Growth/morphology, metabolic activity, differentiation potential and gene expression were evaluated using quantification of lipid accumulation, metabolic activity assay, live-cell imaging, RT-PCR, quantitative PCR and immunocytochemical staining. RESULTS: The adipogenic potential of lipedema and non-lipedema ASCs did not rise in parallel with the donors' BMI and did not differ significantly between groups. However, in vitro differentiated adipocytes from non-obese lipedema donors showed significant upregulation of adipogenic gene expression compared to non-obese controls. All other genes tested were equally expressed in lipedema and non-lipedema adipocytes. The ADIPOQ/LEP ratio (ALR) was significantly reduced in adipocytes from obese lipedema donors compared to their non-obese lipedema counterparts. Increased stress fiber-integrated SMA was visible in lipedema adipocytes compared to non-lipedema controls and appeared enhanced in adipocytes from obese lipedema donors. CONCLUSIONS: Not only lipedema per se but also BMI of donors impact adipogenic gene expression substantially in vitro. The significantly reduced ALR and the increased occurrence of myofibroblast-like cells in "obese" lipedema adipocyte cultures underlines the importance of attention towards the co-occurrence of lipedema and obesity. These are important findings towards accurate diagnosis of lipedema.

Dysfunction of collecting lymphatic vessel pumping is associated with an array of pathologies. S-(-)-Bay K8644 (BayK), a small-molecule agonist of L-type calcium channels, improves vessel contractility ex vivo but has been left unexplored in vivo because of poor lymphatic access and risk of deleterious off-target effects. When formulated within lymph-draining nanoparticles (NPs), BayK acutely improved lymphatic vessel function, effects not seen from treatment with BayK in its free form. By preventing rapid drug access to the circulation, NP formulation also reduced BayK's dose-limiting side effects. When applied to a mouse model of lymphedema, treatment with BayK formulated in lymph-draining NPs, but not free BayK, improved pumping pressure generated by intact lymphatic vessels and tissue remodeling associated with the pathology. This work reveals the utility of a lymph-targeting NP platform to pharmacologically enhance lymphatic pumping in vivo and highlights a promising approach to treating lymphatic dysfunction.

Lipoedema is characterized by disproportionate painful fat accumulation mostly in the lower limbs. The presence of lymphoedema in lipoedema remains controversial. This study aimed to assess the presence or absence of lymphoedema in the lower limbs of women with lipoedema using indocyanine green (ICG) lymphography. A cross-sectional retrospective study was undertaken in women with a clinical diagnosis of lipoedema whose lower limbs were examined with ICG lymphography. MD Anderson Cancer Center (MDACC) ICG staging was used to determine lymphoedema presence and severity. Patient characteristics, ICG lymphography findings, Stemmer sign, body mass index, waist-to-hip ratio, limb volume and bioimpedance spectroscopy measures were recorded. Forty women with lipoedema underwent ICG lymphography for the lower limbs from January 2018 to July 2022. Thirty-four women (85.0%) were determined by ICG lymphography as MDACC ICG Stage 0 representing normal lymphatics. Of the six women who demonstrated dermal backflow on ICG lymphography, all were determined as ICG Stage 1, four had localized traumatic dermal backflow area at their ankles, one had previously diagnosed with primary lymphoedema and one was classified as lipoedema stage 4. ICG lymphography findings suggested the absence of lymphoedema in a clear majority of women with lower limb lipoedema.

Lymphangiogenesis is the mechanism by which the lymphatic system develops and expands new vessels facilitating fluid drainage and immune cell trafficking. Models to study lymphangiogenesis are necessary for a better understanding of the underlying mechanisms and to identify or test new therapeutic agents that target lymphangiogenesis. Across the lymphatic literature, multiple models have been developed to study lymphangiogenesis in vitro and in vivo. In vitro, lymphangiogenesis can be modeled with varying complexity, from monolayers to hydrogels to explants, with common metrics for characterizing proliferation, migration, and sprouting of lymphatic endothelial cells (LECs) and vessels. In comparison, in vivo models of lymphangiogenesis often use genetically modified zebrafish and mice, with in situ mouse models in the ear, cornea, hind leg, and tail. In vivo metrics, such as activation of LECs, number of new lymphatic vessels, and sprouting, mirror those most used in vitro, with the addition of lymphatic vessel hyperplasia and drainage. The impacts of lymphangiogenesis vary by context of tissue and pathology. Therapeutic targeting of lymphangiogenesis can have paradoxical effects depending on the pathology including lymphedema, cancer, organ transplant, and inflammation. In this review, we describe and compare lymphangiogenic outcomes and metrics between in vitro and in vivo studies, specifically reviewing only those publications in which both testing formats are used. We find that in vitro studies correlate well with in vivo in wound healing and development, but not in the reproductive tract or the complex tumor microenvironment. Considerations for improving in vitro models are to increase complexity with perfusable microfluidic devices, co-cultures with tissue-specific support cells, the inclusion of fluid flow, and pairing in vitro models of differing complexities. We believe that these changes would strengthen the correlation between in vitro and in vivo outcomes, giving more insight into lymphangiogenesis in healthy and pathological states.

The lymphatic circulation regulates transfer of tissue fluid and immune cells towards the venous circulation. While obesity impairs lymphatic vessel function, the contribution of lymphatic endothelial cells (LEC) to metabolic disease phenotypes is poorly understood. LEC of lymphatic microvessels are in direct contact with the interstitial fluid, whose composition changes during the development of obesity, markedly by increases in saturated fatty acids. Palmitate, the most prevalent saturated fatty acid in lymph and blood, is detrimental to metabolism and function of diverse tissues, but its impact on LEC function is relatively unknown. Here, palmitate (but not its unsaturated counterpart palmitoleate) destabilized adherens junctions in human microvascular LEC in culture, visualized as changes in VE-cadherin, ⍺-catenin, and β-catenin localization. Detachment of these proteins from cortical actin filaments was associated with abundant actomyosin stress fibers. The effects were Rho-associated protein kinase (ROCK)- and myosin-dependent, as inhibition with Y-27632 or blebbistatin, respectively, prevented stress fiber accumulation and preserved junctions. Without functional junctions, palmitate-treated LEC failed to directionally migrate to close wounds in 2-dimensions and failed to form endothelial tubes in 3-dimensions. A reorganization of the lymphatic endothelial actin cytoskeleton may contribute to lymphatic dysfunction in obesity and could be considered as a therapeutic target.

Lipedema is a pathologic accumulation of adipose tissue in the subcutaneous layer of the extremities. This connective tissue disorder, which predominately affects females, is often misdiagnosed despite an incidence of ∼11%. Misdiagnosis often leads to delays in appropriate treatment, further increasing the morbidity of the condition. The authors report their facilities' experience in treating a patient with lipedema, requiring multiple surgical interventions involving liposuction and skin debulking to achieve desired aesthetic outcomes. The patient presented to the plastic surgery clinic with severe lipedema of the bilateral lower extremities. She previously underwent a panniculectomy and bilateral lower extremity liposuction without achieving the desired aesthetic results. Prior conservative management and liposuction alone were both unsuccessful treatment options and she required debulking procedures, along with further liposuction, as definitive management. The patient underwent 2 procedures at the clinic, both consisting of liposuction and panniculectomy of the lower extremities and buttocks. The procedures were conducted 1 year apart but were able to achieve the patient's desired aesthetics goals. Management of lipedema can be challenging, but not impossible. This case report shows that local excision is a viable option for treatment if minimally invasive options yield limited results.

Lipedema, a chronic disease characterized by excessive fatty tissue deposition in the hips, buttocks, and lower legs, significantly negatively impacts the quality of life of those affected. This disease, which almost exclusively affects women, is often underdiagnosed, and confused with obesity. Diagnosis of lipedema is crucial for initial treatment and improvement of the patient's quality of life. Hormonal changes, inflammation, and tissue fibrosis play an essential role in the pathogenesis of lipedema. This article presents nutritional strategies that may bring relief to patients with lipedema. Nutritional intervention for lipedema patients could be an adjunct to traditional treatment, improving quality of life and reducing pain. However, these findings must be subjected to further research and clinical trials. The exact mechanism by which diet affects lipedema remains incompletely understood and, therefore, requires further study. However, this work provides hope and direction for future therapeutic approaches and research in treating lipedema.

The aim of this pilot study was to investigate the effects of defocused and radial shock wave therapy, mesotherapy, and kinesio taping on pain, circumferences of lower limbs, echographic/ elastosonographic pattern of subcutaneous adipose tissue (SAT), and quality of life in patients with lipedema. Fifteen women affected by lower limb lipedema in stage II were treated with shock wave therapy, mesotherapy, and kinesio taping on thighs and legs (eight sessions, twice a week). The primary outcome was pain, as assessed by Numeric Rating Scale (NRS). Secondary outcomes included the limb circumferences measurements, the SF-12 Health Survey for quality of life, the International Classification of Functioning (ICF) for disability, and echographic/ elastosonographic changes of SAT. Significant reductions of pain and circumference measurements were seen in patients at each follow up. This was associated with significant reduction of thickness, echographic pattern improvement, and increased elasticity of SAT, with consequent positive impact on the quality of life and disability reported by the patients. The results demonstrate improved clinical and functional ultrasound findings in patients affected by lipedema in the early stages of lower limbs, and this combination therapy needs to be investigated in larger populations at multiple centers to confirm the findings.

Enhancing our understanding of lymphatic anatomy from the microscopic to the anatomical scale is essential to discern how the structure and function of the lymphatic system interacts with different tissues and organs within the body and contributes to health and disease. The knowledge of molecular aspects of the lymphatic network is fundamental to understand the mechanisms of disease progression and prevention. Recent advances in mapping components of the lymphatic system using state of the art single cell technologies, the identification of novel biomarkers, new clinical imaging efforts, and computational tools which attempt to identify connections between these diverse technologies hold the potential to catalyze new strategies to address lymphatic diseases such as lymphedema and lipedema. This manuscript summarizes current knowledge of the lymphatic system and identifies prevailing challenges and opportunities to advance the field of lymphatic research as discussed by the experts in the workshop.