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This is a retrospective analysis of all lipedema patients treated by tumescent liposuction at our department in the years 2007-2021: We performed 519 liposuctions in 178 patients with a mean age of 45 ± 15.5 years. By the stage of lipedema the mean age increased significantly, what underlines the concept of lipedema as a chronic progressive disorder. Three-thirds of patients reported at least one comorbidity. The most common were arterial hypertension (32.58%), obesity (24.16%), and hypothyroidism (20.79%). We removed a mean lipoaspirate volume of 4905 ± 2800 mL. A major target for treatment is pain reduction. All patients reported at least a 50% pain reduction after liposuction, while 96 achieved a pain reduction ≥ 90%. The pre-operative pain intensity (p = 0.000) and the lipedema stage (p = 0.032) exerted a significant impact on absolute pain reduction. There was no association of pain reduction to volume loss. The post-operative rate of adverse events was 2.89%. Liposuction in tumescent anesthesia is an effective and safe method to reduce both pain and volume in patients with lipedema.

BACKGROUND: Lipedema is a chronic disease marked by symmetric enlargement of painful nodular and fibrotic adipose tissue, predominantly affecting the limbs. Since there is no specific test or biomarker for this condition, years often pass before the diagnosis of lipedema is established for the first time, thereby causing psychosocial distress, including depression, eating disorders, and social isolation. Over the last few years several advanced Doppler-based technologies have been developed to visualize slow flow blood vessels and superficial microvascular architecture undetectable by traditional color Doppler flow imaging (CDFI). OBJECTIVE: The aim of this study was to evaluate the superficial microvascular anatomy in lipedema patients compared to healthy controls and investigate the clinical significance of the Ultra Micro Angiography (UMA) technology in the diagnosis of lipedema. This new technique may contribute to reduce the diagnostic delay and, eventually, establish and guide treatment strategies toward a better therapeutic outcome in lipedema patients. METHODS: 25 patients with lipedema and ten healthy controls with no history of lipedema were included in this study. All ultrasound examinations were performed on a novel high-performance ultrasound system (Resona R9/Mindray) using CDFI and the UMA technique. RESULTS: In all of the patients, Ultra Micro Angiography achieved the excellent visualization of microvascular structures, revealing that most lipedema patients showed grade 3 (n = 13) or grade 2 (n = 8) flow. UMA was superior to CDFI for depicting the microvascular structures. CONCLUSIONS: Here we show that UMA imaging characterizes the subcutaneous microvasculature with an unprecedented accuracy. The method has the advantage of being sensitive to small, slow-flowing vessels. This allows for the assessment of the course of vessels and vascular pathologies in great detail. Thus, UMA as a non-invasive diagnostic method can improve diagnostic accuracy in lipedema.

Pain, which is a central characteristic of lipedema, allows differentiation from other fat tissue diseases. The analysis of the multiple aspects of pain beyond a quantification of pain scale scores could make molecular disease and therapy mechanisms accessible. Lipedema pain is causally linked to lipedema fat. First robust data show peripheral sensory changes. Tissue weight and systemic inflammation are becoming less likely as causes for the experianced pain. Furthermore, genetics and hormonal influences need to be investigated. Lipedema pain cannot currently be treated with drugs. Physical therapy shows transient relief. Liposuction has been shown to have a long-term effect on pain. The potential of modulating the perception of pain with psychotherapeutic approaches is emerging as a potentially effective new therapeutic approach.

Lipohyperplasia dolorosa (LiDo) is a genetic, painful fat tissue distribution disorder with lymphological high-volume transport insufficiency. It often has negative effects on the psychological well-being of affected female adolescents and adults. Similar in appearance to the development of obesity, the patients experience similar negative reactions in their families, partners and friends. The development of the LiDo usually occurs in adolescence or following pregnancy and represents a considerable psychological burden in central phases of narcissistic development. These psychological impairments caused by LiDo are long-term companions and influence interpersonal relationships. Three case vignettes serve for clarification. In the first case, the LiDo seems to be "grafted" onto a neurotic conflict, which intensifies the acute and chronic pain of the person affected. In the second case, the affected person shows defense mechanisms in contact, which are evidence of a high level of stress and require considerable sensitivity by the person's social circle during interactions. In the third case, after intensively addressing various aspects of the disease, the person received medical treatment from a specialist and underwent several surgeries. The positive effects on physical and psychological well-being are stabilized by psychological support. Seen as an option, those affected can decide for or against surgical treatment. As a consequence of the treatment, the previously rejected extremities become more integrated, arms and legs fit back into the person's own physical image of the body. This positive change also extends to the intrapsychic self-image of the body.

The billing of lipoedema treatment in Germany has come to be heterogeneous. This is due to the decision of the Federal Joint Committee ("Gemeinsamer Bundesausschuss", G-BA) to acknowledge lipoedema stage III as a treatment to be paid by the statutory health insurance funds ("Gesetzliche Krankenversicherung", GKV) until the completion of the trial study "LipLeg" at the end of 2024. Based on this decision, inpatient and outpatient surgical treatment of stage III lipoedema can be billed to the GKV, while the reimbursement of costs for surgical treatment of the other two stages remains a case-by-case decision of the GKV and is currently often rejected. Therefore, treatment costs are often paid by patients themselves. The question of the correct settlement of lipoedema treatment repeatedly arises in the context of legal disputes, which, in turn, repeatedly faces experts and courts with a major challenge. In the following article, the Task Force Lipoedema of the German Society for Plastic, Reconstructive and Aesthetic Surgery presents an overview of the various billing modalities and presents a proposal for the correct billing of lipoedema within the framework of the German medical fee schedule ("Gebührenordnung für Ärzte", GOÄ).

BACKGROUND: Lipedema, as a disabling and consequential disease, is gaining more awareness due to its potential omnipresence. Patients suffering from lipedema show a characteristic painful display of symmetric accumulations of adipose tissue. The combination of swelling, pain and decreased quality of life (QOL) is outstanding for the diagnosis. The aim of this study was to identify the effect of liposuction in terms of the QOL for patients and underline important factors of current and pending research regarding surgical therapy of lipoedema. METHODS: Patients suffering from lipedema prior to and after receiving liposuction at our hospital were included in this study. Patients completed a lipedema-specific self-designed 50 item questionnaire: the World Health Organization Quality of Life BREF (WHOQOL-BREF) and the Patient Health Questionnaire 9 (PHQ-9). A linear mixed model was used for outcome analysis. RESULTS: In total, 511 patients completed a questionnaire prior to the surgery at primary presentation to the hospital and a total number of 56 patients completed a questionnaire after liposuction. A total of 34 of these patients filled in both questionnaires prior to and after surgery. The general characteristics of the disease, such as daily symptoms and psychological health, pertinently improved after surgery. CONCLUSIONS: Liposuction can have a general improving effect on the QOL of patients, both in private and professional life. Liposuction may currently be the most evident and promising method in the treatment of lipedema.

Background  Posttraumatic lymphedema (PTL) is sparsely described in the literature. The aim of this study is to propose a comprehensive approach for prevention and treatment of PTL using lymphovenous anastomosis (LVA) and lymphatic vessels free flap, reporting our experience in the management of early-stage lymphedema. Methods  A retrospective observational study was performed between October 2017 and July 2022. Functional assessment with magnetic resonance lymphangiography and indocyanine green lymphography was performed. Patients with lymphedema and functional lymphatic channels were included. Cases with limited soft tissue damage were proposed for LVA, and those with acute or prior soft tissue damage needing skin reconstruction were proposed for superficial circumflex iliac artery perforator lymphatic vessels free flap (SCIP-LV) to treat or prevent lymphedema. Primary and secondary outcomes were limb volume reduction and quality of life (QoL) improvement, respectively. Follow-up was at least 1 year. Results  Twenty-eight patients were operated using this approach during the study period. LVA were performed in 12 patients; mean reduction of excess volume (REV) was 58.82% and the improvement in QoL was 49.25%. SCIP-LV was performed in seven patients with no flap failure; mean REV was 58.77% and the improvement QoL was 50.9%. Nine patients with acute injury in lymphatic critical areas were reconstructed with SCIP-LV as a preventive approach and no lymphedema was detected. Conclusion  Our comprehensive approach provides an organized way to treat patients with PTL, or at risk of developing it, to have satisfactory results and improve their QoL.

INTRODUCTION: The aim was to reflect the established interdisciplinary aspects of general/abdominal and plastic surgery by means of a narrative review. Methods: (i) With specific references out of the medical literature and (ii) own clinical and perioperative as well as operating technical and tactical management experiences obtained in surgical daily practice, we present a choice of options for interdisciplinary cooperation that could be food of thought for other surgeons. CONTENT: - Decubital ulcers require pressure relieve, debridement and plastic surgery coverage, e.g., by a rotation flap plasty, V-Y flap or "tensor-fascia-lata" (TFL) flap depending on localization (sacral/gluteal defects, ischiadic tuber). - Coverage of soft tissue defects, e.g., after lymph node dissection, tumor lesions or disturbance of wound healing can be managed with fasciocutaneous or muscle flaps. - Bariatric surgery: Surgical interventions such as butt lift, tummy tuck should be explained and demonstrated in advance and performed commonly after reduction of the body weight. - Abdominoperineal rectum extirpation (APE): Holm's procedure with greater circumferential extent of resection at the mesorectum and the insertion site of the levator muscle at the anal sphicter muscle resulting in a substantial defect is covered by myocutaneous flap plasty. - Hernia surgery: Complicated/recurrent hernias or abdominal wall defect can be covered by flap plasty to achieve functional reconstruction, e.g., using innervated muscle. Thus, abdominal wall can respond better onto changes of pressure and tension. - Necrotising fasciitis: Even in case of suspicious fasciitis, an immediate radical debridement must be performed, followed by intensive care with calculated antibiotic treatment; after appropriate stabilization tissue defects can be covered by mesh graft of flap plasty. - Soft tissue tumor lesions cannot be resected with primary closure to achieve appropriate as intended R0 resection status by means of local radical resection all the time - plastic surgery expertise has to be included into interdisciplinary tumor concepts. - Liposuction/-filling: Liposuction can be used with aesthetic intention after bariatric surgery or for lipedema. Lipofilling is possible for reconstruction and for aesthetic purpose. - Reconstruction of lymphatic vessels: Lymphedema after tumor operations interrupting or blocking lymphatic drainage can be treated with microsurgical reconstructions (such as lympho-venous anastomoses, lympho-lymphatic anastomoses or free microvascular lymph node transfer). - Microsurgery: It is substantial part of modern reconstructive plastic surgery, i.e., surgery of peripheral nerves belongs to this field. For visceral surgery, it can become important for reconstruction of the recurrent laryngeal nerve. - Sternum osteomyelitis: Radical debridement (eventually, complete sternal resection) with conditioning of the wound by vacuum-assisted closure followed by plastic surgery coverage can prevent chronification, threatening mediastinitis, persisting infectious risk, long-term suffering or limited quality of life. SUMMARY: The presented selection of single topics can only be an excerpt of all the options for surgical cooperation in daily clinical and surgical practice. OUTLOOK: An interdisciplinary approach of abdominal and plastic surgery is characterized by a highly developed cooperation in common surgical interventions including various techniques and tactics highlighting the specifics of the two fields.

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.