Chronic lymphedema is a progressive, disfiguring disease that results from dysfunction of the lymphatic vasculature, causing distal accumulation of interstitial fluid, localized development of tissue edema, and expansion of subcutaneous adipose tissue (SAT). As the molecular mechanisms governing SAT remodeling in this disease are unclear, we performed single-nucleus RNA sequencing on paired control and affected SAT biopsies from patients with unilateral lymphedema. Lymphedema samples were characterized by expansion of SAA + adipocytes, pro-adipogenic stem cells, and proliferation of lymphatic capillaries. A GRIA1 + lymphedema-enriched stromal cell population expressing VEGFC , ADAMTS3 , and CCBE1 was identified, suggesting an enhanced axis of communication between adipose stem and progenitor cells (ASPCs) and lymphatic endothelial cells. Furthermore, lymphedema ASPC-conditioned media promoted lymphatic endothelial tube elongation in vitro . These findings indicate a critical role for ASPCs in regulating adipocyte differentiation and lymphatic vascular remodeling in lymphedema, and provide a valuable resource for better understanding this disease.

This position paper was developed by the World Society for Reconstructive Microsurgery Task Force on Lymphedema to establish consensus-based recommendations for the management of extremity lymphedema. The document addresses key domains of care, including assessment, treatment strategies, surgical interventions, and postoperative management, with the goal of providing practical and adaptable guidance applicable across diverse clinical settings. Effective management of extremity lymphedema requires a structured and standardized approach encompassing comprehensive evaluation, individualized treatment, and long-term follow-up. Initial assessment should include a detailed history and physical examination, supplemented by standardized limb circumference measurements and clinical photography to ensure objective and reproducible documentation. Imaging modalities, such as lymphoscintigraphy and indocyanine green (ICG) fluorescent lymphography, are essential for accurate disease characterization and surgical planning. Preoperative optimization with conservative therapy and compression remains a critical step prior to intervention. Surgical management should be tailored to disease severity and patient-specific factors, incorporating physiologic procedures-including lymphaticovenous anastomosis (LVA), vascularized lymph node transfer (VLNT), and lymphaticovenular anastomosis (LNVA)-as well as excisional techniques such as liposuction and direct excision when indicated. Postoperative care should include regular noninvasive assessments at three-month intervals and annual imaging to monitor outcomes. Long-term follow-up, extending up to five years, is recommended to ensure sustained clinical improvement and to guide ongoing management.

BACKGROUND AND OBJECTIVES: Superficial-to-deep lymphatic drainage has been proposed as a mechanism to reduce an individual's risk of developing breast cancer-related lymphedema (BCRL). The epitrochlear-humeral pathway provides superficial-to-deep lymphatic drainage and may be preferentially recruited when the superficial lymphatic system becomes inadequate. We evaluated the presence or absence of epitrochlear-humeral lymph node drainage in breast cancer survivors post-axillary lymph node dissection (ALND) who did not develop BCRL.

METHODS: Female breast cancer survivors without BCRL after ALND underwent lymphatic mapping with ICG lymphography and SPECT/CT lymphoscintigraphy. The presence of epitrochlear and/or humeral drainage was recorded and compared between volunteers based on linear versus nonlinear patterns on ICG lymphography.

RESULTS: Twenty-five volunteers, a median of 13.0 years after ALND, met the inclusion criteria. Drainage to both the epitrochlear and humeral nodes was observed in 56% (14/25). Linear ICG patterns were present in 32% (8/25), while 68% (17/25) demonstrated nonlinear patterns. Epitrochlear and humeral drainage was observed in 38% (3/8) of volunteers with linear patterns compared with 65% (11/17) of those with nonlinear patterns.

CONCLUSIONS: Superficial-to-deep lymphatic drainage is common in breast cancer survivors without BCRL after ALND and may represent an important compensatory mechanism of the deep lymphatic system.

BACKGROUND: Lymphedema remains a chronic, progressive, and currently incurable condition. Historically, surgical treatment options were severely limited and largely palliative. Over recent decades, however, advances in the understanding of lymphatic anatomy and innovations in surgical equipment, imaging, and technique have reshaped operative management. Early operations were largely ablative, aiming to reduce limb bulk without addressing lymphatic physiology. Subsequent innovations introduced physiologic reconstruction aimed at restoring and redirecting lymphatic drainage pathways. Notably, supermicrosurgical operating microscopes, enabled reliable submillimeter anastomoses, catalyzing the broader adoption of lymphaticovenous anastomosis and preventive strategies such as immediate lymphatic reconstruction. Despite an expanding armamentarium-spanning ablative, physiologic, and adjunctive approaches combined with lymphatic surgery-consensus on optimal procedure selection and timing remains limited, in part due to heterogeneity in staging systems, patient phenotypes, and outcome measures.

METHODS: This review traces the historical progression of surgical management for lymphedema from ablative to physiologic and preventive strategies, emphasizing the impact of key advancements in diagnostic imaging and microsurgery. We then consider how these developments have shaped present-day clinical practices.

CONCLUSION: By situating current techniques within their historical context, we aim to clarify prevailing practice patterns and highlight priorities for future research in lymphedema surgery.

BACKGROUND: In 1996, Ciucci et al. described the presence of a lymphatic channel in the palmar skin that spanned the first interdigital space and anastomosed with lymphatic collaterals on the dorsal surface of the hand. This palmar lymphatic channel (a pathway we have named the Ciucci pathway) has yet to be described with in-vivo imaging. As the Ciucci pathway is a superficial-to-deep lymphatic communication, its visualization may provide insight into altered lymphatic routing following axillary lymph node dissection (ALND). Therefore, we investigated our ability to image this pathway with indocyanine green (ICG) lymphography.

METHODS: Healthy female volunteer and female breast cancer survivors without a history of BCRL at least two years after ALND underwent lymphatic mapping of the upper extremities with ICG lymphography. ICG was injected in six standard sites in the hand/wrist and upper arm. The presence of the Ciucci pathway was recorded and compared between cohorts with Fisher's exact test.

RESULTS: 110 arms of 55 healthy volunteers and 31 at-risk arms of 31 breast cancer survivors without BCRL were included. The Ciucci pathway was present in one of 110 (0.9%) healthy female volunteer arms and present in five of 31 (16.1%) at-risk arms of breast cancer survivors (p = 0.002).

CONCLUSION: The Ciucci pathway was more frequently observed in the at-risk arms of volunteers with a history of ALND without BCRL than in the arms of healthy female volunteers. While the functional significance of this pathway remains unclear, its presence may represent superficial-to-deep lymphatic collateralization following ALND.

BACKGROUND AND OBJECTIVES: The posterior upper arm (PUA), or tricipital, pathway is a superficial lymphatic channel that has been postulated to be a compensatory pathway for lymphatic drainage of the upper extremity following axillary lymph node dissection (ALND). The PUA pathway has been characterized in the breast cancer population but not in the healthy population.

METHODS: Healthy female volunteers were recruited for bilateral mapping of the upper extremities using indocyanine green (ICG) lymphography. Phenotypic variants of the PUA pathway were recorded.

RESULTS: 57 volunteers underwent ICG lymphography of the bilateral arms. The PUA pathway was visualized in 100% of arms. In 46% of arms, the pathway was continuous with the forearm (long bundle phenotype), whereas in 54% of arms, the pathway had no continuity with the forearm (short bundle phenotype).

CONCLUSION: The PUA pathway was universally present in healthy volunteers. However, in comparison to our prior study, which was performed in patients with breast cancer prior to ALND, healthy volunteer arms more often displayed the short bundle phenotype. Defining the incidence of PUA pathway anatomic variants in healthy subjects is important to further understand its potential role in the development of lymphedema.

BACKGROUND: Lymphedema is a prevalent and underserved condition. Expanding diagnostic and therapeutic options have increased interest in multidisciplinary care. This study examines clinical characteristics and geographic patterns of lymphedema care within a multidisciplinary lymphatic center.

METHODS: A retrospective review included all patients evaluated for edema at the BIDMC Lymphatic Center from January 2018 through December 2023. The multidisciplinary team comprised cardiovascular medicine, radiology, plastic surgery, and physical therapy. A RedCap registry captured demographics, clinical characteristics, imaging and surgeries. Patients were stratified by etiology as primary, secondary, or non-lymphatic edema. Bivariate and geospatial analyses assessed differences across groups and geographic access to care.

RESULTS: Of the total 2,031 participants, 76% were female, with a mean age of 60 years (±15.2) and BMI of 33.6 kg/m2 (±10.7). The average duration of edema symptoms at evaluation was 9.47 years (±11.8). Secondary lymphedema was most common (n=1,104, 54%), often due to cancer (54%) or chronic venous disease (23%). Lymphatic imaging was performed in 549 patients (27%). Of those 549, lymphoscintigraphy (83%) and MRI (69%) were most common. Only 149 patients (11%) underwent surgery. Patients residing outside the state had longer symptom duration (12.3 vs 9.1 years, p<0.0001) and higher surgical rates (16.6% vs 6%, p<0.001) than those residing in-state.

CONCLUSIONS: In this large, single-center description, over one-third of patients did not have lymphedema. Lymphatic imaging was frequently performed, though few underwent surgery. Geographic barriers delayed evaluation and increased surgical intervention, emphasizing the need for broader access to multidisciplinary lymphatic care.

The sixth most common cancer in developing countries is the esophageal squamous cell carcinoma (ESCC), with a poor prognosis because the 5-year survival rate of patients with ESCC is only 35%. The incidence of ESCC is influenced by various factors, including diet, genetics, environmental exposures, and socio-economic status; almost all biological drivers of ESCC involve cancer stem cells (CSCs), which drive tumor initiation, therapy resistance, recurrence, and metastasis. CSC-related biomarkers in ESCC provide useful information on prognosis, diagnosis, and treatment methods. The accessory characteristics that identify CSCs are unique enzymatic activity, surface markers, and drug resistance; hence, contributing to their ability to overcome traditional forms of chemotherapy and radiotherapy. These biomarkers not only enable the isolation of CSCs but are also highly correlated with the clinical outcome of ESCC. A multiconjugation of certain CSC markers can improve detection accuracy and inform more precise treatment strategies. In addition, the development of ESCC-specific CSC biomarkers has the potential to develop targeted immunotherapy, which will eventually result in better patient outcomes. A CSC-based therapeutic approach provides a holistic understanding of CSC biology and the development of comprehensive treatment options for ESCC. Although several studies have investigated CSCs across various contexts, a comprehensive review focusing on their role, biomarkers, and therapeutic potential in ESCC is currently lacking, and this review aims to address that gap.