Publications

BACKGROUND: Axillary reverse mapping (ARM) identifies lymph vessels and nodes draining the arm to preserve them during axillary lymph node dissection (ALND) and thus reduce the risk of breast-cancer related lymphedema (BCRL). The ideal location for dye injections has not been previously studied. This study compared transected lymphatic vessels visualized for immediate lymphatic reconstruction (ILR) after ALND between patients who received fluorescein isothiocyanate (FITC) injections in the hand/wrist and those who received traditional medial upper-arm location.

METHODS: A retrospective review of ILR patients from September 2017 through May 2023 was performed. Dye injection site, number of channels visualized, channel distances from the axillary vein (cm), and channel diameters (mm) were collected. A chi-square test was used to compare the number of channels between injection sites. Mann-Whitney U tests were used to compare channel distances and channel diameters between injection sites.

RESULTS: Of 323 patients, 180 received hand/wrist injections, and 143 received medial upper-arm injections. Altogether, 755 channels were visualized. Fewer lymphatic channels were visualized in the hand/wrist injection group (p = 0.011). The median channel distance from the axillary vein was 2.3 cm after hand/wrist injections and 2.7 cm after medial upper-arm injections (p < 0.001). Channel diameters did not differ between injection-site groups (p = 0.066).

CONCLUSIONS: With the hand/wrist injections, fewer channels closer to the axillary vein were visualized. These findings corroborate prior anatomic and intraoperative studies identifying main lymphatic vessels of the arm as traveling closely along the axillary vein. Hand/wrist injections are more likely to identify main lymphatic channels draining the arm when ARM is performed.

BACKGROUND: The lateral upper arm lymphatic pathway is theorized as a route of superficial lymphatic drainage protective against breast cancer-related lymphedema (BCRL) after axillary lymph node dissection (ALND). This study describes lymph nodes draining the lateral upper arm pathway.

METHODS: Healthy female volunteers underwent bilateral ICG lymphography and nuclear lymphoscintigraphy. Nuclear tracer was injected over the cephalic vein in the upper arm. Lymph nodes with tracer uptake were recorded as deltopectoral, Station 1 (Axillary Levels I or II and Interpectoral), or Station 2 (Axillary Level III, Infraclavicular, Supraclavicular Levels IV or Vb, and Cervical Level Va).

RESULTS: 72 arms of 36 volunteers were included. Functional drainage to deltopectoral lymph nodes was observed in 38% (27/72) of arms. Drainage to Station 1, Station 2, and neither station was observed in 96% (69/72), 36% (26/72), and 3% (2/72) of arms, respectively. No differences were observed between arms with or without deltopectoral lymph nodes draining to Station 1 lymph nodes (93% vs 98%, p = 0.286) or neither station (4% vs 2%, p = 0.711), respectively. A significant difference was observed between arms with or without deltopectoral lymph nodes draining to Station 2 lymph nodes (52% vs 27%, p = 0.031).

CONCLUSIONS: Deltopectoral lymph node drainage is significantly correlated with Station 2 lymph node drainage. As Station 2 lymph nodes are preserved in an ALND, the presence of deltopectoral lymph node drainage represents an important potential protective biomarker for BCRL development.

BACKGROUND: Superficial to deep system rerouting of lymph protects against breast cancer-related lymphedema (BCRL). Humeral lymph nodes are a marker for deep lymphatic drainage. Epitrochlear lymph nodes are a site of superficial to deep collateralization based on cadaveric dissections. Functional connectivity between epitrochlear and humeral lymph nodes remains unexamined with in vivo imaging. We utilized lymphoscintigraphy to document epitrochlear and humeral lymph node drainage in healthy volunteers.

METHODS: Healthy female volunteers received four intradermal hand/wrist injections of 99-Tcm sulfur colloid to each upper extremity and were imaged with SPECT/CT at 2 h. Two nuclear medicine physicians independently reviewed the SPECT/CT scans to document lymph nodes with tracer uptake. A Chi-square test was performed to assess the correlation between functional epitrochlear and humeral lymph node drainage.

RESULTS: A total of 72 arms of 36 volunteers were included. Drainage to epitrochlear and humeral lymph nodes was observed in 57% (41/72) and 51% (37/72) of arms, respectively. Drainage to both epitrochlear and humeral lymph nodes was observed in 40% (29/72) of arms. Epitrochlear and humeral lymph node drainage were absent in 32% (27/72) of arms. The proportion of arms with humeral lymph node drainage was significantly greater in arms with (71%, 29/41) versus without (26%, 8/31) epitrochlear lymph node drainage [χ2 = 14.262 (1), p < 0.001].

CONCLUSIONS: Epitrochlear and humeral lymph node drainage are significantly correlated, suggesting a superficial to deep pathway may function at baseline in 40% of arms. The absence of epitrochlear and humeral lymph node drainage may represent a biomarker for BCRL risk.

Vascularized lymph node transplant (VLNT) is widely performed for chronic upper and lower extremity lymphedema. However, ideal recipient sites for the transplant are still under debate. The placement of VLNTs distally in an extremity can be challenging as the small cross-sectional area of the limb at this level does not allow for flap inset without gross contour deformity, which can adversely impact aesthetic outcomes and preclude fitting of an adequate compression garment. In this article, we introduce the Kager triangle as a potential distal lower extremity VLNT recipient site for the lower extremity. The Kager triangle is bordered by the Achilles tendon, the flexor hallucis longus, and the calcaneus, which accommodates the Kager fat pad, the largest adipose structure in the lower extremity. We transferred an omentum lymph node flap to the Kager triangle, and the posterior tibial artery and the anterior lateral malleolar artery were utilized as recipient vessels in a flow-through fashion. The incisions were directly closed with excellent cosmesis.

BACKGROUND: Despite advancements in the surgical treatment and prevention of lymphedema, there are no standards for reporting outcomes of lymphatic surgery. Developing consensus on a minimum standard set of outcome measures for lymphatic surgery represents an important step toward standardizing treatment options and comparing patient outcomes between institutions.

METHODS: A modified Delphi method with an expert panel of five Society of Lymphatic Surgery (SLS) board members was conducted. Participants completed two rounds of virtual, anonymous surveys from February 2024 to March 2024. Participants rated outcome measures to develop consensus for their inclusion in a minimum standard set. The initial list was developed from outcome measures voted upon at an SLS panel during the 2023 American Society of Reconstructive Microsurgery (ASRM) meeting. Results were analyzed using predefined criteria to establish the core set of outcome measures.

RESULTS: The expert panel completed two rounds of surveys, including six baseline characteristics for lymphatic surgery to establish a minimum standard set of outcome measures. Characteristics included compression, limb volume measurements, patient-reported outcome measures, cellulitis, follow-up time, and lymphedema surveillance parameters. Consensus was not reached in how to best measure time in compression or the L-dex diagnostic threshold for lymphedema surveillance programs.

CONCLUSION: The SLS leadership established a first minimum standard set of outcome measures for lymphatic surgery with six baseline characteristics for evaluating outcomes of lymphatic surgery. This outcome set will support the collection of meaningful data to further standardize lymphatic surgery approaches for the treatment and prevention of lymphedema.

BACKGROUND: Intrinsic lymphatic contractility is essential for tissue fluid balance, immunity and organ function, yet no FDA-approved pharmacologic treatments specifically restore lymphatic contractility. Lymph is returned to the circulation by ion channel-driven cyclic contractions of collecting lymphatic vessels. Although voltage-gated sodium (Na V ) channels drive cardiomyocyte excitability, their role in lymphatic muscle cell (LMC) physiology is not well defined. We identified Na V 1.3, a Na V channel historically viewed as developmentally restricted and limited in adult tissues, as unexpectedly and selectively expressed in adult lymphatic muscle but absent from heart, vascular smooth muscle, and mature brain. We tested whether selective Na V 1.3 activation restores impaired lymphatic pumping in aging and radiation injury.

METHODS: Na V 1.3 expression in LMCs was confirmed through single-cell RNA sequencing analysis and immunostaining of mouse and human lymphatic vessels. Lymphatic contractility was quantified by in vivo fluorescence lymphangiography and interstitial fluid clearance was measured with a new bioluminescence assay. Na V 1.3 function was assessed in young, aged, and radiation-injured mice. Na V 1.3 knockout ( Scn3a -/- ) mice established the requirement of Na V 1.3 for basal lymphatic excitability and responsiveness to the Na V 1.3-specific activator, Tf2.

RESULTS: In mouse and human lymphatic vessels, Na V 1.3 is expressed in adult LMCs. Although dispensable for basal lymphatic contractions, Na V 1.3 acted as a pharmacologically recruitable reserve that amplified contractile output. Acute Na V 1.3 activation with Tf2 increased lymphangion ejection fraction and accelerated interstitial fluid clearance. Tf2 fully restored lymphatic pumping in aged mice and partially rescued radiation-induced contractile deficits. All Tf2 responses were abolished in Scn3a -/- mice, confirming Na V 1.3 dependence.

CONCLUSIONS: Na V 1.3 is a selectively druggable ion channel in adult lymphatic muscle that can be recruited to restore lymphatic pump function across aging and injury. Targeted Na V 1.3 activation provides a molecular entry point for treating diseases characterized by lymphatic pump failure, a domain with no existing pharmacologic therapies.

BACKGROUND: The inability to directly measure real-time lymphatic transport hinders our understanding of lymphatic disorders and effective monitoring of therapeutic interventions. Here, we report three refinements to the use of novel near-infrared fluorophores in a large animal model for assessment of lymphatic function using optical fluorescence with the ultimate goal of direct clinical translation.

METHODS: A lymphadenectomy and lymphovenous bypass was performed in the left groin. Two different near-infrared (NIR) fluorophores composed of the identically same scaffold were injected into the respective hind limbs of female swine. Transit from injection sites into the lymphatic system and systemic circulation was assessed over three hours of NIR imaging immediately following injections. Albumin-conjugated fluorophores with 700 nm and 800 nm emission, respectively, were delivered with manual intradermal injection. Blood and urine samples were collected at standard time points. Continuous NIR imaging of the lymphovenous bypass and the superficial epigastric vein and its adjacent skin was also performed at standard time points. Blood and urine samples were collected to analyze systemic concentrations and renal excretion of both fluorophores, respectively. NIR imaging was performed to analyze real-time lymphatic transport of the fluorophores through the lymphovenous bypass and in the central circulation.

RESULTS: Fluorophore pharmacokinetics with albumin conjugation and manual intradermal injections produced inconsistent results. Three modifications to the study protocol were designed. Fluorophores were modified from albumin conjugation to polyethylene glycol (PEG) conjugation. Fluorophores were delivered with VAX-ID ® devices instead of manual intradermal injections. Additionally, a novel correction factor was developed to account for differences in NIR fluorescence between the fluorophores.

CONCLUSION: The refinement of a large animal model to assess real-time lymphatic function represents a crucial step toward clinical translation. The optimized fluorophore composition and delivery mechanism captures dynamic changes in lymphatic function.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12880-025-02057-6.

Lymphedema is a chronic, progressive condition characterized by the accumulation of protein-rich interstitial fluid due to impaired lymphatic transport. It significantly impairs quality of life and presents complex diagnostic and therapeutic challenges. Despite its prevalence, lymphedema remains underdiagnosed and undertreated, in part due to limited provider education and a lack of access to coordinated care. For this reason, a multidisciplinary approach to lymphedema management is crucial. Early diagnosis is critical and requires collaboration across primary care, oncology, vascular medicine, radiology, lymphatic therapy, and surgery. There are increasing imaging techniques available, but require unique skill sets to perform and interpret. Similarly, there are growing surgical treatment options, but conservative therapy remains the mainstay for most patients. A structured, collaborative model is essential for high-quality, patient-centered lymphedema care. Establishing multidisciplinary lymphedema centers can enhance outcomes, reduce delays, and promote innovation in treatment strategies.

ObjectiveThe incidence of lipedema is poorly described due to its confusion with lymphedema. Patient education is crucial for treatment and prevention strategies but also for improving healthcare outcomes. This study assessed and compared the quality of English and Spanish online resources for patients suffering from lipedema using a multimetric approach.MethodsA deidentified Google search using the terms "lipedema" and "lipedema español" was conducted. The first 10 academic/organizational websites in each language were selected. Quality assessment was performed using the Patient Education and Materials Assessment Tool (PEMAT), Cultural Sensitivity Assessment Tool (CSAT), Simple Measure of Gobbledygook (SMOG), and facticity criteria to evaluate understandability and actionability, cultural sensitivity, readability, and factual quality, respectively.ResultsEnglish webpages scored 73.70% for understandability and 35.0% for actionability, while Spanish webpages scored 75.05% and 21.0%, respectively; no significant differences were found between languages in understandability (p = .970) and actionability (p = .895). A significantly higher proportion of Spanish resources was found to be culturally sensible than English resources (90% vs 70%; p < .001). However, no significant differences were found in the cultural sensitivity score (English 2.87 vs Spanish 3.01; p = .677). The grade reading level for Spanish materials was significantly lower compared to English materials (11.08 vs 13.45; p = .006). Factual quality was low across both languages according to the facticity framework, though English materials scored higher than Spanish (2.20 vs 1.00; p = .051).ConclusionOur results suggest that online English and Spanish materials on lipedema have inadequate actionability, facticity, and reading grade levels for patients. Nonetheless, the levels of understandability and cultural sensitivity are acceptable. Enhancing the quality of online health literature for lipedema patients presents an opportunity to alleviate psychosocial burdens and address misconceptions.

BACKGROUND: Recent advances in breast cancer have progressed toward less aggressive axillary surgery. However, axillary lymph node dissection (ALND) remains necessary in specific cases and can increase the risk of lymphedema. Performing ALND with immediate lymphatic reconstruction (ILR) can help lower this risk. This report outlines the implementation of an Axillary Surgery Referral Program (ASRP) to broaden access to ILR, providing insights for institutions considering similar initiatives.

METHODS: A retrospective study analyzed patients referred to the ASRP at Beth Israel Deaconess Medical Center (BIDMC) between 6 January 2017 and 10 December 2022. Patients were identified from a prospective registry, with data subsequently extracted from electronic medical records. This analysis specifically centered on patients referred from external institutions to undergo ALND with ILR.

RESULTS: The program received referrals for 131 patients from institutions across five different states. Annual referrals steadily increased over time. The primary indication for referral was residual axillary disease after neoadjuvant chemotherapy (41.2%). Among the referrals, 20 patients (15.3%) no longer required ALND due to axillary pathologic complete response to neoadjuvant therapy. Care coordination played a crucial role in streamlining the patient care process for both efficiency and effectiveness.

CONCLUSION: The ASRP expands access to ILR for patients with breast cancer, the majority referred for surgical management of residual disease after chemotherapy. The program provides a model for health care institutions aiming to establish similar specialized referral services. Continued program evaluation will be instrumental in refining axillary surgery referral practices and ensuring optimal patient care.