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.
Anatomy & Function
OBJECTIVE: To identify vulnerable upper extremity regions in native lymphatic anatomy that predispose women to the development of breast cancer-related lymphedema. Additionally, to identify currently available imaging technologies that could be repurposed for in-vivo lymphatic imaging of these anatomic regions and pathways.
BACKGROUND: Breast cancer-related lymphedema remains an incurable complication of breast cancer treatment, but improvements to knowledge of upper extremity lymphatic anatomy and imaging can unlock new techniques for prevention and treatment.
METHODS: "Bringing to Light the Invisible Lymphatic Anatomy of the Human Body" was a two day accelerator workshop held in May 2024 at the Harvard Radcliffe Institute attended by sixteen experts in lymphatic anatomy and imaging including four lymphatic anatomists, five imaging clinicians, three lymphatic scientists, and three program officers from the National Heart, Lung and Blood Institute (NHLBI) and Advanced Research Projects Agency for Health (ARPA-H).
RESULTS: Collateral pathways of the superficial lymphatic system, perforating lymphatic vessels, and the deep lymphatic system were implicated in preventing or reducing the severity of BCRL. Several strategies were proposed for repurposing existing imaging technology and developing new imaging technology that can improve understanding of the anatomy, function, and connectivity of lymphatic vessels in these three regions of the arm.
CONCLUSION: Advancements in lymphatic imaging are central to refining our knowledge of lymphatic anatomy. Key challenges to lymphatic imaging are visualization of the deep lymphatic system and perforating lymphatic vessels.
BACKGROUND: The lateral upper arm (LUA) pathway is a route of superficial lymphatic drainage that bypasses the axilla by draining to the deltopectoral, clavicular, and cervical lymph nodes. Despite the fact that anatomic variations of the LUA pathway have been implicated in breast cancer-related lymphedema (BCRL) risk after axillary lymph node dissection (ALND), the incidence of the LUA pathway variations in the healthy population has never been reported.
METHODS: Healthy female volunteers underwent bilateral lymphatic mapping of the upper extremities with indocyanine green (ICG) lymphography. ICG was injected in six standard sites in the hand/wrist and upper arm. Major anatomic variations of the LUA pathway were recorded including bundle phenotype (long, short, or absent), proximal visualization sites, and forearm pathway continuation to the long bundle phenotype.
RESULTS: 90 arms of 45 volunteers were included. The LUA pathway was present in 99% of arms and a long-versus-short bundle phenotype was observed in 71% versus 28% of arms. When the long bundle was present, it was formed by continuity with the forearm posterior radial channel alone (47%), posterior ulnar channel alone (34%), or both channels (19%). The LUA pathway was traced proximally to the deltopectoral groove in 89% of arms and to the axilla in 11% of arms.
CONCLUSIONS: We observed similar proportions of arms with long and short bundle phenotypes in comparison to our previous report of the LUA pathway in breast cancer patients with nodal disease. Defining the incidence of the LUA pathway with its variations in the general population is important as variations in this pathway may have implications for an individual's risk of developing BCRL.
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.
BACKGROUND: Upper extremity lymphedema occurs in 25 to 40% of patients after axillary lymph node dissection (ALND). Immediate lymphatic reconstruction (ILR) or the lymphatic micro- surgical preventative healing approach has demonstrated a significant decrease in postoperative rates of lymphedema (LE) from 4 to 12%. Our objective was to map the Mascagni -Sappey pathway, the lateral upper arm draining lymphatics, in patients undergoing ILR to better characterize the drainage pattern of this lymphosome to the axilla.
METHODS: A retrospective review of our institutional lymphatic database was conducted and consecutive breast cancer patients undergoing ILR were identified from November 2017 through June 2018. Patient demographics, clinical characteristics, and intraoperative records were retrieved and analyzed.
RESULTS: Twenty-nine consecutive breast cancer patients who underwent ILR after ALND were identified. Patients had a mean age of 54.6years and body mass index (BMI) of 26.6 kg/m2. Fluorescein isothiocyanate (FITC) was injected at the medial upper arm and isosulfan blue was injected at the cephalic vein, or lateral upper arm, prior to ALND. After ALND, an average 2.5 divided lymphatics were identified, and a mean 1.2 lymphatics were bypassed. In all patients, divided FITC lymphatics were identified. However, in only three patients (10%), divided blue lymphatics were identified after ALND.
CONCLUSION: In this study, variable drainage of the lateral upper arm to the axillary bed was noted. This study is the first to provide a description of intraoperative findings, demonstrating variable drainage patterns of upper extremity lymphatics to the axilla. Moreover, we noted that the lateral- and medial-upper arm lymphosomes have mutually exclusive pathways draining to the axilla. Further study of lymphatic anatomy variability may elucidate the pathophysiology of lymphedema development and influence approaches to immediate lymphatic reconstruction.
Lymphedema arises from impaired lymphatic function. Quantification of lymphatic contractility has previously been shown using a custom-built near-infrared imaging system. However, to broaden the clinical use of functional lymphatic measurements, these measurements need to be performed using a standard-of-care, clinically available camera. The authors propose an objective, algorithmic, and clinically accessible approach to quantify lymphatic contractility using a 3-minute indocyanine green lymphangiograph recorded with a commercially available near-infrared camera. A retrospective review of the authors' indocyanine green lymphangiography video repository maintained in a Research Electronic Data Capture database was performed. All patients with a newly diagnosed unilateral breast cancer undergoing preoperative indocyanine green lymphangiography were included in the analysis. Patient medical records were then analyzed for patient demographics, and videos were analyzed for contractility. Seventeen consecutive patients with unilateral breast cancers underwent video processing to quantify lymphatic contractility of the ipsilateral extremity in contractions per minute. All patients were women, with an average age of 60.5 years (range, 38 to 84 years). The average lymphatic contractility rate was 1.13 contractions per minute (range, 0.67 to 2.5 contractions per minute). Using a clinically accessible standard-of-care device for indocyanine green lymphangiography, the authors were able to determine lymphatic contractility rates of a normal extremity. The authors' finding falls within the range of previously published data quantifying lymphatic contractility using a research device, suggesting that the authors' technique provides a clinically accessible, time-effective means of assessing lymphatic contractility. Potential future applications include both lymphedema surveillance and evaluation of nonsurgical and surgical interventions. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Diagnostic, IV.
BACKGROUND: Anatomic variations in lymphatic drainage pathways of the upper arm may have an important role in the pathophysiology of lymphedema development. The Mascagni-Sappey (M-S) pathway, initially described in 1787 by Mascagni and then again in 1874 by Sappey, is a lymphatic drainage pathway of the upper arm that normally bypasses the axilla. Utilizing modern lymphatic imaging modalities, there is an opportunity to better visualize this pathway and its potential clinical implications.
METHODS: A retrospective review of preoperative indocyanine green (ICG) lymphangiograms of consecutive node-positive breast cancer patients undergoing nodal resection was performed. Lymphography targeted the M-S pathway with an ICG injection over the cephalic vein in the lateral upper arm.
RESULTS: In our experience, the M-S pathway was not visualized in 22% (n = 5) of patients. In the 78% (n = 18) of patients where the pathway was visualized, the most frequent anatomic destination of the channel was the deltopectoral groove in 83% of patients and the axilla in the remaining 17%.
CONCLUSION: Our study supports that ICG injections over the cephalic vein reliably visualizes the M-S pathway when present. Further study to characterize this pathway may help elucidate its potential role in the prevention or development of upper extremity lymphedema.
BACKGROUND: A distinct pattern of edema distribution is seen in breast cancer-related lymphedema. The area of edema sparing has not been characterized in relation to anatomy. Specifically, alternate lymphatic pathways are known to travel adjacent to the cephalic vein. Our study aims to define the location of edema sparing in the arm relative to the cephalic vein.
METHODS: A retrospective review of patients who underwent magnetic resonance imaging (MRI) between March 2017 and September 2018 was performed. Variables including patient demographics, arm volumes, and MRI data were extracted. MRIs were reviewed to define the amount of sparing, or angle of sparing, and the deviation between the center of sparing and the cephalic vein, or angle of deviation.
RESULTS: A total of 34 consecutive patients were included in the analysis. Five patients demonstrated circumferential edema (no sparing) and 29 patients demonstrated areas of edema sparing. Advanced age (69.7 vs. 57.6 years) and greater excess arm volume (40.4 vs. 20.8%) correlated with having circumferential edema without sparing (p = 0.003). In 29 patients with areas of edema sparing, the upper arm demonstrated the greatest angle of sparing (183.2 degrees) and the narrowest in the forearm (99.9 degrees; p = 0.0032). The mean angle of deviation to the cephalic vein measured 3.2, -0.1, and -5.2 degrees at the upper arm, elbow, and forearm, respectively.
CONCLUSION: Our study found that the area of edema sparing, when present, is centered around the cephalic vein. This may be explained by the presence of the Mascagni-Sappey (M-S) pathway as it is located alongside the cephalic vein. Our findings represent a key springboard for additional research to better elucidate any trends between the presence of the M-S pathway, areas of sparing, and severity of lymphedema.
BACKGROUND: The real-time quantification of lymphatic flow remains elusive. Efforts to provide a metric of direct lymphatic function are not clinically translatable and lack reproducibility. Early reports demonstrate the promise of immediate lymphatic reconstruction (immediate lymphovenous bypass after lymphadenectomy) to reduce the risk of lymphedema development. However, there remains a heightened need to appraise this technique in a clinically translatable large-animal model. The aim of the authors' experiment was to evaluate the role of molecular imaging in the quantification of real-time lymphatic flow after lymphadenectomy, and lymphadenectomy with lymphovenous bypass using novel fluorophores in a swine model.
METHODS: A lymphadenectomy or lymphadenectomy with subsequent lymphovenous bypass was performed in 10 female swine. After subdermal fluorophore injection, near-infrared molecular imaging of blood samples was used to evaluate change in lymphatic flow after lymphadenectomy versus after lymphadenectomy with lymphovenous bypass. Continuous imaging evaluating fluorescence of the superficial epigastric vein in the torso and adjacent skin was performed throughout all experiments. Findings between modalities were correlated.
RESULTS: The near-infrared dye signal in central and peripheral blood samples was often difficult to separate from background and proved challenging for reliable quantification. Venous and skin near-infrared imaging demonstrated a lymphatic clearance rate decrease of 70 percent after lymphadenectomy versus a decrease by only 30 percent after lymphadenectomy with immediate lymphovenous bypass.
CONCLUSIONS: In this article, the authors describe a noninvasive, swine, large-animal model to quantify lymphatic clearance using skin imaging. The authors' findings were consistent with results yielded from real-time imaging of the vein. The authors believe this model may have important implications for eventual direct translation to the clinical setting.
BACKGROUND: Knowledge of detailed lymphatic anatomy in humans is limited, as the small size of lymphatic channels makes it difficult to image. Most current knowledge of the superficial lymphatic system has been obtained from cadaveric dissections.
METHODS: Indocyanine green lymphography was performed preoperatively to map the functional arm lymphatics in breast cancer patients without clinical or objective evidence of lymphedema. A retrospective review was performed to extract demographic, indocyanine green imaging, and surgical data.
RESULTS: Three main functional forearm channels with variable connections to two upper arm pathways were identified. The median forearm channel predominantly courses in the volar forearm (99 percent). The ulnar forearm channel courses in the volar forearm in the majority of patients (66 percent). The radial forearm channel courses in the dorsal forearm in the majority of patients (92 percent). Median (100 percent), radial (91 percent), and ulnar (96 percent) channels almost universally connect to the medial upper arm channel. In contrast, connections to the lateral upper arm channel occur less frequently from the radial (40 percent) and ulnar (31 percent) channels.
CONCLUSIONS: This study details the anatomy of three forearm lymphatic channels and their connections to the upper arm in living adults without lymphatic disease. Knowledge of these pathways and variations is relevant to any individual performing procedures on the upper extremities, as injury to the superficial lymphatic system can predispose patients to the development of lymphedema.
Lymphedema is a devastating disease that has no cure. Management of lymphedema has evolved rapidly over the past two decades with the advent of surgeries that can ameliorate symptoms. MRI has played an increasingly important role in the diagnosis and evaluation of lymphedema, as it provides high spatial resolution of the distribution and severity of soft tissue edema, characterizes diseased lymphatic channels, and assesses secondary effects such as fat hypertrophy. Many different MR techniques have been developed for the evaluation of lymphedema, and the modality can be tailored to suit the needs of a lymphatic clinic. In this review article we provide an overview of lymphedema, current management options, and the current role of MRI in lymphedema diagnosis and management. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 5.
PURPOSE: The tricipital, or Caplan's, lymphatic pathway has been previously identified in cadavers and described as a potential compensatory pathway for lymphatic drainage of the upper extremity, as it may drain lymphatic fluid directly to the scapular lymph nodes, avoiding the axillary lymph node groups. The aim of this study was to map the anatomy of the tricipital pathway in vivo in patients without lymphatic disease.
METHODS: A retrospective review was performed to identify patients with unilateral breast cancer undergoing preoperative Indocyanine green (ICG) lymphography prior to axillary lymph node dissection from May 2021 through January 2022. Exclusion criteria were evidence or known history of upper extremity lymphedema or non-linear channels visualized on ICG. Demographic, oncologic, and ICG imaging data were extracted from a Lymphatic Surgery Database. The primary outcome of this study was the presence and absence of the tricipital pathway. The secondary outcome was major anatomical variations among those with a tricipital pathway.
RESULTS: Thirty patients underwent preoperative ICG lymphography in the study period. The tricipital pathway was visualized in the posterior upper arm in 90% of patients. In 63% of patients, the pathway had a functional connection to the forearm (long bundle variant) and in 27%, the pathway was isolated to the upper arm without a connection to the forearm (short bundle variant). In those with a long bundle, the contribution was predominantly from the posterior ulnar lymphosome. Anatomic destinations of the tricipital pathway included the deltotricipital groove and the medial upper arm channel, which drains to the axilla.
CONCLUSION: When present, the tricipital pathway coursed along the posterior upper arm with variability in its connections to the forearm distally, and the torso proximally. Long-term follow-up studies will help determine the significance of these anatomic variations in terms of individual risk of lymphedema after axillary nodal dissection.
Immediate lymphatic reconstruction (ILR) has become increasingly utilized for the prevention of breast cancer-related lymphedema (BCRL). A growing body of evidence has demonstrated the long-term efficacy of ILR in reducing the rate of BCRL. While certain risk factors for BCRL are well-recognized, such as axillary lymph node dissection, regional lymph node radiation, and elevated body mass index, other potential risk factors such as age and taxane-based chemotherapeutics remain under discussion. Our experience with ILR has highlighted an additional potential risk factor for BCRL. Lymphatic anatomy, specifically compensatory lymphatic channels that bypass the axilla, may play a largely underrecognized role in determining which patients will develop BCRL after ILR. Foundational anatomic knowledge has primarily been based on cadaveric studies that predate the twentieth century. Modern approaches to lymphatic anatomical mapping using indocyanine green lymphography have helped to elucidate baseline lymphatic anatomy and compensatory channels, and certain variations within these channels may act as anatomic risk factors. Therefore, the purpose of this review was to highlight ways in which variations in lymphatic anatomy can inform the application and improve the accessibility of this procedure. As ILR continues to advance and evolve, anatomical mapping of the lymphatic system is valuable to both the patient and lymphatic microsurgeon and is a critical area of future study.
BACKGROUND: The lateral upper arm channel is an accessory lymphatic pathway that drains the upper extremity by means of the deltopectoral groove and supraclavicular nodes, thereby bypassing the axilla. Its variable connectivity to the forearm has not been studied in vivo.
METHODS: Indocyanine green (ICG) lymphography was performed preoperatively to map the superficial and functional arm lymphatics in breast cancer patients without clinical or objective evidence of lymphedema. A retrospective review was performed to extract demographic, ICG imaging, and surgical data.
RESULTS: Sixty patients underwent ICG lymphography before axillary lymph node dissection between June of 2019 and October of 2020. In 59%, the lateral upper arm lymphatic channel was contiguous with the forearm (long bundle). In 38%, the lateral upper arm lymphatic channel was present but not contiguous with the forearm (short bundle). In 3%, the lateral upper arm pathway was entirely absent. Seven patients developed at least one sign of lymphedema during postoperative surveillance, of which 71% demonstrated the short bundle variant.
CONCLUSION: Although the lateral upper arm pathway is most often present, its connections to the forearm are frequently absent (short bundle), which, in this pilot report, appears to represent a potential risk factor for the development of lymphedema.
CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, V.
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.
INTRODUCTION: Magnetic resonance imaging (MRI) stage 1 (early stage) upper extremity lymphedema is characterized by fluid infiltration in the subcutaneous tissues that does not exceed 50% of the extremity circumference at any level. The spatial fluid distribution in these cases has not been detailed and may be important to help determine the presence and location of compensatory lymphatic channels. The aim of this study is to determine whether there was a pattern of distribution of fluid infiltration in patients with early-stage lymphedema that could correspond to known lymphatic pathways in the upper extremity.
METHODS: A retrospective review identified all patients with MRI stage 1 upper extremity lymphedema who were evaluated at a single lymphatic center. Using a standardized scoring system, a radiologist graded the severity of fluid infiltration at 18 anatomical locations. A cumulative spatial histogram was then created to map out regions where fluid accumulation occurred most and least frequently.
RESULTS: Eleven patients with MRI stage 1 upper extremity lymphedema were identified between January 2017 and January 2022. The mean age was 58 years and the mean BMI was 30 m/kg2. One patient had primary lymphedema and the remaining 10 had secondary lymphedema. The forearm was affected in nine cases, and fluid infiltration was predominantly concentrated along the ulnar aspect, followed by the volar aspect, while the radial aspect was completely spared. Within the upper arm, fluid was primarily concentrated distally and posteriorly, and occasionally medially.
CONCLUSIONS: In patients with early-stage lymphedema, fluid infiltration is concentrated along the ulnar forearm and the posterior distal upper arm, which aligns with the tricipital lymphatic pathway. There is also sparing of fluid accumulation along the radial forearm in these patients, suggesting a more robust lymphatic drainage along this region, possibly due to a connection to the lateral upper arm pathway.
Immediate lymphatic reconstruction (ILR) at the time of axillary lymph node dissection (ALND) has become increasingly utilized for the prevention of breast cancer related lymphedema. Preoperative indocyanine green (ICG) lymphography is routinely performed prior to an ILR procedure to characterize baseline lymphatic anatomy of the upper extremity. While most patients have linear lymphatic channels visualized on ICG, representing a non-diseased state, some patients demonstrate non-linear patterns. This study aims to determine potential inciting factors that help explain why some patients have non-linear patterns, and what these patterns represent regarding the relative risk of developing postoperative breast cancer related lymphedema in this population. A retrospective review was conducted to identify breast cancer patients who underwent successful ILR with preoperative ICG at our institution from November 2017-June 2022. Among the 248 patients who were identified, 13 (5%) had preoperative non-linear lymphatic anatomy. A history of trauma or surgery of the affected limb and an increasing number of sentinel lymph nodes removed prior to ALND appeared to be risk factors for non-linear lymphatic anatomy. Furthermore, non-linear anatomy in the limb of interest was associated with an increased risk of postoperative lymphedema development. Overall, non-linear lymphatic anatomy on pre-operative ICG lymphography appears to be a risk factor for developing ipsilateral breast cancer-related lymphedema. Guided by the study's findings, when breast cancer patients present with baseline non-linear lymphatic anatomy, our institution has implemented a protocol of prophylactically prescribing compression sleeves immediately following ALND.
PURPOSE: There are limited existing data on the lymphatic anatomy of patients with primary lymphedema (LED), which is caused by aberrant development of lymphatic channels. In addition, there is a paucity of contemporary studies that use groin intranodal lymphangiography (IL) to evaluate LED anatomy. The purpose of this retrospective observational study was to better delineate the disease process and anatomy of primary LED using groin IL.
MATERIALS AND METHODS: We identified common groin IL findings in a cohort of 17 primary LED patients performed between 1/1/2017 and 1/31/2022 at a single institution. These patients were clinically determined to have primary lymphedema and demonstrated associated findings on lower extremity MR and lymphoscintigraphy.
RESULTS: Ten patients (59%) demonstrated irregular lymph node morphology or a paucity of lymph nodes on the more symptomatic laterality. Eight patients (47%) demonstrated lymphovenous shunting from pre-existing anastomoses between the lymphatic and venous systems. Eight patients (47%) demonstrated passage of contrast past midline to the contralateral lymphatics. Finally, 12 patients (71%) failed to opacify the cisterna chyli and thoracic duct on their initial lymphangiograms. Delayed computed tomography of 3 patients showed eventual central lymphatic opacification up to the renal veins, but none of these patients showed central lymphatic opacification to the thorax.
CONCLUSION: This descriptive, exploratory study demonstrates common central groin IL findings in primary LED to highlight patterns interventional radiologists should identify and report when addressing primary LED.
Piezo1 regulates multiple aspects of the vascular system by converting mechanical signals generated by fluid flow into biological processes. Here, we find that Piezo1 is necessary for the proper development and function of meningeal lymphatic vessels and that activating Piezo1 through transgenic overexpression or treatment with the chemical agonist Yoda1 is sufficient to increase cerebrospinal fluid (CSF) outflow by improving lymphatic absorption and transport. The abnormal accumulation of CSF, which often leads to hydrocephalus and ventriculomegaly, currently lacks effective treatments. We discovered that meningeal lymphatics in mouse models of Down syndrome were incompletely developed and abnormally formed. Selective overexpression of Piezo1 in lymphatics or systemic administration of Yoda1 in mice with hydrocephalus or Down syndrome resulted in a notable decrease in pathological CSF accumulation, ventricular enlargement and other associated disease symptoms. Together, our study highlights the importance of Piezo1-mediated lymphatic mechanotransduction in maintaining brain fluid drainage and identifies Piezo1 as a promising therapeutic target for treating excessive CSF accumulation and ventricular enlargement.
BACKGROUND: While substantial anatomical study has been pursued throughout the human body, anatomical study of the human lymphatic system remains in its infancy. For microsurgeons specializing in lymphatic surgery, a better command of lymphatic anatomy is needed to further our ability to offer surgical interventions with precision. In an effort to facilitate the dissemination and advancement of human lymphatic anatomy knowledge, our teams worked together to create a map. The aim of this paper is to present our experience in mapping the anatomy of the human lymphatic system.
METHODS: Three steps were followed to develop a modern map of the human lymphatic system: (1) identifying our source material, which was "Anatomy of the human lymphatic system," published by Rouvière and Tobias (1938), (2) choosing a modern platform, the Miro Mind Map software, to integrate the source material, and (3) transitioning our modern platform into The Human BioMolecular Atlas Program (HuBMAP).
RESULTS: The map of lymphatic anatomy based on the Rouvière textbook contained over 900 data points. Specifically, the map contained 404 channels, pathways, or trunks and 309 lymph node groups. Additionally, lymphatic drainage from 165 distinct anatomical regions were identified and integrated into the map. The map is being integrated into HuBMAP by creating a standard data format called an Anatomical Structures, Cell Types, plus Biomarkers table for the lymphatic vasculature, which is currently in the process of construction.
CONCLUSION: Through a collaborative effort, we have developed a unified and centralized source for lymphatic anatomy knowledge available to the entire scientific community. We believe this resource will ultimately advance our knowledge of human lymphatic anatomy while simultaneously highlighting gaps for future research. Advancements in lymphatic anatomy knowledge will be critical for lymphatic surgeons to further refine surgical indications and operative approaches.