Publications

PURPOSE: Axillary lymph node dissection (ALND) and regional nodal irradiation (RNI) are the primary causes of breast cancer-related lymphedema (BCRL). Immediate lymphatic reconstruction (ILR) is a novel surgical procedure that reduces the incidence of BCRL after ALND. The ILR anastomosis is placed in a location thought to be outside the standard radiation therapy fields to prevent radiation-induced fibrosis of the reconstructed vessels; however, there is excess risk of BCRL from RNI even after ILR. The purpose of this study was to understand the radiation dose distribution in relation to the ILR anastomosis.

METHODS AND MATERIALS: This prospective study included 13 patients treated with ALND/ILR from October 2020 to June 2022. A twirl clip deployed during surgery was used to identify the ILR anastomosis site during radiation treatment planning. All cases were planned using a 3D-conformal technique with opposed tangents and an obliqued supraclavicular (SCV) field.

RESULTS: RNI deliberately targeted axillary Levels 1 to 3 and the SCV nodal region in 4 patients and was limited to Level 3 and SCV nodes in 9 patients. The ILR clip was located in Level 1 in 12 patients and Level 2 in 1 patient. In patients with radiation directed at only Level 3 and SCV, the ILR clip was still within the radiation field in 5 of these patients and received a median dose of 3939 cGy (range, 2025-4961 cGy). The median dose to the ILR clip was 3939 cGy (range, 139-4961 cGy) for the entire cohort. The median dose was 4275 cGy (range, 2025-4961 cGy) when the ILR clip was within any radiation field and 233 cGy (range, 139-280 cGy) when the clip was outside all fields.

CONCLUSION: The ILR anastomosis was often directly irradiated with 3D-conformal techniques and received substantial radiation dose, even when the site was not deliberately targeted. Long-term analysis will help determine whether minimizing radiation dose to the anastomosis will decrease BCRL rates.

PURPOSE: Immediate lymphatic reconstruction (ILR) is a procedure known to reduce the risk of lymphedema in patients undergoing axillary lymph node dissection (ALND). However, patients who receive adjuvant radiotherapy are at increased risk of lymphedema. The aim of this study was to quantify the extent of radiation at the site of surgical prevention.

METHODS: We recently began deploying clips at the site of ILR to identify the site during radiation planning. A retrospective review was performed to identify breast cancer patients who underwent ILR with clip deployment and adjuvant radiation therapy from October 2020 to April 2022. Patients were excluded if they had not completed radiotherapy. The exposure and dose of radiation received by the site was determined and recorded.

RESULTS: In a cohort of 11 patients, the site fell within the radiation field in 7 patients (64%) and received a median dose of 4280 cGy. Among these 7 patients, 3 had sites located within tissue considered at risk of oncologic recurrence and the remaining 4 sites received radiation from a tangential field treating the breast or chest wall. The median dose to the ILR site for the 4 patients whose sites were outside the radiation fields was 233 cGy.

CONCLUSION: Our findings suggest that even when the site of surgical prevention was not within the targeted radiation field during treatment planning, it remains susceptible to radiation. Strategies for limiting radiation at this site are needed.

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.

The Human BioMolecular Atlas Program (HuBMAP) aims to create a multi-scale spatial atlas of the healthy human body at single-cell resolution by applying advanced technologies and disseminating resources to the community. As the HuBMAP moves past its first phase, creating ontologies, protocols and pipelines, this Perspective introduces the production phase: the generation of reference spatial maps of functional tissue units across many organs from diverse populations and the creation of mapping tools and infrastructure to advance biomedical research.

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.

Background and Objectives: One of the surgical treatments for breast cancer-related lymphedema (BCRL) is debulking lipectomy. The aim of this study is to investigate whether dermal thickness could be utilized as an objective indicator of post-operative changes following debulking. Materials and Methods: A retrospective review of BCRL patients who underwent debulking lipectomy was conducted. MRI-based dermal thickness was measured by two separate trained readers at 16 regions of the upper extremity. Pre- and post-operative reduction in dermal thickness was compared across the affected and unaffected (control) arms for each patient. The Wilcoxon rank sum test was used to assess for significant change. Univariate linear regression was used to assess the relationship between dermal thickness reduction and changes to LYMPH-Q scores, L-Dex scores, and relative volume change. Results: Seventeen patients were included in our analysis. There was significant reduction in dermal thickness at 5/16 regions in the affected arm. Dermal thickness change was significantly correlated with LYMPH-Q scores, L-Dex scores, and relative volume change in 2/16 limb compartments. There was predominant dermal thickening in the dorsal compartment of the upper arm and in the ventral and ulnar compartments of the forearm. Conclusions: Dermal thickness shows promising utility in tracking post-operative debulking procedures for breast cancer-related lymphedema. Further studies with larger patient populations and a variety of imaging modalities are required to continue to develop a clinically objective and reproducible method of post-surgical lymphedema staging and monitoring.

OBJECTIVE: To implement and evaluate outcomes from a comprehensive, multi-disciplinary debulking program in the United States.

SUMMARY OF BACKGROUND DATA: Interest in and access to surgical treatment for chronic lymphedema (LE) in the United States have increased in recent years, yet there remains little attention on liposuction, or debulking, as an effective treatment option. In some other countries, debulking is a common procedure for the surgical treatment of LE, is covered by insurance, and has demonstrated excellent, reproducible outcomes. In this study we describe our experience implementing a debulking technique from Sweden in the United States.

METHODS: Patients who presented with chronic LE followed a systematic multi-disciplinary work-up. For debulking with power assisted liposuction, the surgical protocol was modeled after that developed by Håkan Brorson. A retrospective review of consecutive patients who underwent debulking at our institution was conducted.

RESULTS: Between December 2017 and January 2020, 39 patients underwent 41 debulking procedures with power assisted liposuction, including 23 upper and 18 lower extremities. Mean patient age was 58 years and 85% of patients had LE secondary to cancer, the majority of which (64%) was breast cancer. Patients experienced excess volume reductions of 116% and 115% in the upper and lower extremities, respectively, at 1 year postoperatively. Overall quality of life (LYMQOL) improved by a mean of 33%. Finally, patients reported a decreased incidence of cellulitis and decreased reliance on conservative therapy modalities postoperatively.

CONCLUSIONS: Debulking with power assisted liposuction is an effective treatment for patients with chronic extremity LE. The operation addresses patient goals and improves quality of life, and additionally reduces extremity volumes, infection rates and reliance on outpatient therapy. A comprehensive, multi-disciplinary debulking program can be successfully implemented in the United States healthcare system.

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.