Publications

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: Closed-incision negative pressure therapy (CINPT) with the Prevena system has been used and clinically evaluated in high-risk groin incisions to reduce the risk of postoperative complications. We performed a cost-effectiveness analysis evaluating CINPT in femoral-popliteal bypass with prosthetic graft.

METHODS: A literature review looking at prospective randomized trials determined the probabilities and outcomes for femoral-popliteal bypass with and without CINPT. Reported utility scores were used to estimate the quality adjusted life years (QALYs) associated with a successful procedure and postoperative complications. Medicare current procedure terminology and diagnosis-related group codes were used to assess the costs for a successful surgery and associated complications. A decision analysis tree was constructed with rollback analysis to highlight the more cost-effective strategy. An incremental cost-effectiveness ratio (ICER) analysis was performed with a willingness to pay at $50,000. Deterministic and probabilistic sensitivity analyses were performed to validate the robustness of the results, and to accommodate for the uncertainty in the literature.

RESULTS: Femoral-popliteal bypass with CINPT is less costly ($40,138 vs $41,774) and more effective (6.14 vs 6.13) compared to without CINPT. This resulted in a negative ICER of -234,764.03, which favored CINPT, indicating a dominant strategy. In one-way sensitivity analysis, surgery without CINPT was more cost-effective if the probability of successful surgery falls below 84.9% or if the cost of CINPT exceeds $3139. Monte Carlo analysis showed a confidence of 99.07% that CINPT is more cost-effective.

CONCLUSIONS: Despite the added device cost of CINPT, it is cost-effective in vascular surgical operations using groin incisions.

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.

SUMMARY: Vascularized lymph node transplantation is a surgical approach for the treatment of chronic lymphedema. However, there is no clinical standard for flap placement nor vascular anastomoses. The authors propose a novel flowthrough configuration for an omental vascularized lymph node transplant in the popliteal space. To prepare the popliteal space for an omental free flap, the medial popliteal fat pad and medial head of the gastrocnemius muscle were debulked. Venous anastomoses were completed with vein couplers, joining the right gastroepiploic vein to the medial sural venae comitantes and the left gastroepiploic vein to the lesser saphenous vein. Arterial anastomoses were hand sewn, joining the right gastroepiploic artery to the proximal medial sural artery and the left gastroepiploic artery to the distal medial sural artery, to create the flowthrough configuration. A retrospective review of patients who underwent this procedure at a single institution was performed. Six patients with chronic lymphedema of the lower extremity underwent vascularized lymph node transplantation from June of 2019 to November of 2020. Five patients underwent at least 3 months of postoperative surveillance, with no postoperative complications reported. In this technique contribution, the authors describe a novel flowthrough configuration for an omental free flap to the popliteal space. The popliteal space offers an aesthetically favorable recipient location when appropriately prepared. The medial sural vessels are ideal recipient vessels for the flowthrough omental flap.

CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Immediate lymphatic reconstruction (ILR) is targeted at preventing breast cancer related lymphedema (BCRL) by anastomosing disrupted arm lymphatic channels to axillary vein tributaries. Inadequate vein length and venous back-bleeding are two technical reasons that lead to ILR procedures being aborted intraoperatively. Recently, our team began routinely harvesting a lower extremity vein graft (LEVG) for all ILR procedures to reduce our abort rate. We describe the surgical approach of an LEVG and evaluate the effects on aborted case rates and intraoperative time. A retrospective review of our institutional lymphatic database was conducted. Two hundred and forty-seven breast cancer patients were taken to the operating room for attempted ILR in the past 5 years. Prior to the use of an LEVG (n = 205), our abort rate was 14%. Since routinely performing an LEVG with ILR (n = 42), we have not aborted a single case. Despite an LEVG requiring one additional anastomosis to connect the vein graft to the native axillary vein tributary, this technique has not changed the intraoperative time for ILR procedures. In this technical contribution, we describe our early experience performing immediate lymphatic reconstruction utilizing a lower extremity vein graft. Implementation of this technique appears to have promising effects on aborted case rates without affecting intraoperative time, and greatly facilitates the lymphovenous anastomosis.

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.