Publications

2023

Johnson AR, Otenti D, Bates KD, et al. Creating a Policy for Coverage of Lymphatic Surgery: Addressing a Critical Unmet Need.. Plastic and reconstructive surgery. 2023;152(1):222-234. doi:10.1097/PRS.0000000000010239

This article describes the key stakeholders and process involved in developing an insurance policy in the United States to establish medical necessity criteria for lymphatic surgery procedures. Lymphedema is a chronic health issue that impacts over 1.2 million patients and is associated with lifelong health, economic, and psychosocial costs. Patients affected have been described as "medical nomads," as they often interface with multiple providers before receiving an accurate diagnosis and treatment. This underscores the lack of attention and understanding about this disease across all sectors of the medical system. Unlike nations including Sweden and the United Kingdom, which provide insurance coverage for treatment, the United States has lagged behind. As a country, we have neglected to fully recognize the consequences of inadequate treatment of lymphedema, including chronic morbidities such as loss of mobility, psychosocial sequelae, recurrent infections, and even death. Recently, the authors' lymphatic center had the unique opportunity to help develop a policy that merged their clinical experience, recently established lymphatic care center of excellence criteria, and third-party payer policy expertise. This experience spanned 1 year from June of 2018 to June of 2019. The authors identify how key partnerships helped fill evidentiary gaps that ultimately resulted in policy change.

Granoff MD, Pardo J, Shillue K, et al. Variable Anatomy of the Lateral Upper Arm Lymphatic Channel: An Anatomical Risk Factor for Breast Cancer-Related Lymphedema.. Plastic and reconstructive surgery. 2023;152(2):422-429. doi:10.1097/PRS.0000000000010245

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.

See also: Anatomy & Function

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.

See also: Anatomy & Function
Granoff MD, Fleishman A, Shillue K, et al. A 4-Year Institutional Experience of Immediate Lymphatic Reconstruction.. Plastic and reconstructive surgery. 2023;152(5):773e-778e. doi:10.1097/PRS.0000000000010381

BACKGROUND: Up to one in three patients may go on to develop breast cancer-related lymphedema (BCRL) after treatment. Immediate lymphatic reconstruction (ILR) has been shown in early studies to reduce the risk of BCRL, but long-term outcomes are limited because of its recent introduction and institutions' differing eligibility requirements. This study evaluated the incidence of BCRL in a cohort that underwent ILR over the long term.

METHODS: A retrospective review of all patients referred for ILR at the authors' institution from September of 2016 through September of 2020 was performed. Patients with preoperative measurements, a minimum of 6 months of follow-up data, and at least one completed lymphovenous bypass were identified. Medical records were reviewed for demographics, cancer treatment data, intraoperative management, and lymphedema incidence.

RESULTS: A total of 186 patients with unilateral node-positive breast cancer underwent axillary nodal surgery and an attempt at ILR over the study period. Ninety patients underwent successful ILR and met all eligibility criteria, with a mean patient age of 54 ± 12.1 years and median body mass index of 26.6 kg/m 2 [interquartile range (IQR), 24.0 to 30.7 kg/m 2 ]. The median number of lymph nodes removed was 14 (IQR, eight to 19). Median follow-up was 17 months (range, 6 to 49 months). Eighty-seven percent of patients underwent adjuvant radiotherapy, and among them, 97% received regional lymph node irradiation. The overall rate of lymphedema was 9% at the end of the study period.

CONCLUSIONS: With the use of strict follow-up guidelines over the long term, the authors' findings support that ILR at the time of axillary lymph node dissection is an effective procedure that reduces the risk of BCRL in a high-risk patient population.

CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Bustos VP, Friedman R, Pardo JA, Granoff M, Fu MR, Singhal D. Tracking Symptoms of Patients With Lymphedema Before and After Power-Assisted Liposuction Surgery.. Annals of plastic surgery. 2023;90(6):616-620. doi:10.1097/SAP.0000000000003430

PURPOSE: Lymphedema negatively impacts patients from a psychosocial standpoint and consequently affects patient's quality of life. Debulking procedures using power-assisted liposuction (PAL) are currently deemed an effective treatment for fat-dominant lymphedema and improves anthropometric measurements as well as quality of life. However, there have been no studies specifically evaluating changes in symptoms related to lymphedema after PAL. An understanding of how symptoms change after this procedure would be valuable for preoperative counseling and to guide patient expectations.

METHODS: A cross-sectional study was performed in patients with extremity lymphedema who underwent PAL from January 2018 to December 2020 at a tertiary care facility. A retrospective chart review and follow-up phone survey were conducted to compare signs and symptoms related to lymphedema before and after PAL.

RESULTS: Forty-five patients were included in this study. Of these, 27 patients (60%) underwent upper extremity PAL and 18 patients (40%) underwent lower extremity PAL. The mean follow-up time was 15.5±7.9 months. After PAL, patients with upper extremity lymphedema reported having resolved heaviness (44%), as well as improved achiness (79%) and swelling (78%). In patients with lower extremity lymphedema, they reported having improved all signs and symptoms, particularly swelling (78%), tightness (72%), and achiness (71%).

CONCLUSIONS: In patients with fat-dominant lymphedema, PAL positively impacts patient-reported outcomes in a sustained fashion over time. Continuous surveillance of postoperative studies is required to elucidate factors independently associated with the outcomes found in our study. Moreover, further studies using a mixed method approach will help us better understand patient's expectations to achieve informed decision and adequate treatment goals.

Friedman R, Johnson AR, Shillue K, et al. Acupuncture Treatment for Breast Cancer-Related Lymphedema: A Randomized Pilot Study.. Lymphatic research and biology. 2023;21(5):488-494. doi:10.1089/lrb.2022.0001

Background: Methods of conservative management for breast cancer-related lymphedema (BCRL) are burdensome in terms of time, cost, and convenience. In addition, many patients are not candidates for surgical treatment. Preliminary results have demonstrated possible beneficial effects of acupuncture for patients with BCRL. In this small pilot study, we examined the safety and feasibility of an acupuncture randomized control trial (RCT) in this patient cohort, utilizing a battery of standardized clinical and patient-centered outcome measures. Methods and Results: Patients with BCRL were randomized 2:1 to the acupuncture (n = 10) or the control (n = 4) group. Patients received acupuncture to the unaffected extremity biweekly for 6 weeks. Feasibility was defined as enrollment ≥80%, completion of ≥9 of 12 acupuncture sessions per person, and ≥75% completion of three of three measurement visits. To inform a future adequately powered RCT, we describe within-group changes in patient-centered outcomes, including circumferential measurements, bioimpedance spectroscopy, perometry, cytokine levels, and patient quality of life. Adverse events were systematically tracked. Fourteen patients completed the study. Of those who received acupuncture (n = 10), 8 completed all 12 acupuncture sessions, and 2 patients completed 11 sessions. Ninety-three percent of all participants completed all three measurement visits. There was no consistent improvement in arm volumes. Inflammatory marker levels had inconclusive fluctuations among both groups. All patients receiving acupuncture demonstrated an improvement in their functional quality-of-life score. No severe adverse events occurred. Conclusions: A randomized controlled study of acupuncture for BCRL is feasible. The acupuncture intervention is acceptable in this population, without safety concerns in a small sample and warrants further investigation.

Spiegel DY, Willcox J, Friedman R, Kinney J, Singhal D, Recht A. A Prospective Study of Radiation Therapy After Immediate Lymphatic Reconstruction: Analysis of the Dosimetric Implications.. International journal of radiation oncology, biology, physics. 2023;117(2):446-451. doi:10.1016/j.ijrobp.2023.04.027

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.

Friedman R, Spiegel DY, Kinney J, Willcox J, Recht A, Singhal D. Quantifying radiation in the axillary bed at the site of lymphedema surgical prevention.. Breast cancer research and treatment. 2023;201(2):299-305. doi:10.1007/s10549-023-06988-y

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.