Publications

2021

Johnson AR, Asban A, Granoff MD, et al. Is Immediate Lymphatic Reconstruction Cost-effective?. Annals of surgery. 2021;274(6):e581-e588. doi:10.1097/SLA.0000000000003746

MINI: We conducted a cost-utility analysis to evaluate the cost and quality of life of patients undergoing axillary lymph node dissection (ALND) and ALND with regional lymph node radiation (RLNR), with and without lymphatic microsurgical preventive healing approach (LYMPHA), in a node-positive breast cancer population. We found that the addition of LYMPHA to both ALND or ALND with RLNR is more cost-effective.

OBJECTIVE: This manuscript is the first to employ rigorous methodological criteria to critically appraise a surgical preventative technique for breast cancer-related lymphedema from a cost-utility standpoint.

SUMMARY OF BACKGROUND DATA: Breast cancer-related lymphedema is a well-documented complication of breast cancer survivors in the US. In this study, we conduct a cost-utility analysis to evaluate the cost-effectiveness of the LYMPHA.

METHODS: Lymphedema rates after each of the following surgical options: (1) ALND, (2) ALND + LYMPHA, (3) ALND + RLNR, (4) ALND + RLNR + LYMPHA were extracted from a recently published meta-analysis. Procedural costs were calculated using Medicare reimbursement rates. Average utility scores were obtained for each health state using a visual analog scale, then converted to quality-adjusted life years (QALYs). A decision tree was generated and incremental cost-utility ratios (ICUR) were calculated. Multiple sensitivity analyses were performed to evaluate our findings.

RESULTS: ALND with LYMPHA was more cost-effective with an ICUR of $1587.73/QALY. In the decision tree rollback analysis, a clinical effectiveness gain of 1.35 QALY justified an increased incremental cost of $2140. Similarly, the addition of LYMPHA to ALND with RLNR was more cost-effective with an ICUR of $699.84/QALY. In the decision tree rollback analysis, a clinical effectiveness gain of 2.98 QALY justified a higher incremental cost of $2085.00.

CONCLUSIONS: Our study supports that the addition of LYMPHA to both ALND or ALND with RLNR is the more cost-effective treatment option.

Kim G, Johnson AR, Hamaguchi R, Adondakis M, Tsai LL, Singhal D. Breast Cancer-Related Lymphedema: Magnetic Resonance Imaging Evidence of Sparing Centered Along the Cephalic Vein.. Journal of reconstructive microsurgery. 2021;37(6):519-523. doi:10.1055/s-0040-1722648

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.

See also: Anatomy & Function
Granoff MD, Pardo J, Singhal D. Power-Assisted Liposuction: An Important Tool in the Surgical Management of Lymphedema Patients.. Lymphatic research and biology. 2021;19(1):20-22. doi:10.1089/lrb.2020.0115

Background: Debulking via power-assisted liposuction has been established internationally as the gold standard for patients with chronic fat-dominant lymphedema. In this study we share our experience implementing a debulking surgery program in the United States. Methods and Results: A retrospective review was performed of patients who underwent debulking surgery using power-assisted liposuction at a single institution. Between December 2017 and January 2020, 39 patients with lymphedema underwent 41 extremity debulking procedures. In patients with lymphedema of the upper extremity, median excess volume reduction was 111% at 6 months and 116% at 12 months post-operatively. In patients with lymphedema of the lower extremity, excess volume reduction was 82% at 6 months and 115% at 12 months post-operatively. L-Dex and quality of life improved across all domains in upper and lower extremity patients as well. Conclusion: Debulking with power-assisted liposuction is an effective treatment for chronic lymphedema, supported by improvement in both objective and subjective metrics.

Chang D, Dayan J, Fried P, et al. Establishing Standards for Centers of Excellence for the Diagnosis and Treatment of Lymphatic Disease.. Lymphatic research and biology. 2021;19(1):4-10. doi:10.1089/lrb.2020.0022

Background: Lymphatic disease patients make up a significant proportion of the US and world populations. Due to inadequate medical school training and underestimation of the impact of lymphatic circulation, lymphatic disease patients often have difficulty finding competent diagnosis and care. Methods and Results: The Lymphatic Education & Research Network has initiated a Centers of Excellence program to designate institutions that provide services for lymphatic disease patients. Committees of experts drafted standards for five types of Centers of Excellence. Conclusions: The Centers of Excellence program is now launched, and the description of the formation process herein could provide other organizations guidance for similar ventures.

Johnson AR, Fleishman A, Granoff MD, et al. Evaluating the Impact of Immediate Lymphatic Reconstruction for the Surgical Prevention of Lymphedema.. Plastic and reconstructive surgery. 2021;147(3):373e-381e. doi:10.1097/PRS.0000000000007636

BACKGROUND: Breast cancer-related lymphedema affects one in five patients. Its risk is increased by axillary lymph node dissection and regional lymph node radiotherapy. The purpose of this study was to evaluate the impact of immediate lymphatic reconstruction or the lymphatic microsurgical preventative healing approach on postoperative lymphedema incidence.

METHODS: The authors performed a retrospective review of all patients referred for immediate lymphatic reconstruction at the authors' institution from September of 2016 through February of 2019. Patients with preoperative measurements and a minimum of 6 months' follow-up data were identified. Medical records were reviewed for demographics, cancer treatment data, intraoperative management, and lymphedema incidence.

RESULTS: A total of 97 women with unilateral node-positive breast cancer underwent axillary nodal surgery and attempt at immediate lymphatic reconstruction over the study period. Thirty-two patients underwent successful immediate lymphatic reconstruction with a mean patient age of 54 years and body mass index of 28 ± 6 kg/m2. The median number of lymph nodes removed was 14 and the median follow-up time was 11.4 months (range, 6.2 to 26.9 months). Eighty-eight percent of patients underwent adjuvant radiotherapy of which 93 percent received regional lymph node radiotherapy. Mean L-Dex change was 2.9 units and mean change in volumetry by circumferential measurements and perometry was -1.7 percent and 1.3 percent, respectively. At the end of the study period, we found an overall 3.1 percent rate of lymphedema.

CONCLUSION: Using multiple measurement modalities and strict follow-up guidelines, the authors' findings support that immediate lymphatic reconstruction at the time of axillary surgery is a promising, safe approach for lymphedema prevention in a high-risk patient population.

CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Coriddi M, Mehrara B, Skoracki R, Singhal D, Dayan JH. Immediate Lymphatic Reconstruction: Technical Points and Literature Review.. Plastic and reconstructive surgery. Global open. 2021;9(2):e3431. doi:10.1097/GOX.0000000000003431

Recent studies have provided evidence that lymphovenous bypass-microsurgical re-routing of divided lymphatics to an adjacent vein-performed at the time of lymph node dissection decreases the rate of lymphedema development. Immediate lymphatic reconstruction in this setting is technically demanding, and there is a paucity of literature describing the details of the surgical procedure. In this report, we review the literature supporting immediate lymphatic reconstruction and provide technical details to demystify the operation for surgeons who wish to provide this option to their patients.

Sekigami Y, Char S, Mullen C, et al. Cost-Effectiveness Analysis: Lymph Node Transfer vs Lymphovenous Bypass for Breast Cancer-Related Lymphedema.. Journal of the American College of Surgeons. 2021;232(6):837-845. doi:10.1016/j.jamcollsurg.2021.02.013

BACKGROUND: Lymph node transfer (LNT) and lymphovenous bypass (LVB) have been described as 2 major surgical options for patients with breast cancer-related lymphedema (BCRL) who have failed conservative therapy. The objective of our study was to perform a cost-effectiveness analysis comparing LNT and LVB for the treatment of BCRL.

STUDY DESIGN: Rates of infection, lymph leak, and failure of LNT and LVB were obtained from a previously published meta-analysis. Failure of surgery was defined as the inability to cease compression therapy postoperatively. Procedural costs were calculated from Medicare reimbursement rates. Cost of conservative management of postoperative surgical site infection, lymph leak, and continued decongestive physiotherapy after failed surgery were obtained from literature review. Average utility scores for each health state were calculated using a visual analog scale survey, then converted to quality-adjusted life years (QALYs). A decision tree was constructed, and incremental cost-effectiveness ratio was assessed at $50,000/QALY. Deterministic and probabilistic sensitivity analyses were performed to evaluate the robustness of our findings.

RESULTS: LNT was less costly ($22,492 vs $31,927) and more effective (31.82 QALY vs 29.24 QALY) than LVB. One-way (deterministic) sensitivity analysis demonstrated that LNT became cost-ineffective when its failure rate was more than 43.8%. LVB became more cost-effective than LNT when its failure rate was less than 21.4%. Probabilistic sensitivity analysis using Monte-Carlo simulation indicated that even with uncertainty present in the variables analyzed, the majority of simulations (97%) favored LNT as the more cost-effective strategy.

CONCLUSIONS: LNT is a dominant, cost-effective strategy compared to LVB for the treatment of BCRL.

Kim G, Donohoe K, Smith MP, et al. Use of non-contrast MR in diagnosing secondary lymphedema of the upper extremities.. Clinical imaging. 2021;80:400-405. doi:10.1016/j.clinimag.2021.08.018

PURPOSE: The purpose of the study is to determine if a combination of dermal thickening and subcutaneous fluid honeycombing on non-contrast MRI, termed the dermal rim sign (DRS), can be diagnostically analogous to dermal backflow seen on lymphoscintigraphy in patients with secondary upper extremity lymphedema.

MATERIALS AND METHODS: Upper extremity MRI and lymphoscintigraphy were performed on patients referred to a multidisciplinary lymphedema clinic for suspicion of secondary lymphedema. Sensitivity, specificity, and positive and negative predictive values of DRS on MRI in detecting dermal backflow on lymphoscintigraphy and the correlation between DRS, Indocyanine Green (ICG) lymphography, bioimpedence L-Dex® ratio and MRI Lymphedema Staging were calculated. Weighted interobserver agreements on the presence and location of DRS on MRI were calculated.

RESULTS: Of the 45 patients in the study, 91.1% (41/45) of patients had history of breast cancer. The average age was 58.4 ± 10.5 years, with a mean symptom duration of 4.7 ± 4.4 years. The mean BMI was 30.5 ± 7.0 kg/m2. Interobserver agreement on the presence and the extent of DRS on MRI was 0.93 [95% confidence-interval: 0.80-1]. DRS was present in 97% (32/33) of patients who demonstrated dermal backflow on lymphoscintigraphy. Sensitivity, specificity, PPV, and NPV of DRS were 96.6% [81.7%-99.9%], and 75.0% [47.6%-92.7%], 87.5% [74.9%-94.3%], and 92.3% [63.1%-98.8%]. DRS was associated with severity on ICG lymphography and bioimpedance (both p < 0.001).

CONCLUSIONS: DRS on non-contrast MRI is highly predictive of dermal backflow and correlates with clinical measures of lymphedema severity. DRS may be used as an independent diagnostic biomarker to identify patients who would benefit from dedicated exams.