Publications

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.

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.

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.

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.

OBJECTIVES: Staging of upper extremity lymphedema is needed to guide surgical management, but is not standardized due to lack of accessible, quantitative, or precise measures. Here, we established an MRI-based staging system for lymphedema and validate it against existing clinical measures.

METHODS: Bilateral upper extremity MRI and lymphoscintigraphy were performed on 45 patients with unilateral secondary lymphedema, due to surgical intervention, who were referred to our multidisciplinary lymphedema clinic between March 2017 and October 2018. MRI short-tau inversion recovery (STIR) images were retrospectively reviewed. A grading system was established based on the cross-sectional circumferential extent of subcutaneous fluid infiltration at three locations, labeled MRI stage 0-3, and was compared to L-Dex®, ICG lymphography, volume, lymphedema quality of life (LYMQOL), International Society of Lymphology (ISL) stage, and lymphoscintigraphy. Linear weighted Cohen's kappa was calculated to compare MRI staging by two readers.

RESULTS: STIR images on MRI revealed a predictable pattern of fluid infiltration centered on the elbow and extending along the posterior aspect of the upper arm and the ulnar side of the forearm. Patients with higher MRI stage were more likely to be in ISL stage 2 (p = 0.002) or to demonstrate dermal backflow on lymphoscintigraphy (p = 0.0002). No correlation was found between MRI stages and LYMQOL. Higher MRI stage correlated with abnormal ICG lymphography pattern (rs = 0.63, p < 0.0001), larger % difference in limb volume (rs = 0.68, p < 0.0001), and higher L-Dex® ratio (rs = 0.84, p < 0.0001). Cohen's kappa was 0.92 (95% CI, 0.85-1.00).

CONCLUSION: An MRI staging system for upper extremity lymphedema offers an improved non-invasive precision marker for lymphedema for therapeutic planning.

KEY POINTS: • Diagnosis and staging of patients with secondary upper extremity lymphedema may be performed with non-contrast MRI, which is non-invasive and more readily accessible compared to lymphoscintigraphy and evaluation by lymphedema specialists. • MRI-based staging of secondary upper extremity lymphedema is highly reproducible and could be used for long-term follow-up of patients. • In patients with borderline clinical measurements, MRI can be used to identify patients with early-stage lymphedema.

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: Breast cancer-related lymphedema (BCRL) is one of the most significant survivorship issues in breast cancer management. Presently, there is no cure for BCRL. The single greatest risk factor for developing BCRL is an axillary lymph node dissection (ALND). Lymphatic Microsurgical Preventative Healing Approach (LYMPHA) is a surgical procedure to reduce the risk of lymphedema in patients undergoing an ALND. We present our single institution results after offering LYMPHA in the context of an established lymphedema surveillance program.

MATERIALS AND METHODS: A retrospective review of our lymphedema surveillance program at the University of Florida was performed over a 2-year period (March 2014-March 2016). LYMPHA was offered to patients undergoing ALND beginning in March 2015. Patients who developed lymphedema were compared with those who did not. Demographics and potential risk factors for development of lymphedema such as age, body mass index, clinical stage, radiotherapy, and chemotherapy were reviewed.

RESULTS: Eighty-seven patients participated in the surveillance program over the study period with an average age of 60 y (range 32-83) and body mass index of 30 kg/m2 (range 17-46). The single most significant risk factor for the development for lymphedema was an ALND (P < 0.001). One of 67 patients undergoing a sentinel lymph node biopsy developed lymphedema (1.5%). Four of 10 patients who underwent an ALND alone developed lymphedema (40%). One of 8 patients in the ALND + LYMPHA group developed transient lymphedema (12.5%).

CONCLUSIONS: Offering LYMPHA with ALND decreased our institutional rate of lymphedema from 40% to 12.5%. Long-term follow-up and randomized control trials are necessary to further elucidate the promise of this surgical technique to reduce the incidence of BCRL.

Lymphatic surgery has become an integral and flourishing component of the field of plastic surgery. The diversity of ongoing technological innovations in perioperative imaging, including intraoperative dyes and cameras, allows plastic surgeons to work at the supermicrosurgical level. This study aims to highlight innovations that have shaped and will continue to revolutionize the perioperative management of the lymphatic surgery patient in the future. As additional advances emerge, we need a systematic and objective way to evaluate the efficacy and clinical integration readiness of such technologies. Undoubtedly, these technologies will help lymphatic surgery trend toward increasing objectivity, which will be critical for continued evolution and advancement.