BACKGROUND: Immediate lymphatic reconstruction (ILR) has been proposed to decrease lymphedema rates. The primary aim of our study was to determine whether ILR decreased the incidence of lymphedema in patients undergoing axillary lymph node dissection (ALND).
METHODS: We conducted a two-site pragmatic study of ALND with or without ILR, employing surgeon-level cohort assignment, based on breast surgeons\' preferred standard practice. Lymphedema was assessed by limb volume measurements, patient self-reporting, provider documentation, and International Classification of Diseases, Tenth Revision (ICD-10) codes.
RESULTS: Overall, 230 patients with breast cancer were enrolled; on an intention-to-treat basis, 99 underwent ALND and 131 underwent ALND with ILR. Of the 131 patients preoperatively planned for ILR, 115 (87.8%) underwent ILR; 72 (62.6%) were performed by one breast surgical oncologist and 43 (37.4%) by fellowship-trained microvascular plastic surgeons. ILR was associated with an increased risk of lymphedema when defined as ≥10% limb volume change on univariable analysis, but not on multivariable analysis, after propensity score adjustment. We did not find a statistically significant difference in limb volume measurements between the two cohorts when including subclinical lymphedema (≥5% inter-limb volume change), nor did we see a difference in grade between the two cohorts on an intent-to-treat or treatment received basis. For all patients, considering ascertainment strategies of patient self-reporting, provider documentation, and ICD-10 codes, as a single binary outcome measure, there was no significant difference in lymphedema rates between those undergoing ILR or not.
CONCLUSIONS: We found no significant difference in lymphedema rates between patients undergoing ALND with or without ILR.

UNASSIGNED: Various surgical treatments are increasingly adopted and gaining popularity for lymphedema treatment. However, challenges persist in selecting appropriate treatment modalities targeted for individual patients and achieving consensus on choice of treatment as well as outcomes. The systematic review aimed to create a treatment algorithm incorporating the latest scientific knowledge, to provide healthcare professionals and patients with a tool for informed decision-making, when selecting between treatments or combining them in a relevant manner. This systematic review evaluated and synthesized the evidence on the effectiveness of three surgical treatments for breast cancer-related lymphedema (BCRL): lymphovenous anastomosis (LVA), vascularized lymph node transfer (VLNT), and liposuction.
UNASSIGNED: We conducted a systematic search of electronic databases on 18 June 2023, including Medline, Embase, Cochrane Library, Google Scholar, and ClinicalTrials.org. Eligible studies were randomized controlled trials, non-randomized comparative studies, and observational studies that assessed the outcomes of LVA, VLNT, or liposuction in managing BCRL. The primary results of interest were changes in arm volume, lymphatic flow, and quality of life. Two independent reviewers performed the study selection and data extraction. Following this, we systematically reviewed and conducted a risk of bias assessment. Results were qualitatively presented, and a treatment algorithm was developed based on the available data.
UNASSIGNED: We identified 16,593 papers, after removal of duplicates. Following assessment of studies, 73 articles met the inclusion criteria, including 2,373 patients. We were not able to conduct a meta-analysis due to considerable heterogeneity in the methodologies and outcome measures across the studies. Liposuction appears effective for patients presenting with non-pitting lymphedema. LVA indicates variable success rate, with some evidence indicating a reduction in limb volume and symptomatic relief amongst early stages of lymphedema. VLNT showed promising results for limb volume reduction and symptom improvement in patients presenting with mild and moderate lymphedema.
UNASSIGNED: Liposuction, LVA, and VLNT seem to be effective treatments for BCRL, when targeted for the appropriate patient. Well-conducted high evidence clinical studies in the field are still lacking to uncover the efficacy of surgical treatment for BCRL.

Bioelectrical impedance analysis (BIA) as a measure of lymphedema has been gaining popularity because of its measurement simplicity and noninvasiveness. This study was performed to investigate the effectiveness of BIA for assessment of the outcomes of lymphaticovenular anastomosis (LVA) in patients with breast cancer-related lymphedema.
This study involved 25 patients with unilateral breast cancer-related lymphedema who underwent LVA. Segmental multifrequency BIA and conventional circumferential volume measurement were performed preoperatively and 6 months postoperatively from June 2018 to June 2021 at Hiroshima University Hospital International Center for Lymphedema. The patients\' clinicopathological data, operative details, and preoperative and postoperative BIA results were investigated.
Segmental multifrequency BIA and circumferential volume measurement were strongly correlated in the lymphedema-affected upper limb both before and after LVA. The interlimb volume, interlimb extracellular water ratio (r = 0.784; P < .001), and interlimb extracellular water/total body water ratio were positively correlated (r = 0.612; P < .01), whereas the phase angle was negatively associated (r = -0.556; P < .01).
Segmental multifrequency BIA can be a useful tool for assessing the severity of lymphedema and monitoring the outcomes of LVA.

In our previous study, intravenous (IV) injection of selenium alleviated breast cancer-related lymphedema (BCRL). This secondary analysis aimed to explore the metabolic effects of selenium on patients with BCRL. Serum samples of the selenium-treated (SE, n = 15) or the placebo-controlled (CTRL, n = 14) groups were analyzed by ultra-high-performance liquid chromatography with Q-Exactive Orbitrap tandem mass spectrometry (UHPLC-Q-Exactive Orbitrap/MS). The SE group showed a lower ratio of extracellular water to segmental water (ECW/SW) in the affected arm to ECW/SW in the unaffected arm (arm ECW/SW ratio) than the CTRL group. Metabolomics analysis showed a valid classification at 2-weeks and 107 differential metabolites were identified. Among them, the levels of corticosterone, LTB4-DMA, and PGE3-which are known anti-inflammatory compounds-were elevated in the SE group. Pathway analysis demonstrated that lipid metabolism (glycerophospholipid metabolism, steroid hormone biosynthesis, or arachidonic acid metabolism), nucleotide metabolism (pyrimidine or purine metabolism), and vitamin metabolism (pantothenate and CoA biosynthesis, vitamin B6 metabolism, ascorbate and aldarate metabolism) were altered in the SE group compared to the CTRL group. In addition, xanthurenic acid levels were negatively associated with whole blood selenium level (WBSe) and positively associated with the arm ECW/SW. In conclusion, selenium IV injection improved the arm ECW/SW ratio and altered the serum metabolic profiles in patients with BCRL, and improved the anti-inflammatory process in lipid, nucleotide and vitamin pathways, which might alleviate the symptoms of BCRL.

BACKGROUND: Upper-limb lymphedema is a well-known complication of breast cancer and its treatment. This retrospective cohort study aims to determine what risk factors affect breast cancer-related lymphedema in patients with breast cancer.
METHODS: This retrospective study comprised patients diagnosed with breast cancer and who underwent surgery at Wakayama Medical University Hospital between January 1, 2012 and December 31, 2018. Assessed factors using univariate and multivariate analyses were patient-related factors (age, gender, and BMI), breast cancer-related factors (tumor size, nodal status, histology, tumor location, and intrinsic subtype), and treatment-related factors (type of surgery, application, timing and regimen of chemotherapy, and application of radiotherapy).
RESULTS: This study included 1041 patients. BMI did not affect the onset of breast cancer-related lymphedema. There were only six sentinel lymph node biopsy cases in the breast cancer-related lymphedema group (6.6%). In cases of axillary lymph node dissection, adjuvant chemotherapy was marginally associated with increased risk of breast cancer-related lymphedema compared to no chemotherapy (HR 2.566; 95% CI 0.955-6.892; p = 0.0616). Among anti-cancer agents, docetaxel (HR 3.790; 95% CI 1.413-10.167; p = 0.0081) and anti-HER2 therapy (HR 2.507; 95% CI 1.083-5.803; p = 0.0318) were associated with increased risk of lymphedema according to multivariate analysis. Neo-adjuvant chemotherapy did not affect the onset of breast cancer-related lymphedema. Radiotherapy (HR 2.525; 95% CI 1.364-4.676; p = 0.0032) was an important risk factor for breast cancer-related lymphedema.
CONCLUSIONS: Axillary lymph node dissection, radiotherapy and adjuvant chemotherapy, especially docetaxel, were risk factors for breast cancer-related lymphedema, but BMI and neo-adjuvant chemotherapy were not.

Bioimpedance spectroscopy (BIS) has enabled the early identification of breast cancer-related lymphedema. In this study, differences in health service metrics and in the incidence of breast cancer-related lymphedema are evaluated in an early surveillance model of care compared with a traditional referral model of care.
In a retrospective analysis of data from 753 women who underwent BIS measures between January 1, 2007 and December 31, 2016, 188 women were assigned to the \"early surveillance\" group if they began lymphedema monitoring presurgery (n = 121) or within 90 days postsurgery (n = 67), and 285 women were assigned to the \"traditional referral\" group if they began monitoring after 90 days postsurgery. Health service metrics were calculated as the time to the first BIS measure after 90 days postsurgery, the median follow-up, and the number of health care visits. Lymphedema was diagnosed based on BIS measures.
Women in the early surveillance group received lymphedema care significantly earlier than those in the traditional referral group. However, there was no difference in the number of visits per year to the clinic between groups. Significantly more women in the traditional referral group were diagnosed with clinical lymphedema (stage I-III, 39 % vs 14%; P < .001) and with greater severity (stage II-III, 24%) compared with those in the early surveillance group (4%).
The current findings support the adoption of an early prospective surveillance model of care using BIS for the early detection and management of breast cancer-related lymphedema.

Breast cancer-related lymphedema (BCRL) is a negative sequela of breast cancer treatment, and well-established risk factors include axillary lymph node dissection (ALND) and regional lymph node radiation (RLNR). BCRL affects approximately 1 in 5 patients treated for breast cancer, and it has a significant negative impact on patients\' quality of life after breast cancer treatment, serving as a reminder of previous illness. This paper is a comprehensive review of the current evidence regarding BCRL risk factors, precautionary guidelines, prospective screening, early intervention, and surgical and non-surgical treatment techniques. Through establishing evidence-based BCRL risk factors, researchers and clinicians are better able to prevent, anticipate, and provide early intervention for BCRL. Clinicians can identify patients at high risk and utilize prospective screening programs, which incorporate objective measurements, patient reported outcome measures (PROM), and clinical examination, thereby creating opportunities for early intervention and, accordingly, improving BCRL prognosis. Innovative surgical techniques that minimize and/or prophylactically correct lymphatic disruption, such as axillary reverse mapping (ARM) and lymphatic-venous anastomoses (LVAs), are promising avenues for reducing BCRL incidence. Nonetheless, for those patients with BCRL who remain unresponsive to conservative methods like complete decongestive therapy (CDT), surgical treatment options aiming to reduce limb volume or restore lymphatic flow may prove to be palliative or corrective. It is only through a strong team-based approach that such a continuum of care can exist, and a multidisciplinary approach to BCRL screening, intervention, and research is therefore strongly encouraged.

As treatment for breast cancer improves and the threat of life-long chronic lymphedema becomes more prevalent, the need for effective screening tools emerges as crucial. This review was conducted using literature beginning in 1992 to analyze primary research testing the accuracy of bioimpedance spectroscopy as a diagnostic and early detection tool for breast cancer-related lymphedema. We concluded bioimpedance is an accurate diagnostic tool for pre-existent lymphedema, however, it has not been validated for early detection. J. Surg. Oncol. 2016;114:537-542. © 2016 Wiley Periodicals, Inc.