Lymphedema Rates Following Axillary Lymph Node Dissection With and Without Immediate Lymphatic Reconstruction: A Prospective Trial.

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. CONCLUSION: We found no significant difference in lymphedema rates between patients undergoing ALND with or without ILR.

Axillary Reverse Mapping Aids in Reducing the Rates of Breast Cancer-Related Lymphedema in Underserved Ethnically Diverse Population.

BACKGROUND: Breast cancer-related lymphedema (BCRL) poses a significant risk following sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND), particularly affecting ethnic minorities, with a twofold increased risk. Axillary reverse mapping (ARM), a novel technique, shows potential in reducing BCRL rates, yet its utility in ethnic minorities lacks sufficient exploration. Therefore, our study aims to investigate the utility and outcomes of ARM on BCRL in an ethnic diverse group. METHODS: A retrospective chart review of ARM patients from January 2019 to July 2022 was conducted, monitoring patients over 24 months at 3-month intervals using SOZO® scores, with comparisons with preoperative baselines. RESULTS: Of the 212 patients, 83% belonged to ethnic minorities. SLNB was performed in 83%, ALND in 17%, and 62.3% underwent radiation therapy. Positive lymph nodes were found in 31.6%, with 22.2% exhibiting blue nodes and 25.9% exhibiting blue lymphatics. Of identified blue nodes, 70.2% were excised, including 51.5% crossover nodes. Lymphedema occurred in 3 patients, resulting in a BCRL rate of 1.4%. Compared with an historical BCRL incidence of 40.4% following ALND in ethnic minorities, our study reported a significantly lower rate of 8% (p < 0.001). CONCLUSION: The ARM procedure can significantly lower BCRL in ethnic minority groups. The combination of ARM and bioimpedance spectroscopy led to a remarkably low BCRL rate of 1.4%. Notably, none of the patients in our study developed an axillary recurrence at 24-month follow-up. Nevertheless, future studies with larger sample sizes are warranted to better understand the utility of the ARM technique in this population.

Evaluation of Circulating MicroRNAs and Adipokines in Breast Cancer Survivors with Arm Lymphedema.

Breast cancer-related lymphedema (BCRL) is a form of secondary lymphedema that is characterized by abnormal swelling of one or both arms due to the accumulation of lymph fluid in the interstitial tissue spaces, resulting from obstruction of the lymphatic vessels due to surgery insults, radiotherapy, or chemotherapy. Due to the multifactorial nature of this condition, the pathogenesis of secondary lymphedema remains unclear and the search for molecular factors associated with the condition is ongoing. This study aimed to identify serum microRNAs and adipokines associated with BCRL. Blood was collected from 113 breast cancer survivors and processed to obtain serum for small RNA-sequencing (BCRL vs. non-BCRL, n = 7 per group). MicroRNAs that were differentially expressed (fold change >1.5, p < 0.05) between lymphedema cases and those without lymphedema were further quantified in a validation cohort through quantitative reverse transcription PCR (BCRL n = 16, non-BCRL, n = 83). Leptin and adiponectin levels were measured in a combined cohort (BCRL n = 23, non-BCRL n = 90) using enzyme-linked immunosorbent assays. Two of the most significantly upregulated microRNAs, miR-199a-3p and miR-151a-3p, were strongly correlated with the onset of lymphedema and diabetes mellitus in the BCRL group. Leptin levels were higher in the BCRL cohort compared to the non-BCRL cohort (p < 0.05). A metabolic syndrome biomarker, the adiponectin/leptin ratio, was found to be lower in the BCRL group than in the non-BCRL group (median: 0.28 vs. 0.41, p < 0.05). Extensive studies on the mechanisms of the identified microRNAs and association of leptin with arm lymphedema may provide new insights on the potential biomarkers for lymphedema that should be followed up in a prospective cohort study.

Early surveillance is associated with less incidence and severity of breast cancer-related lymphedema compared with a traditional referral model of care.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Acupuncture for breast cancer-related lymphedema: a randomized controlled trial.

PURPOSE: Approximately 20% of breast cancer survivors develop breast cancer-related lymphedema (BCRL), and current therapies are limited. We compared acupuncture (AC) to usual care wait-list control (WL) for treatment of persistent BCRL. METHODS: Women with moderate BCRL lasting greater than six months were randomized to AC or WL. AC included twice weekly manual acupuncture over six weeks. We evaluated the difference in circumference and bioimpedance between affected and unaffected arms. Responders were defined as having a decrease in arm circumference difference greater than 30% from baseline. We used analysis of covariance for circumference and bioimpedance measurements and Fisher's exact to determine the proportion of responders. RESULTS: Among 82 patients, 73 (89%) were evaluable for the primary endpoint (36 in AC, 37 in WL). 79 (96%) patients received lymphedema treatment before enrolling in our study; 67 (82%) underwent ongoing treatment during the trial. We found no significant difference between groups for arm circumference difference (0.38 cm greater reduction in AC vs. WL, 95% CI - 0.12 to 0.89, p = 0.14) or bioimpedance difference (1.06 greater reduction in AC vs. WL, 95% CI - 5.72 to 7.85, p = 0.8). There was also no difference in the proportion of responders: 17% AC versus 11% WL (6% difference, 95% CI - 10 to 22%, p = 0.5). No severe adverse events were reported. CONCLUSIONS: Our acupuncture protocol appeared to be safe and well tolerated. However, it did not significantly reduce BCRL in pretreated patients receiving concurrent lymphedema treatment. This regimen does not improve upon conventional lymphedema treatment for breast cancer survivors with persistent BCRL.

A comprehensive review of bioimpedance spectroscopy as a diagnostic tool for the detection and measurement of breast cancer-related lymphedema.

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.

Effect of Kinesiology Taping on Breast Cancer-Related Lymphedema: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PURPOSE: The objective of this systematic review and meta-analysis was to evaluate the impact of kinesiology taping on individuals suffering from breast cancer-related lymphedema. METHODS AND METHODS: We conducted a comprehensive search in PubMed, Cochrane Library, and Embase databases, spanning from their inception date to December 20, 2023, to identify pertinent studies. Inclusion criteria comprised studies that (1) enrolled participants diagnosed with breast cancer-related lymphedema; (2) implemented kinesiology taping as the intervention; (3) incorporated either complete decongestive therapy, exercise, or sham taping as the control treatment; and (4) included clinical measurements such as the severity of lymphedema, upper limb function assessment, quality of life, and perceived comfort. RESULTS: Information was extracted from 14 randomized controlled trials (RCTs). The analyses demonstrated statistically significant improvement, indicating a preference for kinesiology taping in the outcomes of upper limb functional assessment (standardized mean difference [SMD] = -0.88, 95% confidence interval [CI]: [-1.22, -0.55]), quality of life (SMD = 0.50, 95% CI: [0.16, 0.84]), and perceived comfort (SMD = 0.85, 95% CI: [0.34, 1.36]). CONCLUSION: The findings suggest that kinesiology taping could be considered a viable option for individuals dealing with breast cancer-related lymphedema. Nevertheless, acknowledging certain limitations within this study, further confirmation of its benefits necessitates additional larger-scale and better-designed RCTs.

Conservative medical intervention as a complement to CDT for BCRL therapy: a systematic review and meta-analysis of randomized controlled trials.

Background: The effect of first-line complex decongestive therapy (CDT) for breast cancer-related lymphedema (BCRL) depending on various factors forces patients to seek additional treatment. Therefore, this meta-analysis was conducted to evaluate the effect of different conservative medical interventions as a complement to CDT. This is the first meta-analysis that includes various kinds of conservative treatments as adjunctive therapy to get broader knowledge and improve practical application value, which can provide recommendations to further improve BCRL patients' health status. Methods: RCTs published before 18 December 2023 from PubMed, Embase, Cochrane Library, and Web of Science databases were searched. RCTs that compared the effects of conservative medical intervention were included. A random-effects or fixed-effects model was used based on the heterogeneity findings. Study quality was evaluated using the Cochrane risk of bias tool. Results: Sixteen RCTs with 690 participants were included, comparing laser therapy, intermittent pneumatic compression (IPC), extracorporeal shock wave therapy (ESWT), electrotherapy, ultrasound, diet or diet in combination with synbiotic supplement, traditional Chinese medicine (TCM), continuous passive motion (CPM), and negative pressure massage treatment (NMPT). The results revealed that conservative medical intervention as complement to CDT had benefits in improving lymphedema in volume/circumference of the upper extremity [SMD = -0.30, 95% CI = (-0.45, -0.15), P < 0.05, I 2 = 51%], visual analog score (VAS) for pain [SMD = -3.35, 95% CI (-5.37, -1.33), P < 0.05, I 2 = 96%], quality of life [SMD = 0.44, 95% CI (0.19, 0.69), P < 0.05, I 2 = 0], and DASH/QuickDASH [SMD = -0.42, 95% CI (-0.70, -0.14), P < 0.05, I 2 = 10%] compared with the control group. Subgroup analysis revealed that laser therapy and electrotherapy are especially effective (P < 0.05). Conclusion: Combining conservative medical interventions with CDT appears to have a positive effect on certain BCRL symptoms, especially laser therapy and electrotherapy. It showed a better effect on patients under 60 years old, and laser therapy of low to moderate intensity (5-24 mW, 1.5-2 J/cm2) and of moderate- to long-term duration (≥36-72 sessions) showed better effects. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=354824, identifier CRD42022354824.

Breast Cancer-Related Lymphedema Assessed via Tissue Dielectric Constant Measurements.

This review describes the use of tissue dielectric constant (TDC) measurements mainly in the assessment of breast cancer-related lymphedema (BCRL). PubMed, Web of Science, and EMBASE databases were initially searched using criteria that included the terms "dielectric" and "lymphedema." The initial search yielded a total of 131 titles. After removing studies not focused on upper extremity lymphedema, 56 articles remained. These articles, together with relevant articles from their bibliographies, formed the basis of the review. The findings show the potential utility and applications of TDC measurements to help detect and track BCRL, whether present in limbs, breasts, or trunks. It is reported as a non-invasive, simple-to-use method, with each measurement requiring less than 10 seconds, suggesting its practicality and useability as an in-office or in-clinic screening and tracking method. Although there are various ways to quantitatively evaluate lymphedema, most, if not all, are restricted to measurements on limbs. Thus, one significant advantage of the TDC approach is that almost any local region of interest can be effectively measured and tracked, which, for BCRL, could include specific regions of arms or hands, breasts, and truncal areas.

Breast Cancer-related Lymphedema: Recent Updates on Clinical Efficacy of Therapies and Bioengineering Approaches for a Personalized Therapy.

BACKGROUND: Post-mastectomy lymphedema is a chronic progressive disease characterized by a significant reduction in quality of life and a range of complications. AIM: To this date, no single treatment method provides pathological correction of the mechanisms associated with tissue reorganization observed in later-stage breast cancer-related lymphedema (BCRL). METHODS: To define a personalized approach to the management of patients with iatrogenic lymphedema, we performed a systematic review of literature without a comprehensive meta-analysis to outline existing molecular- genetic patterns, overview current treatment methods and their efficacy, and highlight the specific tissue-associated changes in BCRL conditions and other bio-engineering approaches to develop personalized therapy. RESULTS: Our results show that several tissue-specific and pathological molecular markers may be found, yet current research does not aim to define them. CONCLUSION: As such, currently, a strong foundation for further research into molecular-genetic changes in lymphedema tissue exists, and further research should focus on finding specific targets for personalized treatment through bio-engineering approaches.

Surgical treatment algorithm for breast cancer lymphedema-a systematic review.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Comprehensive strategies in breast cancer-related lymphedema prevention: insights from a multifaceted program.

Background: Breast cancer-related lymphedema (BCRL) profoundly impacts patients' quality of life, causing heightened depression, anxiety, and physical limitations. Surgical removal of the axillary nodes, combined with radiation therapy, is a significant risk factor for BCRL. Smarter axillary surgery, coupled with early detection and fostering lymphedema education, significantly improves BCRL management, promoting timely diagnosis and treatment. A lymphedema prevention program encompassing all these factors can significantly aid in preventing, treating, and reducing the severity of BCRL cases. Therefore, our study aims to share our insights and experiences gained from implementing a lymphedema prevention program at our institution. Methods & Results: At our institution, axillary reverse mapping (ARM) is performed on all patients undergoing axillary surgery. We surveil these patients with pre- and postoperative SOZO® measurements using bioimpedance spectroscopy to detect sub-clinical lymphedema. Concerning education, we use a 3-pronged approach with surgeons, nurse practitioners, and video representation for patients. We have had 212 patients undergo the ARM procedure since 2019, with three (1.41%) developing persistent lymphedema. Conclusion: Our study underscores the significance of a comprehensive lymphedema prevention program, integrating smarter axillary surgery, early detection, and patient education. The lymphedema rate of 1.41% not only validates the success rate of these interventions but also advocates for their widespread adoption to enhance the holistic care of breast cancer survivors. As we continue to refine and expand our program, further research, and long-term follow-up are crucial to improve prevention strategies continually and enhance the overall well-being of individuals at risk of BCRL.

Complete Decongestive Therapy Effect on Breast Cancer Related to Lymphedema: A Systemic Review and Meta-Analysis of Randomized Controlled Trials.

PURPOSE: To review and analyze critically the available evidence for Complete Decongestive Therapy Effect on Breast Cancer Related to Lymphedema. DATA SOURCES: Publications were retrieved from the major database search engines, included  Google scholar, EBSCO host, and PubMed database. The search terms including: "Complete decongestive therapy (CDT)", "breast cancer", "Breast cancer related to lymphedema (BCRL)" "breast surgery" and "mastectomy". STUDY SELECTION: The studies were initially selected based on keywords associated with inclusion criteria. Then, articles were chosen based on their titles. Then, based on the fill text and design, randomized control with a comprehensive description of the outcomes. The authors analyzed 3,181 articles, of which 15 randomized controlled trials met inclusion criteria with no publication date constraint. DATA EXTRACTION: Each article's authors, nations, participants, outcomes variables, measuring instruments, intervention technique and follow-up, outcomes, and results were retrieved. After reaching consensus among authors, study quality was evaluated using the Jadad scale, and risk of bias was determined using the Cochrane Rob2 tool. DATA SYNTHESIS: The levels of evidence were of excellent quality. The retrieved articles were of "high" methodological caliber. The major outcome variables were in QOL, pain, ROM and edema. The effect size of CDT on QOL was 2.347 (95% CI: -1.41, 6.11) (p=0.22). Pain was -0.068 (95% CI: -35.21) (p=0.64). ROM was 0.324 (95% CI: -0.44,0.09) (p=0.41) and edema was -2.9 (95% -1.53,1.11) (p=0.76). CONCLUSIONS: The CDT is still recommended as the primary therapy for BCRL and is regarded the most practical and cost-effective treatment for BCRL. This result recommends patients to perform CDT to improve their QOL, ROM, and to lessen pain and edema volume. To improve the body of evidence supporting the effectiveness of the CDT on BCRL, additional trials with bigger sample sizes, longer follow-ups, blindness outcomes, and patient compliance evaluations are required.

Bioelectrical impedance analysis in patients with breast cancer-related lymphedema before and after lymphaticovenular anastomosis.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Segmental multifrequency BIA can be a useful tool for assessing the severity of lymphedema and monitoring the outcomes of LVA.

Medical Applications of Skin Tissue Dielectric Constant Measurements.

Tissue dielectric constant (TDC) values assess certain skin properties that are dependent on multiple factors but mainly on the relative amount of water content within a locally measured tissue volume. Because of the non-invasive nature of these measurements and their ease of use, the method has been widely used in various medically related applications. The goal of this paper was to review and describe the uses and findings of such TDC measurements, considering and including the wide array of medical applications. The review is in part based on information derived from an analysis of published material obtained via literature searches of four major electronic databases and, in part, based on the author's experience with the TDC measurement methods and their various applications and his professional experiences. The databases searched were PubMed, Web of Science, EMBASE, and CINAHL Complete. Based on the initial search criteria, a total of 1257 titles were identified. After removing duplicates and filtering according to relevancy, 160 remained for detailed further review. In some cases, the bibliography of these retrieved articles provided additional sources. The findings demonstrate multiple research and medical uses and applications of TDC measurements, focusing on detecting and quantifying localized edema and lymphedema in multiple target sites. These include the upper and lower extremities, breasts, and trunk as regions involved in medical conditions causing lymphedema. In addition, the findings suggest that TDC evaluations are a convenient, non-invasive method to study and evaluate other conditions impacting skin, including diabetes mellitus and skin wounds or ulcers. Its ability to detect aspects of tissue changes simply and rapidly at almost any anatomical location makes it a useful tool for investigating multiple dermatological conditions and their treatment as future applications of this method.

Relationship between Viscoelastic Properties of Tissues and Bioimpedance Spectroscopy in Breast-Cancer-Related Lymphedema.

The aim of this study was to assess the relationship between the viscoelastic properties of tissues and breast-cancer-related lymphedema (BCRL). After a mastectomy, 46 females were allocated into a lymphedema group (L; n = 15, lymphedema occurred) and a control group (C; n = 31, lack of lymphedema). Bioimpedance spectroscopy was used to test BCRL. The mechanical properties of the tissues in both upper limbs were tested using myotonometry. In group L, tone, stiffness, relaxation time, and creep measured on the biceps brachii of the impaired limb significantly differed from the results on the unimpaired limb. In group C, the differences were not significant. Moreover, both tone and stiffness were inversely correlated with the level of lymphedema (r = -0.72 and r = -0.88, respectively), and both relaxation and creep were significantly related to the level of lymphedema (r = 0.71 and r = 0.59, respectively), when myotonometry was completed on the biceps brachii of the impaired limb in group L. The relationships were not significant in group C. Measurements of viscoelastic properties can provide useful information concerning lymphedema. Our findings suggest that significant correlations between selected mechanical properties of the tissues and BCRL can be used in BCRL detection and treatment.

Phase 1 Lymfactin® Study: 24-month Efficacy and Safety Results of Combined Adenoviral VEGF-C and Lymph Node Transfer Treatment for Upper Extremity Lymphedema.

BACKGROUND: Lymphedema is a common problem after breast cancer treatment. Lymfactin® is a prolymphangiogenic growth factor vector inducing the expression of human vascular endothelial growth factor C (VEGF-C). It promotes growth and repair of lymphatic vessels. METHODS: Lymfactin® was combined with microvascular lymph node transfer surgery (VLNT) to study the safety and efficacy of the treatment in breast cancer-related upper limb lymphedema (BCRL) patients. This is a continuation study with a 3 year efficacy and 5 year safety follow-up. RESULTS: Fifteen patients were recruited in the study between June 2016 and February 2018. Three patients received a lower dose (1 × 1010 viral particles (vp)), and 12 patients received a higher dose (1 × 1011 vp) of Lymfactin®, respectively. In the higher dose group, the reduction of excess arm volume was on average 46% after the 12 month follow-up, and the transport index was improved in 7/12 patients. At baseline, removal of the compression garment for 7 days resulted in significant arm swelling (105.7±161.0 ml, p=0.0253). However, at 12 months, there was less and not significant swelling after removal of the garment (84.4±143.0 ml, p=0.0682). Lymphedema Quality of Life Inventory (LQOLI or LyQLI) questionnaire showed significant and sustained improvement of quality of life. CONCLUSIONS: During 24 months' of follow-up, the results indicate that Lymfactin® is well tolerated. The most promising findings were a 46% reduction in excess arm volume and a nonsignificant volume increase after garment removal at 12 months, suggesting that there is potential for the reduction of lymphedema.

Assessment of Potential Risk Factors and Skin Ultrasound Presentation Associated with Breast Cancer-Related Lymphedema in Long-Term Breast Cancer Survivors.

Breast cancer has been reported to have the highest survival rate among various cancers. However, breast cancer survivors face several challenges following breast cancer treatment including breast cancer-related lymphedema (BCRL), sexual dysfunction, and psychological distress. This study aimed to investigate the potential risk factors of BCRL in long term breast cancer survivors. A total of 160 female breast cancer subjects were recruited on a voluntary basis and arm lymphedema was assessed through self-reporting of diagnosis, arm circumference measurement, and ultrasound examination. A total of 33/160 or 20.5% of the women developed BCRL with significantly higher scores for upper extremity disability (37.14 ± 18.90 vs. 20.08 ± 15.29, p < 0.001) and a lower score for quality of life (103.91 ± 21.80 vs. 115.49 ± 16.80, p = 0.009) as compared to non-lymphedema cases. Univariate analysis revealed that multiple surgeries (OR = 5.70, 95% CI: 1.21-26.8, p < 0.001), axillary lymph nodes excision (>10) (OR = 2.83, 95% CI: 0.94-8.11, p = 0.047), being overweight (≥25 kg/m2) (OR = 2.57, 95% CI: 1.04 - 6.38, p = 0.036), received fewer post-surgery rehabilitation treatment (OR = 2.37, 95% CI: 1.05-5.39, p = 0.036) and hypertension (OR = 2.38, 95% CI: 1.01-5.62, p = 0.043) were associated with an increased risk of BCRL. Meanwhile, multivariate analysis showed that multiple surgeries remained significant and elevated the likelihood of BCRL (OR = 5.83, 95% CI: 1.14-29.78, p = 0.034). Arm swelling was more prominent in the forearm area demonstrated by the highest difference of arm circumference measurement when compared to the upper arm (2.07 ± 2.48 vs. 1.34 ± 1.91 cm, p < 0.001). The total of skinfold thickness of the affected forearm was also significantly higher than the unaffected arms (p < 0.05) as evidenced by the ultrasound examination. The continuous search for risk factors in specific populations may facilitate the development of a standardized method to reduce the occurrence of BCRL and provide better management for breast cancer patients.

Extracorporeal Shock Wave Therapy Combined with Complex Decongestive Therapy in Patients with Breast Cancer-Related Lymphedema: A Systemic Review and Meta-Analysis.

Breast cancer-related lymphedema (BCRL) is one of the most significant complications seen after surgery. Several studies demonstrated that extracorporeal shock wave therapy (ESWT), in addition to conventional complex decongestive therapy (CDT), had a positive effect on BCRL in various aspects. The systematic review and meta-analysis aim to explore the effectiveness of ESWT with or without CDT on BRCL patients. We searched PubMed, Embase, PEDro, Cochrane Library Databases, and Google Scholar for eligible articles and used PRISMA2020 for paper selection. Included studies were assessed by the PEDro score, Modified Jadad scale, STROBE assessment, and GRADE framework for the risk of bias evaluation. The primary outcomes were the volume of lymphedema and arm circumference. Secondary outcome measures were skin thickness, shoulder joint range of motion (ROM), and an impact on quality-of-life questionnaire. Studies were meta-analyzed with the mean difference (MD). Eight studies were included in the systemic review and four in the meta-analysis. In summary, we found that adjunctive ESWT may significantly improve the volume of lymphedema (MD = -76.44; 95% CI: -93.21, -59.68; p < 0.00001), skin thickness (MD = -1.65; 95% CI: -3.27, -0.02; p = 0.05), and shoulder ROM (MD = 7.03; 95% CI: 4.42, 9.64; p < 0.00001). The evidence level was very low upon GRADE appraisal. ESWT combined with CDT could significantly improve the volume of lymphedema, skin thickness, and shoulder ROM in patients with BCRL. There is not enough evidence to support the use of ESWT as a replacement for CDT. This study was registered with PROSPERO: CRD42021277110.

Effects of Sodium Selenite Injection on Serum Metabolic Profiles in Women Diagnosed with Breast Cancer-Related Lymphedema-Secondary Analysis of a Randomized Placebo-Controlled Trial Using Global Metabolomics.

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.