Advances in the prevention and treatment of breast cancer-related lymphedema.

PURPOSE: Breast cancer-related lymphedema (BCRL) represents a lifelong risk for breast cancer survivors and once acquired becomes a lifelong burden. This review summarizes current BCRL prevention and treatment strategies. FINDINGS: Risk factors for BCRL have been extensively studied and their identification has affected breast cancer treatment practice, with sentinel lymph node removal now standard of care for patients with early stage breast cancer without sentinel lymph node metastases. Early surveillance and timely management aim to reduce BCRL incidence and progression, and are further facilitated by patient education, which many breast cancer survivors report not having adequately received. Surgical approaches to BCRL prevention include axillary reverse mapping, lymphatic microsurgical preventative healing (LYMPHA) and Simplified LYMPHA (SLYMPHA). Complete decongestive therapy (CDT) remains the standard of care for patients with BCRL. Among CDT components, facilitating manual lymphatic drainage (MLD) using indocyanine green fluorescence lymphography has been proposed. Intermittent pneumatic compression, nonpneumatic active compression devices, and low-level laser therapy appear promising in lymphedema management. Reconstructive microsurgical techniques such as lymphovenous anastomosis and vascular lymph node transfer are growing surgical considerations for patients as well as liposuction-based procedures for addressing fatty fibrosis formation from chronic lymphedema. Long-term self-management adherence remains problematic, and lack of diagnosis and measurement consensus precludes a comparison of outcomes. Currently, no pharmacological approaches have proven successful. CONCLUSION: Progress in prevention and treatment of BCRL continues, requiring advances in early diagnosis, patient education, expert consensus and novel treatments designed for lymphatic rehabilitation following insults.

The efficacy in shoulder range of motion of a snapping manual maneuver added to a standardized exercise protocol in axillary web syndrome: a randomized controlled trial.

PURPOSE: Axillary Web Syndrome (AWS) is a common sequela after surgical axillary lymph node dissection (ALND) often manifesting with reduced range of motion (ROM) of the limb, which requires rehabilitation. Notwithstanding, a standardized rehabilitation protocol is currently lacking in clinical practice. Our primary objective was therefore to evaluate the effectiveness of the use of a snapping manual maneuver (SMM, used in our clinical practice) to increase ROM during abduction (ABD) when compared with a standardized stretching exercise (SSE) protocol. A three-year follow-up of the enrolled patients was also carried out to determine the incidence of Breast Cancer-Related Lymphedema (BCRL). MATERIALS AND METHODS: Between July 2013 and January 2019, we conducted a single-blinded randomized clinical trial. A total of 60 patients, who underwent ALND in our hospital, came to our clinic under medical advice or on voluntary access and reported AWS symptoms. The patients were randomly assigned into two equally divided groups. The treatment of group one consists in the execution of a supervised SSEs protocol, while group two additionally received a manual snapping maneuver. Patients of both groups received two treatment sessions within two weeks. At the end of the session, they were asked to continue the exercises autonomously on a daily basis, three times per day, for one month. RESULTS: There were no statically significant differences in ROM at our one-month follow-up and the incidence of BCRL was equally distributed after three years. CONCLUSIONS: The use of the manual snapping maneuver in addition to stretching once per week for two weeks does not appear to improve the outcome of the patients in comparison with stretching alone and does not appear to be related to lymphedema in our 3 years follow-up.

Ultrasonography as an instrument to evaluate lymphedema secondary to breast cancer: systematic review.

Lymphedema is a chronic and progressive disease characterized by fluid accumulation, causing tissue edema as a result of a compromised lymphatic system. Diagnostic ultrasound (DUS) is a method capable of assessing soft tissue characteristics that can be used reliably to diagnose lymphedema as well as for measuring tissue compliance in a clinical setting. This is a systematic review, aiming to evaluate articles that made use of DUS in management of lymphedema secondary to breast cancer. A total of 570 articles were selected, exported to the Rayyan QCRI review program, and then screened by two researchers. From this search, 25 articles were selected after the authors reached consensus and were catalogued as to their main results. Diagnostic ultrasound was identified as an advantageous method that is safe, minimally invasive, low cost, and radiation free and is useful for evaluating the efficacy of therapies used in lymphedema treatment.

Risk factors of unilateral breast cancer-related lymphedema: an updated systematic review and meta-analysis of 84 cohort studies.

PURPOSE: To review and update the incidence and risk factors for breast cancer-related lymphedema based on cohort studies. METHODS: The study was guided by the Joanna Briggs Institute methodology and the Cochrane handbook for systematic reviews. PubMed, EMBASE, CINAHL, Scopus, Web of Science, The Cochrane Library, CNKI, SinoMed, and Wan Fang Database were searched from inception to November 15, 2021. Cohort studies reported adjusted risk factors were selected. PRISMA guideline was followed. Study quality were evaluated using the Newcastle-Ottawa scale. Random-effects models were adopted. The robustness of pooled estimates was validated by meta-regression and subgroup analysis. Lymphedema incidence and adjusted risk factors in the multivariable analyses with hazard / odds ratios and 95% CIs were recorded. RESULTS: Eighty-four cohort studies involving 58,358 breast cancer patients were included. The pooled incidence of lymphedema was 21.9% (95% CI, 19.8-24.0%). Fourteen factors were identified including ethnicity (black vs. white), higher body mass index, higher weight increase, hypertension, higher cancer stage (III vs. I-II), larger tumor size, mastectomy (vs. breast conservation surgery), axillary lymph nodes dissection, more lymph nodes dissected, higher level of lymph nodes dissection, chemotherapy, radiotherapy, surgery complications, and higher relative volume increase postoperatively. Additionally, breast reconstruction surgery, and adequate finance were found to play a protective role. However, other variables such as age, number of positive lymph nodes, and exercise were not correlated with risk of lymphedema. CONCLUSION: Treatment-related factors still leading the development of breast cancer-related lymphedema. Other factors such as postoperative weight increase and finance status also play a part. Our findings suggest the need to shift the focus from treatment-related factors to modifiable psycho-social-behavioral factors.

Body image and sexuality concerns in women with breast cancer-related lymphedema: a cross-sectional study.

PURPOSE: (1) To determine, in women with breast cancer-related lymphedema (BCRL), the frequency, intensity and distress of body image and sexuality concerns. (2) To examine relationships between body image and sexuality concerns, and lymphedema, personal and cancer treatment factors. METHOD: Women with BCRL (n = 64) completed the Lymphedema Symptom Intensity and Distress Scale - Arm (LSIDS-A), which focuses on the intensity and distress of a range of lymphedema symptoms. They also underwent a lymphedema assessment. Responses to eight questions from the LSIDS-A regarding sexuality, body image and intimate relationships were considered. Frequency of responses was tabulated. Multiple linear regressions were used to determine if specific factors were related to higher intensity and distress scores associated with body image and sexuality issues. RESULTS: Body image and sexuality concerns were common (48%, 23% respectively). Participants reported a range (0-10) of intensity and distress related to body image and sexuality symptoms. Univariate linear regression revealed greater intensity of sexuality concerns was associated with younger age, whilst distress related to sexuality concerns was associated with higher inter-arm bioimpedance ratio and shorter duration of lymphedema. Body image concerns were not related to any considered factors. CONCLUSION: Body image and sexuality concerns are common, intense and distressing for patients with breast cancer lymphedema. Assessment of both the intensity and distressed caused by these symptoms is necessary to understand the impact of lymphedema.

Treatment of Breast Cancer-Related Lymphedema Using Negative Pressure Massage: A Pilot Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy of negative pressure massage treatment (NPMT) compared with manual lymphatic drainage (MLD) in women with chronic breast cancer-related lymphedema (LE). We hypothesized that NPMT would result in greater improvements in LE and upper limb function. DESIGN: Pilot single-blinded randomized controlled trial. SETTING: Health sciences university. PARTICIPANTS: Of 64 women screened, 28 met eligibility requirements (ie, >18y of age; completed active treatment for breast cancer; had unilateral arm LE for ≥1y; were not receiving LE care; had stable LE) and were randomized to the NPMT (n=15) and control groups (n=13). INTERVENTIONS: The intervention group received NPMT and the control group received MLD; both received twelve 60-minute sessions over 4-6 weeks. MAIN OUTCOME MEASURES: Bioimpedance (lymphedema index [L-Dex] units]), limb volume (mL) calculated from limb circumference, and Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH) score. RESULTS: Outcomes were analyzed for 28 women. Compared to the MLD group, the NPMT group demonstrated greater improvement with a large effect size in L-Dex scores (P=.001; standardized mean difference [SMD]=-1.15; 95% confidence interval, -1.96 to -0.35) and interlimb volume differences (P=.038; SMD=-0.83; 95% confidence interval, -1.60 to -0.05). Differences in DASH scores were not statistically significant (P=.067). CONCLUSIONS: Compared to MLD, treatment with NPMT resulted in greater improvement in L-Dex scores and interlimb volume differences in women with a duration of unilateral upper limb LE of >1 year. Our findings need to be confirmed in a larger randomized controlled trial.

Efficacy of Ultrasound and Shear Wave Elastography for the Diagnosis of Breast Cancer-Related Lymphedema.

OBJECTIVES: To assess the feasibility of ultrasound and shear wave elastography (SWE) in the diagnosis of breast cancer-related lymphedema. METHODS: Forty-one patients with a history of unilateral breast surgery and axillary dissection or sentinel lymph node excision were included in this prospective study. The patients were classified as having normal findings, latent lymphedema, and clinical lymphedema on the basis of a physical examination, lymphedema index scores, and limb circumference measurements. The thickness and stiffness of the cutaneous and subcutaneous tissue of the forearm and arm were measured by ultrasound and SWE. The thickness and stiffness of the cutaneous and subcutaneous tissue of the affected limb and contralateral limbs of the normal, latent lymphedema, and clinical lymphedema groups were compared. RESULTS: The mean age ± SD of the 41 patients was 55.42 ± 10.12 years. There were 15 patients with normal findings, 10 with latent lymphedema, and 16 with clinical lymphedema. In the latent lymphedema group, the thickness measurements of the cutaneous tissue of the affected forearm and the cutaneous and subcutaneous tissue of the affected arm were significantly greater than those of the contralateral forearm and arm (P = .034; P = .022; and P = .002, respectively), and the stiffness measurements of the cutaneous and subcutaneous tissue of the affected forearm were significantly greater than those of the contralateral forearm (P = .011; and P = .002). In the clinical lymphedema group, the thickness and stiffness measurements of the cutaneous and subcutaneous tissue of the affected forearm and arm were significantly greater than those of the contralateral limb (P < .001-P = .032). CONCLUSIONS: Ultrasound and SWE are effective for diagnosing breast cancer-related lymphedema even at a latent stage.

Strategic recruitment of an ethnically diverse cohort of overweight survivors of breast cancer with lymphedema.

BACKGROUND: Black women are more likely to experience adverse effects from cancer treatment such as lymphedema. Thus, black women may particularly benefit from research regarding interventions to improve lymphedema. Herein, the authors report the challenges and strategies related to the recruitment of minority survivors of breast cancer and to the recruitment of survivors of breast cancer with lymphedema into the Women In Steady Exercise Research (WISER) Survivor Clinical Trial. METHODS: Subjects for this community-based trial were recruited from the Philadelphia area through active (mailings) and passive (printed materials and Web site) recruitment strategies. In addition, education sessions coordinated through partner hospitals in communities with a predominantly minority population were conducted to increase awareness of lymphedema in survivors of breast cancer. Women who were interested in the study were screened for lymphedema via telephone questionnaire and invited to see a study-related certified lymphedema therapist to confirm the presence of lymphedema. RESULTS: Screening was conducted among 2295 women: 628 were eligible, 450 consented, and 351 were randomized. Minority women comprised 38% of the study population. Letters to women on state and hospital registries resulted in a 0.4% randomization rate; education sessions yielded a 10% randomization rate. The authors observed that approximately 23.6% of the study sample had no previous diagnosis of lymphedema. CONCLUSIONS: The WISER Survivor Clinical Trial faced multiple recruitment challenges and used unique strategies to successfully enroll minority survivors of breast cancer into a lifestyle intervention. Cancer 2018;124:95-104. © 2017 American Cancer Society.

Evaluating the Surgical Outcome of Lymphovenous Anastomosis in Breast Cancer-Related Lymphedema Using Tc-99m Phytate Lymphoscintigraphy: Preliminary Results.

Background: Breast cancer-related lymphedema (BCRL) remains a significant postcancer treatment challenge with no definitive cure. Recent supermicrosurgical treatments, such as lymphovenous anastomosis (LVA), have shown promise but lack established objective indicators for outcome evaluation. We investigated the utility of Technetium-99m (Tc-99m) lymphoscintigraphy, an imaging technique providing objective information on lymphatic fluid flow, for assessing LVA surgical outcomes. Methods and Results: A retrospective cohort analysis of patients undergoing LVA for BCRL was conducted. Lymphoscintigraphy images pre- and 1-year postsurgery were compared to determine changes in lymphatic fluid flow of 18 patients based on newly defined parameters "uptake ratio" and "washout rates." Statistically significant reduction in the uptake ratio was observed in the forearm at 30 and 60 minutes postinjection phases. In addition, the forearm showed higher washout rate, indicating an improved lymphatic function in the forearm. Conclusion: Tc-99m lymphoscintigraphy can provide valuable objective data for evaluating LVA surgical outcomes in BCRL patients. However, site-specific differences in outcomes highlight the need for individualized surgical planning. Further large-scale studies are necessary to validate these preliminary findings and develop a standardized approach for LVA assessment.

Treatment of Breast Cancer-Related Lymphedema With Topical Tacrolimus: A Prospective, Open-Label, Single-Arm, Phase II Pilot Trial.

PURPOSE: Breast cancer-related lymphedema (BCRL) is a chronic, progressive side effect of breast cancer treatment, occurring in one-third of patients treated with axillary lymph node dissection and nodal radiotherapy. Cluster of differentiation 4-positive (CD4+) cells plays a key role in BCRL by facilitating inflammation and inhibiting lymphangiogenesis. Tacrolimus is an anti-inflammatory and immunosuppressive macrolide that targets CD4+ cells. Treatment of lymphedema with topical tacrolimus has revealed promising results in preclinical trials. This clinical trial was aimed at evaluating the feasibility, safety, and effect of tacrolimus in women with stage I or II BCRL, according to the International Society of Lymphology. METHODS: We conducted this open-label, single-arm, phase II pilot trial from September 2020 to April 2021. Eighteen women with BCRL stage I or II BCRL were treated with topical tacrolimus for 6 months and followed up at 3 and 6 months. The primary outcome was arm volume, and secondary outcomes were the lymphedema index (L-Dex), health-related quality of life (HRQoL), lymph flow and function, and safety and feasibility of the trial design. RESULTS: The mean lymphedema arm volume and L-Dex reduced significantly by 130.44 ± 210.13 mL (p < 0.05; relative reduction: 3.6%) and 3.54 ± 4.98 (p < 0.05), respectively, and health-related quality of life scores was improved significantly (p < 0.05). According to the MD Anderson scale, in terms of lymph flow and function, three patients (16.7%) showed improvement, while none showed worsening. Lymph flow or function showed no change according to the Arm Dermal Backflow scale. CONCLUSION: In this trial, treatment with tacrolimus was safe and feasible in women with stage I or II BCRL. Tacrolimus alleviated BCRL in terms of improved arm volume, L-Dex, and HRQoL. Assessments of lymph flow and function were positive, although inconclusive. Larger randomized controlled trials are required to verify these findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04541290.

Complex physical therapy employing self-adjusting garment (ReadyWrap®) in breast cancer-related lymphedema cases in Brazilian women: a protocol for a randomized controlled trial.

BACKGROUND: Lymphedema is a common complication following breast cancer treatment. The aim of this study is to evaluate the effectiveness of a self-adjusting compression garment (ReadyWrap®) in reducing (phase 1) and maintaining (phase 2) upper limb volume in women presenting breast cancer-related lymphedema. METHODS: This study will comprise a randomized, controlled, single-blind clinical trial concerning women with breast cancer-related lymphedema undergoing treatment at a public cancer treatment reference hospital in the city of Rio de Janeiro, Brazil. The intervention will be carried out by adapting self-dressing versus the standard treatment of compressive bandaging (phase 1) and compressive mesh (phase 2). Both groups will be assessed at the beginning and end of intensive treatment and followed up for up to 12 months to evaluate immediate and late outcomes. Assessments will be carried out by physical upper limb examination (inspection, palpation, volume, dynamometry, and thermography) and questionnaires application to assess patient's quality of life pertaining to the health, functionality, and symptoms of the affected upper limb, as well adverse effects and adherence to treatment. Data will be analyzed descriptively and analytically through univariate and multiple linear regressions. P values < 0.05 will be considered statistically significant. DISCUSSION: This study will evaluate the effectiveness of a self-adjustable garment (ReadyWrap®) in the treatment of lymphedema secondary to breast cancer in Brazilian women compared to the gold standard treatment for limb volume reduction (phase 1) and maintenance (phase 2) phases comprising, respectively, a compressive bandaging and a compressive mesh. The outcome results will provide data based on both quantitative responses and self-reported participant outcomes. The study will also assess the cost-effectiveness of the ReadyWrap® treatment versus standard care. Finally, we expect to reaffirm one more product/therapy as a treatment for this extremely complex and impactful condition following the data analysis. TRIAL REGISTRATION: NCT04934098 [Clinical trials phase 1]. Registered on June 22, 2021. NCT04881604 [Clinical trials phase 2]. Registered on May 11, 2021.

Underreporting and Underrepresentation of Racial and Ethnic Minority Patients in Lymphedema Clinical Trials: A Systematic Review.

The generalizability of findings from Clinical Trials (CTs) investigating lymphedema treatment modalities requires an accurate representation of the target population. This study aims to evaluate racial and ethnic reporting and representation in lymphedema CTs. A comprehensive systematic literature search was conducted during May 2023 using multiple databases, following the PRISMA guidelines. All CTs published from 2018 to 2023 were included. A total of 84 articles were included in this review, from which 6,546 participants were included in the analysis. Seventy-four (88.1%) articles addressed secondary lymphedema, of which 60 (81.1%) were related to breast cancer. Only 12 (13%) of CTs reported at some extend race or ethnicity. Of these, five (41.6%) reported race and two (16.6%) reported ethnicity according to FDA guidelines. White race had the highest pooled prevalence (80%; 95% CI 72-86%; I2=90%), followed by Black (7%; 95% CI 2- 15%; I2= 94.3%) and Asian (4%; 95% CI 1-8%; I2= 89.9%). In studies reporting ethnicity, participants were predominantly non-Hispanic (92.1%; 95% CI 90 - 94%). There is an underreporting and underrepresentation of racial and ethnic minorities among lymphedema CTs, limiting their generalizability. It is imperative to future development of strategies to enhance diversity in the study sample.

A phase II randomized clinical trial to assess toxicity and quality of life of breast cancer patients with hypofractionated versus conventional fractionation radiotherapy with regional nodal irradiation in the context of COVID-19 crisis.

Purpose: This study, conducted during the COVID-19 crisis, primarily aimed to compare the acute toxicity between conventional fractionated radiation therapy (CF-RT) with hypofractionated radiation therapy (HF-RT) among patients who underwent breast-conserving surgery or mastectomy in whom breast or chest wall and regional nodal irradiation (RNI) were indicated. The secondary endpoints were both acute and subacute toxicity, cosmesis, quality of life, and lymphedema features. Methods: In this open and non-inferiority randomized trial, patients (n = 86) were randomly allocated 2:1 in the CF-RT arm (n = 33; 50 Gy/25 fractions ± sequential boost [10 Gy/5 fractions]) versus the HF-RT arm (n = 53; 40 Gy/15 fractions ± concomitant boost [8 Gy/15 fractions]). Toxic effects and cosmesis evaluation used the Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE) and the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/Radiation Therapy Oncology Group (RTOG) scale. For the patient-reported quality of life (QoL), the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) and the breast cancer-specific supplementary questionnaire (QLQ-BR23) were used. Lymphedema was assessed by comparing volume differences between the affected and contralateral arms using the Casley-Smith formula. Results: Grade 2 and grade 3 dermatitis were lower with HF-RT than with CF-RT (28% vs. 52%, and 0% vs. 6%, respectively; p = 0.022). HF-RT had a lower rate of grade 2 hyperpigmentation (23% vs. 55%; p = 0.005), compared to CF-RT. No other differences in overall rates of physician-assessed grade 2 or higher and grade 3 or higher acute toxicity between HF-RT and CF-RT were registered. There was no statistical difference between groups regarding cosmesis, lymphedema rate (13% vs. 12% HF-RT vs. CF-RT; p = 1.000), and functional and symptom scales, during both the irradiation period and after 6 months of the end of treatment. The results revealed that the subset of patients up to 65 years or older did not show a statistical difference between both arm fractionation schedules (p > 0.05) regarding skin rash, fibrosis, and lymphedema. Conclusion: HF-RT was non-inferior to CF-RT, and moderate hypofractionation showed lower rates of acute toxicity, with no changes in quality-of-life outcomes. Clinical trial registration: ClinicalTrials.gov, identifier NCT40155531.

Risk factors for arm lymphedema following breast cancer surgery: a Japanese nationwide database study of 84,022 patients.

BACKGROUND: Although arm lymphedema is a well-known complication following breast cancer surgery, previous studies involving a small population showed inconsistent results regarding the risk. Therefore, we examined the risk factors using a Japanese nationwide database. METHODS: Female patients who underwent breast cancer surgery from April, 2016, to March, 2020, were identified from a Japanese nationwide database. Multivariable survival analyses for 19 baseline factors (12 patient characteristics, four tumor characteristics, and three surgical procedures) were conducted to investigate risk factors associated with treatments for postoperative lymphedema (such as lymphatic bypass, compositive drainage therapy, hospitalization, and Kampo use) with a multilevel model to adjust for within-hospital clustering. We also conducted multivariable analysis for five postoperative factors (two local complications and three postoperative therapies) with adjustment for 19 baseline factors. RESULTS: The study included 84,022 patients; 1547 (1.8%) received treatments for lymphedema during a median follow-up of 119 weeks (interquartile range, 59-187 weeks). Young age, obesity, smoking, collagen diseases, advanced cancer stage, total mastectomy, axillary dissection, postoperative bleeding, chemotherapy, and radiotherapy were identified as risk factors. Postoperative chemotherapy (hazard ratio, 3.78 [95% confidence interval, 3.35-4.26]) and axillary dissection (2.46 [1.95-3.11]) showed the highest odds ratio among the risk factors. The cumulative probabilities in high-risk patients reached approximately 3% at 1 year and 6% at 4 years after surgery. CONCLUSIONS: This study identified several risk factors for postoperative lymphedema in breast cancer surgery. The treatment initiation increased markedly within the first year and gradually after 1 year post-surgery.

The efficacy and safety of acupuncture and moxibustion for breast cancer lymphedema: a systematic review and network meta-analysis.

Background: Breast cancer lymphedema (BCL) is one of the most common complications of breast cancer. Common western medical treatments for BCL, such as western medicine and lymphatic drainage, are ineffective, and recurrence may easily occur, making treatment more challenging and placing a heavier burden on patients. Acupuncture therapy is commonly used to treat BCL in China, and there are many acupuncture therapies, including acupuncture, moxibustion, and the combination of acupuncture and moxibustion. Given the difference in operation difficulty, efficacy and safety of these acupuncture types, how to the most effective therapy is controversial. Therefore, the purpose of this study was to compare the efficacy and safety of different acupuncture and moxibustion methods, so as to provide guidance for clinical practice. Methods: The PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, VIP, and SinoMed databases were searched to September 30, 2022. Participants were diagnosed with BCL. Acupuncture was used in the intervention group, and other acupuncture were used in the control group. Outcomes included arm circumference, visual analogue scale (VAS), and safety evaluation. Risk of Bias Assessment Tool 2 (ROB2) was used to assess the risk of bias, Stata 16 was used for network meta-analysis. Results: A total of 7 studies were included, with 422 patients. The interventions included fire acupuncture, acupuncture (face), moxa-moxibustion, heat-sensitive moxibustion, moxibustion [traditional Chinese medicine (TCM)], acupuncture combine with moxibustion, acupoint application. The risk of overall bias was low or some concerns. The meta-analysis showed that: (I) arm circumference: acupuncture combined with moxibustion was superior to acupoint application [mean difference (MD) =-0.54; 95% confidence interval (CI): (-0.67, -0.41); P<0.05]. The surface under the cumulative ranking probability area (SUCRA) ranking results showed that acupuncture combined with moxibustion may be the optimal method. (II) VAS: acupuncture (face) was more effective than acupuncture (body) [MD =-0.85; 95% CI: (-1.09, -0.61); P<0.01]. The SUCRA ranking results showed that acupuncture (face) had the best effect. Conclusions: Based on the current evidence, acupuncture and moxibustion is of great efficacy and safety for the treatment of BCL. Acupuncture combined with moxibustion is the most effective in reducing the arm circumference, and acupuncture (face) is of the greatest analgesic effect.

Surgical management of breast cancer-related lymphedema: a narrative review of contemporary practices.

Background and Objective: Breast cancer-related lymphedema (BCRL) represents a colossal burden in terms of health and patient-reported outcomes. Surgical management plays a prominent role in the psychological and physical well-being of women suffering from BCRL. Therefore, we performed a narrative review of the current surgical management of BCRL and analyzed the postoperative results. Methods: A literature search was conducted across PubMed MEDLINE, Scopus, and Web of Science from database inception through January 2, 2023. We included English-written studies evaluating postoperative outcomes of lymphatic surgery for the management of BCRL. Key Content and Findings: The surgical management of lymphedema can be classified into two approaches: (I) physiologic procedures and (II) debulking or ablative procedures. While ablative procedures are intended to lessen the symptomatic burden of lymphedema via the removal of pathological tissues, physiologic procedures are performed to restore the abnormal lymphatic flow by creating bypasses into the venous or lymphatic circulation, or by creating new lymphatic connections by means of lymphangiogenesis. Physiologic procedures generate better outcomes in the early stages of lymphedema as there is some residual physiologic flow and vessels are less fibrotic, while ablative procedures are regarded to be the best alternative in very advanced lymphedema stages. A combination of physiologic and ablative procedures provides more comprehensive surgical management to BCRL. Conclusions: Lymphedema is a common complication of breast cancer treatment with an extensive incidence range. Postoperative outcomes of the surgical management of BCRL are heterogeneous despite most studies indicating favorable results after lymphatic surgery.

Optimizing Treatment of Breast Cancer Related Lymphedema Using Combined DIEP Flap and Lymphedema Surgery.

Patients undergoing treatment for breast cancer who undergo an axillary dissection and require adjuvant therapies such as radiation and chemotherapy are at high risk of developing lymphedema of the associated extremity. Historically, patients with lymphedema were treated with ablative procedures aimed simply to remove excess fluid and adiposity; however, the field of lymphatic surgery employing super-microsurgery techniques has witnessed tremendous advances in a relatively short period of time. Advancements in surgical instruments, microscope magnification and optics, imaging technology, and surgeon experience have ushered in a new era of hope to treat patients suffering from breast cancer-related lymphedema (BCRL). Here we aim to present the available options for patients suffering from BCRL, and the pinnacle in reconstruction and restoration for these patients.

Sun-burn induced upper limb lymphedema 11 years following breast cancer surgery: A case report.

BACKGROUND: Upper arm lymphedema is a common complication one year after breast cancer surgery, which profoundly impacts patients' quality of life. CASE SUMMARY: We reported a case of lymphedema induced by prolonged sun exposure 11 years after breast cancer surgery. CONCLUSION: Breast screening, patient education and follow-up after hospital discharge could help to prevent upper-arm lymphedema.

The Impacts of Prepared Plasma-Activated Medium (PAM) Combined with Doxorubicin on the Viability of MCF-7 Breast Cancer Cells: A New Cancer Treatment Strategy.

Background: For many years, the chemotherapeutic agent doxorubicin (DOX) has been used to treat various cancers; however, DOX initiates several critical adverse effects. Many studies have reported that non-thermal atmospheric pressure plasma can provide novel, but challenging, treatment strategies for cancer patients. To date, tissues and cells have been treated with plasma-activated medium (PAM) as a practical therapy. Consequently, due to the harmful adverse effects of DOX, we were motivated to elucidate the impact of PAM in the presence of DOX on MCF-7 cell proliferation. Methods: MTT assay, N-acetyl-L-cysteine (NAC) assay, and flow cytometry analysis were utilized in this research. Results: The results demonstrated that 0.45 µM DOX combined with 3-min PAM significantly induced apoptosis (p< 0.01) through intracellular ROS generation in MCF-7 when compared with 0.45 µM DOX alone or 3-min PAM alone. In contrast, after treatment with 0.45 µM DOX plus 4-min PAM, cell necrosis was increased. Hence, DOX combined with 4-min PAM has cytotoxic effects with different mechanisms than 4-min PAM alone, in which the number of apoptotic cells increases. Conclusion: Although further investigations are crucial, low doses of DOX plus 3-min PAM could be a promising strategy for cancer therapy. The findings from this research may offer advantageous and innovative clinical strategies for cancer therapy using PAM.

Effect of Supervised Resistance Training on Arm Volume, Quality of Life and Physical Perfomance Among Women at High Risk for Breast Cancer-Related Lymphedema: A Study Protocol for a Randomized Controlled Trial (STRONG-B).

Objectives: To determine the preventive effects of supervised resistance training on arms volume, quality of life, physical performance, and handgrip strength in Chilean women at high risk for breast cancer-related lymphedema (BCRL) undergoing chemotherapy. Design: Randomized control trial. Participants: One hundred and six women at high risk for breast cancer-related lymphedema aged 18 to 70 years. Interventions: Participants will be randomized into two groups: [a] intervention, who will receive 12 weeks of supervised resistance training (STRONG-B) during adjuvant chemotherapy; and [b] control, who will receive education to promote lymphatic and venous return, maintain range of motion, and promote physical activity. Main Outcome Measures: The primary outcome will be arms volume measured with an optoelectric device (perometer NT1000). Secondary outcomes will be quality of life, handgrip strength, and physical performance. Primary and secondary outcomes will be measured at baseline, just after the intervention, and 3 and 6 months after. Statistical analysis will be performed following intention-to-treat and per-protocol approaches. The treatment effect will be calculated using linear mixed models. Discussion: The STRONG-B will be a tailored supervised resistance training that attempts to prevent or mitigate BCRL in a population that, due to both intrinsic and extrinsic factors, will commonly suffer from BCRL. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT04821609], identifier NCT04821609.