Multi-omics characterization of lymphedema-induced adipose tissue resulting from breast cancer-related surgery.

Secondary lymphedema (LE) following breast cancer-related surgery is a life-long complication, which currently has no cure. LE induces significant regional adipose tissue deposition, requiring liposuction as a treatment. Here, we aimed to elucidate the transcriptional, metabolomic, and lipidomic signature of the adipose tissue developed due to the surgery-induced LE in short- and long-term LE patients and compared the transcriptomic landscape of LE adipose tissue to the obesity-induced adipose tissue. Adipose tissue biopsies were obtained from breast cancer-operated females with LE from the affected and non-affected arms (n = 20 patients). To decipher the molecular properties of the LE adipose tissue, we performed RNA sequencing, metabolomics, and lipidomics combined with bioinformatics analyses. Differential gene expression data from a cohort of lean and obese patients without LE was used for comparisons. Integrative analysis of functional genomics revealed that inflammatory response, cell chemotaxis, and angiogenesis were upregulated biological processes in the LE arm, indicating a sustained inflammation in the edematous adipose tissue; whereas, epidermal differentiation, cell-cell junction organization, water homeostasis, and neurogenesis were downregulated in the LE arm. Surprisingly, only a few genes were found to be the same in the LE-induced and the obesity-induced adipose tissue expansion, indicating a different type of adipose tissue development in these two conditions. In metabolomics analysis, we found reduced levels of a branched-chain amino acid valine in the LE arm and downregulation of the mRNA levels of its transporter SLC6A15. Lipidomics analyses did not show any significant differences between the LE and non-LE arms, suggesting that other factors affect the lipid composition of the adipose tissue more than the LE in these patients. Our results provide a detailed molecular characterization of adipose tissue in secondary LE after breast cancer-related surgery. We also show distinct differences in transcriptomic signatures between LE-induced adipose tissue and obesity-induced adipose tissue, but only minor differences in metabolome and lipidome between the LE and the non-LE arm.

Breast cancer survivors suffering from lymphedema: What really do affect to corporeality/body image? A qualitative study.

Breast cancer-related lymphedema is currently one of the most serious complications that most affect the quality of life of women undergoing breast cancer. The aim of this study was to explore in-depth the experience of women who suffer from lymphoedema after breast cancer and how does this condition affect corporeality, with no judgements. For this purpose, a qualitative methodology was followed. In-depth interviews, interviewer's field notes and participants' letters were used for data collection. The participants were twenty Spanish women with lymphoedema after overcome a breast cancer in the past. Healthcare specialists with experience in the topic were also included. Results showed 2 main categories: "From cancer to lymphedema, another disease another disease" and "Potential for transition and transformation towards a new way of life". As a conclusion, the difficulty in accessing adequate treatment, the need for greater awareness of lymphedema and the importance of the emotional and psychological dimension of this chronic disease. Highlighting the attitudes that these women develop for self-care and the concept of new corporeality. After breast cancer, women with lymphedema experience a drastic change that affects all areas of their lives. The adaptation process, and the search for resources and aid, play a fundamental role in overcoming this process.

BE-WEL trial (breast: evaluation of weight and exercise for lymphoedema) testing weight control and exercise programmes for women with breast cancer related lymphoedema: a feasibility trial.

PURPOSE: A combined body weight loss and upper body/arm exercise programme is a potential strategy for managing Breast cancer related lymphoedema (BCRL), but there is limited data on the best method for delivery or its potential efficacy. METHODS: Fifty-seven women with overweight/obesity and BCRL were randomised to a 12 week supervised (n = 12) or home-based combined weight loss and upper body/arm exercise programme (n = 16), a home-based upper-body arm exercise only programme (n = 17) or standard care (n = 12). Primary outcomes were uptake, retention and changes in weight and change in Relative Arm Volume Increase (RAVI) using analysis of covariance (ANCOVA). RESULTS: Sixteen percent of women invited joined the study and 49 completed the trial (85% retention). Reductions in weight occurred in the supervised and home-based weight control and exercise programmes; Mean (95% CI) change compared to standard care - 1.68 (- 4.36 to - 1.00), - 2.47(- 4.99 to - 0.04) Kg. Reductions in perometer assessed RAVI were seen in the supervised and home-based combined weight control and arm exercise groups and the weight stable home-based arm exercise only group: mean (95% CI) change compared to standard care - 2.4 (- 5.0 to + 0.4),- 1.8 (- 4.3 to + 0.7), - 2.5(- 4.9 to - 0.05)%. CONCLUSION: Women with BCRL and overweight and obesity engaged in diet and exercise weight loss programmes. Both weight loss/arm exercise programmes led to modest changes in weight and BCRL. Comparable reductions in BCRL were reported in the weight stable group undertaking arm exercise only. The independent and combined effects of weight loss and exercise on BCRL need further study. TRIAL REGISTRATION: ISRCTN86789850 https://doi.org/10.1186/ISRCTN86789850 , registered 2011.

Breast lymphedema following breast-conserving treatment for breast cancer: current status and future directions.

PURPOSE: To examine the current evidence on breast lymphedema (BL) diagnosis and treatment after breast-conserving surgery, identify gaps in the literature, and propose future research directions. METHODS: A comprehensive literature review was conducted using Ovid, PubMed, and Cochrane, including studies published between 2000 and 2023. References were reviewed manually for eligible studies. Inclusion criteria were as follows: patients who underwent breast conserving treatment (surgery ± radiation) for breast cancer, goals of the paper included analyzing or reviewing BL measurement with ultrasound or tissue dielectric constant, or BL treatment. Twenty-seven manuscripts were included in the review. RESULTS: There is variation in incidence, time course, and risk factors for BL. Risk factors for BL included breast size, primary and axillary surgery extent, radiation, and chemotherapy but require further investigation. Diagnostic methods for BL currently rely on patient report and lack standardized criteria. Tissue dielectric constant (TDC) and ultrasound (US) emerged as promising ambulatory BL assessment tools; however, diagnostic thresholds and validation studies with ICG lymphography are needed to establish clinical utility. The evidence base for treatment of BL is weak, lacking high-quality studies. CONCLUSION: The natural history of BL is not well defined. TDC and US show promise as ambulatory assessment tools for BL; however, further validation with lymphatic imaging is required. BL treatment is not established in the literature. Longitudinal, prospective studies including pre-radiation measurements and validating with lymphatic imaging are required. These data will inform screening, diagnostic criteria, and evidence-based treatment parameters for patients with BL after breast-conserving surgery and radiation.

Impact of neoadjuvant chemotherapy on breast cancer-related lymphedema after axillary lymph node dissection: a retrospective cohort study.

PURPOSE: We aimed to evaluate whether neoadjuvant chemotherapy (NAC) could be a risk factor for breast cancer-related lymphedema (BCRL) associated with axillary lymph node dissection (ALND). PATIENTS AND METHODS: A total of 596 patients with cT0-4N0-3M0 breast cancer who underwent ALND and chemotherapy were retrospectively analyzed between March 2012 and March 2022. NAC was administered in 188 patients (31.5%), while up-front surgery in 408 (68.5%). Univariate and multivariable Cox regression analyses were performed to determine whether NAC was an independent risk factor for BCRL. With propensity score matching (PSM), the NAC group and up-front surgery group were matched 1:1 by age, body mass index (BMI), molecular subtypes, type of breast surgery, and the number of positive lymph nodes. Kaplan-Meier survival analyses were performed for BCRL between groups before and after PSM. Subgroup analyses were conducted to explore whether NAC differed for BCRL occurrence in people with different characteristics. RESULTS: At a median follow-up of 36.3 months, 130 patients (21.8%) experienced BCRL [NAC, 50/188 (26.60%) vs. up-front surgery, 80/408 (19.61%); P = 0.030]. Multivariable analysis identified that NAC [hazard ratio, 1.503; 95% CI (1.03, 2.19); P = 0.033] was an independent risk factor for BCRL. In addition, the hormone receptor-negative/human epidermal growth factor receptor 2-negative (HR-/HER2-) subtype, breast-conserving surgery (BCS), and increased positive lymph nodes significantly increased BCRL risk. After PSM, NAC remained a risk factor for BCRL [hazard ratio, 1.896; 95% CI (1.18, 3.04); P = 0.007]. Subgroup analyses showed that NAC had a consistent BCRL risk in most clinical subgroups. CONCLUSION: NAC receipt has a statistically significant increase in BCRL risk in patients with ALND. These patients should be closely monitored and may benefit from early BCRL intervention.

Impact of sentinel node use in lymphedema formation among gynecologic cancer patients.

PURPOSE OF REVIEW: The most common surgical procedure associated with lymphedema formation is the regional lymphadenectomy. One of the advantages of sentinel node biopsy is the reduction of the risk of lymphedema formation. The purpose of this review is to collect and analyze the most relevant and recent evidence of the use of sentinel node biopsy and its implication on the development of postoperative lymphedema in gynecological cancer. RECENT FINDINGS: The current evidence of the use of sentinel node biopsy in cervical cancer to reduce lymphedema is heterogeneous and more data is needed to establish its role.Sentinel lymph node biopsy in endometrial cancer is a staging procedure with lower surgical complications, as well as lymphedema formation; while the results of prospective trials evaluating its impact on quality of life are still lacking.Sentinel lymph node biopsy in vulvar cancer minimizes the need for extensive dissection and reduces the incidence of complications associated with overharvesting of lymph nodes such as lymphedema without compromising oncological outcomes. SUMMARY: The prevalence of lymphedema in gynecological cancer varies based on the surgical treatment or additional therapies applied. Over the past years, one of the most important surgical modifications to decrease lymphedema formation has been implementation of sentinel lymph node technique mainly in vulvar cancer patients.

Lymphedema self-assessment among endometrial cancer survivors.

PURPOSE: Lower extremity lymphedema (LEL), which causes ankle, leg, and feet swelling, poses a significant challenge for endometrial cancer survivors, impacting physical functioning and psychological well-being. Inconsistent LEL diagnostic methods result in wide-ranging LEL incidence estimates. METHODS: We calculated the cumulative incidence of LEL based on survivor-reported Gynecologic Cancer Lymphedema Questionnaire (GCLQ) responses in addition to survivor- and nurse-reported leg circumference measurements among a pilot sample of 50 endometrial cancer survivors (27 White, 23 Black) enrolled in the ongoing population-based Carolina Endometrial Cancer Study. RESULTS: Self-leg circumference measurements were perceived to be difficult and were completed by only 17 survivors. Diagnostic accuracy testing measures (sensitivity, specificity, positive and negative predictive value) compared the standard nurse-measured ≥ 10% difference in leg circumference measurements to GCLQ responses. At a mean of ~11 months post-diagnosis, 54% of survivors met established criteria for LEL based on ≥ 4 GCLQ cutpoint while 24% had LEL based on nurse-measurement. Percent agreement, sensitivity, and specificity approximated 60% at a threshold of ≥ 5 GCLQ symptoms. However, Cohen's kappa, a measure of reliability that corrects for agreement by chance, was highest at ≥ 4 GCLQ symptoms (κ = 0.27). CONCLUSION: Our findings emphasize the need for high quality measurements of LEL that are feasible for epidemiologic study designs among endometrial cancer survivors. Future studies should use patient-reported survey measures to assess lymphedema burden and quality of life outcomes among endometrial cancer survivors.

Breast Articles From 2023: Informing Practice Across the Continuum of Care.

With new investigations and clinical trials in breast oncology reported every year, it is critical that surgeons be aware of advances and insights into the evolving care paradigms and treatments available to their patients. This article highlights five publications found to be particularly impactful this past year. These articles report on efforts to select the minimal effective dose of tamoxifen for prevention, to challenge the existing age-based screening guidelines as they relate to race and ethnicity, to refine axillary management treatment standards, to optimize systemic therapy in multidisciplinary care settings, and to reduce the burden of breast cancer-related lymphedema after treatment. Taken together, these efforts have an impact on all facets of the continuum of care from prevention and screening through treatment and survivorship.

The Effects of Daily-Living Risks on Breast Cancer-Related Lymphedema.

BACKGROUND: Conventional advice to reduce the risk of breast cancer-related lymphedema (BCLE) suggests avoidance of daily-living risks, and limited research has investigated these risks. OBJECTIVE: This study aimed to examine the occurrence, patterns, and effects of daily-living risks on BCLE. METHODS: A cross-sectional design was used to collect data from 567 patients at a metropolitan cancer center in the United States. The Lymphedema Risk-Reduction Behavior Checklist was used to assess the occurrence of 11 daily-living risks. Descriptive, regression, and factor analyses were performed. RESULTS: Significant odds of BCLE were associated with infection (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.95-3.42), cuts/scratches (OR 2.65, 95% CI 1.97-3.56), sunburn (OR 1.89, 95% CI 1.39-3.56), oil splash or steam burns (OR 2.08, 95% CI 1.53-3.83), and insect bites (OR 1.59, 95% CI 1.18-2.13). The daily-living risks were clustered into factors related to skin trauma and carrying objects. Skin trauma risk was significantly associated with BCLE (B = 0.539, z = 3.926, OR 1.714, 95% CI 1.312-2.250; p < 0.001). Having three, four, or five skin trauma risks significantly increased the odds of BCLE to 4.31, 5.14, and 6.94 times, respectively. The risk of carrying objects had no significant or incremental effects on BCLE. CONCLUSION: Complete avoidance of daily-living risks is challenging given 52.73% of patients incurred more than five daily-living risks. Our study findings underscore the importance of 'what to do' strategies to minimize infection and skin trauma.

Risk Factors for Breast Cancer-Related Lymphedema: An Umbrella Review.

BACKGROUND: Identification of risk factors facilitates the prevention of breast cancer-related lymphedema (BCRL). Several published systematic reviews have already addressed the risk factors for BCRL. This study aimed to systematically identify potential risk factors for BCRL and evaluate the quality of evidence. METHODS: The study followed methodologic guidance from the Joanna Briggs Institute, and the Cochrane Handbook. The following electronic databases were systematically searched from inception to 15 November 2022: PubMed, Embase, CINAHL, Web of Science, Scopus, CNKI, SinoMed, Wanfang, JBI Database, Cochrane Database, ProQuest, and PROSPERO. Two authors independently screened studies, extracted data, and assessed methodologic quality using AMSTAR2, risk of bias using ROBIS, and evidence quality using GRADE. The study evaluated overlap, assessed the small-study effect, and calculated the I2 statistic and Egger's P value as needed. RESULTS: The study included 14 publications comprising 10 meta-analyses and 4 systematic reviews. The authors identified 39 factors and 30 unique meta-analyses. In the study, 13 innate personal trait-related risk factors, such as higher body mass index (BMI) and axillary lymph nodes dissection, showed statistically significant associations with BCRL incidence. Breast reconstruction was found to be a protective factor. The methodologic quality was low or critically low. The majority of the systematic reviews and/or meta-analyses were rated as having a high risk of bias. Evidence quality was low for 22 associations and moderate for 8 associations. CONCLUSIONS: The currently identified risk factors for BCRL all are innate personal trait-related factors. Future well-designed studies and robust meta-analyses are needed to explore potential associations between behavioral-, interpersonal-, and environmental-related factors and BCRL, as well as the role of genetic variations and pathophysiologic factors.

Long-Term Patient-Reported Arm Symptoms in Breast Cancer Survivors.

BACKGROUND: Understanding long-term arm symptoms in breast cancer survivors is critical given excellent survival in the modern era. METHODS: This cross-sectional study included patients treated for stage 0-III breast cancer at our institution from 2002 to 2012. Patient-reported arm symptoms were collected from the EORTC QLQ-BR23 questionnaire. We used linear regression to evaluate adjusted associations between locoregional treatments and the continuous Arm Symptom (AS) score (0-100; higher score reflects more symptoms). RESULTS: A total of 1126 patients expressed interest in participating and 882 (78.3%) completed the questionnaire. Mean time since surgery was 10.5 years. There was a broad distribution of locoregional treatments, including axillary lymph node dissection (ALND) in 37.1% of patients, mastectomy with reconstruction in 36.5% of patients, and post-mastectomy radiation in 38.2% of patients. Overall, 64.3% (95% confidence interval [CI] 61.1-67.4%) of patients reported no arm symptoms, 17.0% (95% CI 14.7-19.6%) had one mild symptom, 9.4% (95% CI 7.7-11.5%) had two or more mild symptoms, and 9.3% (95% CI 7.6-11.4%) reported one or more severe symptoms. Adjusted AS scores were significantly higher with ALND versus sentinel node biopsy (ß 3.5, p = 0.01), and with autologous reconstruction versus all other breast/reconstructive surgery types (ß 4.5-5.5, all p < 0.05). There was a significant interaction between axillary and breast/reconstructive surgery, with the greatest effect of ALND in those with mastectomy with implant (ß 9.7) or autologous (ß 5.7) reconstruction. CONCLUSIONS: One in three patients reported arm symptoms at a mean of 10 years from treatment for breast cancer, although rates of severe symptoms were low (<10%). Attention is warranted to the arm morbidity related to both axillary and breast surgery during treatment counseling and survivorship.

Leg Lymphoedema After Inguinal and Ilio-Inguinal Lymphadenectomy for Melanoma: Results from a Prospective, Randomised Trial.

BACKGROUND: The Evaluation of Groin Lymphadenectomy Extent for Melanoma (EAGLE FM) study sought to address the question of whether to perform inguinal (IL) or ilio-inguinal lymphadenectomy (I-IL) for patients with inguinal nodal metastatic melanoma who have no clinical or imaging evidence of pelvic disease. Primary outcome measure was disease-free survival at 5 years, and secondary endpoints included lymphoedema. METHODS: EAGLE FM was designed to recruit 634 patients but closed with 88 patients randomised because of slow recruitment and changes in melanoma management. Lymphoedema assessments occurred preoperatively and at 6, 12, 18, and 24 months postoperatively. Lymphoedema was defined as Inter-Limb Volume Difference (ILVD) > 10%, Lymphoedema Index (L-Dex®) > 10 or change of L-Dex® > 10 from baseline. RESULTS: Prevalence of leg lymphoedema between the two groups was similar but numerically higher for I-IL at all time points in the first 24 months of follow-up; highest at 6 months (45.9% IL [CI 29.9-62.0%], 54.1% I-IL [CI 38.0-70.1%]) and lowest at 18 months (18.8% IL [CI 5.2-32.3%], 41.4% I-IL [CI 23.5-59.3%]). Median ILVD at 24 months for those affected by lymphoedema was 14.5% (IQR 10.6-18.7%) and L-Dex® was 12.6 (IQR 9.0-17.2). There was not enough statistical evidence to support associations between lymphoedema and extent of surgery, radiotherapy, or wound infection. CONCLUSIONS: Despite a trend for patients who had I-IL to have greater lymphoedema prevalence than IL in the first 24 months after surgery, our study's small sample did not have the statistical evidence to support an overall difference between the surgical groups.

Establishment and Feasibility of an Immediate Lymphatic Reconstruction Program in a Community Health System.

BACKGROUND: Breast cancer-related lymphedema (BCRL) remains a significant post-surgical complication of breast cancer treatment. Immediate lymphatic reconstruction (ILR) at the time of axillary lymph node dissection (ALND) has shown promise in preventing BCRL. While the primary literature supporting ILR comes from academic institutions, the majority of breast cancer care in the USA occurs in the community setting. This study evaluated a preventative lymphedema program performing ILR at a community health system. PATIENTS AND METHODS: A prospective database including all patients who underwent ALND with concurrently attempted ILR from 2019 to 2021 was retrospectively reviewed. The historical benchmark lymphedema rate was calculated through retrospective review of electronic medical records for all patients who underwent ALND without ILR from 2011 to 2021. RESULTS: Ninety patients underwent ALND with ILR, of which ILR was successful in 69 (76.7%). ILR was more likely to be aborted in smokers (p < 0.05) and those with fewer lymphatic channels (p < 0.05) or a higher body mass index (BMI) (p = 0.08). Patients with successful versus aborted ILR had lower lymphedema rates (10.9% versus 66.7%, p < 0.01) and improved Disability of the Arm, Shoulder, and Hand (DASH) scores (8.7 versus 19.8, p = 0.25), and lower lymphedema rates than the historical benchmark (10.9% versus 50.2%, p < 0.01). Among patients with successful ILR, older patients were more likely to develop lymphedema (p < 0.05). CONCLUSIONS: Successful ILR after ALND significantly reduced the lymphedema rate when compared with patients with aborted ILR and our institution's historical benchmark. Our experience supports the efficacy of ILR and highlights the feasibility of ILR within a community health system.

Contemporaneous Symptom Networks of Breast Cancer-Related Upper Limb Lymphedema: A Network Analysis.

BACKGROUND: Upper limb lymphedema (ULL) is a common and deliberating complication for breast cancer survivors (BCSs). Breast cancer survivors with ULL reported a wide range of symptoms. However, little is known about symptom patterns and interrelationships among them. This study was designed to explore symptom clusters and construct symptom networks of ULL-related symptoms among BCSs and to identify the core symptoms. METHODS: This study is a secondary data analysis using datasets from three cross-sectional studies of BCSs in China. A total of 341 participants with maximum interlimb circumference ≥2 cm and complete responses in Part I of the Breast Cancer and Lymphedema Symptom Experience Index were included. Symptom clusters were identified through principal component analysis, and multiple linear regression analysis was employed to explore factors associated with severity of overall ULL-related symptoms. A contemporaneous network with 20 frequently reported symptoms were constructed after controlling for covariates. RESULTS: Three symptom clusters, including lymph stasis symptom cluster, nerve symptom cluster, and movement limitation symptom cluster, were identified. Postsurgery time, axillary lymph node dissection, and radiotherapy were associated with the severity of ULL-related symptoms. Tightness (rs = 1.379; rscov = 1.097), tingling (rs = 1.264; rscov = 0.925), and firmness (rs = 1.170; rscov = 0.923) were the most central symptoms in both networks with and without covariates. CONCLUSIONS: Breast cancer survivors with ULL experienced severe symptom burden. Tightness, tingling, and firmness were core symptoms of ULL among BCSs. Our findings demonstrated that the assessment and targeted intervention of specific core symptoms might help to relive effectively the burden of ULL-related symptom among BCSs.

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.

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.

Lymphedema self-management mobile application with nurse support for post breast cancer surgery survivors: description of the design process and prototype evaluation.

BACKGROUND: Self-management is the key to control breast cancer related lymphedema (BCRL). This study aimed to develop a mobile application with nurse support for lymphedema self-management and evaluate its usability from the patients' points of view. METHODS: This applied developmental study was conducted on 87 women in a lymphedema clinic, Shiraz, Iran, May-November 2023. The study included three phases: development, distribution of the application and usability evaluation. In the development phase, the researchers developed application using the Java programming language. In distribution phase, the application was installed on the participants' phones. For usability evaluation, 87 patients completed the user satisfaction questionnaire after three months access to the application. Data was analyzed using descriptive and analytical statistics using SPSS software 22. P-value less than 0.05 was considered significant. RESULTS: We designed a self-management application specific to BCRL that included ten unique modules mainly related to patient education, interaction with peers and nurse, self-management support, and settings. The application mean usability score was 7.72 ± 1.08. The usability dimensions of "screen" (8.06 ± 1.02) and "terminology and systems information" (7.29 ± 1.62) received the highest and lowest mean scores, respectively. CONCLUSION: The application has new features to meet more patients' needs compared to what other existing lymphedema self-management applications already have addressed. The findings showed that the participants rated the application usability at the "good" level that is similar to some previous studies. Considering the unique nature of the application and its favorable usability, we recommend its use for BCRL self-management.

Lymphatic endothelial cell RXRα is critical for 9-cis-retinoic acid-mediated lymphangiogenesis and prevention of secondary lymphedema.

Secondary lymphedema is a debilitating disease characterized by abnormal soft tissue swelling and caused by lymphatic system dysfunction. Despite a high prevalence of secondary lymphedema after cancer treatments, current management is supportive and there are no approved therapeutic agents that can thwart disease progression. We have previously demonstrated that 9-cis-retinoic acid (9-cisRA) has the potential to be repurposed for lymphedema as it mitigates disease by promoting lymphangiogenesis at the site of lymphatic injury. Although the efficacy of 9-cisRA has been demonstrated in previous studies, the mechanism of action is not completely understood. In this study, we demonstrate that when RXRα is specifically deleted in lymphatic endothelial cells, 9-cisRA fails to induce lymphangiogenesis in vitro and prevent pathologic progression of postsurgical lymphedema in vivo. These findings demonstrate that downstream nuclear receptor RXRα plays a critical role in the therapeutic efficacy of 9-cisRA in postsurgical lymphedema.

Assessing breast cancer-related lymphedema screening and treatment gaps in a safety-net hospital.

BACKGROUND AND OBJECTIVES: We evaluated the unmet breast cancer-related lymphedema (BCRL) treatment and education needs at New England's largest safety-net hospital serving a diverse population by assessing prevalence, risk factors, and treatment. METHODS: This was a retrospective cohort study examining breast cancer surgery patients from September 2016 to September 2021. The primary outcome was BCRL diagnosis. Secondary outcomes included BCRL risk factors, and physical and occupational therapy (PT/OT) referral frequency and completion. RESULTS: Of 639 patients, 17% of patients had documented BCRL, which was significantly associated with axillary lymph node dissection (ALND). There were no racial, insurance, breast radiation, or BMI category differences between patients with and without a BCRL diagnosis. Of those with BCRL, 58% received a PT/OT referral, and 56% completed their referral. There were no racial, insurance, or BMI category differences between those who received a PT/OT referral and those who did not. CONCLUSION: In our high-risk population, rates of documented BCRL were higher than expected, approaching rates of ALND, despite the majority undergoing sentinel lymph node biopsy (SLNB). PT/OT referral and completion rates were low, concerning for an unmet BCRL treatment and education need. No disparities in care delivery were seen, but a program that addresses treatment gaps and ensures accessible and patient-centered BCRL care is urgently needed.

Advances in lymphedema: An under-recognized disease with a hopeful future for patients.

Lymphedema has traditionally been underappreciated by the healthcare community. Understanding of the underlying pathophysiology and treatments beyond compression have been limited until recently. Increased investigation has demonstrated the key role of inflammation and resultant fibrosis and adipose deposition leading to the clinical sequelae and associated reduction in quality of life with lymphedema. New imaging techniques including magnetic resonance imaging (MRI), indocyanine green lymphography, and high-frequency ultrasound offer improved resolution and understanding of lymphatic anatomy and flow. Nonsurgical therapy with compression, exercise, and weight loss remains the mainstay of therapy, but growing surgical options show promise. Physiologic procedures (lymphovenous anastomosis and vascularized lymph node transfers) improve lymphatic flow in the diseased limb and may reduce edema and the burden of compression. Debulking, primarily with liposuction to remove the adipose deposition that has accumulated, results in a dramatic decrease in limb girth in appropriately selected patients. Though early, there are also exciting developments of potential therapeutic targets tackling the underlying drivers of the disease. Multidisciplinary teams have developed to offer the full breadth of evaluation and current management, but the development of a greater understanding and availability of therapies is needed to ensure patients with lymphedema have greater opportunity for optimal care.