Prevention and Treatment of Lymphedema in Breast Cancer.

Breast cancer related lymphedema (BCRL) affects many breast cancer survivors and drastically affects their quality of life. There are several surveillance methods for BCRL that are critical at early detection. Prevention of BCRL involves knowledge of alternatives to aggressive axillary surgery, avoidance of axillary surgery, and de-escalation of axillary surgery. There are also techniques to better delineate the anatomy in the axilla to avoid taking nodes that drain the upper extremity. A multidisciplinary approach with medical oncology and radiation oncology can also help avoid unnecessary surgery or radiation that can together strongly increase the risk of BCRL.

Chronic Wound Caused by Lymphorrhea after Skin Abscess Drainage on Lower Extremity: A Case Report.

ABSTRACT: Surgical operations such as lymph node dissection may inadvertently damage the lymphatic system and lead to lymphorrhea. Excessive lymphatic exudation can cause a chronic wound. However, for surgery that does not involve the lymphatic system, lymphorrhea is a rare postoperative complication. This case report describes a 38-year-old patient who presented with lymphatic cutaneous leakage after incision and drainage of a skin abscess on the lower extremity. Persistent lymphorrhea increased the amount of wound exudation, which affected wound healing. After treatment of the lymphorrhea, the lower extremity wound healed completely within 4 weeks and did not result in lymphedema. Ligation of lymphatic vessels is a simple and easily performed treatment method for lymphatic leakage.

Analysis of Different Lymphedema Assessment Tools in Women with Breast Cancer After Mastectomy.

Background: Lymphedema is a common complication after mastectomy in women with breast cancer. Several methods have been described to assess and diagnose lymphedema, one of the most studied being the perimeter and ultrasonography. However, the reliability of these methods and the correlation between them are still controversial. The aim of this study was to analyze the reliability of cytometry and ultrasound imaging in the assessment of lymphedema after mastectomy in women with breast cancer and to study the correlation between them. Methods and Results: A cross-sectional study was conducted in 29 women with mastectomy after breast cancer. Lymphedema in the arm was measured both with cytometry and ultrasonography. Reliability was calculated with intraclass correlation coefficient. The correlation between the two methods was carried out with the Pearson correlation coefficient. Both cytometry (M1: α = 0.999, ICC = 0.996; M2: = α = 0.998, ICC = 0.994) and ultrasonography (M1: α = 0.992, ICC = 0.976; M2: = α = 0.991, ICC = 0.973) are reliable methods to assess lymphedema in the arm. No significant correlation was found between them (p > 0.05). Conclusions: Cytometry and ultrasonography appear to be adequate for the measurement of edema in women with breast cancer after mastectomy. However, for an accurate measurement of lymphedema, these measurements should not be used interchangeably.

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.

Evidence for the clinical effectiveness of decongestive lymphoedema treatment for breast cancer-related arm lymphoedema, a systematic review.

PURPOSE: Early treatment is advised for breast cancer-related arm lymphoedema (BCRL), a common sequelae of breast cancer treatment. Expert guidance recommends two-phase decongestive lymphoedema treatment (DLT), although evidence is lacking for current treatment protocols and UK women are routinely offered self-treatment with hosiery. This systematic review considered evidence regarding treatment of early BCRL, that is, within 12 months of developing BCRL. METHODS: A systematic review of evidence for clinical effectiveness of DLT for women with less than 12-month BCRL duration (early BCRL) was undertaken using the Joanna Briggs Institute (JBI) method. Studies included women with < 12-month or mean < 9-month BCRL duration; some studies reported only one eligible group. The original search was conducted in 2016 and updated in 2018 and 2022. Methodological quality of identified studies was assessed using JBI critical appraisal instruments. Outcomes of interest were extracted with eligible results displayed in narrative and tabular format. Strength of evidence was rated using the GRADE system. RESULTS: Seven trials and three descriptive studies provided weak evidence (grade B) for effectiveness of DLT for early BCRL. Heterogeneous protocols limited comparison of findings. There was no evidence for the most effective treatment or treatment combination or optimal frequency or duration of treatment. CONCLUSION: There is no evidence to justify change in current lymphoedema treatment, whether self-treatment with hosiery (UK) or two-phase DLT (other countries). Further research for the early BCRL population is required. IMPLICATIONS FOR CANCER SURVIVORS: Women with early BCRL require early and effective treatment although this updated review shows there is still no evidence for what that treatment should be.

Lower limb lymphedema after surgical staging for endometrial cancer: Current insights and future directions.

Lower extremity lymphedema (LEL) is a common complication following surgical staging of endometrial cancer. LEL is a chronic condition associated with significant impact on patient morbidity and quality of life (QoL). This review aimed to report the current evidence in the literature on secondary LEL after surgical staging for endometrial cancer, focusing on the incidence based on different approaches to lymph node staging, diagnosis, risk factors, and the impact on QoL. Due to the absence of a standardized agreement regarding the methodology for evaluating LEL, the documented frequency of occurrence fluctuates across different studies, ranging from 0% to 50%. Systematic pelvic lymphadenectomy appears to be the primary determinant associated with the emergence of LEL, whereas the implementation of sentinel lymph node biopsy has notably diminished the occurrence of this lymphatic complication after endometrial cancer staging. LEL is strongly associated with decreased QoL, lower limb function, and negative body image, and has a detrimental impact on cancer-related distress reported by survivors. Standardization of lymphedema assessment is needed, along with cross-cultural adaptation of subjective outcome measures for self-reported LEL. The advent of sentinel lymph node mapping represents the ideal approach for accurate nodal assessment with less short- and long-term morbidity. Further research is needed to definitively assess the prevalence and risk factors of LEL and to identify strategies to improve limb function and QoL in cancer survivors with this chronic condition.

A comparative evaluation of the efficacy of complete decongestive therapy in the treatment of unilateral breast cancer-related lymphedema with and without metabolic syndrome.

AIM: This study aimed to investigate the effect of the presence of metabolic syndrome (MetS) on the limb volume and quality of life (QoL) of patients who underwent complex decongestive therapy (CDT) due to unilateral breast cancer-related lymphedema (BCRL). METHODS: Forty female patients with unilateral BCRL, of whom 20 had MetS (MetS group) and 20 did not have MetS (control group), were included in the study. The participants received CDT 5 days a week for 3 weeks. The participants' limb volume (percentage of excess volume (PEV) and percentage reduction of excess volume (PREV) was determined using a tape measure, and their QoL was assessed using the Lymphedema Quality of Life questionnaire (LYMQoL) before and after treatment. RESULTS: After the treatment, the PEV and PREV values and LYMQoL-symptoms scores of the patients improved (p < 0.05); however, the LYMQoL-function, appearance/body image, mood/emotions, and overall QoL scores did not change in the MetS group (p > 0.05). In the control group, the PEV and PREV values and the LYMQoL-appearance/body image, mood/emotions, and overall QoL scores improved (p < 0.05), but the LYMQoL-symptoms and LYMQoL-function scores did not change (p > 0.05). There was a greater increase in the post-treatment PEV and PREV values of the control group compared to the MetS group (p < 0.001). CONCLUSION: The study yielded that CDT was an effective treatment in BCRL with and without MetS; however, the improvement was greater in BCRL cases without MetS than in those with MetS. Therefore, the presence of MetS should be taken into account in the treatment of lymphedema in patients who develop BCRL. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT05426993. Registered 2022-06-16. https://clinicaltrials.gov/search?cond=NCT05426993.

Vascular Endothelial Growth Factor C (VEGF-C) Sensitizes Lymphatic Endothelial Cells to Oxidative-Stress-Induced Apoptosis through DNA Damage and Mitochondrial Dysfunction: Implications for Lymphedema.

Secondary lymphedema is caused by damage to the lymphatic system from surgery, cancer treatment, infection, trauma, or obesity. This damage induces stresses such as oxidative stress and hypoxia in lymphatic tissue, impairing the lymphatic system. In response to damage, vascular endothelial growth factor C (VEGF-C) levels increase to induce lymphangiogenesis. Unfortunately, VEGF-C often fails to repair the lymphatic damage in lymphedema. The underlying mechanism contributing to lymphedema is not well understood. In this study, we found that surgery-induced tail lymphedema in a mouse model increased oxidative damage and cell death over 16 days. This corresponded with increased VEGF-C levels in mouse tail lymphedema tissue associated with macrophage infiltration. Similarly, in the plasma of patients with secondary lymphedema, we found a positive correlation between VEGF-C levels and redox imbalance. To determine the effect of oxidative stress in the presence or absence of VEGF-C, we found that hydrogen peroxide (H2O2) induced cell death in human dermal lymphatic endothelial cells (HDLECs), which was potentiated by VEGF-C. The cell death induced by VEGF-C and H2O2 in HDLECs was accompanied by increased reactive oxygen species (ROS) levels and a loss of mitochondrial membrane potential. Antioxidant pre-treatment rescued HDLECs from VEGF-C-induced cell death and decreased ROS under oxidative stress. As expected, VEGF-C increased the number of viable and proliferating HDLECs. However, upon H2O2 treatment, VEGF-C failed to increase either viable or proliferating cells. Since oxidative stress leads to DNA damage, we also determined whether VEGF-C treatment induces DNA damage in HDLECs undergoing oxidative stress. Indeed, DNA damage, detected in the form of gamma H2AX (γH2AX), was increased by VEGF-C under oxidative stress. The potentiation of oxidative stress damage induced by VEFG-C in HDLECs was associated with p53 activation. Finally, the inhibition of vascular endothelial growth factor receptor-3 (VEGFR-3) activation blocked VEGF-C-induced cell death following H2O2 treatment. These results indicate that VEGF-C further sensitizes lymphatic endothelial cells to oxidative stress by increasing ROS and DNA damage, potentially compromising lymphangiogenesis.

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.

Complex decongestive therapy improves finger tapping score in patients with breast cancer-related lymphedema.

PURPOSE: Breast cancer-related lymphedema (BCRL) impairs upper limb function and cognitive performance. This study aimed to evaluate the effects of fifteen sessions of complex decongestive therapy (CDT) on fine motor performance and information processing speed in women with BCRL. METHODS: Thirty-eight women with BCRL (54.97 ± 10.78 years) were recruited in the study. Participants either received five times weekly CDT consisting of manual lymphatic drainage, skin care, compression bandaging, and remedial exercises (n = 19) or served as a wait-list control group (n = 19). We used the Finger Tapping Task to assess fine motor performance and the Digit Symbol Substitution Test to assess information processing speed. ANCOVA was performed to analyze the effect of CDT on the dependent variables, adjusting for covariates and baseline values. RESULTS: CDT significantly improved finger tapping score (p < 0.001) compared to the wait-list to the control group, whereas information processing speed did not significantly change (p = 0.673). CONCLUSION: The findings suggest that CDT is an effective conservative therapeutic approach to improve upper extremity fine motor function in women with BCRL. Future studies are needed to investigate the effect of CDT on different cognitive domains.

YouTube videos on lymphedema as an information source for Spanish speaking breast cancer survivors.

BACKGROUND: Breast cancer-related lymphedema in the upper limb remains one of the most distressful complications of breast cancer treatment. YouTube is considered a potential digital resource for population health and decision making. However, access to inadequate information or misinformation could have undesirable impacts. This cross-sectional study aimed to evaluate the reliability, quality and content of YouTube videos on lymphedema as an information source for Spanish-speaking breast cancer survivors. METHODS: A search of YouTube was conducted in January 2023 using the key words "breast cancer lymphedema" and "lymphedema arm breast cancer." Reliability and quality of the videos were evaluated using the Discern tool, content, source of production, number of likes, comments, views, duration, Video Power Index, likes ratio, view ratio and age on the platform. RESULTS: Amongst the 300 Spanish language videos identified on YouTube, 35 were selected for analysis based on the inclusion and exclusion criteria. Of the 35 selected videos, 82.9% (n = 29) were developed by healthcare or academic professionals and 17.1% (n = 9) by others. Reliability (p < 0.017) and quality (p < 0.03) were higher in the videos made by professionals. The Discern total score (r = 0.476; p = 0.004), reliability (r = 0.472; p = 0.004) and quality (r = 0.469; p = 0.004) were positively correlated with the duration of the videos. CONCLUSIONS: Our findings provide a strong rationale for educating breast cancer survivors seeking lymphedema information to select videos made by healthcare or academic professionals. Standardised evaluation prior to video publication is needed to ensure that the end-users receive accurate and quality information from YouTube.

The effect of exercise and educational programs for breast cancer patients on the development of breast cancer-related lymphoedema: secondary endpoint from a randomized controlled trial in the Setouchi Breast Project-10.

BACKGROUND: Although the association between higher physical activity and preventive effect on breast-cancer-related lymphoedema (BCRL) has been reported, it is unclear what intervention is optimal. We aimed to investigate the effect of exercise and educational programs on BCRL development. METHODS: This study was a secondary endpoint analysis from a prospective randomized controlled trial. We enrolled patients with stage 0-III breast cancer from March 2016 to March 2020 and randomly assigned them to the control (n = 111), education (n = 115), or exercise (n = 104) group. As secondary endpoint, we assessed the incidence of and preventive effect on BCRL at 12 months post-intervention. RESULTS: There were no significant differences in the incidence of BCRL at 12 months post-intervention between the exercise and control groups (9.8% and 10.8%, P = 0.83) and the education and control groups (11.6% and 10.8%, P = 1.00). There were no significant differences in time to BCRL onset from the day of surgery between the exercise and control groups (event rate at 12 months: 20.7% and 17.2%, log-rank, P = 0.54) and the education and control groups (18.8% and 17.2%, log-rank, P = 0.57). The multivariable analyses indicated that axillary dissection and obesity significantly increased the risk of BCRL [hazard ratio (HR): 2.36, 95% confidence interval (CI) 1.52-3.67 and HR: 1.68, 95% CI 1.07-2.63, respectively]. CONCLUSIONS: The intervention did not decrease the risk of BCRL, and axillary dissection and obesity were the risk factors of BCRL. TRIAL REGISTRATION NUMBER: UMIN000020595 at UMIN Clinical Trial Registry.

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.

[Research progress of breast reconstruction in the prevention and treatment of breast cancer-related lymphedema].

Advances in the diagnosis and treatment of breast cancer have significantly improved survival rates. Breast cancer-related lymphedema is the most common mid-and long-term complication after breast cancer surgery, which seriously affects the quality of life. Breast reconstruction can not only restore the shape of the breasts after mastectomy, but also reduce the occurrence of lymphedema to some extent. Immediate autologous breast reconstruction combined with lymphatic venous anastomosis (LVA) or vascularized lymph node transfer (VLNT) can effectively prevent lymphedema. Delayed breast reconstruction combined with LVA or VLNT can achieve the dual benefits of restoring the appearance and treating lymphedema at the same time. The autologous tissue flap can function as a bridge to promote lymphatic drainage, thus enhancing the treatment of lymphedema. The advances mentioned above in surgical techniques have provided a basis for decision making in breast reconstruction and the prevention and treatment of breast cancer-related lymphedema, and have also brought hope for improving the quality of life of patients.

New Strategy for Breast Cancer Related Lymphedema Treatment by Endermology: ELOCS Phase II Randomized Controlled Trial.

BACKGROUND: This phase II trial sought to be the first of its kind to estimate the success rate of endermology in reducing breast cancer-related lymphedema. PATIENTS AND METHODS: ELOCS is a French, monocentric, randomized, open-label phase II trial. Patients were randomized to receive the following over a 5-day treatment period: standard intensive decongestant treatment (IDT) (bandages and manual lymphatic drainage MLD) (group 1); IDT including bandages, MLD, and Cellu M6 (group 2); and IDT including bandages and Cellu M6 (Group 3). The main endpoint was the success rate in each group, (reduction of at least 30% in the excess volume). We estimated that endermology treatment (groups 2 and 3) would be of interest successes occurred in at least 21 out of 31 patients. RESULTS: A total of 93 patients were included (31 patients in each of the 3 groups). The median age was 64.5 years (IQR: [56.4-71.3]). Patients were treated with mastectomy (n = 35), axillary lymphadenectomy (n = 80), radiotherapy (n = 91), and chemotherapy (n = 68). The mean relative reduction in excess volume was 38% in group 1, 33% in group 2, and 34% in group 3. Success rate was 58.1% in group 1 (18/31, P = ,0237), 51.6% (16/31, P = ,5) in group 2, and 64.5% (20/31, P = ,075) in group 3. In the LPG groups (2 and 3), 10/62 (16%) patients found LPG painful and 9/62 (15%) patients considered it to be unpleasant. CONCLUSION: Even though the critical threshold of 21 successes was not met, this study was the first to validate a standardized and reproducible endermology protocol.

An arabinogalactan isolated from Cynanchum atratum promotes lymphangiogenesis and lymphatic vessel remodeling to alleviate secondary lymphedema.

Secondary lymphedema is a chronic and incurable disease lacking satisfactory therapeutic drugs. It primarily results from lymphatic vessel dysfunction resulting from factors such as tumor-related surgery, injury, or infection. Promoting lymphangiogenesis and lymphatic vessel remodeling is crucial for restoring tissue fluid drainage and treating secondary lymphedema. In this study, we discovered that the oral administration of a type-II arabinogalactan (CAPW-1, molecular weight: 64 kDa) significantly promoted lymphangiogenesis and alleviated edema in mice with secondary lymphedema. Notably, the tail diameter of the CAPW-1200 group considerably decreased in comparison to that of the lymphedema group, with an average diameter difference reaching 0.98 mm on day 14. CAPW-1 treatment also reduced the average thickness of the subcutaneous area in the CAPW-1200 group to 0.37 mm (compared with 0.73 mm in the lymphedema group). It also facilitated the return of injected indocyanine green (ICG) from the tail tip to the sciatic lymph nodes, indicating that CAPW-1 promoted lymphatic vessel remodeling at the injury site. In addition, CAPW-1 enhanced the proliferation and migration of lymphatic endothelial cells. This phenomenon was associated with the activation of the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway, thereby promoting the expression of vascular endothelial growth factor-C (VEGF-C), which can be abolished using a TLR4 antagonist. Despite these findings, CAPW-1 did not alleviate the symptoms of lymphedema or restore lymphatic drainage in VEGFR3flox/flox/Prox1-CreERT2 mice. In summary, CAPW-1 alleviates secondary lymphedema by promoting lymphangiogenesis and lymphatic vessel remodeling through the activation of the TLR4/NF-κB/VEGF-C signaling pathway, indicating its potential as a therapeutic lymphangiogenesis agent for patients with secondary lymphedema.

Shoulder proprioception changes in postmastectomy patients: an observational study.

PURPOSE: Breast cancer surgery can cause changes in the anatomical structure of the shoulder and in shoulder mobility, leading to the increased possibility of long-term arm morbidity such as lymphedema. This study aims to evaluate the active shoulder joint position sense (AJPS) with and without lymphedema in postmastectomy patients. METHODS: A total of 66 women, including 22 patients with lymphedema, 22 patients without lymphedema, and 22 healthy controls, were enrolled in the study. Pain severity was evaluated with the Numeric Pain Scale and edema severity was measured with circumferentially at 10 cm intervals. The normal range of motion of the shoulder joint was evaluated with the universal goniometer and the AJPS was assessed by active position repetition testing at 55°, 90°, and 125° shoulder flexion targets using the smartphone application "Clinometer." RESULTS: AJPS at 55°, 90°, and 125° shoulder flexion target angles with and without lymphedema were different in all target angles compared to healthy controls (p < 0.01). There was a difference between the absolute error value of AJPS at 55° flexion (p < 0.05), and no difference at 90° and 125° flexion between the with and without lymphedema groups (p > 0.05). CONCLUSION: This study shows that the AJPS was negatively affected in with and without lymphedema postmastectomy patients compared to healthy controls. This result emphasizes the importance of adding personalized methods for the restoration of joint position sense in addition to rehabilitation programs generally applied to the patient group.