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.

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.

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.

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.

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.

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.

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.

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.

The Impact of Obesity on Success of Immediate Lymphatic Reconstruction for Prevention of Breast Cancer-Related Lymphedema.

BACKGROUND: Breast cancer-related lymphedema (BRCL) is a potential sequela of high-risk breast cancer treatment. Preventive treatment with immediate lymphatic reconstruction (ILR) at the time of axillary lymph node dissection (ALND) has emerged as the standard of care; however, there is relatively little known about factors that may contribute to procedural failure. METHODS: A retrospectively maintained, institutional review board-approved study followed patients who underwent ILR at the time of ALND at our tertiary care center between May 2018 and May 2023. Patients who presented for at least one follow-up visit in our multidisciplinary lymphedema clinic met the criteria for inclusion. Patients who developed lymphedema despite ILR and potential contributing factors were further explored. RESULTS: 349 patients underwent ILR at our institution between May 2018 and May 2023. 341 of these patients have presented for follow-up in our multidisciplinary lymphedema clinic. 32 (9.4%) patients developed lymphedema despite ILR. This cohort was significantly more likely to be obese (56% vs 35%, P = 0.04). Multivariate logistic regression demonstrates increased odds of procedural failure in patients with a body mass index (BMI) ≥30 kg/m2 (odds ratio 2.6 [1.2-5.5], P = 0.01). CONCLUSION: These data comment upon our institutions outcomes following ILR. Patients who develop lymphedema despite ILR tend to have a higher BMI, with a significantly increased risk in patients with a BMI of 30 or greater. Consideration of these data is critical for preprocedural counseling and may support a BMI cutoff when considering candidacy for ILR going forward, as well as when optimizing failures for secondary lymphedema procedures.

Defining breast cancer-related lymphedema (BCRL) prevalence and risk factors: A pragmatic approach to lymphedema surveillance.

Introduction: We presented the key findings from Singapore's Changi General Hospital Breast Centre's lymphedema surveillance strategy that used patients' reported symptoms, standard arm circumference measurements and clinical assessment in the diagnosis of breast cancer-related lymphedema (BCRL). Our secondary aim was to highlight and discuss important elements of a surveillance strategy that can be implemented to track this outcome measure of breast cancer treatment for future research. Method: We conducted a cross-sectional study of 511 breast cancer patients to assess the prevalence of BCRL and its associated risk factors. We defined BCRL prevalence rates based on patients' self-reporting, objective arm circumference measure-ments and clinical diagnosis based on International Society of Lymphology (ISL) staging. Results: The median follow-up of patients was 88.8 months. The cumulative prevalence rate in the cohort was 30.9%. The cohort of BCRL patients were older (58.4 versus [vs] 54.9 years), had higher mean Body Mass Index (27.7 vs 25.2), higher proportion of mastectomy (77% vs 64.3%), axillary clearance, less likely breast reconstruction, higher-grade tumour, more lymph nodes excised, more advanced nodal disease, and had undergone adjuvant chemotherapy. However, clinically apparent BCRL was only 6.5% (33 out of 511 patients). The proportion of clinically significant BCRL in patients undergoing sentinel lymph node biopsy (SLNB) or axillary sampling was 1.7% compared to 9.9% in patients who had undergone axillary clearance. Majority of the BCRL were subclinical or mild in severity. Conclusion: Our study showed that our rates of BCRL were comparable to international rates and highlighted similar patient profiles who were at risk of developing the disease. Having a comprehensive lymphedema surveillance strategy is paramount in paving the way for future studies.

Primary Lymphovenous Anastomosis After Extended Soft Tissue Resection in the Medial Thigh for Reduction of Lymphocele and Lymphedema.

INTRODUCTION: Postoperative chronic lymphocele and lymphedema represent severe burdens for soft tissue sarcoma patients who are already physically handicapped after an extensive surgery and a long recovery time. Incidences are high in the upper medial thigh. We have shifted our focus to lymphedema and lymphocele risk reduction with immediate lymphovenous anastomosis (LVA) after sarcoma resection. METHODS: We performed immediate lymphatic reconstruction in 11 patients after soft tissue sarcoma resection in the upper medial thigh. The postoperative course was followed up closely, and postoperative occurrence of lymphocele and lymphedema was clinically assessed. A literature search outlining the latest clinical data, current treatment strategy landscape, and their application into clinical practice was added to the investigation. RESULTS: A total of 19 LVA and 2 lympho-lymphatic anastomoses were performed in 11 patients immediately after tumor resection in an end-to-end manner. We found a postoperative lymphedema rate of 36% and a postoperative lymphocele rate of 27%. Mean follow-up time was 17 months. Average tumor volume was 749 cc. Our literature search yielded 27 articles reporting on immediate LVA in cancer patients. Incidences of secondary lymphedema after LVA for lymphedema prevention vary between 0% and 31.1%. Lymphocele prevention with LVA is poorly studied in sarcoma patients. CONCLUSION: Immediate lymphatic reconstruction improved the overall postoperative course of our patients. The current literature does not serve with high-quality studies about primary LVA preventing lymphedema and lymphocele formation. We conclude that this technique should be seen as an additional concept to achieve overall better postoperative outcomes in these challenging surgical settings. We strongly recommend to either anastomose or ligate severed lymphatics under the microscope primarily after sarcoma resection in the upper medial thigh area.

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.

Comparing complex decongestive therapy in patients with lymphedema of different causes by measuring: extremity volume, quality of life, and functionality.

OBJECTIVE: This study aimed to investigate the effects of complex decongestive therapy (CDT) applied to the lower extremities of patients with lymphedema of different causes on the extremity volume, quality of life (QoL), and functionality. MATERIALS AND METHOD: The study included 90 patients, of whom 28 had primary lymphedema, 30 had secondary lymphedema, 18 had phlebolymphedema, and 14 had lipolymphedema. A total of 137 extremities were treated with CDT. The patients who received CDT for 5 days a week for 3 weeks (15 sessions in total) were included in the sample. Extremity volume was measured using a tape measure. The lymphedema QoL-Leg Questionnaire was used to evaluate QoL, and the lower extremity functional scale (LEFS) was administered to assess lower extremity functionality. RESULTS: The changes in QoL before and after treatment significantly differed in the primary lymphedema, phlebolymphedema, and lipolymphedema groups (p < 0.05). The post-treatment LEFS scores indicated a significant decrease in the phlebolymphedema and lipolymphedema groups compared to the pre-treatment scores (p < 0.05). CONCLUSIONS: The difference in appearance, which is one of the sub-parameters of QoL, significantly decreased in the comparisons performed between the groups, whereas the changes in the remaining parameters were not significant.

OBJETIVO: Investigar los efectos de la terapia descongestiva compleja (TDC) aplicada a las extremidades inferiores de pacientes con linfedema de diferentes causas sobre el volumen de la extremidad, la calidad de vida y la funcionalidad. MATERIALES Y MÉTODO: Se incluyeron en el estudio 90 pacientes, de los cuales 28 tenían linfedema primario, 30 linfedema secundario, 18 flebolinfedema y 14 lipolinfedema. Un total de 137 extremidades fueron tratadas con TDC. Se incluyeron en la muestra pacientes que recibieron TDC durante 5 días a la semana durante 3 semanas (15 sesiones en total). El volumen de las extremidades se midió con una cinta métrica. Se utilizó el Cuestionario de calidad de vida (QoL) de las piernas para el linfedema para evaluar la calidad de vida, y se administró la Escala funcional de las extremidades inferiores (LEFS) para evaluar la funcionalidad de estas. RESULTADOS: Los cambios en la calidad de vida antes y después del tratamiento difirieron significativamente en los grupos de linfedema primario, flebolinfedema y lipolinfedema (p < 0.05). Las puntuaciones LEFS posteriores al tratamiento indicaron una disminución significativa en los grupos de flebolinfedema y lipolinfedema en comparación con las puntuaciones previas al tratamiento (p < 0.05). CONCLUSIONES: La diferencia de apariencia, que es uno de los subparámetros de la calidad de vida, disminuyó significativamente en las comparaciones realizadas entre los grupos, mientras que los cambios en los demás parámetros no fueron significativos.