BACKGROUND:There is no standardized method for identifying fibrosis in the subcutaneous tissue of lymphedematous limbs. This study evaluated the relationship between ultrasonographic findings and fibrosis severity in patients with lower limb lymphedema. METHODS:A retrospective analysis included 92 sites in 40 limbs of 26 female patients undergoing lymphaticovenous anastomosis. Skin thickness and subcutaneous echogenicity were assessed preoperatively using an 18-MHz linear ultrasound probe and classified into four grades (U0-U3). Fibrosis severity was evaluated intraoperatively and classified into five grades (F0-F4). Receiver operating characteristic (ROC) curve analysis determined the diagnostic accuracy of skin thickness for predicting severe fibrosis (F3/F4), and a regression model was developed to predict fibrosis severity. RESULTS:Skin thickness was significantly greater in the calves (2.7 mm) than in the thighs (2.1 mm, p < 0.01) and increased with lymphedema stage. Fibrosis severity was higher above the superficial fascia and more prevalent in calves (p < 0.01). ROC analysis showed an area under the curve of 0.80 for calf (above the superficial fascia), with a cutoff of 2.65 mm. The regression model (R2 = 0.51, p < 0.001) demonstrated that skin thickness and fat echogenicity significantly predicted fibrosis severity: Fibrosis severity = 0.21 + 0.32 × skin thickness (mm) + 0.45 × fat echogenicity grade. CONCLUSIONS:Ultrasound-based measurements of skin thickness and fat echogenicity are reliable and noninvasive predictors of fibrosis severity in patients with lymphedema. These findings support the use of ultrasound imaging to guide treatment planning and improve surgical outcomes. However, further validation is needed in diverse populations.
The incidence of gynecological malignancies continues to increase worldwide. Lower limb lymphedema is perhaps the most dreaded long-term complication related to gynecological malignancy surgery. Identifying the early risk factors for lower limb lymphedema can facilitate targeted prevention and improve the prognosis of patients. To systematically review and evaluate existing studies on prediction models for lower limb lymphedema after surgery in patients with gynecological malignancies. PubMed, Embase, Web of Science, the Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database, China Biomedical Literature Database, ProQuest Dissertations & Theses, medRxiv, and Google Scholar were systematically searched from inception to December 1, 2024. Studies were appraised critically, and data were extracted by two authors independently based on the Prediction Model Risk of Bias Assessment Tool and Data Extraction for Systematic Reviews of Prediction Modeling Studies. A total of 9 studies were included, involving 10 relevant prediction models. Five studies reported calibration; validation involved internal (n = 7) or both (n = 2). Discrimination varied across models (the area under the curve [AUC] range: 0.63-1.00), with 9 of 10 models reporting AUC values >0.70. However, calibration reporting was incomplete, and all studies were rated as high risk of bias. Although all studies demonstrated good applicability, all were rated as high risk of bias. Across all included studies, age, body mass index, hypertension, diabetes, tumor stage, postoperative drainage time, lymph node dissection, and radiotherapy were the most frequently reported predictors. Among them, lymph node dissection-related variables were included in eight of the ten models, while radiotherapy was included in 7 of 10 models. Although several models reported moderate to good discrimination, overall methodological quality was limited. The predominance of high risk of bias, scarce external validation, and restricted geographic diversity constrains the strength of the current evidence. More rigorously designed and externally validated models are needed before routine clinical implementation.
The connection between the peripheral lymphatic system (PLS) and the central lymphatic system (CLS) plays a crucial role for the overall circulatory system. Notably, there are several similarities between lymphedema and Alzheimer's disease (AD). Accumulating evidence suggests that lymphedema might be associated with AD, potentially influencing its progression through mechanisms related to the peripheral-central lymphatic circulation. This review summarizes the lymphatic system's structure, function, and drainage pathways, emphasizing how aging and blockage of the CLS can exacerbate the progression of AD. Additionally, we discuss the relationship between lymphedema and AD, highlighting the significance of the PLS-CLS and exploring lymphaticovenous anastomosis as a promising treatment for both lymphedema and AD.
BACKGROUND:Ultrasonographic subcutaneous tissue parameters have previously been used as outcome measures in the evaluation of breast cancer-related lymphedema (BCRL). However, their ability to detect clinically meaningful changes-referred to as responsiveness-has not yet been examined. This study aimed to investigate the responsiveness of ultrasonographic subcutaneous tissue thickness measurements, subcutaneous echogenicity (SEG), and subcutaneous echo-free space (SEFS) changes. METHODS AND RESULTS:Forty patients with International Society of Lymphology Stage 2-3 unilateral lymphedema underwent phase 1 complex decongestive therapy three times weekly for 4 weeks. Ultrasonographic subcutaneous tissue thickness, SEG, and SEFS, alongside circumferential measurements, limb volume, and visual analog scale scores for pain, heaviness, and tightness, were evaluated pre- and posttreatment. Significant symptomatic improvement was observed (p < 0.0001). Edema volume and percentage decreased significantly (p = 0.012 and p = 0.006). Subcutaneous tissue thickness significantly decreased at the upper arm medial, medial epicondyle, and wrist (p < 0.02), demonstrating the highest responsiveness (effect size = 1.74). In contrast, changes in SEG and SEFS were statistically significant only at limited sites and showed small to negligible responsiveness overall; however, SEFS showed comparatively higher responsiveness at the wrist, the site with the greatest baseline free-fluid accumulation. Circumferential and volumetric measures showed low responsiveness. CONCLUSION:Subcutaneous tissue thickness was the most sensitive ultrasonographic marker in BCRL, followed by symptom scores. SEG and SEFS showed limited overall responsiveness, although SEFS remained meaningful at the wrist. Edema volume and percentage showed greater responsiveness than overall limb volume and circumferential measurements. Integrating subcutaneous thickness with edema-specific and symptom assessment may enhance monitoring of therapeutic outcomes.
The connection between the peripheral lymphatic system (PLS) and the central lymphatic system (CLS) plays a crucial role for the overall circulatory system. Notably, there are several similarities between lymphedema and Alzheimer’s disease (AD). Accumulating evidence suggests that lymphedema might be associated with AD, potentially influencing its progression through mechanisms related to the peripheral–central lymphatic circulation. This review summarizes the lymphatic system’s structure, function, and drainage pathways, emphasizing how aging and blockage of the CLS can exacerbate the progression of AD. Additionally, we discuss the relationship between lymphedema and AD, highlighting the significance of the PLS–CLS and exploring lymphaticovenous anastomosis as a promising treatment for both lymphedema and AD.
PURPOSE:Cancer-related fatigue (CRF) is the most common symptom of cancer patients. This study aimed to investigate the prevalence of CRF among patients with breast cancer-related lymphedema (BCRL) and to indentify the factors associated with its occurrence. METHODS:In this cross-sectional study, women with BCRL (N = 260) were recruited from the three general hospitals. Lymphedema status was determined using the Norman telephone questionnaire as the patient-reported occurrence of hand/lower arm/upper arm swelling. CRF status was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire. Multiple binary logistic regression analysis was used to identify factors associated with CRF. RESULTS:The median time from BC diagnosis was 29 months (interquartile range, 15.0-62.0 months). The prevalence of CRF among BCRL patients was 88.46%. The median sedentary time was 245 min/day (IQR: 150-330min/day), and 34.23% of the patients did not meet the moderate-intensity physical activity level. Abnormal postoperative wound healing status, radiotherapy, hormonal therapy, lymphedema severity and failure to meet moderate-intensity physical activity level were associated with an increased risk of CRF. CONCLUSION:CRF is highly prevalent among patients with BCRL. Targeted interventions aimed at promoting moderate-intensity physical activity and improving long-term symptom management may help alleviate fatigue.
PURPOSE:In times when health and physical activity are gaining in value, the search for effective methods to support fitness and improve quality of life is becoming a priority. One of the therapies that is gaining increasing popularity is pressotherapy, which supports the regeneration of the body on many levels. METHODS:The study was conducted on a group of 15 healthy, young women. The participants underwent 10 pneumatic compression therapy treatments using the CarePump Expert8 device. The participants were examined 4 times: a week before the first treatment, immediately before the first treatment, after the 10th treatment and a week after the 10th treatment. RESULTS:Statistical analysis of mean changes in the range of motion values showed significant decrease in: right (p < 0.05) and left (p < 0.05) hip joint extension; right (p < 0.05) hip joint horizontal abduction; horizontal adduction of the right (p < 0.05) and left (p < 0.05) hip joint; dorsiflexion of the right (p < 0.05) and left (p < 0.05) ankle joint, and also an increase in: right (p < 0.05) and left (p < 0.05) hip external rotation. Statistical analysis of changes in mean values of circumferences showed significant decrease at all tested levels: P1 right (p < 0.05) and left (p < 0.05); U1 right (p < 0.05) and left (p < 0.05); U2 right (p < 0.05) and left (p < 0.05); K right (p < 0.05) and left (p < 0.05); G1 right (p < 0.05); and left (p < 0.05); G2 right (p < 0.05) and left (p < 0.05). CONCLUSIONS:A series of pressotherapy sessions did not improve lower limb range of motion or body composition indices; however, it did reduce circumferences at all levels of the lower limbs. Long-term use of pressotherapy can help maintain healthy fluid levels, improve circulation, and improve overall physical fitness.
BACKGROUND:There are few objective tools to quantify lymphatic disease changes in anatomy and physiology of affected tissues. Tissue sodium could be a relevant physiological indicator of lymphatic disease. However, the importance of sodium to lymphatic physiology in humans has not been well-characterized nor exploited for clinical applications due to a lack of imaging methods to observe sodium and lymphatics together in vivo. The purpose of this study was to apply 23Na-MRI to measure tissue sodium content (TSC) in human subjects with or without lower extremity lymphedema (LEL) and investigate the relationship between lymphatic dysfunction and tissue sodium. METHODS AND RESULTS:A prospective, cross-sectional observational clinical trial enrolled participants with LEL and controls without lymphedema. 23Na-MRI measured standardized TSC in the mid-calf. For each leg with lymphedema, clinical stage was determined by a licensed clinician, and lymphedema severity was determined by radiology assessment of noncontrast hydrogen (1H)-magnetic resonance lymphangiography (MRL). Linear mixed-effects models determined differences in TSC between cases and controls and measured the association of TSC with clinical stage and lymphedema severity. Image subregions were analyzed to observe spatial patterns of TSC involvement. Results found that TSC was nearly 50% higher in lymphedema (n = 52 legs) in the skin (1.51-fold) and adipose tissue (1.47-fold) compared with controls (n = 31 legs; p < 0.001) and was directly related to both clinical stage and lymphedema severity by 1H-MRL in the skin (p < 0.001) and adipose tissue (p < 0.001). TSC accumulated in patterns in the anterior subcutaneous adipose tissue, increasing with disease severity. CONCLUSION:23Na-MRI demonstrates that standardized TSC is distinctly elevated in lymphedema, sensitive to lymphedema disease severity, and a potential objective imaging tool for evaluating lymphedema in future clinical trials.
BACKGROUND/AIM:Although various distinctive morphological features such as hyperproliferation of adipocytes, fibrosis, and inflammation have been described in the progression of lipedema, the underlying mechanisms of these changes are not yet fully understood. In this study, we aimed to investigate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), and platelet distribution width (PDW) to demonstrate the role of inflammation in lipedema. METHODS:The retrospective study consisted of 60 lipedema patients (Group 1) and 40 healthy controls (Group 2). The age, height, weight, and body mass index (BMI) of all participants were recorded, along with the lipedema type and stage for Group 1. Laboratory results, including complete blood count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), were obtained for all participants. Hemoglobin, leukocyte, lymphocyte, neutrophil, and platelet counts, NLR, PLR, MPV, PDW, CRP, and ESR were evaluated. RESULTS:The mean age was 45.45 ± 10.17 years in Group 1 and 44.90 ± 10.69 years in Group 2; the BMI was 32.15 ± 5.05 in Group 1 and 30.94 ± 4.98 in Group 2, with no significant difference between the groups (p > 0.05). The most common type was Type 2 lipedema. Platelet counts, CRP, NLR, and PLR levels were significantly higher in Group 1 than in Group 2 (p < 0.05). There was no difference between groups in MPV and PDW values (p > 0.05). There was a positive correlation between BMI and both leukocyte count and CRP levels (p < 0.05). CONCLUSION:In our study investigating inflammation in lipedema-an etiology that is still not fully understood-NLR, PLR, platelet count, and CRP levels were found to be significantly higher in the patient group. The increase in BMI was correlated with leukocyte count and CRP levels. This finding is important for elucidating the etiopathogenesis of the disease, and we believe it may guide future research in this area.
BACKGROUND:Lipedema is a chronic connective tissue disorder characterized by painful subcutaneous adipose accumulation, mainly in the lower extremities. Pain is a hallmark feature, yet its mechanisms remain poorly defined. Neuropathic components may contribute, but direct comparisons with lymphedema are scarce. METHODS:In this exploratory cross-sectional study, 118 female patients with lipedema (n = 62) or bilateral lower extremity lymphedema (n = 56) were assessed. Pain intensity was measured with the Visual Analogue Scale (VAS). Neuropathic pain was evaluated with painDETECT and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS). Psychological status was measured using the Hospital Anxiety and Depression Scale (HADS), cognitive-emotional aspects with the Pain Catastrophizing Scale (PCS), and health-related quality of life with the WHOQOL-BREF. RESULTS:Lipedema patients reported higher pain severity (VAS 6.2 ± 1.4 vs. 5.5 ± 1.5, p = 0.02) and greater neuropathic pain prevalence (42% vs. 21%, p < 0.01) than lymphedema. painDETECT and LANSS scores were significantly higher in lipedema (p < 0.001). HADS-Anxiety (10.2 ± 3.8 vs. 7.8 ± 3.5, p = 0.005) and PCS scores (29.5 ± 7.2 vs. 25.4 ± 6.5, p = 0.03) were also elevated, while HADS-Depression was slightly higher in lymphedema without significance. WHOQOL-BREF scores were similarly reduced in both groups compared to population norms. Correlation analyses showed strong associations between pain intensity, neuropathic features, catastrophizing, and anxiety, particularly in lipedema. CONCLUSIONS:A substantial proportion of lipedema patients exhibit neuropathic pain features and higher pain severity compared with lymphedema, while anxiety and pain catastrophizing appear to amplify symptom burden; however, quality-of-life impairment is substantial in both conditions, and the findings should be interpreted as hypothesis-generating with implications for more individualized management approaches.
BACKGROUND:Recent studies have consistently shown that patients with lipedema are at a higher risk for depression and anxiety. The aim of this study is to identify the psychological factors associated with lipedema syndrome (LS) and their link to the patient's psychological symptomatology. METHODS:A mixed-methods approach was employed, combining quantitative and qualitative components. The quantitative component involved anonymous online questionnaires, including a Health and Demographic Questionnaire, the body satisfaction and global self-perception questionnaire (BSGSPQ), the lymphedema quality of life questionnaire (LYMQOL), and the Hospital Anxiety and Depression Scale (HADS). The qualitative component consisted of oral interviews to explore the complexity of the phenomenon. Participants included those with "easy bruising," a waist-to-hip ratio ≤0.7 (W/H), and pain levels ≥4/10 on the visual analogue scale (VAS). RESULTS:Our findings indicate that the level of depression is positively correlated with spontaneous pain (p = 0.002; r = 0.331) and the lack of medical understanding (p = 0.011; r = 0.229). Anxiety scores are inversely correlated with body satisfaction (r = -0.317) and global self-perception (r = -0.393); similarly, depression scores show similar correlations with body satisfaction (r = -0.445) and global self-perception (r = -0.608), all with p value of <0.0001. DISCUSSION AND CONCLUSION:This study highlights significant connections between the physical symptoms and mental health in patients with LS. The more affected the self-perception, the greater the depression and anxiety levels. These multiple contributing factors may explain the decline in quality of life (QOL) and deterioration of mental health. It is therefore crucial to proactively integrate mental health management into the care of LS patients. Future research should focus on identifying concrete, actionable methods to support women experiencing LS.
BACKGROUND:Primary lymphedema is a rare, chronic condition characterized by impaired lymphatic function, leading to the development of edema. It is caused by genetic mutations affecting lymphatic vessel development, and its clinical presentation is highly variable. While research has focused on identifying genetic causes, the underlying pathophysiology remains poorly understood, limiting the efficacy of available therapeutic strategies. In this monocentric case-control study, we investigate the histological and molecular characteristics of primary lymphedema patients and microsurgical outcomes. METHODS AND RESULTS:Biopsies from affected and unaffected extremities of 15 primary lymphedema patients undergoing lymphatic reconstructive surgery were collected, analyzed, and compared with eight healthy control samples. Histological and molecular markers were assessed on skin and fat samples, respectively. In addition, clinical data, pre- and postoperative volume measurements, and patient-related outcomes following lymphatic reconstructive surgery were evaluated. Our findings reveal significantly reduced cutaneous fibrosis as well as downregulation of CLDN5 and VEGFD expression in primary lymphedema patients. Notably, expression of TJP1 was significantly decreased in the affected, but not the unaffected side of these patients. Microsurgical outcomes, including volume loss and patient-reported quality of life measures, showed notable variability, being inconclusive. CONCLUSIONS:Our findings highlight a distinct pathophysiological profile in primary lymphedema, characterized by unexpected extracellular matrix alterations and increased vascular permeability, both locally and systemically. These insights improve our understanding of the disease mechanisms and potentially suggest a novel link between lymphatic dysfunction and fibrosis development. Further research is needed to address the demand for individualized treatment strategies.
OBJECTIVE(S):Sentinel lymph node (SLN) mapping commonly involves presurgical administration of a radioactive colloid and intraoperative injection of a blue dye near the tumor. Combining gamma scintigraphy and visual inspection could reduce false-negative rates. This study introduces novel imaging agents-radioactive nanoliposomes (NLs) encapsulating patent blue dye-for lymph node scintigraphy. MATERIALS AND METHODS:PEGylated (PEG-NLs) and non-PEGylated (non-PEG-NLs) NLs were prepared using the thin-film hydration method with patent blue dye and labeled with 99mTc-hexamethylpropylene-amine-oxime (99mTc-HMPAO). Lymphatic drainage of the radiolabeled liposomes was assessed in BALB/c mice following subcutaneous footpad injections. Planar imaging was performed at 0.5 and 1 hour postinjection. RESULTS:The mean diameter, zeta potential, and polydispersity index of the PEG-NLs were 130.7 ± 0.348 nm (n = 3), -22.4 ± 0.54 mV, and 0.118 ± 0.12, respectively. These values for the non-PEG-NLs were 120.46 ± 0.506 nm (n = 3), 7.5 ± 0.65 mV, and 0.055 ± 0.009, respectively. 99mTc-HMPAO-PEG-NLs had a significantly higher lymph node uptake at earlier times after injection (28.27 ± 5.22% ID/g at 1 hour and 16.65 ± 4.23% ID/g at 2 hours), which was followed by fast washout at 4 hours postinjection and showed fast migration of PEGylated NLs through lymphatic system. 99mTc-HMPAO-non-PEG-NLs had an increased lymph node accumulation through entire time after injection (11.95 ± 0.8% ID/g, 22.95 ± 4.56% ID/g, 29.71 ± 2.16% ID/g at 1, 2, and 4 hours, respectively). Encapsulation efficiency of patent blue dye was determined to be 1.26 ± 0.1%. CONCLUSION:99mTc-HMPAO PEG-NLs and non-PEG-NLs containing Paten Blue dye are promising agents for SLN mapping, offering distinct advantages in uptake kinetics and retention for lymphatic imaging and visual detection.
Background: Lower extremity lymphedema affects a growing number of cancer survivors. Standard-of-care therapy for lymphedema is complete decongestive therapy (CDT), yet the primary outcome measurement of therapeutic efficacy is limb volume, which is relatively insensitive to both well-managed and severe disease. The primary goal of this study was to examine whether physiological sodium magnetic resonance imaging ( 23 Na-MRI) is sensitive to the effect of CDT on leg lymphedema, and how this effect compares with the measurement reproducibility limits. Methods and Results: Participants with lymphedema ( n = 11) underwent ≥5 sessions of CDT per participant in their affected leg(s) ( n = 12) over 9.2 ± 5.6 weeks, following individual treatment plans with a licensed therapist. At the baseline visit and intervention visit, at least one leg was scanned with 23 Na-MRI to measure tissue sodium content (TSC) in the skin, muscle, and adipose tissue. Control subjects ( n = 16) were scanned at two visits separated by a similar timeframe with no treatment to establish measurement reproducibility. Skin TSC significantly reduced by 4.32 mmol/L ( p = 0.027) in affected legs treated by CDT, a change greater than the reproducibility coefficient (RPC) (3.82 mmol/L) in controls. Adipose TSC decreased in treated legs (2.27 mmol/L; p = 0.046), a change less than the RPC (5.83 mmol/L). Muscle TSC ( p = 0.171) and leg circumference ( p = 0.764) did not decrease in treated legs. Conclusions: TSC is reduced in the skin of affected legs with lymphedema treated by CDT, which is observable within the reproducibility limits of 23 Na-MRI. Results provide a basis for applying sodium MRI to observe the physiological effects of emerging lymphedema therapies.
Background: Case management models (CMM) have proven effective in improving cancer patients' transition from hospitals back into the community. However, whether a CMM has long-term effects in improving cancer patients' health requires further investigation. Therefore, this study aimed to evaluate the short-term and long-term effects of a nurse-led CMM on upper limb function and the incidence of affected limb complications among postoperative breast cancer patients.Methods and Results: A non-concurrent, quasi-experimental design was used to compare upper limb function and the incidence of affected limb complications between two groups: a care as usual group (CAU; control group) and a CMM group (intervention group). This study was conducted in the largest department for breast cancer in south China, where women newly diagnosed with breast cancer (N = 157) were assigned to either the CMM group (n = 77, recruited from June to July 2017) or the CAU group (n = 80, recruited from June to July 2016). Data on limb function-including objective shoulder range of motion (ROM), muscle strength, and the subjective Functional Evaluation Scale of the Ipsilateral Shoulder and Arm Function (FESISA)-were collected at baseline (upon admission), and at 3, 6, and 12 months after surgery. Additionally, the incidence of limb pain, paresthesia, and lymphedema was measured at 3, 6, and 12 months postoperatively. The results showed that affected limb function decreased for more than one year, and the incidence of upper limb complications in both groups declined over time, except for lymphedema in the CAU group. Furthermore, patients in the CMM group demonstrated significantly better limb function and a lower incidence of limb complications compared to those in the CAU group.Conclusion: The nurse-led CMM is a feasible and effective approach to improve the short-term and long-term quality of care and patient outcomes among patients with breast cancer.
BACKGROUND:Breast cancer-related lymphedema (BCRL) remains a major chronic complication following axillary lymph node dissection (ALND), particularly in regions where locally advanced breast cancer is prevalent. While several clinical factors have been identified, the role of genetic predisposition in BCRL development remains underexplored. This study aimed to identify genetic and clinical factors associated with the development of BCRL, focusing on the Gap Junction Protein Alpha-4 (GJA4) rs705193 mutation as a potential biomarker. METHODS:This prospective cohort study was conducted on 106 breast cancer patients who consecutively underwent ALND in Dharmais Cancer Hospital from October 2022 until October 2024. BCRL was assessed using indocyanine green (ICG) lymphography during a 12-month follow-up. Clinical data were obtained from medical records. The GJA4 rs705193 mutations were analyzed in DNA samples from peripheral blood using Sanger sequencing. A multivariate Cox regression was used to evaluate the association of GJA4 mutation and clinical factors with BCRL. RESULTS:BCRL developed in 56 (52.8%) patients during follow-up. Subjects with BCRL exhibited a significantly higher body mass index (BMI) than those without BCRL (27.3 vs. 25.0 kg/m2, p = 0.023). GJA4 mutations were identified in 40 (37.7%) patients, comprising 25 (44.6%) patients with BCRL and 15 (30.0%) patients without BCRL. The multivariate Cox regression analysis demonstrated that GJA4 mutation (HR = 1.73, 95% CI: 1.01-2.99, p = 0.047) and BMI (HR = 1.75; 95% CI: 1.02-3.02; p = 0.043) were significantly associated with an increased risk of BCRL. CONCLUSIONS:The GJA4 rs705193 mutations and elevated BMI independently increase the risk of BCRL in patients undergoing ALND. These findings enable the development of targeted preventive strategies for individuals at high risk.
PURPOSE:To examine the association between clinical severity and lymphatic function of breast cancer-related lymphedema. METHODS AND RESULTS:A total of 151 patients with lymphedema after breast cancer-related mastectomy were enrolled. The clinico-functional correlation was determined after examining lymphatic function via indocyanine green (ICG) lymphography in patients with breast cancer-related lymphedema and the severity of edema and degree of fibrosis via ultrasound, bioimpedance analysis, and tissue dielectric constant of the upper extremity. The results indicated a significant correlation of ICG dermal backflow (DB) patterns with subcutaneous thickness, limb index ratio, and the extracellular fluid accumulation in the affected side in the medial and lateral forearm and hand. However, no significant correlation was observed between ICG DB patterns and parameters related to fibrotic changes of the lesion, including regional resistance to compression and shear wave velocity. CONCLUSION:In patients with upper-extremity lymphedema, superficial lymphatic function had a significant correlation with subcutaneous edema and extracellular fluid accumulation.
BACKGROUND:Breast cancer-related lymphedema (BCRL) is associated with lymphatic fluid accumulation and subcutaneous tissue thickening, influencing the skin's biomechanical properties. Although several studies have used the Cutometer® to assess skin elasticity in lymphedema, the relationship between viscoelastic parameters and subcutaneous fluid retention remains unclear. This study aimed to clarify how skin viscoelasticity relates to subcutaneous tissue thickening and fluid accumulation in patients with BCRL. METHODS AND RESULTS:The study included 17 women who underwent unilateral breast cancer treatment and subsequently developed BCRL; 3-Tesla magnetic resonance imaging (MRI) system was used to confirm subcutaneous lymphedema. An ultrasound device was used to measure skin and subcutaneous tissue thickness, and Cutometer® was used to measure skin elasticity. Based on all measurement sites were categorized into the following three groups according to the presence or absence of lymphatic fluid accumulation, based on MRI results: with water, without water, and unaffected side. Among the 10 skin viscoelasticity parameters, significant differences were observed among the three groups for Ur (immediate retraction), Ur/Ue (net elasticity), and Ur/Uf (biological elasticity). Spearman's rank correlation coefficient showed that Ur was not significantly correlated with skin thickness (ρ = 0.072, p = 0.56) or subcutaneous thickness (ρ = 0.197, p = 0.107). CONCLUSION:Ur was not significantly associated with tissue thickness, suggesting its sensitivity to lymphatic fluid accumulation. Ur may be a sensitive indicator for detecting subcutaneous fluid retention in BCRL. As a noninvasive parameter, it could complement current diagnostic tools and may be useful for longitudinal BCRL monitoring.
PURPOSE:Breast cancer-related upper limb lymphedema (BCRL), once established, requires lifelong self-management. Indocyanine green lymphography (ICGL) imaging is an approach used to visualize lymphatics to diagnose, stage, and guide lymphedema treatment. The impact of ICGL-based personalized conservative management on clinical outcomes (extracellular fluid measured by Lymphedema index [L-Dex] units) is unknown. This study aimed to explore the changes in strategies for BCRL management and clinical outcomes for 3 months following ICGL imaging. METHODS:Data from 20 female adults with BCRL who underwent ICGL imaging at the Australian Lymphedema Education Research and Treatment Center clinic at Macquarie University were included in this study. Data related to the ICGL findings, personalized conservative recommendations, and objective outcome measures were extracted. Data were analyzed retrospectively. RESULTS:Conservative recommendations post-ICGL were significantly different in the number of strategies from the pre-ICGL (median [IQR] = 6 [2] vs. 3 [6], p < 0.001). Likewise, the number of compression garments and types of fabric (flat knit) prescribed were significantly higher following ICGL, and these changes were largely maintained by participants at 3 months. There were positive influences of ICGL-guided conservative management changes on bioimpedance spectroscopy, indicating improvements in lymphedema severity. CONCLUSION:ICGL-guided personalized conservative recommendations often led to changes in participants' management, resulting in positive clinical outcomes.
BACKGROUND:Early diagnosis and treatment of breast cancer-related arm lymphedema (BCRAL) is essential to prevent progression. Local tissue water (LTW) can be assessed using the tissue dielectric constant (TDC), enabling detection before an increase of arm volume occurs. However, knowledge of the variation of LTW during cancer treatment and appropriate LTW thresholds for early detection of BCRAL is limited. The aim of this study was to examine differences in LTW between the arms, assess changes in LTW in each arm during adjuvant treatment, and calculate theoretical inter-arm thresholds for BCRAL. METHOD AND RESULTS:This retrospective cohort study included 120 women treated with axillary lymph node dissection and radiotherapy. At 4-6 weeks post-surgery, LTW was significantly higher in the contralateral upper arm and the forearm at the lateral site compared to the ipsilateral arm. At 3-4 months post-radiotherapy, LTW remained higher in the contralateral upper arm at the lateral site and the forearm at the medial site. LTW decreased at the medial site of the ipsilateral upper arm and at the ventral site of the contralateral upper arm. Potential TDC ratio thresholds to detect BCRAL, including 3 SD, were calculated as 1.40 in the upper arm and 1.30 in the forearm. CONCLUSION:At both follow-ups, LTW was higher in the contralateral arm at specific sites compared to the ipsilateral arm and decreased at specific sites in both arms during oncological treatment. The calculated TDC thresholds may improve detection of BCRAL and enhance the interpretation of lymphedema status during oncological treatment.
