Lymphatic Research And Biology[JOURNAL]
Sun
200 papers
Prevalence and Predictors of Cancer-Related Fatigue in Breast Cancer-Related Lymphedema Patients: A Cross-Sectional Study.
Liu Y, Wang L, Zhou X … +5 more , Li Z, Ruan X, Su H, Zhang W, Liu F
Lymphat Res Biol · 2026 Jun · PMID 42334920 · Publisher ↗
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...
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 ( = 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.
The Effect of a Series of Lower Limb Pressotherapy Treatments on the Range of Motion of the Lower Limb Joints, Lower Limb Circumferences, and Body Composition in Young, Healthy Women.
Ptaszek B, Kurek O, Podsiadło S
Lymphat Res Biol · 2026 Jun · PMID 42322135 · Publisher ↗
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 incre...
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 ( < 0.05) and left ( < 0.05) hip joint extension; right ( < 0.05) hip joint horizontal abduction; horizontal adduction of the right ( < 0.05) and left ( < 0.05) hip joint; dorsiflexion of the right ( < 0.05) and left ( < 0.05) ankle joint, and also an increase in: right ( < 0.05) and left ( < 0.05) hip external rotation. Statistical analysis of changes in mean values of circumferences showed significant decrease at all tested levels: P1 right ( < 0.05) and left ( < 0.05); U1 right ( < 0.05) and left ( < 0.05); U2 right ( < 0.05) and left ( < 0.05); K right ( < 0.05) and left ( < 0.05); G1 right ( < 0.05); and left ( < 0.05); G2 right ( < 0.05) and left ( < 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.
Na-MRI Measures Tissue Sodium in Human Leg Lymphedema.
Taylor SL, Crain VN, Chen SC … +13 more , Pridmore MD, Garza ME, Beasley JA, Whaley CN, Darrington MP, Scott AO, Aumann M, Luo Y, Opoku A, Nwumeh N, Brown AJ, Donahue PMC, Crescenzi RL
Lymphat Res Biol · 2026 Jun · PMID 42286847 · Publisher ↗
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...
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 . The purpose of this study was to apply Na-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. Na-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 (H)-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 ( = 52 legs) in the skin (1.51-fold) and adipose tissue (1.47-fold) compared with controls ( = 31 legs; < 0.001) and was directly related to both clinical stage and lymphedema severity by H-MRL in the skin ( < 0.001) and adipose tissue ( < 0.001). TSC accumulated in patterns in the anterior subcutaneous adipose tissue, increasing with disease severity. CONCLUSION: Na-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.
Inflammatory Markers in Lipedema: A Comparative Analysis of Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Mean Platelet Volume.
Cagliyan Turk A, Erden E, Borman P
Lymphat Res Biol · 2026 Jun · PMID 42261591 · Publisher ↗
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 th...
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 ( > 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 ( < 0.05). There was no difference between groups in MPV and PDW values ( > 0.05). There was a positive correlation between BMI and both leukocyte count and CRP levels ( < 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.
Neuropathic Pain Features in Lipedema Compared to Lymphedema: An Exploratory Cross-Sectional Study.
Pervane S, Uzun Ö
Lymphat Res Biol · 2026 Jun · PMID 42253059 · Publisher ↗
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 defin...
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 ( = 62) or bilateral lower extremity lymphedema ( = 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, = 0.02) and greater neuropathic pain prevalence (42% vs. 21%, < 0.01) than lymphedema. painDETECT and LANSS scores were significantly higher in lipedema ( < 0.001). HADS-Anxiety (10.2 ± 3.8 vs. 7.8 ± 3.5, = 0.005) and PCS scores (29.5 ± 7.2 vs. 25.4 ± 6.5, = 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.
Lipedema: Exploring Relationship Between Physical and Psychological Symptoms in Affected Patients-A Mixed-Methods Study.
Seynhaeve B, Stoichkova V, Belgrado JP … +3 more , Janssens E, Lison E, Foucart J
Lymphat Res Biol · 2026 Jun · PMID 42249783 · Publisher ↗
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 synd...
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 ( = 0.002; = 0.331) and the lack of medical understanding ( = 0.011; = 0.229). Anxiety scores are inversely correlated with body satisfaction ( = -0.317) and global self-perception ( = -0.393); similarly, depression scores show similar correlations with body satisfaction ( = -0.445) and global self-perception ( = -0.608), all with 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.
Pathophysiological Changes in Primary Lymphedema: A Comprehensive Analysis of Histological and Molecular Alterations and Lymphatic Reconstruction Outcomes.
Plau J, Cassina C, Wolf S … +5 more , Grünherz L, Zurfluh CE, Giovanoli P, Gousopoulos E, Lindenblatt N
Lymphat Res Biol · 2026 May · PMID 42198873 · Publisher ↗
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...
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 and expression in primary lymphedema patients. Notably, expression of 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.
Formulation and Characterization of Patent Blue Dye Nanoliposome Labeled with Tc-HMPAO and Evaluation by Sentinel Lymph Node Mapping.
Heidari N, Abbasian H, Sahafi P … +8 more , Aghaee A, Beheshti S, Abbasi A, Badiee A, Zakavi SR, Jaafari MR, Sadeghi R, Sadri K
Lymphat Res Biol · 2026 Apr · PMID 42047043 · Publisher ↗
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 ins...
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 Tc-hexamethylpropylene-amine-oxime (Tc-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 ( = 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 ( = 3), 7.5 ± 0.65 mV, and 0.055 ± 0.009, respectively. Tc-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. Tc-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: Tc-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.
Lymphedema Care after Breast Cancer Surgery: Insights from a New Meta-Analysis.
Yan Z, Jiejie F, Wenhua S … +1 more , Yilin K
Lymphat Res Biol · 2026 Apr · PMID 41999182 · Publisher ↗
BACKGROUND: Lymphedema is a common complication after breast cancer surgery that significantly affects quality of life. This study aimed to synthesize current evidence on effective interventions for lymphedema care posts...
BACKGROUND: Lymphedema is a common complication after breast cancer surgery that significantly affects quality of life. This study aimed to synthesize current evidence on effective interventions for lymphedema care postsurgery. METHODS: A systematic literature search was conducted in PubMed, Cochrane Library, and Scopus to identify randomized controlled trials and observational studies published until September 2024. Included studies evaluated interventions for preventing and managing lymphedema, such as physical therapy [manual lymphatic drainage (MLD), exercise], compression therapy, and pharmacological treatments, reporting on lymphedema incidence, severity, or quality-of-life outcomes. Data were extracted by two independent reviewers, and a random-effects model estimated pooled effect sizes. Subgroup analyses were based on intervention types and design. RESULTS: Nine studies comprising 1183 patients were included. The pooled lymphedema incidence in control groups was 22.5% [95% confidence interval (CI): 19.3%-26.1%]. MLD reduced lymphedema incidence by 38% [risk ratio (RR) = 0.62, 95% CI: 0.52-0.74], whereas compression therapy decreased limb circumference by 15% (standardized mean difference = -0.33, 95% CI: -0.46 to -0.19). Exercise programs offered a 12% risk reduction (RR = 0.88, 95% CI: 0.76-1.03). Combined interventions, such as MLD with compression garments, yielded a 44% reduction in incidence (RR = 0.56, 95% CI: 0.47-0.67) and significantly improved quality of life (mean Functional Assessment of Cancer Therapy-Breast difference = 7.4, 95% CI: 5.1-9.7). Early and integrated care approaches showed the greatest benefit. CONCLUSIONS: This meta-analysis confirms MLD and compression therapy's effectiveness in managing postsurgical lymphedema. A multimodal approach provides optimal outcomes for reducing lymphedema burden and improving quality of life.
Tissue Sodium Response to Complete Decongestive Therapy in Lower Extremity Lymphedema.
Taylor SL, Crain VN, Donahue PMC … +10 more , Chen SC, Pridmore MD, Garza ME, Beasley JA, Darrington MP, Scott AO, Whaley CN, Luo Y, Brown AJ, Crescenzi RL
Lymphat Res Biol · 2026 Mar · PMID 41883042 · Publisher ↗
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 effi...
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 (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 ( = 11) underwent ≥5 sessions of CDT per participant in their affected leg(s) ( = 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 Na-MRI to measure tissue sodium content (TSC) in the skin, muscle, and adipose tissue. Control subjects ( = 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 ( = 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; = 0.046), a change less than the RPC (5.83 mmol/L). Muscle TSC ( = 0.171) and leg circumference ( = 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 Na-MRI. Results provide a basis for applying sodium MRI to observe the physiological effects of emerging lymphedema therapies.
Identifying Genetic Predisposition and Clinical Risk Factors for Breast Cancer-Related Lymphedema: Toward Personalized Prevention.
Putri RI, Sutandyo N, Siregar NC … +8 more , Wanandi SI, Harimurti K, Hernowo BS, Brahma B, Perdana AB, Widiasti I, Sari EK, Panigoro SS
Lymphat Res Biol · 2026 Feb · PMID 41700660 · Publisher ↗
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 s...
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/m, = 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, = 0.047) and BMI (HR = 1.75; 95% CI: 1.02-3.02; = 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.
Clinico-Functional Correlation of Upper Extremity Lymphedema Severity in Patients with Breast Cancer.
Lee BJ, Kong IJ, Yoon JA
Lymphat Res Biol · 2026 Jun · PMID 41700658 · Publisher ↗
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 mastectom...
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.
Indocyanine Green Lymphography-Guided Personalized Conservative Management Recommendations in Breast Cancer-Related Upper Limb Lymphedema: A Retrospective Study.
Paramanandam VS, Rogers C, Heydon-White A … +3 more , Gaitatzis K, Thompson B, Koelmeyer LA
Lymphat Res Biol · 2026 Feb · PMID 41700654 · Publisher ↗
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, sta...
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], < 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.
Evaluation of Skin Viscoelasticity in Breast Cancer-Related Lymphedema-Relationship with Subcutaneous Thickening and Fluid Retention.
Niwa S, Mawaki A, Nakanishi K … +8 more , Hisano F, Tsukioka K, Fukuyama A, Kikumori T, Shimamoto K, Imai K, Fujimoto E, Oshima C
Lymphat Res Biol · 2026 Jun · PMID 41700650 · Publisher ↗
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...
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, = 0.56) or subcutaneous thickness (ρ = 0.197, = 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.
Local Tissue Water Variations in Women at Risk of Developing Arm Lymphedema Following Breast Cancer Treatment-A Retrospective Study.
Blom K, Brogårdh C, Nilsson-Wikmar L … +2 more , Sackey H, Johansson K
Lymphat Res Biol · 2026 Jun · PMID 41640124 · Publisher ↗
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...
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.
Molecular Characterization of Vascular Anomalies Tissues Guides Clinical Diagnosis.
Henslee SB, Wooderchak-Donahue WL, Grimmer JF … +6 more , Szankasi P, Bolia A, Frigerio A, Stevenson DA, Flores Daboub JA, Bayrak-Toydemir P
Lymphat Res Biol · 2026 Jan · PMID 41574430 · Publisher ↗
BACKGROUND: Vascular anomalies are a group of common endothelial disorders that manifest a wide range of overlapping phenotypes, which complicate diagnosis. Next-generation sequencing (NGS) has led to the ability to dete...
BACKGROUND: Vascular anomalies are a group of common endothelial disorders that manifest a wide range of overlapping phenotypes, which complicate diagnosis. Next-generation sequencing (NGS) has led to the ability to detect low-frequency somatic variants, which may aid in the correct diagnosis and treatment of patients. Our goal was to identify the pathogenic variants in affected tissue taken from a cohort of 58 unrelated patients with various clinically diagnosed vascular anomalies. METHODS: DNA was extracted from fresh/frozen affected tissue samples and evaluated using a custom 735 vascular anomaly/cancer gene NGS panel down to 1% somatic mosaicism. RESULTS: Pathogenic or likely pathogenic variants were identified in 47% (27/58) of vascular anomaly tissue biopsies, including 61.5% (16/26) of lymphatic malformation (LM), 15% (3/20) of hemangioma (congenital and infantile), and 67% (8/12) of other various vascular anomalies. Two novel variants, c.3205_3206insTTTT (p.*1069Pheext*4) and c.1384_1395del (p.Glu462_Arg465del), were identified in LM tissue. In addition, we report a likely pathogenic variant c.512C>T (p.Thr171Ile) identified in a GLUT-1 positive infantile hemangioma lesion. The majority (52%) of the negative results were in infantile hemangioma tissue, for which a genetic cause has not yet been established. CONCLUSIONS: The 735 gene vascular anomaly/cancer NGS panel is an effective way to detect low levels of somatic mosaicism in these lesions. Given the challenge that many vascular anomalies present to diagnose, genetic testing is an invaluable tool for clinicians to utilize in the process of diagnosis and determining treatment.
CT Lymphangiography and Nonenhanced Magnetic Resonance Lymphangiography of Central Lymphatic Abnormalities in Patients with Central Conducting Lymphatic Anomalies.
Zhang Y, Zhang Y, Li X … +4 more , Liu M, Zhang M, Sun X, Wang R
Lymphat Res Biol · 2026 Feb · PMID 41460681 · Publisher ↗
OBJECTIVE: To investigate the diagnostic value of computed tomography lymphangiography (CTL) and nonenhanced magnetic resonance lymphangiography (MRL) for central conducting lymphatic anomaly (CCLA). MATERIALS AND METHOD...
OBJECTIVE: To investigate the diagnostic value of computed tomography lymphangiography (CTL) and nonenhanced magnetic resonance lymphangiography (MRL) for central conducting lymphatic anomaly (CCLA). MATERIALS AND METHODS: Clinical and laboratory examinations and imaging data of patients with CCLA diagnosed by lymphangiography between January 2017 and July 2023 were retrospectively analyzed. CTL and nonenhanced MRL were performed for all patients. And the evaluation indices of CTL and nonenhanced MRL included lymphatic ducts and trunks. The differences in the presence of any imaging abnormality between CTL and nonenhanced MRL were statistically analyzed, and < 0.05 was considered to indicate statistical significance. RESULTS: Forty-three patients had a greater percentage of nonenhanced MRL than CTL for the main trunk of the thoracic duct, the end of the thoracic duct, the main trunk of the right lymphatic duct, the end of the right lymphatic duct, the double subclavian trunk, and the iliac lymphatic vessels and a greater CTL display rate than did MRL for the intestinal trunk. Nonenhanced MRL in all CCLA patients revealed a tortuous and dilated thoracic duct trunk. Moreover, the end of the thoracic duct dilatation, increased number of branches, and cystic degeneration nonenhanced MRL were better than CTL. Right lymphatic duct dilatation nonenhanced MRL showed better than CTL, CTL showed intestinal trunk reflux better than nonenhanced MRL. CONCLUSION: CTL and nonenhanced MRL can be used to image the central lymphatic system. Nonenhanced MRL showing tortuous, and dilated thoracic duct trunk is one of the main diagnostic criteria for CCLA.
Ultrasonographic Evaluation of Distal Femoral Cartilage Thickness in Patients with Lower Extremity Lymphedema.
Kuzu Ö, Doğan Tosun GC, Aras B … +3 more , Özlemiş B, Kara T, Borman P
Lymphat Res Biol · 2026 Feb · PMID 41355451 · Publisher ↗
BACKGROUND: Cartilage thickness has been evaluated in many diseases, and its relationship with osteoarthritis has been investigated. However, the effect of lower extremity lymphedema on knee joint cartilage has not been...
BACKGROUND: Cartilage thickness has been evaluated in many diseases, and its relationship with osteoarthritis has been investigated. However, the effect of lower extremity lymphedema on knee joint cartilage has not been well investigated. This study aimed to evaluate the distal femoral cartilage thickness ultrasonographically in patients with unilateral lower extremity lymphedema and to investigate its relationship with clinical features. METHODS AND RESULTS: This cross-sectional study included 27 patients (mean age: 49.56 ± 12.06 years; 92.6% female) with unilateral lower extremity lymphedema. Distal femoral cartilage thickness of both knees was measured at the medial condyle, lateral condyle, and intercondylar notch by using ultrasound. Functional status and quality of life were assessed with the Lower Extremity Functional Scale and Lymphedema Quality of Life Questionnaire, respectively. The mean intercondylar notch cartilage was significantly thinner on the lymphedema side compared to the contralateral side (2.03 ± 0.41 mm vs. 2.24 ± 0.58 mm, < 0.05). Although the medial (1.96 ± 0.36 mm vs. 2.04 ± 0.42 mm) and lateral (1.90 ± 0.37 mm vs. 2.03 ± 0.41 mm) condyles were also thinner on the affected side, they were not statistically significant ( > 0.05). No significant correlations were identified between distal femoral cartilage thickness at the intercondylar notch and clinical features, functionality, and quality of life ( > 0.05). CONCLUSIONS: This study showed that distal femoral cartilage thickness, particularly at the intercondylar notch, is thinner in the affected limbs of patients with unilateral lower extremity lymphedema. These findings suggest that knee joint cartilage integrity may be affected in patients with lower extremity lymphedema and that ultrasonographic evaluation may be useful in this regard.
Effects of Aerobic Exercise with Manual Lymphatic Drainage in Chronic Venous Insufficiency Patients.
Sakızlı Erdal E, Özer A, Devecı Bulut TS … +3 more , Gülbahar Ö, Cindil E, Keser İ
Lymphat Res Biol · 2026 Feb · PMID 41335510 · Publisher ↗
BACKGROUND: This study aimed to examine the effects of aerobic exercise added to manual lymphatic drainage (MLD) on venous hemodynamics, inflammatory-vascularization markers, local tissue water percentages (LTW%), calf m...
BACKGROUND: This study aimed to examine the effects of aerobic exercise added to manual lymphatic drainage (MLD) on venous hemodynamics, inflammatory-vascularization markers, local tissue water percentages (LTW%), calf muscle endurance, exercise capacity, and quality of life (QoL) in patients with chronic venous insufficiency (CVI). METHODS: Participants were randomly assigned to one of two groups: (1) MLD group, which received MLD 5 days per week, and (2) MLD + aerobic exercise group, which received the same MLD plus aerobic exercise (30-minute walking sessions, three times per week) for 6 weeks. Venous hemodynamics was evaluated using Doppler ultrasonography. Inflammatory-vascularization markers, such as interleukin-6, vascular endothelial growth factor-A (VEGF-A), and some blood values were examined. LTW%, calf muscle endurance, exercise capacity, and QoL were evaluated with MoistureMeterD device, heel-rise test, 6-minute walk test (6MWT), and Venous Insufficiency Epidemiological and Economic Study on Quality-of-Life Questionnaire/Symptoms (VEINES-QOL/Sym), respectively. RESULTS: There was a significant increase in venous blood flow in the right great saphenous vein (GSV), VEGF-A, and QoL and a significant decrease in the diameter of the right GSV, monocytes, and LTW% in both groups. However, there was no superiority between groups. There was a significant increase in calf muscle endurance and exercise capacity in the group that added aerobic exercise compared to the MLD group ( < 0.05). CONCLUSIONS: Since positive effects of MLD on venous flow, edema, and QoL have been found, MLD can be used in physiotherapy programs for CVI. Adding aerobic exercise to MLD is an effective treatment for CVI by increasing calf muscle endurance and exercise capacity, in addition to these positive effects.
Using Group Concept Mapping to Define Priorities for Lymphedema Care and Research.
Myers SP, Cho MJ, Burke EE … +14 more , Ashworth K, Brophy L, Knauss B, Blaszkiewicz M, McAlearney AS, Quiroga D, Carson WE, Stover DG, Paskett ED, Rosas SR, Hock K, Skoracki RJ, Kotian C, Contreras CM
Lymphat Res Biol · 2026 Feb · PMID 41335506 · Publisher ↗
BACKGROUND: Cancer-related lymphedema is a common, lifelong, and disabling condition resulting from oncologic treatments. Although multidisciplinary collaboration enhances patient outcomes, a framework for research and t...
BACKGROUND: Cancer-related lymphedema is a common, lifelong, and disabling condition resulting from oncologic treatments. Although multidisciplinary collaboration enhances patient outcomes, a framework for research and therapeutic priorities for prevention and treatment is lacking. This study utilizes group concept mapping (GCM), a participatory research methodology, to highlight clinical and scholarly priorities. METHODS: Providers and researchers involved in lymphedema care at The Ohio State University, a Lymphatic Education & Research Network (LE&RN) Center of Excellence, participated in a GCM study between November 2024 and January 2025. The groupwisdom® web-platform was used to (1) generate ideas for clinical/academic priorities for multidisciplinary collaboration, (2) sort priorities into categories, and (3) rate priorities on (a) the basis of their contribution to value-based care and (b) likelihood to secure research funding. Hierarchical cluster analysis yielded two-dimensional representations of conceptual similarity between items. Ratings were synthesized into GoZone plots demonstrating priorities most likely to secure funding and contribute to high-value care. RESULTS: Thirty-five participants identified 74 priority areas. Cluster domains included: (1) identification/validation of patient-reported outcome metrics, (2) optimizing prospective surveillance, (3) surgical prevention/management of lymphedema, (4) diagnosis of lymphedema and downstream sequelae, (5) identifying risk factors/prediction tools, (6) basic/translational research, and (7) access to care/resource utilization. Improving access to care and mitigating resource barriers were deemed most impactful for delivering high-value care and ability to secure research funding. CONCLUSIONS: Priorities identified at our LE&RN Lymphedema Center of Excellence provide a framework for multidisciplinary collaboration to improve care delivery and patient outcomes for those with and at-risk for cancer-related lymphedema.
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