Limb Lymphedema Research Articles

Collagen Hydrogel Loaded With 9-cisRA-Lip Is an Option for Treatment of Secondary Lymphedema after Surgery.

Background: Secondary upper limb lymphedema is easy to occur after breast cancer surgery, for which treatment is limited. 9-cis-retinoic acid (9-cisRA) has been demonstrated to increase lymphangiogenesis without enhancing tumor metastasis but has the disadvantages of poor water solubility, easy decomposition in light, unstable to heat, and short half-life. Methods: Based on this, 9-cisRA-Lip with a particle size of roughly 143 nm and high dispersibility was prepared by thin-film dispersion method and verified by Malvern Laser Particle Size Analyzer and electron microscopy. Results: In vitro, 9-cisRA-Lip demonstrated good biosafety and tumor safety, promoting the proliferation of L929 cells while having no effect on 4T1 and Human Umbilical Vein Endothelial (HUVEC) cells. Compared with 9-cisRA, 9-cisRA-Lip was more effective at encouraging mouse lymphatic endothelial cell (SVEC4-10) migration, proliferation, and tube formation. In vivo, 9-cisRA-Lip-Gel showed good slow-release effect, mice treated with 9-cisRA-Lip-Gel one-time local injection had considerably less tail edema than the control group from day 9 to day 39 postsurgery (p < 0.05). This may be attributed to the greater capacity of 9-cisRA-Lip to enhance the phosphorylation of FGFR3 (Fibroblast Growth Factor Receptor 3) at Tyr 724. Conclusions: 9-cisRA-Lip-Gel presents a potential treatment option for lymphedema following surgery.

Mapping lymphatic filariasis morbidities in 24 endemic districts of Ethiopia through the health extension program

BackgroundThe primary strategy for achieving the second goal of the Global Program to Eliminate Lymphatic Filariasis (GPELF) is morbidity management and disability prevention (MMDP), aimed at alleviating the suffering of affected populations. A significant challenge in many LF-endemic areas is the effective registration and identification of individuals with LF, which is crucial for planning and ensuring access to MMDP services. This study seeks to map the geographical distribution of LF-related morbidities across 24 endemic districts in Ethiopia.MethodsA community-based cross-sectional study was conducted to identify individuals affected by LF in 24 endemic districts using primary health care units (PHCUs). The study involved 946 trained health extension workers (HEWs) conducting house-to-house visits to identify and register cases of lymphedema and hydrocele, with support from 77 trained supervisors and 87 team leaders coordinating the morbidity mapping. Certified surgeons performed confirmatory evaluations through clinical assessments on a randomly selected sample of cases to validate HEW diagnoses, ensuring accurate identification of lymphedema and hydrocele. Statistical analysis of the data, including the severity of lymphedema and acute attacks, was conducted using STATA 17.ResultsThis study involved 300,000 households with nearly 1.2 million individuals, leading to the identification of 15,527 LF cases—14,946 (96.3%) with limb lymphedema and 581 (3.7%) with hydrocele. Among those with lymphedema, 8396 (54.1%) were women. Additionally, 13,731 (88.4%) patients resided in rural areas. Of the 14,591 cases whose acute attack information was recorded, 10,710 (73.4%) reported experiencing at least one acute attack related to their lymphedema in the past 6 months, with a notable percentage of males (74.5%; n = 4981/6686). Among the 12,680 recorded cases of leg lymphedema, the percentage of acute attacks increased with severity: 64% (n = 5618) mild cases, 68% (n = 5169) moderate cases and 70% (n = 1893) severe cases.ConclusionThis study successfully mapped the geographical distribution of LF morbidities across 24 LF-endemic districts in Ethiopia, identifying a substantial number of lymphedema and hydrocele cases, particularly in rural areas where healthcare access is limited. The findings underscore the potential of Ethiopia’s health extension program to identify affected individuals and ensure they receive necessary care. The findings inform targeted interventions and access to MMDP services, contributing to Ethiopia’s goal of eliminating LF by 2027.

Adjustable compression wraps: back to the future

Adjustable Compression Wraps (ACWs) are used to treat a variety of conditions, in particular venous leg ulcers, edema and lymphedema. Publications on the use of these devices are ultimately few and far between, with limitations or biases (small sample sizes, methodological weaknesses, non-comparative studies, lack of interface pressures). A development model like that used in the study of a drug could be more rational. We propose five phases: phase 1) discovery and development, phase 2) in vitro testing, phase 3) clinical trials, phase 4) real-life data analysis, medico-economic investigation using Artificial Intelligence (AI), and phase 5) preparation of regulatory dossiers. This lack of coherence in development could be an obstacle to widespread clinical use. Using AI to analyse large quantities of data could reduce the cost and number of clinical trials needed to generate more robust evidence. This would make it possible to better define the clinical effects of ACWs in specific situations (e.g., leg wounds in the elderly, diabetic wounds, mixed leg ulcers, secondary lymphedema of the upper limb, efficacy, and comfort...) and to compare treatment costs between bandages and ACWs. If we don't explore the future with AI, we'll never know what will be useful for the present - hence the title “Back to the Future”.

Clinical Utility of Bioimpedance Analysis for Upper Limb Lymphedema with Surgical Treatment.

Background: In lymphedema, the accumulation of subcutaneous interstitial fluid is the most characteristic feature. Bioimpedance analysis (BIA) is a promising technique to measure the amount of body components using a noninvasive method. In this study, we determined the clinical significance of BIA parameters in upper limb lymphedema with surgical treatment such as lymphovenous anastomosis or vascularized lymph node transfer. Methods and Results: A single-center retrospective study using a multifrequency BIA. Perioperative BIA parameters such as extracellular water ratio or fat-free mass (FFM) ratio and limb volume defined as percentage of excess volume (PEV) were measured. The relationships between the magnitude of change in PEV and BIA parameters during surgery were evaluated. Out of 48 unilateral lymphedema patients, 46 were female and the average age was 55.4 years. PEV and all BIA parameters showed a significant decrease after surgery (p < 0.001). There were significant correlations between ΔPEV and the degree of changes in all BIA parameters. ΔFFM ratio showed the highest correlation with the amount of change in PEV (r = 0.599, p < 0.001). Conclusion: BIA parameters correlated well with the volume change after surgery. BIA could be useful as a quick and easy tool for follow-up after lymphedema surgery.

Construction of a nomogram for personalized prediction of lower limb lymphedema risk after cervical cancer surgery

ObjectiveThis study aims to construct and evaluate an individualized nomogram for predicting the risk of lower limb lymphedema after cervical cancer surgery. Healthcare professionals can utilize line chart models to predict the probability of postoperative lower limb lymphedema in different patients, allowing for the early identification of high-risk patients and facilitating early prevention and treatment.MethodsA retrospective study was conducted among 411 cervical cancer patients treated at our hospital from May 2021 to December 2023. The patients were randomly divided into a modeling group (313 cases) and a validation group (98 cases) according to an approximate 3:1 ratio. The modeling group was further divided into a lower limb lymphedema group (61 cases) and a non-lower limb lymphedema group (252 cases) based on the presence of postoperative lower limb lymphedema. Multiple factors Logistic regression was used to identify risk factors, and a nomogram was constructed using R software version 4.0.2, with internal and external validation performed.ResultsRisk factors for lower limb lymphedema following cervical cancer surgery include age 60 years or older, a Body Mass Index (BMI) of 24 kg/m² or higher, hypertension, the removal of 30 or more lymph nodes, adjuvant radiotherapy and chemotherapy, and prolonged standing for six hours or more (P < 0.05). Internal and external validation results demonstrated that the calibration curve closely aligned with the ideal curve. The Area Under Curve(AUC) of the Receiver Operating Characteristic(ROC) curve was 0.890 (95% CI: 0.844 ∼ 0.936) and 0.876 (95% CI: 0.821 ∼ 0.930), indicating high model calibration and discrimination. Decision Curve Analysis(DCA) curve revealed that the Logistic model had good net returns and high clinical practicality when the probability range of the high-risk threshold was 0.11 ∼ 0.98.ConclusionThe nomogram, developed using factors such as age, BMI, hypertension, number of lymph nodes dissected, adjuvant radiotherapy and chemotherapy, and duration of standing, has strong predictive value and offers significant clinical benefits, making it a valuable tool for clinical decision-making.

Elephantiasis and its cure: case report

Introduction: Lymphedema is a clinical condition stemming from a lymphatic system failure. The insufficiency of the lymphatic system can causes the abnormal accumulation of protein-rich fluid in the interstitial, which triggers a adverse consequence such a and fibrosis. This study describes a case of a patient who has been cured of elephantiasis for ten years but continues to have lymphedema. Description case: Patient information: A 78-year-old woman had a history of bilateral lower limb lymphedema, clinical diagnosis that had been worsening throughout her life bilateral despite undergoing treatment and had progressed to stage III (elephantiasis). Clinical findings: The patient was sent to the Clínica Godoy-Sao Jose do Rio Preto-Brazil ten years ago and reported having undergone several forms of treatment, but without impeding the progression of the condition. Therapeutic intervention: The patient was submitted to intensive treatment for three weeks, during which time a 21-kilogram reduction in weight and a 66-cm reduction in circumference occurred. After three weeks, the patient began undergoing treatment at home with laced compression stockings. At the follow-up evaluation, electrical bioimpedance analysis, perimeter measurements and volumetry were performed, which revealed the reduction in lymphedema to standards of normality. The patient has completed 10 years of treatment and has maintained the results using compression stockings. Conclusion: Elephantiasis is curable, but lymphedema is not. Like any other chronic disease, constant treatment is needed to maintain the results.

The effects of lumbar sympathetic ganglion block therapy on secondary lower limb lymphedema among patients with gynecologic cancer surgery

The effects of lumbar sympathetic ganglion block therapy on secondary lower limb lymphedema among patients with gynecologic cancer surgery

Prospective surveillance and early intervention to prevent chronic breast cancer-related arm lymphedema-what are the barriers?

Up to one in five early breast cancer patients develop chronic upper limb lymphedema after breast cancer treatments. This treatment complication is irreversible and can significantly impact the quality of life of breast cancer survivors. The model of prospective surveillance and early intervention has emerged as a potential strategy to prevent the development of this debilitating treatment-related complication. However, the widespread implementation of such programs worldwide is challenging. The aim of this review is to identify barriers of implementation, including selecting suitable patients to be enrolled, determining the optimal method for lymphedema screening, and choosing the most effective treatment to prevent progression when early or subclinical breast cancer-related arm lymphedema (BCRAL) is detected. Future research should develop accurate predictive models for the development of upper limb lymphedema using population based datasets with artificial intelligence and investigate the comparative efficacy of different screening methods and treatment options for early intervention for BCRAL. The medical community should also regularly review whether new treatments such as immunotherapy, targeted therapies and new surgical or radiation techniques could contribute to the development of arm lymphedema. By overcoming these barriers, we can improve the feasibility of implementing early prospective surveillance programs in clinical practice, ultimately improving the care and outcomes for breast cancer survivors at risk of treatment-related upper limb lymphedema.

MRI features of primary lower extremity lymphedema: a retrospective analysis of 228 patients

BackgroundThe value of MRI presentation of primary lower extremity lymphedema in assessing the severity of lower extremity lymphedema is uncertain. The purpose of this study was to assess the role of MRI presentation in staging primary lower extremity lymphedema. Methods228 patients with clinically diagnosed primary lower limb lymphoedema from January 2018 to December 2019 in our hospital were enrolled retrospectively. Patients were divided into stages I, II, and III based on the 2020 International Society of Lymphology (ISL) clinical staging standards. Two radiologists assessed the following characteristics of the Short Term Inversion Recovery (STIR) sequence: the extent of edema (longitudinally and transversely), the frequency of MRI manifestations, including the presence of dermal thickening, and the morphology of edema (grid, honeycomb, parallel-lines, banded, crescent, and lymphatic lake). The Kappa test was used to assess interobserver agreement. The chi-square test was used to compare the frequency differences of MRI manifestations between different clinical stages. The Spearman test evaluated the correlation between edema extent and clinical stage. ResultsThe extent of edema was positively correlated with clinical stage, both longitudinally and transversely. When comparing stages, the incidence of dermal thickening in stages II and III was significantly higher than in stage I. The incidence of parallel-lines in stage I was significantly higher than that in stages II and III. The grid and banded sign incidence in stages I and II were significantly higher than in stage III. The incidence of honeycomb in stages II and III was significantly higher than in stage I. The incidence of lymphatic lake and crescent in stage III was significantly higher than in stages I and II (P<0.001). ConclusionSTIR can sensitively diagnose lymphedema and assist in clinical staging. MRI manifestations of primary lower extremity lymphedema in different stages have specific MRI features.

Effect of scapular and shoulder strengthening exercises on prevention of upper limb lymphedema – a pilot study

Background. The most frequent type of cancer among women is breast cancer. According to the report published by Indian Council for Medical Research (ICMR, 2019), there are 1.5 lakh new instances of breast cancer nationwide and around 70,000 people in India die from breast cancer each year. Secondary lymphedema (SL) following breast cancer surgery can occur due to the removal of lymph nodes during breast cancer surgery. Objective. This pilot study was done with the objectives to improve the strength of scapular and shoulder muscles, increase the shoulder range of motion, prevent the development of upper limb lymphedema, to reduce shoulder pain and disability and to improve the quality of life among women who underwent breast cancer surgery. Methodology. Ten patients with a mean age of 49.9 ± 8.6 and mean Body mass index (BMI) of 28.4 ± 3.9 were included according to the inclusion and exclusion criteria. They were randomized into interventional group (Group A n = 5) and conventional group (Group B n = 5). The interventional group performed the routine exercises prescribed along with the scapular and shoulder muscle strengthening exercises, while the conventional group performed only the routine exercises for 12 weeks. Result. The mean change score values of the outcome variables of both the groups were analyzed using Independent ‘t’ test. Discussion. Arm circumference measurement, shoulder pain, disability and quality of life measures showed significant difference between groups at p &lt; 0.05. Shoulder range of motion, muscle strength and arm volumetry did not show much difference between groups indicating the need for long term continuation of the exercises to produce improvement in those parameters. Conclusion. Long term effect of strengthening exercises will have an effect on improvement of shoulder range of motion, arm volume and muscle strength among the women following breast cancer surgery. Strengthening exercises should be recommended as a part of breast cancer rehabilitation protocol to prevent secondary lymphedema and other postsurgical complications.

Combined pedicled and free omentum flaps for chronic lower limb lymphoedema: novel approach with robotic surgery.

Combined pedicled and free omentum flaps for chronic lower limb lymphoedema: novel approach with robotic surgery.

Reliability, concurrent validity and clinical feasibility of measurement methods determining local tissue water in patients with lower limb lymphedema and healthy controls

Purpose To investigate reliability, concurrent validity and clinical feasibility of local tissue water measurements in patients with lower limb lymphedema and healthy controls. Methods In this cross-sectional study the Moisture Meter D Compact device® (MMDC) measurement and “pitting test” were performed three times by two assessors to test intra- and inter-rater reliability in 47 patients and 30 healthy controls. To investigate the between-session reliability, 29 patients and 21 healthy controls were reassessed two weeks later. Time efficiency and practical limitations were evaluated. The concurrent validity was investigated between the two tests. Clinical trial registration number: NCT:05269264. Results Of the MMDC values, 58% showed strong to very strong intra-rater reliability, 32% showed strong to very strong inter-rater reliability and 36% had strong to very strong between-session reliability. Absolute values had generally a higher reliability than inter-limb or leg-to-arm ratio values. The pitting test had nil to perfect agreement between assessments (Cohen’s kappa = −0.03–1.00) with fewer practical limitations and shorter performance time than the MMDC. Between both tests nil to a moderate relationship was found (Kendall’s tau c = 0.00–0.60). Conclusion The MMDC and pitting test are reliable and feasible measurements to assess local tissue water depending on the location, but should not be used interchangeably.

Nutritional assessment of Chinese gynecologic cancer survivors with post-surgical lower limb lymphedema: a cross-sectional study.

This study aims to evaluate the nutritional status of Chinese gynecologic cancer survivors with post-surgical lower limb lymphedema (LLL) by analyzing serum albumin levels and the prognostic nutritional index (PNI). A retrospective cross-sectional study was conducted at two Chinese medical centers. The cohort comprised 155 gynecologic cancer survivors who developed symptomatic unilateral LLL post-surgery, during the period from September 2021 to June 2024. Nutritional status was assessed by measuring serum albumin and PNI. Statistical analysis was performed using univariate and multivariate logistic regression models to identify factors associated with low serum albumin and PNI. The mean age of the cohort was 55.47 ± 10.56 years, and the median total survival time was 72.0 months (36.5, 111.5 months). The prevalence of low serum albumin (< 40 g/L) was 40.0%, and low PNI (< 45) was 80.6%. Significant associations were found between low hemoglobin levels and both low serum albumin (OR = 1.05, 95% CI: 1.02-1.08, p < 0.001) and low PNI (OR = 1.09, 95% CI: 1.04-1.13, p < 0.001). Advanced International Society of Lymphology stage 3 was also associated with low albumin (OR = 0.18, 95% CI: 0.03-0.99, p < 0.05). The study highlights a significant prevalence of high risk of malnutrition among Chinese gynecologic cancer survivors with LLL, underscoring the need for regular nutritional assessments and interventions.

Chylous Reflux in Pediatric Primary Lymphedema of the Lower Limbs and Genitalia: A Retrospective Study of 167 Patients.

Background: Chylous reflux (CR) in primary lymphedema (PL) of the lower extremities is rare and requires particular diagnostic procedures. This study aimed to determine clinical and lymphoscintigraphic traits for efficient screening. Methods and Results: Pediatric patients with PL of lower extremities treated in our institution between January 2020 and December 2023 were reviewed. The medical history, lymphoscintigraphy, non-contrast MR lymphography, and direct lymphangiography were analyzed. Lymphoscintigraphic visual patterns were classified to detect CR. Patients with CR showed significantly higher proportions of childhood symptom onset (65.63% vs. 25.19%, p < 0.01), genital lymphedema (62.50% vs. 19.26%, p < 0.01), and proximal-to-distal swelling (31.25% vs. 8.89%, p < 0.01). Eight patients without skin lesions had milk discharge after acupuncture or skin breakdown. Pattern 4 shows diffused dermal backflow of the leg and an absence of superficial lymphatic drainage, or normal initial cephalad flow with subsequent reflux of tracer into the affected limb. CR showed significantly higher percentages of pattern 4 (87.50% vs. 12.59%, p < 0.01), normal/widened iliac lymphatics (78.13% vs. 11.11%, p < 0.01), and thigh/calf outlining (87.50% vs. 29.63%, p < 0.01). Genital swelling preceding limb swelling and genital radioactivity were more common in the CR group. Conclusions: CR tends to occur in childhood initially, begin centrally and progress distally, and involve genitals prior to lower extremities. Milk discharge after acupuncture or skin breakdown is important for screening CR without chylous vesicles. The patterns with typical "profiling of the leg" and normal or widened iliac lymphatic trunks strongly correlate with CR. Genital lymphedema with increased radioactivity indicates CR.

EDITORIAL: RETURNING THE CENTRAL LYMPHATIC SYSTEM TO THE CENTER OF LYMPHOLOGY

After the introduction of conventional oil contrast lymphography and the founding of the discipline of lymphology, great impetus was given to investigating central lymphatic system and its disorders along with lymphatic involvement and specifically lymphostasis in common diseases of major organs such as the liver (cirrhosis) and heart (heart failure). Gradually interest shifted to more peripheral disorders such as limb lymphedema and its treatment by physical and surgical measures. At the same time, basic lymphology turned to the study of isolated ex vivo and in vitro, including lymphatic endothelial models and more recently, molecular lymphology focusing on lymphatic growth and modulating factors, genes and proteins underlying primary lymphedema, and more potential biomarkers of lymphatic disease have gained prominence. However, it has been advances in lymphatic imaging, namely lymphoscintigraphy with SPECT-CT high resolution 3-D pictures and magnetic resonance imaging (contrast and non-contrast) of the peripheral and particularly central lymphatic system by more invasive means combined with endovascular interventional techniques to treat complex and life-threatening lymphatic disorders that has returned the central lymphatic system to the center of lymphology, where the journey began.

Breast cancer-related upper limb lymphoedema: an overview

Melanie Thomas provides an update on management of lympoedema in those with breast cancer

Developing new practices for managing breast and chest lymphoedema.

Some patients develop breast/chest lymphoedema following breast cancer treatment. Historically this group of patients has been managed in the same way as those with limb lymphoedema, through the application of compression in the form of vests or bras. Some patients reported pain and the feeling of being in a 'strait jacket' and, therefore, abandoned these items for lighter and more comfortable garments without any adverse effects. Reflecting on this insight, the author adapted breast/chest lymphoedema management by suggesting a change to lighter garments to patients who reported improved comfort, with no obvious negative impact on their lymphoedema. Within this article, the author gives a brief explanation of lymphatic mechanisms and factors relating to lymphoedema including signs and symptoms of breast oedema. There will be an exploration of the available treatments for lymphoedema along with treatment plans found to be effective by the author.

The“Overlapping”Lymphaticovenous Anastomosis: an overlapped end-to-end anastomosis supermicrosurgical technique

ObjectiveLymphaticovenular anastomosis (LVA) is increasingly utilized in the treatment of lymphedema. This study aims to assess the efficacy and safety of the “Overlapping” LVA technique, which addresses the size mismatch between lymphatic and venous vessels in lymphedema treatment.MethodsBetween August 2022 and April 2023, seventeen patients diagnosed with lymphedema were enrolled in this study. The severity of lymphedema in these patients was classified according to the International Society of Lymphology (ISL) staging system.All patient underwent LVA procedures, anastomosis techniques including the Overlapping, end-to-end and octopus anastomosis. The techniques of anastomosis, anastomosis time, patency rate, and volume of limb lymphedema were evaluated.ResultsOur study enrolled 17 lymphedema patients who underwent the LVA procedure. All patients showed significant postoperative improvement in limb edema. The mean drainage volume was 472.29 ml. The Overlapping technique demonstrated a 100% success rate as assessed by clinical observation and intraoperative Indocyanine Green (ICG) lymphography. The average anastomosis time was 5.3 min, reducing operative time compared to traditional methods.ConclusionsThese findings suggest that the Overlapping technique could serve as a valuable addition to the current LVA technique. This Overlapping anastomosis technique provides a wide range of applications for lymphatic anastomosis treatment and prevention of lymphedema.

Case report: A Large Fibroepithelial Polyp of the Vulva

Fibroepithelial polyps are one of the most common benign masses of the vulva and are characterized by relatively small size, vague symptomatology, and morphological diversity. These lesions mainly affect women of reproductive age and are hormone dependent. They are usually found around the urogenital area. A biopsy and histological examination are necessary to exclude the possibility of malignant neoplasm. The pathophysiology of the disease appears to be associated with the coexistence of diabetes mellitus, chronic inflammation and chronic friction. Below we will describe the case of a 17-year-old Somali patient who had undergone female genital mutilation type IIb tyand who presented to the regular clinic with a reported unspecified vulvar mass with coexisting chronic lower limb lymphedema.

Paraneoplastic Yellow Nail Syndrome: A Case Report

Yellow Nail Syndrome (YNS) is a rare clinical condition affecting multiple districts. Distinctive signs include nail abnormalities, pulmonary manifestations, and lymphedema. The aetiology is unknown; usually presents isolated or as a paraneoplasticsyndrome. There is no established treatment and resolution is limited. Low dose azithromycin with mucolytics and long-acting muscarinic antagonist could improve the respiratory component of the YNS when present. Here we describe a case of paraneoplastic YNS presenting with cough, sputum, rhinosinusitis, and nail discoloration appearing after a recent history of breast cancer. In a patient with an oncological history, nail abnormalities associated with pulmonary manifestations and/or lower limbs lymphedema, the diagnosis of paraneoplastic YNS should be considered.