Lymphedema Research Articles

Chronic infection and severe mitral regurgitation: first of all, do not harm.

techniques of mitral valve repair has improved in the last decades. Percutaneous approach is now a reliable and safe therapy in those patients with high surgical risk. However, the presence of an implanted prothesis increases the risk of endocarditis. we describe a case of a 75-year-old man with medical history of recurrent cellulitis due to chronic lymphedema, who had percutaneous edge-to-edge mitral valve treatment. After three months he developed fever without any specific symptoms. Emocolture were positive for Staphilococcus lugdunensis. Transesophageal echocardiogram demonstrated a huge vegetation at the level of Edwards Pascal device. Patients was then referred to cardiac surgery for mitral valve replacement with bioprothesis. in patients needing a prothesis implantation the management and treatment of chronic infection is of paramount importance to reduce the risk of prothesis infection procedure. Endocarditis after percutaneous edge-to-edge mitral valve treatment represents a rare but a life-threatening condition.

Successful Surgical Treatment of Coronavirus Disease 2019 (COVID-19) Vaccination Related Upper Extremity Lymphedema : Case Report

Lymphedema is rare adverse effect of COVID-19 vaccination which was reported at several literatures. We present a case of surgically treated secondary lymphedema after the COVID-19 vaccination. The patient presented lymphedema at the upper extremity with no specific history except the COVID-19 vaccination 18 months before the visit. LVA and liposuction for the posterolateral aspect of forearm and upper arm was performed. The volume of the affected arm was reduced to more than 54 percent at the postoperative 8 months. With precise surgical planning, secondary lymphedema occurred after the COVID-19 vaccination could be successfully treated surgically.

Effects of Short-Term Educational Hospitalization with Multidisciplinary Approach for Lymphedema on Limb Circumference and Quality of Life.

Background: Lymphedema is an intractable disease requiring lifelong treatment. Daily self-care by the patient is essential; however, establishing care is often difficult. Our hospital offers a short-term educational hospitalization program that involves intensive, multidisciplinary intervention to develop self-care. This study aimed to evaluate the effectiveness of this program. Methods and Results: Among the patients diagnosed with primary or secondary lymphedema who underwent educational hospitalization, 31 cases (33 limbs) were included in this study. The upper extremity lymphedema (UEL) index and lower extremity lymphedema (LEL) index were used for objective evaluation, and the Lymphedema Quality of Life Questionnaire was used for subjective evaluation. The therapeutic effects of educational hospitalization were examined before admission, at discharge, and at 6 months postdischarge. The UEL/LEL index significantly decreased for both the upper and lower limbs after educational hospitalization. In addition, the UEL/LEL index change rate from prehospitalization to 6 months postdischarge was compared between the continued and discontinued exercise groups; the former index showed significantly more improvement than the latter. Comparing the quality of life (QOL) assessments pre- and posthospitalization, statistically significant improvements were observed in all categories, including function, appearance, symptoms, and psychological state. Conclusions: Short-term educational hospitalization led to a sustained reduction in the circumference of lymphedema-affected limbs and an improvement in the QOL. The multidisciplinary approach resulted in improved self-efficacy and established daily self-care.

Improved lymphangiogenesis around vascularized lymph node flaps by periodic injection of hyaluronidase in a rodent model

Vascularized lymph node transfer (VLNT) is an advanced surgical approach for secondary lymphedema (SLE) treatment, but tissue fibrosis around the lymph node flap (VLNF) inhibiting lymphangiogenesis is the biggest challenge undermining its therapeutic efficacy. This study explored the effects of periodic hyaluronidase (HLD) injection in reducing fibrosis and promoting lymphangiogenesis in 52 Sprague–Dawley rats with a VLNF over 13 weeks. The results demonstrated that HLD administration significantly enhanced swelling reduction, lymphatic drainage efficiency, and lymphatic vessel regeneration, with up to a 26% decrease in tissue fibrosis around the VLNF. These findings suggest that combining VLNT with periodic injections of HLD could substantially improve SLE treatment outcomes in clinical settings. It offers a promising direction for future therapeutic strategies and drug development aimed at increasing the efficacy of surgical treatment for SLE patients.

Cancer and lymphatic marker FOXC2 drives wound healing and fibrotic tissue formation

IntroductionThe FOXC2 transcription factor has been tied to a wide range of disease states, serving as a promising prognostic biomarker associated with aggressive basal-like human breast cancers (increased cancer invasion and metastasis). Dysregulation of FOXC2 expression has also been found to promote defects in lymphatic remodeling and hyperplastic lymphedema-distichiasis (LD). Since chronic lymphedema is a forerunner of several malignancies and cancers have been known to arise from poorly healing chronic wounds (e.g., Marjolin ulcers), we examined the effect of Foxc2 dysfunction on skin wound healing.MethodsWe used our splinted excisional wounding model that mimics human-like wound healing on wildtype and Foxc2+/− mice (n = 4), which demonstrate incomplete lymphatic vasculature and lymphatic dysfunction. Wound size was measured over the course of 18 days. Tissue was explanted from both groups at post-operative day (POD) 14 and 18 and stained with Masson’s Trichrome to assess scar formation, Picrosirius Red for dermal integrity, or immunofluorescence to assess lymphatic (LYVE1) cell populations.ResultsWildtype mice completely healed by POD 14, while Foxc2+/−mice did not completely heal until POD18. Scar area of healed Foxc2+/−mice (POD 18) was larger than that of healed wild-type mice (POD 14; p = 0.0294). At POD 14, collagen "bers in the scars of Foxc2+/−mice to be narrower (p = 0.0117) and more highly aligned (p = 0.0110), indicating signi"cantly more "brosis in these mice. Collagen "bers in both groups became longer (p = 0.0116) and wider (p = 0.0020) from POD 14 to 18, indicating a temporal evolution of "brosis. Foxc2+/−mice also had lower numbers of LYVE1+, F4/80+ and CD4+ cells compared to wildtype mice.DiscussionIndividuals over 65 years old are more likely to develop cancer and are highly susceptible to developing chronic wounds. Here, we found that FOXC2, which is tied to cancer metastasis and lymphatic dysregulation, also impairs wound healing and promotes "brotic tissue architecture. With FOXC2 proposed as a potential therapeutic target for cancer metastasis, its downstream systemic effects should be considered against the increased chance of developing nonhealing wounds. Further delineation of the microenvironment, cellular events, and molecular signals during normal and Foxc2-associated abnormal wound healing will improve clinical therapies targeting this important marker.

The influence of non-cancer-related risk factors on the development of cancer-related lymphedema: a rapid review.

Extensive research supports an evidence-base for cancer treatment-related risk factors, including extent of lymph node dissection and use of radiotherapy, as contributing to secondary lymphedema. Additionally, comorbidities, such as higher body mass index, and vascular-related conditions are identified to further augment risk. While social determinants of health (SDOH) and socioeconomic factors are widely regarded as influencing an individual's healthcare outcomes, including cancer risk and survival, these factors have not been explored as risk factors for developing secondary lymphedema. A rapid literature review explored the current evidence for SDOH as risk factors for lymphedema. Studies that were published over the last 10years and that specifically analyzed social factors as variables associated with lymphedema were included. Studies that only characterized the social determinants of the study population were not included. Forty-nine studies were identified through a rapid literature review, and 13 studies that expressly analyzed social determinants as risk factors for secondary lymphedema were reviewed and extracted. All studies were conducted in patients with breast cancer-related lymphedema. Social risk factors included race, educational level, insurance type, and income level. These are consistent with the socioeconomic inequalities related to cancer survival. SDOH may influence the risk of developing cancer treatment-related health conditions like secondary lymphedema. Research trials studying cancer treatment-related conditions should collect consistent and robust data across social, behavioral, environmental, and economic domains and should analyze these variables to understand their contribution to study endpoints. Risk prediction modeling could be a future pathway to better incorporate social determinants, along with medical and co-morbidity data, to holistically understand lymphedema risk.

Consensus statement on non-cancer-related risk factors for development of secondary lymphedema.

Non-cancer-related risk factors for secondary lymphedema were defined across four categories: co-morbidity, social determinants of health, behavioral factors, and environmental effectors. Based on rapid reviews of the literature and presentations at the ACS/LANA Lymphedema Summit, this working group categorized these risk factors according to the strength of evidence. Consensus agreement on level of evidence was achieved through one face-to-face working session and three follow-up virtual meetings. Findings elucidate strong evidence for co-morbidities, such as cardio/metabolic and vascular factors contributing to the risk for lymphedema. Evidence is low-to-moderate for social and behavioral factors and is lacking for environmental factors. Panel recommendations suggest a tailored approach to prospective surveillance when monitoring for secondary lymphedema that includes social determinants of health considering the growing awareness and evidence of these factors' influence on cancer and cancer-related morbidity.

Multi-omics characterization of lymphedema-induced adipose tissue resulting from breast cancer-related surgery.

Secondary lymphedema (LE) following breast cancer-related surgery is a life-long complication, which currently has no cure. LE induces significant regional adipose tissue deposition, requiring liposuction as a treatment. Here, we aimed to elucidate the transcriptional, metabolomic, and lipidomic signature of the adipose tissue developed due to the surgery-induced LE in short- and long-term LE patients and compared the transcriptomic landscape of LE adipose tissue to the obesity-induced adipose tissue. Adipose tissue biopsies were obtained from breast cancer-operated females with LE from the affected and non-affected arms (n = 20 patients). To decipher the molecular properties of the LE adipose tissue, we performed RNA sequencing, metabolomics, and lipidomics combined with bioinformatics analyses. Differential gene expression data from a cohort of lean and obese patients without LE was used for comparisons. Integrative analysis of functional genomics revealed that inflammatory response, cell chemotaxis, and angiogenesis were upregulated biological processes in the LE arm, indicating a sustained inflammation in the edematous adipose tissue; whereas, epidermal differentiation, cell-cell junction organization, water homeostasis, and neurogenesis were downregulated in the LE arm. Surprisingly, only a few genes were found to be the same in the LE-induced and the obesity-induced adipose tissue expansion, indicating a different type of adipose tissue development in these two conditions. In metabolomics analysis, we found reduced levels of a branched-chain amino acid valine in the LE arm and downregulation of the mRNA levels of its transporter SLC6A15. Lipidomics analyses did not show any significant differences between the LE and non-LE arms, suggesting that other factors affect the lipid composition of the adipose tissue more than the LE in these patients. Our results provide a detailed molecular characterization of adipose tissue in secondary LE after breast cancer-related surgery. We also show distinct differences in transcriptomic signatures between LE-induced adipose tissue and obesity-induced adipose tissue, but only minor differences in metabolome and lipidome between the LE and the non-LE arm.

The Usefulness of Portable Echo in the Preoperative Mapping of Lymphaticovenular Anastomosis.

This study evaluated the effectiveness of a pocket-sized ultrasound device in preoperative planning for lymphaticovenular anastomosis (LVA) to enhance lymphedema treatment outcomes. A retrospective analysis was performed on 24 patients who underwent LVA for secondary upper extremity lymphedema between June 2020 and August 2022. Patients were categorized into two groups: the ultrasound group, which used a pocket-sized device (Vscan Air), for preoperative vein identification, and a control group that did not. Preoperative lymphatic mapping was performed using indocyanine green lymphography, and suitable veins for anastomosis were identified using ultrasound. Upper extremity lymphedema index and incision length were compared. Participants in the ultrasound group had a shorter average incision length (2.85 ± 0.48 cm) than those in the control group (3.23 ± 0.78 cm, p = 0.038), indicating a more targeted and minimally invasive approach. Although volume reduction rates were not significantly different, the pocket ultrasound device facilitated more precise vein selection, enhancing surgical planning. Pocket-sized ultrasound devices provide a cost-effective and practical solution for vein identification during LVA, particularly in resource-limited settings. While high-frequency ultrasound offers superior resolution, portable devices could become standard tools for lymphatic surgery with continued technological advancement.

Cross-Sectional Analysis of Patients Referred to a Tertiary Lymphatic Surgery Center.

Secondary lymphedema has become an increasingly common reason for referral to plastic surgery. Understanding referral patterns for lymphedema patients is crucial to optimizing care. Patients referred to plastic surgery for lymphedema at a lymphatic surgery center between January 2016 and 2023 were identified. Primary outcomes of interest included clinical lymphedema staging and characteristics, patient demographics, and referral sources. Secondary outcomes were prior lymphedema treatment, agreement between referring provider and plastic surgeon's diagnosis, and patient disposition after surgical evaluation. Descriptive statistics and multivariate logistic regression analysis were performed. A total of 285 patients with extremity edema were referred to plastic surgery; 60.0% of patients had prior malignancy, 45.6% of patients had undergone a prior lymph node procedure, and 40% had received radiation, while 56.8% of patients had previously seen occupational therapy. Body mass index (BMI, OR 1.09, p = 0.013), age (OR 1.25, p = 0.005), and prior physical oroccupational therapy (OR 1.23, p = 0.011) were associated with later stages of lymphedema upon presentation, while prior radiation (OR 0.79, p = 0.006) and malignancy (OR 0.85, p = 0.034) were associated with earlier stages of lymphedema. Self-referral (27.4%), primary care (17.9%), and medical oncology (14.7%) were the most common referral sources. Lymphedema was confirmed in 68.1% of referrals, and 28.5% of these patients proceeded to surgery. Patients were more likely to be operative candidates if referred by primary care (RR 2.1, p = 0.006) or occupational therapy (RR 4.6, p = 0.010). Referred patients ultimately undergo lymphedema surgery at relatively low rates, indicating that most referred patients are not ideal surgical candidates. Optimizing referral patterns through multidisciplinary education may enhance the referral process and improve access to lymphedema surgery.

Progress in lymphedema.

A century ago, the first description of secondary lymphedema resulting from mastectomy was published in the medical literature. For most of the remaining twentieth century, evidence about cancer treatment related lymphedema grew slowly, and mostly through clinicians who wished to understand its causes, natural-history, and post-treatment risks, as well as from clinicians involved with its treatment. In the late 1990s, there was growing recognition that there were large gaps in our understanding of predisposing and post-treatment risks of onset, the near and long-term prevalence of lymphedema, andhow to educate patients. Moreover, there was no consensus on best practices for treating lymphedema, and how to ensure the quality of treatment. In 1998, with support from the Longaberger Company®, the American Cancer Society began a long-standing commitment to address enduring challenges associated with lymphedema. This commitment began with a landmark international workshop on lymphedema that was held in New York City in February 1998, millions of dollars in research funding, support to establish the Lymphology Association of North America (LANA), a second workshop convened in February 2011 on the prospective surveillance model for rehabilitation for women with breast cancer, and most recently, the 2023 Lymphedema Summit: Forward momentum; Future Steps in Lymphedema Management, co-sponsored with the LANA, Washington University School of Medicine in St. Louis, and the Stryker Corporation. This editorial introduces the papers and expert consensus statements from that Summit.

Adherence to Hygiene Protocols and Doxycycline Therapy in Ameliorating Lymphatic Filariasis Morbidity in an Endemic Area Post-Interruption of Disease Transmission in Ghana.

Filarial lymphedema (LE) remains a significant global problem despite the progress made toward elimination of lymphatic filariasis (LF). In Ghana, the main approach to LF is preventive chemotherapy, but this has minimal impact on individuals who have already developed LE. In 2018-2020, a 24-month randomized, double-blind, placebo-controlled trial was conducted to evaluate the efficacy of stringent hygiene measures using the Essential Package of Care with or without additional administration of doxycycline (DOX) to improve filarial leg LE. This study enrolled 356 participants with LE stages 1-3 from two districts in the Upper East Region of Ghana. In addition to regular training on appropriate care for their affected legs, participants were randomized to receive 6 weeks of either 200 mg/day DOX (n = 117), 100 mg/day DOX (n = 120), or matching placebo (n = 119). Participants were seen every 2 months, with clinical measurements done at 6, 12, 18, and 24 months to assess the status of affected legs. There was a trend toward later appearance of acute attacks after DOX, but surprisingly, DOX showed no effect on LE stage progression. In all groups, leg LE improvement was more common (DOX 200 mg: n = 23 [20%]; DOX 100 mg: n = 23 [19.5%]; placebo: n = 32 [27.4%]) than LE worsening (DOX 200 mg: n = 2 [1.7%]; DOX 100 mg: n = 3 [2.5%]; placebo: n = 2 [1.7%]). Overall, these data show a strong benefit from adherence to a strict hygiene protocol, with some added potential benefit for DOX in preventing acute attacks.

Percutaneous balloon venoplasty for symptomatic lead-related venous stenosis

BackgroundLead-related venous stenosis (LRVS) is common after transvenous lead implantation and generally diagnosed incidentally. Symptomatic LRVS, causing discomfort and swelling, is less common. ObjectiveWe report on the management and outcomes of patients with symptomatic LRVS after percutaneous balloon venoplasty. MethodsWe included patients with symptomatic LRVS unresponsive to >30 days of anticoagulation who underwent venoplasty at the Hospital of the University of Pennsylvania between 2014 and 2020. Transvenous lead extraction (TLE) was performed first if the lesion could not be crossed with a wire. ResultsEighteen patients (mean age, 62 ± 10 years; 44% female) underwent 27 venoplasty procedures. Symptoms included arm swelling in 9 (50%), facial/neck swelling in 1 (6%), and both in 8 (44%). Venography revealed LRVS in the axillary/subclavian veins in 10 (56%), the brachiocephalic vein in 6 (33%), and the superior vena cava in 4 (11%). Most patients (83%) required TLE before venoplasty, and only 5 of 18 (28%) remained with leads crossing the stenosed segment. Thirteen patients (72%) had complete symptom resolution, 4 (22%) had partial resolution due to secondary lymphedema, and 1 showed no improvement. Patients with complete resolution had shorter times from symptom onset to intervention (195 vs 690 days; P = .02). ConclusionLRVS can affect any part of the venous system and may be manifested with swelling of the arm, face/neck, or both. Balloon venoplasty is safe and effective, often requires TLE, and is particularly durable when leads no longer cross the stenosed region. Venoplasty is less effective for secondary lymphedema, highlighting the need for timely intervention.

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.

Timing of Breast Cancer Related Lymphedema Development Over 3 Years: Observations from a Large, Prospective Randomized Screening Trial Comparing Bioimpedance Spectroscopy (BIS) Versus Tape Measure.

The PREVENT randomized control trial monitored progression to chronic breast cancer-related lymphedema (cBCRL) following intervention for subclinical breast cancer-related lymphedema (sBCRL) assessed by bioimpedance spectroscopy (BIS) versus tape-measure (TM). This multi-institutional trial demonstrated a 92% risk reduction of developing cBCRL. This secondary analysis reviews the timing of sBCRL and cBCRL following breast cancer (BC) treatment. Women at risk of cBCRL (n = 919) were screened regularly up to 36 months after BC treatment using either BIS or TM. Following diagnosis of sBCRL, patients underwent a 4-week compression sleeve intervention. The time in months from BC treatment to detection was reviewed at 3-month intervals. In total 209 patients developed sBCRL (BIS: n = 89, TM: n = 120) and were eligible for intervention. 30 progressed to cBCRL postintervention (BIS: 7, TM: 23). More than half of patients had measurements consistent with sBCRL within 9 months of BC treatment. Patients continued to have initial detections of sBCRL, regardless of screening method, with rates remaining consistent in years two and three (p > 0.242) post surgery. Additionally, 39 patients progressed to cBCRL without developing sBCRL or receiving intervention across the 3-year period. The timing of sBCRL detection demonstrates that patients continue to be at risk years after treatment and may continue to progress to cBCRL years after surgery. Early detection of sBCRL allows for early intervention decreasing the likelihood of progression to cBCRL. Patients should continue to be monitored for a minimum of 3 years following completion of cancer treatment. Specifically, careful targeted monitoring over the initial 9-month period is important.

The Effect of Complex Decongestive Therapy on Sleep Quality and Quality of Life in Patients with Secondary Lymphedema After Cancer Surgery

The Effect of Complex Decongestive Therapy on Sleep Quality and Quality of Life in Patients with Secondary Lymphedema After Cancer Surgery

Optimizing strategies for lymphaticovenular anastomosis in lower secondary extremity lymphedema

BackgroundLymphovenous anastomosis (LVA) has become an increasingly common treatment for patients with secondary extremity lymphedema. The objective of this study was to optimize strategies for lower secondary extremity lymphedema using LVA techniques, with the aim of enhancing patient outcomes. MethodsWe conducted a retrospective analysis of 121 patients who underwent LVA at Taizhou Hospital of Zhejiang Province from January 2020 to December 2023. Preoperative and postoperative assessments included intraoperative observations, functional parameters, and clinical outcomes. The efficacy of LVA was evaluated based on circumferential reduction, quality of life improvements (Lymphoedema Quality of Life Questionnaire), and postoperative complications. ResultsThis study enrolled 121 patients with lower secondary extremity lymphedema, with an average age of 58.19 years. The results revealed significant associations between incision depth, lymphatic vessel size, the number of LVAs performed, and the number of incisions per patient, all of which correlated with postoperative volume reduction. The resulted analysis that identified optimal incision depths of 10 to 15 mm, lymphatic vessel size of 0.4 to 0.6 mm, and a recommended number of 6 to 8 LVAs. After LVA, there was a marked improvement in patient quality of life, with particularly notable enhancements in functionality and appearance. ConclusionsThis study’s findings optimizing the strategy for LVA surgery recommend the depth of incision, the size of lymphatic vessels, and the number of anastomoses to improve the quality of life and limb volume in patients with secondary lymphedema of the lower limbs.

CN78 The effects of lumbar sympathetic ganglion block therapy on secondary lower limb lymphedema

CN78 The effects of lumbar sympathetic ganglion block therapy on secondary lower limb lymphedema

Comparison of Immediate versus Delayed Lymphatic Reconstruction: Which Option Works Better to Prevent Post-Mastectomy Lymphedema?

Comparison of Immediate versus Delayed Lymphatic Reconstruction: Which Option Works Better to Prevent Post-Mastectomy Lymphedema?

Arm symptom pattern among breast cancer survivors with and without lymphedema: a contemporaneous network analysis.

Arm symptoms commonly endure in post-breast cancer period and persist into long-term survivorship. However, a knowledge gap existed regarding the interactions among these symptoms. This study aimed to construct symptom networks and visualize the interrelationships among arm symptoms in breast cancer survivors (BCS) both with and without lymphedema (LE). We conducted a secondary analysis of 3 cross-sectional studies. All participants underwent arm circumference measurements and symptom assessment. We analyzed 17 symptoms with a prevalence >15%, identifying clusters and covariates through exploratory factor and linear regression analysis. Contemporaneous networks were constructed with centrality indices calculated. Network comparison tests were performed. 1116 cases without missing data were analyzed, revealing a 29.84% prevalence of LE. Axillary lymph node dissection [ALND] (vs sentinel lymph node biopsy [SLNB]), longer post-surgery duration, and radiotherapy significantly impacted overall symptom severity (P < .001). "Lymphatic Stasis," "Nerve Injury," and "Movement Limitation" symptom clusters were identified. Core symptoms varied: tightness for total sample network, firmness for non-LE network, and tightness for LE network. LE survivors reported more prevalent and severe arm symptoms with stronger network connections than non-LE group (P = .010). No significant differences were observed among different subgroups of covariates (P > .05). Network structures were significantly different between ALND and SLNB groups. Our study revealed arm symptoms pattern and interrelationships in BCS. Targeting core symptoms in assessment and intervention might be efficient for arm symptoms management. Future research is warranted to construct dynamic symptom networks in longitudinal data and investigate causal relationships among symptoms.