Bilateral axillary web syndrome in a patient with primary lymphoedema of upper limbs and non-Hodgkin lymphoma.

Primary lymphoedema, axillary web syndrome (AWS) and yellow nail syndrome may be related. Mr B is a 66-year-old gentleman with genital lymphoedema and lymphoedema of all four extremities. In 2023, he was diagnosed with non-Hodgkin lymphoma and also underwent cardiac surgery. In November 2023, he completed an inpatient rehabilitation at the Földi clinic in Germany, where he received intensive treatment for his lymphoedema and was also diagnosed with bilateral AWS. The presence of AWS in a patient with primary lymphoedema and no history of axillary surgery is unique. Although AWS typically presents after axillary surgery, this case highlights that it can also occur in patients without lymph node surgery. While the precise cause of this presentation of AWS is not known, it may be connected to yellow nail syndrome or potentially the recent chemotherapy treatment. This article will describe the clinical case, highlighting the need for further research on AWS present in primary lymphoedema.

The N-LVA Study: effectiveness and cost-effectiveness of lymphaticovenous anastomosis (LVA) for patients with cancer who suffer from chronic peripheral lymphoedema - study protocol of a multicentre, randomised sham-controlled trial.

INTRODUCTION: Cancer-related lymphoedema is one of the most debilitating side-effects of cancer treatment with an overall incidence of 15.5%. Patients may suffer from a variety of symptoms, possibly resulting in a diminished health-related quality of life (HRQoL). A microsurgical technique known as lymphaticovenous anastomosis (LVA) might be a promising treatment option. The objective of this study is to evaluate whether LVA is effective and cost-effective compared with sham surgery in improving the HRQoL. METHODS AND ANALYSIS: A multicentre, double-blind, randomised sham-controlled trial conducted in three university hospitals in the Netherlands. The study population comprises 110 patients over the age of 18 years with unilateral, peripheral cancer-related lymphoedema, including 70 patients with upper limb lymphoedema and 40 patients with lower limb lymphoedema. A total of 55 patients will undergo the LVA operation, while the remaining 55 will undergo sham surgery. The follow-up will be at least 24 months. Patients are encouraged to complete the follow-up by explaining the importance of the study. Furthermore, patients may benefit from regular monitoring moments for their lymphoedema. The primary outcome is the HRQoL. The secondary outcomes are the limb circumference, excess limb volume, changes in conservative therapy, postoperative complications, patency of the LVA and incremental cost-effectiveness. ETHICS AND DISSEMINATION: The study was approved by the Medical Ethical Committee of Maastricht University Medical Center on 20 September 2023 (NL84169.068.23). The results will be presented at scientific conferences and published in peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT06082349.

Positive Impact of a New Compressive Garment in Patients with Genital Lymphedema: OLYMPY Study.

Purpose: Genital lymphedema is a chronic debilitating condition associated with highly impaired health-related quality of life (QoL). This prospective multicenter study evaluated the use of a new compressive garment in patients with secondary and primary genital lymphedema. Methods: Thirty-two patients prospectively enrolled were advised to wear the compressive garment for 12 weeks (day and night). The primary endpoint was change in patient-reported QoL at 12 weeks via the patient global impression of change (PGI-C) instrument. Secondary outcomes included change in other QoL measures at 12 weeks (visual analog scale, Lymphedema Quality of Life Inventory [LyQLI], and EQ-5D questionnaires), lymphedema severity (genital lymphedema score [GLS]), and physician assessment (Clinical Global Impression-Improvement [CGI-I]). Safety and tolerability were also assessed. Results: After 12 weeks, improvement was reported in 78.6% of patients (PGI-C). Physician assessment (CGI-I) indicated clinical improvement in 82.8% of patients. Patient assessment of lymphedema symptoms showed a significant decrease in discomfort (p = 0.02) and swelling (p = 0.01). Significant declines in the mean global GLS (p < 0.0001), and in the proportion of patients reporting heaviness, tightness, swelling, or urinary dysfunction (p < 0.05 for all), were also observed. LyQLI scores decreased (indicating improved QoL) in each of the physical, psychosocial (p = 0.05), and practical domains. The compressive garment was well tolerated with high compliance, and adverse events (due to swelling or discomfort) led to permanent discontinuation in only three patients. Conclusion: The use of a new genital compression garment over 12 weeks improves the QoL and clinical measures in patients with genital lymphedema (ClinicalTrials.gov ID: NCT04602559; Registration: October 20, 2020).

Time-Dependent Changes of Extremity Volume and Tissue Alterations in Swollen Arms Caused by Taxanes.

Background: We aimed to determine the course of arm swelling caused by the use of taxanes and to identify valid predictors of persistent swelling. Methods and Results: A total of 15 patients with unilateral arm swelling that developed during the course, or within 3 months after termination, of postoperative taxane-based chemotherapy were included in the present study. The patients attended follow-up appointments every 3-6 months for 24 months after their initial visit. Their arm circumference was measured at each follow-up appointment, while ultrasonography of the skin and subcutaneous tissues was performed at the 0-, 6-, 12-, and 24-month follow-ups. Of the 15 patients, 12 (80%) saw their taxane-induced arm swelling resolved within a median of 12 months (range, 3-29 months) after their final taxane administration. Of the 12 patients whose swelling resolved, 9 did not use compression sleeves; however, their course of resolution did not differ from the other 3 patients who regularly used compression sleeves. In the three patients with persistent swelling, the excess subcutaneous thickness in the medial upper arm (median, 283%) was significantly greater than that in the patients whose swelling resolved (120%; p < 0.05) during their initial visits. Conclusions: Of the 15 patients included in the present study, 80% saw their taxane-induced arm swelling resolve within a median of 12 months after their final taxane administration, independent of the use of compression therapy. Persistent swelling may be predicted during the initial visit based on subcutaneous thickening of the medial upper arm.

High Pressure 3 × 30 Minute Compression Methods for Advanced Lower Limb Lymphedema Patients.

Introduction: In advanced lymphedema of lower limbs, stage III bandaging under the routinely applied pressure of 40-60 mmHg remains largely ineffective. This is caused by skin and subcutaneous tissue stiffness due to fibrosis. Edema fluid accumulates deep in the subcutaneous tissue. Evacuating this fluid requires a high external compression force to overcome the resistance of fibrous tissue. We aimed to investigate the effectiveness of the compression method, with high pressure lasting for 3 days. Methods and Results: Twenty-one patients with lower limb lymphedema, stage III, of the postinflammatory type were included. Patients with acute inflammatory symptoms, venous thrombosis, profuse varicose veins, diabetes, and cardiac insufficiency with edema were excluded. A 10-cm-wide rubber bandage was applied to the foot and calf. The interface pressure measured using PicoPress ranged from 58 to 120 mmHg. Skin and deep tissue tonometry, skin water concentration, leg circumference, and drop of interface pressure were measured. Ultrasound examination was done before and after each compression session. The calf circumference decreased by 15.9 ± 5.4%, deep tissue stiffness by 58.9 ± 18.9%, skin stiffness by 69.6 ± 13.5%, and skin water concentration by 43.8 ± 11.5%. Interface pressure dropped to 66.3 mmHg (28-110 mmHg); ultrasonography images showed less fluid in the tissue. Conclusions: High-pressure 30-minute leg compression can remove excess edema fluid within 3 days and enable adjustment of nonstretch compression stockings. This method is more effective in advanced lymphedema at the beginning of therapy than the standard 30-50-mmHg bandaging as it provides an immediate effect.

Comparing the Impact of Diluents and Injection Techniques on Patient Comfort During Indocyanine Green Lymphangiography: A Prospective Study.

Background: Indocyanine green (ICG) lymphography, a key diagnostic tool for lymphedema, is influenced by the dilution process of ICG dye, impacting patient experience. Methods and Results: In our study, we assessed three different ICG diluents-water for injection (WFI), normal saline (NS), and Dextrose® plus human albumin-in five healthy volunteer individuals undergoing superficial lymphography of the upper limb over 3 weeks. Results indicated that NS, as a diluent for ICG, caused the least discomfort during injection, in contrast to WFI, which led to the highest levels of discomfort. Transport time of ICG from the injection site to the axillary lymph nodes was notably shorter in intradermal injections than in subdermal injections. Conclusion: Our findings advocate for using NS as the optimal and cost-effective diluent for ICG, enhancing patient experience.

Sensitivity of Each Index of Doppler, Cross, Uncollapsible, Parallel, and Superficial Fascia in Lymphatic Ultrasound.

Background: Recently, the usefulness of lymphatic ultrasound has been reported. It is beneficial not only to identify lymphatic vessels but also to evaluate lymphatic degeneration and diagnose lymphedema. We previously proposed D-CUPS (Doppler, Cross, Uncollapsible, Parallel, and Superficial fascia) to identify the lymphatic vessels on ultrasound. The purpose of this study was to clarify the sensitivity of each index of D-CUPS. Methods: We performed a retrospective study of 27 patients (44 limbs, 98 sites) with lower extremity lymphedema, who underwent lymphaticovenous anastomosis (LVA). We performed a lymphatic ultrasound the day before surgery. We used a linear probe commonly used for venous ultrasound (Noblus EUP-L65; Hitachi Medical Corp., Tokyo, Japan). We applied the D-CUPS index to identify the lymphatic vessels on ultrasound. We checked whether lymphatic vessels consistent with preoperative lymphatic ultrasound findings were observed during the LVA. We also calculated the sensitivity of each D-CUPS index. Results: All the 27 patients were women, with a mean age of 59.7 years. Totally, 98 incisions were made (59 incisions on the thigh and 39 incisions on the lower leg). During LVA, lymphatic vessels consistent with the preoperative lymphatic ultrasound findings were observed at all the sites. The sensitivities of each indicator of D-CUPS were 100.0%, 100.0%, 68.4%, 19.4%, and 100.0%, respectively. Conclusion: The sensitivity was 100.0% in D, C, and S. Although each index separately was not perfect, by combining them appropriately, we were able to identify lymphatic vessels with certainty.

An innovative flat-knit compression garment for lymphoedema patients led to better outcomes: a multicentre study.

OBJECTIVE: To evaluate the clinical performance, quality of life (QoL) and patient satisfaction with an innovative flat-knit compression garment for the daytime treatment of lymphoedema patients in daily routine. METHOD: In a prospective multicentre observational study, patients with leg or arm lymphoedema (stage I-II, International Society of Lymphology (ISL) standards, 2016) received a made-to-measure flat-knit compression class 2 JOBST Confidence (BSN-JOBST GmbH, Germany) thigh-high stocking or arm sleeve. Primary endpoint was the oedema status as determined by the mean sum of the circumferences at the beginning and the end of the wearing period. Secondary endpoints included QoL-related parameters and patient satisfaction with product features assessed through questionnaires. The observation period lasted three weeks. RESULTS: A total of 97 patients (87 females, 10 males), of which 65 had leg lymphoedema and 32 had arm lymphoedema, received the study device. The oedema status was effectively maintained (slight reduction in mean sum of circumferences by -3.1±7.3cm; p=0.0001). For QoL-related parameters, the patients reported fewer limitations in work, leisure and psychological wellbeing after wearing the stocking or arm sleeve (all p-values <0.0001). They also experienced less limitations in function and movement, feeling of tension and heaviness, and fewer difficulties wearing clothes, shoes, jewellery or watches at study end (all p-values <0.0001). In terms of pleasant feeling on the skin, moisture management, softness of material, range of motion, overall wearing comfort and heat build-up under the garment, patients were more satisfied with the tested compression garment than with previously worn compression garments (all p-values <0.001). CONCLUSION: In this study, the tested innovative compression product increased patient satisfaction with the improved product features while the lymphoedema status was successfully maintained.

Alternative Lymphatic Drainage Pathways in the Trunk Following Oncologic Therapy.

BACKGROUND: Anatomic and functional descriptions of trunk and breast lymphedema following breast cancer treatment are emerging as indicators of lymphatic dysfunction. Indocyanine green-lymphangiography has been instrumental in characterizing this dysfunction in the extremity and can be applied to other regions. Previous work has established a validated Pittsburgh Trunk Lymphedema Staging System to characterize such affected areas. This study aims to identify risk and protective factors for the development of truncal and upper extremity lymphedema using alternative lymphatic drainage, providing implications for medical and surgical treatment. METHODS: Patients undergoing revisional breast surgery with suspicion of upper extremity lymphedema between 12/2014 and 3/2020 were offered lymphangiography. The breast and lateral/anterior trunks were visualized and blindly evaluated for axillary and inguinal lymphatic flow. A linear-weighted Cohen's kappa statistic was calculated comparing alternative drainage evaluation. Binomial regression was used to compute relative risks (RRs). Significance was assessed at alpha = 0.05. RESULTS: Eighty-six sides (46 patients) were included. Twelve sides underwent no treatment and were considered controls. Eighty-eight percent of the noncontrols had alternative lymphatic flow to the ipsilateral axillae (64%), ipsilateral groins (57%), contralateral axillae (20.3%), and contralateral groins (9.3%). Cohen's kappa for alternative drainage was 0.631 ± 0.043. Ipsilateral axillary and contralateral inguinal drainage were associated with reduced risk of developing truncal lymphedema [RR 0.78, confidence interval (CI) 0.63-0.97, P = 0.04; RR 0.32, CI 0.13-0.79, P = 0.01, respectively]. Radiation therapy increased risk of truncal and upper extremity lymphedema (RR 3.69, CI 0.96-14.15, P = 0.02; RR 1.92, CI 1.09-3.39, P = 0.03, respectively). Contralateral axillary drainage and axillary lymph node dissection were associated with increased risk of upper extremity lymphedema (RR 4.25, CI 1.09-16.61, P = 0.01; RR 2.83, CI 1.23-6.52, P = 0.01, respectively). CONCLUSIONS: Building upon previous work, this study shows risk and protective factors for the development of truncal and upper extremity lymphedema. Most prevalent alternative channels drain to the ipsilateral axilla and groin. Ipsilateral axillary and contralateral inguinal drainage were associated with reduced risk of truncal lymphedema. Patients with radiation, axillary dissection, and contralateral axillary drainage were associated with increased risk of upper extremity lymphedema. These findings have important clinical implications for postoperative manual lymphatic drainage and for determining eligibility for lymphovenous bypass surgery.

Lymphadenectomy After Melanoma-A National Analysis of Recurrence Rates and Risk of Lymphedema.

INTRODUCTION: Treatment for melanoma after a positive sentinel lymph node biopsy includes nodal observation or lymphadenectomy. Important considerations for management, however, involve balancing the risk of recurrence and the risk of lymphedema after lymphadenectomy. METHODS: From the Merative MarketScan Research Databases, adult patients were queried from 2007 to 2021. International Classification of Disease, Ninth (ICD-9) and Tenth (ICD-10) Editions, diagnosis codes and Current Procedural Terminology codes were used to identify patients with melanoma diagnoses who underwent an index melanoma excision with a positive sentinel lymph node biopsy (SLNB). Main outcomes were completion lymph node dissection (CLND) utilization after a positive SLNB, developing lymphedema with or without CLND, and nodal basin recurrence 3 months or more after index excision. Subanalyses stratified by index excision year (2007-2017 and 2018-2021) and propensity score matched were additionally conducted. Demographics and comorbidities (measured by Elixhauser index) were recorded. RESULTS: A total of 153,085,453 patients were identified. Of those, 359,298 had a diagnosis of melanoma, and 202,456 patients underwent an excision procedure. The study cohort comprised 3717 patients with a melanoma diagnosis who underwent an excision procedure and had a positive SLNB. The mean age of the study cohort was 49 years, 57% were male, 41% were geographically located in the South, and 24% had an Elixhauser index of 4+. Among the 350 patients who did not undergo CLND, 10% experienced recurrence and 22% developed lymphedema. A total of 3367 patients underwent CLND, of which 8% experienced recurrence and 20% developed lymphedema. Completion lymph node dissection did not significantly affect risk of recurrence [odds ratio (OR), 1.370, P = 0.090] or lymphedema (OR, 1.114, P = 0.438). After stratification and propensity score matching, odds of experiencing lymphedema (OR, 1.604, P = 0.058) and recurrence (OR, 1.825, P = 0.058) after CLND were not significantly affected. Rates of CLND had significantly decreased (P < 0.001) overtime, without change in recurrence rate (P = 0.063). CONCLUSIONS: Electing for nodal observation does not increase the risk of recurrence or reduce risk of lymphedema. Just as CLND does not confer survival benefit, its decreased utilization has not increased recurrence rate.

The Role of Inflammation in Lymphedema: A Narrative Review of Pathogenesis and Opportunities for Therapeutic Intervention.

Lymphedema is a chronic and progressive disease of the lymphatic system characterized by inflammation, increased adipose deposition, and tissue fibrosis. Despite early hypotheses identifying lymphedema as a disease of mechanical lymphatic disruption alone, the progressive inflammatory nature underlying this condition is now well-established. In this review, we provide an overview of the various inflammatory mechanisms that characterize lymphedema development and progression. These mechanisms contribute to the acute and chronic phases of lymphedema, which manifest clinically as inflammation, fibrosis, and adiposity. Furthermore, we highlight the interplay between current therapeutic modalities and the underlying inflammatory microenvironment, as well as opportunities for future therapeutic development.

Outcomes from a proof-of-concept specialist lymphoedema clinic in the community.

The Health and Safety Execultive lymphoedema model of care was published in 2018 highlighting the lack of dedicated lymphoedema services in Ireland. This led to the introduction of a proof-of-concept primary care specialist lymphoedema clinic. The clinic was responsible for all patients from their county. A comprehensive dataset was gathered which included the patient's history for 1 year prior to their presentation at clinic and then 6 monthly. A quality of life tool (LymQoL) and a patient satisfaction survey were completed. Completed 1-year data showed a significant reduction in GP and public health nurse visits as well as a reduction in the occurrence of cellulitis and associated hospital admissions. All areas of quality of life were improved and patient satisfaction was either excellent (89%) or very good (11%). The 1-year findings strongly support the roll-out of specialist clinics to all regional health areas.

National Lymphoedema Conference 2024: session summaries.

The 11th annual National Lymphoedema Conference, organised by the British Journal of Community Nursing in association with the British Lymphology Society and Lipoedema UK, was hosted at the America Square Conference Centre, London, on 22 February 2024. The conference, which aims to provide new insights into the latests developments in lymphoedema care and management through talks by leading experts in the field, was attended by an impressive number of delegates and exhibitors. The sessions were Chaired by BLS Trustee Rebecca Elwell, and are summarised below.

The assessment and management of foot and toe oedema as part of holistic lower limb care.

Toe and foot swelling can manifest as lymphoedema or chronic oedema but can also be a complication of the treatment of these conditions. In this article, the authors discuss the assessment and treatment options for toe and foot swelling, highlighting the importance of prevention in the first instance.

Integrated lymphoedema and tissue viability service: improving patient and wound outcomes.

This article will focus on the integration of tissue viability and lymphoedema services to improve outcomes for patients with leg ulceration. It will highlight why there is a need for lymphoedema specialist knowledge within the care of patients with leg ulceration and how the services are closely aligned. Lymphoedema can adversely affect wound healing and the article will provide case studies that highlight how developing a hybrid tissue viability and lymphoedema clinician or integration of the specialists can provide effective patient-centred care at reduced cost. The article offers potential strategies and suggestions on how to address inequalities in care and how to improve service provision.

Improving quality of life after breast cancer: a comparison of two microsurgical treatment options for breast cancer-related lymphedema (BCRL).

PURPOSE: Vascularized lymph node transfer (VLNT) entails the autologous relocation of lymph nodes to a lymphedematous region of the body, whereas lymphaticovenous anastomosis (LVA) creates a direct bypass between the lymphatic and venous system. Both techniques are meant to lastingly bolster the local lymphatic drainage capacity. This study compared safety and effectiveness of VLNT and LVA in patients with chronic breast cancer related lymphedema (BCRL). METHODS: A retrospective cohort study was conducted using data from our encrypted database composed of patients with chronic BCRL who were treated with either VLNT or LVA and had a minimum follow-up of two years. Patient-specific variables analyzed included pre- and postoperative arm circumferences, lymphedema stages and postoperative complications. RESULTS: A total of 105 patients met the inclusion criteria, of which 96 patients demonstrated a complete follow-up period of two years. The VLNT group displayed larger preoperative circumferential measurements, evident in both in the isolated examination of the affected arm, as well as when adjusted for the contralateral unaffected arm. Significant reduction in arm volume was achieved by both groups. However, VLNT demonstrated superior relative reduction rates than LVA, neutralizing any significant arm size disparities after 24 months. Surgery duration was slightly longer for VLNT than LVA. Postoperative complications, predominantly minor, were exclusively observed in the VLNT group. CONCLUSIONS: Both VLNT and LVA offer significant improvement for patients suffering from chronic BCRL. VLNT shows an even greater potential for improvement in more severe cases of BCRL, but involves a higher risk for (mostly minor) complications.

Lymphoedema specialists embedded into community nurse and wound services: impacts and outcomes.

BACKGROUND: Lymphoedema is a progressive condition causing significant alterations to life, exerting pressures on unscheduled care from complications including cellulitis and wounds. An on the ground education programme (OGEP) was implemented to raise knowledge, competence and confidence in lymphoedema management in community clinical services. The aim of this study was to explore the impact and outcomes of the OGEP intervention. METHODS: Data were captured before and after OGEP on 561 lymphoedema patients in the community setting. Data recorded included resource use, costs and outcomes (EQ-5D-5L and LYMPROM). RESULTS: Data demonstrated statistically significant reductions in resource allocations including staff visits (P<0.001), cellulitis admissions (P<0.001), compression consumables and wound dressing costs (P<0.001). Overall, the total mean per patient cost decreased from £1457.10 to £964.40 (including intervention) with outcomes significantly improved in EQ-5D-5L/LYMPROM scores. CONCLUSION: The analysis suggests the OGEP intervention may offer reductions in resource costs and improvements in patient outcomes. OGEP may therefore provide an innovative solution in future care delivery.

Diagnóstico oftalmológico del síndrome de linfedema-distiquiasis a través de la mutación FOXC2 / Ophthalmologic diagnosis of lymphedema-distichiasis syndrome through the FOXC2 mutation

El síndrome de linfedema-distiquiasis es uno de los fenotipos más frecuentes de aparición de linfedema primario; aun así, su prevalencia es baja.Este síndrome cursa con la aparición en la infancia o en la pubertad de pestañas aberrantes y otras formas de distiquiasis que pueden disminuir la calidad de vida, especialmente en pacientes en edades tan tempranas. La valoración clínica de este tipo de signos debe hacernos tener en mente este grupo de síndromes, ya que contamos, en este caso, con el diagnóstico de certeza gracias al análisis genético en suero del gen FOXC2, como ocurre en el caso que presentamos.De esta manera podemos prevenir, diagnosticar y tratar tanto los síntomas oftalmológicos como el resto de los síntomas sistémicos de forma precoz y más efectiva, aumentando así la calidad de vida de nuestros pacientes. (AU)

Lymphedema-distichiasis syndrome is one of the most frequent phenotypes of primary lymphedema, even so, its prevalence is still low.This syndrome courses with the appearance of abnormal eyelashes and distichiasis during childhood or puberty. This can cause a notable discomfort on our patients, especially at such an early age. The clinic evaluation of this signs must make us have in mind this group of syndromes, because in the case of lymphedema distichiasis syndrome, we can certainly diagnose it with the genetic analysis of the FOXC2 gen on patient's serum.With this we could prevent, diagnose and treat the ophthalmologic syndrome alongside the rest of systemic symptoms of this syndrome in a more effective way, giving our patients a higher quality of life. (AU)