The Vascularized Omentum Lymph Node Transfer - A Key Point in the Lymphedema Management.

Background: As an increased number of women beat breast cancer worldwide, the breast cancer related lymphedema has gained more attention recently. The vascularized omentum lymph node transfer has been approached as an useful tool for advanced and recurrent cases. The purpose of the paper is to emphasize the advantages and disadvantages of this method. Materials and Methods: This retrospective study consists of 17 patients known with breast cancer related lymphedema who received vascularized omentum lymph node transfer. Data was recorded between January 2022 and January 2023. Patients diagnosed with secondary lymphedema stage II or III, unresponsive to previous microsurgical lymphovenous bypass were included. Results: The most prevalent affected site was the left upper limb (59%), where edema was mainly identified in the forearm (75%). Nevertheless, more than half of the subjects have previously received lymphaticovenous anastomosis. The correlation between the stage of lymphedema and the postoperative reduction of the volume of the affected limb was -0.26, the slope to reached -0.33, with an intercept value of 2.64. The follow-up period showed reduced upper limb volume and an improved quality of life. Conclusion: Through an experienced hand, this versatile flap brings hope to breast cancer survivors with lymphedema.

SurLym trial: study protocol for a multicentre pragmatic randomised controlled trial on the added value of reconstructive lymphatic surgery to decongestive lymphatic therapy for the treatment of lymphoedema.

INTRODUCTION: Lymphoedema is a chronic condition caused by lymphatic insufficiency. It leads to swelling of the limb/midline region and an increased risk of infection. Lymphoedema is often associated with mental and physical problems limiting quality of life. The first choice of treatment is a conservative treatment, consisting of exercises, skin care, lymph drainage and compression. Reconstructive lymphatic surgery is also often performed, that is, lymphovenous anastomoses, lymph node transfer or a combination. However, robust evidence on the effectiveness of reconstructive lymphatic surgery is missing. Therefore, the objective of this trial is to investigate the added value of reconstructive lymphatic surgery to the conservative treatment in patients with lymphoedema. METHODS AND ANALYSIS: A multicentre randomised controlled and pragmatic trial was started in March 2022 in three Belgian university hospitals. 90 patients with arm lymphoedema and 90 patients with leg lymphoedema will be included. All patients are randomised between conservative treatment alone (control group) or conservative treatment with reconstructive lymphatic surgery (intervention group). Assessments are performed at baseline and at 1, 3, 6, 12, 18, 24 and 36 months. The primary outcome is lymphoedema-specific quality of life at 18 months. Key secondary outcomes are limb volume and duration of wearing the compression garment at 18 months. The approach of reconstructive lymphatic surgery is based on presurgical investigations including clinical examination, lymphofluoroscopy, lymphoscintigraphy, lymph MRI or CT angiography (if needed). All patients receive conservative treatment during 36 months, which is applied by the patient's own physical therapist and by the patient self. From months 7 to 12, the hours a day of wearing the compression garment are gradually decreased. ETHICS AND DISSEMINATION: The study has been approved by the ethical committees of University Hospitals Leuven, Ghent University Hospital and CHU UCL Namur. Results will be disseminated via peer-reviewed journals and presentations. TRIAL REGISTRATION NUMBER: NCT05064176.

Edema of the upper extremity on the unaffected side in unilateral breast cancer patients.

Breast cancer-related lymphedema (BCRL) occurs usually on the affected side, and its cause and pathophysiology are well known. However, the cause of edema of the upper extremity on the unaffected side is barely known. It is often considered to be chemotherapy-induced general edema, and clinical evaluation is rarely performed in these patients. This study aimed to present the clinical characteristics of unilateral breast cancer patients with edema of upper extremity on the unaffected side, and to emphasize the importance of early diagnosis and medical interventions. This study retrospectively analyzed the medical records of unilateral breast cancer patients complaining edema of upper extremity on the unaffected side, from January 2020 to May 2021. Lymphoscintigraphy was used to assist in confirming the diagnosis of lymphedema, and Doppler ultrasonography or 3D computed tomography angiography were performed to differentiate vascular problems. Fourteen patients were enrolled in the study. Seven, 3, and 4 patients had edema of both upper extremities, edema of the upper extremity on the unaffected side only, and edema of all extremities, respectively. None of the 4 patients with edema of all extremities showed abnormal findings on examination. In patients with edema in the upper extremity on the unaffected side alone, lymphatic flow dysfunction was seen in 2 patients, and deep vein thrombosis (DVT) was diagnosed in 1. In patients with edema of both upper extremities, lymphatic flow dysfunction was seen in 2 patients, and DVT was diagnosed in 3. One patient had DVT and accompanying lymphatic flow dysfunction. Lymphedema and DVT were diagnosed in a number of patients with edema of the upper extremity on the unaffected side, and lymphedema can occur without direct injury to the lymphatic flow system. Therefore, clinicians should not overlook the fact that diseases that require early diagnosis and treatment can occur in patients with edema of the unaffected upper extremity.

The mechanosensory channel PIEZO1 functions upstream of angiopoietin/TIE/FOXO1 signaling in lymphatic development.

Lymphedema is a debilitating disease with no effective cure and affects an estimated 250 million individuals worldwide. Prior studies have identified mutations in piezo-type mechanosensitive ion channel component 1 (PIEZO1), angiopoietin 2 (ANGPT2), and tyrosine kinase with Ig-like and EGF-like domains 1 (TIE1) in patients with primary lymphedema. Here, we identified crosstalk between these molecules and showed that activation of the mechanosensory channel PIEZO1 in lymphatic endothelial cells (LECs) caused rapid exocytosis of the TIE ligand ANGPT2, ectodomain shedding of TIE1 by disintegrin and metalloproteinase domain-containing protein 17 (ADAM17), and increased TIE/PI3K/AKT signaling, followed by nuclear export of the transcription factor FOXO1. These data establish a functional network between lymphedema-associated genes and provide what we believe to be the first molecular mechanism bridging channel function with vascular signaling and intracellular events culminating in transcriptional regulation of genes expressed in LECs. Our study provides insights into the regulation of lymphatic function and molecular pathways involved in human disease.

Surgical Treatment of Breast Lymphedema: A Distinct Pathology With Unique Challenges.

BACKGROUND: Supermicrosurgical advances such as lymphovenous bypass (LVB) have enabled effective physiologic treatment of lymphedema affecting the extremities. Reports of surgical treatment for breast lymphedema (BL) are sparse, consisting of case reports and almost exclusively LVB. We report our experience with BL, including a case of mastectomy and breast reconstruction with abdominal free flap and inguinal vascularized lymph node transfer (VLNT) for BL. We compare our series with the surgical literature to discern unique characteristics and treatment limitations inherent to this disease. METHODS: A database was prospectively maintained from September 2020 to May 2023 including all patients diagnosed with BL who were referred to our institution. Breast lymphedema was diagnosed using clinical criteria, and relevant patient data were recorded. Patients interested in surgical management underwent indocyanine green lymphography to determine candidacy for LVB or other interventions. All patients, including those surgically managed, were treated with complex decongestive therapy. RESULTS: Nine patients with BL were included. Eight had undergone breast-conserving therapy for breast cancer with whole breast irradiation. One patient was treated for Hodgkin lymphoma with axillary lymphadenectomy and axillary radiation. Indocyanine green lymphography was performed in 6 patients, of which 4 patients had diffuse dermal backflow. Two patients had lymphatic targets suitable for LVB, including the patient without breast irradiation. Three patients were managed surgically. One patient without bypass targets underwent breast reduction with partial symptomatic relief, later followed by a mastectomy with abdominal free flap reconstruction and VLNT. Two patients with suitable bypass targets underwent LVB, with resolution of breast swelling and subjective symptoms. CONCLUSIONS: The diffuse lymphatic obliteration due to radiation field effect in BL results in a distinct pathophysiology compared with extremity lymphedema. Although published reports of surgical BL treatment almost exclusively describe LVB, other surgical options may be more frequently required. Ablative strategies such as mastectomy and regenerative techniques such as VLNT should be considered potential first-line treatment options for these patients.

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.

100 anastomoses: a two-year single-center experience with robotic-assisted micro- and supermicrosurgery for lymphatic reconstruction.

Robotic-assisted microsurgery has gained significant attention in recent years following the introduction of two dedicated microsurgical robotic systems specifically designed for this purpose. These feature higher degrees of movement and motion scaling which are useful tools, especially when performing surgery in areas of the body which are difficult to access. Robotic-assisted microsurgery has been implemented in lymphatic surgery as well as soft tissue reconstructive surgery at our institution over the past 2.5 years. Our study gives an insight into the details and outcomes of the first 100 consecutive (super-) microsurgical anastomoses in peripheral and central lymphatic reconstruction performed with the Symani® Surgical System between 2021 and 2024. In total, 67 patients were treated, receiving robotic-assisted lymphatic reconstruction with lymphatic tissue transfer (LTT) and/or lymphovenous anastomoses (LVA)/lympholymphatic anastomoses (LLA). No anastomosis-associated complications were recorded postoperatively. The majority of patients reported a postoperative improvement of their lymphedema or central lymphatic disorder. In conclusion, we show the successful implementation of the Symani® Surgical System into our clinical practice of lymphatic reconstruction. Although the necessary intraoperative setup and the use of intrinsic motion scaling lead to a slight increase in operating time, the presented study demonstrates the advantages of robotic assistance which becomes particularly evident in lymphatic surgery due to the involved deep surgical sites and the need for supermicrosurgical techniques.

Impact of risk factors, early rehabilitation and management of lymphedema associated with breast cancer: a retrospective study of breast Cancer survivors over 5 years.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a potentially disabling and often irreversible consequence of breast cancer treatment, caused by the mechanical incompetence of the lymphatic system, resulting in reduced drainage capacity and functional overload due to an excessive volume of interstitial fluid surpassing the system's transport capacity in the arm. We wanted to determine the impact and explore the differences in independent risk factors for the occurrence of BCRL; incidence of BCRL over a five-year period at the Institute of Oncology Vojvodina in Sremska Kamenica and to answer the research question regarding the influence of the prehabilitation program on the overall incidence of BCRL during the observed five-year period. METHODS: From 2014 to 2018, a retrospective study was conducted at the Institute of Oncology of Vojvodina in Sremska Kamenica, analyzing female patients who had undergone breast cancer surgery. RESULTS: The study included 150 breast cancer patients who developed secondary lymphedema following surgery with the mean age of 59.2 ± 11.3 years. Fluctuations in hospitalization rates were observed over the five-year period, with the highest number of admissions in 2014 (24.0%) and a decline in 2018 (14.0%). The most common surgical procedure performed was left quadrantectomy (24.0%), followed by right quadrantectomy (20.0%) and left amputation (15.3%). The mean number of removed lymph nodes was 15.2 ± 6.1, with no statistically significant association between the number of removed lymph nodes and the manifestation of secondary lymphedema. The severity of secondary lymphedema varied based on patient age, with a higher incidence of moderate and severe lymphedema observed in patients aged 61 years and older. Patients who underwent radical surgery were more likely to experience severe lymphedema compared to those who had conservative surgery, although this difference was not statistically significant. CONCLUSION: In our study, the type of surgery, elapsed time since surgery, and the number of removed lymph nodes were not influencing factors for the occurrence of BCRL. However, concerning its severity, a greater number of systemic therapy modalities combined with radiotherapy were associated with a more frequent occurrence of mild and moderate BCRL. Also, the severity of BCRL varied among different age groups, with a higher incidence of moderate and severe lymphedema observed in patients aged 61 years and older. Ultimately, improving the quality of life for individuals affected by secondary lymphedema remains a crucial goal in the field of oncology.

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.

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.

Primary lymphedema of childhood: Treatment results from a tertiary center.

BACKGROUND: Primary lymphedema is the most common form of lymphedema presenting in the pediatric age group. Childhood lymphedema is caused by hereditary or congenital malformations in the lymphatic system that can manifest at birth or during childhood or adolescence. OBJECTIVES: Complex decongestive therapy (CDT) is the cornerstone of conservative management of lymphedema in both adult and pediatric lymphedema patients, although pediatric treatment guidelines are still lacking. In this study we aimed to assess the effects of CDT on pediatric patients. METHODS: Childhood lymphedema patients who presented to the lymphedema rehabilitation unit of our university hospital before the age of 18 and who were treated for lymphedema with CDT were included in the study. Data on patient demographics, disease characteristics, and treatment duration were recorded. Limb volumes were calculated from patient measurements using a spreadsheet software (Limb Volume Calculator) that utilized the geometric formula for volume of a truncated cone. Measurements were taken before treatment and also weekly after initiation of treatment. Percent excess volume (PEV) was used instead of absolute volume difference to define the severity of lymphedema. RESULTS: A total of 34 limbs from 24 patients were included in the study. The mean age of the patients was 10.1 ± 4.9 years and 14 (58.3 %) were female. Most patients had one affected limb but 16 had bilateral lower-extremity lymphedema. The mean duration of treatment with CDT was 153.6 ± 155.8 days. Excess volume percentage change between pre-treatment PEV (602.8 ± 713.8) and post-treatment PEV (514.6 ± 699.1) was found to be statistically significant (p < 0.05). CONCLUSION: Pediatric lymphedema management is a difficult and less well studied area in lymphedema rehabilitation. Our data support the use of CDT, which is a safe and effective treatment method, for pediatric lymphedema patients.

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.

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.