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Tumescent technique in lymph-sparing fashion was adopted. Areas were infiltrated with a mix of a standard tumescent solution consisting for each liter of in 1000 ml of saline solution, 50 ml lidocaine 1%, 1 ml epinephrine 1:1000, 10 ml bicarbonate 8,4%. Infiltration volume was approximately from 0,5 to 1 liter for the upper extremities and 1-2 liters for lowers. Three to 4 mm 3 holes blunt cannulas were employed. Aspiration technique was as parallel as possible along the lymphatic network pattern and from superficial to deep layers.

Lymphatic vessels identified at ICG lymphography were spared. Volume of the aspirate was aimed to approximate 80 percent of the volume difference between the affected and non affected side.

The number and type of anastomosis were recorded as well as amount of removed lipoaspirate versus the excess limb volume.

LVA and liposuction

* cooperation of an International team with many years of experience in surgical management of lymphedema
* description of an effective surgical strategy to treat cancer-related lymphedema, a high incidence pathology
* the combination of LVA and liposuction guarantees long lasting results

Cancer-related lymphedema represents one of the major complications of cancer treatment, especially for breast and gynecologic cancers. Moreover, it has high impact on cancer survivors and healthcare systems. Lymphedema management still remains challenging. The better understanding of lymphedema physiopathology as well as the development of sophisticated surgical and diagnostic techniques have led to effective strategies to address lymphedema patients but, despite the considerable interest in international literature, no consensus exist.

The authors present a retrospective analysis of 24 consecutive patients affected by cancer-related lymphedema treated by the combination of LVA and liposuction in the same surgical session. Patients data regarding limb volume, lymphangitis rate and quality of life index were assessed before surgery and 1 year after surgery.

One year after surgery an average volume reduction of 37,9% was registered. Lymphangitis rate significantly decreased after surgery to 0.95 per year. Quality of life score improved.

CONCLUSIONS The combination of LVA and liposuction represents an effective strategy in treating patients with cancer-related lymphedema, ensuring a significant decrease in volume and reduction of lymphangitis rate as well as stable results in time. In addition, it appears to be minimally invasive and well tolerated by patients, since it can be performed under local anesthesia with low risk of complications.

COMBINATION OF LYMPHATICO-VENULAR ANASTOMOSIS AND LIPOSUCTION IN TREATING LYMPHEDEMA

COMBINATION OF LYMPHATICO-VENULAR ANASTOMOSIS AND LIPOSUCTION TO TREAT CANCER-RELATED LYMPHEDEMA: RATIONALE FOR A REGIONAL APPROACH

University of Siena

Neoplasms

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Breast Neoplasms

Neoplasm Metastasis

Syndrome

Skin Diseases

Postoperative Complications

Breast Cancer Lymphedema

Breast Diseases

Lymphovenous anastomosis surgery with pre-operative planning using ICG lymphography and ultra high frequency ultrasound.

Pre-operative planning prior to lymphovenous anastomosis using ICG lymphography and ultra high frequency ultrasound for mapping of applicable vessels.

During surgery, mapped vessels are freely dissected and anastomosed.

Lymphovenous anastomosis

Caroline Lilja, MD

Jens Ahm Sørensen, MD, Prof, PhD

Jørn Bo Thomsen, MD, Prof, PhD

The primary aim of this study is to investigate and test whether the use of combined indocyanine green (ICG) lymphography and ultra high frequency ultrasonography can correctly identify lymphatic vessels and venoles in close proximity to each other, for identification prior to lymphovenous anastomosis (LVA) surgery.

BACKGROUND

Breast-cancer related lymphedema is a life-disabling side-effect of breast cancer treatment, affecting more than 1 in every 5 patients. With breast-cancer being the most common cancer diagnosis in women, affecting up to 2.3 million new cases globally, and with a generally high survival rate of 80% or higher in developed countries, the number of breast-cancer survivors with long-term sequela is significant. Compression garments have been considered the standard treatment and rehabilitation for lymphedema. Some of the disadvantages with these treatments include variability in patient compliance, clinical effect and lack of statistical significant results. Therefore, the rehabilitation and treatment options for lymphedema are in high demand, affecting patients physical and mental health.

Lymphovenous anastomosis (LVA) surgery is an attempt to re-establish the lymphatic flow, utilizing the patient's own lymphatic- and venous vessels. Surgical treatment seems effective in selective patient groups, but systematic studies for this are lacking. It is based on this lack of knowledge of patient characteristics and preoperative planning that the project's hypothesis and idea was formed.

Indocyanine green (ICG) lymphography is commonly used for identification of lymphatic vessels pre-operatively, and is considered superior to other modalities. However, until recently, the identification of adjacent venoles has remained a challenge. Ultra high frequency ultrasound may have solved the challenge of identifying the small venoles prior to surgery. The combined use of ICG lymphography and ultra high frequency ultrasound may be the key to optimise patient selection and pre-operative planning of lymphovenous anastomosis surgery.

METHOD

This study is designed as a pilot study with a planned inclusion of 10 patients with a 3 months follow-up period.

The inclusion of patients, the surgical procedure and 3 months follow-up evaluation will take place at the Department of Plastic Surgery Odense University Hospital (OUH), Denmark.

The ICG lymphography is performed by injecting ICG subcutaneously, and used for visualization of the superficial lymphatics for preoperative planning. During real-time visualization, lymphatic vessels are drawn up on the patients arm using a permanent marker.

Ultra high frequency ultrasound (\>30MHz) has the ability to visualize small, superficial anatomical layers. Using this ultra high frequency ultrasound (70MHz), following the mapped lymphatic vessels, venous vessels are found nearby and likewise mapped for anastomosis.

The number of LVA anastomosis sites is set to a minimum of two sites per extremity. The number of mapped lymphatics vessels and venoles are compared to the number identified during surgery and recorded.

Prior to and 3 months after surgery, patients are seen for objective measures of upper extremity volume, body composition, L-Dex score of the affected arm and health-related quality-of-life, in addition to ICG lymphography.

Lymphaticovenous Anastomosis as Treatment for Lymphedema

Lymphaticovenous Anastomosis as a Surgical Treatment for Breast Cancer-Related Lymphedema

The number of mapped lymphatics vessels and venoles.

The number of vessels found during surgery. This number will be compared to the number of vessels planned for surgery.

The change of arm volume difference at baseline and at three months follow-up after surgery.

Volume calculation Manual circumferential measurements are taken from both arms for volume calculation, based on the formula for multiple blunt cones.

Water displacement for volume assessment The water displacement test estimates the volume of the arm, based on lowering the extremity in a basin of water, and calculating the water volume difference in mL. Both extremities are measured.

The change in extracellular fluid (liters), relative to total body water (liters), measured by a stand-on bioimpedance at baseline and 3 months follow-up. The stand-on device measure the body composition through small electric impulses between two electrodes.

Extracellular fluid and total body water measures will be aggregated to one reported value (extracellular fluid (liters) / total body water (liters)).

The change in intracellular fluid (liters), relative to body water (liters), measured by a stand-on bioimpedance at baseline and 3 months follow-up. The stand-on device measure the body composition through small electric impulses between two electrodes.

Intracellular fluid and total body water measures will be aggregated to one reported value (intracellular fluid (liters) / total body water (liters)).

The change in total body water (liters), relative to body weight (kg), measured by a stand-on bioimpedance at baseline and 3 months follow-up. The stand-on device measure the body composition through small electric impulses between two electrodes.

Total body water and weight measures will be aggregated to one reported value (total body water (liters) / weight (kg)).

The change in proteins and minerals (kg), relative to body weight (kg), measured by a stand-on bioimpedance at baseline and 3 months follow-up. The stand-on device measure the body composition through small electric impulses between two electrodes.

Proteins and minerals and weight measures will be aggregated to one reported value (proteins and minerals (kg) / weight (kg)).

The change in fat mass (kg), relative to body weight (kg), measured by a stand-on bioimpedance at baseline and 3 months follow-up. The stand-on device measure the body composition through small electric impulses between two electrodes.

Fat mass and weight measures will be aggregated to one reported value (fat mass (kg) / weight (kg)).

The change in active tissue mass (kg), relative to body weight (kg), measured by a stand-on bioimpedance at baseline and 3 months follow-up. The stand-on device measure the body composition through small electric impulses between two electrodes.

Active tissue mass and weight measures will be aggregated to one reported value (active tissue mass (kg) / weight (kg)).

The change in skeletal muscle mass (kg), relative to body weight (kg), measured by a stand-on bioimpedance at baseline and 3 months follow-up. The stand-on device measure the body composition through small electric impulses between two electrodes.

Skeletal muscle mass and weight measures will be aggregated to one reported value (skeletal muscle mass (kg) / weight (kg)).

L-Dex score is a measurement of extracellular fluid of the arm. A stand-on bioimpedance device, estimates the extracellular fluid trough electric impulses between its electrodes. Based upon the impedance ratio of the affected and unaffected arm, the bioimpedance calculates a Lymphedema index, called L-Dex ratio score. A number between -10 and 10 is considered normal, and diagnostic for lymphedema if above 10. Its sensitivity and specificity are 0.66 and 0.99, respectively, at a receiver operating characteristic curve (ROC) value of 10. The score correlates with the limb volume and lymphatic function.

The LYMPH-Q Upper extremity module questionnaire is a validated patient-reported outcome tool for women with breast cancer related lymphedema. The module contains seven individual scales, measuring: symptoms, function, appearance, psychological function, and satisfaction with information on lymphedema and satisfaction with arm sleeve. Each scale gives an independent score reaching from 0 (worst) to 100 (best), which can be used for comparison of change over time. A higher score indicates a better outcome.

Patients will complete the questionnaire at baseline and 3 months follow-up.

Video recordings of ICG lymphographies are stored for later classification of the lymphedema. Staging will be done using the MD Anderson scale; a classification system based upon pattern recognition of the dermal backflow from the ICG lymphography, see table 1.

MD Anderson stage ICG lymphography findings Stage 0 No dermal backflow Stage 1 Many patent lymphatics and minimal dermal backflow Stage 2 Moderate number of patent lymphatics and segmental dermal backflow Stage 3 Few patent lymphatics with extensive dermal backflow Stage 4 Dermal backflow involving the hand Stage 5 ICG does not move proximally to injection site Table 1: MD Anderson classification based upon ICG lymphography findings.

Danish Cancer Society

Odense University Hospital

Principal Investigator

Rare Diseases

Chronic Graft Versus Host Disease

Anesthetics

Patients in this group will undergo lymphaticovenous anastomosis at one or more locations on the affected limb, and the procedure will be performed under local anesthesia. During the operation, patients will be blinded using a noise-canceling headphone and blindfolds. Incisions will be made at the sites where lymphatic vessels are obstructed, ensuring no harm to the viable part of the lympahtic system. The locations will be determined prior to the surgery using ICG lymphography. The LVA(s) will be made in the subdermal plane with the aid of a surgical microscope. Generally, 1 to 4 LVAs are made. The LVA(s) is made using a surgical microscope and the operation will take approximately 60 to 90 minutes.

Patients in this group will undergo sham surgery at one location on the affected limb, and the procedure will be performed under local anesthesia. During the operation, patients will be blinded using a noise-canceling headphone and blindfolds. The locations for LVA surgery will be determined prior to the surgery using ICG lymphography. However, the incision for the sham procedure will be made 2 centimeters medial or lateral to the predetermined site. This is done in order to avoid damage to the lymph vessels as to allow for future LVA surgery. After the incision, no LVA is made. Rather than performing the actual operation, the plastic surgeon will simulate the procedure by applying pressure in the surgical area. To mimic the approximate duration of a regular LVA procedure, the sham operation will take approximately 60 to 90 minutes.

Lymphaticovenous anastomosis (LVA) involves connecting a lymphatic vessel to a adjacent vein of similar size, thereby facilitating the ouflow of lymphatic fluid in patients suffering from secondary lymphedema

Lymphaticovenous anastomosis

Sham surgery involves the process of surgery, including local anesthesia and incisions, but no LVA is made.

Sham surgery

Alieske Kleeven, MSc

Stefan Hummelink, MSc, PhD

Yasmine Jonis, MSc

Shan Shan Qiu Shao, MSc, PhD

Dalibor Vasilic, MSc, PhD

The goal of this randomized controlled trial is to compare the effectiveness and cost-effectiveness of lymphaticovenous anastomosis (LVA) with sham surgery for patients suffering from unilateral cancer-related lymphedema in either the upper or lower extremity. It aims to answer whether LVA is more effective than sham surgery in terms of improvement in Lymph-ICF score.

A total of 110 participants will be allocated randomly into two groups at a 1:1 ratio. The first group will receive lymphaticovenous anastomosis (LVA), while the second group will undergo sham surgery.

One of the most debilitating side effects of cancer treatment is cancer-related lymphedema (CRL), with an overall incidence of 15.5%. To date, there is no definite cure for lymphedema. Conservative therapy, namely complex decongestive therapy is the golden standard for the treatment. Lymphaticovenous anastomosis (LVA) might be a promising treatment modality for patients with CRL, but available studies are small and the quality is lacking. No large-scale prospective or randomized studies have been published on the efficacy of LVA.

The main objective of this randomized controlled trial is to assess whether LVA is more effective than sham surgery in terms of improvement in Lymph-ICF score, volume reduction, reduction of complex decongestive therapy, and cost-effectiveness.

The study will take place in three centers in the Netherlands: Maastricht University Medical Center, Radboud University Medical Center, and Erasmus University Medical Center.

The patients will be randomly distributed into two groups: the LVA group or the Sham group. Both procedures are performed under local anesthesia. Patients in both groups are subject to minor surgical complications (wound infection, bleeding, wound dehiscence). Special care will be taken to prevent damage to lymphatic vessels in the Sham group, to allow a future LVA operation once the study ends. The follow-up moments will be at 3, 6, 12, 18, and 24 months. Additionally, a subset of patients will partake in an annual extended follow-up, ongoing until the start of the analysis. Each follow-up moment will last 45 minutes in total. The patient also receives two digital questionnaires at each follow-up moment.

Multicenter, double-blind, randomized sham-controlled trial

The researcher, research nurse and patients will be blinded. The blinded researcher and research nurse will perform the measurements during follow-up, as well as the assessment of the outcomes. Due to the nature of the study, the surgeon performing both procedures cannot be blinded.

The N-LVA Study: RCT Comparing LVA vs. Sham Surgery in Cancer-related Lymphedema

Effectiveness and Cost-effectiveness of Lymphaticovenous Anastomosis for Cancer Patients Who Suffer From Chronic Peripheral Lymphedema: a Randomized Controlled Trial

The results will be published under an Open Access license, making them accesible to everyone at all times. Requests for sharing individual participant data (IPD) will be evaluated on a case-by-case basis, assessing them for suitable research purposes following the trial's completion.

The Dutch version of the 'Lymphedema Functioning, Disability, and Health" (Lymph-ICF) questionnaire is used. There are two versions of the Lymph-ICF; one for the upper extremity and one for the lower extremity. The questionnaires assess the impairments in function, activity limitations, and participation restrictions of patients with lymphedema. It is a validated, disease-specific questionnaire, consisting of items across 5 domains. Each item is scored on a VAS, ranging from 0 to 100.

The excess limb volume will be measured with BioImpedance Spectroscopy (BIS). With a bioimpedance device, the volume of the extremities can be measured together with the fluid in different compartments of the extremities.

The extremity circumference will be measured using measuring tape according to the fixed measuring points of the UEL- and LEL-indices. The UEL- and LEL-indices are corrected for BMI.

Discontinuation of conservative treatment, being complex decongestive therapy, will be assessed with a patient diary to record the frequency of treatments received (i.e. skin therapy visits, number of compression garments, etc.).

All postoperative complications for both treatment groups will be recorded to monitor safety. SAEs will be directly reported to the sponsor.

The patency of the LVAs will be measured with ICG lymphography

Patients costs are registered by the patient in the patient diary. The QALY will be calculated using the EQ-5D-5L questionnaire. The EQ-5D is a questionnaire responsive to changes in health in cancer-patients after the conclusion of treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
COMBINATION OF LYMPHATICO-VENULAR ANASTOMOSIS AND LIPOSUCTION IN TREATING LYMPHEDEMA	NCT04536064	Description of ...	LVA and liposuc...	-	University of Siena
Lymphaticovenous Anastomosis as Treatment for Lymphedema	NCT05441943	Breast Cancer L... Secondary Lymph... Iatrogenic Lymp... Lymphedema Lymphedema of U... Lymphedema Arm Lymphedema, Bre... Breast Neoplasm Neoplasms Breast Cancer Breast Diseases Lymphatic Disea... Skin Diseases Postoperative C... Pathologic Proc... Anastomose Surgery Surgical; Lymph... Postmastectomy ... Postmastectomy ... Postmastectomy ... Postmastectomy ...	Lymphovenous an...	18 Years -	Odense University Hospital
Lymphaticovenous Anastomosis as Treatment for Lymphedema	NCT05441943	Breast Cancer L... Secondary Lymph... Iatrogenic Lymp... Lymphedema Lymphedema of U... Lymphedema Arm Lymphedema, Bre... Breast Neoplasm Neoplasms Breast Cancer Breast Diseases Lymphatic Disea... Skin Diseases Postoperative C... Pathologic Proc... Anastomose Surgery Surgical; Lymph... Postmastectomy ... Postmastectomy ... Postmastectomy ... Postmastectomy ...	Lymphovenous an...	18 Years -	Odense University Hospital
The N-LVA Study: RCT Comparing LVA vs. Sham Surgery in Cancer-related Lymphedema	NCT06082349	Lymphedema, Sec... Lymphedema of U... Lymphedema, Low... Lymphedema Arm Lymphedema of L...	Lymphaticovenou... Sham surgery	18 Years -	Maastricht University Medical Center
The N-LVA Study: RCT Comparing LVA vs. Sham Surgery in Cancer-related Lymphedema	NCT06082349	Lymphedema, Sec... Lymphedema of U... Lymphedema, Low... Lymphedema Arm Lymphedema of L...	Lymphaticovenou... Sham surgery	18 Years -	Maastricht University Medical Center

Spots Global Cancer Trial Database for lva

Every month we try and update this database with for lva cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for lva

Every month we try and update this database with for lva cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for lva cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.