Lymphaticovenous Anastomosis as Treatment for Lymphedema

Not Applicable

Active, not recruiting

• Conditions: Breast Cancer Lymphedema; Lymphedema of Upper Limb; Lymphedema Arm; Lymphedema, Breast Cancer; Neoplasms; Postoperative Complications; Pathologic Processes; Anastomose; Secondary Lymphedema; Iatrogenic Lymphedema
• Interventions: Procedure: Lymphovenous anastomosis

• Registration Number: NCT05441943
• Lead Sponsor: Odense University Hospital

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2022-05-11
• Study First Submitted: 2022-06-07
• Study First Submitted QC: 2022-06-28
• Study First Posted: 2022-07-01
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-04
• Last Update Posted: 2024-03-05
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 10

Inclusion Criteria

• Female
• Iatrogenic lymphedema following treatment for breast cancer in upper extremity
• Possible to obtain informed consent
• Age>18

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Exclusion Criteria

• Duration of disease over 24 months
• Smoker
• Untreated or uncontrolled primary cancer
• No applicable lymphatic vessels identified, using ICG lymphangiography
• No applicable venous vessels identified using ultra high frequency ultrasound

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Number of vessels planned for surgery surgery	Preoperative	The number of mapped lymphatics vessels and venoles.
Number of vessels found during surgery	Perioprative	The number of vessels found during surgery. This number will be compared to the number of vessels planned for surgery.

Secondary Outcome Measures

Name	Time	Method
Changes of fat mass (kg) relative to weight (kg), measured in percentage.	Baseline and 3 months follow-up	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)).
Changes in L-Dex score	Baseline and 3 months follow-up	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.
Changes of arm volume	Baseline and 3 months follow-up	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.
Change of extracellular fluid (liters) relative to total body water (liters), measured in percentage.	Baseline and 3 months follow-up	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)).
Changes of intracellular fluid (liters) relative to total body water (liters), measured in percentage.	Baseline and 3 months follow-up	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)).
Changes of total body water (liters) relative to weight (kg), measured in percentage.	Baseline and 3 months follow-up	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)).
Changes of proteins and minerals (kg) relative to weight (kg), measured in percentage.	Baseline and 3 months follow-up	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)).
Changes in health-related quality-of-life measured by the LYMPH-Q questionnaire	Baseline and 3 months follow-up	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.
Changes in active tissue mass (kg) relative to weight (kg), measured in percentage.	Baseline and 3 months follow-up	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)).
Changes of skeletal muscle mass (kg) relative to weight (kg), measured in percentage.	Baseline and 3 months follow-up	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)).
Changes of lymphatic flow pattern before and after surgery by ICG lymphangiography	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.

Trial Locations

Locations (1)

Department of Plastic Surgery, Odense University Hospital; 🇩🇰 Odense, Region Of Southern Denmark, Denmark