Lymphaticovenous Anastomosis as Treatment for Lymphedema

March 4, 2024 updated by: Caroline Lilja, Odense University Hospital

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

10

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Denmark
    • Region Of Southern Denmark
      • Odense, Region Of Southern Denmark, Denmark, 5000
        • Department of Plastic Surgery, Odense University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lymphovenous anastomosis surgery
Lymphovenous anastomosis surgery with pre-operative planning using ICG lymphography and ultra high frequency ultrasound.
Procedure: Lymphovenous anastomosis

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.

Other Names:
  • LVA
  • Lymphaticovenous anastomosis
  • Lymphaticovenular anastomosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of vessels planned for surgery surgery
Time Frame: Preoperative
The number of mapped lymphatics vessels and venoles.
Preoperative
Number of vessels found during surgery
Time Frame: Perioprative
The number of vessels found during surgery. This number will be compared to the number of vessels planned for surgery.
Perioprative

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Odense University Hospital

Collaborators

Danish Cancer Society

Investigators

  • Principal Investigator: Caroline Lilja, MD, Department of Plastic Surgery at Odense University Hospital
  • Study Chair: Jens Ahm Sørensen, MD, Prof, PhD, Department of Plastic Surgery at Odense University Hospital
  • Study Chair: Jørn Bo Thomsen, MD, Prof, PhD, Department of Plastic Surgery at Odense University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 11, 2022

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

June 7, 2022

First Submitted That Met QC Criteria

June 28, 2022

First Posted (Actual)

July 1, 2022

Study Record Updates

Last Update Posted (Estimated)

March 5, 2024

Last Update Submitted That Met QC Criteria

March 4, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 21/59848
  • S-20210169 (Other Identifier: The Research Ethics Committee of the Region of Southern Denmark)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Pathologic Processes

Clinical Trials on Lymphovenous anastomosis

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Azerbaijan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe