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«TOPIC: The Diagnosis And Treatment Of Lymphedema Introduction Lymphedema is caused by an abnormality of the lymphatic system leading to excessive ...»

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Position Statement of the

National Lymphedema Network

By: NLN Medical Advisory Committee Updated February 2011

TOPIC: The Diagnosis And Treatment Of Lymphedema

Introduction

Lymphedema is caused by an abnormality of the lymphatic system leading to excessive build up of tissue fluid that

forms lymph, known as interstitial fluid. Stagnant lymph fluid contains protein and cell debris that causes swelling

of affected tissues. Lymph is responsible for transporting essential immune chemicals and cells. Left untreated, lymphedema leads to chronic inflammation, infection and hardening of the skin that, in turn, results in further lymph vessel damage and distortion of the shape of affected body parts. 1-4,199,201 Interstitial fluid can build up in any area of the body that has inadequate lymph drainage and cause lymphedema.

Lymphedema is a condition that develops slowly and once present is usually progressive.143,192 People can be born with abnormalities in the lymphatic system. This type of lymphedema is known as Primary Lymphedema.

Depending on how severe the condition is, swelling can be present at birth or may develop later in life.198 Most lymphedema in the United States is Secondary Lymphedema. This type of lymphedema occurs from damage to the lymphatic system, commonly from cancer and its treatment but also from trauma to the skin such as from burns or infections. 5,189 Lymphedema after breast cancer has been studied the most, but lymphedema can occur as a result of other cancers, including melanoma, gynecologic cancer, head and neck cancer and sarcoma.76-78, 185-187 The overall risk of lymphedema for all cancers is reported to be 15.5%.186 The risk of developing lymphedema does not diminish over time but is a lifelong risk. 6,143 Progressive lymphedema is complicated by recurrent infections, non-healing wounds, discomfort or pain, difficulty with daily tasks, emotional and social distress.7-9 Effective treatment for lymphedema is available. Early diagnosis is important since treatment is most effective when lymphedema is diagnosed at the earliest stage.188,193,194 Every patient with lymphedema should have access to established effective treatment for this condition. Lymphedema has no cure but can be successfully managed when properly diagnosed and treated.

Diagnosis of Lymphedema Since lymphedema is progressive and early diagnosis leads to more effective treatment, the diagnosis of lymphedema at the earliest possible stage is very important. Treatment of lymphedema is based on correct diagnosis.

Many conditions that cause swelling (edema) are not lymphedema. True lymphedema is swelling caused by abnormality in the lymphatic system. Lymphedema can also co-exist with other medical and swelling conditions. Correct diagnosis of lymphedema may require evaluation by a physician or other health-care provider with expertise in lymphedema who can, when needed, perform specialized diagnostic testing.10,198 Diagnostic tests for lymphedema

come under the following categories:

• History and physical examination

• Soft tissue imaging

• Lymph vessel and lymph node imaging

• Measures of volume

• Changes in electrical conductance

• Changes in biomechanical properties

• Genetic testing

–  –  –

• Other vascular imaging

• Blood tests for other conditions that can look like lymphedema History and Physical Examination A history and physical examination by a health-care provider who has experience with diagnosis and treatment of lymphedema is important for all patients with chronic swelling.193,194,198 Primary and Secondary lymphedemas have characteristic features that can be seen over time. The history should include age of onset, location(s) of swelling, pain and other symptoms, medications that can cause swelling, the course of progression of the swelling, and factors associated with swelling onset such as cancer, injury, or infection. A family history is important to the diagnosis of inherited forms of lymphedema. The physical examination includes an assessment of the vascular system (lymphatics, veins and arteries), skin and soft tissues in the swollen body part(s), palpation of lymph nodes, and looking for changes in body systems associated with various forms of inherited lymphedemas.181,182,202 Diagnostic tests and imaging must be paired with the information from the history and physical examination to make a correct diagnosis. For trunk, breast, genital, head and neck lymphedema, the history and physical examination is the currently accepted method of diagnosis.76,78 Soft Tissue Imaging Magnetic resonance imaging (MRI), computed tomography (CT) and some types of ultrasound (US) are able to detect the presence of extra fluid in the tissues.159,160,170 Fluid that is outside of cells (extracellular) and also outside of vessels (extravascular) is called tissue fluid or interstitial fluid. Lymphedema is one type of interstitial fluid build up that occurs when fluid is not being removed effectively by the lymph vessels. MRI, CT and US can show the presence of increased interstitial fluid but cannot tell the cause. These imaging techniques have to be put together with history, physical examination and sometimes other imaging tests.194 Other conditions such as heart failure or low proteins in the blood from liver disease or malnutrition can cause fluid to build up in the tissues. MRI, US and CT scans may be required to determine the cause of lymphedema, especially if there is a concern that the lymphedema might be the result of an untreated cancer.





Lymph Vessel Imaging Lymphoscintigraphy is a nuclear medicine study used for imaging lymph vessels and lymph nodes.195 Radio-labeled particles of protein are injected just under the skin of the area of the body to be imaged. Usually technetium labeled sulphur colloid is used. Lymphoscintigraphy is accurate for detecting abnormalities of the lymphatic system in the extremities regardless of the cause.163,165,189 It demonstrates slow or absent lymph flow and areas of reflux (backflow). Lymphoscintigraphy can reveal abnormalities of lymph uptake in lymph nodes with some forms of lymphedema.168 Lymphoscintigraphy can predict response to treatment.167 Lymphoscintigraphy shows the main, larger lymph vessels and nodes. It shows the basic architecture of the peripheral lymphatic system. It does not show the deep transport lymph vessels carrying lymph from the nodes back to the blood circulation. Lymphoscintigraphy identifies lymphatic abnormalities at a late stage, after lymphedema has occurred. The type of lymphoscintigraphy done for the diagnosis of lymphedema is not available at all radiology departments. Most radiology departments, however, can do a form of lymphoscintigraphy used to identify the sentinel lymph node for cancers such as breast and melanoma. These studies for the sentinel lymph node are different from the lymphoscintigraphy studies done for diagnosis of lymphedema. Before undergoing a lymphoscintigraphy study the patient should inquire if the radiologist performing and reading the study has a large amount of experience with lymphoscintigraphy studies for the diagnosis of lymphedema. Lymphoscintigraphy, in combination with other vascular studies, can differentiate venous edema from lymphedema.190,196 Lymphoscintigraphy may not be necessary in some forms of secondary lymphedema where the diagnosis is clear from the history and physical examination or other imaging.

In order to diagnose primary lymphedema, however, a lymphoscintigraphy must be done. Especially in children, a detailed study must be done that includes all potential areas of involvement and the contralateral normal limb or body part for comparison.166,169 These studies must be done by a radiologist familiar with primary lymphedema

–  –  –

and genetic forms of edema. In children being evaluated for lymphedema, other vascular and imaging studies are necessary because primary lymphedema can occur in combination with many vascular abnormalities and other organ defects. The specific tests needed should be determined by a specialist in lymphedema.

A new technique for imaging lymph vessels is Near Infra-Red Florescence Imaging (NIR) using a substance known as indocyanine green (ICG).82,171-175 The ICG is injected into the skin and immediately imaged with a dynamic (real time) infrared florescence camera. With NIR-ICG, even very small lymphatic vessels can be seen. The study is dynamic which means that the actual function of the lymphatic vessels can be analyzed. Diseased lymphatics that do not contract (or pulse) normally can be seen with NIR-ICG. ICG is a green dye that has been used safely in other areas of the body such as the liver and eyes. It can be used in very small amounts to image the lymphatics.

NIR-ICG can diagnose lymphedema and find abnormalities at an early stage, possibly before swelling is obvious.

Although this technique shows promise for the diagnosis of lymphedema, it is currently available at very few centers, most of which are involved in research.

Measures of Volume Measures of limb (arm and leg) volume have been the standard way of detecting lymphedema for years and have been shown to be accurate when properly done.156,157,161,170 Enlargement of the limb (increase in volume) is the end result of fluid building up in the tissues. Therefore, volume measurements are used to quantify the presence and severity of lymphedema and follow the response to treatment. Volume is measured by 3 main methods: tape measurements, perometry, and water displacement.170 Tape measurements are taken at defined intervals, using geometric formulas to calculate the total volume. This technique can be accurate if it is done in precisely the same way each time, and is most accurate when the same person takes the measurements each time. Perometry uses an infra-red optical electronic scanner and computer to calculate the volume of the body part. Perometry is accurate if the body part is positioned exactly the same way each time and the machine has been calibrated for accuracy. Perometry has been used for a decade in research on lymphedema and has been accurate when compared to the long used ‘gold standard’ of water displacement.149 Perometry has been demonstrated to detect as little as a 3% change in limb volume in breast cancer survivors followed over time.207 Water displacement, the bench ‘gold standard’ for assessing volume, is rarely used these days due to its inconvenience. The body part to be measured is immersed in a large cylinder and the water that is pushed out (displaced) is measured. All of these volume methods are effective and accurate when done properly.170 They are most accurate on arms and legs. Measures of volume cannot differentiate lymphedema from other types of edema and do not determine when temporary post-operative arm edema becomes chronic lymphedema. Although tape measurements have been developed for head and neck,78 they are not true volume measurements, nor have they been standardized. They are best used for following the effects of treatment rather than making a diagnosis.

Electrical Conductance Testing (BIS) Bioimpedance Spectroscopy (BIS) is a method for measuring water content in tissues. It has been used for many years to assess the total water content of the body and body composition for fitness and weight loss purposes.

BIS is now available to measure interstitial fluid as a component of assessment leading to the diagnosis of lymphedema.144,148,149 BIS has been shown to provide reliable data to be used in the diagnosis of breast cancer-related lymphedema.150 BIS can detect early changes associated with lymphedema.162,164 BIS is done by passing a small, painless, electrical current through the limb and measuring the resistance to current (impedance). The machine uses certain electrical current frequencies to determine if more fluid exists as compared to the contralateral limb.

It does this by comparing the difference in resistance to electricity passed through interstitial fluid compared to intracellular fluid. BIS currently is done on the whole limb since the resistance to current flow for standard technique is calculated to the length of the body part. The higher the water content in the interstitial tissue, the lower the resistance (impedance). BIS may show promise for detecting smaller areas of localized lymphedema, but this application has not been subjected to adequate study to recommend it.206 BIS is not as accurate in advanced, fibrotic edema. As in measures of volume, BIS cannot differentiate lymphedema from other types of edema and does not determine when temporary post-operative arm edema becomes chronic lymphedema.145,170,191

–  –  –

Changes in Biomechanical Properties of Tissues Lymphedema causes the affected skin and subcutaneous tissues to become inflamed and hardened (fibrotic).199 Lymphedema is graded clinically, not just by increased size or volume, but also by the progressive change in the skin texture as it becomes denser and harder.10,158 Currently, these skin changes are documented by physical examination of tissue texture, pitting, enlarged skin folds and other dermatologic conditions such as wounds or papillomas (benign growths on the skin in areas of lymphedema). Methods available for measuring skin texture and resistance quantitatively are: tissue dielectric constant151-153 and tonometry.148,152,154,155 The tissue dielectric constant is a measure of tissue water content. The test is performed with a device that passes an electrical current of a specific frequency to one location of the skin and measures the reflected wave that returns. The reflected wave form indicates the amount of water present in the tissue. Tonometry uses a device that measures the amount of force required to indent a tissue which gives a specific measurement value to the degree of firmness or fibrosis.

There are some technical difficulties to the use of these tools and a number of environmental factors and operator differences can give variable values. These measures of the biomechanical properties of tissues are important for research. Hopefully continued development will lead to better tools for clinical use so that diagnostic methods will include quantitative methods of skin and subcutaneous tissue changes associated with progressive lymphedema.



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