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Atthawit Mongkronwong, M.D.*, Chanatip Nilkarn, M.D.**, Nutthawut Akaranuchat, M.D.***

*Division of Plastic and Reconstructive Surgery, Department of Surgery, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, ailand,

**Department of Surgery, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, ailand, ***Division of Plastic Surgery, Department of

Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ailand.

What do we know about lymphedema? Review

Article

ABSTRACT

Lymphedema can cause by a congenital anomaly, an infectious disease, chronic inammation, connective tissue

disease, and cancer. e most common presenting symptoms are swelling of the aected limb, diculty wearing

clothes, and disturbances to daily life activities. Most of the time, patients have a high chance of developing a so

tissue infection that will jeopardize the quality of their life and socioeconomic status. As to management of the

disease, it necessary to make a precise diagnosis and clinico-pathological staging in order to guide the treatment plan

and yield optimum results. Currently, surgical management for lymphedema is based on the use of 1) physiological

treatment, and 2) reductive or ablative procedures. Conservative treatment (especially for complete decongestive

therapy) is still the mainstay for the management of lymphedema.

Keywords: Lymphedema; lymphatic obstruction; lymphatic reconstruction; lymphatic surgery; lymphaticovenous

anastomosis; lymph node transfer (Siriraj Med J 2021; 73: 293-304)

Corresponding author: Nutthawut Akaranuchat

E-mail: nutthawut.joe@gmail.com

Received 23 November 2020 Revised 18 March 2021 Accepted 2 April 2021

ORCID ID: http://orcid.org/0000-0003-1798-8484

http://dx.doi.org/10.33192/Smj.2021.39

INTRODUCTION

e lymphatic system performs three main functions:

1) draining excess uids from body tissues, 2) fat-absorption,

and 3) the production of immune cells. Intercellular uid

is the uid that leaks from the circulatory system, and

90% of it is reabsorbed by the venous circulatory system.

e remaining 10% of this protein-rich uid accumulates

between cells and ows into the lymphatic system (Fig 1);

once this uid enters the lymphatic system, it is termed

“lymph”. It is transported through the collecting lymphatic

vessels and ltered through the lymph nodes, through

which approximately 2-3 liters of circulating lymph passes

daily. e dierence between the accumulated lymphatic

and capillary lymphatic pathways is the presence of

smooth muscle on the lymph vessel walls that results

in compression. Intermittent valve blocking also forces

lymphatic ow in one direction. Consequently, a loss

of drainage ability (whether caused by a blockage of the

lymphatic tract or by the lymphatic system not growing)

causes lymph to accumulate between cells, with a subsequent

swelling of so tissue, inammation, and brosis. is

adverse condition is called “lymphedema”.

1,38,39

Anatomy and pathophysiology of lymphatic system

e lymphatic system is divided into lymph capillaries,

which drain much of the intercellular uid from the dermal

layer. is uid is subsequently passed to pre-collector

and collecting vessels located in the subcutaneous fat

layer before moving into the lymph nodes. e lymphatic

ow is one direction because there is a valve blocking

period (Fig 2).

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e etiology of lymphedema

Primary lymphedema

Primary lymphedema is the type of lymphedema that

occurs from an inherited abnormality (not a consequence

of other conditions). e cause is an abnormal growth of

the lymphatic tract (aplasia, dysplasia, or malformation).

Primary lymphedema can be subdivided into the following

3 groups, based on their etiology and the onset of the

disease.

1. Congenital lymphedema (Milroy’s disease)

- The second most common type of primary

lymphedema (10%-25%)

- Occurs within rst 2 years of age

- Usually presents as bilateral extremity edema

- Autosomal dominant, inherited disorder caused

by an inactive mutation of VEGFR-3 tyrosine

kinase (VEGFR, vascular endothelial growth

factor receptor)

2. Familial lymphedema praecox (Meige’s disease)

- e most common form of primary lymphedema

(65%–80%)

- Incidence is about 1:100,000 in the population,

with a 4:1 female/male ratio

- Typically presents during puberty (adolescence),

and usually as a unilateral edema (especially of

the foot and calf)

- Transfers through autosomal dominant inheritance,

and can associate with multiple anomalies, such

as a double row of eyelashes (distichiasis), vertebral

and cerebrovascular malformations, and hearing

loss

3. Lymphedema tarda

- e rarest form of primary lymphedema (< 10%)

- Usually occurs aer 35 year of age (adulthood)

- Histological ndings of this lymphedema type

are usually tortuous and hyperplastic, with an

absence of competent valves

Fig 1. Lymphatic system

Fig 2. Anatomy of lymphatic system

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Secondary lymphedema

Secondary lymphedema is the type of lymphedema

that occurs from adverse events related to other conditions.

ese include cancer, infectious diseases, inammation,

obesity, and postoperative tumor extirpation with lymph

node surgery and/or radiotherapy (Table 1).

Epidemiology and risk factors

Worldwide, the most common cause of lymphedema

is lariasis, which results from an infection by the parasitic

worm, Wuchereria bancroi.

However, in developed

countries, its major cause is cancer and post-cancer

treatment (postoperative tumor extirpation with lymph

node surgery and/or radiotherapy).

e etiology of lymphedema induced by cancer

and post-cancer-treatment can be explained by many

mechanisms. For instance, there may be a blockage of

the lymphatic ducts from which the cancer is directly

pressed, or a cancer may have spread directly into the

lymphatic system (lymphangitic carcinomatosis). In

addition, surgery for lymph node removal and radiotherapy

may have injured the lymphatic partway.

Studies have shown that the incidence of upper

extremity lymphedema in breast cancer patients is about

17%. Most patients who undergo axillary lymph node

dissection develop symptoms of lymphedema within 3

years of the surgery.

Other forms of cancer have been

reported to have an overall lymphedema incidence of

15.5%.

Adjuvant radiotherapy aer surgery signicantly

increases the risk of lymphedema. A systematic study

in 2001 found that patients who had a mastectomy

and received radiotherapy at the axilla subsequently

developed lymphedema more frequently than patients who

only underwent surgery (41% versus 17%, respectively).

Other risk factors for lymphedema include older age

and obesity; these populations are at risk of developing

a greater level of lymphatic uid formation and have a

higher chance of presenting with symptoms than the

general population.

In 2010, Helyer et al. studied the relationship between

obesity and the occurrence of lymphedema in breast

cancer patients. ey found that patients with a body

mass index > 30 kg/m

had a higher chance of developing

lymphedema than those with an index < 25 kg/m

(odds

ratio, 2.93; 95% CI, 1.03–8.31).

Diagnosis

History and physical examination

Patients with lymphedema oen present with unilateral

arm or leg edema, and they usually describe a feeling of

heaviness around the aected limb. Some patients may

present with abnormal skin changes, such as thicker,

stier, and/or orange-peel-like skin (Paul d’orange).

A physical examination can establish the dierence

in circumference of the limbs and size will gradually

grow equally entire the aected limb. In the early stage

of lymphedema, the aected limb can still be depressed

TABLE 1. Causes of lymphedema.

Primary lymphedema

Congenital

Praecox (adolescence)

Tarda (adulthood)

Secondary lymphedema

Cancer

Recurrent cellulitis

Connective tissue disease

Infectious disease (lariasis)

Contact dermatitis

Lymphatic drainage (surgery, radiation therapy, burn, etc.)

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when pressure is applied to the skin; however, depression

is no longer possible once nonpitting edema forms

during the late stage of the disease. e specic physical

examination for lymphedema draws upon the “Kaposi-

Stemmer sign”. is is looked for by trying to pinch

the skin on the dorsum of the second toe into a fold

(alternatively, the procedure can be performed on the

index nger of the hand). If a fold cannot be made, the

patient is considered positive for lymphedema (Fig 3).

As to the circumference measurement (Fig 4), the patient

should be in a standard position; the circumference size

is used to calculate the volume of the limb by using the

truncated-cone formula (Fig 5). e volume measurement

obtained by using this anatomical-landmark circumference

method is more accurate than the volume determined

by water displacement.

Dierential diagnosis

1. Venous insuciency

Lymphedema has some clinical features that mimic

chronic venous degeneration. To dierentiate them, the

limb that has venous insuciency usually has accompanying

symptoms, such as varicose veins, a reddish-brown

skin color (from hemosiderin deposition), and possibly

ulcerative lesions above the medial malleolus area. e

limb swelling that has caused the venous insuciency

oen presents as pitting edema, which can be reduced

in size by elevation.

2. Deep vein thromboembolism (DVT)

Unilateral limb swelling is also the presenting sign

and symptom of DVT. However, DVT usually presents

during the acute phase with rapid disease progression.

Some patients with DVT may present with severe and

unexplained pain, or a throbbing and cramping pain

(especially at the calf), redness of the skin, and warmth

in the aected limb.

3. Lipedema

is condition is caused by an accumulation of

adipose tissue around the extremities, and it frequently

occurs in young women. Normally, lipedema usually

presents on both side of the extremities. e aected

area is oen painful when pressed, which can be used

to distinguish it from a lymphatic obstruction (Table 2).

Investigation

1. Lymphoscintigraphy

is investigation is used to assess the lymphatic

drainage of both the supercial and the deep lymphatic

systems, which drain from distal to proximal to the

regional lymph node basin. e test involves injecting a

radioactive substance (Technetium-99m sulfur colloid)

intradermally at the web space of the aected limb; serial

radiographic measurements are subsequently used to

detect the pattern of lymphatic ow over a period from

15 to 240 minutes.

12,13

is noninvasive investigative

technique is relatively safe due to the very low radiation

exposure; it also has very good accuracy (sensitivity, 96%;

specicity, 100%).

e common ndings of lymphedema

from lymphoscintigraphy are:

- Not found, or a delayed lymphatic drainage

- An absence of, or a decrease in the number of,

lymph nodes at the regional lymphatic basin

- A reverse ow of radioactive substance in the dermis

(dermal backow)

Fig 4. e truncated-cone formula

Fig 3. Kaposi–Stemmer sign

Fig 5. Anatomical landmark

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2. Computed tomography (CT) scan/magnetic resonance

imaging (MRI)

Both investigative techniques facilitate the evaluation

of the uid accumulation in tissues. e ndings of

lymphedema from a CT-scan or MRI are:

- ickening of the skin layer (skin thickening)

- Swelling of the subcutaneous layer (subcutaneous

edema)

- A honey-combed appearance

3. Indocyanine green (ICG) uorescence lymphography

ICG is a near-infrared dye that is injected intradermally

to facilitate the identication of the supercial lymphatic

tract beneath the skin. Aer injection, the substance

binds to albumin before being drained proximally via

the lymphatic channel through the regional node basin.

is method can be used to assess lymphatic leakage,

pumping capacity, and lymph reux into the dermis.

Moreover, ICG lymphography can be utilized to grade

the severity of the disease and guide the selection of an

appropriate choice of treatment.

4. Duplex ultrasound

While not used specically as a diagnostic tool,

it provides benets in terms of excluding deep venous

thromboembolism and venous insuciency, and it is

able to investigate a space-occupying lesion that may be

compressing the lymphatic channel. Many surgeons also

use it to locate and map the supercial lymphatic vessels

and supercial veins before performing a lymphaticovenous

anastomosis procedure.

5. Ankle-brachial pressure index (ABI)

As with duplex ultrasound, ABI is not used for the

diagnosis of lymphedema. However, it is recommended

for patients with a history of, or with suspected, peripheral

arterial disease. Because of the lymphedema, patients

almost always need to do compression therapy, which

might aect their peripheral blood circulation. If the ABI

value is < 0.5, compression therapy is contraindicated

for patients.

Staging of lymphedema

ere are currently many clinical staging systems

for the grading of lymphedema severity. However, the

most commonly used worldwide are the staging system

of the International Society of Lymphology (ISL) and the

Campisi staging system. e details of each are listed in

Tables 3 and 4.

TABLE 2. Key clinical dierences between lipedema and lymphedema of the lower extremities.

Lipedema Lymphedema

Almost always female patients Both males and females

Spares the foot Foot involved

Usually bilateral Usually unilateral

Negative Kaposi–Stemmer sign Positive Kaposi–Stemmer sign

No pitting No pitting when it becomes chronic

Tender Usually not tender

Soft Firm/tense

TABLE 3. International Society of Lymphedema (ISL) stagings.

ISL stage Description

0 Subclinical state; swelling is not evident despite impaired lymph transport

I Accumulation of tissue uid (higher protein content), which subsides with limb elevation

IIa Limb elevation alone rarely reduces swelling, and pitting is manifest

IIb (late stage) Limb may or may not be pitted as fat and tissue brosis is more evident

III Lymphostatic elephantiasis; the tissue is hard (brotic), and pitting is absent. Skin (changes)

thickening, hyperpigmentation, increased skin folds, fat deposits, and warty overgrowths develop

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Lymphedema management

Chronic lymphedema is an irreversible process if le

untreated. e mainstay of treatment is a conservative

protocol. If the clinical status does not improve within

6 months of the commencement of therapy, surgical

management is recommended.

e conservative treatment protocol consists of general

measures of self-care, compression therapy, and

physiotherapy.

1. Self-care

is aims to reduce swelling and slow the progression

of disease. e measures are comprised of the following.

1.1 Self-monitoring. e size of the swollen arm or leg

should be monitored, with observations made of the

feeling of the skin, the skin color, and changes in skin

appearance.

1.2 Limb elevation. is helps to reduce swelling of

the aected limb in the early stages of the disease. e

patient should be advised to avoid postures that cause

the limbs to fall with gravity, such as standing for long

periods of time or sitting cross-legged.

1.3 Diet and exercise. Being obese is not only a risk factor

for lymphedema, but it also greatly hampers compression

therapy. e patient should therefore be advised to

exercise regularly, control food intake, and wear a pressure

garment. A study on breast cancer patients with upper

extremity lymphedema, divided the patients into two

groups: rst, those who are advised to control food

and lose weight. Second, a group that provides general

dietary recommendations. At 12 weeks of follow-up,

the rst group showed a signicant loss weight of arm

(P-value = 0.02) and a signicant decrease in swelling

and arm volume (P-value = 0.03).

For exercise by liing

weights in patients with undergoing axillary lymph

node dissection without lymphedema. e study did

not nd that liing weights made the lymphedema more

severe.

Additionally, in the lymphedema group, the

liing of weights reduced the pain and swelling in the

aected arm, with the incidence of swelling declining

from 29% to 14%.

1.4 e avoidance of skin infection. Regular skin and

nail care can help to prevent the cracking that leads to

skin infections. If there are piercings or abrasions on the

skin, an antibiotic cream or ointment should be applied.

e use of a sunscreen should also be recommended if

the aected limb is likely to be exposed to the sun. In

addition, as exposure to extremely hot environments

(such as saunas and hot springs) can cause swelling,

the patient should be advised to avoid such situations.

1.5 e avoidance of local limb concussion. Wearing

tight-tting clothing or performing local constriction

procedures (such as the measurement of blood pressure)

exacerbates lymphedema by stimulating the production

of lymph while causing a narrowing of lymphatic ducts.

is diers from the use of a compression garment

(discussed below): it provides a rm and even pressure

from the distal to proximal limb, thereby improving

the ow of lymph.

2. Compression therapy

2.1 Stockings and sleeves. Wearing arm or leg restraints,

such as a compression sleeve, is an appropriate treatment

for the early stage (ISL I) and should be employed in

conjunction with skin care, exercise, and elevation.

As the compression apparatus typically has a pressure

range of 20-50 mmHg, it is able to stimulate lymphatic

return by exerting greater force on the distal than the

proximal limb. e rmness of the particular material

to be selected depends on the condition of the patient’s

arteries and, more importantly, the patient’s ability to

tolerate the proposed compression garment. Evaluation

TABLE 4. Campisi stagings.

Campisi stage Description

Ia No overt swelling despite impaired lymph drainage

Ib Reversible swelling with limb elevation

II Mild, persistent swelling with elevation

III Persistent swelling, with recurrent lymphangitis

IV Fibrotic change with column-like limb

V Elephantiasis with limb deformation, including widespread lymphostatic warts

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of the patient’s treatment should therefore be undertaken

early, aer 4-6 weeks’ usage of the compression sleeve.

Further reviews should be conducted every 3-6 months if

the condition has stabilized. In addition, the compression

device should be replaced every 3-6 months, or even

earlier if it appears to be starting to slacken.

2.2 Multilayer lymphedema bandaging. An elastic

bandage is used to treat intermediate-stage lymphedema

(ISL II), which is when the limb is so large that stockings

or compression sleeves cannot be worn. e bandage is

used in conjunction with skin care, limb elevation, and

short-stretch bandages. Force is applied to the limbs by

the elastic bandage only when the aected muscles are

contracted; the pressure that is generated compresses the

lymphatic vessels and increases lymph ow, resulting in

decreased swelling. e appropriate ankle sub-bandage

pressure is 45 mmHg. During the rst week of treatment,

the bandage should be changed every day; aer that,

changing it 2-3 times a week is acceptable.

e contraindications to the use of multilayer lymphedema

bandaging are:

- ABI < 0.5

- Uncontrolled heart failure

- Severe peripheral neuropathy

2.3 Intermittent pneumatic compression device. e

ecacy of intermittent pneumatic compression is still

controversial. It involves the placement of cus around

an aected limb; they are then lled with air. In turn, the

cus squeeze the limb, compressing it from the distal to

the proximal region while applying a pressure of 30-60

mmHg. It is recommended that an intermittent pneumatic

compression device be used for 30-120 minutes per day,

with a newer generation, multichambered device being

preferable.

e contraindications to the use of intermittent pneumatic

compression are:

- Untreated, nonpitting, chronic lymphedema

- Deep vein thrombosis

- Pulmonary embolism

- Acute cellulitis

- Uncontrolled heart failure

- ABI < 0.5

- Active tumor at the aected region

3. Physiotherapy

3.1 Manual lymphatic drainage. is massage technique

aims to stimulate uid ow in the lymphatic system. e

force produced by the massage causes the lymph to ow

from the distal to the proximal. Aer the massage, the

patient still needs to wear a pressure garment during

daily activities. A massage of at least one hour per day

is recommended. Although the efficacy of manual

lymphatic drainage has not yet been clearly identied,

this technique is still recommended as a component of

complete decongestive therapy (discussed below) during

the treatment phase.

e contraindications to manual lymphatic drainage are:

- Acute cellulitis in the position to be massaged.

- Unstable hypertension

- Uncontrolled heart failure

- Tumor at the aected part

3.2 Complete decongestive therapy. is multi-modality

treatment aims to reduce the swelling of the limbs in

two phases:

3.2.1 Treatment phase. is comprises 1) skin and

nail care, 2) exercise, 3) manual lymphatic drainage or

massage, and 4) compression (bandage therapy). Patients

must perform these procedures ve days a week for 2-4

weeks. During the treatment phase, it is recommended that

the patients take circumference and volume measurements

themselves once weekly to facilitate the assessment of

the treatment outcomes.

3.2.2. Maintenance phase. e treatment in this

period consists of wearing a compression garment (during

the day), bandaging (at night), maintaining skin care,

and exercise. Lymphatic squeezing can be performed

on its own aer the patient has received appropriate

training. During the maintenance phase, patients should

measure the circumference and volume every 6 months

to monitor the treatment progress.

e absolute contraindications to complete decongestive

therapy are:

- Infection

- Active cancer

- Heart attack

- Acute deep vein thrombosis

e relative contraindications to complete decongestive

therapy are:

- High blood pressure that has not been controlled

- Diabetes

- Asthma

- Paralysis

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4. Pharmacotherapy

The use of medications to treat edema is not

recommended. Some studies investigated the use of

diuretics to reduce limb swelling, but the results were not

as good as expected. Apart from diuretics, coumarin (a

benzopyrone) has been reported to reduce the incidence of

cellulitis or lymphangitis.

However, recent studies have

found that the use of this drug resulted in a reduction in

the volume of swollen limbs compared with a placebo,

with an incidence of hepatic toxicity of approximately

6%.

So, e use of medications to treat edema is still

not recommended.

5. Experimental therapy

Low-level laser therapy (or cold laser therapy)

has been investigated in patients with lymphedema

aer mastectomy. e therapy is believed to reduce

brosis, stimulate macrophages in the immune system,

and result in the formation of new lymphatic vessels

(lymphangiogenesis). e results of one study showed that

1 in 3 patients who underwent laser therapy demonstrated

a reduction in the volume of their swollen arm at their

3-month follow-up visit.

Moreover, low-level laser

therapy produced a better limb-swelling reduction than

pneumatic compression therapy aer 12 months of

treatment.

6. Surgical management

Surgery is an ideal treatment option for patients

with localized disease, a failed conservative treatment,

recurrent cellulitis or lymphangitis, leakage of lymph to

externally, or a signicantly diminished quality of life.

Preoperative assessment

1. Assess degree of lymphedema

Evaluation of the degree of lymphedema is based

on the dierence in the circumference and volume of

the aected limb relative to the contralateral, normal

limb.

2. Lymphedema staging

Assessment of the stage of the disease is undertaken

in order to select a suitable treatment option. e most

commonly used staging system is the ISL system.

3. Venous duplex ultrasound

In patients who plan to undergo surgery, venous

duplex ultrasound might be required to rule out

venous thrombosis, venous insuciency, and valvular

incompetency.

Surgical treatment

Surgical treatment can be divided into two broad

approaches: reductive or ablative procedures, and

physiological treatment.

1. Reductive or ablative procedures

1.1 Direct excision. In 1912, Dr. Charles wrote a

book entitled “Elephantiasis Scroti”, which describes

how to treat lymphedema around the scrotum. e

principle of the surgery is to remove the swollen tissue

of the scrotum and then cover the wound with a skin

gra from the thigh.

In 1940, Dr. Macey from the Mayo Clinic applied the

Charles procedure to surgery on extremities lymphedema.

e benet of this surgical technique is that it totally

removes the swelling and brotic tissues. Nevertheless,

there are still many postoperative complications, such

as surgical site infection, hematoma, gra loss, and

scars. erefore, the procedure is usually recommended

only for late-stage lymphedema patients, or for patients

with wounds on the aected limb that are signicantly

disturbing their quality of life.

1.2 Liposuction. is treatment involves the insertion

of a steel canula into the subcutaneous layer; the cannula

is connected to a vacuum that suctions the brofatty

tissue via negative pressure. O’Brien et al.

reported

that this treatment reduced the volume of the swelling

by 20% - 23%. e advantages of this treatment are,

rstly, it only leaves a very small incisional scar and,

secondly, patients recover rapidly (approximately 48

hours). e disadvantage, however, is that there may

be injury to the lymphatic tract during the liposuction

procedure; consequently, it is recommended that the

canula is kept parallel to the limbs to reduce injuries.

Another consideration is that, aer liposuction, patients

need to permanently wear compression devices.

2. Physiological treatment

This treatment principle aims to creates a new

lymphatic channel in order to increase the ability of

the lymph to ow. ese surgical procedures are only

suitable for the early stages of lymphedema (ISL stages

I or II)

, being ineective in late-stage patients. e

physiological treatment procedures are comprised of 4

main types, as described below.

2.1 Flap interposition. e procedure uses a ap with

good blood vessels and lymphatic vasculature obtained

from another site of the body. e ap is placed in the

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area where the lymphatic ow is blocked or disrupted,

and then anastomosis of the blood vessels and lymphatic

vessels is performed.

In 1935, Gills and Fraser

were the rst doctors

to use this procedure to treat a patient with leg edema.

Flaps taken from the arms were pasted to the thighs

and body of the patient; the aps became bypasses that

allowed lymphatic uid to cross the obstructed areas.

In 1974, Goldsmith et al.

reported the use of a

greater omental ap to treat patients with lymphedema.

e ap was inset in a subcutaneous layer, thereby allowing

lymph in an arm or leg to drain into the lymphatic system.

Twenty-two patients from their study reported satisfactory

results. Nonetheless, this surgery is not popular because

it has a relatively high number of complications, such as

intestinal obstruction, blood clots, atherosclerosis, and

hernia.

2.2 Lymphatic bypass procedure. e principle of

this surgery is to create a link between distal lymphatic

vessels and lymphatic vessels above the point of an

obstruction. Alternatively, a bypass from the obstructed

lymphatic channels into the venous system is created.

Before surgery, the functional lymphatic vessels

should be identied by specic dyes transported through

the lymphatic channels

, for example, isosulfan blue or

indocyanin green.

e indications for this surgery are:

- No response to conservative treatment

- Recurrence of skin infection

- Disease signicantly aecting the quality of life and

daily activities

e limitations of lymphatic bypass surgery are:

- Tissue brosis

- Late stage lymphedema

- Inferior surgical outcomes for venous hypertension

or venous insuciency patients

- Recurrence of cancer

- Patients unable to take care of themselves aer

surgery

- Uncooperative patient

2.2.1 Lymphatic-lymphatic bypass. An attempt

was made to bypass the problematic lymphatic tract by

connecting the distal lymphatic vessels to the proximal

lymphatic vessels above the area of obstruction.

In 1990, Baumeistier and Suida

30,31

performed a

series of lymphatic reconstructions to manage arm

lymphedemas by using lymphatic vessels from thighs.

Lymphatic vessels were harvested from the patients’

thighs and then implanted in the subcutaneous fat layer

between the upper arm and shoulder area, above the

clavicular bone. In the case of lower extremity lymphedema,

the surgery was performed by harvesting contralateral,

normal lymphatic vessels and moving them to the groin

of the aected leg. e procedure was performed on 55

patients. e treatment outcome was reductions of up

to 80% in the volume of the aected areas during the

3-year follow-up period.

2.2.2 Lymphovenous bypass and lymphaticovenous

anastomosis. In 1962, Jacobson et al. attempted to connect

lymphatic vessels to veins by conducting an experimental

study in an animal model. Aer that, Yamada et al. applied

the technique to treat lymphedema patients by using a

saphenous vein connection to an obstructed lymphatic

tract. However, some concern had been expressed about

using a high-pressure gradient large vein, which might

cause problems if there is a poor lymphatic ow.

Consequently, Yamada et al. modied the protocol

so that venules with a diameter of 0.8 mm or less were

used.

e outcomes of lymphaticovenous anastomosis

were studied in 100 patients with lymphedema of the

arms or legs. e results showed clinical improvements

for 96% of the patients, and a volume reduction for 74%

of the cases. e overall lower-limb-volume reduction

at 12 months was 42%; the decline was greater for early-

stage patients (61%) than late-stage patients (17%).

e eect of lymphaticovenous bypass surgery has

been studied at the cell level by skin biopsy. e ndings

revealed a decline in the white-blood-cell and CD4 +

values of the aected limb, and tissue brosis.

Fluorescence lymphangiography is currently been

used to identify the location of the lymphatic tract in

real time.

It is also used to stage the disease. With

the early stage, the lymphatic tract is seen to have a

clear linear pattern. In contrast, the late stage shows

a diuse stain of substance due to obstruction and a

reversed lymphatic ow. If good lymphatic vessels are

identied, lymphaticovenous anastomosis is performed.

e supercial lymphatic vessels are localized again using

isosulfan blue dye during surgery conducted under a

surgical microscope.

2.3 Vascularized lymph node transfer (VLNT). e

procedure involves harvesting a free lymph node ap

from outside the aected region, implanting it into the

aected limb, and anastomosing it to recipient vessels

via a microsurgical technique (without connecting the

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Mongkronwong et al.

lymphatic tract). Two mechanisms explain the eect

of VLNT:

- Bridging mechanism. The transplanted lymph

node ap secretes vascular endothelial growth factor

C (VEGF-C), which stimulates the formation of a

new lymphatic tract.

- Pumping mechanism. e dierence in the pressure

gradient between arterial anastomosis and venous

anastomosis acts like a pump suctioning excess

lymph back to the systemic circulation system (like

lymphatic-venous drainage).

In 1982, Clodius et al.

reported the results of 2

cases of VLNT to manage lower extremity lymphedema,

with the lymph node ap being obtained from the groin.

Although the swelling rapidly subsided during the early

post-operation period, the edema had returned by the

6-month follow-up session.

In 2006, Becker et al.

reported the long-term

eects of free lymph node ap transfers using inguinal

lymph nodes to manage 24, post-mastectomy, upper

extremity lymphedema patients, sixteen of who had

postoperative lymphoscintigraphic evaluations. e

results showed that 5 out of the 16 patients (who had

lymphoscintigraphy) had functional lymph nodes and

lymphatic tract regeneration.

In 2012, Saaristo et al.

performed vascularized

lymph node transfer in conjunction with autologous

breast reconstruction in 9 patients with post-mastectomy

lymphedema. ere was an improved lymphatic circulation

in 5 out of 6 patients, and 3 out of the 9 patients no longer

needed to use a pressure garment aer the surgery.

Additionally, an increase in endogenous lymphatic vessel

growth factors was demonstrated, suggesting that new

lymphatic regeneration in the axilla had been stimulated.

e indications for vascularized lymph node transfer are:

- Segmental dermal backow or a non-functioning

lymphatic vessel detected by lymphoscintigraphy

- ISL stage II with repeated cellulitis

- No acute cellulitis

- Follow up > 12 months

ere are two principles for lymph node implantation: 1)

orthotopic (anatomical) placement, and 2) heterotopic

(nonanatomical) placement.

2.3.1 Anatomical placement. e lymph nodes

are implanted in the area where the obstruction occurs,

such as the axilla or groin.

e advantages of anatomical placement are:

- Removal of the brosis that caused the lymphatic

tract obstruction

- Nearby tissue can be sewn or closed without any

skin graing

- Less postoperative scarring

2.3.2 Nonanatomical placement. e lymph nodes

are implanted in the distal limb, with the transplanted

lymph node acting like a lymphatic pump.

e advantages of nonanatomical placement are:

- Avoidance of surgery in the area of brosis

e disadvantages of nonanatomical placement are:

- Bulkiness of lymph node ap in the distal limb

- Oen need to do skin graing

If a scar cannot be properly removed, it is recommended

that the lymph nodes be implanted in an area that will

produce less scarring. Many studies have demonstrated

that VLNT can relieve symptoms in 100% of cases, reduce

the volume in 91% of cases, and allow 78% of patients

to stop using pressure garments.

As to complications, lymphatic leakage develops

in 15% of cases, postoperative infection arises in about

8%, and a need to reoperate occurs with 3% of patients.

2.4 Lymphatic microsurgical preventive healing approach

(LYMPHA). is procedure aims to connect lymphatic

vessels to a branch of the axillary vein simultaneously

with axillary lymph node dissection. One study found

that, aer 4 years of follow-up, only 3 (4%) out of 74

patients continued to have lymphedema in the arm that

had been operated on.

However, this new technique

needs further long-term studies to prove its ecacy

and to determine any adverse outcomes, such as cancer

recurrence.

CONCLUSION

Lymphedema is a condition caused by an obstruction

in the lymphatic system arising from a congenital anomaly,

infectious disease, chronic inammation, connective

tissue disease, or cancer. Patients who are faced with

this disease usually have a poor quality of life due to

infection and limits to their ability to perform daily

activities. Consequently, it is critical to provide early

diagnosis and treatment as these are key to managing

and conquering the lymphedema. A multidisciplinary

team approach yields the best solutions and long-term

outcomes for patients.

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303

Review Article

SMJ

What is already known on this topic?

Lymphedema is a congenital and acquired disease

with can cause swelling of the limbs. e most common

symptoms are limb swelling and recurrent cellulitis of

the limbs.

What this study adds?

It reviews the related clinical presentations, physical

examinations, radiological studies, and new treatment

options.

Potential conicts of interest

e authors declare that there are no conicts of

interest related to this study.

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