SHORT COMMUNICATION

Anatomical and Surgical Concepts in LymphaticRegeneration

Tomer Avraham, MD,* Sanjay V. Daluvoy, MD,* Essie Kueberuwa, MBBS,Jennifer L. Kasten, BA and Babak J. Mehrara, MD

The Division of Plastic and Reconstructive Surgery, The Department of Surgery,Memorial Sloan-Kettering Cancer Center, New York City, New York

n Abstract: Chronic post-surgical lymphedema is common condition that afflicts nearly 2 million Americans. In the USA,it is most commonly encountered in the upper extremities of patients who have undergone axillary lymph node dissectionfor breast cancer. Lymphedema has a significant negative effect on cosmesis, limb function, and overall quality of life.Despite the impact of this condition, very little is known about how to effectively prevent or treat lymphedema. While thera-peutic options for chronic extremity lymphedema remain limited, several surgical approaches have been suggested. Theseinclude techniques aimed at reducing limb volume, as well as techniques that aim to reconstitute disrupted lymphatic chan-nels. Operations proposed to re-establish lymphatic continuity include lymphatico-venous anastomoses, lymphatico-lympha-tico anastomoses, and tissue transfer. n

Key Words: lymphatic regeneration, lymphedema, surgery

THE BURDEN OF LYMPHEDEMA

Chronic lymphedema is a significant problem with

limited treatment options. Lymphedema occurs

when the capacity of the lymphatic system to drain

interstitial fluid is exceeded. It is defined as chronic

when the condition persists for more than 3–

6 months. The most common cause of lymphedema

worldwide is the parasitic infection filariasis (1). In

the USA, lymphedema occurs in most cases following

axillary lymph node dissection for breast cancer and

affects about 2 million people (2,3). It is estimated

that as many as 40% of patients who undergo axillary

lymph node dissection for breast cancer will go on to

develop some degree of lymphedema (4). Sentinel

lymph node biopsy is associated with an approxi-

mately 5% risk of lymphedema (5). Interestingly,

breast reconstruction either with autologous tissues or

implants does not seem to affect the incidence of lym-

phedema (6).

Conventional treatments for lymphedema, consist-

ing of compressive garments, specialized massages,

and physical therapy, are suboptimal and usually

directed at the manifestations of extremity swelling

(7). Life-long treatment and use of uncomfortable

compressive garments is required to prevent progres-

sion of lymphedema. Treatment efficacy is further

hindered by the use of complex regimens requiring

strict patient compliance. Surgical treatments have

been reported, but are not yet widely accepted.

ANATOMY AND PHYSIOLOGY OF THE

LYMPHATIC SYSTEM

Lymph is a protein rich fluid that escapes the circu-

latory system into the interstitium as a result of onco-

tic and hydrostatic pressures. This fluid is taken up by

thin walled, blind ended, capillary lymphatics (8).

These in turn drain into larger, valved collecting lym-

phatics (9). Valves are necessary for the unidirectional

flow of lymph, as flow is largely dependent on local

tissue compression. Collecting lymphatics are sur-

rounded by a layer of smooth muscle which allows

for contractility augmented lymphatic flow (10).

Transport of lymph via the lymphatic network is

necessary for homeostasis, and plays important roles

in immunity and digestion. The lymph carries both

antigens and immune cells to the lymph nodes, a

function important to the initiation of the immune

Address correspondence and reprint requests to: Babak J. Mehrara,

MD, FACS, 1275 York Avenue, Room MRI 1005, New York, NY 10065,

USA, or e-mail: mehrarab@mskcc.org.

*These authors contributed equally to this manuscript.

DOI: 10.1111/j.1524-4741.2010.00978.x

� 2010 Wiley Periodicals, Inc., 1075-122X/10The Breast Journal, Volume 16 Number 6, 2010 639–643

response. Lymphatics also carry lipids and lipopro-

teins for processing and utilization, contributing to the

digestive system.

Radioisotope lymphoscintigraphy, first described in

1953 (11), is perhaps the most commonly employed

modality for lymphatic imaging, often used for lymph

node mapping prior to sentinel lymph node biopsy

(12). It is performed by intradermal injection of a

technetium-99 labeled colloid, followed by dynamic

imaging of lymph node uptake. It also has significant

research implications (Fig. 1). Experimentally, lym-

phoscintigraphy is used to evaluate lymphatic function

by measuring the rate and degree of isotope uptake in

the lymph nodes (13). A single study has shown that

lymphedema following axillary lymph node dissection

is correlated with impairment in axillary node uptake

of following distal injection (14).

Recently, Ian Taylor’s group reported the use of a

novel radiographic technique to identify and visualize

lymphatic vessels in cadavers (15). In this technique,

hydrogen peroxide is used to generate bubbles in the

lymphatics which are then injected with led oxide

using super-fine catheters and visualized using a radio-

graph. Using this technique even micro-lymphatics

(<0.3 mm) can be visualized (16). In the upper limb

this analysis has demonstrated that superficial lympha-

tic vessels are relatively uniform in diameter, usually

course along the basilic and cephalic veins, have

multiple connecting channels in a horizontal matrix

but no direct communication between the deep and

superficial systems (17). In a subsequent study of a

human cadaver who had been previously treated with

mastectomy and unilateral axillary lymph node dissec-

tion without chronic lymphedema, the deep and

superficial systems displayed detectable connections

proximal to the elbow (18). The authors hypothesized

that lymphedema in this patient, these connections

and redirection via backflow to other unobstructed

superficial lymphatic vessels prevented onset of lym-

phedema. Interestingly, these studies have demon-

strated that most of the lymphatic vessels in the hand

and forearm converge and drain into a single node in

the axillary region thereby providing a potential mech-

anism for the finding of lymphedema following senti-

nel lymph node biopsy in breast cancer patients (17).

Although additional studies are needed, based on the

current studies one can speculate that lymphatic dam-

age resulting in lymphedema can occur if the common

pathways draining the breast and the ipsilateral arm

are sufficiently damaged.

SURGICAL MANAGEMENT OF LYMPHEDEMA

Surgical management of lymphedema is generally

reserved for patients who are refractory to con-

servative measures (Table 1). Surgery in most cases is

(a)

(b)

Figure 1. Mouse tail lymphoscintigraphy. Lym-

phoscintigraphy images of a mouse tail using

a Tc99 labeled sulfur colloid (panel a). Note

radio-isotope uptake in the lymph node basin

at the base of the tail (open arrow) following

injection at the tip of the tail (solid arrow).

Graphical representation of decay adjusted

uptake of radioisotope in the lymph nodes

over time (panel b).

640 • avraham et al.

palliative rather than curative and often serves as an

adjunct to conservative measures. Traditionally, surgi-

cal management is divided into two categories: exci-

sional and physiologic.

Excisional procedures decrease limb volume via

resection. The Charles procedure, described in 1912

(19), involved debulking the entire subcutaneous tissue

of the lymphedematous extremity down to the deep

fascia layer, followed by immediate grafting of the

removed skin to the exposed area. There is a paucity

of published reports on this procedure (20). The

Thompson procedure, of historical interest only, con-

sists of debulking the tissue of the affected limb and

reattaching the deepithelialized dermal flap to the

muscle to divert fluid into the deeper lymphatic system

(21,22).

Today, excisional procedures are most commonly

performed in a staged-manner, with repeated primary

closures. In general, complications arising from exci-

sional procedures include poor wound healing, exten-

sive scarring, skin ulceration, sensory nerve

damage ⁄ loss, worsening edema due to damage of

residual normal lymphatics, as well as a poor cosmetic

outcome (23).

The use of liposuction of accumulated fatty tissues

in concert with compression therapy, is growing in

popularity and has shown promising symptomatic

improvement (24). A 4-year follow-up study of upper

extremity lymphedema secondary to breast cancer

surgery, demonstrated a significant reduction in arm

volume without changes in lymphatic function (25,26).

Microsurgery involving lymphatic anastomoses and

flap transfers aims at primarily restoring physiologic

lymphatic function. This concept was first described in

1935 by Sir Harold Gillies who used a donor skin and

subcutaneous tissue flap from the forearm to connect

the groin to the trunk, in a patient with lower extrem-

ity lymphedema (27). Resolution of symptoms was

presumed to be a result of re-directed lymph flow

from the obstructed groin to the normal axilla.

Today, improved microsurgical techniques have

enabled surgeons to directly re-connect the lymphatics

and restore lymph flow. Campisi and Boccardo

describe two microsurgical approaches, ‘‘derivative’’

and ‘‘reconstructive’’ in the management of lymphe-

dema (28). Derivative microsurgery focuses on re-

directing lymph flow at the level of obstruction to the

venous circulation through lymphatic-venous anasto-

moses (29). In contrast, the goal of reconstructive lym-

phatic repair is to restore lymphatic flow by bypassing

the site of obstruction either directly or with interposi-

tion vein or lymphatic grafts (28,30). These techniques

have shown promising results in a large cohort with

excellent follow-up. Volume measurements showed

significant improvement in 83% of patients with an

average follow-up of 10 years (31). Patients had an

average reduction in excess extremity volume of 69%

and most were able to stop using compression gar-

ments (31). In addition, there was an 87% reduction

in the incidence of cellulitis. Lymphoscintigraphy in a

subset of patients with a follow-up of 15 years dem-

onstrated patent anastomoses and return of physiology

Table 1. Excisional and Physiologic Surgeries for Lymphedema Management

Procedure ⁄ surgery Surgeon (date) Category Description

Charles Charles (1912) Excisional Debulking of entire affected area with immediate skin grafting

Sistrunk Sistrunk (1918) Excisional Similar to Charles procedure but raised skin flaps for closure

Homans–Miller Homan and Miller (1936) Excisional Similar to Charles procedure with use of more cosmetically

appealing, thin skin flaps

Thompson Thompson (1962) Excisional Debulking affected tissue and re-attaching dermal flap to muscle

Liposuction Nava and Lawrence (1988) Excisional Debulking with liposuction and resection of redundant skin

of affected area which can be used as a skin graft to the residual defect

Gillies Gillies (1935) Physiological Donor skin and subcutaneous flap from forearm grafted in tubed

manner in antero-lateral portion of trunk

Autologous lymph vessel

auto-transplantation

Baumeister and Siuda

(1986)

Physiological Harvesting of ventromedial bundle of lymphatics in patient’s thighs

and transplanting tissue to affected upper extremity tissue

Derivative lymphatic microsurgery Campisi et al. (1995) Physiological Creation of end-to-side or end-to-end lymphatic–venous anastomosis

at level of lymphatic obstruction

Reconstructive lymphatic

microsurgery

Campisi et al. (1995) Physiological Bypassing site of lymphatic obstruction with interposition of autologous

venous grafts between lymphatic vessels upstream and downstream

Myocutaneous pedicle flap Sumner Slavin (1999) Physiological In mouse model, resected superficial tail lymphatics and covered

wound with rectus abdominis myocutaneous pedicle flap

Free muscle flap Classen and Irvine (2005) Physiological Used a free muscle flap for a circumferential scar of

obstructed lymphedematous forearm

Anatomical and Surgical Concepts in Lymphatic Regeneration • 641

lymphatic function (28,31). More recently this group

has advocated axillary reverse mapping to identify

lymphatics during an axillary dissection for breast

cancer surgery. The authors claim that this technique

may serve as a means to prevent lymphedema (32).

Despite promising results, microsurgical techniques for

lymphatic repair have not gained widespread accep-

tance due to technical complexity, and require further

study.

Baumeister et al. demonstrated efficacy in restoring

lymphatic flow with the use of autologous lymph ves-

sel autotransplantation in a smaller series. Vessel

grafts were harvested from the ventromedial lymphatic

bundle in patient’s thighs and transplanted to affected

upper extremities (33). Lymphoscintigraphy was then

used in follow-up studies to show that lymphatic func-

tion had been improved significantly (34).

CONCLUSIONS

Lymphedema is a debilitating and poorly under-

stood disorder. Current techniques for treatment are

suboptimal and further study is required to develop

targeted therapeutic and preventative strategies. A bet-

ter understanding of the anatomy and physiology of

the lymphatic system is critical.

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