Lymphedema-current Issues in Research and Mang

l y m p h e d e m d a : C u r r e n t I s s u e s

292 Ca—A cancer Journal for Clinicians

AbstractLymphedema is a common and trouble-some problem that can develop follow-ing breast cancer treatment. As withother quality-of-life and nonlethal condi-tions, it receives less research fundingand attention than do many other areasof study.

In 1998, an invited workshop spon-sored by the American Cancer Societyreviewed and evaluated the current stateof knowledge about lymphedema.Recommendations and research initia-tives proposed by the 60 internationalparticipants are presented in the conclu-sion section of the article, following asummary of current knowledge of theanatomy, physiology, detection, and cur-rent treatment of lymphedema.

The etiology of lymphedema is mul-tifaceted; all of the factors that contributeto the condition and the nature of theirinteraction have not yet been identified.To compound the problem, methods ofassessing the degree of arm and handswelling vary and are not agreed upon,and reliable methods of assessing thefunctional impact of lymphedema havenot yet been developed.

In the absence of a cure for lym-phedema, precautions and preventionare emphasized. Current treatmentsinclude elevation, elastic garments, pneu-matic compression pumps, and completedecongestive therapy; surgical and med-ical techniques remain controversial.Elements and details of these treatmentsare described. (CA Cancer J Clin2000;50:292-307.)

IntroductionApproximately 15% to 20% of breastcancer patients develop lymphedema fol-lowing breast cancer treatment. Thismeans that of perhaps two million USbreast cancer survivors, after lympha-denectomy, approximately 400,000 copeon a daily basis with the disfigurement,discomfort, and disability associated witharm and hand swelling. Lymphedema isamong the most dreaded sequelae ofbreast cancer treatment.

Lymphedema is a common and trou-blesome problem: The cosmetic deformi-ty can not be disguised with normal cloth-ing; physical discomfort and upper-extremity disability are associated withenlargement and recurrent episodes ofcellulitis, and lymphangitis may be ex-pected in this setting.

In addition to these physical symp-toms, patients may experience distresscaused unintentionally by clinicianswhose primary focus is cancer recurrenceand who may therefore trivialize lym-phedema because of its nonlethal nature.For the patient, however, the appearanceof arm swelling may be more distressingthan living with a mastectomy, as the lat-ter can be easily hidden while the disfig-

Lymphedema: Current Issues in Research and Management

Jeanne A. Petrek, MD; Peter I. Pressman, MD; and Robert A. Smith, PhD

Dr. Petrek is Director, Surgical Program, Evelyn H.Lauder Breast Center, and Attending Surgeon,Breast Service, Department of Surgery at MemorialSloan-Kettering Cancer Center in New York City,NY.

Dr. Pressman is Clinical Professor of Surgery atAlbert Einstein School of Medicine and Beth Israeland Lenox Hill Hospitals, New York City, NY.

Dr. Smith is Director of Cancer Screening with theAmerican Cancer Society, Atlanta, GA.

This article is also available online at www.ca-journal.org.

ured arm/hand is a constant reminder ofthe breast cancer and a subject of curiosi-ty to others.

The American Cancer SocietyWorkshop and Invited Conferenceon LymphedemaThe study of the incidence, etiology, andtreatment of lymphedema is hampered bythe decades-long course of this complica-tion. Furthermore, lymphedema, alongwith other quality-of-life and nonlethalconditions, has received less researchfunding than have many other areas ofstudy. To generate new attention for theproblem of breast-cancer-treatment-relat-ed lymphedema, the American CancerSociety and the Longaberger Company(Newark, Ohio) sponsored an invitedworkshop to review and evaluate the cur-rent state of knowledge of the condition.The workshop, which took place in Febru-ary 1998 in New York City, featured 60 in-

ternational experts (including the authorsof this article) who made recommenda-tions for basic research, clinical practice,and public and professional education andadvocacy. (See “Recommendations andResearch Initiatives,” page 303).

The workshop carefully reviewedthe standard treatment of lymphedema,and faculty from each of the four maintreatment schools and clinics discussedtheir respective techniques of manuallymphatic drainage (MLD). The entireproceedings of the meeting, includingrecommendations summarized in work-group reports are available as a journalsupplement (Cancer 1998;83:2775-2890)and as a separate 129-page monographfrom the American Cancer Society1

(Fig.). The publication concludes with alymphedema resource guide listing in-formation on professional organizations addressing lymphedema, lymphedema support groups, online groups and infor-mation sources, suppliers of lymphedemapumps and garments, and schools forcomplex decongestive therapy, as well asa recommended reading list.

Anatomy and Physiopathology ofLymphedemaLymph is normally cleared from tissuespaces through a network of thin-walledlymphatics, which traverse the axillarynodal basin and ultimately empty into thevenous system. Lymphedema is the accu-mulation of protein-rich fluid in soft tis-sues resulting from overload of these lym-phatics (i.e., when lymph volume exceedstransport capabilities). Primary lymphe-dema refers to rare developmental abnor-malities in the lymphatics and can presentearly or late in life. Secondary lymphede-ma is more common and includes amongits causes surgery, irradiation, and infec-tion (e.g., filariasis).

In secondary lymphedema, lymphtransport is interrupted due to physicaldisruption or compression of lymphaticchannels.2 Patients with breast cancer de-

Vol. 50 No. 5 september/october 2000 293

C A C a n c e r J C l i n 2 0 0 0 ; 5 0 : 2 9 2 - 3 0 7

Figure

Copies of the “Lymphedema” monograph areavailable from the American Cancer Society for$9.95 by calling 1-888-227-5552.


velop lymphedema from surgical resec-tion of lymphatic vessels and lymphnodes, from radiation-induced fibrosisaround these structures, and from ob-struction of lymphatics and lymph nodesby metastatic tumor.

The accumulation of interstitialmacromolecules raises tissue oncotic pres-sure, while the disruption and blockage oflymphatics raise the hydrostatic pressurewithin the remaining lymphatics. Bothcontribute to increased tissue edema. Sta-sis of protein-rich fluid, combined withimpaired immune clearance in the ex-tremity devoid of lymph nodes, permit re-peated episodes of lymphangitis and cel-lulitis. Such chronic inflammation leads tofurther fibrosis and impairment of the af-fected limb. In this way, lymphedema canbegin insidiously at variable periods afteraxillary treatment and progress from abarely noticeable condition to one involv-ing a severely impaired limb.

Presentation and Progression ofLymphedemaLymphedema is the result of a functionaloverload of the lymphatic system inwhich lymph volume exceeds transportcapabilities. The build-up of interstitialmacromolecules leads to an increase inoncotic pressure in the tissues, producingmore edema. Persistent swelling and thebuild-up of stagnant protein eventuallylead to fibrosis and provide an excellentmedium for repeated bouts of cellulitisand lymphangitis. With dilatation of thelymphatics, the valves become incompe-tent, causing further stasis. The musclecompartments below the deep fascia,however, are spared.

Lymphedema can begin insidiouslyat variable periods after axillary treat-ment. The swelling may range in severityfrom mild and barely noticeable in theearly stages, to extreme in later stages,causing a seriously disabling enlargementof the affected limb. A brawny skin ap-pearance develops owing to the fibroscle-

rosis of the skin and subcutaneous tissue.With repeated episodes of cellulitis andlymphangitis, the skin becomes indurat-ed, leathery, and hyperkeratotic.

Lymphedema Assessment: PhysicalMeasures and Imaging TechniquesAbout 50% of patients with documentedminimal enlargement (1 to 2 cm) suffersymptoms of “arm heaviness.”3 A mailquestionnaire found that half of the pa-tients describing lymphedema had never-theless not reported this problem to anydoctor.4 The psychosocial aspects of lym-phedema, which have been unforgivablyignored in the past, were recently re-viewed by Passik and McDonald.5Women who experience pain, have lym-phedema in the dominant hand, enjoypoor social support, and/or have a passiveand avoidant coping style report the high-est level of disability.6

Three physical measures of lym-phedema7 are available, including circum-ferential measures at various points (withbony landmarks as references), volumet-ric measures using limb submersion in flu-id, and skin/soft-tissue tonometry in whichsoft-tissue compression is quantified.

The traditional method for measur-ing lymphedema is the tape-measuredarm circumference 10 cm below or 10 cmabove either the olecranon or the lateralepicondyle. While seemingly straightfor-ward, such measurements can vary ac-cording to the degree to which the tape it-self constricts soft tissue. Furthermore, itis wise to measure at least one location onthe lower arm and two locations on theupper arm (instead of relying on a singlevalue), as the shape of the arm can differbefore and after swelling.

Measurement of the arm volume bywater displacement is more accurate andresults in a single value, but the techniqueis unwieldy and infrequently employed.Skin/soft-tissue tonometry, performedwith a tension-measuring device thatpresses on the skin, is not a standardized



procedure. Other, more sophisticatedmethods that are still experimental in-clude dichromatic differential absorp-tiometry,8 CT scanning,9 MRI,10 and op-toelectronic scanning.11

There is no standard degree of en-largement that constitutes lymphedema.Although a 2-cm difference betweenarms is the most common definition, suchswelling could be severe in a thin arm andunnoticeable in others. In rare cases, nat-ural variation can account for up to a 2-cm greater circumference in the domi-nant and overused extremity.12 Thus,both arms must be measured preopera-tively for an accurate lymphedema as-sessment. While physical measures andimaging techniques provide quantitativeassessment of arm enlargement, no reli-able or standard measure exists to assessthe functional impact of lymphedema.

Recently, some investigators havebegun to explore noninvasive, and tosome extent invasive, imaging techniquesto diagnose and help manage lymphede-ma.13 Lymphoscintigraphy, for example,has been used in a preliminary way topredict which patients are at increasedrisk for lymphedema after axillary treat-ment14,15 with the hope of emphasizingprevention strategies and the value of fre-quent follow-up. In the future, lym-phoscintigraphy, dichromatic differentialabsorptiometry,8 CT scanning,9 and opto-electronic scanning11 may all be used todirect management and assess results.

Lymphedema Incidence

The incidence of lymphedema reportedin different studies has varied widely as aresult of variations in a number of factors,including the extent of axillary treatment,the interval between axillary treatmentand measurement, methods used to de-fine lymphedema, and the completenessof follow-up.

A comprehensive computerizedsearch16 of the worldwide medical litera-ture on the incidence of lymphedema re-

lated to breast cancer treatment yielded35 reports since 1970. Data from seven ofthe reports with the greatest relevance forcurrent patients (dating from 1990; fivecountries) are presented in Table 1. Thereports of Ferrandez et al17 and Schune-mann and Willich18 have been translatedfrom the French and German, respective-ly. Unfortunately, the type of breast car-cinoma treatment used in the studies thatare detailed in Table 1 could not be in-cluded because only a few investigatorsreported this important variable. (Themajority of participants in the study byLin19 and all patients in those by Wern-er20 and Ivens,21 underwent breast-con-servation therapy.) Nevertheless, as theyare all recently published reports, theseseven studies should be most relevant forcurrent patients.

All reports on the incidence of lym-phedema, including the seven studieshighlighted in Table 1, are retrospective,and the denominator (i.e., the number ofpatients at risk for developing lymphede-ma in a particular population) is impre-cise or unknown. The incidence of lym-phedema in the seven selected reportsvaried from 6%22 to 30%.23 The reportwith the lowest incidence of lymphedemaalso had the shortest follow-up, and thesame surgeon, one of its authors, operat-ed on all of the reported patients.22

Lymphedema: Etiologic FactorsSURGERY

Surgery that includes extensive removalof lymph nodes has been an integral partof breast carcinoma treatment since theend of the last century. In the standardradical mastectomy, virtually all lymphat-ics were interrupted and removed, alongwith the adjacent muscles of the chestwall, the breast, and the overlying skin, sothat skin grafting was required to closethe defect. Operations for breast cancerhave become progressively moremodest,24 and almost all studies in thepast 20 years12,21,25-29 report that the inci-

C A C a n c e r J C l i n 2 0 0 0 ; 5 0 : 2 9 2 - 3 0 7



Year

Fi

rst A

utho

r/Co

untry

Type

of

Defin

ition

Inci

denc

eFo

llow

up

No. o

f Pai

tent

sJo

urna

lM

easu

rem

ent

Sour

ce

Trea

tmen

t Yrs

1991

Wer

ner20

USCi

rcum

fere

nce

≥2.

5 cm

19.5

%37

mon

ths*

282

Radi

olog

yCl

inic

F/U

1980

-198

9

1992

Ball22

Engl

and

Circ

umfe

renc

e>

3 c

m6%

> 1

2 m

onth

s50

An

n R

Coll

Surg

1 su

rgeo

nEn

glPa

tient

Rep

ort

N/A

16%

1982

-199

0

1992

Iven

s21En

glan

dVo

lum

etric

> 2

00 m

l10

%2

yrs*

106

Br J

Can

cer

Clin

ic F

/U19

86-1

990

1993

Lin19

USCi

rcum

fere

nce

a) <

3 c

m16

%2

yrs*

283

J Cl

in O

ncol

b) 3

cm

– 4

cm

6%4

surg

eons

c) >

4 c

m2%

1988

-199

0

1996

Ferr

ande

z17Fr

ance

Circ

umfe

renc

ea)

> 3

cm

– <

10

cm14

.3%

14 m

onth

s*

683

Bull

Canc

erb)

≥10

cm

2.6%

Clin

ic F

/U19

94

1996

Paci

23Ita

lyCi

rcum

fere

nce

a) ≤

4 cm

8.7%

5 yr

s*23

8Tu

mor

ib)

> 4

cm

– <

8 c

m13

.7%

Tum

or R

egis

tryc)

≥8

cm7.

9%19

85-1

986

1997

Schu

nem

ann18

Germ

any

Circ

umfe

renc

e≥

2 cm

24%

11 y

rs†

5,86

8Dt

sch

Med

Clin

ic F

/UW

oche

nsch

r19

72-1

995

* M

edia

n tim

e F/

U†

Tota

lF/

U =

follo

w-u

pCo

pyrig

ht 1

998

Amer

ican

Can

cer S

ocie

ty. R

eprin

ted

with

per

mis

sion

from

Can

cer1

998;

83:2

778.

Tab

le 1

Inci

den

ce o

f Lym

phed

ema

Bas

ed o

n R

eport

s P

ub

lish

ed S

ince

19

90

dence rate and the degree of resultantlymphedema correlate with the extent ofsurgical dissection. As more nodes are ex-cised—such as in sampling (retrievingthree to eight lymph nodes) or in stan-dard axillary dissection26—the incidencerate of lymphedema increases in an ap-proximately linear fashion. In two largestudies,20,30 however, a relationship be-tween extent of dissection and lymphede-ma could not be demonstrated, perhapsbecause rather small differences in extentof dissection were compared.

Today, a level I-II axillary dissectionis generally routine and in rare cases, if thelymph nodes are found to be positive, thedissection is extended to include level III.Attempts are now made to modify thescope of the operation to fit the extent ofthe disease being treated. Aware of therisks of lymphedema, surgeons often care-fully attempt to preserve fatty axillary tis-sue medial, lateral, and superior to the ax-illary vein, because this tissue may containimportant lymphatic trunks, preferring todissect the tissue below the vein.

RADIATION THERAPY

In every study that has evaluated the re-lationship between lymphedema and ex-tent of surgical dissection, the additionof radiation therapy to the dissected ax-illa has proved to be a strong predictorof lymphedema.12,26,28,30 Therefore, if acomplete axillary dissection has beencarried out—even with findings of posi-tive lymph nodes and extracapsular ex-tension—axillary radiation can often beavoided without high risk of axillary re-currence.

Even when the intent is to irradiateonly the breast (such as following lum-pectomy), some radiation dosage reacheslevel I and even level II of the axilla, de-pending on the radiation-therapy tech-nique used and on the patient’s anatomy.Breast radiation-therapy techniques de-signed specifically to avoid the dissectedaxilla and the pathophysiology of radia-tion-related lymphedema were recently

reviewed.31 For precise radiation tech-nique, it is helpful to mark the surgicalboundary with radiopaque clips, thus in-dicating the extent of the axillary dissec-tion. The radiation therapist can then seethe dissected area on the simulation filmsand avoid it with greater accuracy.

SENTINEL LYMPH NODE BIOPSY

Sentinel lymph node biopsy (SLNB) (seeHsueh et al, page 279) should decreasethe risk of lymphedema.32 If only one ortwo lymph nodes are carefully excised, itstands to reason that edema will probablynot occur. The sentinel node operation isnot always so limited, however. The sen-tinel node may, in fact, be located veryhigh at the level of the axillary vein andthe lymph trunks. Dissection at that sitecould theoretically result in lymphede-ma. The risk of lymphedema has not yetbeen assessed in the follow-up of patientstreated with sentinel lymph node technol-ogy. Further, if axillary radiation therapyis added to SLNB, the risk of lymphede-ma increases. It is important to remem-ber that in international series reportingaxillary radiation therapy but no axillarysurgery at all, lymphedema incidenceranged from 2% to 5%.20,21,25,30,31 There-fore, lymphedema incidence will be atleast that high if SLNB and axillary radia-tion therapy are combined. Lymphede-ma after axillary radiation therapy alonewas shown to develop later than that de-veloping after combined axillary surgeryand breast radiation therapy.21

Beyond these two definite factors—extent of surgical dissection and radiationto the axilla—exists a wide range of possi-ble etiologic factors that have not beenevaluated systematically. Some womentreated decades ago with radical mastec-tomies and full radiation therapy, ribsthinly covered with skin grafts, did notdevelop lymphedema. On the otherhand, there are women recently treatedwith modest tumorectomies, limited axil-lary dissections, and radiation to thebreast who have developed lymphedema.


C A C a n c e r J C l i n 2 0 0 0 ; 5 0 : 2 9 2 - 3 0 7

Research to date has revealed fewconsistent clues to the etiology of lym-phedema. One study,27 for example, re-ported older age at diagnosis to be a sig-nificant factor; in another,12 this variablewas unrelated to lymphedema incidence;in still others, it was curiously omitted al-together. In one study, a tendency towardlymphedema was seen when the domi-nant hand was on the side that had beenoperated on,21 but another report12 couldnot confirm this. Patient weight (heightwas not recorded) was a significant factorin two studies,20,29 but obesity, surprising-ly, was not evaluated in other studies.One study on surgical technique found ahigher incidence of lymphedema withsplitting the pectoralis minor muscle,25

and two studies correlated lymphedemawith greater postoperative fluid forma-tion.33,34 It is surprising that the incidenceof lymphedema with bilateral axillary dis-section is not any higher than that afterunilateral axillary dissection.16,35

In sum, etiologic factors for lym-phedema have not been well studied be-cause: 1) the course of the condition isprolonged; 2) individual patients lacklong-term contact with the original sur-geon and/or the radiation therapist whotreated them; and, most importantly, 3)lymphedema, along with other quality-of-life issues, is perceived as less worthy ofresearch funding.

Prevention of Lymphedema

As controlling lymphedema requires dai-ly attention, and as a “cure” for lym-phedema has not been established, em-phasis must be placed on prevention.Nevertheless, without evidence-basedknowledge of etiologic factors, the list ofpost-treatment arm precautions is basedon intuitive reasoning.

It is important to remember thateach woman has a congenitally differentanatomy, which, like the rest of the vas-cular system, is probably uniquely proneto degenerative conditions. Such anatom-

ic factors have been studied in a limitedfashion with lymphoscintigraphy.13-15 In-dividual patient factors, combined withaxillary treatment factors, must be themain determinants of preventive strate-gies, notwithstanding the fact that lym-phedema may occur several years aftertreatment. The study of events or activi-ties in the subsequent years and decadesof the patient’s life for the purpose of de-termining which are causative factors andto what degree has not been carried out.In fact, so little is known that it may bethe case for some women that precau-tionary advice is, in fact, counterproduc-tive, as “overprotection” can lead to un-deruse and muscle atrophy.

ARM AND HAND PRECAUTIONS

Arm and hand precautions are looselybased on two overarching principles: 1)The production of lymph, which is directlyproportional to blood flow, should not beincreased; and 2) the blockage to lymphtransport should not be increased. Heat,such as that in a sauna, significant infec-tions, and vigorous arm exercise increaseblood flow in the arm and thereby in-crease lymph production. Likewise, tightarm garments or infections with ensuingfibrosis and stenosis of lymphatic vesselsmay result in obstruction of lymph flow.

To avoid arm swelling and/or infec-tion, the patient should be instructed to:1. Avoid vaccinations, injections, blood-

pressure monitoring, blood drawing,and intravenous administration in theaffected arm.

2. Avoid puncturing or injuring the skinin any way. Use meticulous skin andnail/cuticle care. Pay immediate atten-tion to and use standard first-aid careon all small or large injuries. Utilize an-tibiotics liberally.

3. Avoid constricting sleeves or jewelryand wear a padded bra strap to avoidconstriction and pressure.

4. Avoid heat, including sunburns or tanning, hot baths, and saunas.

5. Avoid violent exercise and strenuous



exertion. Consider vigorous aerobic armexercise only when the arm is supportedby compression garments.

There are no data to govern any ofthese recommendations. The finding thatno increase in risk of lymphedema wasnoted in women who had had bilateralaxillary dissection compared with thosewho had had unilateral axillary dis-section16,35 calls into question the implica-tion that blood drawing, intravenous ad-ministration, blood-pressure monitoring,and injections hasten the development oflymphedema. Data for any of the otherarm and hand precautions are even morespeculative. On the other hand, breakingthe skin barrier, even during medical pro-cedures, could predispose to infection,and blood-pressure monitoring couldcause injury.

Lymphoscintigraphic techniques arenow being used to study the lymphatics ofthe upper limb after axillary treatmentand may help to provide answers regard-ing arm and hand precautions.13 Dynamicas well as static images may be obtained atvarious levels in the affected arm and un-der various standardized conditions (dur-ing and/or after various periods of rest,during and/or after exercise, etc.).

Such research is desperately needed.All patients are currently instructed inthe same arm and hand care precautions;however, these precautions may be toosevere for those at low risk, while not ag-gressive enough for those at the greatestrisk. Furthermore, as lymphedema mayoccur even several decades36 after axillarytreatment, patients are admonished tofollow these demanding precautions forthe remainder of their lives.

LYMPHEDEMA TREATMENTS

Therapeutic nihilism (i.e., no treatment atall) for lymphedema is deplorable, al-though quite common. All too often, awoman is told that she “should be thank-ful to be alive” and that she must “learnto live with it.” The fact that the averageclinician is ill prepared to both detect and

recognize early signs of lymphedemamust be remedied, as data suggest thatthe sooner the treatment is started, thesmaller the amount of treatment requiredto prevent further progression, and thebetter the ultimate result.

The treatment of established lym-phedema varies from doing nothing at allto pursuing a host of aggressive surgicalprocedures, as was particularly the case inthe past. Between these two extremes lievarious combinations of conservativetreatments, the most important of whichare elevation, the use of compression gar-ments, centripetal massage and exercises,the use of pneumatic compression de-vices, and a program of complete (orcomplex) decongestive physiotherapy,known as CDP.1. CDPCDP has been widely available in Europefor many years. This therapeutic ap-proach takes into account the fact thatlymphedema exists in an entire bodyquadrant, although its effects are mostdistressing in the arm or hand, and in-cludes skin care, gentle specific massage,known as manual lymphatic drainage orMLD, low-stretch multilayer compres-sion bandaging (followed by a fitted com-pression garment when edema is re-duced), and therapeutic exercises withthe garment or bandages in place.

The 1998 American Cancer SocietyWorkshop on Breast Cancer Treatment-Related Lymphedema included a reviewof the modifications and features of thevarious CDP programs described by Vod-der,37 Leduc,38 Foldi,39 and Casley-Smith.40 Although the principles followedare the same for each school, the massagetechniques vary somewhat in terms of thedegree of pressure and motion appliedand the timing of strokes. Additionally,the Leduc technique uses low, intermit-tent pneumatic pressure (< 40 mm Hg)pumps, and the Casley-Smith group usesbenzopyrone medication.

CDP must be performed by skilled,specially trained therapists. A typical


C A C a n c e r J C l i n 2 0 0 0 ; 5 0 : 2 9 2 - 3 0 7



American program includes four phases.During Phase I (the treatment phase), thepatient is given one or two 75- to 90-minute treatments daily over a period ofone to four weeks. In Phase II (the main-tenance phase), the patient maintains andoptimizes the results by applying some ofthe techniques learned in the treatmentphase, as well as by wearing an elasticsleeve during the day, bandaging the af-fected limb overnight (as described be-low), and exercising for 15 minutes a daywhile wearing the bandages. Phase II iscontinued indefinitely or until the limb nolonger swells.

Phase I of CDP treatment consists offour steps:1. Meticulous skin and nail care, which

can optimize the supple normal tex-ture.

2. MLD or manual lymph therapy(MLT), a delicate massage techniquethat stimulates lymph vessels to con-tract more frequently, directing andchanneling fluid toward adjacent, func-tioning lymph basins. Manual lymphdrainage begins with stimulation of the

lymph vessels and nodes in unaffectedand opposite basins (neck, contralater-al axilla, ipsilateral groin). Edema fluidand obstructed lymphatics are made todrain toward functioning lymph basinsacross the midline of the body, downtoward the groin, over the top of theshoulder, around the back, etc. Finally,in segmental order, massage of the in-volved trunk, the shoulder, upper arm,forearm, wrist, and hand.

3. Multilayer low-stretch bandaging isdone immediately following manu-al lymph drainage. Bandages arewrapped from the fingertips to the axil-la with maximal pressure distally andless pressure proximally. Many layersof minimally elastic cotton bandagesare used, beneath which layers of foamrubber padding are inserted to ensureuniform pressure distribution or to in-crease pressure in areas that are partic-ularly fibrotic.

4. The bandaged patient is next guidedthrough exercises involving activerange of motion with the muscles andjoints functioning within the closedspace of the bandaging. Isometric exer-cise is generally avoided.

The steps involved in the mainte-nance phase of CDP are shown in Table2. After volume reduction has been ac-complished, well-fitted compressive gar-ments continue ongoing control of ede-ma. It is generally not helpful to fit thegarment prior to volume reduction. Thepatient should be re-measured and thegarment replaced every three months.The patient and the patient’s family willhave been trained to continue the main-tenance program at home. Follow-up vis-its to the center usually take place at six-month intervals for measurements andcontinued instruction about differentcomponents of the program.

A recent short-term study of 28women randomized to either the Voddertechnique or to sequential pneumaticcompression (“pumping”) favored theCDP program.41 Low-stretch compres-

Phase I: Treatment—1 to 4 weeks

• Meticulous skin and nail care

• Manual lymphatic drainage

• Low-stretch multilayer bandaging

• Physical therapy in bandages

Phase II: Maintenance

• Meticulous skin and nail care

• Low-stretch multilayer bandages worn overnight

• Prescribed exercises in bandages[Surgical support garments (30-50mm Hg) for ongoing control]

Table 2Complex Decongestive

Therapy (CDT)

sion bandaging, as in Phase I, has alsobeen used alone (without MLD) withsome good effects.42 Although this bur-geoning technique appears more success-ful than other modalities in reversinglymphedema, the availability of patientservices and treatment centers that canutilize CDP is limited.

Representatives of the four schoolshave recently reviewed and discussed is-sues of patient accessibility43 and profes-sional education for physical therapists.44

Ongoing training of therapists and physi-cians is offered at several centers to teachCDP techniques. (The theories and clini-cal applications of the four schools ofmanual lymphatic technique are reviewedin the American Cancer Society mono-graph by their respective faculties.37-40)2. Elevation and Elastic Garments The elements of elevation and some de-tails of the use of elastic garments are pre-sented here.45 Although elevation maybe helpful in reducing swelling from lym-phedema through the use of gravity, it isimpractical. A patient with lymphedemashould be fitted with an elastic sleevefrom wrist to axilla if the edema is mild; ifthe edema is moderate, the fitting shouldtake place after the reduction of swelling.A separate, removable gauntlet or hand-piece allows the patient to wash herhands without removing the entire sleeve.

The physician who prescribes thesupport garment should be aware of thedifferent products that are available andshould order a garment in the propercompression class. These classes are:

I. 20 to 30 mm HgII. 30 to 40 mm Hg

III. 40 to 50 mm HgIV. 50 to 60 mm Hg

For upper extremity lymphedema, aClass II or III support is generally re-quired.

The person measuring the lym-phedematous arm and hand should betrained in fitting such garments and in in-structing patients in their proper applica-tion. Too often, however, this task is left

to a clerk in a surgical supply store wholacks specific training.

A statistically significant reductionin edema has been reported in womenwho wore compression garments for sixconsecutive hours per day.46 Using thesegarments during exercise, physical activi-ty, and air travel is recommended. 3. Pneumatic PumpsThe older intermittent, single-chamber,nonsegmented compression pumps pro-vide even pressure throughout the treatedarm; however, they also allow backflow ofthe lymphatic fluid, which may cause anincrease of fluid in the distal arm. Newerdevices have multiple chambers and canprovide sequential compression.

The standard sequential system is amultichamber pump that delivers thecompression at the same pressure in eachgarment section from distal to proximaltissues. The gradient sequential systemdelivers pressures that differ by approxi-mately 10 mm Hg between each cham-ber, with the higher pressures deliveredto the distal chamber. A minimum of onehour per pumping session is required, andlower pressures for longer periods aremore effective than higher pressures forshorter periods. The arm should be ele-vated during pumping. Women with lym-phedema should not simply be dis-patched to the medical supply house witha prescription and instructions to buy apump and to begin using it after readingthe accompanying instructions.

Individualized, tailored pumpingprograms are based on empirical knowl-edge of what will work for each individualpatient. Recommendations for the use ofa particular pump and program should bebased on measurable efficacy and tolera-bility, as evidenced by serial assessmentin that patient. The patient is then in-structed about the limitations and use ofher pump before she is placed on a homeprogram.

Several controlled studies47-51 havereported reductions in lymphedema withthe use of various devices. Although the


C A C a n c e r J C l i n 2 0 0 0 ; 5 0 : 2 9 2 - 3 0 7

use of machinery for the pumping actionon the arm lymphatics is theoretically at-tractive, pumping has not been as effec-tive clinically as had been hoped.

While CDP is quite successful forlymphedema, constraints created by theneed for experienced personnel and bytime requirements for treatment limit itsavailability. It has been hoped that pneu-matic compression devices or “pumps”could duplicate the beneficial effects ofmassage.45 Such pumps can force pro-tein-rich edema fluid toward the shoul-der, an area already congested, but not,however, through the axillary blockage;lymphedema involves the whole quad-rant of the ipsilateral trunk, the area thatthe obstructed axillary channels wouldnormally drain. In particular, pneumaticcompression therapy appears less usefulin advanced lymphedema because of skinthickening and fibrosis. For recent re-views of the rationale for and controver-sies about pumps, see Brennan andMiller45 and Rinehart-Ayres.52

4. Surgical TreatmentOperations with intent to cure lymphede-ma are cited here mainly for historical interest. Numerous surgical procedureshave been proposed and attempted in thetreatment of chronic lymphedema yetnone has been clinically successful.

Surgical approaches can be dividedinto two categories, physiologic and re-ductive. Physiologic approaches aim torestore lymphatic flow to the limb eitherby reconstruction of lymphatic channelsor by bridging lymphedematous tissue toareas with normal lymphatics, usually bydirect microsurgical anastomosis of sev-eral lymphatics to veins. Reductive ap-proaches simply remove excess tissue andedema to reduce the limb to a more func-tional size. These operations include re-moval of skin and subcutaneous tissuefollowed by skin grafting (Charles proce-dure), or staged subcutaneous excisionbeneath skin flaps (Sistrunk procedure).

Very recently, short-term success with li-posuction has been noted in Sweden byone group,53-55 although the long-term ef-ficacy of the procedure is not known. Thestate of knowledge about surgical proce-dures for lymphedema was recently re-viewed by Brennan and Miller.45

5. MedicationsDiuretics are not effective in high-proteinedemas such as lymphedema. Althoughthe diuretics can temporarily mobilizewater, the osmotic pressure from the in-creased protein in the interstitial spacecauses rapid reaccumulation of edema.

Benzopyrones belong to a group ofdrugs that include the bioflavonoids andthe coumarins. The former occur wide-ly in nature, especially in fruits and veg-etables. Benzopyrones improve chroniclymphedema56-57 by stimulating macro-phage activity for increased proteolysisand, thereby, for the removal of stag-nant, excess protein in the tissue spaces;this results in decreased oncotic pres-sure and edema fluid.

Several European and Australianresearchers58-62 have experimented with5,6-benzo-α-pyrone and reported that itproduces a slow reduction of lymphede-ma. Their centers include these drugs inphysical rehabilitation programs. Thebenzopyrones may cause liver toxicity,and deaths have been reported.

In 1993, in an Australian study, arandomized, double-blind, placebo-con-trolled, crossover trial of 5,6-benzo-α-pyrone demonstrated its efficacy.63 Al-though the effect was mild, it was statistically significant. More recently,however, a larger number of lymphede-matous breast cancer patients participat-ed in an American multicenter study ofsimilar study design led by the MayoClinic. In this study, the benzopyroneshowed no value beyond the placebo ef-fect.64 Moreover, 6% of the study sub-jects had worrisome elevation of liver-function tests.



C A C a n c e r J C l i n 2 0 0 0 ; 5 0 : 2 9 2 - 3 0 7


Approximately 60 invited participants were organizedinto five concurrent workgroups, each of which fo-cused on a dimension of the current challenge oflymphedema, and each of which was charged withissuing recommendations for research, clinical prac-tice, public and professional education, and advoca-cy. Workgroup reports and recommendations werepublished as part of the proceedings of the confer-ence and are summarized here.

Workgroup I: Treatment of the Axilla with Surgeryand Radiation—Preoperative and Postoperative Risk Assessment

Lymphedema of the arm is caused by treatment ofthe axilla with surgery or radiation, and risk of lym-phedema is increased when the axilla is treated withboth modalities. Recommendations to reduce risk oflymphedema without compromising the fundamentalintent of breast cancer treatment included:

1. Avoidance of axillary lymph node dissection for pa-tients with low-risk lesions (i.e., ductal carcinomain situ or certain T1 lesions)

2. Support for continued research on lymphatic map-ping and SLNB, and for training and credentialingin these new techniques. Although these newtechniques appear to offer great potential to re-duce the risk of lymphedema in patients with low-er-risk lesions, patients undergoing treatment withSLNB should be informed of the lack of long-termfollow-up with these techniques and, ideally,should be enrolled in a prospective study.

3. For patients who must be managed with standardtreatment, painstaking care in the technical as-pects of surgery itself and radiation planning canreduce the risk of lymphedema.

4. Research is needed on pre- and post-imagingstudies (e.g., lymphoscintigraphy) to evaluate thestatus of the axillary lymph nodes and lymphaticdrainage of the arm and breast.

5. Include assessment of symptoms associated withearly signs of lymphedema in routine follow-up af-ter breast cancer treatment. All clinical trials ofbreast cancer treatment, such as chemotherapyassessment, should include lymphedema assess-ment as an additional endpoint.65

Workgroup II: Patient Education—Pre- and Post-treatment

Most breast cancer patients do not appear to be in-formed about the potential for lymphedema as a con-sequence of treatment for breast cancer. Pre- andpost-treatment education is needed, as early signs oflymphedema may not be recognized, leading to de-lays in treatment and potentially to irreversible pro-gression. Furthermore, although little is definitelyknown about activities or trigger events associatedwith lymphedema onset, patients should be fully in-formed so that risk-reducing behavior can be adopt-ed. Treatment advances may offer women opportu-nities for informed decisions about breast cancertreatment based in part on risk of subsequent lym-phedema. Informed decision-making must takeplace when these treatment options exist. Specificrecommendations included the following:

1. Verbal and written pretreatment education on therisk of lymphedema should be introduced into dis-cussion of breast cancer treatment options; writtenmaterial should be culturally sensitive and evi-dence-based.

2. Post-treatment education should stress the impor-tance of recognizing early signs of lymphedema,include information on hand and arm precautions,and offer practical advice for avoiding situationsassociated with lymphedema risk. Advice shouldbe offered about what to do if these situations areencountered (i.e., a wound on the affected arm).

3. Patients who develop lymphedema should be eval-uated comprehensively by experienced profession-als and be fully informed about treatment options,management of acute lymphedema, and self-maintenance of stable but chronic forms of lym-phedema.66

Workgroup III: Diagnosis and Management

Although lymphedema is a prevalent disorder, there isa tendency toward “therapeutic neglect” of lym-phedema following treatment for breast cancer. Sec-ond, while there are different therapeutic approachesto lymphedema, consensus has not been reached onwhether one approach is preferable to another, or un-der what circumstances one approach may be moreappropriate than another.

American Cancer Society Workshop on Breast Cancer Treatment-Related Lymphedema: Recommendations and Research Initiatives



Chronic lymphedema is best treated by specialistsusing a multimodal approach of decongestive lym-phatic therapy, which includes proper skin care, man-ual lymphatic therapy, multilayered low-stretch ban-dages, and exercise. After arm-volume reduction,ongoing control of edema must be maintained throughproperly fitted compression garments. Anothermodality that may be used in addition to decongestivelymphatic therapy is intermittent compression pumps.The workgroup recommended :

1. All patients treated for breast cancer should be as-sessed for signs and symptoms of lymphedema atan early interval following completion of healingfrom breast cancer therapy (within the first 12weeks). Clinicians should pay attention to physicalsigns of lymphedema as well as to the patient’ssubjective awareness of symptoms, as the lattermay reveal early signs of an underlying pathology.

2. Research should focus on the development ofscreening modalities predictive of lymphedema,such as enhanced lymphoscintigraphic techniquesused to measure degrees of lymphatic dysfunction.

3. Investigation of the importance of early detectionand aggressive intervention for reducing severityand progression of lymphedema should be under-taken.

4. Research to determine the relative efficacy of eachcomponent of a comprehensive treatment pro-gram, including optimal timing of application.67

Workgroup IV: Lymphedema Treatment Resource—Professional Education and Availabilityof Patient Services

Health care providers are not sufficiently informedabout lymphedema, may not recognize early symp-toms of the condition, and generally are uninformedabout treatment options and the availability of treat-ment in their communities. Because of the pivotalrole played by health care professionals in terms ofinforming and meeting the needs of patients, rec-ommendations relate to the development and cost-effectiveness of both professional education and pa-tient interventions. These included:

1. Development of clinical-practice guidelines focus-ing on professional education, lymphedema recog-nition, and intervention strategies in patients treat-ed for breast cancer;

2. Promotion of professional education focused onlymphedema, including grand rounds, continuingmedical education, and greater attention to lym-phedema in medical textbooks and graduate med-ical education;

3. Establishment of a multidisciplinary task force toestablish certification guidelines for specific treat-ments and treatment facilities;

4. Expansion of the number of facilities available totreat lymphedema, and development of a resourceguide for lymphedema clinical services;

5. Development of cost/economic analysis of the bur-den and treatment of lymphedema.68

Workgroup V: Collaboration and Advocacy

Meeting the current and future challenge of lym-phedema will be accomplished faster and more effi-ciently if organizations work together and address acommon mission. Collaboration has the potential toreduce duplication, maximize resources, encouragegreater innovation, and hasten progress. A commonadvocacy position among leading and influential or-ganizations can also be more persuasive and moreeffective in changing policy than uneven and uncoor-dinated efforts.

The workgroup focused on the need for collabora-tion and called for the inclusion of representativesfrom all advocacy positions (including the AmericanCancer Society, the National Lymphedema Network,the National Alliance of Breast Cancer Organizations,the Susan G. Komen Foundation, Y-ME NationalBreast Cancer Organization, Arm-in-Arm, and BosomBuddies) in future initiatives. Collaborative effortsshould focus on patient and provider education, stan-dards for informed consent and information, and leg-islative and patient advocacy. A workgroup should beestablished to develop a model for insurance cover-age of lymphedema treatment services; the provisionof coverage was advocated for state-of-the-art treat-ment by third-party payers. The workgroup stressedthe need for effective advocacy for standards of treat-ment and management of lymphedema, calling forcollaboration within the medical and scientific com-munity to establish the evidence upon which futureadvocacy and collaborative efforts could be built.69

Lymphedema Workshop -Continued

C A C a n c e r J C l i n 2 0 0 0 ; 5 0 : 2 9 2 - 3 0 7

CERTIFIED THERAPISTS, such asphysical and occupational therapists,typically plan rehabilitation interven-tions, generally in concert with a pre-scribing physician. Other individuals,including nurses and licensed massagetherapists, may employ these tech-niques as well. Therapists should alsoidentify and address pain, limitationsin range of motion, and impaired activ-ities of daily living.

• For mild lymphedema (resolves com-pletely overnight):

1. Counsel: Use arm/hand precau-tions; normalize body weight; em-ploy meticulous arm/hand care.

2. Elevate; employ centripetal self-administered massage.

3. Use compression garment, partic-ularly during work, exercise, andair travel.

• For moderate and severe lymphede-ma: (referral to a rehabilitation centerrecommended)

1. Counsel: Use arm/hand precau-tions; normalize body weight; em-ploy meticulous arm/hand care.

2. Elevate; employ centripetal self-administered massage.

3. Use compression garment.

4. Employ complete decongestivephysiotherapy (CDP) programAND/OR intermittent pneumaticcompression devices under guid-ance of a therapist.

Multidisciplinary Treatment ConclusionLymphedema is an important healthproblem for many women who have beentreated for breast cancer. It is especiallydispiriting to women who have been as-sured that their prognosis is excellent andthat reconstruction will allow them tocontinue their lives with few visible re-minders of their disease. For manywomen, lymphedema is not only a debili-tating condition, but also a daily reminderof the health care system’s failure to edu-cate them appropriately and to respondeffectively to their condition. Many ofthe recommendations for addressing thechallenge of lymphedema are interrelat-ed and are thus dependent on concomi-tant and synchronous progress in the de-velopment of a solid research base,treatment modalities for the reduction ofrisk of lymphedema, improvements in theclinical response to symptoms of lym-phedema, improvements in provider andpatient education, and changes in healthcare policy. In the interim, patients andhealth care providers must be fully ap-praised of what we know and what we donot know about breast-cancer-treatmentrelated lymphedema.

References1. American Cancer Society Workshop on BreastCancer Treatment-Related Lymphedema. NewYork, New York, USA. February 20-22, 1997.Cancer. 1998 Dec 15;83(12 Suppl American):2775-2890. 2. Mortimer PS: The pathophysiology of lymphede-ma. Cancer 1998;83(12 Suppl American):2798-2802.3. Brennan MJ: Lymphedema following the surgicaltreatment of breast cancer: A review of pathophys-iology and treatment. J Pain Symptom Manage1992;7:110-116.4. McCaffrey JF: Lymphedema: Its treatment. InPaterson AHG, Lees AW (eds): Fundamentalproblems in breast cancer. Boston, MartinusNijhoff Publishing, 1987; pp. 259-263.5. Passik SD, McDonald MV: Psychosocial aspectsof upper extremity lymphedema in women treatedfor breast carcinoma. Cancer 1998;83(12 SupplAmerican):2817-2820.6. Passik SD, Newman M, Brennan M, Tunkel R:Predictors of psychological distress, sexual dysfunc-tion and physical functioning among women withupper extremity lymphedema related to breast can-cer. Psycho-Oncology 1995;4:255-263.

CA


7. Gerber LH: A review of measures of lymphede-ma. Cancer 1998;83(12 Suppl American):2803-2804. 8. Bolin FP, Preuss LE, Beninson J: Di-chromaticdifferential absorptiometry for assessment of lym-phedema. Int J Nucl Med Biol 1980;7:359-360.9. Stewart G, Hurst PAE, Thomas ML, BurnandKG: CAT scanning in the management of the lym-phedematous limb. Immunol Haematol Res1988;2:241.10. Duwell S, Hagspiel KD, Zuber J, et al: Swollenlower extremity: Role of MR imaging. Radiology1992;184:227-231.11. Stanton AW, Northfield JW, Holroyd B, et al:Validation of an optoelectronic limb volumeter(Perometer). Lymphology 1997;30:77-97.12. Kissin MW, Querci della Rovere G, Easton D,Westbury G.: Risk of lymphoedema following thetreatment of breast cancer. Br J Surg 1986;73:580-584. 13. Bourgeois P, Leduc O, Leduc A: Imaging tech-niques in the management and prevention of post-therapeutic upper limb edemas. Cancer 1998;83(12Suppl American):2805-2813.14. Carena M, Baiardi P, Saponaro M, et al:Scintigraphic evaluation of predisposition to post-mastectomy lymphedema, in Lokiec FM, CluzanRV, Pecking AP et al: (eds): Progress inLymphology XIII. Berlin, Springer-Verlag, 1992; p.325.15. Pecking AP, Floiras JL, Rouesse J: Upper limblymphedema’s frequency in patients by conserva-tive therapy in breast cancer. Lymphology1996;29(Suppl):293.16. Petrek JA, Heelan MC: Incidence of breast car-cinoma-related lymphedema. Cancer 1998;83(12Suppl American):2776-2781.17. Ferrandez JC, Serin D, Bouges S: Frequency oflymphedema of the upper limb after treatment ofbreast cancer. Risk factors. Apropos of 683 cases.Bull Cancer 1996;83:989-995.18. Schunemann H, Willich N: Lymphedema afterbreast carcinoma. A study of 5868 cases. DtschMed Wochenschr 1997;122:536-541.19. Lin PP, Allison DC, Wainstock J, et al: Impactof axillary lymph node dissection on the therapy ofbreast cancer patients. J Clin Oncol 1993;11:1536-1544.20. Werner RS, McCormick B, Petrek JA, et al:Arm edema in conservatively managed breast can-cer: Obesity is a major predictive factor. Radiology1991;180:177-184.21. Ivens D, Hoe AL, Podd TJ, et al: Assessment ofmorbidity from complete axillary dissection. Br JCancer 1992;66:136-138.22. Ball AB, Waters R, Fish S, Thomas JM: Radicalaxillary dissection in the staging and treatment ofbreast cancer. Ann R Coll Surg Engl1992;74(2):126-129.23. Paci E, Cariddi A, Barchielli A, et al: Long-term sequelae of breast cancer surgery. Tumori1996;82:321-324.24. Pressman PI: Surgical treatment and lymphede-ma. Cancer 1998;83(12 Suppl American):2782-2787.

25. Pezner RD, Patterson MP, Hill LR, et al: Armlymphedema in patients treated conservatively forbreast cancer: Relationship to patient age and axil-lary node dissection technique. Int J Radiat OncolBiol Phys 1986;12:2079-2083.26. Yeoh EK, Denham JW, Davies SA, Spittle MF:Primary breast cancer. Complications of axillarymanagement. Acta Radiol Oncol 1986;25:105-108.27. Delouche G, Bachelot F, Premont M, Kurtz JM:Conservation treatment of early breast cancer:Long term results and complications. Int J RadiatOncol Biol Phys 1987;13:29-34.28. Aitken RJ, Gaze MN, Rodger A, et al: Armmorbidity within a trial of mastectomy and eithernodal sample with selective radiotherapy or axillaryclearance. Br J Surg 1989;76:568-571.29. Larson D, Weinstein M, Goldberg I, et al:Edema of the arm as a function of the extent of axil-lary surgery in patients with stage I-II carcinoma ofthe breast treated with primary radiotherapy. Int JRadiat Oncol Biol Phys 1986;12:1575-1582.30. Dewar JA, Sarrazin D, Benhamou E, et al:Management of the axilla in conservatively treatedbreast cancer: 592 patients treated at InstitutGustave-Roussy. Int J Radiat Oncol Biol Phys1987;13:475-481.31. Meek AG: Breast radiotherapy and lymphede-ma. Cancer 1998;83(12 Suppl American):2788-2797.32. Giuliano A, Jones RC, Brennan M, Statman R:Sentinel lymphadenectomy in breast cancer. J ClinOncol 1997;15:2345-2350.33. Tadych K, Donegan WL: Postmastectomy sero-mas and wound drainage. Surg Gynecol Obstet1987;165:483-487. 34. West JP, Ellison JB: A study of the causes andprevention of edema of the arm following radicalmastectomy. Surg Gynecol Obstet 1959;109:359.35. Mortimer PS, Bates D, Brassington H, et al:The prevalence of arm oedema following treatmentfor breast cancer. QJM 1996;89:377-380.36. Brennan MJ, Weitz J: Lymphedema 30 yearsafter radical mastectomy. Am J Phys Med Rehabil1992;71:12-14.37. Kasseroller RG: The Vodder School: TheVodder method. Cancer 1998;83(12 Suppl Ameri-can):2840-2842.38. Leduc O, Leduc A, Bourgeois P, Belgrado JP:The physical treatment of upper limb edema.Cancer 1998;83(12 Suppl American):2835-2839.39. Foldi E: The treatment of lymphedema. Cancer1998;83(12 Suppl American):2833-2834.40. Casley-Smith JR, Boris M, Weindorf S, LasinskiB: Treatment for lymphedema of the arm—theCasley-Smith method: A noninvasive method pro-duces continued reduction. Cancer 1998;83(12Suppl American):2843-2860.41. Johansson K, Lie E, Ekdahl C, Lindfeldt J: Arandomized study comparing manual lymphdrainage with sequential pneumatic compressionfor treatment of postoperative arm lymphedema.Lymphology 1998;31:56-64.42. Johansson K, Albertsson M, Ingvar C, EkdahlC: Effects of compression bandaging with or with-out manual lymph drainage treatment in patients



C A C a n c e r J C l i n 2 0 0 0 ; 5 0 : 2 9 2 - 3 0 7


with postoperative arm lymphedema. Lymphology1999;32:103-110.43. Thiadens SR: Current status of education andtreatment resources for lymphedema. Cancer1998;83(12 Suppl American):2864-2868.44. Augustine E, Corn M, Danoff J: Lymphedemamanagement training for physical therapy studentsin the United States. Cancer 1998;83(12 SupplAmerican):2869-2873.45. Brennan MJ, Miller LT: Overview of treatmentoptions and review of the current role and use ofcompression garments, intermittent pumps, andexercise in the management of lymphedema.Cancer 1998;83(12 Suppl American):2821-2827.46. Bertelli G, Venturini M, Forno G, et al: Ananalysis of prognostic factors in response to conser-vative treatment of postmastectomy lymphedema.Surg Gynecol Obstet 1992;175:455-460.47. Klein MJ, Alexander MA, Wright JM, et al:Treatment of adult lower extremity lymphedemawith the Wright Linear pump: Statistical analysis ofa clinical trial. Arch Phys Med Rehabil 1988;69:202-206.48. Kim-Sing C, Basco VE: Postmastectomy lym-phedema treated with the Wright linear pump. CanJ Surg 1987;30:368-370.49. Pappas CJ, O’Donnell TF Jr: Long-term resultsof compression treatment for lymphedema. J VascSurg 1992;16:555-562.50. Richmand DM, O’Donnell TF Jr, Zelikovski A:Sequential pneumatic compression for lymphede-ma: A controlled trial. Arch Surg 1985;120:1116-1119.51. Zanolla R, Monzeglio C, Balzarini A, MartinoG: Evaluation of the results of three differentmethods of postmastectomy lymphedema treat-ment. J Surg Oncol 1984;26:210-213.52. Rinehart-Ayres ME: Conservative approachesto lymphedema treatment. Cancer 1998;83(12Suppl American):2828-2832. 53. Brorson H, Svensson H: Complete reduction oflymphoedema of the arm by liposuction after breastcancer. Scand J Plast Reconstr Surg Hand Surg1997;31:137-143.54. Brorson H, Svensson H: Liposuction combinedwith controlled compression therapy reduces armlymphedema more effectively than controlled com-pression therapy alone. Plast Reconst Surg1998;102:1058-1067.55. Brorson H, Svensson H, Norrgren K, ThorssonO: Liposuction reduces arm lymphedema withoutsignificantly altering the already impaired lymphtransport. Lymphology 1998;31:156-172.56. Piller NB, Clodius L: The role of the mononu-clear phagocytic system in lymphoedema and itsrelationship with histopathological changes in thefunctioning of the blood-tissue system. Z Lymphol1980;4:35-42.57. Casley-Smith JR, Gaffney RM: Excess plasma

proteins as a cause of chronic inflammation andlymphodema: Quantitative electron microscopy. JPathol 1981;133:243-272.58. Cluzan R, Pecking A: Benzopyrone (Lysedem)double blind cross-over study in patients with sec-ondary upper limb edemas, in Nishi M, Uchino S,Yabuke S (eds): Progress in lymphology XII,Excerpta Med Int Cong Ser 887. Amsterdam,Elsevier, 1990, pp. 453-454.59. Pecking AP, Fevrier B, Wargon C, Pillion G:Efficacy of Daflon 500 mg in the treatment of lym-phedema (secondary to conventional therapy ofbreast cancer). Angiology 1997;48:93-98.60. Casley-Smith JR: There are many benzo-pyrones for lymphedema. Lymphology 1997;30:38-39.61. Taylor HM, Rose KE, Twycross RG: A double-blind clinical trial of hydroxyethylrutosides inobstructive arm lymphedema. Phlebologie 1993;22(Suppl 1):190.62. Burgos A, Alcaide A, Alcoba C, et al:Comparative study of the clinical efficacy of twodifferent coumarin dosages in the management ofarm lymphedema after treatment for breast cancer.Lymphology 1999;32:3-10.63. Casley-Smith JR, Morgan RG, Piller NB:Treatment of lymphedema of the arms and legswith 5,6-benzo-[alpha]-pyrone. N Engl J Med1993;329:1158-1163.64. Loprinzi CL, Kugler JW, Sloan JA, et al: Lackof effect of coumarin in women with lymphedemaafter treatment for breast cancer. N Engl J Med1999;340:346-350.65. Leitch AM, Meek AG, Smith RA, et al:American Cancer Society Lymphedema Workshop.Workgroup I: Treatment of the axilla with surgeryand radiation—preoperative and postoperative riskassessment. Cancer 1998:83(12 Suppl American):2877-2879.66. Runowics CD, Passik SD, Hann D, et al:American Cancer Society LymphedemeaWorkshop. Workgroup II: Patient education—pre-and posttreatment. Cancer 1998;83(12 SupplAmerican):2880-2881.67. Rockson SG, Miller LT, Senie R, et al:American Cancer Society Lymphedema Workshop.Workgroup III: Diagnosis and mamagement oflymphedema. Cancer 1998;83(12 Suppl American):2882-2885.68. Walley DR, Augustine E, Saslow D, et al:American Cancer Society Lymphedema Work-shop. Workgroup IV: Lymphedema treatmentresources—professional education and availabilityof patient services. Cancer 1998;83(12 SupplAmerican):288602887.69. Canceira M, Schuch W, Greiner L, et al:American Cancer Society Lymphedema Workshop:Workgroup V: Collaboration and advocacy. Cancer1998;83(Suppl American):2888-2890.

Lymphedema-current Issues in Research and Mang

Documents

Transcript of Lymphedema-current Issues in Research and Mang