Is intra-operative gamma probe detection really necessary for inguinal sentinel lymph node biopsy?

165

Original Article

REVISTA PAULISTA DE MEDICIN A

Is intra-ope rative gamma probe

de te ction re ally ne ce ssary for

inguinal se ntine l lymph node biopsy?

Discipline of Plastic Surgery/Tumor branch, Universidade Federal de São Paulo/

Escola Paulista de Medicina, São Paulo, Brazil

a b s t r a c t

CON TEX T:

Sentinel no de (SN ) b io psy ha s c ha ng ed the surg ic a l treatment o f malig nant melano ma. The literature has emphasiz ed the impo rtance o f g amma pro be detectio n (G PD) o f the SN .

OBJECTIVE:

O ur o bjective was to evaluate the efficacy o f patent blue dye (PBD) and G PD fo r SN bio psy in different lymphatic basins.

DESIGN :

Patients with cutaneo us malig nant melano ma in stag es I and II were submitted to bio psy o f the SN , identified by PBD and G PD, as part o f a research pro ject.

SETTIN G :

Pa tie nts w e re se e n a t Ho sp ita l Sã o Pa ulo b y a multidisc iplina ry g ro up (Pla stic Surg e ry Tumo r Bra nc h, N uc le a r Medicine and Patho lo g y).

PATIEN TS

: 6 4 patients with lo caliz ed malig nant melano ma were studied. The median ag e was 4 6 .5 years. The primary tumo r was lo cated in the neck, trunk o r extremities.

IN TERV EN TIO N S:

Pre o p e ra tive lymp ho sc intig ra p hy, lymp ha tic mapping with PBD and intrao perative G PD was perfo rmed o n all patients. The SN was examined by co nventio nal and immuno his-to c he mic a l sta ining . If the SN w a s no t fo und o r c o nta ine d micro metastases, o nly co mplete lymphadenecto my was perfo rmed.

M AIN M EASUREM EN TS

: The SN was identified by PBD if it was blue-stained, and by G PD if demo nstrated activity five times g reater than the adipo se tissue o f the neig hbo rho o d.

RESU LTS:

Se ve nty ly mp ha tic b a sins w e re e x p lo re d . Lympho scintig raphy sho wed ambig uo us drainag e in 7 patients. G PD identified the SN in 6 8 basins (9 7 %) and PBD in 5 3 (7 6 %). PBD and G PD identified SN in 1 0 0 % o f the ing uinal basins. Fo r the remaining basins bo th techniques were co mplementary. A metastatic SN was fo und in 1 0 basins. Three patients with neg ative SN had recurrence (median fo llo w-up = 1 1 mo nths).

CON CLUSION :

Altho ug h bo th G PD and PBD are useful and co mple-menta ry, PBD a lo ne identified the SN in 1 0 0 % o f the ing uina l lymphatic basins.

KEY W ORDS:

Sentinel no de. Lympho scintig raphy. G amma detec-tio n. Lymphatic mapping .

• Renato Santo s de O liveira Filho • Ivan Dunshe Abranches O liveira Santo s • Lydia Massako Ferreira • Fernando Aug usto de Almeida • Milvia Maria Simõ es e Silvia Eno kihara • Anto nio Barbieri • Reinaldo To vo Filho

INTRODUCTION

Surgical treatment o f regio nal lymph no des in

cutaneo us malignant melano ma stage I and II is still

co ntro versial.

1-4

_{The main pro blem is to characterize}

which patients must have lymphadenecto my. In 13.3%

o f stage I and 20% o f stage II patients, clinically hidden

lymph no de metastases are remo ved at an early stage

with elective lymph no de dissectio n. In the remaining

cases, no tumo r is fo und in the lymph no des and these

patients receive excessive treatment and are submitted

to the risk o f po sto perative co mplicatio ns.

5-11

_{Balch et al.}

characterized a subgro up o f patients under 60 years o ld

with tumo r thickness o f 1-4 mm who benefited fro m

elec-tive lymph no de dissectio n.

12,13

The co ncept o f sentinel lymph no de (SN), the first

no de in the lymphatic basin that drains the area o f the

primary tumo r, has changed the surgical appro ach in

melano ma patients. This technique invo lves fo ur pro

-cedures: pre-o perative lympho scintigraphy, intrao

pera-tive lymphatic mapping, intrao perapera-tive gamma-pro be

detectio n (GPD) and histo patho lo gy. Pre-o perative

lympho scintigraphy identifies the lymphatic basins at

risk fo r metastatic disease, ano malo us drainage and

in-transit metastasis. Intrao perative lymphatic mapping

with a vital dye (we have used patent blue dye, PBD)

anato mically and functio nally mimics the lymphatic

spread o f neo plastic cells fro m the primary site to the

lymphatic basin

.

Blue staining o f lymphatic vessels

al-lo ws identificatio n o f the SN, as initially demo nstrated

by Mo rto n et al.

14,15

GPD allo ws better lo calizatio n o f SN with less

extensive dissectio n.

16

_{The SN is submitted to co}

166

Sao Paulo Med J/Rev Paul Med 2000; 118(6):165-8.

tio nal histo patho lo gical examinatio n (hemato

xylin-eo sin) and immuno histo chemical staining with HMB

45 antigen and S-100 pro tein. Only patients with po sitive

SN are submitted to co mplete lymphadenecto my.

17,18

The accuracy o f SN in predicting the histo patho lo gical

status o f the lymphatic basin has been co nfirmed by

several gro ups aro und the wo rld.

19-23

SN bio psy has changed surgical treatment o f

melano ma. The literature has emphasized the impo

r-tance o f GPD in the SN bio psy. Befo re intro ducing GPD

in o ur practice, we had used PBD alo ne with very go o d

results fo r lymph no des o f the inguinal regio n. Our

o bjective was to evaluate the efficacy o f PBD and GPD

in the SN bio psy o f different lymphatic basins.

The ro le o f PBD and GPD in the identificatio n o f

the SN in different lymphatic b asins o f cutaneo us

malignant melano ma patients was studied.

METHODS

Setting.

Patients were treated at Ho spital São

Paulo o f the Universidade Federal de São Paulo /Esco la

Paulista de Me dicina (UNIFESP/EPM) b y a m

ulti-disciplinary gro up (Plastic Surge ry Tum o r Branch,

Nuclear Medicine and Patho lo gy).

Patients.

Sixty-fo ur patients with clinically lo calized

malignant melano ma with Breslo w thickness equal to o r

greater than 0.8 mm were enro lled. Excisio n bio psy o f the

primary tumo r was perfo rmed at mo st 60 days befo re the

sentinel lymph node biopsy. Informed consent was obtained

fro m all patients. Of the 64 patients, 31 were men and 33

wo men. The median age was 46.5 years o ld (range, 18-81

years o ld). The median thickness o f the primary tumo r was

1.3 mm (range, 0.8-7.0 mm). Thirty-eight patients were at

clinical stage IB, 19 IIA and 7 IIB. The primary sites were the

neck,

2

_trunk

32

_{and extremities.}

30

_{Clinico patho lo gically, there}

were 4 accrual melano ma, 36 superficial spreading

melano ma and 24 no dular melano ma. Ulceratio n was

present in 9 cases

(Table 1).

Interventions.

Befo re o peratio n, all patients

un-derwent lympho scintigraphy to characterize the

lym-phatic basin o f drainage and to lo calize the SN. A do se

o f 250 micro curie (

99m

_{TC-dextran 500) was injected}

intradermally at 2 to 4 po ints aro und the bio psy scar

o r the melano ma lesio n if still present.

Immediately afterwards, dynamic images were

o btained to visualize the lymphatic drainage. Dynamic

acquisitio n o f images co ntinued fo r a minimum o f 20

min to a maximum o f 45 min. Anterio r and lateral static

images, using a dual-head gamma camera (Eucint

He-lix HR), were o btained until the SN was fo und. The last

image was o btained after 2 ho urs. These images were

co mplemented by o blique views whenever the

injec-tio n site co uld o bscure the SN. The po siinjec-tio n o f the SN

was then marked o n the skin.

In the o perating ro o m, a similar injectio n o f

99m

_{TC-dextran was given fo r GPD. A co nvenient site fo r}

inc isio n was c o nfirm e d and d e te rm ine d using a

Neo pro be 1500 device as a gamma pro be detecto r

(Co lumbus, OH). To co nsider a no de as an SN it had

to demo nstrate at least 5 times mo re activity than the

adipo se tissue o f the neighbo rho o d.

Intrao perative lymphatic mapping with patent blue

dye (PBD) was perfo rmed acco rding to the technique

described by Mo rto n et al.

12

_{A small incisio n was made,}

and the subcutaneo us tissue was explo red in the search

fo r a blue-stained lymphatic channel. The channel was

carefully dissected do wn to the blue-stained SN.

After the bio psy was perfo rmed, the SN (

ex vivo

)

and the o perative field were checked by pro be. The

excised SN was sent fo r patho lo gical examinatio n,

using a paraffin hemato xylin-eo sin sectio n and

immu-no histo chemical staining with S-100 pro tein and

HMB-45 antigen. Only when micro metastases were present

was a fo rm al re g io n al lym p h n o d e d is s e c tio n

perfo rmed. The average fo llo w-up fo r this gro up o f

patients was 11 mo nths (range, 1 - 25 mo nths).

Main measurement.

The SN was identified by PBD

if it was blue-stained and by GPD if it demo nstrated at

least five times mo re activity than the adipo se tissue

aro und it.

RESULTS

Se ve nty lym p hatic b as ins we re e xp lo re d .

Lympho scintigraphy sho wed ambiguo us drainage in 7

patients. The distributio n o f the basins were: axillary,

35

inguinal

29

_{and cervical.}

6

_{In all cases PBD and GPD were}

perfo rmed, identifying a to tal o f 98 SN (1.4 SN per

lym-phatic basin). GPD identified the SN in 68 basins (97%)

Table 1.

General patient characteristics

Sex

3 1 Men : 3 3 W o men

Age

1 8 - 8 1 years (median = 4 6 .5 years)

Breslow

0 .8 - 7 mm (median = 1 .3 mm)

Prima ry site

N eck 2

Trunk 3 2

Members 3 0

Clinica l Sta ge

IB 3 8

IIA 1 9

IIB 7

Histopa thologica l type

Superficial spreading 3 6

N o dular 2 4

Accrual 4

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Sao Paulo Med J/Rev Paul Med 2000; 118(6):165-8.

and PBD in 53 basins (76%). In the axillary regio n, GPD

identified SN in 34 basins (97%) and PBD in 22 basins

(63%). In cervical basins, GPD identified SN in 5 (83%)

and PBD in 2 (33%). Fo r the 29 inguinal basins, bo th GPD

and PBD identified 100% o f the SN

(Table 2).

A tumo r-po sitive SN was fo und in 10 patients (8

o n permanent sectio ns and 2 o n immuno histo

chemis-try o nly). Regio nal no de dissectio n was perfo rmed o n

all 10 patients with tumo r-co ntaining SN. In additio n

to the SN, o ther invo lved no des were fo und in three

patients. Altho ugh with a sho rt fo llo w-up (11 mo nths),

three patients with a tumo r-negative SN bio psy had a

relapse: o ne in the same basin, ano ther develo ped

in-transit metastasis and the third had liver metastasis

(Breslo w = 1.2 mm, 2.4 mm and 2.3 mm, respectively).

Po sto perative co mplicatio ns were seen in fo ur patients,

whic h we re c linic ally tre ate d ( wo und infe c tio n,

hemato ma and sero ma).

DISCUSSION

The SN p ro c e d ure ap p e ars to b e a re liab le

metho d fo r regio nal lo catio n micro staging o f

mela-no m a patie nts with clinically hidde n lym ph mela-no de

metastases. The patho lo gical status o f SN is the mo st

impo rtant pro gno stic facto r fo r tumo r recurrence.

24,25

When using o nly PBD, the literature has

regis-tered a lo wer identificatio n rate fo r the SN (85%) than

with GPD (98-100%).

26-29

Similar data were o btained in

o ur study (PBD = 76% and GPD = 97%). Sub gro up

analysis o f the basins sho wed that GPD and PBD

iden-tifie d 100% o f the inguinal SN. Fo r the re maining

b asins (axillary and ce rvical), GPD and PBD we re

co mplementary, but GPD identified mo re SN than PBD.

Lympho scintigraphy had a crucial ro le in lo calizing the

SN basin and allo wing skin lo calizatio n o f the SN,

especially in the inguinal regio n.

So me autho rs have questio ned whether there

is any ro le fo r PBD in the SN bio psy,

27

_emphasizing

the ro le o f GPD in the o utpatient clinic. Others

indi-cate PBD as a standard pro cedure.

30

Our data sho wed

that PBD alo ne is a very go o d technique fo r the

in-guinal SN, po sing a different questio n: is intra-o

pera-tive gam m a p ro b e d e te c tio n re ally ne c e ssary fo r

inguinal sentinel lymph no de bio psy? PBD simplifies

the pro cedure, can be do ne witho ut an intrao perative

gamma de te ctio n de vice , and impro ve s the co st /

benefit relatio nship.

Three patients with tumo r-negative SN bio psy

had relapses. Perhaps a mo re po werful metho d fo r

evaluating the SN status wo uld be able to identify

hidden micro metastases in tho se negative SN.

We are in tro d u c in g d e te c tio n o f m - RNA

thyro sinase in the SN b y the reverse transcriptase

po lymerase chain reactio n (RT-PCR). The sentinel no de

bio psy technique will co ntribute to o btaining better

kno wledge o f the natural histo ry o f melano ma cell

disseminatio n.

Table 2.

Percentage o f SN identificatio n

by PBD and GPD techniques fo r lymphatic

basins

Technique Inguinal (29) ax illary (35) Cervical (6) Total of basins (70)

PBD 1 0 0 % 6 3 % 3 3 % 7 6 % G PD

1 0 0 % 9 7 % 8 3 % 9 7 %

1. Kro o n BB, Jo nk A. Elective lymph no de dissectio n in melano ma: still a co ntro versial issue. Neth J Surg 1991;43:129-32.

2. Cascinelli N, Mo rabito A, Santinami M, Mackie RM, Belli F. Immediate o r delayed dissectio n o f regio nal no des in patients with melano ma o f the trunk: a rando m ize d trial. WHO Me lano m a Pro gram . Lanc e t 1998;351:793-6.

3. Balch CM. The ro le o f elective lymph no de dissectio n in melano ma: ratio nale, results, and co ntro versies. J Clin Onco l 1988;6:163-72.

4. McNeer G, Das Gupta TK. Pro gno sis in malignant melano ma. Surgery 1964;56:512-8.

5. Balch CM, Milto n GW, Cascinelli N, Sim FH. Elective lymph no de dissectio n: Pro s and Co ns. In: Balch CM, Ho ughto n NA, Milto n GW, So b e r AJ, So o ng SJ, Ed ito rs. Cutane o us m e lano m a. 2nd _{e d itio n.} Philadelphia: Lippinco tt; 1992:345-66.

6. Milto n GW, Shaw HM, McCarthy WH, et al. Pro phylactic lymph no de dissectio n in clinical stage I cutaneo us malignant melano ma: results o f surgical treatment in 1319 patients. Br J Surg 1982;69:108-11.

7. Vero nesi U, Adamus J, Bandiera DC, et al. Inefficacy o f immediate no de dissectio n in stage l melano ma o f the limb s. N Engl J Med 1977;297:627-30.

REFERENCES

8. Vero nesi U, Adamus J, Bandiera DC, et al. Delayed regio nal lymph no de dissectio n in stage l melano ma o f the skin o f the lo wer extremities. Cancer 1982;49:2420-30.

9. McCarthy WH, Shaw HM, Milto n GW. Efficacy o f elective lymph no de disse ctio n in 2347 patie nts with clinical stage l me lano ma. Surg Gyneco l Obstet 1985;161:575-80.

10. Baas PC, Schraffo rdt Ko o ps H, Ho efkstra JH, Van Bruggen JJ, Van der Weele LT, Oldho ff J. Gro in dissectio n in the treatment o f lo wer-extremity m e lan o m a: s h o rt- te rm an d lo n g te rm m o rb id ity. Ac h Su rg 1992;127:281-6.

11. Bro wsher WG, Taylo r BA, Hughes LE. Mo rbidity, mo rtality and lo cal recurrence fo llo wing regio nal no de dissectio n fo r melano ma. Br J Surg 1986;73:906-8.

12. Balch CM, So o ng SJ, Barto lucci AA, et al. Efficacy o f an elective regio nal lymph no de dissectio n o f 1 to 4 mm thick melano mas fo r patients 60 years o f age and yo unger. Ann Surg 1996;224:255-63.

13. Dreeper H, Ko hler CO, Bastian B, et al. Benefit o f elective lymph no de dissectio n in subgro ups o f melano ma patients. Cancer 1993;72:741-9.

168

r e s u m o

CON TEXTO:

A bió psia de linfo no do sentinela (LS) mudo u a abo rdagem c irúrg ic a do mela no ma ma lig no . A litera tura tem enfa tiz a do a impo rtância da detecção gama intra-o perató ria (DG ) do LS.

OBJETIVO:

N o sso o bjetivo é avaliar a eficácia do co rante az ul patente (AP) e da DG na bió psia de LS em diferentes bases linfáticas.

TIPO DE ESTUDO:

Pacientes po rtado res de melano ma malig no cutâneo fo ram submetido s à bió psia do LS, usando AP e DG co mo parte de um pro jeto de pesquisa.

LO CAL:

Ho sp ita l Sã o Pa ulo , g rup o multid isc ip lina r (c irurg iã o o nco ló g ico , médico nuclear e pato lo g ista).

PACIEN TES:

Fo ram estudado s 6 4 pacientes po rtado res de melano ma malig no lo caliz ado , co m idade mediana de 4 6 ,5 ano s. O sítio primário estava lo caliz ado no pesco ço , tro nco e no s membro s.

IN TERVEN ÇÕ ES:

Linfo c intilo g ra fia pré-o pera tó ria , ma pea mento linfático co m AP e DG fo ram realizado s em to do s o s pacientes. O LS fo i examinado po r histo pato lo g ia co nvencio nal e imuno histo química. Q uando o LS não fo i enco ntrado o u co ntinha micro metástases, linfadenecto mia co mpleta da base linfática fo i realizada.

VARIÁVEIS ESTUDADAS:

O LS fo i co nsiderado co mo identificado pelo AP se co rado em az ul e pela DG quando demo nstro u pelo meno s 5 vez es mais atividade do que o tecido g o rduro so viz inho .

RESULTADOS:

Fo ram explo radas 7 0 bases linfáticas. A linfo cintilo grafia mo stro u drenagem ambígua em 7 pacientes. DG identifico u o LS em 6 8 bases linfáticas (9 7 %) e o AP o fez em 5 3 bases (7 6 %). O s do is méto do s identificaram separadamente 1 0 0 % do s LS inguinais. Nas demais bases, as técnicas fo ram co mplementares. O LS estava invadido po r células tumo rais em 1 0 bases. Três pacientes co m LS negativo apresentaram reco rrência (seguimento mediano de 1 1 meses).

CON CLUSÃO:

Embo ra o empreg o de AP e G P na pesquisa de LS sejam co mplementares, o AP demo nstro u ser um méto do suficiente para a lo caliz ação do LS ing uinal.

PALAVRAS-CHAVE:

Linfo no do sentinela. Linfo cintilo g rafia. detecção g ama. Mapeamento linfático .

Re nato Santos de Olive ira Filho, MD, PhD. Research Pro fesso r, Discipline o f Plastic Surgery/Tumo r branch, Universidade Federal de São Paulo / Esco la Paulista de Medicina, São Paulo , Brazil.

Ivan Dunshe Abranche s Olive ira Santos, MD, PhD. Adjunct Pro fesso r, Discipline o f Plastic Surgery/Tumo r branch, Universidade Federal de São Paulo / Esco la Paulista de Medicina, São Paulo , Brazil.

Lydia Massako Fe rre ira, MD, PhD. Head and Chairman, Discipline o f Plastic Surgery/Tumo r branch, Universidade Federal de São Paulo / Esco la Paulista de Medicina, São Paulo , Brazil.

Fe rnando Augusto de Alme ida, MD, PhD. Adjunct Pro fesso r, Department o f Dermato lo gy, Universidade Federal de São Paulo / Esco la Paulista de Medicina, São Paulo , Brazil.

Milvia Maria Simõe s e Silvia Enokihara, MD. Patho lo gist, Discipline o f Plastic Surgery/Tumo r branch, Universidade Federal de São Paulo / Esco la Paulista de Medicina, São Paulo , Brazil.

Antonio Barbie ri, MD, PhD. Head and Chairman, Department o f Nuclear Medicine, Universidade Federal de São Paulo / Esco la Paulista de Medicina, São Paulo , Brazil.

Re inaldo Tovo Filho, MD. Po stgraduate Student, Discipline o f Plastic Surgery/ Tumo r branch, Universidade Federal de São Paulo / Esco la Paulista de Medicina, São Paulo , Brazil.

Source s of funding: Suppo rted by FAPESP (97/02516-0)

Conflict of inte re st: No t declared

Last re ce ive d: 23 February 2000

Acce pte d: 10 May 2000

Addre ss for corre sponde nce :

Renato Santo s de Oliveira Filho Rua Carlo s Milan, 37

São Paulo /SP - Brasil - CEP 01456-030 E-mail: rso ff@ ig.co m.br

publishing in fo r m a t io n

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