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Comparison of blue dye and gammaprobe guided sentinel lymph nodebiopsy techniques in breast cancerpatients
Turkish Journal of CancerVolume 33, No.2, 2003
ABSTRACT
The introduction of sentinel lymph node (SLN) biopsy has
brought an innovative approach to the staging of early
breast cancer. Up to date two methods have been described:
a blue dye-guided lymphatic mapping procedure and a
radioactivity guided SLN biopsy technique using a hand-
held gamma probe. Aim of this study was to test the sentinel
lymph node concept which states the histopathological
analysis of sentinel lymph node is highly predictive of
metastatic involvement of other lymph nodes and to compare
gamma probe and blue dye techniques in the detection of
sentinel lymph node in breast cancer. Twenty-eight patients
with unifocal primary invasive breast cancer and clinically
negative axilla scheduled for mastectomy/lumpectomy and
ALND were included into the study. Gamma probe success-
fully identified SLN in 71% (20/28) of patients. Blue Dye
identified SLN in 61% (17/28) of patients. Either Blue dye
or gamma probe identified SLN in 79% (22/28) of patients.
The mean number of SLNs that were identified was 1.36.
Gamma probe identified more SLNs compared to blue dye
and results of statistical analysis show a significant difference
between them (Fisher’s exact chi-square test, p=0.03).
Analysis of data revealed that learning curve has a significant
effect on the success of SLN identification. The success
rate in first 6 patients was 33% (2/6) while it was 91%
(20/22) in the last 22 patients. Histopathological analysis
of SLN accurately predicted absence of the disease in the
axilla in 15 patients. In four patients there were metastatic
involvement in both SLN and other axillary lymph nodes. In
two patients micrometastasis was detected in SLN by
immunohistochemistry while non-SLNs were negative. There
was one false negative SLN biopsy, where histopathological
investigation of SLN was negative for metastases while non-
SLN were positive. We concluded that there is statistically
significant difference between blue dye and gamma probe
techniques for identifying SLN and gamma probe identifies
more SLN compared to blue dye. However, they are com-
plementary techniques and combined method works better.
This study also supports the clinical validity of SLN biopsy
in breast cancer and confirms that histopathological analysis
of sentinel lymph node is highly predictive of metastatic
involvement of other non-SLNs in axilla. [Turk J Cancer
2003;33(2):82-90]
KEY WORDS:
Sentinel lymph node, breast cancer, lymphoscintigraphy,
gamma probe, blue dye
INTRODUCTION
Routine axillary node dissection is currently the standard
of care in clinically node negative breast cancer patients.
ÖMER UGUR1, M. FANI BOZKURT1, ISKENDER SAYEK2, GÖKHAN GEDIKOGLU3, ATAÇ BAYKAL2,
ERHAN HAMALOGLU2, ILKER ETIKAN4, ALI KONAN2, BELKIS ERBAS1
Departments of 1Nuclear Medicine, 2Surgery, 3Pathology and 4Biostatistics, Hacettepe University Faculty of Medicine, Ankara-Turkey
83Ugur et a l .
Axillary lymph node dissection (ALND) has a well estab-
lished role in regional disease control and it provides
information about histopathological status of axillary lymph
nodes which has significant prognostic and adjuvant ther-
apeutic implications (1,2). However, 70-80% of clinically
node negative patients prove to be histopathologically node
negative and they must still sustain the expense and mor-
bidity of this procedure including complications such as
neuropathies, seromas, shoulder movement restriction and
upper extremity lymphedema in 5-8% (3-5). After the
widespread use of screening mammography, patients with
breast cancer now present with smaller tumors than in the
past and as a result the incidence of axillary nodal involve-
ment is lower than before (6). There is a tendency to use
breast conserving surgery without compromising local
control or long term survival. Sentinel lymph node (SLN)
biopsy is a recently developed minimally invasive technique
for staging the axilla in patients with breast cancer (7). SLN
is the first lymph node in a given lymphatic basin to receive
lymphatic flow from a primary tumor site. This technique
introduces a new concept, namely that of selective lym-
phadenectomy in breast cancer on the basis of the histolog-
ical status of the SLN and avoiding unnecessary ALND
(8).
Moreover, relapse rates of up to 30% in node negative
breast cancer patients with single section hematoxylin and
eosin (H&E) histopathological examination gives out
skepticism about the routine histopathological examination
of ALND specimen (9). Detailed histopathological investi-
gation of the SLN including multiple sections and immu-
nohistochemistry for micrometastases gives us the oppor-
tunity to accurately predict the status of the distant lymph-
node basin (10). However, the optimal technique for SLN
biopsy is still debated. Initial studies to locate sentinel
lymph node were conducted with vital blue dyes with less
favorable results (11,8). Though, for this technique to
become widely accepted in the management of breast cancer,
it needs to identify the SLN reliably. Recently, intraoperative
gamma probe was used for this purpose. Aim of this study
was to test the sentinel lymph node concept which states
the histopathological analysis of sentinel lymph node is
highly predictive of metastatic involvement of other lymph
nodes and to compare gamma probe and blue dye techniques
in the detection of sentinel lymph node in breast cancer.
MATERIALS AND METHODS
Patients and study protocol
Twenty-eight patients with unifocal primary invasive
breast cancer with clinically negative axilla scheduled for
mastectomy/lumpectomy and ALND were included into
the study. Patients with multicentric primary breast cancer
or clinically positive regional lymph nodes were excluded.
The study protocol was approved by the Hacettepe Univer-
sity Institutional Review Board, and prior written informed
consent was obtained from all patients.
Radiopharmaceutical injection technique
and lymphoscintigraphy
2-12 hours before operation 500-2500 uCi of either Tc-
99m-colloidal rhenium sulphide (Nanocolloid, CIS bioint-
ernational, France) or Tc-99m-colloidal tin (Amerscan
Hepatate II Agent, Nycomed Amersham plc, UK) was
injected intradermally at the same quadrant with the tumor.
Immediately following injection, dynamic lymphoscintig-
raphy was performed using gamma camera (e-cam, Siemens,
Erlangen, Germany) equipped with a high resolution, low-
energy, parallel hole collimator. Dynamic 64x64 matrix
images were recorded every minute for 30 min. After
dynamic imaging 5 min static images of anterior and lateral
breast were acquired at 256x256 matrix (Figure 1). In
addition, Co-57 flood source transmission imaging was
used to delineate body contours. Any radioactivity accumu-
lation suggestive of SLN was marked on the skin with the
help of Co-57 tipped pencil marker.
Fig 1. Lymphoscintigraphy revealed SLN in the axilla (arrow:SLN, arrow head: injection site)
84 Sent inel Node Biopsy and Breast Cancer
Gamma detection probe
Intraoperative radioactive SLN localization was per-
formed using a gamma photon detection probe (Neoprobe
2000, Neoprobe corporation, Dublin, Ohio, U.S.A) with
energy peak set at 140 keV-20% window.
Blue dye
Injectable sterile solutions of 1% isosulphan blue (mono-
sodium salt of 2,5-disulphonated triphenyl methane) was
prepared by the Department of Pharmaceutical Technology
at Hacettepe University Faculty of Pharmacy using a stock
solution obtained from Sigma company (5 g isosulphan
blue, Sigma catalog no: P1888, Sigma-Aldrich chemical
co., Deisenhofen, Germany).
Intraoperative lymphatic mapping and
sentinel lymph node biopsy
The gamma probe was ensheathed in a sterile endoscopic
probe cover and a sterile tape was tied over the end of
probe. After the induction of general anesthesia, 5 ml 1%
Isosulphan Blue was injected and gentle massage was
applied for a few minutes. Following the skin preparation
and draping of the operative field a 10 sec probe count was
taken from the sternal notch as a background count. The
pencil mark on the axilla correspondent to the SLN was
counted and then intramammary, supraclavicular, infraclav-
icular, parasternal and rectus sheath regions were surveyed
with gamma probe methodically in a grid pattern over the
skin. Cutaneous hot spots were delineated and carefully
marked; these signify the accumulation of radioactivity in
one or more SLN. SLN biopsy was performed through a
standard anteroposterior incision placed in the lower axillary
hair-bearing skin, as routinely performed in formal axillary
lymphadenectomy. The gamma probe counts guided the
dissection and any radioactive node(s) that have in-vivo
counts of at least 3 times more than background counts
were excised. Ex-vivo counts from the excised node(s)
were recorded. The lymph node(s) with in-vivo counts of
at least 3 times and with ex-vivo counts of at least 10 times
that of the background was accepted as SLN(s). After
excision of the SLN(s), mastectomy was performed by
developing mastectomy flaps. Routine axillary lymph node
dissection through levels 1, 2 and/or 3 was then completed.
The SLN(s), mastectomy and axillary lymph node dissection
material were kept as separate specimen for the pathological
examination (Figure 2).
Pathologic evaluation
Histopathologic analysis was
performed by detailed micro-
scopic examination of three sec-
tions from each bivalved SLN and
one section from non-SLN. In
addition to H&E staining cytok-
eratin and epithelial membrane
antigen (EMA) immunohis-
tochemistry was also applied to
SLN.
Statistical analysis
The significance of the dif-
ference between gamma probe
and blue dye for SLN detection
were made by Fisher’s exact chi-
square test.Fig 2. Gamma probe (A). Gamma probe detection of SLN (B). Blue dye injection (C). Excisionof blue node (arrow) (D)
85Ugur et a l .
RESULTS
Tumor characteristics
Histopathological diagnosis and location of the primary
tumor were given in table 1. Twenty patients had infiltrating
ductal carcinoma. Primary tumor stage was T1 in 16 patients,
T2 in 6 patients, and T3 in 3 patients.
Comparison of blue dye and gamma probe
technical success in localising SLN
Gamma probe successfully identified SLN in 71%
(20/28) of patients. Blue dye identified SLN in 61% (17/28)
of patients. Either Blue dye or gamma probe identified
SLN in 79% (22/28) of patients. The mean number of SLNs
that were identified was 1.36.
Table 1
Histopathological diagnosis, primary tumor size and location
Patient no. Histopathological Primary tumor Gamma Blue Number Location of
(Age/sex) Diagnosis size (cm) Probe Dye of SLN primary tumor
1. (SH) (74/F) Infiltrative ductal carcinoma 6 - - - UOQ
2. (SK) (45/F) Infiltrative ductal carcinoma NA + + 1 LOQ
3. (ME) (53/F) Infiltrative ductal carcinoma 1.2 + + 2 LOQ
4. (AK) (55/F) Infiltrative ductal carcinoma 1.1 - - - UOQ
5. (FK) (49/F) Mixed infiltrative ductal-lobular 3.5 - - - LOQ
carcinoma
6. (AD) (57/F) Infiltrative ductal carcinoma 0.3 - - - Central
7. (SP) (46/F) Infiltrative ductal carcinoma 5 + + 1 UOQ
8. (YÜ) (68/F) Microinvasive ductal carcinoma 0.5 + + 1 UOQ
9. (CG) (25/F) Mucinous carcinoma 6 + + 1 UOQ
10. (AÇ) (53/F) Infiltrative lobular carcinoma 2.5 - - - Outer central
11. (HA) (46/F) Infiltrative ductal carcinoma 1.2 + - 1 UIQ
12. (MA) (51/F) Microinvasive ductal carcinoma 0.8 + - 1 UIQ
13. (SS) (40/F) Infiltrative ductal carcinoma 1.7 + - 2 UOQ
14. (EFS) (62/F) Infiltrative ductal carcinoma 3 + + 1 UOQ
15. (SS) (59/F) Intraductal carcinoma NA + + 2 LOQ
16. (NG) (50/F) Mixed infiltrative ductal-lobular 2 - + 1 Central
carcinoma
17. (LT) (57/F) Mixed infiltrative ductal-lobular 1.5 + + 2 Bilateral UOQ
carcinoma
18. (AS) (46/F) Infiltrative ductal carcinoma 1.8 + - 2 Upper central
19. (HÇ) (51/F) Infiltrative ductal carcinoma 3 + + 1 Outer central
20. (RC) (44/M) Intraductal carcinoma 2.5 + + 1 UOQ
21. (NC) (49/F) Ductal carcinoma in situ NA + + 1 UOQ
22. (SY) (44/F) Infiltrative ductal carcinoma 1.8 + + 3 UOQ
23. (SS) (76/F) Infiltrative ductal carcinoma 1.7 + + 1 LOQ
24. (SK) (48/F) Ductal carcinoma in situ <2 mm - + 1 LOQ
25. (HÇ) (49/F) Infiltrative ductal carcinoma 1.6 + + 1 UOQ
26. (ST) (57/F) Ductal carcinoma in situ 0.1 - - - Outer central
27. (FÇ) (58/F) Infiltrative ductal carcinoma 1.3 + - 2 UOQ
28. (FK) (57/F) Infiltrative ductal carcinoma 1.5 + + 1 UOQ
UOQ: Upper outer quadrant, LOQ: Lower outer quadrant, UIQ: Upper inner quadrant, NA: Primary tumor size is not
available because pathologic examination of the primary tumor was undertaken by another institute
86 Sent inel Node Biopsy and Breast Cancer
In a patient (patient no: 5) whom there was extensive
local and axillary tumoral involvement, gamma probe
identified a hot spot in internal mammary region but neither
gamma probe nor blue dye was capable of identifying SLN
in axillary region probably due to complete infiltration of
the nodes with tumor and leaving no lymphoid parenchyma
to localize radiocolloid and blue dye in axilla (Figure 3).
We did not explore internal mammary area to identify hot
spot and accepted this case as directional lymphatic flow
change due to mechanical obstruction. In another patient
(patient no: 8) lymphoscintigraphy showed a dim lymphatic
truct with an activity 4x background with in-vivo gamma
probe. Although counts were less than expected, it was
accepted as a sentinel lymph node. However blue dye could
not identify any SLN intraoperatively. Histopathological
examination demonstrates widespread fatty degeneration
in the lymph node with decreased functional parenchyma
for radiocolloid uptake (Figure 4). In other 4 patients with
unsuccessful localization no obvious reason for failure can
be identified but these patients were within the first 6
patients and inexperience of the team can be a reason for
the failure. Comparison of blue dye and gamma probe in
identifying sentinel lymph node is tabulated in table 2.
Gamma probe identified more SLNs compared to blue dye
and results of statistical analysis shows a significant differ-
ence between them (Fisher’s exact chi-square test, p=0.03).
Fig 3a. Diffuse infiltrative metastasis in sentinel lymph node(H&E, x30) (patient no:5)
Fig 3b. High power view from diffuse infiltrative metastasisin sentinel lymph node (x115)
Fig 4. Lipomatous infiltration in sentinel lymph node (H&E,x30)(Patient no:8)
87
Effect of learning curve on the success
of SLN identification
Analysis of data revealed that learning curve has a
significant effect on the success of SLN identification. The
success rate in first 6 patients was 33% (2/6) while it was
91% (20/22) in the last 22 patients.
Correlation with histopathologic status
of SLN and axillary involvement
Histopathological analysis of SLN accurately predicted
absence of the disease in the axilla in 15 patients. In 4
patients there were metastatic involvement in both SLN
and other axillary lymph nodes. In two patients microme-
tastasis was detected in SLN by immunohistochemistry
while other axillary lymph nodes were negative (Figure 5).
There was one false negative SLN biopsy, where histopatho-
logical investigation of SLN was negative for metastases
while non-SLN were positive (patient no: 25).
Toxicity and adverse effects
There were no allergic or idiosyncratic events related
to the use of Tc-99m labeled colloid lymphoscintigraphic
agents and blue dye.
Table 2
Comparison of the gamma probe and blue dye for the localization of the SLN*
Blue Dye
Positive Negative Total
Gamma Probe
Positive 15 (75%) 5 (25%) 20 (100%)
Negative 2 (25%) 6 (75%) 8 (100%)
Total 17 (60.7%) 11 (39.3%) 28 (100%)
* Gamma probe identified more SLN compared to blue dye and this is statistically significant
(Fisher’s exact chi-square test p=0.03)
Fig 5a. Micrometastasis in sentinel lymph node (arrow) (H&E,x30) patient no.18)
Ugur et a l .
88 Sent inel Node Biopsy and Breast Cancer
Both methods have merits and disadvantages (12). Using
blue dye technique surgeon can visualize and follow lym-
phatic truct to dissect SLN. Moreover, blue dye is widely
available and simple to use. However, timing of the blue
dye is crucial for the success of the procedure. If it is
injected too early there would be extensive blue staining
in the nodal basin making the dissection of SLN very
difficult. On the other hand if the injection is administered
too late, successful localization may fail owing to the
inability of the dye to reach the sentinel node because of
disruption of lymphatic channels during dissection. Pre-
operative lymphoscintigraphy and intraoperative gamma
probe techniques give us the knowledge about the location
of SLN before the surgery. Another important advantage
of probe guided surgery is that complete excision of the
SLNs can be verified by directing the probe into the incision
to measure residual activity. Moreover, gamma probe will
give the surgeon a sense of direction and allows detection
of non-visible nodes due to their radioactive content. There
DISCUSSION
The introduction of SLN biopsy has brought an innova-
tive approach to the staging of early breast cancer. Up to
date two methods have been described: a blue dye-guided
lymphatic mapping procedure and a radioactivity guided
SLN biopsy technique using a hand-held gamma probe.
Fig 5b. EMA (+) micrometastasis (Strept ABC, x30)
Fig 5d. High power view from EMA (+) micrometastasis (Strept
ABC, x115)
Fig 5c. High power view from micrometastasis (H&E, x115)
89
is increased evidence in the literature to support better
results when both detection methods are combined, com-
pared with the use of these techniques alone (13). Cserni
and associates (14) reported that combined technique has
advantages like higher identification rate, higher accuracy
level and a lower false negative rate.
In the present study, we present Hacettepe University
Medical Center experience with dye-guided and dye plus
gamma probe guided SLN biopsy and compared these two
methods. As demonstrated in earlier studies on SLN biopsy
in breast cancer, we experienced a learning period (14,15).
In the first 6 patients our success rate to identify SLN was
only 33%, compared to 91% in the last 22 patients. We
used intradermal radiocolloid injection technique in our
study as suggested to be a superior technique compared to
peritumoral injection and this may result our high success
rate at the end of the learning curve (12).
It has also been suggested that false negative rate (SLN
histopathology (-) for metastases, non SLNs histopathology
(+) for metastases) is higher during the introductory phase
(16). This is not validated by our results that we observed
only one false negative case. As the number of patients in
our series increased we may observe increase in false
negative rate. In order to SLN biopsy to replace axillary
lymphadenectomy false negative rate should be low. Meta-
analysis of the data from 685 patients who had SLN biopsy
for breast cancer shows that the false negative rate ranges
between 5.1% and 7.6% (6). Several factors may account
for the increased false negative rate in SLN biopsy such
as previous surgery, multifocality of tumor and extensive
lymphovascular invasion. Previous surgery may explain
the false negative case in our series. Another reason for
false negative rate in blue dye only method is that surgeon
may be satisfied with the number of SLNs identified and
only some of these may be true SLNs. However, in the
combined method surgeon can detect non-visible SLNs
due to their radioactive content and this may explain our
low false negative rate. The mean number of SLN identified
in our study (1.36) and the number of both blue and radio-
active nodes (53%) are in concordance with the larger
series in the literature (17,18). Although gamma probe
identified more SLNs compared to blue dye, statistical
analysis could not find a significant difference between
them. Lymphatic flow change due to mechanical obstruction
and fatty degeneration in the lymph node are responsible
for 2 of the 6 cases which both methods are unsuccessful
in localising SLN. These are also common reasons reported
in the literature for failure (12). We also did not observe
lymphatic drainage occurring to lymph nodes outside the
axilla which is a less common finding with intradermal
technique compared to peritumoral injection such as the
lymphatic drainage which Uren and associates (19) observed
occurring to lymph nodes outside the axilla including the
internal mammary in more than half of the patients with
peritumoral injection technique (6). In two patients mi-
crometastases in SLN were detected using cytokeratin and
EMA immunohistochemistry. At present, there are conflict-
ing data on the prognostic significance of detecting mi-
crometastatic disease in the SLN by immunohistochemistry,
how this information could be used in clinical practice is
unclear (6). Should these patients be subjected to toxicity
of adjuvant chemotherapy or further radiotherapy of axilla?
However, there is evidence that sensitive detection of SLN
micrometastases, enhanced by paraffin step sections and
cytokeratin immunohistochemistry is important because a
significant number of patients with SLN micrometastases
have additional non-SLN metastases, and further surgery
and adjuvant therapies may be warranted. However, the
prognostic significance of a few cytokeratin-positive cells
remains to be determined (20).
We concluded that there is statistically significant
difference between blue dye and gamma probe techniques
for identifying SLN and gamma probe identifies more SLN
compared to blue dye. However, they are complementary
techniques and combined method works better. This study
also supports the clinical validity of SLN biopsy in breast
cancer and confirms that histopathological analysis of
sentinel lymph node is highly predictive of metastatic
involvement of other non-SLNs in axilla.
ACKNOWLEDGEMENT
This work was supported in part by the Hacettepe
University Research Fund no: 00.01.101.011.
Ugur et a l .
90 Sent inel Node Biopsy and Breast Cancer
References
1. Carter CL, Allen C, Henson DE. Relation of tumour size,
lymph node status, and survival in 24740 breast cancer
cases. Cancer 1989;63:181-7.
2. Fisher B, Bauer M, Wickerham L, et al. Relation of number
of positive nodes to the prognosis of patients with primary
breast cancer. An NSABP update. Cancer 1983;52:1551-
7.
3. Kissin MW, Querci della Rovere G, Easton D, et al. Risk
of lymphedema after the treatment of breast cancer. Br J
Surg 1986;73:580-4.
4. Aitken RJ, Gaze MN, Rodger A, et al. Arm morbidity
within a trial of mastectomy and either nodal sample with
selective radiotherapy or axillary clearance. Br J Surg
1989;76:568-71.
5. Gulec SA, Moffat FL, Carroll RG, et al. Sentinel lymph
node localization in early breast cancer. J Nucl Med
1998;39:1388-93.
6. Keshtgar MRS, Ell PJ. Clinical role of sentinel lymph
node biopsy in breast cancer. Lancet Oncol 2002;3:105-
10.
7. Krag DN, Weaver DL, Alex JC, et al. Surgical resection
and radiolocalization of the sentinel node in breast cancer
using a gamma probe. Surg Oncol 1993;2:335-40.
8. McIntosh SA, Purushotham AD. Lymphatic mapping and
sentinel node biopsy in breast cancer. Br J Surg
1998;85:1347-56.
9. Rosen PP, Groshen S, Saigo PE, et al. A long term follow
up study of survival in stage I (T1N0M0) and stage II
(T1N1M0) breast carcinoma. J Clin Oncol 1989;226:271-
8.
10. Turner RR, Ollila DW, Krasne DL, et al. Histopathological
validation of the sentinel lymph node hypothesis for breast
carcinoma. Ann Surg 1997;226:271-8.
11. Folscher DJ, Langman G, Panieri E, et al. Sentinel axillary
lymph node biopsy: helpful in axillary management in
patients with breast cancer? Br J Surg 1997;84:1586.
12. Keshtgar MRS. Surgical techniques. In: Keshtgar MRS,
Waddington WA, Lakhani SR, Ell PJ, editors. Sentinel
node in surgical oncology. Berlin, Heidelberg, Germany:
Springer-Verlag, 1999;79-89.
13. Cody HS, Fey J, Akhurst T, et al. Complementarity of
blue dye and isotope in sentinel node localization for
breast cancer: univariate and multivariate analysis of 966
procedures. Ann Surg Oncol 2001;8:13-9.
14. Cserni G, Rajtar M, Boross G, et al. Comparison of vital
dye-guided lymphatic mapping and dye plus gamma probe-
guided sentinel node biopsy in breast cancer. World J Surg
2002:26;592-7.
15. Giuliano AE, Kirgan DM, Guenther JM, et al. Lymphatic
mapping and sentinel lymphadenectomy for breast cancer.
Ann Surg 1994:220;391-8.
16. Cody H, Hill ADK, Tran KN, et al. Credentialing for
breast lymphatic mapping: how many cases are enough?
Ann Surg 1999:229;723-8.
17. Doting MHE, Jansen L, Nieweg OE, et al. Lymphatic
mapping with intralesional tracer administration in breast
carcinoma patients. Cancer 2000:88;2546-52.
18. Cox CE, Bass SS, McCann CR, et al. Lymphatic mapping
and sentinel lymph node biopsy in patients with breast
cancer. Annu Rev Med 2000:51;525-42.
19. Uren RF, Howman-Giles R, Renwick SB, et al. Lymphatic
mapping of the breast: Locating the sentinel lymph nodes.
World J Surg 2001:25;789-93.
20. Turner RR, Giuliano AE, Hoon DSB, et al. Pathologic
examination of sentinel lymph node for breast carcinoma.
World J Surg 2001:25;798-805.