Occasional survey
Summary of the Second International Sentinel Node
Conference
Omgo E. Nieweg, Pieter J. Tanis, Emiel J.T. Rutgers
Department of Surgery, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam,
The Netherlands
Published online: 4 April 2001
© Springer-Verlag 2001
Abstract. A personal account is given of the most nota-
ble developments in lymphatic mapping that were dis-
cussed at the international conference “Sentinel Node
2000”, held in December 2000 in Santa Monica. The lat-
est advances in tracers, imaging, instrumentation and ra-
diation are first outlined. Thereafter, techniques, results
and controversies with respect to melanoma, breast can-
cer and other cancers are discussed. It is concluded that
lymphatic mapping is quickly gaining momentum. The
technique that is best used for lymphatic mapping is well
established in melanoma but not in breast cancer. The re-
sults of large randomised studies are awaited in both
these diseases. Gastrointestinal cancer is the main new
focus.
Keywords: Sentinel lymph node – Review
Eur J Nucl Med (2001) 28:646–649
DOI 10.1007/s002590100513
Introduction
The second international conference on lymphatic map-
ping, “Sentinel Node 2000”, was held 1–4 December
2000 in Santa Monica. This was an appropriate location
since it is the birthplace of lymphatic mapping. Its initia-
tors, Drs. Morton, Cochran and Giuliano, hosted the
event. The meeting was well organised and took place in
a pleasant atmosphere. In attendance were 400 partici-
pants from 36 countries. Europe was well represented,
with 127 participants. Most participants were surgeons,
but there were also nuclear medicine physicians, pathol-
Omgo E. Nieweg (✉)
Department of Surgery, The Netherlands Cancer Institute/
Antoni van Leeuwenhoek Hospital, Plesmanlaan 121,
1066 CX Amsterdam, The Netherlands
e-mail: Nieweg@nki.nl
Tel.: +31-20-5122977, Fax: +31-20-5122554
ogists, gynaecologists, urologists and basic scientists.
The abstracts of the conference will be published in a
forthcoming issue of the Annals of Surgical Oncology.
This summary is a personal account of the most notable
developments.
Tracers, imaging, instrumentation and radiation
The various tracers that are currently used for lymphatic
mapping all have their flaws. What are the properties of
the ideal tracer for this purpose? The ideal tracer is easy
to prepare and remains stable. After administration, it is
accumulated in the lymphatic system and quickly travels
to the first lymph node. A few hours later, there should
be no residual activity at the injection site. Complete
clearance eliminates the problem of background scatter
from a nearby injection site that can obscure a sentinel
node. The tracer is avidly accumulated and retained in
the first node without some of it passing through and
moving on to subsequent nodes: a radioactive node is a
sentinel node. This obviates the need for dynamic imag-
ing and also eliminates the need for the surgeon to use
the blue dye technique. The ideal tracer causes limited
radiation to the patient and hospital personnel and there
are no other side-effects. Since the resolution of gamma
cameras is not likely to improve dramatically in the fore-
seeable future, advances in lymphoscintigraphy will
have to come from the use of better tracers. Developing
new tracers is extremely difficult. Only a single new
agent was announced at the meeting. A group of investi-
gators from San Diego presented results from animal
studies with a new tracer, 99mTc-DTPA-mannosyl-dex-
tran. This tracer exhibits rapid injection site clearance
and low secondary node accumulation. Results from
clinical studies are eagerly awaited.
Radiolabelled colloids will be used primarily in the
years to come. A study by Dr. Van der Schors from
Hoorn, the Netherlands, revealed that a 2.5-fold greater
radiochemical purity can be obtained by preparing
99mTc-colloid in vacuum vials. Dr. Valdés Olmos showed
European Journal of Nuclear Medicine Vol. 28, No. 5, May 2001

an increased visualisation rate with an increased colloid
particle concentration and an increased tracer dose
(106 MBq).
Small gamma cameras for intraoperative use were
presented. Dr. Tsuchimochi from Nigata, Japan, devel-
oped a device with a 44.8 mm by 44.8 mm field of view.
Its spatial resolution is 1.6 mm FWHM. Laparoscopic
probes are being used. Probes from different manufactur-
ers are now being rigorously tested under standardised
conditions.
Radiation measurements by Dr. Brenner from Kiel
and Dr. Mitsui from Tokyo confirmed that the radiation
doses to which surgical and pathology staff are exposed
are within the acceptable range.
Melanoma
There is consensus on how lymphatic mapping should be
done in melanoma patients. Lymphoscintigraphy is es-
sential. Preoperative imaging identifies sentinel nodes in
unexpected locations. Dr. Uren showed drainage to un-
usual sites in a quarter of his patients. Dynamic studies
can help distinguish first-echelon nodes from second-
echelon nodes that need not be removed. The fact that
different tracers are used on different continents does not
seem to matter. Surgeons agree that both a gamma ray
detection probe and blue dye need to be used. The main
reason for using blue dye is to visualise the lymphatic
duct and thereby identify the hot node that receives
drainage directly from the primary tumour. Unnecessary
removal of secondary nodes can then be avoided. Four
studies from community hospitals showed that the senti-
nel node can be identified in 94% to 98% of patients.
There is lack of consensus on whether sentinel node
biopsy is now the standard of care. Most Americans at
the conference supported this point of view, albeit with
some notable exceptions. Dr. Thompson of the Sydney
Melanoma Unit stated that sentinel node biopsy is not
accepted as the standard of care in Australia. Although
European guidelines recommend restriction of sentinel
node biopsy to patients in trials [1], a few prominent in-
vestigators appeared to disagree. What good can lym-
phatic mapping do? First of all, early regional node dis-
section may improve survival and regional control. And
secondly, this approach may help to select patients for
adjuvant systemic treatment. However, no evidence was
presented at the meeting to support either objective. As
far as the latter objective is concerned, none of the
experts we talked to at the meeting routinely gave their
patients adjuvant systemic treatment. Several studies of
adjuvant interferon-alpha and vaccines are in progress.
Dr. Morton is currently conducting a 16-centre ran-
domised trial to investigate the impact of lymphatic
mapping on regional control and survival. A total of
1,784 patients have been included in the trial so far. The
sentinel node has been identified in 94% of cases. The
European Journal of Nuclear Medicine Vol. 28, No. 5, May 2001
647
participating European centres will continue to enrol pa-
tients for another year. A potential survival benefit will
be limited by a high incidence of false-negative sentinel
node biopsies. Dr. Cascinelli presented the results of a
series of 1,062 patients studied in a WHO trial. The 27%
false-negative rate is worrying, but the great majority of
the failures occurred early on. This illustrates that senti-
nel node biopsy is a technically challenging procedure
which requires an (ill-defined) learning phase. Five other
presenters with a combined 812 patients had more
favourable false-negative rates in single institutions
ranging from 0% to 7%, albeit with a median follow-up
duration that was less than a year in some studies.
A strong point in favour of lymphatic mapping is that
it provides important prognostic information. Dr. Morton
showed 5-year survival to be 90%–95% if the sentinel
node is disease-free and around 65% if the node contains
metastatic disease. A number of other investigators pre-
sented similar data but with a shorter follow-up. Dr.
Hans Starz from Augsburg showed how pathologists can
provide even more accurate prognostic information by
looking at tumour burden and growth pattern.
A new staging system has been developed that in-
cludes sentinel node status and allows patients to be clas-
sified into more homogeneous prognostic categories.
Most patients with thick melanomas (>4 mm) will
have distant metastases from which they will die. There-
fore, the value of sentinel node biopsy in these patients
has been questioned. A study from Tampa demonstrated
that the tumour status of the sentinel node does have
prognostic value in these patients. As was to be expect-
ed, PET has a limited capacity to detect metastases in
non-palpable lymph nodes: Dr. Lockwood from St.
Louis found the sensitivity to be a mere 44%. Ultra-
sound, however, is emerging as a useful technique to
identify involved lymph nodes both before sentinel node
biopsy and during follow-up after removal of a tumour-
free sentinel node.
Breast cancer
Breast cancer was the largest topic at the meeting. Twen-
ty-six investigators presented their identification rate. It
varied between 79% and 100%, with a median of 93%.
Twenty-seven investigators presented their false-nega-
tive rate. These data were recalculated (if necessary) as a
percentage of tumour-free sentinel nodes in patients with
a tumour-positive axilla. The false-negative rates ranged
from 0% to 33%, with a median of 7%. Ten of the 26 in-
vestigators (37%) had no false-negative results. None of
the investigators with a false-negative rate exceeding
10% used all three detection techniques. It is our feeling
that the false-negative rate should be less than 5%.
A survey in the United States showed that 56% of the
community surgeons performed sentinel node biopsy in
breast cancer patients. Slightly more than half of them
routinely used preoperative lymphoscintigraphy.
648
Dr. Waddington from London demonstrated the value
of dynamic imaging in patients with breast cancer. Dr.
Glass (Santa Monica), Professor Ell (London) and Dr.
Uren (Sydney) presided over a well-attended “Meet the
nuclear medicine professor” session. All three recom-
mended massaging of the injection site to speed up tracer
clearance from that site. Dr. Glass also uses heat and ex-
ercise to speed up the lymph flow. Dr. Uren recommend-
ed the use of a super-high-resolution collimator. Oblique
views and views with the breast taped medially or with
the breast hanging down help delineate sentinel nodes in
the axilla. Use of the probe facilitates placement of a
skin mark in the axilla.
What about the indications for lymphatic mapping in
breast cancer? Was there agreement on the patient
groups in which this can be done? It remains uncertain
whether sentinel node biopsy can reliably be done after
excisional biopsy and in patients with multicentric le-
sions. A prior excisional biopsy did not have a negative
impact on sentinel node biopsy results in a study by Dr.
Van der Ent, but did limit the identification in a study by
Dr. Kuehn: 97% versus 84%. A Swedish multicentre
study showed that a high S-phase fraction and tumour
multicentricity increase the false-negative rate threefold.
In contrast to this observation, a study from Linz in Aus-
tria revealed a sensitivity of 100% in 19 patients with
multicentric carcinomas. Several presenters stated that
sentinel node biopsy can reliably be done in patients
with non-palpable tumours using radiographic or ultra-
sound-guided tracer administration.
Studies from Tampa and Paris showed that obesity
hampers sentinel node identification. A Belgian study
showed that the detection rate is lower in fatty breasts as
compared to more glandular breasts. Dr. Nogaret from
Brussels advocated that sentinel node biopsy should not
be done in the presence of a grade III primary lesion.
The false-negative rate in these patients was 17%. Dr.
Schwartzberg from Denver showed encouraging results
of lymphatic mapping after neoadjuvant chemotherapy:
a 93% detection rate and one false-negative biopsy in
15 patients. Prior radiotherapy is associated with a high
failure rate. Dr. Beitsch from Dallas confirmed earlier
observations that some 10% of patients with ductal carci-
noma in situ have a tumour-involved sentinel node.
Whether this is enough to recommend sentinel node bi-
opsy for this indication was considered questionable in a
discussion on the subject. Experts like Dr. Giuliano and
Dr. Ross advised against it.
Dr. Giuliano, Dr. Cox, Dr. Hansen and Dr. Wu (Amer-
ican National Cancer Institute) cautioned that routine ax-
illary lymph node dissection should not be abandoned
too hastily because lymphatic mapping has not yet been
compared to the time-tested standard of complete node
dissection in clinical trials designed to assess cancer re-
currences and survival. Dr. Zurrida showed that no axil-
lary recurrences had occurred in his patients when the
sentinel node was free of disease and no axillary node
dissection was done. However, the average follow-up
was less than a year. A number of similar studies are in
progress. Dr. Morrow faced the difficult task of explain-
ing why sentinel node biopsy will not replace axillary
node dissection. She, too, pointed out that long-term fol-
low-up data on risk of axillary recurrence and success of
salvage surgery are lacking. She also questioned whether
lymphatic mapping teams in community hospitals can
duplicate the success rates reported by high-volume
teams. Five representatives from community hospitals
presented their data at the meeting: The sentinel node
identification rate ranged from 90% to 99% and the
false-negative rate ranged from 0% to 10%.
Dr. Bergkvist reported the results of the Swedish
multicentre study, which show that 26% of the sentinel
nodes are only radioactive and that 8% are only blue. Dr.
Fougo from Oporto, Dr. Tsugawa from Kanazawa, Dr.
Kuehn from Ulm and Dr. Robin from Arlington Heights
also found that sentinel nodes can be “hot”, blue or both.
Dr. Bergkvist’s sound advice was that surgeons use both
blue dye and a gamma ray detection probe.
The injection technique is still a topic of considerable
debate. Should tracers be administered underneath the
areola, intradermally, subdermally, in the breast paren-
chyma, or around or into the tumour? Intratumoural in-
jection is gaining popularity but, for reasons unclear to
us, only in patients with non-palpable primary tumours.
A study by Dr. Martin (Memorial Sloan Kettering Can-
cer Center, New York) compared intradermal and intra-
parenchymal administration in 298 patients. The sentinel
node was more frequently found with the intradermal
technique (98% vs 89%). The false-negative rate and the
sentinel node to background ratio were also better with
the intradermal injection technique. A number of other
studies comparing various injection sites suggest that the
correct node in the axilla is identified no matter where
the tracer is administered in the breast. Only one investi-
gator found more false-negative procedures with superfi-
cial administration (33%) than with deep administration
(17%).
Superficially administered tracers do not identify sen-
tinel nodes outside the axilla. Dr. Van der Ent and Dr.
Tanis from the Netherlands showed that extra-axillary
sentinel nodes are encountered in some 25% of patients
when using a peri- or intratumoural injection technique.
They can be located in the internal mammary chain, in
the breast parenchyma, in between the pectoralis muscles
and in the supraclavicular fossa, and can be removed
without undue morbidity. Harvesting such nodes modi-
fied the treatment plan in 24% of the patients. Pursuit of
sentinel nodes outside the axilla and a more detailed
pathological evaluation enable more accurate staging in
addition to sparing patients an unnecessary axillary node
dissection. Several other investigators reported seeing in-
ternal mammary sentinel nodes on lymphoscintigraphy
images and removing these occasionally with no or mini-
mal morbidity.
European Journal of Nuclear Medicine Vol. 28, No. 5, May 2001

Other cancers
Encouraging results were reported in squamous cell car-
cinoma of the head and neck, papillary thyroid cancer,
Merkel cell carcinoma, penile cancer and carcinoma of
the vulva and cervix. Professor Ell demonstrated the nee-
dleless tracer administration technique, which appears
applicable in a number of these categories. Lymphatic
mapping in cancers of the gastrointestinal tract was the
big news. Dr. Bilchik from the John Wayne Cancer Cen-
ter in Santa Monica showed that sentinel node biopsy
can be successfully performed in patients with cancer of
the pancreas, small bowel or colon and in patients with
carcinoid. The false-negative rate was 11%. Twenty-
three percent of the patients were classified in a higher
stage just because of the histological findings in the
sentinel node. This information can be used to select
patients for adjuvant chemotherapy. Aberrant drainage
occurs in some instances and may modify the extent of
the operation.
Dr. Saha shared his experience with lymphatic map-
ping in 203 patients with colorectal cancer. The sentinel
node(s) were found in all except five patients. The pres-
ence or absence of nodal metastasis was accurately de-
termined in more than 96% of cases. This was good
news after the disappointing results in this disease that
had been reported at the First Sentinel Node Conference
in Amsterdam [2, 3]. Preliminary results were presented
in malignancies of the oesophagus and anus.
Impressive “high tech” presentations about lymphatic
mapping in gastric cancer were given by Drs. Aikou,
Fujimura and Kitigawa. Each of these representatives
from Japan presented results in series of more than 100 pa-
tients. In some cases lymphoscintigraphy was performed
European Journal of Nuclear Medicine Vol. 28, No. 5, May 2001
649
after endoscopic administration of the tracer. Despite the
obvious fact that the technique needs to be refined, intra-
operative sentinel node localisation was successful in
some 90% of the patients, with a sensitivity of around
90% as well. The tumour status of the sentinel lymph
node can guide the extent of gastric resection.
Concluding remarks
The technique that is best used for lymphatic mapping is
well established in melanoma but not in breast cancer.
We are waiting for the results of the large randomised
studies in both these diseases. Gastrointestinal cancer is
the main new focus.
Lymphatic mapping is quickly gaining momentum. A
third international sentinel node conference seems to be
appropriate. It will be held in Yokohama in the fall of
2002, co-hosted by Drs. Fujimura from Kanazawa Uni-
versity and Thompson from The Sydney Melanoma
Unit.
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in colon cancer [abstract]. Eur J Nucl Med 1999; 26 Suppl:S63.
3. Joosten JJ, Strobbe LJ, Wauters CA, Pruszczynski M, Wobbes
T, Ruers TJ. Intraoperative lymphatic mapping and the sentinel
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