This document discusses radioguided surgery for thyroid cancer. It begins by introducing radioguided surgery as a technique used for recurrent or residual thyroid cancer when initial treatment is incomplete. It then discusses various radiopharmaceuticals that can be used for radioguided surgery depending on the type of thyroid cancer, including I-131 for differentiated thyroid cancer and MIBI for non-functioning thyroid cancer. The document provides details on protocols for radioguided surgery using I-131 and I-123, and discusses how the gamma probe is used intraoperatively to detect cancer foci not seen on other imaging and to verify complete resection. Studies are cited that found radioguided surgery was decisive in localizing

1. Cirugía Radioguiada en Cáncer
de Tiroides
Dr. José Ferrer Rebolleda
Servicio de Medicina Nuclear ERESA
Hospital General Universitario de Valencia

2. Introducción
• A pesar de un tratamiento completo inicial (Qx
+I131), del 5 al 20% de los pacientes con
tumores diferenciados y cerca del 50% de los
pacientes con carcinoma medular de tiroides
presentan enfermedad residual o recurrencia.
• Cirugía /I131/ RT.
• Los principales objetivos deberían ser evitar las
recurrencias y conseguir una buena calidad de
vida.
publications regarding the effectiveness and safety of the
central neck dissection for thyroid cancer.
Therapeutic versus prophylactic=elective
central neck dissection
A therapeutic central compartment neck dissection
implies that nodal metastasis is apparent clinically (preoper-
atively or intraoperatively) or by imaging (clinically N1a).
A prophylactic=elective central compartment dissection
implies nodal metastasis is not detected clinically or by im-
aging (clinically N0). The importance of this distinction when
reporting results from studies cannot be overemphasized as
the impact of clinically detectable nodal metastasis may differ
from microscopic pathologic nodal metastasis. Prophylactic
dissection is synonymous with elective dissection.
Describing the extent of central neck dissection
At a minimum, central compartment neck dissection
should include the prelaryngeal, pretracheal, and at least one
paratracheal lymph node basin. Lymph node ‘‘plucking’’ or
‘‘berry picking’’ implies removal only of the clinically in-
volved nodes rather than a complete nodal group within
the compartment and is not synonymous with a selective
compartment-oriented dissection. Isolated removal of only
FIG. 3. Detailed anterior view of the central neck compartment indicating locations of lymph node basins relevant to central
neck dissection for thyroid carcinoma.
CONSENSUS CENTRAL NECK 1157

3. • En general las recurrencias son el resultado de un
tratamiento inicial incompleto, o de tumores
particularmente agresivos y generalmente aparecen
en el seguimiento precoz.
• Las metástasis ganglionares son las más frecuentes
• Pacientes < 16 años y >45, pacientes con tumores
>3 cm, aquellos con rotura capsular y aquellos con
metástasis ganglionares múltiples y bilaterales,
tienen mayor riesgo de desarrollar recurrencias
locorregionales.
17. Sentinel Lymph Node Biopsy in Thyroid Cancer
boring metastases from DTC, but may contain metastatic
disease when the primary site involved is the lip, buccal
mucosa, anterior nasal cavity, or soft tissue of the cheek
(12,14).
Level II extends from the base of the skull to the
carotid bifurcation or the caudal border of the body of
the hyoid bone. It contains the upper jugular lymph
nodes located around the upper one-third of the internal
jugular vein and the upper spinal accessory nerve (level
IIa), and posteriorly to the spinal accessory nerve
(level IIb). These nodes are at greatest risk of harboring
metastases from cancers of the nasal cavity, oral cavity,
nasopharynx, oropharynx, hypopharynx, larynx, and
the major salivary glands (12).
Level III is the caudal extension of level II and con-
tains the middle jugular lymph node group, including the
jugulo-omohyoid nodes, located around the middle third
of the inte
nodes at
metastase
oropharyn
Level IV
the clavicl
surroundi
It has a va
lymphatic
ing lymp
thyroid gl
ing metast
and cervic
Levels
contained
referred to
composed
spinal acc
and the s
the drain
tumors (9
Level V
partment,
nodes, th
thyroidal
recurrent
connectin
the spread
ommende
thyroid ca
I II
IIIVI
V
IV
Figure 17-1. The level system most widely used to describe the
location of lymph nodes in the neck. (Robbins et al. [14], by
permission from Elsevier.)
Table 17-1. Lymph nodes groups located within each level of
the neck.
Level Lymph Node Group
Ia Submental nodes
Ib Submandibular nodes
Iia Upper jugular nodes, anterior to spinal accessory nerve
Iib Upper jugular nodes, posterior to spinal accessory nerve
III Middle jugular nodes
IV Lower jugular nodes
Va Posterior triangle nodes (spinal accessory group)
Vb Posterior triangle nodes (supraclavicular group)
VI Central compartment lymph nodes
Source: Robbins et al. (12), by permission from Elsevier.
Figure 17-2
(Robbins e

4. Pruebas de imagen en cirugía de
recurrencias del Ca de tiroides
Pruebas morfológicas
– Ecografía
– RM
– TC
• Dificultad de interpretación
• Anatomía alterada
• Limitada capacidad de
distinguir entre tejido tumoral
viable o áreas cicatriciales,
diferenciar si ganglios
aumentados de tamaño son
o no malignos, y dificultad de
detectar focos cancerígenos
si son de tamaño inferior a 1
cm.
Pruebas funcionales
• Mala sensibilidad
• Baja resolución espacial en
gammacámara
• Mejor resolución en PET pero
h a b i t u a l m e n te e s c a s a
captación de 18F-FDG
• No es posible la valoración de
la enfermedad microscópica
Figure 12. Thyroglossal duct cyst in a 3-year-old boy. Sagittal (a) and coronal (b) T2-weighted
MR images show a hyperintense midline cystic mass of the foramen cecum (arrow).
940 July-August 2005 RG f Volume 25 ● Number 4
RadioGraphics
5. BIBLIOTECA DE IMÁGENES
– En el rastreo de la primera dosis ablativa es normal detectar
restos cervicales solamente, pues aunque existan metásta-
sis, la intensa captación relativa del trazador por los restos de
tejido tiroideo, impide su objetivación en muchas ocasiones
Manual básico para residentes. Medicina Nuclear
TERAPIAMETABÓLICA
(327-352) Terapia metabólica.qxp 23/05/2008 20:55 Página 330
Staging of thyroid cancer: remnant or m

5. Radiofármacos para Cirugía
Radioguiada en Cáncer de Tiroides
• Carcinoma diferenciado de tiroides
– 131I
– 123I
• Carcinoma de tiroides no funcionante
– 99mTc-MIBI
– 18F-FDG
• Carcinoma medular de tiroides
– 111In-pentetreotido
– 99mTc-DMSA (V)
– Acs monoclonales
• ROLL/Ganglio Centinela
– 99mTc-MAA
– 99mTc-Nanocoloides

6. I-131
scanner with a high-energy collimator for precise ana-
tomical localization of each focus of uptake. In spite of
its limitations, the rectilinear scanner has the advantage
of producing a life-size image of the neck and permitting
precise localization of recurrent or residual functioning
thyroid disease (Figure 26-2). The whole-body scan pro-
vides accurate localization of well-known functional
sites or embedded in sclerosis. Guided according to the
131
I spot view of the neck obtained during the whole-
body scan, the patient’s neck is scanned with the probe
to localize the cutaneous projection of the radioiodine
focal uptake sites. During surgery, the probe is placed in
direct contact with any suspect tumor site and also is
used to search any other area demonstrating a high
lesion-to-background count ratio. Activities in the main
vessels (aorta) and in normal soft tissues are used as
background values. After nodes are removed, radioactiv-
ity is also measured in the lesion bed looking for any
residual activity of the tracer to verify the completeness
of resection. The protocol is completed after 7 days,
when a postoperative neck scan is performed, using the
remaining radioactivity to verify the completeness of the
surgical resection.
Salvatori et al. only minimally modified this protocol,
performing the presurgery whole-body scan 3 days after
131
I administration (instead of 4 days) when the patients
were discharged from isolation because the radiation
exposure rate was >30 µSv/hr at 1 m (11).
Travagli et al. (8) considered radioguided surgery deci-
sive in 20 of 54 patients, revealing neoplastic foci either
inside the postoperative scar (n = 9), at unusual sites
behind vessels or in the mediastinum (n = 10), or both
(n = 1). The probe facilitated the intraoperative detection
RGS
0
131I
(3.7 GBq)
TSH > 30mU/ml
1
RGS: radioguided surgery with intraoperative gamma probe
WBS: highly sensitive whole body scan
2 3 4 5 6 7
days
Post-RGS
WBS/neck scan
Pre-RGS
WBS/neck scan
Figure 26-1. Design of the protocol for radioguided surgery
of lymph node metastases adopted at the Institut Gustave
Roussy, Villejuif, France.
!"#$%!%&'%$()*+,-%(
ients with Thyroid Cancer 271
nclusion in
s (mean, 5
d 14 to 60
alvatori et
e radiogu-
Gustave-
s, ranging
d/or treat-
n inclusion
al. was the
ne-positive
dine treat-
e of lymph
neck and
nd detect-
(8) takes
ypothyroid
t is, a full
H >30 µIU/
Figure 26-2. Preoperative (A) and postoperative (B) scans of
the neck (obtained with a rectilinear scanner) in a patient
submitted to radioguided surgery after iodine 131
I administra-
tion (3.7 GBq) for functioning lymph node metastases. (Salva-
tori et al. 2003 [11], by permission.)
Pacientes en deprivación hormonal
Marcaje cervical de lesiones
Sonda de detección gamma
Decisiva en 20 de 54 pacientes
- 9 focos en cicatriz
- 10 en localizaciones inusuales (retrovasculares,
mediastino) y en ambos (1)
En 26 pacientes focos adicionales de I131 no presentes en el
estudio preoperatorio
El estudio postoperatorio confirmó excisión completa en 46
pacientes (26+20).
La dosis de radiación recibida por el cirujano fue equivalente
a 3 días de exposición a radiación natural en Europa.
Ratios lesión/fondo entre 1.4 y 25.8 (lippi)
No incremento del tiempo quirúrgico 102 (60-180 minutos)
(Salvatori)
Travagli JP, et al. J Clin Endocrinol Metab. 1998; 83: 2675–2860.
Lippi F, et al. Tumori. 2000;86:367– 369.
Salvatori M et al. World J Surg. 2003; 27: 770–75.
Carcinoma diferenciado de tiroides

7. I-123
• Protocolos diversos:
– Oral 37 MBq 18 h antes de la cirugía
– Inyección iv 74MBq 4 horas antes de la cirugía
• Su uso es factible, su vida media permite un
periodo de utilización de 12 a 24 horas por lo
que es flexible de cara a una programación
quirúrgica.
• Las características físicas se acoplan mejor a la
detección por sonda gamma y disminuye la
exposición a radiaciones del paciente y del
cirujano.
Gallowitsh HJ, et al. Clin Nucl Med. 1997;22:591–2.
Gulec SA, et al. Clin Nucl Med. 2002;12:859–61.
Carcinoma diferenciado de tiroides

8. 99mTc-MIBI
ss
ul
n-
ly,
as
ci-
e-
or
u-
nt,
er,
y-
a-
%
ce
on
a
ms
ch
a-
as-
e-
ts
ur-
a-
u-
nt-
ss-
es
ly
er-
ri-
o-
ul-
findings suspicious of neoplastic/metastatic disease in a
lymph node of the left lateral-cervical compartment (14 mm
Figure 1. Neck USG image showing a pathological round-shaped
lymph node 14 mm in diameter. Note the absence of
hyperechoic hilus and the hypervascularization in the color
Doppler examination (A). Planar image (magnification:
2×, matrix: 128×128) of the cervical and thoracic regions
(anterior views) performed ten minutes after intravenous
administration of 185 MBq (5 mCi) of 99m
Tc-MIBI (B). MIBI
scan showed abnormal and very intense uptake in the left
cervical region corresponding to the lymph node detected
by USG, thus confirming the presence of a metastatic focus.
A
B
5 mCi 99mTc-MIBI
2 horas antes de la cirugía
El procedimiento
mínimamente invasivo
permite:
-reducir posibilidades de
complicaciones
- D e te c t a r m e t á s t a s i s
ganglionares incluso no vistas
por técnicas convencionales
- Verificar resección completa
The patient was followed-up at our unit for five years, dur-
ing which thyroid function tests (FT3, FT4, and TSH) were
regularly performed to check the adequacy of the L-T4 sup-
pressive therapy. The follow-up was based on physical ex-
amination, neck USG, and both basal and recombinant hu-
man TSH (rhTSH)-stimulated serum Tg measurement as
well as Ab-Tg measurement. At the last follow-up, five years
following RGS and radioiodine therapy, there was no evi-
dence of disease.
DISCUSSION
Microcarcinomas or occult papillary carcinomas of less than
10 mm in diameter which are virtually undetectable by con-
ventional diagnostic methods and occur as lateral cervical
tumors as the first and sole manifestation in almost 5% of
cases [7–9]. In many cases, the primary thyroid tumor may
also be undetectable intra-operatively because such a micro-
scopic lesion might be missed on routine microscopic sec-
tion or step sections of the entire gland during pathological
examination [12]. Our case report supports prior studies
on large series [7–9,13–17] that suggest that the presence
of malignant thyroid tissue within a cervical lymph node
may be predictive of an undetected primary thyroid malig-
nancy and confirm that any lateral mass requires a careful
evaluation and tissue diagnosis.
Echographic examination is the most useful diagnostic tool
for the study of a mass in the neck and also allows perfor-
mance of FNA cytology [18,19]. With regard to the useful-
ness of FNA in diagnosing lymph node metastases, Baskin et
al. [20] reported their results on 74 PTC patients screened
with USG and Tg measurement during their postopera-
tive follow-up. USG revealed findings suspicious of recur-
rent disease in the lymph nodes of the neck in 21 patients.
Ultrasound-guided FNA to obtain material for cytology and
Tg analysis was done on these 21 patients, 7 of whom tested
positive for Tg in their needle washout. Only 3 of the 7 had
Figure 2. Regional neck lymph node with metastasis of a papillary
thyroid carcinoma. In macroscopic examination the lymph
node size was 15 mm (maximum longitudinal diameter)
(A). In histological examination the pattern of the
metastasis is a mix of both follicular and papillary features
(B).The cortex contains aggregates of follicles lined by cells
with clear nuclei (upper right) associated with short and
stubby papillae projecting into a cystic cavity (lower left).
A lymph node capsule is observed (below). (hematoxylin-
eosin (H&E) stain, original magnification: 130×).
A
B
Campennì A et al – Radio-guided surgery of lymph node metastasis from occult…
Carcinoma de tiroides no funcionante
Campenni et al. Am J Case Rep 2009: 10:

9. F18-FDG SONDA PET
• La detección con Sonda PET depende de:
– Avidez de la neoplasia por el radiofármaco (F18-FDG)
– Tiempo transcurrido desde la inyección
– Localización anatómica de la lesión (ojo también a falsos
positivos por cambios inflamatorios)
– Propiedades técnicas de la sonda
• Ventajas:
– Es útil para detectar ganglios linfáticos localizados en
ecografía incluso en algunos casos con estudio PET
negativo.
– Especialmente útil en la valoración de áreas cicatriciales
– Método intraquirúrgico de valoración de resección
completa
Carcinoma de tiroides no funcionante

10. Fig 1. (A) Ultrasonography showed a single suspicious recurrent metastatic lymph node in the right, uppermost medi-
astinal area. WBS showed faint iodine uptake in the thyroid bed without uptake in the mediastinal area (WBS-negative,
B). 18
F-FDG PET/CT revealed single focal uptake in the right uppermost mediastinal lymph node, with malignant tissue
more likely (PET positive, C). Additional, nonpalpable metastatic lymph nodes were not revealed by 18
F-FDG PET and
neck ultrasonography in the deep superior mediastinum, but were detected by the PET probe (PET probe-positive).
(Color version of figure is available online.)
Surgery
Volume 149, Number 3
Kim et al 421
12 pacientes con CDT (papilar) diagnosticados por PAAF ecoguiada
4 Estudios de extensión
8 Sospechas de recurrencia
F18-FDG (363 MBq de media). No deprivación hormonal ni TSH recombinante
PET basal una hora postinyección
Cirugía con sonda PET
Lesión/Fondo Ratio >1.3 considerado positivo
Prolongación tiempo de cirugía: 10 minutos
En 7 pacientes sin hallazgos en PET detectó la
lesión
The ability of a PET probe to detect a lesion
depends on numerous factors: these include the
the
dec
by P
pati
6 h
time
to 3
diag
pati
A
ing
bee
tion
that
Table III. Sensitivity, specificity, false positive and
false negative rate of PET probe
T/B ratio >1.3 T/B ratio <1.3
Metastasis (+) 46 9
Metastasis (À) 3 109
Sensitivity: 46/55 (84%).
Specificity: 109/112 (97%).
Positive predictive value: 46/49 (94%).
Negative predictive value: 109/118 (92%).
False positive error rate: 3/112 (3%).
False negative error rate: 9/55 (16%).
422 Kim et al
Kim WW et al. Surgery 2011; 149 (3): 416-24.

11. • TNE de origen en las células parafoliculares.
• 5-10% de neoplasias tiroideas
• La detección intraoperatoria de recurrencias
se ha intentado con:
– 123I-MIBG
– 99mTc-V- DMSA
– 111In-pentetreotide
– 111In-Anticuerpos monoclonales
Carcinoma medular de tiroides

12. 111In-pentetreotide 99mTc-V-DMSA
mediastinum exceeded 2 cm in greatest dimension
(Figs. 1a,b, 2).
Preoperative 123
I-MIBG scintigraphy correctly
identified four lesions of metastasizing pheochromo-
cytoma located in the paravertebral subdiaphragmatic
region. Receptor imaging of the female patient with
the MEN II syndrome demonstrated a somatostatin
receptor positive pheochromocytoma of the right ad-
renal gland (MIBG negative). By comparison, CT scans
provided no new information.
Intraoperative Tumor Localization
Surgical palpation identified lymph node metastases
of recurrent MTC with a sensitivity of 65%. By com-
parison, intraoperative radiodetection using the Tec
Probe 2000 localized 64 malignant lesions (sensitivity,
97%). The ␥-probe counting was unable to localize two
e1
]-
ation of
igraphic
ngs
d; um: upper
compartment;
e.
TABLE 3
Comparison of Histologically Proven Lesions Detected by
Preoperative Metabolic/Receptor Imaging, Computed
Tomography, Standard Surgical Exploration, and
Intraoperative ␥-Probe Localization
Method Sensitivity (%)
Computed tomography 21 (32)
111
In-pentetreotide 23 (34)
99m
Tc(V)-DMSA 43 (65)
Palpation 43 (65)
Radioguided surgery 64 (97)
99m
Tc(V)-DMSA: technetium 99m(V)-dimercaptosuccinic acid; 111
In-pentetreotide: [indium 111-
DTPA-D-Phe1
]-pentetreotide.
Radioguided Surgery in Neuroendocrine Tumors/Adams et al. 267
FIGURE 2. Metastasis of medullary thyroid carcinoma identified by intraop-
268 CANCER July 15, 2001 / Volume 92 / Number 2
lesions (size Ն 2 cm) of recurrent pheochromocytoma
seen in the preoperative MIBG scan. Using [111
In-DTPA-
D-Phe1
]-pentetreotide or 123
I-MIBG, tumor-to-back-
ground count ratios of 1.5:1.0 were obtained in all pa-
tients in the localization of primary (female patient with
MEN II syndrome) or recurrent pheochromocytoma.
DISCUSSION
The biologic behavior of MTC generally is regarded as
intermediate between anaplastic and differentiated
thyroid carcinomas.20
The tumor marker CEA has
been suggested for evaluating the prognosis of pa-
FIGURE 2. Metastasis of medullary thyroid carcinoma identified by intraop-
erative radiodetection using the hand-held ␥-detecting probe (not palpated by
the surgeon; size, 2 cm).
Š
FIGURE 1. (a) Somatostatin receptor scintigraphy (anterior planar view of the
thorax; 24 hours after injection) of a patient with recurrent medullary thyroid
carcinoma located in the middle mediastinum (arrow). (b) In comparison,
whole-body scan using technetium 99m(V)-dimercaptosuccinic acid (left, an-
terior view; right, posterior view; 4 hours after injection) demonstrated no tumor
involvement.
268 CANCER July 15, 2001 / Volume 92 / Number 2
Carcinoma medular de tiroides
25 pacientes con sospecha de
recurrencia de CMT
Uso de uno u otro RF según el estudio
preoperatorio
De 71 lesiones extirpadas solo hubo 3
FP (linfadenitis)
En CRG guiada por 99mTc-V-DMSA se
detectaron metástasis de CMT que
medían 5 mm o más, mientras que la
palpación en quirófano solo detectó
aquellas mayores a 1 cm
Los ratios lesión/fondo fueron mayores
en el caso del 99mTc-V-DMSA
Adams S, et al. Cancer. 2001;92:263–70.

13. Ganglio Centinela en Cáncer de tiroides
• El drenaje linfático del tiroides es amplio
• Los vasos linfoides superiores drenan el istmo y la porción medial superior de los
lóbulos tiroideos, ascienden por la laringe y terminan en los ganglios subdigástricos
de la cadena yugular interna.
• Los vasos linfaticos medios, drenan a los ganglios pretraqueales
• Los vasos linfáticos laterales drenan superiormente a los ganglios anteriores y
superiores de la cadena yugular e inferiormente a los ganglios laterales e inferiores
de la cadena yugular.
• El compartimento central (VI) está afecto en el 90% de pacientes con N+, después
los más frecuentes son compartimentos cervicolaterales (III y IV), y el
supraclavicular.
• La afectación contralateral si el tumor es unilateral aparece hasta en el 18% de los
casos e incluso no es extraordinaria la afectación mediastínica (anterosuperior).
• La distribución de la afectación metastásica ganglionar no se relaciona con la
localización del tumor dentro del tiroides, pero en los localizados en tercio superior
se afectan los ganglios subdigástricos y los tumores del istmo suelen causar
afectación cervical bilateral o contralateral.
Thyroid 119
or mediastinal vessels. Cross-sectional diagram of two different parameters of T4b: tumor encases carotid artery;
tumor invades vertebral body.
FIGURE 8.7. N1a is defined as metastasis to Level VI (pretracheal, paratracheal, and prelaryngeal/Delphian lymph
nodes).
119
120 American Joint Committee on Cancer • 2012
FIGURE 8.8. N1b is defined as metastasis to unilateral, bilateral, or contralateral cervical (Levels I, II, III, IV, or V) or
retropharyngeal or superior mediastinal lymph nodes (Level VII).
PROGNOSTIC FACTORS (SITE-SPECIFIC FACTORS)
(Recommended for Collection)
Required for staging None
Clinically significant Extrathyroid extension
Histology
120

14. • El tratamiento quirúrgico estándar incluye:
• Linfadenectomía compartimento central (VI) profiláctica a todos los pacientes
• Linfadenectomia radical modificada ipsilateral en pacientes con ganglios en el compartimento
central, tumores grandes, especialmente en carcinomas medulares de asociación familiar
• Linfadenectomia radical modificada bilateral en pacientes con metástasis ganglionares
bilaterales histológicamente probadas
• Linfadenectomía ipsi o bilateral en aquellos pacientes tiroidectomizados, N0, con elevación o
persistencia de elevación de marcadores tumorales (tiroglobulina o calcitonina)
Pero…
La afectación ganglionar tiene poca influencia en la supervivencia de los
pacientes y la presencia de metástasis ganglionares al inicio no se asocia
con un descenso de la tasa de supervivencia de los pacientes.
Aunque si se relaciona con la aparición de recurrencias locorregionales. Y
además la afectación extracapsular de la metástasis ganglionar si se asocia
con metástasis a distancia y con peor pronóstico de los pacientes.
Ganglio Centinela en Cáncer de tiroides

15. • Ventajas:
– Permite seleccionar pacientes que se beneficiarían de una
linfadenectomía orientada, disminuyendo cirugía innecesaria y
reduciendo morbilidad
– Identifica enfermedad metastásica, proporcionando un método
racional para decidir la terapia con I131
– Identifica metástasis ganglionares fuera del compartimento central,
permitiendo una aproximación más selectiva a la extensión de la
linfadenectomía fuera de dicho compartimento
• Inconvenientes:
– Incierto significado pronóstico de la afectación ganglionar
metastásica (lo que haría esta técnica innecesaria)
– Baja sensibilidad de detección de micrometástasis.
– Elevadas tasas de falsos negativos en algunas series, drenajes
múltiples,…
Ganglio Centinela en Cáncer de tiroides
180 M. Salvatori et al.
Tsugawa et al. (40) examined the feasibility of sentinel
lymph node biopsy for thyroid cancer using patent blue
dye in 38 patients with papillary thyroid carcinoma. Sen-
tinel lymph node biopsy removed 1 to 3 lymph nodes
(median: 2 nodes). Histologic nodal metastasis was
observed in 16 of 27 cases (71%), and the positive rate
of cancer metastases in the sentinel node was 58%, which
was significantly higher than the 11% value in nonsenti-
nel lymph nodes. Sensitivity was 84%, specificity 100%,
and diagnostic accuracy 89%.
In a study by Nakano et al. (42), 32 patients were exam-
ined using intraoperative injection around the tumor of
1% isosulfan blue dye, and 23 patients by 1-day preopera-
tive 99m
Tc-colloid injection. In the first method, the senti-
nel lymph node was identified in 30 (94%) of the 32
patients. Lymph node mapping for detection of sentinel
nodes was performed after thyroidectomy, and central
and modified lateral neck lymph node dissections. All
dissected nodes were then examined postoperatively by
hematoxylin and eosin staining to determine whether
metastasis was present. This method identified sentinel
lymph nodes in 30 (94%) of the 32 patients. Lymph node
metastases were found in 14 patients, and some sentinel
nodes had papillary cancer metastasis in 13 patients.
There was only 1 false-negative case. The sensitivity and
accuracy of sentinel lymph node biopsy was 93% and
97%. With the radiotracer method, detection rate, sensi-
tivity, and accuracy of sentinel lymph node biopsy were
96% (22/23), 90% (9/10) and 95% (21/22), respectively.
In the Chow and colleagues (55) series examining 15
consecutive papillary thyroid cancer patients undergoing
sentinel lymph node dissection, sentinel nodes were traced
in 10 patients, and most were located in the central com-
partment. The overall accuracy of the sentinel lymph node
in predicting nodal status was 90%. The sensitivity, speci-
ficity, positive predictive value, and negative predictive
value were 88%, 100%, 100%, and 67%, respectively.
In the study reported by Stoeckli et al. involving 10
patients with uninodular thyroid disease and clinically
negative lymph node status (46), the overall detection of
sentinel lymph nodes was 50% with lymphoscintigraphy
and 100% with the gamma probe. The sentinel lymph
node was located in the ipsilateral central compartment
(level VI) in 50% of the cases, and in the ipsilateral
lateral compartment in the remaining 50% (level IV and
II). Since a patient experienced a temporary lesion of the
recurrent laryngeal nerve during sentinel lymph node
dissection, the authors concluded that a search for senti-
nel nodes in the lower central compartment enhances the
risk of injury to this nerve.
Rettenbacher and colleagues (48) identified sentinel
lymph nodes (1 to 4 per patient) in 7 of 9 patients, includ-
ing all 4 patients with papillary thyroid cancer (see Figure
17-3). In 1 patient, no sentinel lymph node was visible
with lymphoscintigraphy, but at surgery 3 sentinel lymph
nodes were clearly identified using the gamma probe
after removal of the primary tumor. There were no false-
negative findings.
Table 17-4 summarizes the sensitivity, specificity, and
diagnostic accuracy for sentinel lymph node dissection
in thyroid cancer reported in the literature (39–45, 48).
RAO 5min p.i. RAO 18h p.i.
Figure 17-3. Right anterior-oblique (RAO) lymphoscinti-
graphic images obtained 5 minutes (left) and 18 hours (right)
postinjection (P.I.), showing 2 sentinel lymph nodes in the
medial jugular region (thick arrow) and 1 sentinel node in the
lower jugular region (thin arrow). Injection site is covered with
a lead sheet. (Rettenbacher et al. [48], by permission.)

16. Ganglio Centinela en Cáncer de tiroides
24 Pacientes
CDT (Papilar)
Inyección intratumoral ecoguiada
148 MBq 99mTc-Nanocoloides
0,1-0,2 ml
Imágenes planares y SPECT-CT 2-4 h postiny.
Sonda de detección gamma
Inicio de cirugía con tiroidectomía
Todos LD compartimento central
LD lateral en:
- pacientes con GC+ lateral
- estadio N1b preoperatorio of each SLN was included in the image, so that during surger
the surgeon had information not only about the number an
location of the SLNs, but also had data on the relative activit
of each SLN compared with that of the SLN with the highes
ble 2 Patient-based results (n = 24): SLN, lymphadenectomy and
ratio
rameter Value
ainage, n (%) 23 (96)
mber of SLN
dentified
78
N per patient 3.25
mber of lymph
nodes excised
390
mber of lymph
nodes excised
per patient
16.25
mber of SLN,
n (%)
None 1 (4)
One 3 (12.5)
wo 4 (16.7)
hree or more 16 (66.7)
ients with positive
SLNs, n (%)a
10 (41.7)
ients with positive SLNsa
or lymphadenectomy, n (%)
13 (54.2)
nsitivity (%) 92
ecificity (%) 100
se-negative in relation
o final diagnosis, n (%)
Fig. 3 Lymphatic drainage per patient: central and laterocervical basi
distribution with percentage of SLN positivity in each basin. Lymphati
spread was detected in 13 of the 24 patients
48 Eur J Nucl Med Mol Imaging (2013) 40:1645–165
Garcia-Burillo et al. Eur J Nucl Med Mol Imag 2013; 40: 1645-55Statistical analysis
Data are summarized using the mean ± standard deviation for
24 patients, with a mean of 3.25 SLNs per patient. One SLN
was excised in 3 patients (12.5 %), two lymph nodes in 4
patients (16.7 %) and three or more SLNs in the remaining
Table 3 Lymphatic distribution,
with percentage of positivity in
each basin
a
One patient without SLN
detection
Compartment drainage Patients (n = 24)a
SLN
Total Positive Positive/total
Central 18 (75 %) 8 (44 %) 15/45 (33 %)
Lateral 17 (71 %) 5 (29 %) 8/33 (24 %)
Central only 6 (25 %) 3 (50 %) 4/13 (30.8 %)
Lateral only 5 (21 %) 2 (40 %) 5/14 (35.7 %)
Central and lateral 12 (50 %) 6 (50 %) 14/51 (27.5 %)
Eur J Nucl Med Mol Imaging (2013) 40:1645–1655 1649
Aumenta el estadio de pacientes
inicialmente N0 (12,5 a 16%)

17. excluded because of pregnancy (one patient), patient refusal
(two patients), tracheal invasion (one patient), and nonpapillary
lateral) and SPECT/CT tomographic images (Hawk-eye 4;
General Electric) were obtained 2 to 4 h after the injection.
Fig. 2 Planar and SPECT/CT
images in a patient with
laterocervical and central
compartment drainage.
Quantification of the activity of
the SLN in the images improves
the identification of true SLN
during surgery, avoiding errors
in lymph node removal. Six
SLN were removed during
surgery. One SLN in the central
compartment (420 counts) and
another in the upper
laterocervical basin (555
counts) are triangulated in the
SPECT/CT images

18. ROLL
year-old woman affected by papillary thyroid carcinoma (PTC) was referred to our center for an asymptomatic
m thyroglobulin (Tg) level 3.7 years after thyroidectomy and 131
I thyroid remnant ablation. A single enlarged
found in the central neck compartment by ultrasound (US) (A, arrow). A PTC metastasis was confirmed by US-guided
ation cytology with Tg measurement in needle washouts.1Y3
Additional metastases were excluded by neck US,
tinum MRI, and whole-body 18
F-FDGYPET/CT examinations, respectively.4,5
On the day before excision, 20 MBq
human serum albumin macroaggregates was injected within the lesion under real-time US control.6
SPECT/CT
of the neck and the mediastinum were done 2 hours later7,8
(B, C; arrows). The next day, the surgeon explored
intraoperative handheld probe (Navigator; RMD, Watertown, Massachusetts). Using SPECT/CT images as road
beled lesion was easily identified within few minutes and resected. After excision the background activity was
postexcision bed radioactivity to ensure the completeness of the procedures. The diagnosis of PTC metastasis
y histopathological examination (D). One month after surgery, both unstimulated and recombinant human
ulated serum Tg levels were undetectable, and neck US examination was negative for persistent or relapsing
tes carotid artery; J, jugular vein; T, trachea.
Clinical Nuclear Medicine & Volume 38, Number 4, April 2013
FIGURE 2. A 49-year-old man affected by PTC was referred to our center for an asymptomatic increase of serum
5.2 years after thyroidectomy and 131
I thyroid remnant ablation. A single lymph node metastasis was found in th
compartment by US (A, arrow) and then confirmed by US-guided fine-needle aspiration cytology and Tg measurem
washouts.1Y3
Additional metastases were excluded by neck US, neck and mediastinum MRI, and 18
F-FDGYPET/CT e
respectively.4,5
Combined radioguided occult lesion localization and SPECT/CT were performed as described above
After radioguided excision the diagnosis of PTC was confirmed by histopathological examination (D). One month a
both unstimulated and recombinant human thyrotropinYstimulated serum Tg levels were undetectable, and neck U
were negative for persistent or relapsing disease. C indicates carotid artery; J, jugular vein; T, trachea. In conclusion,
data prove that SPECT/CT is a simple and technically feasible additional tool to conventional preoperative planar
patients submitted to radioguided occult lesion localization surgery for thyroid cancer recurrences within the nec
Clinical Nuclear Medicine & Volume 38, Number 4, April 2013 SPECT/CT-Guided Resection o
49 años, CDT (Papilar) intervenido+I131. Elevación tiroglobulina.
Adenopatía infiltrativa yugular inferior derecha localizada en
ecografía. ROLL
41 años, CDT (Papilar) intervenido+I131. Elevación tiroglobulina.
Adenopatía infiltrativa en compartimento central localizada en
ecografía. ROLL 20 MBq 99mTc-MAA dia previo a la cirugía.
Giovanella L et al. Clin Nucl Med 2013;38: e207-e209

19. ROLLpillary thyroid cancer locoregional recurrences
Figure 1. Tyroid bed exploration with gamma probe (ima 1).
l diag-
s were
gery, a
center
abeled
jected.
or bi-
the lo-
ance of
gure 1).
o with
avia di
ution 2
ns and
Count
r exci-
of in-
d with
(imag-
equent
ment of
were in-
malig-
edures,
e to re-
of re-
nodes
ed and
are the
lesion.
ignifi-
andard
The study was approved by the Ethical Com-
mittee of the II School of Medicine and Surgery,
Sapienza University, Rome, Italy.
Results
The mean age of patients recruited was
43.27±14.8 years. Of them, 14 patients (63.3%)
were females. Demographic features of the popu-
lation under study are shown in Table I. In 41% of
patients, previous surgical procedures were total
thyroidectomy and sixth level lymphoadenectomy
while in the remaining 59% were total thyroidec-
tomy, sixth level lymphoadenctomy and functional
monolateral lymphoadenectomy. The mean surgi-
cal time was 30±10.82 minutes. All patients un-
derwent to 131
I therapy. The mean time between
surgery and the first locoregional lymph nodal
3363
Figure 1. Tyroid bed exploration with gamma probe (ima 1).
Figure 2. Lesion spatial localization with imaging probe (ima 2 + ima 3).
macroaggregate albumin in 0.2 mL was injected.
The injections were US-guided. A unilateral or bi-
lateral thyroid bed exploration was based on the lo-
cation of biopsy proven lesion with the guidance of
intraoperative gamma probe (Neoprobe) (Figure 1).
Intraoperative radioactivity was detected also with
imaging probe (IP, Li Tech Srl, Lauzacco-Pavia di
Udine, Italy, FOV 2.6 × 2.6 cm, spatial resolution 2
mm) for the spatial localization of the lesions and
the confirm of a radical excision (Figure 2). Count
rate for injected lesions and lesions bed after exci-
sion were recorded. The complete excision of in-
jected lesions was assessed and confirmed with
gamma probe and hand-held gamma camera (imag-
ing probe) before the end of surgery. Subsequent
follow up was performed with the measurement of
TG, US and 131
I WBS. The following data were in-
vestigate: age, gender, TNM classification of malig-
nant tumors (TNM), previous surgical procedures,
previous 131
I treatments, operating time, time to re-
currence, number of tracked nodes, number of re-
moved nodes, number of metastatic tracked nodes
removed, mean radioactive count of tumor bed and
lesion, morbidity.
Statistical Analysis
The Student’s t test was used to compare the
mean radioactive count of tumor bed and lesion.
A p-value les than 0.05 was considered signifi-
cant. Results are shown as mean value ± standard
deviation.
The study was approved by the Ethical Com-
mittee of the II School of Medicine and Surgery,
Sapienza University, Rome, Italy.
Results
The mean age of patients recruited was
43.27±14.8 years. Of them, 14 patients (63.3%)
were females. Demographic features of the popu-
lation under study are shown in Table I. In 41% of
patients, previous surgical procedures were total
thyroidectomy and sixth level lymphoadenectomy
while in the remaining 59% were total thyroidec-
tomy, sixth level lymphoadenctomy and functional
monolateral lymphoadenectomy. The mean surgi-
cal time was 30±10.82 minutes. All patients un-
derwent to 131
I therapy. The mean time between
surgery and the first locoregional lymph nodal
A B
3363
papillary thyroid cancer locoregional recurrences
Figure 1. Tyroid bed exploration with gamma probe (ima 1).
ging probe (ima 2 + ima 3).
gical diag-
tients were
f surgery, a
o the center
Tc labeled
as injected.
teral or bi-
d on the lo-
guidance of
(Figure 1).
d also with
co-Pavia di
esolution 2
lesions and
e 2). Count
after exci-
sion of in-
rmed with
mera (imag-
Subsequent
urement of
ata were in-
n of malig-
procedures,
time to re-
mber of re-
cked nodes
mor bed and
ompare the
and lesion.
ed signifi-
± standard
The study was approved by the Ethical Com-
mittee of the II School of Medicine and Surgery,
Sapienza University, Rome, Italy.
Results
The mean age of patients recruited was
43.27±14.8 years. Of them, 14 patients (63.3%)
were females. Demographic features of the popu-
lation under study are shown in Table I. In 41% of
patients, previous surgical procedures were total
thyroidectomy and sixth level lymphoadenectomy
while in the remaining 59% were total thyroidec-
tomy, sixth level lymphoadenctomy and functional
monolateral lymphoadenectomy. The mean surgi-
cal time was 30±10.82 minutes. All patients un-
derwent to 131
I therapy. The mean time between
surgery and the first locoregional lymph nodal
B
Radioguided surgery for papillary thyroid cancer locoregional recurrences
PTC recurrence was 27.9±12.4 months. In all pa-
tients, 39 pathologic nodes were injected and 61
cycles. As described in the literature, the preva-
lence of recurrent laryngeal nerve injury ranges
Value = 0
95% CI for difference
t df Differene of means Lower Upper
Lesions radioactivity 14.568 21 28633.273 24545.92 32720.63
Bed radioactivity 9.388 21 385.727 300.29 471.17
Table II. Comparison between mean lesion radioactivity count and mean bed radioactivity count.
22 Pacientes con sospecha de recurrencia
de CDT (Papilar)
Inyección ecoguiada de 20 MBq 99mTc-MAA
la mañana de la cirugía (0.2 ml)
Detección por sonda gamma y por
gammacámara portátil
Tiempo medio de cirugía 33 minutos (20-52)
Belloti C et al. Eur Rev Med Pharmacol Sci 2013; 17: 3362-66.

20. ROLL
41 años, Carcinoma medular de tiroides. Intervenida en varias
ocasiones. Elevación persitente calcitonina. Remanente tiroideo
ecográfico

21. Conclusiones
• La cirugía radioguiada en cáncer de tiroides, si
bien controvertida, presenta múltiples
aplicaciones potenciales.
• Son necesarios estudios que diriman
subgrupos de pacientes serían los más
beneficiados de las distintas técnicas.
• La creación de equipos de profesionales
multidisciplinares de alta resolución y el
desarrollo de la tecnología permitirá un
crecimiento de la misma.