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16 Radioguided Sentinel Lymph Node Mapping and Biopsy in Gynaecological Malignancies
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259
centres introduced the use of 125I seeds at the tip
of the laparoscopic probe [ 47 ], and the matching
of both hot spots ensures the placement of the
SLN, which is especially useful in endometrial
cancer due to the amount of fat tissue around the
lymphatic drainage pathways (Fig. 16.4 ).
While the main use is these imaging devices
are intraoperative, they can be used to acquire a
preoperative image in centres without conventional diagnostic gamma cameras [ 45 ] or as a
preparation for surgery, where deciding the best
view for SLN identifi cation can reduce the time
spent in the operating room.
16.3.2 Intraoperative SPECT (fhSPECT)
The most recent advance in radioguided surgery
is intraoperative SPECT, known as freehand
SPECT (fhSPECT), a device capable of creating
a three-dimensional image in a few minutes during a surgical procedure.
Freehand SPECT collects image projections of a
defi nite area of interest from different directions/
angles and reconstructs them into a 3D tomographic
image. The difference between freehand SPECT
and regular diagnostic SPECT is the fact that instead
of a 2D gamma camera mounted to a gantry, the
detector uses a handheld gamma probe. Since the
position and orientation of the handheld gamma
probe are arbitrary, a freehand SPECT imaging unit
includes a positioning system, which is able to
record the position of the handheld gamma probe
relative to that of the patient. The imaging procedure for this device differs from conventional diagnostic SPECT. Instead of being acquired at known
positions along a specifi c and predefi ned orbit, the
different projections are generated by the operator
using the handheld gamma probe through the operative fi eld. In our own experience in gynaecological
cancers (cervix and endometrium), a freehand
SPECT system declipse SPECT (SurgicEye GmbH,
Munich, Germany) connected to a 45° angled laparoscopic Tc-99 m- optimised Crystal Probe (Crystal
Photonics, Berlin, Germany) was used. The declipse
SPECT system includes an optical positioning system, updating the relative position of the handheld
gamma probe 20 times per second with an accuracy
of less than 0.5 mm. The handheld gamma probe is
connected to a sterile reference target (gamma
probe reference target) which includes refl ective
spheres (Navigation I-Spheres, SurgicEye GmbH,
Munich, Germany) and is compatible with the positioning system. At least one reference target is
attached to the patient (reference target), which
makes it possible to move the positioning system.
Dependent on lymphatic basin drainage, different positions are selected as patient reference
targets (pubis, iliac). Ideally, the chosen reference
target is unchanged in its position relative to the
SLN basin during patient movements (Fig. 16.5 ).
Generally, the closer the reference target is to the
SLN site, the more accurate the positioning, but
this may cause more disturbances to the surgical
workfl ow. The position of the optical imaging
camera is optimised in such way that the handheld
gamma probe and patient reference targets are
visible during image acquisition and visualisation. Care must be taken to avoid interference
with the system recognition of different references as this can hamper correct data collection
and analysis.
The freehand SPECT system provides several
potential advantages:
1. It provides precise depth information in a
nearly real time fashion, thereby facilitating
SLN detection. It may therefore reduce the
trauma and the risk of lymphatic fi stulas.
2. Intraoperative nearly real-time image acquisi-
tion is usually fast and does not delay the sur-
gical procedure signifi cantly (in our
experience about 15–20 min). It can be done
beforehand after the resection of SLNs and
may be repeated as often as required if the
post- incision fi ndings suggest remnant
activity.
3. Freehand SPECT offers confi rmation of com-
plete SLN removal and provides a reliable
source of documentation as images can be
printed or saved electronically and may be
added to the patient’s record.
4. Previous SPECT/CT data must be uploaded
and included in the image display to give ana-
tomic surroundings and the possibility of a
mixed reality intraoperative navigation.
260
https://t.me/med1917
a
d
P. Paredes and S. Vidal-Sicart
b
c
Fig. 16.5 Radioguided surgery using fhSPECT. Seventynine- year-old patient diagnosed of vulvar cancer. Bilateral
inguinofemoral drainage was observed on late ( b ) lymphos-
cintigraphy and confi rmed in SPECT/CT images ( c ). Early
planar views ( a ) show only one SLN in the right inguinal
area. During surgery fhSPECT was used to guide the SLN
16.4 Other Gynaecological
Tumours
16.4.1 Ovarian Cancer
The experience of SLN mapping in ovarian cancer is limited because of the high risk of tumour
spread. There are two series describing the lymphatic drainage from the ovaries in patients without ovarian malignancy, but with malignancy of
the endometrial or fallopian tube [ 4 , 5 ]. Only one
biopsy ( d ). First scan ( up ) indicates the best approach to
reach the SLN, which is at a great distance ( green spot ). The
injection site is represented on the left. Once soft tissues are
dissected, the target is nearer ( bottom ), 2-mm away the
probe. The green circle with the cross-over the green spot
confi rms the correct placement of the probe over the SLN
surgical team has evaluated the feasibility of SLN
mapping in 21 women with ovarian cancer [ 6 ],
with the administration of blue dye and radiotracer into the proper of ovarian and suspensory
ligaments. The detection rate was 100 %, with
ipsilateral drainage in 90.4 % of patients. The
most frequent location was para-aortic region
(67 %) followed by pelvic or a combination of
both (9 % and 24 %, respectively).
Therefore, ovarian cancer remains as one of
the gynaecologic malignancies for which there is
16 Radioguided Sentinel Lymph Node Mapping and Biopsy in Gynaecological Malignancies
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261
much room for exploring the use of novel hybrid
tracers and intraoperative detection and imaging
devices.
16.4.2 Vaginal Cancer
There are very few studies regarding sentinel
node in vaginal cancer, but they report
successful SLN detection in isolated cases
[ 20 , 21 , 22 ]. Frumovitz et al. [ 23 ] used the
lymphatic mapping of lymphoscintigraphy for
radiotherapy planning in 14 patients. They
found lymphatic drainage in 79 % of patients,
with bilateral lymph nodes in 55 % of cases.
The most frequent location was the inguinal
basin (45 %). There are only 3 reported cases,
all in vulvovaginal melanoma, where detection was higher due to the increase of SLN
locations identified by SPECT/CT [ 48 , 49 ].
16.5 Summary
The accurate harvesting of SLNs in gynaecological cancer (i.e. vulvar, vaginal, cervical, endometrial, or ovarian cancer) is a complex process that
can involve the coordination of several procedural components to successfully accomplish.
These issues have been covered in a recent general guideline from EANM-SNMMI [ 50 ]. There
are some well- established indications for SLNB
(especially in vulvar and cervical cancers), but
some further clarifi cation issues still remain
(SLN detection in endometrial, vaginal, and
ovarian cancer is not a standard of care) and
should be considered an investigational procedure. The use of new intraoperative detection and
imaging devices, as well as hybrid tracers, may
help to broaden the application of radioguided
SLN biopsy in gynaecologic malignancies, and,
therefore, warrant further clinical investigation.
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Part VIII
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Clinical Application: Gastrointestinal Tract
Radioguided Sentinel Lymph Node
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Mapping and Biopsy
in Esophagogastric Cancer
Hiroya Takeuchi and Yuko Kitagawa
1 7
Contents
17.1 Introduction 268
17.2 Esophageal Cancer 268
17.2.1 Sentinel Lymph Node (SLN) Mapping
and Biopsy Procedures in Esophageal
Cancer 268
17.2.2 Results of SLN Biopsy
for Esophageal Cancer 269
17.2.3 Future Application of SLN Biopsy
in Esophageal Cancer 270
17.3 Gastric Cancer 271
17.3.1 Laparoscopic SLN Mapping
and Biopsy Procedures 271
17.3.2 Results of SLN Biopsy for
Gastric Cancer 272
17.3.3 Clinical Application of Laparoscopic
SLN Biopsy for Early
Gastric Cancer 273
Conclusion 276
References 276
H. Takeuchi , MD, PhD (*) • Y. Kitagawa , MD, PhD
Department of Surgery ,
Keio University School of Medicine ,
35 Shinanomachi, Shinjuku-ku ,
Tokyo 160-8582 , Japan
htakeuchi@a6.keio.jp
e-mail:
Abstract
Clinical application of sentinel lymph node
(SLN) mapping and biopsy for early esophageal or gastric cancer had been controversial
for years. However, single-institutional results
of SLN mapping and biopsy for these cancers
are almost acceptable in terms of detection
rate and accuracy to determine the lymph
node status. SLN mapping and biopsy may
play a key role to obtain individual metastatic
information and allows modifi cation of the
surgical procedures for early upper gastrointestinal (GI) cancer.
Radioguided, endoscopic SLN biopsy
using preoperative lymphoscintigraphy and
intraoperative gamma-probe has been established for early esophageal cancer. Previous
reports suggest that the SLN concept seems to
be valid, and radioguided SLN biopsy may be
feasible in cT1N0 esophageal cancer.
Radioguided SLN mapping and biopsy has
proven to be a promising strategy for a less
invasive individualized surgery for early-stage
esophageal cancer.
For early gastric cancer, the Japan Society
of Sentinel Node Navigation Surgery conducted a prospective multicenter trial of SLN
mapping and biopsy by a dual-tracer method
with radioactive colloid and blue dye.
Corresponding detection rates of hot and/or
blue lymph node were 98 %, respectively. The
sensitivity to detect metastasis based on SLN
© Springer International Publishing Switzerland 2016
K. Herrmann et al. (eds.), Radioguided Surgery: Current Applications and Innovative
Directions in Clinical Practice, DOI 10.1007/978-3-319-26051-8_17
267
268
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H. Takeuchi and Y. Kitagawa
status was 93 % and the accuracy 99 %. Based
on these results, minimized gastrectomy (such
as proximal gastrectomy, segmental gastrectomy, and pylorus- preserving gastrectomy),
with individualized selective and modifi ed
lymphadenectomy for early gastric cancer
with negative SLN are now being performed
in specialized institutions. More recently, the
combination of endoscopic resection with
SLN biopsy also appears attractive.
The SLN concept for cN0 early upper GI
cancer has been validated, and modifi ed
esophagectomy/gastrectomy with individualized minimally invasive surgery, which might
retain the patients’ quality of life, should be
established as the next surgical challenge.
17.1 Introduction
Clinical application of sentinel lymph node
(SLN) mapping and biopsy for early esophageal
or gastric cancer had been controversial for years.
However, previous results of SLN biopsy for
these cancers are almost acceptable in terms of
detection rate and accuracy to determine lymph
node status. SLN biopsy may play a key role to
obtain individual metastatic information and
allows modifi cation of the surgical procedures
for early upper gastrointestinal cancer.
standard procedure, even for clinically nodenegative cases [
tomy with extended lymph node dissection is
one of the most invasive procedures in gastrointestinal surgeries even by thoracoscopic and
laparoscopic approaches as minimally invasive
esophagectomy [ 3 – 5 ]. To eliminate the neces-
sity of uniform application of highly invasive
surgery, SLN biopsy may play a signifi cant role
by obtaining individual information to permit
adjustments and modifi cations of the surgical
procedure for that specifi c patient [ 6 ].
1 , 2 ]. However, the esophagec-
17.2.1 Sentinel Lymph Node (SLN)
Mapping and Biopsy
Procedures in Esophageal
Cancer
In general, radioguided method rather than the
conventional blue dye method is preferred to
detect the SLN in esophageal cancer [ 7 – 9 ]. In our
procedures, a 2.0-ml volume of technetium-99m
tin colloid solution (150 MBq) is injected at four
quadrants into the submucosal layer around the
primary tumor using an endoscopic puncture
needle the day before surgery. Preoperative lymphoscintigraphy is usually obtained 3–4 h after
the radiotracer injection (Fig. 17.1 ). Distribution
of SLN was widely spread from cervical to
abdominal areas.
17.2 Esophageal Cancer
Esophageal cancer has one of the highest malignant potentials of any tumor. Lymph node
metastasis has been recognized as one of the
useful indicators for predicting the outcome of
esophageal cancer. Specifi c characteristics of
esophageal cancer are multidirectional lymphatic fl ow from the primary lesion and the
widespread and random patterns of lymph node
metastasis from cervical to abdominal areas [ 1 ].
Moreover lymph node metastasis is not a rare
event in esophageal cancer even in pT1b tumors
[ 1 ]. Based on these clinical observations, radical
esophagectomy with two- or three-fi eld lymph
node dissection has become recognized as a
Primary tumor
Fig. 17.1 Preoperative lymphoscintigraphy in thoracic
esophageal cancer. Arrows , sentinel nodes
17 Radioguided Sentinel Lymph Node Mapping and Biopsy in Esophagogastric Cancer
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269
Intraoperative SLN (i.e., radiolabeled lymph
nodes) sampling is performed using a handheld
gamma-probe (GPS Navigator; RMD Instruments
LLC, Watertown, MA, USA). Gamma probing is
also feasible in thoracoscopic or laparoscopic
sampling of SLNs using the special gammadetector, which is introducible from trocar ports.
SLN located in the cervical area could be identifi ed by percutaneous gamma-probing. On the
back table, the search for residual SLNs in the
resected specimen is carefully investigated using
the gamma- probe, and all SLNs are sent for intraoperative pathology examination.
For abdominal esophageal cancer or adenocarcinoma of gastroesophageal (GE) junction, a
dual-tracer method of the radioactive tracer and
blue dye (isosulfan blue or indocyanine green) is
primarily used for SLN detection [ 10 ]. The blue
dye is injected into the submucosal layer of the
primary lesion endoscopically right after the start
of surgery. Subsequently, the radiotracer passes
through the afferent lymphatics, and blue-stained
lymph nodes are identifi ed as the SLNs approximately 15 min after the injection.
We believe that dye-only-guided SLN mapping is not suitable for thoracic esophageal cancer secondary to the fact that regional lymph
nodes of the thoracic esophagus in the mediastinum are frequently pigmented by anthracosis.
Furthermore, real-time observation of the lymphatic route using blue dye is impossible without
operative mobilization and dissection of the
esophagus; however, mobilization and dissection
itself may interfere with active lymphatic fl ow
from the primary lesion. Intraoperative SLN
sampling using gamma-probe is considerably
accurate and useful for prediction of lymph node
metastasis in esophageal cancer.
17.2.2 Results of SLN Biopsy
for Esophageal Cancer
There have been relatively less number of studies
demonstrating the feasibility and validity of the
SLN concept in esophageal cancer, compared to
those in gastric cancer (Table 17.1 ). To date,
however, a number of single-institutional studies,
Table 17.1 Representative results of sentinel node biopsy for esophageal cancer using radioguided methods
Number of
Author (Ref.) Year Radiotracers Tumor depth
35 ] 2003 RI (
Kato [
Yasuda [
36 ] 2003 RI (
Lamb [
12 ] 2005 RI(
Takeuchi [
Thompson [
Kim [
Uenosono [
RI radioisotope, N.D. not determined, HSA human serum albumin, SCC squamous cell carcinoma, Adeno adenocarci-
noma, SLN sentinel lymph node
9 ] 2009 RI (
14 ] 2011 RI (
37 ] 2011 RI (
15 ] 2011 RI (
99m
technetium
rhenium sulfi de)
99m
technetium
tin colloid)
99m
technetium
nanocolloid)
99m
technetium
tin colloid)
99m
technetium
antimony colloid)
99m
technetium
neomannosyl
HSA)
99m
technetium
tin colloid)
pT1–T4 25 SCC 23/25 (92) 13/15 (87) 21/23 (91)
pT1–T3 23 23/23 (100) 9/12 (75) 20/23 (87)
N.D. 57 Adeno 57/57 (100) 35/37 (95) 55/57 (96)
cT1–T2 75 SCC+
pT1a–T3 16 SCC+
cT1–T4 23 ESCC 21/23 (91) 8/8 (100) 21/21
cT1–T3 134
patients
Adeno
Adeno
SCC+
Adeno
SLN detection
rate (%)
71/75 (95) 29/33 (88) 67/71 (94)
14/16 (88) 3/3 (100) 16/16
cT1: 56/60
(93)
cT2: 31/31
(100)
cT3: 28/32
(88)
CRT: 5/11
(46)
Sensitivity
(%)
cT1: 11/12
(92)
cT2: 12/18
(67)
cT3: 13/24
(54)
CRT: 0/3
(0)
Accuracy
(%)
(100)
(100)
cT1: 55/56
(98)
cT2: 25/31
(81)
cT3: 17/28
(61)
CRT: 2/5
(40)
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