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9 Radioguided Surgery of Non-palpable Breast Lesions: Radio Occult Lesion Localization (ROLL)
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a
Fig. 9.1 Injection techniques. ( a ) Ultrasound-guided tracer injection. The needle is positioned in the lesion. ( b )
Stereotactic-guided tracer injection. The tip of the needle is positioned at the site of the tumor marker
a
b
b
c
Fig. 9.2 Tracer administration procedure. ( a ) Ultrasound-
guided needle tip position in the lesion. ( b ) A 1 ml tuber-
culin syringe with Luer-Lok connection in order to
prevent leakage. ( c ) The syringe with an attached lead
9.1.3 Combining ROLL with SLNB
To combine ROLL with a sentinel lymph node
biopsy (SLNB), two different approaches have
d
cover for radiation protection. ( d ) US-guided Tc 99m
injection. A 0.1 ml air bubble, positioned behind the
radioactivity volume, in the syringe may help to fl ush the
tracer rest from the needle
been described in literature. For the fi rst approach,
Tc 99m MAA is injected intratumorally and Tc
99m albumin nanocolloid for the SLNB is injected
subdermally at the level of the lesion [ 30 , 31 ]. The
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B. Pouw et al.
Li Lat 15 min
Fig. 9.3 Nuclear imaging. ( a ) A lateral and ( b ) an anterior view of the tracer deposit in the tumor
a
c
b
d
Ant 15 min
Fig. 9.4 Sentinel node + radioguided occult lesion localization (SNOLL). ( a ) anterior image with the injection
site. ( b ) Lateral image with an SN. ( c ) Axial CT scan with
second approach combines the two procedures in
one injection using Tc 99m albumin nanocolloid
into the tumor. This tracer has a particle size of
5–80 nm, and a small fraction of the radioactivity
the tumor maker indicated with the arrow . ( d ) Axial
SPECT/CT scan with the radioactivity deposit at the site
of the tumor marker
migrates from the tumor to the lymph nodes
which enables the use of the tracer for combined
ROLL and SLNB in one session; the procedure is
also called SNOLL procedure (SN + ROLL) [ 2 ,
9 Radioguided Surgery of Non-palpable Breast Lesions: Radio Occult Lesion Localization (ROLL)
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19 , 32 – 35 ] (Figs. 9.3 and 9.4 ). The advantage of
using Tc 99m MAA is that it acts more as a point
source compared to the Tc 99m albumin nanocolloid, which partially diverges into the lymphatics.
The advantage of using only one tracer for both
procedures is a more simplistic procedure with
only one injection.
9.1.4 Imaging
Gamma camera imaging for a ROLL procedure
may be performed to ensure that the radioactive
tracer stays locally in the breast lesion and does
not disperse though the breast parenchyma or
small vessels; it is also helpful to depict contaminations, for example, on the skin. Static scintigraphic imaging 10–15 min after administration
is suffi cient to assess this. If contamination has
occurred, skin decontamination is recommended
to avoid spurious intraoperative fi ndings [ 2 ].
When wide spread of the radiotracer through the
breast parenchyma is observed, another localization technique (e.g., wire guided) should be considered; this happened in 4 out of 959 patients in
a large study [ 2 ]. The necessity of gamma camera
imaging after secure injection of the fl uid for
ROLL is according to some authors not required
or recommended [ 26 ]. In case of a SNOLL pro-
cedure, imaging can be accomplished according
to standard SLNB gamma camera imaging. In
our institute, we obtain planar static images
15 min and 3 h after tracer injection followed by
additional SPECT/CT imaging in case of inconclusive static images or aberrant drainage patterns for SLNB procedures [
9.4 ). When planar images are obtained, the
patient contour can be visualized by means of a
fl ood source positioned underneath the patient
during the acquisition (Fig. 9.4 ).
36 ] (Figs. 9.3 and
9.1.5 Surgical Localization
gamma probe, and visualization possibilities
(i.e., acoustic noise and numerical display). The
fi rst three properties, which are mentioned, are
all dependable on each other, and the end user
should decide what parameters do best suit their
needs. For example, a more focused beam, thanks
to more side shielding, will result in a lower sensitivity. The surgical excision of the lesion is performed at the operating theatre. The highest Tc
99m counts detected transcutaneous with the
gamma probe give insight in the location and
guide the placement of the incision. During the
procedure, the probe guides the location of the
tumor by measuring a count drop at the border of
the marked tissue and the surrounding tissue.
After excision, the rest of the cavity is searched
for further radioactivity exceeding the background signal (Fig.
in the cavity exceeding the background signal,
the excision should be enlarged.
9.5 ). If there remains signal
9.1.5.1 Innovative Techniques
Another approach is to use a portable gamma camera to localize the lesion and secure complete
removal of the lesion. The portable gamma camera
is used in conjunction with the conventional
gamma probe. Paredes et al. proposed this method
in 2008 (Fig. 9.6a ). In this study, it was demon-
strated on 43 patients that a pinhole portable
gamma camera was capable of imaging the surgical bed and the specimen. There was 60 % congruence between the images in terms of appropriate
excision and centricity of the radioactivity compared to histopathology [
is another technique, which can be used to localize
the radioactive lesion. This method consists of
hovering an optically tracked gamma probe over
the area of interest, and by measuring the radioactivity from multiple directions, a radioactivity map
is reconstructed. In this way, nearly real-time
localization of radioactivity is facilitated, and at
the same time, navigation with depth measurements is possible [ 40 ] (Fig. 9.6b ).
38 , 39 ]. Freehand SPECT
The radioactive tracer can be detected during
operation with a gamma probe. There are many
types of gamma probes available for intraoperative localization [ 37 ]. Important properties are
the sensitivity, side shielding, thickness of the
9.1.6 Histopathology
Frozen section analysis of imprint cytology can be
performed during the procedure for confi rmation of
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ab
d
c
e
Fig. 9.5 Surgical localization. ( a ) The maximum signal
of Tc 99m is measured on the skin and marked. ( b ) The
surgeon decides the best approach and accordingly places
a
Fig. 9.6 Innovative techniques. ( a ) ROLL procedure with
a portable gamma camera (Paredes et al. [
activity is imaged in a very short time interval. ( b )
Freehand SPECT navigation with declipse SPECT
38 ]). The radio-
appropriate excision. These rapid intraoperative
methods of assessing the excised tissues during the
operative procedure can reduce the need for a subsequent second surgical procedure [ 41 , 42 ].
the incision. ( c ) Measurement after skin incision. ( d )
Wide excision of a large tumor. ( e ) Control for residual
activity after excision
b
(SurgicEye GmbH, Munich, Germany) for a ROLL procedure. The location of the radioactivity is superimposed
over the breast of the patient
Alternatively, standard postoperative permanent
section analysis can be performed for assessing the
fi nal status of the surgical resection margins, as well
as for standard comprehensive evaluation of the pri-
9 Radioguided Surgery of Non-palpable Breast Lesions: Radio Occult Lesion Localization (ROLL)
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145
mary tumor and lymph nodes. At the moment, there
is no general consensus on how to manage minimally involved surgical resection margins. Adjuvant
radiation and chemotherapy might be equally good
compared to secondary surgery [ 43 , 44 ].
9.2 Overall Results of ROLL
The fi rst ROLL procedures are described in 1998
by Luini et al. [ 45 ], and, since then, ROLL rap-
idly increased in use. The rapid introduction was
caused by the increased need for a proper localization method for the increasing number of
non- palpable lesions and the good fi rst results.
At the moment, more than 29 peer-reviewed articles have emerged about ROLL, including multiple series of a thousand patients or more.
9.3 Results Compared to Other
Techniques
9.3.1 ROLL-WGL
The largest meta-analysis comparing ROLL with
WGL is the meta-analysis from Sajid et al. This
study included four randomized controlled trials
(RTCs) with a total of 449 patients randomized to
either one of the procedures [ 1 , 5 , 18 , 46 ]. The
meta- analysis demonstrated a signifi cant favorable outcome considering positive margins and
localization time for the ROLL procedure. The
localization rate, reoperation rate, complication
rate, duration, specimen weight, and specimen
volume were all comparable for both techniques.
The same meta-analysis describes results
from other non-RCTs. Seven of these studies
describe similar results as the 4 RCTs on ROLL
[
5 , 12 , 26 , 46 – 49 ]. Further the results on the
similarity of the excised volume and weight of
the specimen concur with other publications
[ 5 , 18 , 46 ]. Some retrospective studies do not
concur with the results about the specimen volume and weight [ 49 , 50 ]. Furthermore, the meta-
analysis mentions studies with a reduced degree
of positive margins, with 75 to 100 % margin
clearance [ 2 , 19 , 34 , 47 , 48 , 51 ].
9.3.2 ROLL-Ultrasound
Another localization method for non-palpable
breast lesions is intraoperative ultrasound guidance [ 52 , 53 ]. Ultrasound guidance seems to have
strong advantages compared to surgery by palpation only. However, in contrast to invasive breast
cancer, DCIS lesions are usually not visible at
ultrasound, and therefore, this method is not
always applicable. This could be resolved by
placing a nonradioactive marker that is visible on
US, but this would be a cumbersome method. A
study from Krekel et al. compared WGL, ROLL,
and ultrasound-guided localization [ 13 ]. This
study included non-palpable lesions but excluded
in situ carcinomas and neoadjuvant treated
tumors, and, for this selection, it demonstrated
signifi cant favorable results for US-guided procedures based on margin status not taking unexpected DCIS component into account. When
taking the unexpected DCIS component into
account, there was no signifi cant difference in
margin status between the three groups.
Altogether, intraoperative ultrasound use can be
useful for tumor excision in certain groups,
although an ultrasound-trained surgeon is
required and this technique is only applicable for
carcinomas visible on ultrasound.
9.3.3 ROLL (Tc-99m)-RSL
(I-125-Seed)
Ahmed et al. described the comparison between
ROLL and RSL, and regarding the original study
comparing the techniques from Donker et al. [ 54 ,
55 ]. This study demonstrated comparable results
between the ROLL-Tc99m technique and I-125
seed localization when used to perform breastconserving surgery after neoadjuvant systemic
treatment, although the preference was I-125
seed localization because this does not require
additional radiological localization shortly before
surgery, and therefore, it simplifi es surgery
scheduling. The largest study comparing ROLL
with RSL is from Noordaa et al. [ 56 ]. In this
study, 403 patient with either unifocal non-palpable DCIS or invasive carcinoma were retrospec-
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tively analyzed, 128 patients underwent RSL and
275 patients ROLL. Margin status and re-excision rates were comparable for RSL and ROLL in
patients with non-palpable breast lesions. A signifi cant lower weight of the resected specimen
using RSL in the DCIS group was found. Because
of the feasibility of position verifi cation of the
I-125 seed and more convenient logistics, RSL
was favored over ROLL for breast- conserving
therapy.
9.4 Discussion
The general consensus is that the main advantages of ROLL, using Tc 99m, over WGL are the
patient comfort, positive margins, and localization time. The wire localization technique has
disadvantages such as wire dislodging, worsened
cosmetics, and wire migration which are all
negated by the ROLL technique. The 6-hour halflife of Tc 99m allows some fl exibility, up to 24 h,
in planning the surgical procedure after the radiotracer injection. A possible limitation of injection
of a liquid radiotracer, like Tc 99m, is the potential for dispersion of the radiotracer throughout
the breast tissue. Therefore, the more recent
development of RSL, using a I-125 seed, represents a very promising alternative form of
radioguided surgery for non-palpable breast
lesions, and for which we expect the popularity
of RSL to quickly grow [ 57 ].
Working with radioactivity (tracers or markers) requires strict regulations at the nuclear
medicine department and a close collaboration
with the radiology department. The radiation
dose for patients and involved staff is limited
and comparable to SLN procedures, which are
performed on a regular basis in most institutes.
The radiation dose for patient and staff was
analyzed by Rampaul et al. and Cremonesi et al.
The dose for patients was 0.45 mGy and after
100 surgical procedures for surgeons 0.45 mGy.
The mean effective dose was 0.09 mSv.
These numbers did not exceed the limits established by the commission on radiological protection [
58 , 59 ].
Conclusive
ROLL, using Tc 99m, is useful for localization of non-palpable lesions in the breast; this
includes invasive cancers, DCIS, or areas of
microcalcifi cations. The general consensus is
that ROLL is preferable over WGL. There are
however some drawbacks considering the
radiotracer distribution and decay, although in
general the patient comfort, cosmetic outcome, and the localization results outweigh
the drawbacks. In the future, we expect an
increase in the use of RSL using I-125 seeds
that act more as a point source, allow position
verifi cation by mammography, and allow
more fl exibility in the logistics between radiology and the surgical department.
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Part IV
https://t.me/med1917
Clinical Application: Skin
Radioguided Sentinel Lymph Node
https://t.me/med1917
Mapping and Biopsy in Cutaneous
Melanoma
Omgo E. Nieweg , Roger F. Uren ,
and John F. Thompson
1 0
Contents
10.1 Introduction 152
10.2 Defi nition of a Sentinel Lymph Node 152
10.3 Imaging Technique 153
10.4 Surgical Technique 155
10.5 Identifi cation of Sentinel Lymph Nodes,
Staging Information, and Morbidity 155
10.6 False-Negative Rate 156
10.7 Survival 156
10.8 New Developments 158
10.8.1 Need for Completion Node Dissection in Patients
with a Metastatic Sentinel Lymph Node 158
O. E. Nieweg , MD, PhD, FRACS () • J. F. Thompson ,
MD, FRACS, FACS
Sydney Medical School, The University of Sydney ,
Sydney , NSW , Australia
Melanoma Institute Australia ,
40 Rocklands Road , North Sydney , NSW 2060 ,
Australia
The Mater Hospital , North Sydney , NSW , Australia
Royal Prince Alfred Hospital ,
Camperdown , NSW , Australia
omgo.nieweg@melanoma.org.au
e-mail:
R. F. Uren , MD, FRACP, DDU
Sydney Medical School, The University of Sydney,
Nuclear Medicine and Diagnostic Ultrasound ,
Suite 206, RPAH Medical Centre, 100 Carillon Ave. ,
Newtown , NSW , Australia
10.8.2 New Tracers 158
10.8.3 Innovative Imaging Technology 159
10.8.4 Clinical Need for New Technologies 159
10.8.5 New Drugs for Melanoma
Patients with Inoperable Metastases 159
10.9 Current Clinical Practice 159
Conclusions 160
References 160
Abstract
Sentinel lymph node biopsy has developed
into a routine procedure to stage patients
with a clinically localized melanoma. The
node can be found in almost every patient.
The status of the lymph nodes is the most
powerful prognostic factor. Although high
false-negative rates are still being published,
sentinel lymph node biopsy is reliable when
performed by an experienced multidisciplinary team using a meticulous technique.
The Multicenter Selective Lymphadenectomy
Trial I has shown that the procedure leads to
improved survival when combined with completion lymph node dissection in lymph
node-positive patients with an intermediate
Breslow thickness melanoma. The technique
of sentinel lymph node biopsy continues to
evolve and its importance will expand even
further when adequate adjuvant systemic
therapies become available.
© 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_10
151
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