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21 Radioguided Surgery of Small Pulmonary Nodules
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Table 21.1 (continued)
Authors/
Reference Localization technique Patient population Effi cacy Complications
Grogan et al.
19 ]
[
Ambrogi et al.
22 ]
[
Mattioli et al.
75 ]
[
Gonfi otti et al.
55 ]
[
Reproduced with permission from Callister et al. [
VATS video-assisted thoracoscopic surgery
Radiotracer injection 81 patients
undergoing
VATS nodule
resection
Radiotracer injection 211 patients
undergoing
VATS nodule
resection
Transthoracic
ultrasound
Hookwire vs.
radiotracer
54 patients
undergoing
VATS resection
of 65 nodules
50 patients
randomized to
each procedure
for VATS
resection
44 ]
Successful
localization and
excision in 95.1 %
of cases
Successful
localization and
resection in 99 % of
cases
Successful
identifi cation of
15/16 non-visible or
palpable nodules
(94 %)
Successful
localization:
84 % hookwire
96 % for radiotracer
(not signifi cant)
10 % pneumothorax with
drain
10.4 % pneumothorax no
drain
None
24 % pneumothorax no drain
hookwire
4 % pneumothorax
radiotracer
4 % ( n = 1) hookwire
displacement
345
21.4.3 Radiopaque Dyes
After hookwires, the next most commonly
employed technique is CT-guided injection of
a radiopaque marker such as lipiodol, an
iodized oil, or barium sulfate, followed by
intraoperative fl uoroscopy for real-time detection [ 61 – 63 ]. Watanabe et al. reported their
experience with CT-guided lipiodol injection
followed by intraoperative fl uoroscopic detection in 174 patients, reporting 100 % success
but complications including a 17 % incidence
of pneumothorax, with 11 patients requiring
drainage and one patient requiring an emergent
operation for hemopneumothorax [
technique does allow for a delay of a day or
more between injection and surgery. Additional
theoretical risk is systemic embolization of the
contrast media. Interestingly, Okumura et al.
describes bronchoscopic rather than CT-guided
injection of the barium marker [ 65 ]. While
innovative, it requires sophisticated bronchoscopic skill available at few institutions.
Ultimately, the need for intraoperative fl uoroscopy limits the utility and appeal of all of these
techniques.
64 ]. This
21.4.4 Methylene Blue
The oldest marking technique relies on the simple injection of methylene blue in the vicinity of
the pulmonary nodule, enhancing its intraoperative visibility [ 66 – 68 ]. For example, Vandoni
et al. describe successful resection in 91 % of 51
patients undergoing VATS resection of 54 pulmonary nodules, with a 25 % pneumothorax rate
[ 67 ]. Recent data suggest that this approach is
safe and feasible in children as well [
However, simple dye injection is less successful
with pulmonary nodules located deep in the lung
parenchyma, and the blue dye does diffuse away
from the injection site over time.
Methylene blue can also be delivered via
bronchoscopy. Navigational bronchoscopy has
recently been developed as a method for transbronchial biopsy or, alternatively, the delivery of
fi ducial markers, to facilitate either pulmonary
nodule resection or radiation [ 69 , 70 ]. Bolton
et al. describe using intraoperative navigational
bronchoscopy in a series of 19 patients to locate
the lesion, obtain one or two transbronchial needle biopsy specimens, and then inject methylene
blue dye as a local marker to guide immediate
68 ].
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A.W. Maiga and E.L. Grogan
surgical excision [ 71 ]. If the biopsy specimens
returned as positive for malignancy, a formal
lobectomy and lymph node dissection was performed. If the biopsy was negative or inconclusive, a robotic-assisted wedge resection was
performed, using the parenchyma dyed blue to
guide the resection.
In cases where CT-guided percutaneous marking or injection is not feasible or is high risk,
simple noninvasive use of dyes can provide some
benefi t. For example, Okuda et al. describe using
crystal violet to intraoperatively mark the visceral pleura adjacent to the pulmonary nodule
using the preoperative CT scan as a guide [ 72 ].
21.4.5 Ultrasound
Intraoperative thoracoscopic ultrasonography is
another adjunct to pulmonary nodule localization
that can be employed as needed across the entire
pleural surface. A few authors have reported successful identifi cation of small, fi rm pulmonary
nodules with this technique [ 73 – 77 ]. Sortini et al.
reported a small nonrandomized study comparing intrathoracoscopic ultrasound to radioguided
occult lesion localization with Tc-99m human
serum albumin microspheres, demonstrating
96 % success with ultrasound (24 of 25) and
80 % success with radioguidance (20 of 25) [ 78 ,
79 ]. However, thoracoscopic ultrasonography
has a steep learning curve and relies on complete
atelectasis, as visualization is limited by intraparenchymal air causing reverberating artifacts.
tive visualization and palpation [ 80 ]. Although
effective, the hardness of the polymer interferes
with pathologic sectioning, and there is a risk of
systemic embolization, rendering the technique
less useful.
21.4.6.2 RFID Tags
A Japanese group has recently described a canine
model of employing radiofrequency identifi cation (RFID) technology as a wireless marker for
subcentimeter pulmonary nodules [ 81 ]. The
1-mm RFID tags are delivered bronchoscopically, and the detection system is accurate down
to the millimeter for pinpoint pulmonary nodule
localization. Although the RFID tags have been
approved for use in humans, this proof-ofconcept study remains to be replicated in humans.
More work also needs to be done to improve the
current effective communication range of 7 mm
between the RFID tag and the detector probe
(which powers the RFID tag remotely to permit
detection).
21.4.6.3 NIR Technology
Okusanya et al. have described administering
systemic indocyanine green and using nearinfrared technology to successfully identify and
resect pulmonary nodules 24 h later in 14 of the
18 (78 %) patients [ 82 ]. Of note, all patients had
intentional thoracotomies to correlate fi nger palpation with the NIR fi ndings. Five additional pulmonary nodules were identifi ed by NIR that were
not visualized on preoperative CT scans, and
these were also resected. This technique remains
experimental.
21.4.6 Experimental Techniques
Several experimental pulmonary nodule localization techniques have been described in the literature, including local injection of acrylates,
bronchoscopic delivery of radiofrequency identifi cation (RFID) tags, and the use of near-infrared
(NIR) technology.
21.4.6.1 Acrylates
Yoshida et al. have described CT-guided injection
of a cyanoacrylate agent to aid in both intraopera-
21.5 Summary
Radioguided surgery of small pulmonary nodules
provides critical real-time guidance to surgeons
regarding pulmonary nodule identifi cation and
adequacy of surgical resection margins. This is
typically accomplished via the CT-guided transthoracic injection of Tc-99m MAA and intraoperative detection with a handheld gamma probe.
A variety of other percutaneous transthoracic and
intravenous delivery techniques have been
21 Radioguided Surgery of Small Pulmonary Nodules
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347
described, many of which remain experimental.
Management of subcentimeter pulmonary nodules is a critical and timely topic, especially given
the encouraging results of the NLST and the
USPSTF’s recommendations to adopt annual
screening chest CT scans for high-risk
individuals.
Radiotracer-guided thoracoscopic surgery for
small pulmonary nodules has been shown to be
more cost-effective than thoracotomy for the
management of indeterminate subcentimeter pulmonary nodules [ 83 ]. It also avoids the higher
morbidity and mortality of diagnostic thoracotomy. A variety of localization alternatives to
radioguidance exist, including hookwires and
markers, simple and radiopaque dyes, thoracoscopic ultrasound, and more experimental techniques like bronchoscopic delivery of RFID tags
and near-infrared technology. Regardless of other
techniques in use and in development, radioguided surgery is likely to play an increasingly
important role in the management of indeterminate pulmonary nodules.
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P a r t X
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Miscellaneous
Radioguided Localization of Bone
https://t.me/med1917
Lesions
Erik M. Von Meyenfeldt and Karel W. E. Hulsewé
2 2
Contents
22.1 Clinical Value and Relevance in Clinical
Practice 353
22.2 Preoperative Localization 354
22.2.1 Tracers Usually Used and Route of
Administration 354
22.2.2 Preoperative Imaging 355
22.3 Alternatives to Radioguided Surgery
or Combination of Techniques 355
22.4 Radioguided Localization, Biopsy, and
Possible Resection of Bone Lesions 355
22.4.1 Previously Used and/or Alternative
Techniques 356
22.4.2 Success Rates of 1D Gamma Probes for
Intraoperative Detection 356
Conclusion 356
References 357
Abstract
Nuclear medicine techniques are used increasingly in primary staging and follow-up of several malignancies and imaging of benign bone
diseases.
E. M. Von Meyenfeldt ()
Department of Surgery , Albert Schweitzer Hospital ,
Dordrecht , The Netherlands
e.m.von.meyenfeldt@asz.nl
e-mail:
K. W. E. Hulsewé
Departments of Surgery , Zuyderland Hospital ,
Sittard/Heerlen , The Netherlands
k.hulsewe@orbisconcern.nl
e-mail:
Bone scans using Technetium-99m (
99m
Tc)
are highly sensitive in detecting bone lesions,
but due to low specifi city, false-positive
lesions are detected frequently. Although
SPECT and PET techniques have improved
diagnostic imaging accuracy, histological
diagnosis of suspected metastatic lesions is
often needed to be able to make important
treatment decisions. When radiological biopsy
is not successful or feasible due to absence of
a radiologically detectable target, radionuclideguided surgical bone biopsy is a highly accurate and well-tolerated technique to obtain
histological diagnosis. When benign lesions
are not amenable to less invasive treatment
options, radioguided surgery can limit the
extent and increase the success rate of surgical
resection.
22.1 Clinical Value and Relevance
in Clinical Practice
Nuclear medicine imaging techniques are used
increasingly during analysis of primary tumours or
follow-up after their curative treatment. Depending
on primary tumour histology, bone metastases
occur in up to 70 % of patients [ 1 ]. Skeletal scin-
tigraphy with Technetium-99m (
agents has been the mainstay of imaging of osteoblastic bone metastases, but has limited sensitivity
(86.0 %) and especially limited specifi city
99m
Tc)-labeled
© 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_22
353
354
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E.M. Von Meyenfeldt and K.W.E. Hulsewé
(81.4 %), leading to false-positive scintigraphy
results [ 2 ]. Addition of single- photon emission
computed tomography (SPECT) and SPECT/CT
techniques has increased especially specifi city
(92.8 %) of
99m
Tc-based imaging [ 2 – 4 ].
The increased use of highly sensitive (93.7 %)
and specifi c (97.4 %) 18 F-fl uorodeoxyglucose ( 18 FFDG) – positron emission tomography (PET)/CT
imaging, which relies on glucose metabolism of
the tumour itself rather than the osteoblastic activity caused by the tumour, has improved detection
rate of bone metastases as well as extra-skeletal
metastases [ 2 ]. Improved PET technique and PET
availability have revived interest in 18 F-fl uoride as
a specifi c bone tracer. 18 F-Fluoride accumulates in
both osteoblastic and osteolytic lesions, has highly
specifi c bone uptake and has rapid clearance from
the blood pool; these characteristics combined
with CT imaging result in improved detection and
characterisation of bone lesions, compared to
99m
Tc bone imaging [ 5 ].
Despite the use of these more sensitive and specifi c imaging modalities, confi rmation of the histology of a bone lesion is still essential to determine
the appropriate treatment plan in many cases.
Confi rmation of synchronous bone metastases
during primary analysis will often preclude curative
treatment and warrant a change in treatment strategy. Proving a bone lesion, detected during followup, to be benign, rather than cancer recurrence, will
reassure the patient and prevent overtreatment.
When radiological abnormalities are present,
percutaneous biopsy by the radiologist is the preferred, least invasive, technique. In radio-occult
lesions, or when the percutaneous biopsy result is
inconclusive, radioguided surgical biopsy is a
highly reliable, well-tolerated technique to obtain
histological diagnosis [
6 – 8 ].
Radioguided (i.e., gamma probe-guided) bone
biopsy is generally reported to have a specifi city of
approximately 100 % and a sensitivity in the
97 %–100 % range [ 6 – 8 ], and with anywhere
between 30 %–70 % of radioguided biopsied bone
lesions proving to be malignant. An illustrated case
description of radioguided rib biopsy is included in
Chapter 29 of this book.
Radioguided surgery for benign bone lesions,
like enchondroma and especially osteoid osteoma, results in excellent symptom relief with
more limited dissection, more complete resection
of the nidus and less extensive resection of
healthy bone tissue, as compared to conventional
open resection [ 9 – 12 ]. Radioguided resection
therefore provides a valuable alternative, when
other minimally invasive techniques, like radiofrequency ablation (RFA), are not feasible [ 10 ,
11 ]. Reports on the added value of radioguided
surgery in infectious disease have been published
as well, but have not been consistently reproduced [ 13 ].
22.2 Preoperative Localization
Most early and small bone lesions are asymptomatic and are discovered with whole-body imaging
techniques, performed during work up or follow- up
in oncological patient care. These lesions do not
always show on conventional radiological imaging,
which would take around 50 % bone destruction to
be visible [ 7 ]. Especially in osteoblastic bone
lesions, limited bone destruction of 5–10 % can be
visualised on skeletal scintigraphy [ 7 ]. As men-
tioned in 22.1 , detection, characterisation and local-
ization of bone lesions can be enhanced by adding
3-D imaging technique (i.e., SPECT, PET, SPECT/
CT, PET/CT) and by using other radiotracers (i.e.,
18 F-FDG or 18 F-fl uoride).
Lesions detected primarily with PET/CT will
often be detected by skeletal scintigraphy as well.
Considering the wide availability of 140 keV
gamma probes for use in sentinel node biopsy
procedures in breast cancer and melanoma (as
opposed to 511 keV PET probes needed to detect
18
F-FDG or 18 F-fl uoride), performing a
99m
Tc
skeletal scintigraphy to confi rm uptake in the suspected lesion will improve the detection rate during 140 keV probe-guided surgery using
99m
Tc-labeled radiotracers.
22.2.1 Tracers Usually Used
and Route of Administration
Intravenously administered
phonates (hydroxy diphosphonate (HDP) or
methylene diphosphonate (MDP)) are the most
commonly used agents for skeletal scintigraphy.
99m
Tc-labeled diphos-
22 Radioguided Localization of Bone Lesions
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355
For radioguided bone biopsies, doses between
15–30 mCi (550–1110 MBq) have been described,
injected 2–12 h preoperatively [ 6 – 8 , 14 ].
Even though 18 F-labeled agents have increased
sensitivity and specifi city in nuclear medicine,
skeletal imaging and 511 keV probe-guided surgery have been demonstrated to be feasible; however, no series of PET probe-guided bone biopsies
have been published [ 15 ].
In osteoid osteoma, comparable doses of
intravenously administered
99m
Tc-labeled diphos-
phonates or oxidronate were used [ 10 – 12 , 16 ].
22.2.2 Preoperative Imaging
One to four hours after injection, preoperative
scintigraphic images can be obtained, but this is
not described in all series [ 6 – 12 ]. When deemed
necessary by the nuclear medicine specialist,
SPECT or SPECT/CT images can be obtained to
aid precise localization and marking on the skin.
In many surgical cases, skeletal scintigraphy,
SPECT scan or SPECT/CT images will already be
available from the original diagnostic evaluation
of the bone lesion. In addition to intraoperative use
of a140 keV gamma probe, skin marking of the
site of shortest distance between the skin and the
bone lesion by the nuclear medicine specialist
remains helpful to the surgeon.
22.3 Alternatives to Radioguided
Surgery or Combination
of Techniques
Radioguided surgery for bone lesions is indicated
when less invasive techniques, like percutaneous
radiological biopsy or RFA for osteoid osteoma,
is not possible or proves unsuccessful.
For standard radiological biopsy, suffi cient
bone destruction is needed to provide a target on
CT scan. In addition to standard radiologically
guided biopsy, reports on the value of PET/
CT-guided percutaneous biopsy have been published recently with a high rate of adequate biopsies (94.3 %) and up to 100 % sensitivity in
detecting malignant bone lesions [ 17 – 19 ].
22.4 Radioguided Localization,
Biopsy, and Possible
Resection of Bone Lesions
Radioguide surgery is planned 4–12 h after intravenous injection of the
anaesthesia and positioning on the operating table,
the handheld 140 keV gamma probe can be used to
check the activity at the skin mark and confi rm
localization of the bone lesion. After preparation
and draping of the operative fi eld, the handheld
gamma probe is put in a sterile plastic sleeve for
intraoperative use. Since most bone lesions targeted with radioguided surgery are located in
superfi cially located bones (ribs/sternum), a
3–5 cm incision directly over the lesion is suffi cient to expose the bone [ 6 – 8 ]. Depending on the
site of the bone lesion, indication (biopsy or complete excision) and build of the patient (muscular
or obese) exposure might be more extensive.
The target area (i.e., bone lesion) is identifi ed with
the handheld gamma probe; the activity of the target
is generally 1.6–10 times higher than background
activity of the adjacent bone tissue [ 6 – 8 , 11 , 12 ].
Several artefacts might occur during gamma
probe-guided surgery:
1. Use of electrical appliances, like the electro-
cautery, can distort the gamma probe signal.
Simultaneous use of these appliances and the
gamma probe is problematic.
2. Areas of increased concentration of the
labeled agent close to the bone lesion can hin-
der localization. Orientation of the gamma
probe in the direction of the bladder and bony
growth plates should be avoided.
3. Abrupt movement of the gamma probe with
regard to the bone surface can result in arte-
factual alterations of the counts per second.
Slow and even movements with the gamma
probe are advised [
Depending on the indication for gamma probeguided surgery, the outer cortex of the rib or sternum can be opened and biopsied with a rongeur as
well as the medulla. This leaves the inner cortex
intact, reducing the chance of a pneumothorax. If
complete resection is required, the extent of rib
resection can be determined, as based on the
99m
Tc-labeled agent. After
12 ] .
99m
Tc-
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