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ABC
AB
Figure 23.4 A 52-year-old male complaining of hematuria 10 days after right-side partial nephrectomy due to a renal cell carcinoma. (A) Contrast-enhanced
computed tomography scan with two-dimensional angiographic reconstruction shows a renal hematoma and an arterial pseudoaneurysm at the surgical field.
(B) Renal angiogram (arterial phase) shows a vascular injury with a pseudoaneurysm and an arteriovenous fistula. The rest of the kidney is normal, except for the
lack of visualization of the superior pole due to the partial nephrectomy. (C) Postembolization renal angiogram after occlusion of the injured vessel with coils
confirms disappearance of both pseudoaneurysm and arteriovenous fistula. Hematuria relapsed and did not recur at 6-month follow-up.
C
Figure 23.5 A 75-year-old male complaining of hematuria and
flank pain with extrarenal disease and comorbidities contraindicating
nephrectomy. Relapse of hematuria without recurrence at 1-year follow-up.
(A) Contrast-enhanced computed tomography scan shows a giant
right renal tumor with venous invasion and lymph node involvement.
(B) Renal angiogram (arterial phase) shows enlarged tumor vessels and
neovascularization typical of renal carcinoma. (C) Renal angiogram (venous
phase) shows the tumor and its extension inside the inferior vena cava.
(D) Postembolization renal angiogram after tumor embolization with
cyanoacrylate confirms tumor blush disappearance and patency of renal
arteries supplying the normal parenchyma.
D
Chapter23:Embolotherapy in the management of renal cell carcinoma
Other indications are refractory hypertension, hypercalcemia, or polycythemia, sometimes associated with large renal
tumors.
In this clinical setting embolization should be long-lasting
to decrease the symptom recurrence, thus a permanent embolic
material is mandatory. Liquid embolic agents, such as cyanoacrylate or alcohol, are suitable materials to achieve this goal.23
Complete embolization is not always necessary, and interventions must be limited to relieving symptoms (Figure23.5). e
drawbacks of embolization, including deterioration of renal
function, potential infections, and postembolization syndrome,
can thus be reduced. Partial embolization is far less aggressive
than surgery, and is therefore preferred in many institutions,
sometimes in conjunction with new anticancerdrugs.
Partial embolization does not mean incomplete embolization, and the IO should occlude all the capillary tumor vessels,
including extrarenal parasitic vessels if they supply the tumor.
Although the goal of embolization in end-stage tumors is palliative, some authors have reported an increased survival by
several months.
24
Palliative renal embolization is considered a safe procedure, with a relatively low complication rate. e most common
occurrence is a self-limited postembolization syndrome, that
usually resolves in several days. Supportive treatment with
analgesics, antipyretics, and antiemetics is advisable as well as
overnight hospitalization.
Complications
e morbidity and mortality of embolotherapy in renal carcinoma treatment are extremely low provided knowledge of functional vascular anatomy, a meticulous technique, and correct
patient selection are employed. Pretherapeutic clinical workup,
including measures to overcome contrast-induced nephropathy and correct management of comorbidities, is essential to
avoid predictable complications. It has to be remembered that
many patients with renal cancer are old enough to have vascular
219
Section VI:Renal cell carcinoma
comorbidities, therefore care in arterial access puncture and
renal catheterization is essential to avoid complications of endovascular navigation. Contrast medium must be kept to a minimum and nephrotoxic medication (antibiotics, non-steroidal
anti-inammatory drugs) precluded whenever possible. is
is especially important aer palliative embolization of large
tumors, because tumor necrosis leads to an acidotic state that
is a further risk factor for nephrotoxicity.
e use of state-of-the-art technology, including digital subtraction angiography, road mapping, cone-beam CT,
and high-quality uoroscopy, provides excellent visualization
of the renal vessels and territory to be embolized. Mastering
ow-guided embolization and liquid agents are a must to
achieve ecacy and to avoid non-target embolization, while
keeping as much functional parenchyma as possible.
Postembolization syndrome is a rather frequent adverse
event aer embolization of large tumors, especially if normal
functioning parenchyma is compromised. Early treatment
with hydration, bed rest, antipyretics, and analgesics usually
control the self-limited symptoms. Postembolization crucial
pain, a severe, uncommon complication, is unlikely if normal
parenchyma is spared. e IO must be alert to prevent pain
with adequate medication.
Overall, embolization of renal tumors is a well-tolerated
procedure with very low, almost nil, incidence of complications
if performed by an experienced operator.
Conclusion
e role of the IO in the management of renal cancer is increasing, in both percutaneous and endovascular therapies. Amainstay in the latter is embolotherapy that is indicated in dierent
scenarios:(1)preoperative embolization in the management of
large tumors extending into the renal vein or inferior vena cava
to facilitate surgical resection while decreasing the amount of
blood transfusion; (2)preoperative embolization in the management of small renal tumors to avoid vascular clamping,
therefore precluding WIT and function loss; (3) postoperative embolization to resolve symptomatic vascular injuries, the
most serious complication of PN; and (4)palliative embolization to control tumor-related symptoms such as hematuria,
ank pain, or others in otherwise inoperable patients.
e preferred technique for embolization varies depending
on the goal of treatment, tumor characteristics, angioarchitecture, and IO preferences. e use of microcatheters is highly
recommended as well as proper embolic material, such as
microspheres and/or liquid agents.
Performed by experienced operators using state-of-the-art
technology and under the correct indications, embolotherapy
has a denitive role in the armamentarium of renal carcinoma
treatment.
2. Yamaguchi Y, Simmons MN, Campbell S. Small renal
masses:risk prediction and contemporary management.
Hematol/Oncol Clin N Am 2011; 25:717–736.
3. Rini BI, Campbell SC, Escudier B. Renal cell carcinoma. Lancet
2009; 373:1119–1132.
4. Georgiades CS, Rodriguez R. Ecacy and safety of
percutaneous cryoablation for stage 1A/B renal cell
carcinoma:results of a prospective, single-arm, 5-year study.
Cardiovasc Intervent Radiol 2014; 37:1494–1499.
5. Kadir S. Atlas of Normal and Variant Angiographic Anatomy.
Philadelphia:WB Saunders; 1991, pp. 387–428.
6. Mahvash A, Javadi S, Ahrar K. Embolotherapy in the
management of renal cell carcinoma. In Soulen MC, Geschwind
JF, eds. Interventional Oncology:Principles and Practice.
Cambridge:Cambridge University Press.2008.
7. Loroy R, Abualsaud B, Delgal A, Guiu B, Kermarrec I,
Michel F, etal. Place de l’embolisation artérielle percutanée en
pathologie rénale. Prog Urol 2010; 20:161–171.
8. Kalman D, Varenhorst E. e role of arterial embolization in
renal cell carcinoma. Scand J Urol Nephrol 1999; 33:162–170.
9. Bakal CW, Cynamon J, Lakritz PS, Sprayregen S. Value of
preoperative renal artery embolization in reducing blood
transfusion requirements during nephrectomy for renal cell
carcinoma. J Vasc Interv Radiol 1993; 4:727–731.
10. Loroy R, Rao P, Ota S, Geschwind JF. Renal artery
embolisation prior to radical nephrectomy for renal cell
carcinoma:when, how and why? Br J Radiol 2010; 83:630.
11. Zielinski H, Szmigielski S, Petrovich Z. Comparison of
preoperative embolization followed by radical nephrectomy
with radical nephrectomy alone for renal cell carcinoma. Am
J Clin Oncol 2000; 23:6–12.
12. May M, Brookman-Amissah S, Panz S, Roigas J, Hoschke B,
Kendel F. Pre-operative renal arterial embolisation does not
provide survival benet in patients with radical nephrectomy
for renal cell carcinoma. Br J Radiol 2009; 82:724–731.
13. Zini L, Perrotte P, Capitanio U, etal. Radical versus partial
nephrectomy:eect on overall and noncancer mortality. Cancer
2009; 115:1465–1471.
14. Campbell SC, Novick AC, Belldegrun A, etal. Guideline
for management of clinical T1 renal mass. J Urol 2009;
182:1271–1279.
15. ompson RH, Lane BR, Lohse CM, etal. Every minute counts
when the renal hilum is clamped during partial nephrectomy.
Eur Urol 2010; 58:340–345.
16. Gill IS, Patil MB, de Castro Abreu AL, etal. Zero ischemia
anatomical partial nephrectomy:a novel approach. J Urol 2012;
187:807–815.
17. Gallucci M, Guaglianone S, Carpanese L, etal. Super-selective
embolization as rst step of laparoscopic partial nephrectomy.
Urology 2007; 69:642–646.
18. Simone G, Papalia R, Guaglianone S, Carpanese L, Gallucci
M. Zero ischemia laparoscopic partial nephrectomy aer
superselective transarterial tumor embolization for tumors
with moderate nephrometry score:long-term results of a
References
1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics. Cancer J Clin
2010; 60:277–300.
single-center experience. J Endourol 2011; 25:1443–1446.
19. Jung S, Min GE, Chung BI, Jeon SH. Risk factors for
postoperative hemorrhage aer partial nephrectomy. Korean J
Urol 2014; 55:17–22.
220
Chapter23:Embolotherapy in the management of renal cell carcinoma
20. Montag S, Rais-Bahrami S, Seideman CA, etal. Delayed
hemorrhage aer laparoscopic partial nephrectomy:frequency
and angiographic ndings. BJU Int 2011; 107:1460–1466.
21. Uberoi J, Badwan KH, Wang DS. Renal artery pseudoaneurysm
aer laparoscopic partial nephrectomy. J Endourol 2007;
21:330–333.
22. Maxwell NJ, Saleem Amer N, Rogers E, Kiely D, Sweeney P,
Brady AP. Renal artery embolisation in the palliative treatment
23. Seran Z, Karolkiewicz M, Strzesniewski P, Lasek W,
Bryczkowski M, Wolski Z. Palliative percutaneous kidney
embolization with enbucrilate in patients with renal cell
carcinoma:safety and symptom control. Med Sci Monit 2007;
13:98–104.
24. Kaumann GW, Richter GM, Rohrbach R, Wenz W. Prolonged
survival following palliative renal tumor embolization by
capillary occlusion. Cardiovasc Intervent Radiol 1989; 12:22–28.
of renal carcinoma. Br J Radiol 2007; 80:96–102.
221
Section VII
Organ-specific cancers – chest
Chapter
Image-guided ablation in thethorax
24
Erica S. Alexander and Damian E.Dupuy
Surgical resection remains the reference standard for the treatment of early-stage lung cancer and isolated pulmonary metastases in select patients. Although surgery oers patients the best
chance of disease-free survival, only about a third of patients
with non-small cell lung cancer (NSCLC) are considered candidates for surgical resection.1 Historically, these patients have
been treated with chemotherapy or external-beam therapy;
however, these modalities provide only modest improvements
in overall survival. Over the past decade, several new minimally
invasive therapies, such as thermal ablation, stereotactic body
radiotherapy, and targeted receptor inhibitors, have emerged as
promising treatment alternatives for non-operative candidates.
ermal ablation is an exciting and cost-eective therapy
that oers patients an eective and safe treatment to palliate
and, in some cases, cure both primary and metastatic thoracic
malignancies. e benets of thermal ablation include that it
can be repeated, used in previously irradiated elds, and used
in conjunction with pharmacologic treatments, chemotherapy,
or radiotherapy.
e goal of this chapter is to discuss and review the tech-
is converted to heat, leading to thermal injury and cell death in a
controlled manner.2 e goal of RFA is to achieve temperatures
between 60°C and 100°C, which allow for near-instantaneous
protein coagulation, damage to cytosolic and mitochondrial
enzymes, and damage to DNA–histone complexes.
3,4
e unique physiological properties of lung tissue create
particular considerations for ablation of neoplasms within the
lung. e thermal conductivity in lung is lower than that of
other tissues, due to the high percentage of air by volume.5 e
eect of this is twofold:lower conductivity limits heat transfer to
tissues adjacent to solid pulmonary masses and the surrounding
air in normal lung parenchyma acts as an insulator that concentrates RF energy in the targeted solid tissue.
6,7
is suggests that
RFA may be limited in providing adequate ablation of inltrative margins or satellite tumors at the periphery of lung lesions;
however, the insulation properties of lung tissue may create
improved tumor damage at the interior of lesions. Also, the high
vascular ow of the lung creates a “heat-sink” eect, where thermal energy is dissipated away from normal adjacent tissue and
concentrated within the solid component of the target lesion.
8
nologies and techniques available for tumor ablation of thoracic malignancies, including the basic physics of ablation,
procedure technique, imaging follow-up, comparisons between
therapies, and applications and outcomes for ablation therapy
in the thorax.
Physics of ablation therapy
Image-guided tumor ablation utilizes thermal or electrical
energy to create controlled destruction of cells and tissues. e
three mainstays in thermal ablation therapy, radiofrequency
ablation (RFA), microwave ablation (MWA), and cryoablation (CA), are discussed in this chapter. Additionally, irreversible electroporation (IRE), the newest ablation modality, is
reviewed in thispiece.
Radiofrequency ablation
In RFA, an alternating current about the frequency of radio waves
(460–480kHz) is created between an electrode and grounding pads
placed on the patient. e insulated electrode has a conducting
tip that creates ion agitation in adjacent tissue, as electrons move
toward the reference electrodes (grounding pads). is friction
Microwave ablation
MWA utilizes electromagnetic waves in the microwave energy
spectrum (300MHz to 300GHz) to create tissue-heating eects.
Alternating electromagnetic microwaves at frequencies of 915
and 2,450MHz produce rapid rotation, or oscillation, of polar
water molecules, causing the water molecules to ip several billion times a second. e interaction of the water molecules with
the surrounding tissues causes a transfer of kinetic energy and
subsequent tissue heating to cytotoxic levels.
MWA is considered a potentially superior treatment option
to RFA due to a broader energy deposition, the creation of a
larger zone of active heating, higher intratumoral temperatures, larger tumor ablation volumes, faster ablation times,
and a decreased heat-sink eect.
10,11
Antennae generate a larger zone of active tissue heating by creating a broad elliptical
eld of power density deposition extending up to 2 cm in
radius from the active tip. is allows for a more sizeable zone
of active heating and a more uniform induction of cell death
within the ablation zone.12 Additionally, the exibility of using
multiple antennae simultaneously allows for synergistic energy
9
Interventional Oncology, Second Edition, ed. Jean-François H. Geschwind and Michael C. Soulen. Published by Cambridge University Press.
©Cambridge University Press2016
223
Section VII:Chest
deposition and the creation of larger ablation zones in fewer
and faster applications.
13,14
MWA also eliminates the need for
grounding pads, as an electrical current is not passed through
the patient. Additional reported advantages include more eective heating of cystic masses, less char eect, and less procedural
pain secondary to absent electrical nerve stimulation.
9,15
due to comorbid cardiopulmonary disease or an inability to
tolerate lung loss. Ablation is also a viable option for patients
seeking palliation for tumor-related symptoms or who have
recurrences in previously radiated elds. One benet of ablative therapy is that there are generally no lower limits for the
forced expiratory volume in 1second or the diusion capacity
of lungs for carbon monoxide, making ablation feasible even
Cryoablation
CA relies on the Joule–ompson eect, where pressurized
argon gas is transferred to a region of lower pressure, causing expansion of the gas and cooling of temperatures to as low
as–140°C. Helium gas has the opposite Joule–ompson eect
and is used to warm the probe and facilitate its removal at the
end of the procedure. Each CA therapy involves a consecutive
freeze, thaw, and freeze cycle. e osmotic shis that accompany these temperature uctuations are responsible for cellular
membrane rupture and eventual cell death. Protein denaturation occurs as a result of intracellular and extracellular ice crystal formation and tissue ischemia results from vascular injury,
cellular edema, and vessel disruption.
CA has several advantages that make it an appealing thermal ablation option. e ice ball created during treatment is visible on computed tomography (CT), allowing visualization of
the ablation zone. Aer the rst freeze-and-thaw cycle, pulmonary uid enters the alveolar spaces, causing a 20-fold increase
in thermal conductivity; possible benets of this increased
conductivity are more rapid freezing and an expanded ablation
zone on subsequent cycles.16 Additionally, CA preserves the collagenous structure of ablated tissue, making it a safe option near
major vessels, the tracheobronchial tree, and mediastinum.
Irreversible electroporation
IRE is a novel ablation technology being investigated for the
treatment of solid malignancies. It utilizes direct electrical pulses
to create nanoscale defects or pores in cell membranes; these
defects disrupt cellular homeostasis, leading to apoptotic cell
17,18
death.
Electroporation can either be reversible or irreversible,
the latter leading to cell death. e direct electrical pulses in IRE
are deposited using an applicator; this forms an electrical eld
whose magnitude decreases from the applicators outward to the
tissue. Cells immediately adjacent to the applicator undergo cell
death by virtue of irreversibly increased permeability.
Given that IRE is a non-thermal ablation technique, its purported benets include overcoming the heat-sink eect and the
ability to treat near bronchovascular structures without causing structural injury.
18,19
IRE pulses generate denite cell death,
allowing for very precise ablative borders on a cell-scale level.20
eoretically, IRE would be a well-suited ablation modality for
lung lesions close to the chest wall, hilum, and mediastinum
due to the low potential for collateral structural damage.
Performing ablation therapy
Patient selection
Image-guided ablation therapies are best suited for patients
with early-stage malignancies who are non-surgical candidates
in patients with severely impaired pulmonary function or with
a single lung. Patients stable enough to undergo CT-guided
needle biopsy should be considered candidates for lung tumor
ablation. Patients with pulmonary brosis are generally poor
candidates for ablation, as exacerbation of the underlying disease may result in respiratory failure ordeath.
Patients referred for ablation are initially evaluated in a
clinic setting, where the patient’s history and pertinent imaging and laboratory studies are reviewed. e appropriateness
of therapy and the risks and benets of the procedure are
discussed. Side eects, including postablation syndrome (a
transient systemic response marked by fever, malaise, and anorexia), intraprocedural pain (generally mild to moderate and
controlled with analgesics), pneumothorax (possibly requiring
placement of a chest tube), hemorrhage, hemoptysis, bronchopleural stula (possibly requiring treatment with chest tube
suction, Heimlich valves, pleurodesis, surgery, or endobronchial valves),21 acute respiratory distress syndrome, reactive
pleural eusion, damage to adjacent anatomic structures, skin
burns, infection, or abscess formation, are discussed.
Implantable cardiac devices or pacemakers are not contraindications to ablation therapy; however, careful planning
between radiology and cardiology and careful positioning of
grounding pads and electrodes are essential to avoid adverse
outcomes.
22
Procedure
To reduce the possibility of sedation-induced nausea or aspiration of gastric contents, all patients are instructed to fast
overnight prior to procedure. Patients treated for hypertension or cardiac disease are instructed to take their medications as directed. Patients with insulin-dependent diabetes are
instructed to take half of their morning insulin dose. ose
patients receiving anticoagulant and antiplatelet medications
are advised to stop taking them 2–7 days prior to ablation.
Prior to treatment, an abbreviated physical exam is performed
and an intravenous line is placed. Our institution does not routinely administer prophylactic antibiotics.
Most procedures are performed under conscious sedation
with midazolam (0.5–1.0-mg doses) and fentanyl (25–50-μg
doses). General anesthesia is required for IRE and is an option
for pediatric patients or when procedural pain is problematic.
Patients’ vital signs, pulse oximetry, and electrocardiogram
(ECG) are continuously monitored throughout the procedure.
e skin entry site for the ablation applicator or antennae is
determined using preprocedure CT scout images. Laser lights
emitted from the CT gantry correspond to x- and y-axes from
a grid on a computer screen; these lines are used to coordinate the entry site on the patient’s skin. e skin is prepped
and draped in a sterile fashion and local and deep extrapleural
224
Chapter24:Image-guided ablation in thethorax
lidocaine anesthesia is administered. CT uoroscopy is utilized
to obtain real-time images; a spinal needle is used to plan the
appropriate electrode trajectory.
Some institutions have implemented creative adjunctive
procedures to optimize targeting, prevent complications, or
lessen pain during ablation. Use of intercostal and paravertebral nerve blocks with a long-acting local anesthetic has been
reported to decrease postprocedural discomfort and pain.23
Certain institutions have reported using hydrodissections or
articial pneumothoraces when ablating tumors near sensitive structures, including nerves, vessels, or cartilaginous
structures.
24
Vagal nerve stimulation during ablation can cause referred
pain to the jaw, teeth, chest, or upper extremity. Additionally,
vagal nerve stimulation can result in bradycardia; this can be
treated with 0.5-mg doses of atropine.
Aer the targeted tumor is treated, the electrodes are
removed and a CT uoroscopic image is obtained to evaluate for pneumothorax. Large pneumothoraces are treated with
chest catheters and wall suction. Smaller, asymptomatic pneumothoraces are monitored and a 2-hour follow-up radiograph
is obtained. If the pneumothorax has increased in size, a chest
catheter is placed and a 24-hour follow-up chest radiograph is
scheduled to evaluate air leak resolution. ese patients can
be discharged home with a Heimlich valve. For patients with
persistent pain or who are apprehensive about outpatient management, inpatient admission is considered. Patients without
immediate complication or pneumothorax are observed for at
least 2 hours aer treatment and interval follow-up imaging is
scheduled upon discharge.
Specic considerations for each ablation modality are discussed in further detailbelow.
Radiofrequency ablation
In RFA, an electrode connected to a generator is placed directly
into a targeted lesion. Prior to treatment, technical sta place
grounding pads on the opposite chest wall from the site of skin
entry, in order to direct the RF current and prevent damage to
adjacent structures. Once the site of entry is determined based
on review of scout images, the RF electrode is placed through
the skin and pleura. CT uoroscopic images are obtained,
to monitor appropriate placement of the electrode into the
intended target lesion.
e choice of electrode length and active tip length is made
according to the size and depth of the lesion. Decisions regarding the temperature and/or impedance should be made according to manufacturer specications for the RF device utilized.
For pleural-based lesions, a shorter RF electrode is used. e
ideal placement of the electrode is along the longitudinal axis
of the tumor. RF electrodes have internal thermocouples that
measure the temperature of the treated tissues. e electrodes
can also be coupled to an infusion pump with ice water or cold
saline, which internally cools the electrode tip and minimizes
charring. RF activations are typically between 4 and 12minutes
in a single location.
For lesions smaller than 2cm in diameter, central and distal
positioning of the RF electrode is generally adequate for the
rst ablation, with subsequent tandem ablations performed
during more proximal positioning. For lesions larger than
2cm in diameter, one can use larger electrodes or create several
overlapping ablation zones in order to ensure adequate thermocoagulation of the lesion (Figure24.1).
ere are currently three commercially available RFA
systems in the United States. Two of the systems (Boston
Scientic, Radiotherapeutics, Watertown, MA and
RITA Medical Systems, Mountain View, CA) utilize a
deployable-array RF electrode that consists of 4–16 small
wires (tines) deployed through a 14–17-gauge needle. Because
the tines curve backward toward the handle, the Boston
Scientic, Radiotherapeutics Device (Leveen electrode) is
initially deployed at the deep aspect of the tumor. In contrast,
the RITA electrode tines course forward and lateral so the
probe is deployed on the near surface of the tumor. e third
RF system (Cool-tip, Covidien, Boulder, CO) utilizes a single
or triple “cluster” (no tines) perfused electrode. e Covidien
system comes with a switching controller that allows for the
simultaneous placement of up to three single electrodes that
are spaced 1.5–2.5cm apart. is internally cooled RF electrode can increase the volume of induced thermocoagulation
in a single activation.
Microwave ablation
Like RFA, MWA allows for exible approaches to treatment,
including percutaneous, laparoscopic, and open surgical
access. MWA, however, does not distribute energy in an electrical current, obviating the need for groundingpads.
A microwave antenna is attached to the microwave generator with a coaxial cable and an electromagnetic microwave
is emitted from the exposed, non-insulated portion of the
antenna. Intratumoral temperatures can be measured with a
separately placed thermocouple. MWA can be performed using
either a single MW antenna or a conguration of three antennae, which creates a greater ablation volume. We advise that,
for tumors greater than 2cm, operators utilize three electrodes,
spaced 2cmapart.
ere are currently six MW systems commercially available
in the United States. ree of the systems use a 915-MHz generator (Evident, Covidien, Manseld, MA; MicrothermX, BSD
Medical, Salt Lake City, UT; Avecure, Medwaves, San Diego,
CA) and three utilize a 2,450-MHz generator (Certus 140,
Neuwave, Madison, WI; Amica, Hospital Service, Rome, Italy;
Acculis MTA, Microsulis, Hampshire, UT). e MW antennae are all straight applicators and have active tips ranging in
length from 0.6 to 4.0cm.
Cryoablation
Percutaneous CA can be performed under CT guidance, ultrasound (US) guidance, and magnetic resonance imaging (MRI).
All three modalities allow for visualization of the intraprocedural “ice ball,” which serves as a marker for ablative margin
estimation.
Each CA therapy typically involves a 10-minute freeze of
the tumor, an 8-minute helium thaw, and another 10-minute
freeze. Newer CA treatment schemes have been proposed
225
Section VII:Chest
A
C
E F
B
D
Figure 24.1 Radiofrequency ablation
(RFA) for an early-stage lung cancer.
A 68-year-old woman with severe
obstructive airway disease that precluded
surgical resection treated with RFA for
a lesion located in the left upper lobe
near the mediastinum. (A) Pretreatment
positron emission tomography (PET)/
computed tomography (CT) shows a
PET-avid, 3.0-cm lesion (arrow) in the left
upper lobe with a maximum standardized
uptake value of 6.5. (B) CT-fluoroscopic
image shows optimal positioning of
a single RF electrode within the mass.
(C) Pull-back of the RF electrode allows
for a second activation of the lesion,
further enhancing the size of the
ablation zone. (D) Contrast-enhanced
CT image 4 months after RFA shows
a large area of thermocoagulation
with no evidence of enhancement
(arrow). (E) Contrast-enhanced CT
image 11 months after RFA shows
postablation involution of the
thermal scar (arrow). (F) Coronal
reconstruction of contrast-enhanced
CT image at 11 months posttreatment.
(G) Contrast-enhanced CT image
17 months after RFA shows contraction of
the region of thermocoagulation (arrow).
(H) Coronal reconstructions of CT images
at 17 months showing further involution
of the ablated tumor (arrow).
G
H
as a means of shortening the ablation time and creating a
larger ablation zone. ese use a 3-minute freeze, 3-minute
thaw, 7-minute freeze, 7-minute thaw, and a nal 5-minute
freeze. A CT scan is typically obtained aer treatment and
the low-density changes within the targeted tumor are measured and used to approximate the size of the ablated region.
e outer periphery of the freeze zone may not reach cytotoxic temperatures; therefore, a 3–7-mm margin is subtracted
226
Chapter24:Image-guided ablation in thethorax
from the diameter of the low-density ablation region to better
approximate the true volume of tissue necrosis.
25
Two commercially available percutaneous, argon-based CA
devices, Precise (Calil Medical, Arden Mills, MN) and Cryocare
(Endocare, Irvine, CA), are currently available in the United
States. ese systems allow the placement of 1–15 1.5–2.4-mmdiameter cryoprobes and can achieve tumor necrosis with a
single freeze–thaw–freezecycle.
Irreversible electroporation
To date, there have been few published clinical studies evaluating electroporation of lung tissue in humans.
26,27
At our institution, lung IRE has only been evaluated in a swine model. Nine
domestic swine were premedicated with a parasympatholytic,
a sedative, and an alpha-blockade anesthetic. e procedure
was performed under general anesthesia and a neuromuscular blockade was administered to counteract the high direct
current voltages of the IRE pulses. ECG, heart rate, respiratory rate, temperature, pulse oximetry, and end-tidal CO2 were
monitored throughout the procedure. Evoked motor response
was monitored throughout the duration of the procedure until
muscle function was restored. If needed, the muscle relaxation
was reversed using edrophonium and atropine.28 Of note, an
ECG-gated delivery of high-voltage pulses is necessary to prevent potentially serious cardiac arrhythmias.
Currently, there is one IRE system approved for use in the
United States (Nanoknife, AndioDynamics, Latham NY). e
system utilizes monopolar electrodes with a retractable sheath,
which allows the active tip to be adjusted between 1 and 4cm.
e generator allows for the simultaneous use of up to six electrodes with a maximum delivery of 50Å and 3000V.
Cavitation seems to be more common when lesions are located
in close proximity to a segmental bronchus or when ablation
areas vastly exceed the size of the original tumor.
32,33
Bubble
lucencies are frequently seen in those ablation zones that do not
demonstrate cavitation.32 Immediate postablation imaging can
also demonstrate a “cockade” phenomenon, dened as multiple concentric rings with varying densitometric characteristics
at the site of treatment, which are believed to correspond to the
ve histopathological zones described by Miao etal.
34,35,36
e
ve zones are seen on macroscopic pathologic specimens and
represent the tissue gradient between the ablated lesion and the
surrounding parenchyma:(1)zone A, a needle track; (2)zone
B, a large pale area representing tumor coagulation necrosis;
(3)zone C, a layer of ablated parenchyma; (4)zone D, a dark
rim representing congestion and hemorrhage; and (5)zone
E, a peripheral inammatory reaction.34 Additionally, pleural
thickening along the trajectory of the electrode is not uncommon aer ablation.
At 1 week to 1month post-RFA the lesion generally appears
consolidated and/or nodular with a diameter exceeding the
pretreatment size. If the treatment response is complete, then
CT scans 2–6 months aer the ablation should show either
no change or a decrease in size or morphology from the initial post-RFA baseline study. Additionally, successfully ablated
tumors show decreased contrast enhancement. Jin and colleagues described that partially and completely ablated lesions
show similar radiographic changes up until 6months, at which
point the partially ablated lesions demonstrated an interval
increase in size.
37
Positron emission tomography (PET) can also be used to
evaluate the success of treatment, while providing the added
surveillance of extrathoracic disease. Decreased or absent
Imaging follow-up
Imaging immediately aer the procedure and during follow-up
is necessary to measure the success of ablation. Appropriately
evaluating ablated lesions can be challenging, as radiologists
have to account for the residual mass and ablation zone, which
evolves due to the tissue’s inammatory or cytotoxic response.
Imaging studies allow one to measure the success or failure of
the initial ablation, interval growth and need for repeat ablation, and/or metachronous tumor development. ere is currently no consensus as to which imaging modality or time
interval postablation best detects these events. Here we discuss peri- and postprocedural imaging ndings and suggested
follow-up strategies.
Radiofrequency ablation
With RFA, the ablated lesion will generally show vaporization
and wrinkling at the edges within 72hours of treatment. e
most common imaging nding aer ablation is the appearance
of ground-glass opacication. e size of the ground-glass
opacity on immediate postablation follow-up has been shown
to predict the eectiveness of treatment.
29,30
In fact, several studies have shown no tumor recurrence when the ground-glass
opacity extended 5mm beyond the tumor margins.
29,31
Other
positive predictors of treatment include cavitation of the lesion.
PET activity suggests tumor necrosis, while residual or recurrent tumors tend to exhibit PET uptake. It is, however, possible to see PET activity within 6months of ablation due to the
inammatory response of the tissue, especially when lesions
are close to the pleura.
38,39
Deandreis and colleagues prospectively compared the role of uorine 18-uorodeoxygluose
(FDG) combined with CT versus chest CT alone in 34 patients
undergoing lung RFA. eir results indicated that FDG PET/
CT depicts treatment failure earlier than chest CT, without any
false-negative ndings. Given that tumors can show inammatory uptake postablation, the authors suggest distinguishing
recurrence from benign uptake by evaluating uptake pattern.
Diuse, peripheral, and homogeneous FDG uptake is generally related to the inammatory processes, while heterogeneous and focal uptake is more consistent with disease relapse.
40
At our institution, an overall increase in the size of the
so-tissue ablation zone 1.25times that of the greatest diameter noted on initial baseline CT is considered to represent
local progression, as is the presence of any so-tissue focus
larger than 9mm in greatest dimension showing signicant
enhancement (>15HU greater than the non-contrast series).
An enhancing rim of so tissue surrounding the ablation zone
is considered reactive if it is uniform in thickness and 5mm or
less in thickness. PET scans are performed when CT ndings
are suggestive of disease progression.
227
Section VII:Chest
Microwave ablation
On initial postablation contrast-enhanced CT scans,
MW-ablated tumors show the eects of thermally induced
necrosis. e most common nding is a hazy ground-glass
opacication within and around the zone of ablation. Ablation
zones are noted to increase in size at 1-, 3-, and 6-month
follow-ups due to thermal changes in the adjacent lung
parenchyma. e ablation zones should later consolidate and
reduce in diameter. At our institution, we noted that cavitary
changes post-MWA were statistically related to a reduction in
cancer-specic mortality. Additionally, pleural thickening is a
common nding in ablated tumors that abut the pleura.
41
Cryoablation
Ito and colleagues described the CT appearance of 79 lung
tumors aer treatment with percutaneous CA. ey noted that
the majority of lesions showed the following progression on
follow-up scans:at 1-week follow-up a consolidation/atelectasis
or nodular pattern was seen; at 1month or later, involution and/or
a “stripe” were seen; and zones eventually became indistinct. e
“stripe” pattern, dened as a at, linear density without a nodule,
was seen in 80% of those patients who showed local progression
at 6months or later. e authors noted that internal and marginal
enhancement of the ablation zone within 3months of treatment
did not show a direct relationship with local progression.
42
Kawamura etal. reported imaging ndings for 20 patients
who underwent CA. e response of the tumors was evaluated using the Response Evaluation Criteria in Solid Tumors
(RECIST) protocol, which is based on objective measurements
of lesion size before and aer treatment. e response to CA
was 50%. Although tumors developed marked scar formation
postprocedure, CT images still provided an accurate evaluation
of tumor size. Seventy-nine percent of tumors diagnosed as stable showed no signs of recurrence at 14-month follow-up.
43
and nerves. ere is also a theoretical risk of systemic embolic
events caused by gas microbubbles secondary to charring. We
believe this risk is extremely small, as there is only one documented case of acute stroke in the literature, which was likely
unrelated to the ablation treatment.37 Furthermore, animal
studies on lung RFA and its eects on brain circulation failed to
identify any ischemic brain injury related to treatment.
44
e advantages of MWA include consistently higher intratumoral temperatures, broader energy deposition, an improved
convection prole, larger tumor ablation volumes, faster ablation times, and more eective heating of cystic masses.
9,10,11
Additionally, the higher heat potential of MWA is theorized to
better overcome the heat-sink eect caused by adjacent blood
ow or air ow.11 Unlike RFA, MWA does not rely on an electrical circuit, which allows multiple applicators to be used simultaneously; this in turn creates a larger ablation zone in less time.
In a swine model, Brace and colleagues compared the ablation
zones produced by equivalently sized microwave and radiofrequency applicators. Histological examination of the ablated
lung tissue indicated that those ablation zones produced with
microwave energy were 35% larger in mean diameter, 50%
larger in cross-sectional area, and 133% larger in volume than
those produced with RFA (Figure24.2).
10
e advantages of CA over RFA include larger tumor ablation volumes, the ability to use multiple applicators, a highly
visible ablation zone, and less procedural pain due to the analgesic eect of freezing. Compared to heat-based thermal ablation therapies, CA is able to preserve the collagenous tissue
and cellular architecture in frozen tissue, which makes it a safer
option near vasculature or bronchi.
45,46
Bleeding along the needle tract is a theoretical disadvantage of CA; tract coagulation
with brin glue can be used in such instances. Another disadvantage of CA is the long procedural time required to generate adequate tumor coverage compared to heat-based ablative
therapies (Figure24.3).
IRE is the newest of the ablation technologies and currently
Irreversible electroporation
At this time, limited data are available on the use of IRE in
human lungs, making it dicult to evaluate imaging ndings.
Comparison of thermal ablation techniques
e goals of all thermal ablation strategies are to:(1) obtain a
negative margin; (2) avoid injury to adjacent structures; and
(3)create large ablation areas quickly. e ability to gauge our
success at meeting these goals is dicult, as data evaluating outcomes of thermal ablation tend to be inconsistent. Historically,
ablation study groups are heterogeneous and follow-up times and
reporting standards vary across institutions. ere is also a paucity of prospective blinded studies that compare dierent ablation
modalities to one another or to surgical or radiation therapies.
e greatest advantage of RFA is experience; the technology has been used in the lung for over a decade and many institutions have published data regarding the safety and ecacy
of treatment. e greatest limitation of RFA is that it is to be
avoided in the mediastinum and lung apex, due to the risk of
mechanical and thermal injury to blood vessels, central airways,
has minimal data evaluating its use in humans or long-term
ecacy. eoretical benets of IRE include a narrow transition between the ablation zone and healthy parenchyma, the
ability to overcome heat sinks, and preservation of underlying
structures.
18,19,20
At our institution, electroporated lung tissue in
a swine model was histologically evaluated. Analysis revealed
focal areas of diuse alveolar damage with brosis and inammation that were within the boundaries of the interlobular
septa. Bronchioles and blood vessels within the treated region
were intact without signs of tissue injury. Furthermore, review of
pathology 2–4-weeks aer treatment showed evidence of healing
within the lung.28 ere are currently two reports in the literature of the use of IRE in human lung tissue. Overall, ve patients
with lung malignancies were treated, and, while treatments were
without complications, all 5 patients showed recurrent disease
on follow-up.
26,27
Additionally, IRE treatments must be performed under general anesthesia, which presents the additional
risks associated with anesthesia and increases treatmenttime.
To the best of our knowledge, RFA is the only ablation therapy that has been prospectively compared to other mainstays
in lung cancer treatment, including sublobar resection and
228