Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3899_Библиотеки_им_академика_М_И_Перельмана.pdf
year overall survival rates of 77% versus 87.1% with
sublobar resection and 87.5% with RFA (p > 0.05).
There was little difference in the cancer-specific
survival with PCT versus the other two treatment
options.
51
In a retrospective review of 71 consecutive
patients with mixed pulmonary tumors, but
mostly metastatic disease, Yashiro et al found that
1-, 2-, and 3-year local progression-free rates were
80.4%, 69%, and 67.7%, respectively. Presence of a
vessel≥ 3mm no more than 3 mm from the edge of
the tumor was associated with local progression.
52
Yamauchi et al found that, in 160 medically
inoperable stage I NSCLCs treated with PCT, the 2-
and 3-year overall survival was 88% and 88%,
respectively. The mean disease-free 2- and 3-year
survival was 78% and 67%, respectively. Impor-
tantly, there was no decrease in pulmonary func-
tion tests, similar to RFA, as would be seen with
surgical resection or radiation therapy.
53
References
[1] Spira A, Ettinger DS. Multidisciplinary management of lung
cancer. N Engl J Med 2004; 350(4): 379–392
[2] McGarry RC, Song G, des Rosiers P, Timmerman R. Observa-
tion-only management of early stage, medically inoperable
lung cancer: poor outcome. Chest 2002; 121(4): 1155–1158
[3] Burt MMN, Ginsberg RJ. Surgical treatment of lung carcino-
ma. In: Baue AE, ed. Glenn’s Thoracic and Cardiovascular
Surgery. 6th ed. Stamford, CT: Appleton & Lange; 1996:421–
443
[4] Welter S, Cheufou D, Ketscher C, Darwiche K, Maletzki F, Sta-
matis G. Risk factors for impaired lung function after pulmo-
nary metastasectomy: a prospective observational study of
117 cases. Eur J Cardiothorac Surg 2012; 42(2): e22–e27
[5] Littrup PJ, Bang HJ, Currier BP et al. Soft-tissue cryoablation
in diffuse locations: feasibility and intermediate term out-
comes. J Vasc Interv Radiol 2013; 24(12): 1817–1825
[6] Goldberg SN, Gazelle GS, Compton CC, McLoud TC. Radiofre-
quency tissue ablation in the rabbit lung: efficacy and com-
plications. Acad Radiol 1995; 2(9): 776–784
[7] Hiraki T, Gobara H, Mimura H et al. Brachial nerve injury
caused by percutaneous radiofrequency ablation of apical
lung cancer: a report of four cases. J Vasc Interv Radiol
2010; 21(7): 1129–1133
Fig. 3.16 Imaging changes following radiofrequency ablation (RFA) of a biopsy-proven non–small cell lung cancer. (a)
An irregular, juxtapleural tumor is seen on axial computed tomographic (CT) image in lung windows. (b) An RFA single-
tined needle (arrow) is placed adjacent to the tumor (arrowhead). (c) Following subsequent ablation, there is ground
glass and airspace consolidation (arrowheads) surrounding a tangentially viewed RFA probe (arrow). (d) On a 1-month
follow-up CT image, the zone of ablation (arrowheads) is more defined with central cavitation. (e) At 3-month follow-up
CT, the zone of ablation (arrowhead) has decreased in size. (f) Follow-up CT over 5 years from RFA shows the zone of
ablation retracting to a thin, linear scar (arrowhead) without evidence of recurrence.
Ablation of Lung Cancer, Pulmonary Metastatic Disease, and Chest Wall Malignancy
55
[8] Gadaleta C, Mattioli V, Colucci G et al. Radiofrequency abla-
tion of 40 lung neoplasms: preliminary results. Am J Roent-
genol 2004; 183(2): 361–368
[9] VanSonnenberg E, Shankar S, Morrison PR et al. Radiofre-
quency ablation of thoracic lesions: part 2, initial clinical
experience—technical and multidisciplinary considera-
tions in 30 patients. Am J Roentgenol 2005; 184(2): 381–
390
[10] Simon CJ, Dupuy DE, Mayo-Smith WW. Microwave ablation:
principles and applications. Radiographics 2005; 25 Suppl
1: S69–S83
[11] Wright AS, Lee FT, Jr, Mahvi DM. Hepatic microwave abla-
tion with multiple antennae results in synergistically larger
zones of coagulation necrosis. Ann Surg Oncol 2003; 10(3):
275–283
[12] Maiwand MO, Homasson JP. Cryotherapy for tracheobron-
chial disorders. Clin Chest Med 1995; 16(3): 427–443
[13] Lee JM, Jin GY, Goldberg SN et al. Percutaneous radiofre-
quency ablation for inoperable non-small cell lung cancer
and metastases: preliminary report. Radiology 2004; 230
(1): 125–134
[14] Skonieczki BD, Wells C, Wasser EJ, Dupuy DE. Radiofre-
quency and microwave tumor ablation in patients with im-
planted cardiac devices: is it safe? Eur J Radiol 201 1; 79(3):
343–346
[15] Rose SC. Radiofrequency ablation of pulmonary malignan-
cies. Semin Respir Crit Care Med 2008; 29(4): 361–383
[16] Akeboshi M, Yamakado K, Nakatsuka A et al. Percutane-
ous radiofrequency ablation of lung neoplasms: initial
therapeutic response. J Vasc Interv Radiol 2004; 15(5):
463–470
[17] Abtin FWC, Golshan A, Suh R. CT guided percutaneous cry-
oablation of thoracic tumors: technical feasibility, early effi-
cacy and imaging of 27 treated tumors. Paper presented at:
Scientific session 8, #713, 2nd World Congress of Thoracic
Imaging and Diagnosis in Chest Disease; May 30–June 2,
2009; Valencia, Spain
[18] Murthy SC, Kim K, Rice TW et al. Can we predict long-term
survival after pulmonary metastasectomy for renal cell car-
cinoma? Ann Thorac Surg 2005; 79(3): 996–1003
[19] Steinke K, Haghighi KS, Wulf S, Morris DL. Effect of vessel di-
ameter on the creation of ovine lung radiofrequency lesions
in vivo: preliminary results. J Surg Res 2005; 124(1): 85–91
[20] Hinshaw JL, Lee FT, Jr. Cryoablation for liver cancer. Tech
Vasc Interv Radiol 2007; 10(1): 47–57
[21] Oshima F, Yamakado K, Akeboshi M et al. Lung radiofre-
quency ablation with and without bronchial occlusion: ex-
perimental study in porcine lungs. J Vasc Interv Radiol
2004; 15(12): 1451–1456
[22] Yamakado K, Akeboshi M, Nakatsuka A et al. Tumor seeding
following lung radiofrequency ablation: a case report. Cardi-
ovasc Intervent Radiol 2005; 28(4): 530–532
[23] Wang H, Littrup PJ, Duan Y, Zhang Y, Feng H, Nie Z. Thoracic
masses treated with percutaneous cryotherapy: initial expe-
rience with more than 200 procedures. Radiology 2005; 235
(1): 289–298
[24] Rose SC, Thistlethwaite PA, Sewell PE, Vance RB. Lung cancer
and radiofrequency ablation. J Vasc Interv Radiol 2006; 17
(6): 927–951, quiz 951
[25] Simon CJ, Dupuy DE, DiPetrillo TA et al. Pulmonary radiofre-
quency ablation: long-term safety and efficacy in 153 pa-
tients. Radiology 2007; 243(1): 268–275
[26] Wolf FJ, Grand DJ, Machan JT, Dipetrillo TA, Mayo-Smith
WW, Dupuy DE. Microwave ablation of lung malignancies:
effectiveness, CT findings, and safety in 50 patients. Radiolo-
gy 2008; 247(3): 871–879
[27] Dorsey ER, Jarjoura D, Rutecki GW. The influence of control-
lable lifestyle and sex on the specialty choices of graduating
U.S. medical students, 1996–2003. Acad Med 2005; 80(9):
791–796
[28] Wasser EJ, Dupuy DE. Microwave ablation in the treatment
of primary lung tumors. Semin Respir Crit Care Med 2008;
29(4): 384–394
[29] Zhu JC, Yan TD, Morris DL. A systematic review of radiofre-
quency ablation for lung tumors. Ann Surg Oncol 2008; 15
(6): 1765–1774
[30] Sakurai J, Hiraki T, Mukai T et al. Intractable pneumothorax
due to bronchopleural fistula after radiofrequency ablation of
lung tumors. J Vasc Interv Radiol 2007; 18(1 Pt 1): 141–145
[31] Wagner JM, Hinshaw JL, Lubner MG et al. CT-guided lung bi-
opsies: pleural blood patching reduces the rate of chest tube
placement for postbiopsy pneumothorax. Am J Roentgenol
2011; 197(4): 783–788
[32] Shackcloth MJ, Poullis M, Jackson M, Soorae A, Page RD. In-
trapleural instillation of autologous blood in the treatment
of prolonged air leak after lobectomy: a prospective
randomized controlled trial. Ann Thorac Surg 2006; 82(3):
1052–1056
[33] Droghetti A, Schiavini A, Muriana P et al. Autologous blood
patch in persistent air leaks after pulmonary resection. J
Thorac Cardiovasc Surg 2006; 132(3): 556–559
[34] Abtin FG, Eradat J, Gutierrez AJ, Lee C, Fishbein MC, Suh RD.
Radiofrequency ablation of lung tumors: imaging features of
the postablation zone. Radiographics 2012; 32(4): 947–969
[35] Beland MD, Wasser EJ, Mayo-Smith WW, Dupuy DE. Pri-
mary non-small cell lung cancer: review of frequency, loca-
tion, and time of recurrence after radiofrequency ablation.
Radiology 2010; 254(1): 301–307
[36] Vogl TJ, Naguib NN, Gruber-Rouh T, Koitka K, Lehnert T,
Nour-Eldin NE. Microwave ablation therapy: clinical utility
in treatment of pulmonary metastases. Radiology 2011; 261
(2): 643–651
[37] Ito N, Nakatsuka S, Inoue M et al. Computed tomographic
appearance of lung tumors treated with percutaneous cry-
oablation. J Vasc Interv Radiol 2012; 23(8): 1043–1052
[38] Lencioni R, Crocetti L, Cioni R et al. Response to radiofre-
quency ablation of pulmonary tumours: a prospective, in-
tention-to-treat, multicentre clinical trial (the RAPTURE
study). Lancet Oncol 2008; 9(7): 621–628
[39] Hiraki T, Gobara H, Mimura H, Matsui Y, Toyooka S, Kanaza-
wa S. Percutaneous radiofrequency ablation of clinical stage
I non-small cell lung cancer. J Thorac Cardiovasc Surg 2011;
142(1): 24–30
[40] Kodama H, Yamakado K, Takaki H et al. Lung radiofrequency
ablation for the treatment of unresectable recurrent non-
small-cell lung cancer after surgical intervention. Cardiovasc
Intervent Radiol 2012; 35(3): 563–569
[41] Lee H, Jin GY, Han YM et al. Comparison of survival rate
in primary non-small-cell lung cancer among elderly pa-
tients treated with radiofrequency ablation, surgery, or
chemotherapy. Cardiovasc Intervent Radiol 2012; 35(2):
343–350
[42] Grieco CA, Simon CJ, Mayo-Smith WW, DiPetrillo TA, Ready
NE, Dupuy DE. Percutaneous image-guided thermal ablation
and radiation therapy: outcomes of combined treatment for
41 patients with inoperable stage I/II non-small-cell lung
cancer. J Vasc Interv Radiol 2006; 17(7): 1117–1124
[43] Chua TC, Sarkar A, Saxena A, Glenn D, Zhao J, Morris DL.
Long-term outcome of image-guided percutaneous radio-
frequency ablation of lung metastases: an open-labeled pro-
spective trial of 148 patients. Ann Oncol 2010; 21(10):
2017–2022
Ablation of Lung Cancer, Pulmonary Metastatic Disease, and Chest Wall Malignancy
56
[44] Inoue Y, Miki C, Hiro J et al. Improved survival using multi-
modality therapy in patients with lung metastases from col-
orectal cancer: a preliminary study. Oncol Rep 2005; 14(6):
1571–1576
[45] Yamakado K, Inoue Y, Takao M et al. Long-term results of ra-
diofrequency ablation in colorectal lung metastases: single
center experience. Oncol Rep 2009; 22(4): 885–891
[46] Sakurai J, Hiraki T, Mimura H et al. Radiofrequency ablation
of small lung metastases by a single application of a 2-cm
expandable electrode: determination of favorable respon-
ders. J Vasc Interv Radiol 2010; 21(2): 231–236
[47] Chua TC, Thornbury K, Saxena A et al. Radiofrequency abla-
tion as an adjunct to systemic chemotherapy for colorectal
pulmonary metastases. Cancer 2010; 116(9): 2106–2114
[48] Nakamura T, Matsumine A, Yamakado K et al. Lung radiofre-
quency ablation in patients with pulmonary metastases
from musculoskeletal sarcomas [corrected].[corrected] Can-
cer 2009; 115(16): 3774–3781
[49] Lu Q, Cao W, Huang L et al. CT-guided percutaneous micro-
wave ablation of pulmonary malignancies: Results in 69
cases. World J Surg Oncol 2012; 10: 80
[50] Vogl TJ, Worst TS, Naguib NN, Ackermann H, Gruber-Rouh T,
Nour-Eldin NE. Factors influencing local tumor control in
patients with neoplastic pulmonary nodules treated with
microwave ablation: a risk-factor analysis. Am J Roentgenol
2013; 200(3): 665–672
[51] Zemlyak A, Moore WH, Bilfinger TV. Comparison of survival
after sublobar resections and ablative therapies for stage I
non-small cell lung cancer. J Am Coll Surg 2010; 211(1):
68–72
[52] Yashiro H, Nakatsuka S, Inoue M et al. Factors affecting local
progression after percutaneous cryoablation of lung tumors.
J Vasc Interv Radiol 2013; 24(6): 813–821
[53] Yamauchi Y, Izumi Y, Hashimoto K et al. Percutaneous cry-
oablation for the treatment of medically inoperable stage I
non-small cell lung cancer. PLoS ONE 2012; 7(3): e33223
[54] Chan VO, McDermott S, Malone DE, Dodd JD. Percutaneous
radiofrequency ablation of lung tumors: evaluation of the
literature using evidence-based techniques. J Thorac Imag-
ing 2011; 26(1): 18–26
Ablation of Lung Cancer, Pulmonary Metastatic Disease, and Chest Wall Malignancy
57
Chapter 4
Hepatocellular Carcinoma:
Ablation
4.1 Introduction 60
4.2 Indications and
Contraindications
60
4.3 Technique 61
4.4 Imaging 61
4.5 Complications 64
4.6 Clinical Data and Outcomes 64
4 Hepatocellular Carcinoma: Ablation
Riccardo Lencioni
4.1 Introduction
Hepatocellular carcinoma (HCC) is currently the
second leading cause of cancer-related death
worldwide.
1
Unlike most solid cancers, future inci-
dence and mortality rates for HCC were projected
to largely increase in several regions around the
world over the next decade.
2,3
HCC is increasingly diagnosed at an early,
asymptomatic stage owing to surveillance of high-
risk patients.
4
Patients with early-stage HCC
require careful therapeutic management. Given
the complexity of the disease, multidisciplinary
assessment of tumor stage, liver function, and
physical status is required for proper therapeutic
planning. Patients with early-stage HCC should be
considered for any of the available curative thera-
pies, including surgical resection, liver transplan-
tation, and image-guided ablation.
5,6,7
Image-guided ablation is recommended for
patients with early-stage HCC when surgical
options are precluded.
5,6,7
Although tumor abla-
tion procedures can be performed at laparoscopy
or surgery, most procedures aimed at treating HCC
are performed with a percutaneous approach.
Hence several authors refer to these procedures as
percutaneous therapies. Over the past 25 years,
several methods for focal tumor destruction have
been developed and clinically tested.
8
Although
radiofrequency ablation (RFA) has been the most
popular technique, several alternate technologies,
including thermal and nonthermal methods, have
recently attracted attention because they appear
to be able to overcome some specific limitations of
RFA.
9,10,11
4.2 Indications and
Contraindications
A multidisciplinary team must perform a careful
clinical, laboratory, and imaging assessment of
each individual patient to evaluate the patient’s
eligibility for image-guided ablation. Laboratory
tests should include a full evaluation of the
patient’s coagulation status. A prothrombin time
ratio > 50% and a platelet count > 50,000/µL are
required to keep the risk of bleeding at an accept-
ably low level. The tumor staging protocol should
include triple-phase computed tomography (CT)
or magnetic resonance imaging (MRI) of the liver
as well as imaging examinations to rule out extra-
hepatic disease, as appropriate.
To be considered for image-guided ablation,
patients should have either a single tumor smaller
than 5 cm or as many as three nodules smaller
than 3 cm each, no evidence of vascular invasion
or extrahepatic spread, an Eastern Cooperative
Oncology Group (ECOG) performance status test of
0 or 1, and liver cirrhosis in Child–Pugh class A or
B.
5,6,7
Pretreatment imaging must carefully define
the location of each lesion with respect to sur-
rounding structures. Lesions located along the sur-
face of the liver can be considered for thermal
ablation, although their treatment requires ad-
equate expertise and may be associated with a
higher risk of complications. Thermal ablation of
superficial lesions that are adjacent to any part of
the gastrointestinal tract must be avoided because
of the risk of thermal injury of the gastric or bowel
wall. The colon appears to be at greater risk than
the stomach or small bowel for thermally medi-
ated perforation. Gastric complications are rare,
likely owing to the relatively greater wall thickness
of the stomach or the rarity of surgical adhesions
along the gastrohepatic ligament. Thermal abla-
tion of lesions adjacent to the gallbladder or to the
hepatic hilum is at risk of thermal injury of the
biliary tract. In experienced hands, thermal abla-
tion of tumors located in the vicinity of the gall-
bladder was shown to be feasible, although
associated in most cases with self-limited iatro-
genic cholecystitis. In contrast, thermal ablation of
lesions adjacent to hepatic vessels is possible
because flowing blood usually protects the vascu-
lar wall from thermal injury. In these cases, how-
ever, there may be an increased risk of incomplete
treatment of the neoplastic tissue close to the ves-
sel because of the heat loss by convection.
Further studies are needed to establish whether
novel technologies will expand the clinical role of
image-guided ablation with respect to thermal ab-
lation—RFA and microwave ablation (MWA). In
particular, promising data have been reported on
the safety and efficacy of nonthermal technologies,
such as irreversible electroporation (IR E), in treat-
ing tumors in proximity to vital structures. It has
to be pointed out, however, that the oldest and
cheapest ablation technique, percutaneous ethanol
injection (PEI), remains a viable option for small
HCC tumors unsuitable for thermal ablation.
Hepatocellular Carcinoma: Ablation
60
4.3 Technique
RFA is currently established as the standard abla-
tive modality.
12,13
However, several alternate
energy-based methods for focal tissue destruction
have recently become available. These novel abla-
tion technologies destroy a tumor either through
thermal (heat or cold) or nonthermal mechanisms.
Whatever the ablative modality, the ablation of
appropriate margins beyond the visible borders of
the tumor is necessary to achieve therapeutic
results similar to those achieved with surgery.
Ideally, a 360°, 0.5 to 1 cm thick ablative margin
should be produced all around the target tumor.
This cuff would ensure that the peripheral portion
of the lesion as well as any microscopic invasions
located in its close proximity have been eradicated
(▶ Fig. 4.1).
RFA systems function in the 375 to 500 KHz
range. Most devices currently used are monopolar
in that there is a single active electrode, with cur-
rent dissipated at one or more return grounding
pads. Bipolar devices have two active electrode
applicators, usually placed in close proximity to
achieve contiguous coagulation between the two
electrodes, or on a single electrode. Several elec-
trode types are available for clinical RFA, including
internally cooled electrodes and multitined
expandable electrodes with or without perfu-
sion.
12,13
MWA systems function at 915 MHz or 2.45 GHz
frequencies. These wavelengths have specific phys-
ical properties with regard to tissue permeability
and antenna design. Microwaves can generate very
high temperatures in very short time periods,
potentially leading to improved treatment effi-
ciency and larger ablation zones, with less
susceptibility to heat sink effects. Multiple micro-
wave antennas can be powered simultaneously to
take advantage of thermal synergy when placed in
close proximity or widely spaced to ablate several
tumors simultaneously.
The term cryoablation should be exclusively
used for all methods of destroying tissue by the
application of low temperature freezing, or alter-
nating freezing and thawing or slight heating. Rap-
id tissue freezing and thawing produce the
greatest cytotoxic effects by disrupting cellular
membranes and inducing cell death. A distinct
advantage of cryoablation is the ability to monitor
the ice-ball formation during the procedure.
IRE includes those technologies and devices that
cause cell death through the repeated application
of short-duration high-voltage electrical pulses
that create irreversible injuries to cellular mem-
branes. Although there may be some hyperthermic
ablative changes with higher power applications,
the mechanism of cell death with IRE is thought to
be predominantly nonthermal. Hence, issues asso-
ciated with perfusion-mediated tissue cooling are
not relevant for this technology. IRE is adminis-
tered under general anesthesia with administra-
tion of a neuromuscular blocking agent to prevent
undesirable muscle contraction, and by using car-
diac gating to synchronize pulse delivery with the
absolute refractory period to prevent cardiac
arrhythmias.
Other energy-based ablation technologies
include laser ablation and high-intensity focused
ultrasound. These technologies have been adopted
by a few centers worldwide for the treatment of
malignant liver tumors.
4.4 Imaging
Targeting of the lesion can be performed with
ultrasound, CT, or MRI (▶ Fig. 4.2). The guidance
system is chosen largely on the basis of operator
preference and local availability of dedicated
equipment, such as CT fluoroscopy or open MRI
systems. Real-time ultrasound/CT (or ultrasound/
MRI) fusion imaging systems may improve the
ability to guide and monitor liver tumor ablation
procedures. During the procedure, important
aspects to be monitored include how well the
tumor is being covered and whether any adjacent
normal structures are being affected at the same
time. Although the transient hyperechoic zone
that is seen at ultrasound within and surrounding
a tumor during and immediately after RFA can be
used as a rough guide to the extent of tumor
Fig. 4.1 Schematic model of a thermal ablation. The
target diameter of the ablation zone (D*) must be
ideally 2 cm larger than the diameter of the tumor that
undergoes treatment (D).
Hepatocellular Carcinoma: Ablation
61
destruction, MRI is currently the only imaging
modality with validated techniques for real-time
temperature monitoring.
Contrast-enhanced imaging performed at the
end of the procedure may allow an initial evalua-
tion of treatment effects. However, 1-month CT or
MRI examinations are recognized as the standard
to assess treatment outcome. CT and MRI show
successful ablation as a nonenhancing area with or
without a peripheral enhancing rim (▶ Fig. 4.3).
The enhancing rim that may be observed along the
periphery of the ablation zone appears as a rela-
tively concentric, symmetric, and uniform process
in an area with smooth inner margins. This is a
Fig. 4.2 Ultrasound-guided radiofrequency ablation (RFA) of a small hepatocellular carcinoma. (a) The tumor is localized
via intercostal ultrasound scanning (arrow). (b) A multitined expandable needle for RFA is advanced and precisely
deployed within the lesion. (c) At the end of the procedure, a large hyperechoic cloud covering the tumors is seen on
ultrasound.
Hepatocellular Carcinoma: Ablation
62
transient finding that represents a benign physio-
logical response to thermal injury (initially, reac-
tive hyperemia; subsequently, fibrosis and giant
cell reaction). Benign periablational enhancement
needs to be differentiated from irregular
peripheral enhancement due to residual tumor
that occurs at the treatment margin. In contrast to
benign periablational enhancement, residual
unablated tumor often grows in scattered, nodular,
or eccentric patterns. Later follow-up imaging
Fig. 4.3 Complete response of hepatocellular carcinoma (HCC) after radiofrequency ablation. (a) Pretreatment
computed tomography (CT) shows hypervascular HCC with typical arterial phase enhancement (arrow). (b) CTobtained
1 month after treatment shows nonenhancing areas in both the arterial and (c) the portal venous phase replacing the
tumor and consistent with complete ablation.
Hepatocellular Carcinoma: Ablation
63
studies should be aimed at detecting the recur-
rence of the treated lesion (i.e., local tumor pro-
gression), the development of new hepatic lesions,
or the emergence of extrahepatic disease.
4.5 Complications
Several multicenter surveys have reported accept-
able morbidity and mortality rates for RFA of liver
tumors. The mortality rate ranged from 0.1 to
0.5%, the major complication rate ranged from 2.2
to 3.1%, and the minor complication rate ranged
from 5 to 8.9%.
14
The most common causes of
death were sepsis, hepatic failure, colon perfora-
tion, and por tal vein thrombosis, while the most
common complications were intraperitoneal
bleeding, hepatic abscess, bile duct injury, hepatic
decompensation, and grounding pad burns.
15,16,17
Minor complications and side effects were usually
transient and self-limiting. An uncommon late com-
plication of RF ablation can be tumor seeding along
the needle track. In patients with HCC, tumor seed-
ing occurred in 8 (0.5%) of 1,610 cases in a multi-
center survey.
15
Lesions with subcapsular location
and an invasive tumoral pattern, as shown by a
poor differentiation degree, seem to be at higher
risk for such a complication.
18
Although these data
indicate that RFA is a relatively safe procedure, a
careful assessment of the risks and benefits associ-
ated with the treatment has to be made in each
individual patient by a multidisciplinary team.
4.6 Clinical Data and Outcomes
The use of RFA for local ablation of early-stage HCC
is supported by a large amount of data and robust
clinical evidence. Five randomized, controlled tri-
als (RCTs) have compared RFA versus PEI for the
treatment of early-stage HCC. These investigations
consistently showed that RFA has a higher anti-
cancer effect than PEI, leading to a better local con-
trol of the disease
19,20,21,22,23
(▶ Table 4.1). The
assessment of the impact of RFA on survival has
been more controversial. Although a survival ben-
efit was identified in the three RCTs performed in
Asia, the two European RCTs failed to show statis-
tically significant differences in overall survival
between patients who received RFA and those
treated with PEI, despite the trend favoring RFA
(▶ Table 4.1). In patients with early-stage HCC
treated with percutaneous ablation, long-term
survival is often the result of different sequential
interventions, given that about than 80% of the
patients will develop recurrent intrahepatic HCC
nodules within 5 years of the initial treatment and
will received additional therapies.
24
Nevertheless,
three independent meta-analyses including all
RCTs have confirmed that treatment with RFA
offers a survival benefit as compared with PEI, par-
ticularly for tumors larger than 2 cm, thus estab-
lishing RFA as the standard percutaneous
technique.
25,26,27
For studies that reported major
complications, however, the incidence in RFA-
treated patients was 4.1% (95% confidence interval
[CI], 1.8–6.4%), compared to 2.7% (95% CI, 0.4–
5.1%) observed in PEI-treated patients.
28
This dif-
ference was not statistically significant; neverthe-
less, this safety profile should be taken into
consideration as part of the overall risk/benefit
profile in each case.
Recent reports on long-term outcomes of RFA-
treated patients have shown that, in patients with
Child–Pugh class A and early-stage HCC, 5-year
survival rates are as high as 51 to 64% and may
reach 76% in patients who meet the Barcelona
Clinic Liver Cancer (BCLC) criteria for surgical
resection
24,29,30,31
(▶ Table 4.2). Caution, however,
is needed when interpreting and generalizing
these results, in particular in light of studies that
suggest a nonnegligible rate of incomplete histo-
pathological response after RFA. In fact, the ability
of RFA to achieve complete tumor eradication
appears to be dependent on tumor size and loca-
tion. In particular, histological studies performed
in liver specimens of patients who underwent RFA
as a bridge treatment to transplantation showed
that the presence of large (≥ 3 mm) abutting ves-
sels result in a drop of the rate of complete tumor
necrosis to < 50% because of the heat loss due to
perfusion-mediated tissue cooling within the area
to be ablated.
32
Several attempts have been made to increase
the effect of RFA in HCC treatment. Because heat
efficiency is the difference between the amount of
heat produced and the amount of heat lost, most
investigators devote their attention to strategies
that aim primarily at minimizing heat loss due to
perfusion-mediated tissue cooling. Given that HCC
is mostly nourished by the hepatic artery, a combi-
nation of RFA and balloon catheter occlusion of the
tumor arterial supply or prior transarterial chemo-
embolization (TACE) has been used to increase
heat efficiency.
33,34,35,36
The combination of TACE
and RFA did not show significant clinical benefit
when applied to the treatment of small (< 3 cm)
HCC.
37
However, such an approach did show signif-
icant advantages, in terms of both local tumor con-
trol and survival, when used in intermediate-sized
Hepatocellular Carcinoma: Ablation
64