Percutaneous Ablation of Hepatocellular Carcinoma:
State-of-the-Art
Riccardo Lencioni, Dania Cioni, Laura Crocetti, and Carlo Bartolozzi
Percutaneous ablation is considered the best treatment
option for patients with early-stage hepatocellular carci-
noma (HCC) who are not candidates for surgical resection
or liver transplantation. Several methods have been devel-
oped, including intratumoral injection of ethanol or ace-
tic acid, and thermal ablation with radiofrequency, laser,
microwaves, or cryosurgery. Percutaneous ethanol injec-
tion (PEI) has been the most widely used technique. Sev-
eral series have provided indirect evidence that PEI
improves the natural history of HCC. Patients with Child-
Pugh class A cirrhosis and either a single tumor smaller
than 5 cm or as many as three lesions each smaller than 3
cm may achieve a 5-year survival of 50%. The major
limitation of PEI is the high local recurrence rate, which
may reach 33 43%. Radiofrequency (RF) ablation has
emerged as the most powerful alternate method for per-
cutaneous ablation. Recent studies have shown that RF
ablation can achieve more effective local tumor control
than PEI with fewer treatment sessions. In a randomized
trial, local recurrence-free survival rates were signicantly
higher in patients who received RF ablation than in those
treated by PEI, and treatment allocation was conrmed as
an independent prognostic factor by multivariate analysis.
RF ablation could therefore be considered as the percuta-
neous treatment of choice for patients with early-stage
tumors. Further investigation is warranted to clarify
whether current RF technology could offer improved
results in patients with intermediate-stage HCC. (Liver
Transpl 2004;10:S91S97.)
T here is no universal algorithm implemented
worldwide for the treatment of hepatocellular car-
cinoma (HCC) in cirrhosis.1 If diagnosed at an early
stage, patients should be considered for any of the avail-
able options that may provide a high rate of complete
response. These include surgical resection, liver trans-
plantation, and percutaneous techniques of tumor abla-
tion.1 Indication for surgical resection is currently
restricted to patients with single asymptomatic HCC
and extremely well-preserved liver function, that have
neither clinically signicant portal hypertension nor
abnormal bilirubin.2,3 Cadaveric liver transplantation is
limited by the shortage of donors and living donor liver
transplantation is still at an early stage of clinical appli-
cation.2,3 As a result, percutaneous ablation plays a key
role in the therapeutic management of HCC. While
ethanol injection is a well-established technique for per-
cutaneous ablation, several newer methods of tumor
destruction have been developed and clinically tested
over the past few years. Among these methods, radio-
Liver Transplantation, Vol 10, No 2, Suppl 1 (February), 2004: pp S91S97
frequency (RF) thermal ablation constitutes the most
extensively studied alternative to ethanol injection.4
General Eligibility Criteria
A careful clinical, laboratory, and imaging assessment
has to be performed on each individual patient by a
multidisciplinary team to evaluate eligibility for percu-
taneous ablation. Patients classied as stage A according
to the Barcelona Clinic Liver Cancer staging classica-
tion, which are not candidates for surgery, qualify for
percutaneous ablation.5 The tumor to treat by RF must
be a focal, nodular-type lesion. The presence of a clear
and easy-to-detect target for needle placement is crucial
for the outcome of treatment. Tumor size should be
preferentially smaller than 35 cm in greatest dimen-
sion. When using thermal methods of tissue destruc-
tion, some additional points have to be considered.
Treatment of lesions adjacent to the gallbladder or to
the hepatic hilum risks thermal injury of the biliary
tract. Lesions located along the surface of the liver can
be considered for thermal ablation, although their treat-
ment requires experienced hands and may be associated
with a higher risk of complications. A careful assess-
ment of the coagulation status is mandatory before per-
cutaneous ablation. A prothrombin time ratio (normal
time/patients time) greater than 50% as well as a plate-
let count higher than 50,000/l are required to keep
the risk of bleeding at an acceptable low level.
Percutaneous Ethanol Injection
Percutaneous ethanol injection (PEI) is a well-estab-
lished technique for tumor ablation.6 PEI induces local
Abbreviations: HCC, hepatocellular carcinoma; PEI, percutane-
ous ethanol injection; RF, radiofrequency; MCT, microwave coagu-
lation therapy; PCS, percutaneous cryosurgery.
Division of Diagnostic and Interventional Radiology, Department of
Oncology, Transplants, and Advanced Technologies in Medicine, Uni-
versity of Pisa, Italy
Address reprint requests to Prof. Riccardo Lencioni, Diagnostic and
Interventional Radiology, University of Pisa, Via Roma 67, I-56126
Pisa, Italy. Telephone: 39.050.992509 ; Fax: 39.050.551461; E-mail:
Lencioni@med.unipi.it
Copyright 2004 by the American Association for the Study of
Liver Diseases
Published online in Wiley InterScience (www.interscience.wiley.com).
DOI 10.1002/lt.20043
S91
S92 Lencioni et al

Table 1. Survival Rates of Patients With Small Hepatocellular Carcinoma Treated With Percutaneous Ablation*

Survival Rates (%)

Trial Year Type of Study No. Patients Treatment Method 1-yr 3-yr 5-yr
Castells et al.
8 1993 Prospective 30 PEI 83 55 N/A
Lencioni et al.9 1995 Prospective 105 PEI 96 68 32
Livraghi et al.10 1995 Retrospective 293 PEI 98 79 47
Yamamoto et al.11 2001 Prospective 39 PEI 100 82 59
Shiina et al.12 2002 Retrospective 122 MCT 90 68 N/A
Lencioni et al.27 2003 RCT 102 PEI 98 88 N/A
RFTA 100 98 N/A
*Small HCC: single lesion 5 cm in diameter or smaller or as many as 3 lesions each 3 cm or smaller.
PEI, percutaneous ethanol injection; MCT, microwave coagulation therapy; RFTA, radiofrequency thermal ablation.
At 2 years.

tumor necrosis as a result of cellular dehydration, pro-
tein denaturation, and chemical occlusion of tumor
vessels. It is best administered by using ultrasound guid-
ance because real-time control allows for a faster proce-
dure, precise centering of the needle in the target, and
continuous monitoring of the injection. Fine noncut-
ting needles, with either a single end hole or multiple
side holes, are commonly used for PEI. PEI is usually
performed under local anesthesia on an out-patient
basis. The treatment schedule typically includes four to
eight sessions performed once or twice weekly. The
number of treatment sessions, as well as the amount of
ethanol to inject, may vary greatly according to the size
of the lesion, the distribution of the injected ethanol
within the tumor, and the compliance of the patient.
Several studies have shown that PEI is an effective
treatment for small (3 cm or less), nodular-type HCC.
HCC nodules have a soft consistency and are sur-
rounded by a rm cirrhotic liver. Consequently,
injected ethanol diffuses within them easily and selec-
tively, leading to complete tumor necrosis in about
70% of small lesions.7 Although there have not been
any prospective randomized trials comparing PEI and
surgical resection, several series have shown that the
long-term outcome of selected PEI-treated patients was
similar to that of patients who had undergone resection,
with 5-year survival rates of 3259% (Table 1).8 12
While PEI is a low-risk procedure, severe complica-
tions, including cases of tumoral seeding, have been
reported.13
The major limitation of PEI, besides the uncertainty
of tumor ablation and the long treatment time, is the
high local recurrence rate, that may reach 33% in
lesions smaller than 3 cm and 43% in lesions exceeding
3 cm.14,15 The injected ethanol does not always accom-
plish complete tumor necrosis because of its inhomoge-
neous distribution within the lesion especially in the
presence of intratumoral septa and the limited effect
on extracapsular cancerous spread. Also, PEI is unable
to create a safety margin of ablation in the liver paren-
chyma surrounding the nodule, where satellite nodules
are most frequently located.16
RF Thermal Ablation
Basic Principles
The goal of RF ablation is to induce thermal injury to
the tissue through electromagnetic energy deposition.
In RF ablation, the patient is part of a closed-loop
circuit, that includes an RF generator, an electrode nee-
dle, and a large dispersive electrode (ground pads). An
alternating electric eld is created within the tissue of
the patient. Because of the relatively high electrical
resistance of tissue in comparison with the metal elec-
trodes, there is marked agitation of the ions present in
the target tissue that surrounds the electrode, since the
tissue ions attempt to follow the changes in direction of
alternating electric current. The agitation results in fric-
tional heat around the electrode. The discrepancy
between the small surface area of the needle electrode
and the large area of the ground pads causes the gener-
ated heat to be focused and concentrated around the
needle electrode.17
The thermal damage caused by RF heating is depen-
dent on both the tissue temperature achieved and the
duration of heating. Heating of tissue at 55C for 4 6
minutes produces irreversible cellular damage. At tem-
peratures between 60C and 100C near immediate
coagulation of tissue is induced, with irreversible dam-
age to mitochondrial and cytosolic enzymes of the cells.
Over 100 110C, tissue vaporizes and carbonizes. For
 Percutaneous Ablation of Hepatocellular Carcinoma
adequate destruction of tumor tissue, the entire target
volume must be subjected to cytotoxic temperatures.
Thus, an essential objective of ablative therapy is
achievement and maintenance of a 55100C temper-
ature throughout the entire target volume for at least
4 6 minutes. However, the relatively slow thermal
conduction from the electrode surface through the tis-
sues may increase the duration of application up to 30
minutes. On the other hand, the tissue temperature
should not be increased over these values to avoid car-
bonization around the tip of the electrode due to exces-
sive heating.17
In the early experiences with RF ablation, a major
limitation of the technique was the small volume of
necrosis created by conventional monopolar elec-
trodes.17 These devices were capable of producing
cylindrical lesions not greater than 1.6 cm in diameter.
Therefore, multiple electrode insertions were necessary
to treat all but the smallest lesions. Subsequently, sev-
eral strategies for increasing the area of thermal necrosis
achieved with RF treatment have been tested, including
the use of multiprobe arrays, bipolar arrays, and saline
injections during RF application. These devices were
shown to increase the volume of coagulation necrosis
that can be obtained in a single treatment session. How-
ever, such techniques were either technically challeng-
ing and time-consuming or produced irregularly
shaped thermal lesions, thereby substantially limiting
their clinical usefulness.
Major progress in RF technology was achieved with
the introduction of modied electrodes, including
cooled-tip electrode needles and expandable electrode
needles with multiple retractable lateral-exit prongs on
the tip.18 20 Cooled-tip electrodes consist of dual-lu-
men needles with uninsulated active tips, in which
internal cooling is obtained by continuous perfusion
with chilled saline. Needle cooling is aimed at prevent-
ing overheating of tissues nearest to the electrode,
which may cause charring, thereby limiting the propa-
gation of RF waves. They are available either as a single
needle or as a cluster array with three needles spaced 0.5
cm apart. Expandable needles have an active surface
that can be substantially expanded by hooks deployed
laterally from the tip. The number of hooks and the
lenght of the hooks deployment may vary according to
the desired volume of necrosis. These techniques
enabled a substantial and reproducible enlargement of
the volume of thermal necrosis produced with a single
needle insertion, and prompted the start of clinical
application of RF ablation.
S93
Materials and Methods
At our institution, we currently use 150- or 200-W RF gen-
erators and 14-gauge expandable electrode needles (StarBurst
XL, RITA Medical Systems). The needle electrode consists of
an insulated outer cannula that houses nine curved electrodes
of various lengths, which deploy out from the trocar tip. This
design decreases the distance between the tissue and the elec-
trodes, thereby ensuring uniform heating that relies less on
heat conduction over a large distance. Five of the electrodes
are hollow and contain thermocouples in their tips that are
used to measure the temperature of the adjacent tissue. Probe-
tip temperatures, tissue impedance, and wattage are displayed
on the RF generator and graphically recorded by dedicated
software, installed on a personal computer.
Maximum power output of the RF generator, amount of
electrode array deployment from the trocar, and duration of
the effective time of the ablation (time at target temperature)
depend on the desired volume of ablation. This is established
at the beginning of the procedure with the goal of destroying
the visible tumor mass plus a 1-cm safety margin of ablation
all around. To perform a typical ablation, two grounding pads
are placed on the patients thighs. The tip of the needle (with
retracted electrodes) is advanced under ultrasound guidance
to the proximal edge of the lesion, and the electrodes are
deployed to 2 cm. The generator is turned on and runs by an
automated program. The temperatures at the tips of the elec-
trodes are controlled and the peak power is maintained until
the temperature exceeds the preselected target temperature
(typically between 90 and 100C). After the target tempera-
ture is achieved, the curved electrodes are advanced step-by-
step to full deployment. When the electrodes are fully
deployed, the program maintains the target temperature by
regulating the wattage. At the end of the procedure, when the
generator turns off, a cool down cycle is automatically per-
formed. After retracting the hooks, the coagulation of the
needle track can be performed (track ablation) to maintain the
temperature above 75C with the aim of preventing any
tumor cell dissemination.
In our center, percutaneous RF is usually performed under
conscious sedation. The association of a hypnotic drug with
an ultrashort half-life analgesic drug allows a mild sedation
that allows the patient to co-operate with the operator and
bear the pain induced by treatment. Our standard protocol
consists in administering a bolus of ketorolac (0.5 0.8
mg/kg) followed by infusion of propofol (12 mg/kg/h) and
remifentanil (0.1 mg/kg/min). However, drug posology has
to be modulated in relation to the individual patient compli-
ance and to the different phases of the procedure. The infu-
sion of the hypnotic drug can be varied between 0.5 and 2
mg/kg/h to achieve a patient sedation that preserves the ability
to perform simple actions. The infusion of remifentanil can
be varied between 0.05 and 0.15 kg/min to obtain an optimal
analgesia. Attention has to be made in order to avoid bolus
administration of remifentanil, as this may cause respiratory
depression. The procedure is performed under standard car-
S94 Lencioni et al
diac, pressure, and oxygen monitoring with continuous oxy-
gen administration.
A careful post-treatment protocol is to be recommended
following RF ablation. The patient is kept under close medi-
cal observation and re-scanned with ultrasound 12 hours
after the procedure. An overnight hospital stay is scheduled.
Contrast-enhanced ultrasound performed shortly after the
procedure may allow an initial evaluation of tumor response,
by showing disappearance of intratumoral signals.21,22 Spiral
CT obtained 13 days after the ablation shows a core of
hypoattenuation surrounded by an enhancing rim.23 The
peripheral enhancing rim which is due to the inamma-
tory reaction surrounding the area of necrosis should not
be misinterpreted as tumor persistence. Since the enhancing
rim tends to disappear over time, spiral CT at 1 month is
considered the most reliable method to evaluate the outcome
of treatment.1 If there is imaging evidence of residual tumor,
the patient can be considered for repeated RF ablation, pro-
vided that requirements for treatment are still met. Follow-up
ultrasound and spiral CT studies are usually scheduled at 3- or
6-month intervals.
Clinical Results
In most clinical experiences with RF thermal ablation,
patients were treated in the framework of feasibility studies,
aimed at analyzing safety, tolerability, and local therapeutic
effect of the treatment. Rossi et al20 treated 37 patients with
liver tumors with an expandable RF electrode needle, in the
absence of major complications. Twenty-three of the 37
patients had HCC nodules smaller than 3.5 cm. All the HCC
nodules did not show any residual viable tissue on post-treat-
ment CT scans. Complete tumor necrosis was conrmed in
two patients who underwent surgical resection after RF treat-
ment. In the series of Shirato et al,24 28 of 30 HCC nodules
smaller than 3 cm did not show residual tumor on imaging
studies performed after RF ablation, and did not show any
local recurrence after a follow-up period of 315 months
(mean, 8.4 months). Livraghi et al.25 also reported that com-
plete response was seen on post-treatment CT in 47 of 52
HCC lesions smaller than or equal to 3 cm in diameter after
treatment with cooled-tip RF ablation. The rate of complete
responses was higher than that achieved by the same authors
in a group of comparable patients who underwent PEI (90%
vs. 80%). In addition, the average number of treatment ses-
sions needed to achieve ablation was substantially lower for
RF than for PEI. However, one major complication and four
minor complications occurred in patients treated with cooled-
tip RF ablation, whereas no complications occurred in
patients treated with PEI. A similar comparative study was
performed by Ikeda et al.26, who treated a series of 119 con-
secutive patients with solitary HCC smaller than 3 cm with
either RFA (n 23) or PEI (n 96). Complete tumor
response on imaging was achieved in 23 patients (100%)
treated with RF and in and 90 patients (94%) treated by PEI.
RF required an average of 1.5 sessions to achieve complete
ablation vs. an average of 4 sessions of PEI. There were no
serious adverse effects or complications except for one case of
cholangitis after PEI.
One of the current recommendations for research pro-
posed by the European Association for the Study of the Liver
is a comparison of newer methods of tumor destruction, such
as RF, with the well-established and accepted PEI through
randomized trials assessing not only initial tumor response,
but also long-term survival outcomes.1 We therefore under-
took a prospective randomized study aimed at comparing the
efcacy of RF ablation with that of PEI for the rst-line
treatment of small HCC in cirrhosis.27 Primary end-point of
the study was overall survival. Secondary end-points were
local recurrence-free survival and event-free survival (i.e., sur-
vival free from local recurrence, new HCC tumors, and extra-
hepatic metastases). Fifty-two patients with 69 HCC tumors
were treated with RF ablation (RF group), while 50 patients
with 73 HCC tumors received PEI (PEI group). No statis-
tically signicant differences between RF and PEI groups
were observed with respect to baseline characteristics, except
for patients age and albumin concentration.
Due to the relatively short observation period and the
small number of deaths in both treatment groups, we were not
able to demonstrate a statistically signicant difference
between RF ablation and PEI with respect to overall survival.
Nevertheless, a trend towards increased survival in the RF
thermal ablation group was obvious. The overall survival rates
after 1 and 2 years were 96% and 88%, respectively, in the
PEI group, and 100% and 98%, respectively, in the RF group
(p0.138, Table 1). However, 1- and 2-year local recurrence-
free survival rates were signicantly higher in the RF group
(98% and 96%, respectively) than in the PEI group (83% and
62%, respectively, p0.002). One- and 2-year event-free sur-
vival rates were also higher in RF-treated patients (86% and
64%, respectively) than in PEI-treated patients (77% and
43%, respectively, p0.012). RF treatment was conrmed as
an independent prognostic factor for local recurrence-free
survival by multivariate analysis (adjusted RR0.20,
p0.015).
Despite the fact that the RF generator used in this study
has been currently replaced by newer devices, RF ablation was
shown to be more effective than PEI in the treatment of small
HCC in cirrhosis. However, treatment of large tumors is still
problematic. Livraghi et al.28 treated 114 patients with 126
HCC lesions greater than 3 cm in diameter. Complete necro-
sis (on imaging) was attained in only 60 lesions (47.6%),
nearly complete (90 99%) necrosis in 40 lesions (31.7%),
and partial (50 89%) necrosis in the remaining 26 lesions
(20.6%). Medium and/or noninltrating tumors were treated
successfully signicantly more often than large and/or inl-
trating tumors. Therefore, there is currently a focus on a
multimodality strategy in attempts to ensure a more effective
treatment of large tumors.
Recent studies have proved the inuence of perfusion-
mediated tissue cooling on the area of thermal necrosis achiev-
able with RF treatment. Goldberg et al.29 applied RF in vivo
to normal porcine liver without and with balloon occlusion of
 Percutaneous Ablation of Hepatocellular Carcinoma
the portal vein, celiac artery, or hepatic artery, and to ex vivo
calf liver: RF application during vascular occlusion produced
larger areas of coagulation necrosis than RF with unaltered
blood ow. The same authors demonstrated that intraopera-
tive RF application produced greater coagulation diameter for
human hepatic metastases treated during portal inow occlu-
sion than for tumors treated with normal blood ow.
Assuming that the volume of thermal necrosis produced
by RF treatment is strongly dependent on blood ow, and
considering that in HCC blood ow is mainly sustained by
the hepatic artery, we designed a multicenter clinical trial
aimed at investigating whether interruption of the tumor
arterial blood supply by means of occlusion of either the
hepatic artery with a balloon catheter or the feeding arteries
with gelatin sponge particles would increase the extent of
RF-induced coagulation necrosis.30 A series of 62 consecutive
patients with a single, large HCC ranging from 3.5 to 8.5 cm
in diameter (mean, 4.7 cm) accompanying cirrhosis under-
went RF ablation after occlusion of the tumor arterial supply.
The RF energy was delivered by using an expandable elec-
trode needle at the time of balloon catheter occlusion of the
hepatic artery (n 40), at the time of occlusion of the HCC
feeding arteries with gelatin sponge particles (n 13), or 25
days thereafter (n 9). Two patients underwent liver resec-
tion after the thermal ablation; the remaining 60 patients were
followed for a mean of 12.1 months (range, 326 months).
During the follow-up, 49 (82%) of the 60 treated HCC
nodules showed stable complete response, while the remain-
ing 11 (18%) nodules showed local progression. Histopatho-
logic analysis of one autopsy and of the two surgical specimens
revealed more than 90% necrosis in one specimen and 100%
necrosis in two. No fatal or major complications related to the
treatment occurred, despite the more aggressive RF treatment
protocol.
Results of this study provide evidence that areas of coagu-
lative necrosis that are much larger than those previously
reported can be created if RF thermal ablation is performed in
HCC nodules after occlusion of their arterial supply. The
results achieved with this technique were conrmed by two
recent studies. Yamasaki et al.31 compared the coagulation
diameters obtained with balloon-occluded RF and standard
RF in 31 patients with 42 HCC lesions measuring less than 4
cm in the greatest dimension. There were no signicant dif-
ferences in ablation conditions such as the frequency of a fully
expanded electrode, the number of needle insertions, applica-
tion cycles, or treatment times between the two groups. How-
ever, the greatest dimension of the area coagulated by balloon-
occluded RFA was signicantly larger than that coagulated by
standard RFA. Yamakado et al.32 evaluated the local thera-
peutic efcacy of RF ablation after transarterial chemoembo-
lization in 64 patients with 108 lesions. Sixty-ve lesions were
small (3 cm or less), 32 were intermediate in size (3.15 cm),
and 11 were large (5.112 cm). Complete necrosis was
achieved in all lesions, and there were no local recurrences in
small and intermediate-sized lesions during a mean follow-up
of 12.5 months.
S95
In most of the reported series, RF ablation was associated
with acceptable morbidity. Nevertheless, one study raised
concerns regarding the risk of tumor seeding following RF
ablation: in this experience, four (12.5%) of 32 patients
treated by cool-tip RF ablation showed biopsy-proven needle-
track seeding between 4 and 18 months after treatment.33
Iatrogenic tumor dissemination was related to subcapsular
location or an invasive tumoral pattern, as shown by a poor
differentiation degree.33 More recently, the incidence of com-
plications following RF ablation was assessed by two large
analyses. The rst report is a multicenter survey in which
2320 patients with 3554 lesions were included.34 The major-
ity of patients (1610) had HCC with chronic liver disease. Six
deaths (mortality rate, 0.3%) were noted, including two
caused by multiorgan failure following intestinal perforation;
one case each of septic shock following Staphylococcus aureus-
caused peritonitis, massive hemorrhage following tumor rup-
ture, liver failure following stenosis of right bile duct; and one
case of sudden death of unknown cause 3 days after the
procedure. Fifty (2.2%) patients had additional major com-
plications. Tumor seeding, in particolar, occurred in 12
(0.5%) of 2320 patients. The second report is a multicenter
study in which 872 patients (548 of whom with HCC and
324 with or hepatic metastases) were included.35 Overall,
1263 lesions (741 HCCs and 522 metastases) were treated.
The analysis of variance (ANOVA test) was used to evaluate
relationships of complications with patient-, tumor-, and pro-
cedure-related factors. One case of death (mortality rate, 0.1
%) caused by multiorgan failure following peritonitis due to
colonic perforation occurred in a cirrhotic patient with a
supercially located HCC. Major complications were
observed in 27 (3.1 %) of 872 patients, including 7 cases
(0.8%) with tumor seeding along the needle track.35 Results
of these studies conrm that RF ablation is a relatively low-
risk procedure for the treatment of focal liver tumors. Never-
theless, the technique is not entirely free from complications,
and appropriate experience and optimized treatment proto-
cols are needed. Also, subcapsular HCC lesions should be
treated with caution as they appear to be associated with a
higher risk of complications.
Other Methods of Percutaneous Ablation
Other methods of percutaneous ablation have been clinically
tested over the past few years. Ohnishi et al.36 compared
percutaneous acetic acid injection and PEI. Sixty patients
with one to four HCCs smaller than 3 cm were entered into a
randomized controlled trial. Thirty-one and 29 patients,
respectively, were treated by percutaneous acetic acid injec-
tion using 50% acetic acid or by PEI using absolute ethanol.
All original tumors were treated successfully by either therapy.
However, 8% of 38 tumors treated with percutaneous acetic
acid injection and 37% of 35 tumors treated with PEI devel-
oped a local recurrence (p .001) during the follow-up peri-
ods of 29 8 months and 23 10 months, respectively. The
1- and 2-year survival rates were 100% and 92% in percuta-
S96 Lencioni et al
neous acetic acid injection and 83% and 63% in percutaneous
ethanol injection (p .0017). A multivariate analysis of prog-
nostic factors revealed that treatment was an independent
predictor of survival. The authors concluded that percutane-
ous acetic acid injection was superior to PEI in the treatment
of small HCC. However, the results of acetic acid injection
were not established in large series of patients.
Other groups investigated the usefulness of percutaneous
microwave coagulation therapy (MCT). Seki et al.37 performed a
retrospective study in which 90 patients with small HCC were
included. The overall 5-year survival rate for patients with well-
differentiated HCC treated with MCT (70%) and PEI (78%)
were not signicantly different. Among the patients with mod-
erately or poorly differentiated HCC, overall survival with MCT
was signicantly better than with PEI (5-year survival rate, 35%)
(p 0.03), and 9 of 22 patients with moderately or poorly
differentiated HCC treated with PEI experienced recurrence in
the original target subsegment compared to 2 of 25 patients
treated with MCT. The authors concluded that MCT may be
superior to PEI for the local control of moderately or poorly
differentiated small HCC. Shibata et al.38 compared the effec-
tiveness of MCT with that of RF ablation in 72 patients with 94
HCC nodules who were randomly assigned to PMC and RF
ablation groups. The number of treatment sessions per nodule
was signicantly lower in the RF ablation group than in the
MCT group (1.1 vs. 2.4; p .001). Complete therapeutic effect
was achieved in 41 (89%) of 46 nodules treated with MCT and
in 46 (96%) of 48 nodules treated with RF ablation (p .26).
Major complications occurred in four patients treated with
MCT and in one patient treated with RF ablation (p .36).
During follow-up (range, 6 27 months), residual foci of
untreated disease were seen in 8 of 46 nodules treated with MCT
and in 4 of 48 nodules treated with RF ablation. They concluded
that MCT and RF ablation had equivalent therapeutic effects,
but that RF achieves tumor ablation with fewer sessions.
Recently, Adam et al.39 compared the complication and
success rates in patients treated with percutaneous cryosurgery
(PCS) or percutaneous RF ablation for unresectable hepatic
malignancies. Sixty-four patients were treated with either
PCS (n 31) or PRF (n 33). Patient treatment was based
on the random availability of the probes. The distribution of
tumor types was similar in the two groups (p .76). Initial
treatment success was comparable in the two treatment
groups. However, local recurrences occurred more frequently
after PCS than after RF ablation (16 [53%] of 30 vs. 6 [18%]
of 34; p .003). Multivariate analysis demonstrated that the
use of PCS (p .003) was an independent risk factor for local
tumor recurrence. The authors concluded that, while similar
initial treatment success and complication rates are observed
following either PCS or RF ablation, local recurrences occur
more frequently following PCS.
Conclusion
From the early studies with PEI to the latest reports on
RF ablation, percutaneous techniques have been
rened and their clinical efcacy better dened. While
PEI is a valuable and accepted treatment for small HCC
lesions, RF ablation seems to achieve more effective
local control of disease with fewer treatment sessions
and appears to be superior to PEI as well as to other
chemical or thermal methods of tissue destruction. RF
ablation could therefore be currently considered as the
rst-line treatment of choice for patients with small
HCC who are not suitable candidates for resection or
transplantation. Nevertheless, further studies investi-
gating the long-term outcomes of RF-treated patients
are warranted to fully establish the clinical efcacy of
this technique. PEI as well as segmental transarterial
chemoembolization will continue to have a valuable
complementary role in patients with early-stage HCC.
Appropriate use of each treatment technique can only
be done when the therapeutic strategy is decided by a
multidisciplinary team and is tailored to the individual
patient and to the features of the disease.
References
1. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R,
Burroughs AK, et al. EASL Panel of Experts on HCC. Clinical
management of hepatocellular carcinoma. Conclusions of the
Barcelona-2000 EASL conference. European Association for the
Study of the Liver. J Hepatol 2001;35:421 430.
2. Bruix J, Llovet JM. Prognostic prediction and treatment strategy
in hepatocellular carcinoma. Hepatology 2002;35:519 524.
3. Llovet JM, Beaugrand M. Hepatocellular carcinoma: present
status and future prospects. J Hepatol 2003;38:S136 S149.
4. Lencioni R, Cioni D, Bartolozzi C. Percutaneous radiofrequency
thermal ablation of liver malignancies: techniques, indications,
imaging ndings, and clinical results. Abdom Imaging 2001;26:
345360.
5. Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carci-
noma: the BCLC staging classication. Semin Liver Dis 1999;
19:329 338.
6. Bartolozzi C, Lencioni R. Ethanol injection for the treatment of
hepatic tumours. Eur Radiol 1996;6:682 696.
7. Shiina S, Tagawa K, Unuma T, Takanashi R, Yoshiura K, Kom-
atsu Y, et al. Percutaneous ethanol injection therapy for hepato-
cellular carcinoma: a histopathologic study. Cancer 1991;68:
1524 1530.
8. Castells A, Bruix J, Bru C, Fuster J, Vilana R, Navasa M, et al.
Treatment of small hepatocellular carcinoma in cirrhotic
patients: a cohort study comparing surgical resection and percu-
taneous ethanol injection. Hepatology 1993;18:11211126.
9. Lencioni R, Bartolozzi C, Caramella D, Paolicchi A, Carrai M,
Maltinti G, et al. Treatment of small hepatocellular carcinoma
with percutaneous ethanol injection. Analysis of prognostic fac-
tors in 105 Western patients. Cancer 1995;76:17371746.
10. Livraghi T, Giorgio A, Marin G, Salmi A, De Sio I, Bolondi L, et
al. Hepatocellular carcinoma and cirrhosis in 746 patients: long-
term results of percutaneous ethanol injection. Radiology 1995;
197:101108.
11. Yamamoto J, Okada S, Shimada K, Okusaka T, Yamasaki S,
Ueno H, Kosuge T. Treatment strategy for small hepatocellular
 Percutaneous Ablation of Hepatocellular Carcinoma
carcinoma: comparison of long-term results after percutaneous
ethanol injection therapy and surgical resection. Hepatology
2001;34:707713.
12. Shiina S, Teratani T, Obi S, Hamamura K, Koike Y, Omata M.
Nonsurgical treatment of hepatocellular carcinoma: from percu-
taneous ethanol injection therapy and percutaneous microwave
coagulation therapy to radiofrequency ablation. Oncology
2002;62 Suppl 1:64 68.
13. Ishii H, Okada S, Okusaka T, Yoshimori M, Nakasuka H, Shi-
mada K, et al. Needle tract implantation of hepatocellular carci-
noma after percutaneous ethanol injection. Cancer 1998;82:
1638 1642.
14. Khan KN, Yatsuhashi H, Yamasaki K, Yamasaki M, Inoue O,
Koga M, et al. Prospective analysis of risk factors for early intra-
hepatic recurrence of hepatocellular carcinoma following ethanol
injection. J Hepatol 2000;32:269 278.
15. Koda M, Murawaki Y, Mitsuda A, Ohyama K, Horie Y, Suou T,
et al. Predictive factors for intrahepatic recurrence after percuta-
neous ethanol injection therapy for small hepatocellular carci-
noma. Cancer 2000;88:529 537.
16. Okusaka T, Okada S, Ueno H, Ikeda M, Shimada K, Yamamoto
J, et al. Satellite lesions in patients with small hepatocellular
carcinoma with reference to clinicopathologic features. Cancer
2002;95:19311937.
17. Goldberg SN, Gazelle GS, Mueller PR. Thermal ablation ther-
apy for focal malignancies: a uned approach to underlyng prin-
ciples, techniques, and diagnostic imaging guidance. AJR Am J
Roentgenol 2000;174:323331.
18. Goldberg SN, Gazelle GS, Solbiati L, Rittman WJ, Mueller PR.
Radiofrequency tissue ablation: increased lesion diameter with a
perfusion electrode. Acad Radiol 1996;3:636 644.
19. Lencioni R, Goletti O, Armillotta N, Paolicchi A, Moretti M,
Cioni D, et al. Radio-frequency thermal ablation of liver metas-
tases with a cooled-tip electrode needle: results of a pilot clinical
trial. Eur Radiol 1998;8:12051211.
20. Rossi S, Buscarini E, Garbagnati F, Di Stasi M, Quaretti P, Rago
M, et al. Percutaneous treatment of small hepatic tumors by an
expandable RF electrode needle. AJR Am J Roentgenol 1998;
170:10151022.
21. Cioni D, Lencioni R, Rossi S, Garbagnati F, Donati F, Crocetti
L, et al. Radiofrequency thermal ablation of hepatocellular car-
cinoma: using contrast-enhanced harmonic power doppler
sonography to assess treatment outcome. AJR Am J Roentgenol
2001;177:783788.
22. Numata K, Isozaki T, Ozawa Y, Sakaguchi T, Kiba T, Kubota T,
et al. Percutaneous ablation therapy guided by contrast-en-
hanced sonography for patients with hepatocellular carcinoma.
AJR Am J Roentgenol 2003;180:143149.
23. Morimoto M, Sugimori K, Shirato K, Kokawa A, Tomita N,
Saito T, et al. Treatment of hepatocellular carcinoma with radio-
frequency ablation: radiologic-histologic correlation during fol-
low-up periods. Hepatology 2002;35:14671475.
24. Shirato K, Morimoto M, Tomita N, Kokawa A, Sugimori K,
Saito T, et al. Small hepatocellular carcinoma: therapeutic effec-
tiveness of percutaneous radiofrequency ablation therapy with a
LeVeen needle electrode. J Ultrasound Med 2002;21:6776.
25. Livraghi T, Goldberg SN, Lazzaroni S, Meloni F, Solbiati L,
Gazelle GS. Small hepatocellular carcinoma: treatment with
radio-frequency ablation versus ethanol injection. Radiology
1999;210:655 661.
S97
26. Ikeda M, Okada S, Ueno H, Okusaka T, Kuriyama H. Radio-
frequency ablation and percutaneous ethanol injection in
patients with small hepatocellular carcinoma: a comparative
study. Jpn J Clin Oncol 2001;31:322326.
27. Lencioni R, Allgaier HP, Cioni D, Olschewski M, Deibert P,
Crocetti L, et al. Small hepatocellular carcinoma in cirrhosis:
randomized comparison of radiofrequency thermal ablation ver-
sus percutaneous ethanol injection. Radiology 2003;228:235
240.
28. Livraghi T, Goldberg SN, Lazzaroni S, Meloni F, Ierace T,
Solbiati L, et al. Hepatocellular carcinoma: radio-frequency abla-
tion of medium and large lesions. Radiology 2000;214:761768.
29. Goldberg SN, Hahn PF, Tanabe KK, Mueller PR, Schima W,
Athanasoulis CA, et al. Percutaneous radiofrequency tissue abla-
tion: does perfusion-mediated tissue cooling limit coagulation
necrosis? J Vasc Interv Radiol 1998;9:101115.
30. Rossi S, Garbagnati F, Lencioni R, Allgaier HP, Marchiano A,
Fornari F, et al. Percutaneous radio-frequency thermal ablation
of nonresectable hepatocellular carcinoma after occlusion of
tumor blood supply. Radiology 2000;217:119 126.
31. Yamasaki T, Kurokawa F, Shirahashi H, Kusano N, Hironaka K,
Okita K. Percutaneous radiofrequency ablation therapy for
patients with hepatocellular carcinoma during occlusion of
hepatic blood ow. Comparison with standard percutaneous
radiofrequency ablation therapy. Cancer 2002;95:23532360.
32. Yamakado K, Nakatsuka A, Ohmori S, Shiraki K, Nakano T,
Ikoma J, et al. Radiofrequency ablation combined with chemo-
embolization in hepatocellular carcinoma: treatment response
based on tumor size and morphology. J Vasc Interv Radiol 2002;
13:12251232.
33. Llovet JM, Vilana R, Bru C, Bianchi L, Salmeron JM, Boix L, et
al. Increased risk of tumor seeding after percutaneous radiofre-
quency ablation for single hepatocellular carcinoma. Hepatology
2001;33:1124 1129.
34. Livraghi T, Solbiati L, Meloni MF, Gazelle GS, Halpern EF,
Goldberg SN. Treatment of focal liver tumors with percutaneous
radio-frequency ablation: complications encountered in a multi-
center study. Radiology 2003;226:441 451.
35. Lencioni R, Veltri A, Guglielmi A, Bianchini M, Filauro M,
Bartolozzi C, et al. Complications of percutaneous radiofre-
quency ablation of liver malignancies with expandable multi-
probe needles: results of a multicenter study. Radiology 2003;
229 (P):671.
36. Ohnishi K, Yoshioka H, Ito S, Fujiwara K. Prospective random-
ized controlled trial comparing percutaneous acetic acid injec-
tion and percutaneous ethanol injection for small hepatocellular
carcinoma. Hepatology 1998;27:6772.
37. Seki T, Wakabayashi M, Nakagawa T, Imamura M, Tamai T,
Nishimura A, et al. Percutaneous microwave coagulation therapy
for patients with small hepatocellular carcinoma: comparison
with percutaneous ethanol injection therapy. Cancer 1999;85:
1694 1702.
38. Shibata T, Iimuro Y, Yamamoto Y, Maetani Y, Ametani F, Itoh
K, Konishi J. Small hepatocellular carcinoma: comparison of
radio-frequency ablation and percutaneous microwave coagula-
tion therapy. Radiology 2002;223:331337.
39. Adam R, Hagopian EJ, Linhares M, Krissat J, Savier E, Azoulay
D, et al. A comparison of percutaneous cryosurgery and percu-
taneous radiofrequency for unresectable hepatic malignancies.
Arch Surg 2002;137:13321339.