Tesi di Laurea*Facoltà di Scienze Matematiche Fisiche e Naturali*Corso di Lau...
2013 poggi anticancer research mw ablation of hcc using a new percutaneous device_ preliminary results
1. ANTICANCER RESEARCH 33: 1221-1228 (2013)
Microwave Ablation of Hepatocellular Carcinoma Using
a New Percutaneous Device: Preliminary Results
GUIDO POGGI1, BENEDETTA MONTAGNA1, PAMELA DI CESARE2, GIULIA RIVA2,
GIOVANNI BERNARDO1, MAURO MAZZUCCO3 and ALBERTO RICCARDI2
1Oncology Unit, Città di Pavia Institute, University Hospital, Pavia, Italy;
2Oncology, University of Pavia, Pavia, Italy;
3Hepatology Unit, USSL 17, Este-Monselice, Padova, Italy
Abstract. Background: Thermal ablative techniques have effective and safe percutaneous ablative method, capable of
gained increasing popularity as safe and effective options producing large areas of necrosis.
for patients with unresectable solid malignancies.
Microwave ablation has emerged as a relatively new Hepatocellular carcinoma (HCC) is the fifth most common
technique with the promise of larger and faster ablation malignancy and the third leading cause of cancer death
areas without some of the limitations of radiofrequency worldwide (1). Although hepatic resection is the preferred
thermal ablation. Herein, we report our preliminary results treatment option for patients with well-compensated cirrhosis
on the feasibility and efficacy of thermal ablation for with early-stage HCC, other non-surgical treatments, such as
hepatocellular carcinoma (HCC) with a new 2.45-MHz local ablation therapies, have gained a growing popularity as
microwave generator. Patients and Methods: Under alternative therapies due to their minimal invasiveness, efficacy,
ultrasound guidance 194 HCCs in 144 patients were treated easy repeatability, and cost-effectiveness (2). Radiofrequency
through a percutaneous approach. The median diameter of ablation (RFA), the most common technique worldwide, was
lesions was 2.7 cm (range=2.0-11.0 cm); 68 lesions had a developed in Western countries at the beginning of the 1990s
diameter greater than 30 mm. We used a microwave (3, 4). Microwave ablation (MWA), another ablative technique
generator (AMICA-GEM, Apparatus for MICrowave developed mainly in Oriental countries, only recently gained
Ablation) connected to a 14- or 16-gauge coaxial antenna popularity in Western countries (5, 6).
endowed with a miniaturized sleeve choke to reduce back Although both treatments induce thermal ablation of tumor
heating effects and increase the sphericity of the ablated tissues, the mechanisms of heat generation are different due
area. Contrast-enhanced computed tomography scan was to the different source of energy employed and its different
carried out one month after treatment, and then every three propagation in tissues. MWA technology has several
months to assess efficacy. Results: Complete ablation was theoretical advantages compared with RFA: first of all, it
achieved in 94.3% of the lesions after a mean of 1.03 achieves a greater penetration of energy into tissues, resulting
percutaneous sessions. For small HCCs (diameter <3 cm) in less susceptibility to convective heat loss from hepatic blood
complete necrosis was obtained in 100%. Local tumor flow, and low sensitivity to local variation in tissue physical
progressions were found in 10 treated lesions (5.1%) a properties, such as impedance (7, 8). For that reason, MWA
median of 19.5 months after ablation. Minor complications technology was expected to obtain larger volumes and faster
occurred in 5.1% procedures. No deaths, or other major area of thermal ablation with respect to RFA (9). However, the
complications occurred. Conclusion: In our experience, the ablation zones obtained by first-generation MWA devices were
new device for microwave ablation proved to provide an frequently smaller and had a less rounded shape than those
obtained by RFA apparatus. The improvement of microwave
technology has led to the development of more powerful
generators, able to obtain volumes of necrosis greater than
Correspondence to: Guido Poggi, MD, Oncology Unit, Città di Pavia previously, but with ellipsoidal areas of necrosis, due to
Institute, University Hospital, 27 Parco Vecchio Street, 27100 Pavia,
uncontrolled microwave power reflection along the track of
Italy. Tel/Fax: +39 0382433631, e-mail: guidopoggi64@gmail.com/
guido.poggi@grupposandonato.it electrode insertion. This phenomenon, also known as the
‘comet’ effect, has made the MWA method not entirely
Key Words: Image-guided thermal ablation, microwave ablation, suitable for the treatment of substantially spherical lesions,
HCC. such as the nodules of HCC (6, 10).
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2. ANTICANCER RESEARCH 33: 1221-1228 (2013)
We used a new microwave generator (AMICA-GEM, Table I. Patients’ and tumors’ characteristics.
Apparatus for MICrowave Ablation) connected to a 14- or
Median age, years (range) 75 (60-87)
16-gauge (G) coaxial antenna working at 2,450 MHz and
Gender
endowed with a miniaturized sleeve choke in order to reduce Male, n (%) 94 (65)
back-heating effects and increase the sphericity of the area Female, n (%) 50 (35)
of necrosis. Etiology of cirrhosis, n (%)
In the current study we report on the short-term results of HCV 106 (74)
HBV 6 (4)
our mono-institutional experience using this new
HCV-HBV 8 (5)
percutaneous device for the thermal ablation of HCC. Alcohol 10 (7)
Alcohol and HCV 10 (7)
Patients and Methods Other 4 (3)
Child-Pugh score, n (%)
Patients’ characteristics. In our retrospective study, between June A5 132 (68)
2009 and September 2011, percutaneous MWA was performed for A6 52 (27)
194 HCCs in 144 patients affected by hepatic cirrhosis in our B7 10 (5)
institution. Inclusion criteria were as follows: age >18 years; Eastern Tumors size, cm
Cooperative Oncology Group performance status 0 or 1; histological Median (range) 2.7 (2.0-11)
or radiological diagnosis of HCC; disease limited to the liver, with <3 cm, n (%) 126 (65)
no more than three lesions; appropriate visualization of lesions on >3 ≤5 cm, n (%) 49 (25)
>5 cm, n (%) 19 (10)
ultrasounds (US); lesions far from intestinal loops, gallbladder or
HCC location (segment)
main bile ducts; unsuitable for or refused surgical resection; liver
S2/S3/S4/S5/S6/S7/S8 4/24/14/24/36/58/34
function status at Child-Pugh score ≤B8; absence of major portal
vein thrombosis; platelet count greater than 50,000/mm3;
HCV: Hepatitis virus C; HBV: hepatits virus B; HCC: hepatocellular
prothrombin time greater than 60%; total bilirubin concentration carcinoma; S: segment.
<3 mg/dl. The study population consisted of 144 patients, 94 men
(65%) and 50 women (35%), with a median age of 75 years
(range=60-87 years). The etiology of the underlying liver disease
was hepatitis C (HCV) infection in 106 patients, hepatitis B (HBV)
in six, alcoholic-hepatitis in 10, HCV and HBV co-infection in to 80 W for 14-G antenna; up to 40 W for 16-G antenna). A 14-G
eight, HCV infection and alcohol abuse in 10 and cryptogenic antenna was used for the treatment of 134 lesions (69%), while a
chronic liver disease in four patients. Among these 194 HCCs, 35% 16-G one was used for 60 lesions (31%).
were confirmed by histopatological analysis on biopsy samples The approach was subcostal in 47% of cases, intercostal in 52%
obtained with an 18-G cutting needle and the remaining 65% were of cases, while a combined approach was followed in 1% of the
considered HCC on the basis of clinical and radiological criteria of procedures. The duration of the ablation procedures, ranging from 3
the American Association for the Study of Liver Disease (11). The to 16 min, was established according to the size of the lesions (relying
median diameter of these 194 HCCs was 2.7 cm (range=2.0-11 cm). on ex vivo data, supplied by the manufacturer, on bovine liver).
Lesions were defined as small, intermediate or large depending on Furthermore, the size and the shape of the hyperechoic zone
the main diameter, corresponding to <3 cm, ≥3 cm and <5 cm and caused by gas microbubbles appearing in the ablation zone the
≥5 cm respectively. Patients’ and tumors’ characteristics are reported during MWA procedure was monitored by US to assess the
in Table I. completeness of therapy. Treatment was stopped when the entire
Before treatment, all patients underwent routine laboratory tests target was completely hyperechoic. The hyperhecoic zone did not
and an abdomen ultrasound to evaluate the location of the lesion always perfectly reproduce the shape of the lesion, neither was it
and its relationship to closer vessels, gallbladder or bowel loops. A perfectly confined to the lesion. In some instances, for example the
written informed consent for the ablation procedure approved by the use of high powers, the hyperechoic spots also extended along the
Ethics Committee of the Institution was obtained from each patient needle track producing a tent-shaped ablation area with the vertex at
before the treatment. the point of the needle insertion into the liver.
Patients were treated under unconscious sedation with
Treatment modality. MWA was performed using a dedicated solid- intravenous administration of fentanyl and propofol, in spontaneous
state programmable microwave 2.45-MHz generator (AMICA-GEN; breathing with oxygen mask support.
HS Hospital Service SpA, Aprilia, Italy) delivering energy of 40- Treatment was defined as the whole number of sessions or
100 W through a 14- or 16-G internally cooled, coaxial antenna procedures required to achieve complete ablation of the lesion;
(AMICA-PROBE; HS Hospital Service SpA), featuring a specifically, one treatment was defined as a maximum of four
miniaturized quarter-wave impedance transformer (mini-choke) for procedures in an interval time of three months.
reflected wave confinement. An automatic peristaltic pump was used
for applicator cooling to avoid probe overheating (Figure 1). Assessment of treatment response. An abdominal contrast-enhanced
MWA was performed with US guidance through a percutaneous computed tomographic scan was performed for all patients 30±10 days
approach; the choice at using a 14-G or 16-G antenna was made after the treatment, then every three months for the first year of follow-
according to the size and site of the lesion, taking into account the up, and then every six months during the next follow-up period.
different powers that can be used with the two types of antennas (up Complete ablation was defined as complete absence of contrast
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3. Poggi et al: Microwave Ablation of HCC with a New Percutaneous Device
Figure 1. 2.45-MHz microwave generator (a) and coaxial antenna (b) used in this study.
enhancement, with homogeneous hypodensity in the ablation zone; the therapies (four with TACE and two with TACE combined
opposite was defined as incomplete ablation. with MWA), obtaining complete response. One tumor with
Patients in whom complete ablation was achieved after the a 5.7 cm diameter, located in the fifth segment not more far
treatment underwent follow-up, while patients in whom complete
than 1 cm from the gallbladder wall, was surgically removed;
ablation was not achieved were scheduled for other therapies, such
as a new session of percutaneous MWA, surgery, laparoscopic histopathological examination demonstrated nearly complete
thermal ablation, percutaneous ethanol injection (PEI), transarterial necrosis, with an area of less than 1 cm2 of residual
chemoembolization (TACE), medical therapies, or a combination of pathological tissue, as shown in the preoperative CT scan.
two or more of the above treatments, depending on the features of With reference to the remaining four lesions, each belonging
each single clinical case. to a single patient, a multifocal progression of disease was
The tumor re-growth in the ablated zone or in the adjacent detected and treated with sorafenib in three patients, while
territory was defined as local tumor progression (LTP), while the
the other patient was treated only with supportive care,
appearance of new lesions within the liver parenchyma or at another
site was defined as distant tumor progression (DTP) according to owing to a rapid decline of liver function. During the follow-
standards of the terminology (12). Patients with new lesions or LTP up period, LTP was found in 10 treated lesions (two small,
were planned for further treatment (such as MWA, PEI, TACE or six intermediate and two large HCCs) belonging to eight
others), depending on the individual case features. patients, a median of 19.5 months (range=12-27 months)
To estimate the amplitude of the ablation zone obtained by MWA after MWA treatment. LTPs were subsequently treated with
for each lesion, we calculated the difference between the volume of MWA in four cases and with TACE in the other six. DTPs
the ablation zone and the baseline volume of the treated lesion: this
with lesions within the liver parenchyma were found in 40
difference was defined as Δ volume. Using the equation for the
volume of an ellipsoid, multiplying the largest three diameters on out of 144 patients (27.7%), at a median of 6 months
sagittal and axial planes obtained by enhanced abdominal CT scans (range=4-23 months) after MWA treatment. Among these
(performed immediately before and one month after MWA), the patients, six had concomitant extra-hepatic disease
volumes before and after MWA were calculated (13). progression, with lung metastases in two patients and bone
metastases in four.
Statistical analysis. Descriptive statistics were calculated for all For small lesions, the median Δ volume obtained with a
variables reporting mean and standard deviation for quantitative
14-G antenna was 11.2 cm3, representing an increase of
variables with Gaussian distribution, median and range for ordinal
or quantitative variables with Gaussian distribution, and frequency almost 100% of the volume of a 3-cm diameter lesion, while
and percentage for qualitative categorical or variables. for intermediate and large lesions, the increase was less
extensive. In the intermediate and large HCCs in which
Results complete ablation was not reached, the Δ volume was a
negative value (Table II).
The median follow-up period of the study population was Our study confirmed that MWA is a very fast procedure.
nine months (range 1-31 months). Complete ablation was As shown in Table III, the time of energy application differed
achieved in 183 lesions (94.3%), after a mean of 1.03 according to the diameter of nodules. A mean time of only
(SD=0.17) percutaneous MWA sessions (Figure 2). The rate 6.3 minutes was sufficient to obtain an adequate ablation
of complete ablation was mainly related to the lesion size. area for small HCCs, while for intermediate and large HCCs,
For small HCCs, complete ablation was obtained in 100%, the mean duration of the ablation was 10.1 min and 13.7
while the rate of complete ablation was 90% and 69% for the min, respectively.
intermediate and large lesions, respectively. Out of the 11 As already explained, the major limitation of first-
tumors (5.6%) for which complete ablation was not obtained generation microwave technology was represented by the
(Figure 3), six were subsequently treated with locoregional tendency to form an elliptical-shape area of necrosis. To
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4. ANTICANCER RESEARCH 33: 1221-1228 (2013)
Figure 2. Computed tomography scan pre (a)- and post (b)-microwave ablation, showing complete ablation of the tumor.
Figure 3. Computed tomography scan pre (a)- and post (b)-microwave ablation, showing incomplete ablation of the tumor (arrows).
Table II. Δ-Volume and ratio diameters.
Lesion diameter Needle gauge Median Δ-volume (range) Diameter ratio
Median (range) Mean (DS)
<3 cm 14-G 11.2 cm3 (0.92-44.8) 1.105 (0.44-1.6) 1.1 (0.33)
16-G 3.45 cm3 (0.37-27.1)
≥3 cm to <5 cm 14-G 5.89 cm3 (-1.7-36.68) 1.07 (0.47-1.56) 1.09 (0.25)
≥5 cm 14-G 1.7 cm3 (-12,3-5,9) 1.13 (0.57-1.62) 1.15 (0.32)
G: Gauce; SD: standard deviation; Δ-volume: difference between ablation zone volume and baseline volume.
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5. Poggi et al: Microwave Ablation of HCC with a New Percutaneous Device
Table III. Time of procedures in relation to the diameter of the lesions.
Lesion diameter Mean duration of application (SD)
<3 cm 6.3 (2.1) min
≥3 cm to <5 cm 10.1 (3.7) min
>5 cm 13.7 (3.1) min
SD: Standard deviation.
completely overcome in a more recent model of the same
probe, featuring zirconium instead of aluminium oxide.
Nevertheless, tip detachment did not cause symptoms or
long-term local or distant complications.
Discussion
Local ablation is considered the first line treatment option
for patients with early-stage disease, not suitable for surgical
Figure 4. Computed tomography scan showing the probe tip in the therapy (2). For many years, PEI has been the main
subcutaneous tissue (arrow). technique for percutaneous treatment of HCC. Thermal
ablative techniques were then developed, including RFA,
MWA, laser ablation and cryoablation. RFA, with respect to
other methods, showed a higher anticancer effect than PEI
assess how the ablated area was similar to a spherical shape, in patients with HCC, leading to a better control of the
for each lesion, we calculated the greater and the smaller disease and a survival advantage than PEI of lesions larger
diameter ratio (with spherical lesion having a ratio equal to than 20 mm (15-19). RFA is, thus, currently the most
1). The results obtained, reported in Table II, show that the popular and widely used thermal ablation modality. RFA has
new device, limiting the backscattering of the reflected proved to be particularly effective for lesions smaller than 3
microwaves, was able to form ablation areas of almost cm, with the best reported rate of complete necrosis
spherical shape, independently of the dimension of the approaching 99% of treated lesions, offering a 5-year overall
treated tumor. survival of around 40% (20). A liver transplant center
reported less enthusiastic data, with a histological evidence
Complications. Some complications occurred in our series, of complete response of 63% for explanted livers for HCCs
have already been reported in a recent study by Livraghi et with a diameter <3 cm (21). However, despite the high
al. who collected the results of a multicenter study (14). No percentage of necrosis reported by various authors, the
ablation-related death nor major complication (defined as recurrence rate is highly variable, from 2% to 39%,
any event that leads to substantial morbidity and disability, depending on the technique used (22-24). Indeed for HCCs
increasing the level of care, or results in hospital admission >3 cm, the success of RFA decreases, and combined
or substantially lengthened hospital stay) occured. Minor therapies are adopted to increase the rate of complete
complications occurred in 10 out of 194 sessions (5.1%). ablation. RFA may not be effective within the periphery of
These cases included: a small asymptomatic pleural effusion the ablation area because of the presence of blood vessels,
not requiring drainage (n=4), a cutaneous burn occurring in which can create a protective heat-sink effect (25).
the treatment of a partially esophytic subcapsular lesion Combining RFA with TACE, technical success was obtained
(n=2). Mechanical damage to the probe tip (composed of a in 85% of medium-size HCCs (26, 27).
ceramic sleeve surrounding the antenna coaxial emitter, in MWA has recently emerged as a new therapeutic option,
turn loaded with a sharp stainless steel point) was observed offering many of the benefits of RFA with other theoretical
in four procedures, either during probe insertion into the advantages. The promised benefits of MWA are consistently
target or when withdrawing the probe after ablation (Figure wider ablation areas, faster ablation times, ability to perform
4). All probe tip fragility issues refer to an early version of multiple ablations simultaneously, and no requirement for
the MWA applicator, featuring an aluminium oxide sleeve in grounding pads (9). In the past, however, the greatest
its distal emitting portion. These issues seemed to have been limitation of microwave technology was the difficulty of
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obtaining spheroidal areas of necrosis due to the comet effect 3 Fraker DL: Percutaneous radiofrequency interstitial thermal
(6, 10). The system we used included the Amica-Probe, a ablation. Cancer J Sci Am 1: 122-130, 1995.
coaxial antenna with a patented miniaturized device for 4 Buscarini L, Rossi S, Fornari F, Di Stasi M and Buscarini E:
Laparoscopic ablation of liver adenoma by radiofrequency
entrapping reflected waves lodged inside a metallic
electrocauthery. Gastrointest Endosc 41: 68-70, 1995.
introducer. This device allows for maximum control over the 5 Sato M, Watanabe Y, Ueda S, Iseki S, Abe Y, Sato N, Kimura S,
size and shape of the coagulative lesion, both in radial and Okubo K and Onji M: Microwave coagulation therapy for
longitudinal directions. Our preliminary data confirm that the hepatocellular carcinoma. Gastroenterology 110: 1507-1514, 1996.
latest generation of microwave technology is very promising. 6 Shibata T, Niinobu T and Ogata N: Comparison of the effects of
Complete necrosis was achieved in 100% of small HCC in vivo thermal ablation of pig liver by microwave and
cases, with a very limited number of sessions of very short radiofrequency coagulation. J Hepatobiliary Pancreat Surg 7:
592-598, 2000.
duration. The treatment of medium HCCs also showed very
7 Brace CL: Radiofrequency and microwave ablation of the liver,
promising results: ablation was complete in 90% of HCCs of
lung, kidney, and bone: What are the differences? Curr Probl
between 3 and 5 cm. The large volume of necrosis obtained Diagn Radiol 38: 135-143, 2009.
by MWA creates a great safety margin around the lesion 8 Brace CL: Microwave ablation technology: What every user
treated, well-evidenced by the values of Δ volume. This is should know. Curr Probl Diagn Radiol 38: 61-67, 2009.
reflected in the low number of local failures, especially for 9 Andreano A, Huang Y, Meloni MF, Lee FT Jr. and Brace C:
small and intermediate HCCs, and may be explained by the Microwaves create larger ablations than radiofrequency when
peculiar mechanism of propagation of microwave energy in controlled for power in ex vivo tissue. Med Phys 37: 2967-2973,
2010.
tissues. While RF currents flow only in high conductivity
10 Ohmoto K, Yoshioka N, Tomiyama Y, Shibata N, Kawase T,
paths, microwaves are capable of propagating through tissues Yoshida K, Kuboki M and Yamamoto S: Radiofrequency
with low conductivity, such as charred tissues. MWA actively ablation versus percutaneous microwave coagulation therapy for
heats a large, homogeneous volume around the applicator small hepatocellular carcinomas: a retrospective comparative
antenna, while RFA heating is limited to areas of high study. Hepatogastroenterology 54: 985-989, 2007.
current density located very close to the antenna (7, 8). The 11 Bruix J and Sherman M: Practice Guidelines Committee, American
other side of the coin is a hypothetical increased risk of Association for the Study of Liver Diseases. Management of
hepatocellular carcinoma. Hepatology 42: 1208-1236, 2005.
complications due to an excessively large volume of
12 Goldberg SN, Grassi CJ, Cardella JF, Charboneau JW, Dodd GD
necrosis, even if in our limited experience, we did not
3rd, Dupuy DE, Gervais DA, Gillams AR, Kane RA, Lee FT Jr.,
observe any such major complications. Livraghi T, McGahan J, Phillips DA, Rhim H, Silverman SG,
In conclusion, our preliminary data show that MWA is an Solbiati L, Vogl TJ, Wood BJ, Vedantham S and Sacks D: Image-
effective and safe ablative method. Considering the relatively guided tumor ablation: Standardization of terminology and
short period of follow-up, we preferred not to report survival reporting criteria. J Vasc Interv Radiol 20: S377-390, 2009.
data, reserving further analysis for when such data will be 13 Dachman AH, MacEneaney PM, Adedipe A, Carlin M and
available. Schumm LP: Tumor size on computed tomography scans: Is one
measurement enough? Cancer 91: 555-560, 2001.
It would also be appreciable comparing the two most
14 Livraghi T, Meloni F, Solbiati L and Zanus G: Complications of
widely used methods, RFA and MWA in randomized studies, Microwave Ablation for Liver Tumors: Results of a Multicenter
to establish which technique is superior. Moreover, the Study. Cardiovasc Intervent Radiol 35: 868-874, 2012
evaluation of a combined treatment of MWA and TACE in 15 Shiina S, Teratani T, Obi S, Sato S, Tateishi R, Fujishima T,
order to achieve a better rate of necrosis in lesions >3 cm Ishikawa T, Koike Y, Yoshida H, Kawabe T and Omata M: A
should be of great interest. randomized controlled trial of radiofrequency ablation with
The encouraging results that emerge after almost two ethanol injection for small hepatocellular carcinoma.
Gastroenterology 129: 122-130, 2005.
years experience in the use of MWA certainly urge us to
16 Lin SM, Lin CJ, Lin CC, Hsu CW and Chen YC:
believe in further future development of this method. Radiofrequency ablation improves prognosis compared with
ethanol injection for hepatocellular carcinoma ≤4 cm.
Conflicts of Interest Gastroenterology 127: 1714-1723, 2004.
17 Lin SM, Lin CJ, Lin CC, Hsu CW and Chen YC: Randomised
There are no conflicts of interest and financial disclosures. controlled trial comparing percutaneous radiofrequency thermal
ablation, percutaneous ethanol injection, and percutaneous acetic
References acid injection to treat hepatocellular carcinoma of 3 cm or less.
Gut 54: 1151-1156, 2005.
1 Venook AP, Papandreou C, Furuse J and de Guevara LL: The 18 Lencioni RA, Allgaier HP, Cioni D, Olschewski M, Deibert P,
incidence and epidemiology of hepatocellular carcinoma: a global Crocetti L, Frings H, Laubenberger J, Zuber I, Blum HE and
and regional perspective. Oncologist 15(Suppl 4): 5-13, 2010. Bartolozzi C: Small hepatocellular carcinoma in cirrhosis:
2 EASL–EORTC Clinical Practice Guidelines: Management of Randomized comparison of radio-frequency thermal ablation versus
hepatocellular carcinoma. J Hepatol 56: 908-943, 2012. percutaneous ethanol injection. Radiology 228: 235-240, 2003.
1226
7. Poggi et al: Microwave Ablation of HCC with a New Percutaneous Device
19 Shiina S, Teratani T, Obi S, Hamamura K, Koike Y and Omata 24 Curley SA and Izzo F: Laparoscopic radiofrequency. Ann Surg
M: Nonsurgical treatment of hepatocellular carcinoma: From Oncol 7: 78-79, 2000.
percutaneous ethanol injection therapy and percutaneous 25 Lu DS, Raman SS, Vodopich DJ, Wang M, Sayre J and Lassman
microwave coagulation therapy to radiofrequency ablation. C: Effect of vessel size on creation of hepatic radiofrequency
Oncology 62: 64-68, 2002. lesions in pigs: Assessment of the heat-sink effect. Am J
20 N'Kontchou G, Mahamoudi A, Aout M, Ganne-Carrié N, Grando Roentgenol 178: 47-51, 2002.
V, Coderc E, Vicaut E, Trinchet JC, Sellier N, Beaugrand M and 26 Veltri A, Moretto P, Doriguzzi A, Pagano E, Carrara G and
Seror O: Radiofrequency ablation of hepatocellular carcinoma: Gandini G: Radiofrequency thermal ablation (RFA) after
long-term results and prognostic factors in 235 Western patients transarterial chemoembolization (TACE) as a combined therapy
with cirrhosis. Hepatology 50: 1475-1483, 2009. for unresectable non-early hepatocellular carcinoma (HCC). Eur
21 Mazzaferro V, Battiston C, Perrone S, Pulvirenti A, Regalia E, Radiol 16: 661-669, 2006.
Romito R, Sarli D, Schiavo M, Garbagnati F, Marchianò A, 27 Liao GS, Yu CY, Shih ML, Chan DC, Liu YC, Yu JC, Chen TW
Spreafico C, Camerini T, Mariani L, Miceli R and Andreola S: and Hsieh CB: Radiofrequency ablation after transarterial
Radiofrequency ablation of small hepatocellular carcinoma in embolization as therapy for patients with unresectable
cirrhotic patients awaiting liver transplantation: A prospective hepatocellular carcinoma. Eur J Surg Oncol 34: 61-66, 2008.
study. Ann Surg 240: 900-909, 2004.
22 Shiina S, Tateishi R, Arano T, Uchino K, Enooku K, Nakagawa
H, Asaoka Y, Sato T, Masuzaki R, Kondo Y, Goto T, Yoshida H,
Omata M and Koike K: Radiofrequency ablation for
hepatocellular carcinoma: 10-Year outcome and prognostic
factors. Am J Gastroenterol 107: 569-577, 2012.
23 Jiao LR, Hansen PD, Havlik R, Mitry RR, Pignatelli M and
Habib N: Clinical short-term results of radiofrequency ablation Received December 25, 2012
in primary and secondary liver tumors. Am J Surg 177: 303-306, Revised February 4, 2013
1999. Accepted February 5, 2013
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