DOI:10.2214/AJR.05.2079
AJR 2007; 188:480-488
© American Roentgen Ray Society
Radiofrequency Ablation of Hepatocellular Carcinoma: Correlation Between Local Tumor Progression After Ablation and Ablative Margin
Takahide Nakazawa1,
Shigehiro Kokubu,
Akitaka Shibuya,
Koji Ono,
Masaaki Watanabe,
Hisashi Hidaka,
Takeshi Tsuchihashi and
Katsunori Saigenji
1 All authors: Gastroenterology Division of Internal Medicine, Kitasato
University East Hospital, 2-1-1 Asamizodai, Sagamihara, Kanagawa 228-8520,
Japan.
Received November 30, 2005;
accepted after revision February 14, 2006.
Address correspondence to T. Nakazawa
(tnakazaw{at}kitasato-u.ac.jp).
Abstract
OBJECTIVE. To identify the determinants of tumor progression, we
examined the ablation zones and patterns of local progression of small single
primary hepatocellular carcinomas after radiofrequency ablation.
MATERIALS AND METHODS. Eighty-five patients with single primary
hepatocellular carcinoma less than 3 cm in diameter underwent complete tumor
ablation. Clinical and biochemical features, tumor characteristics, tumor
location within 5 mm from intrahepatic vessels, needle biopsy before
treatment, and presence of ablative margin of 5 mm or more were statistically
analyzed as determinants of local tumor progression. The Kaplan-Meier method
and a Cox model were used for the analyses. Patterns of local tumor
progression were examined by image analysis.
RESULTS. During a median observation period of 30.3 months, 14
(16.5%) of the 85 patients had local tumor progression. The results of the
log-rank test showed that the presence of vessels contiguous with the tumor
(p = 0.0292) and the absence of an ablative margin of at least 5 mm
(p = 0.019) significantly correlated with local tumor progression.
Cox regression analysis showed that the absence of an ablative margin of at
least 5 mm was an independent factor (p = 0.04). The most common
pattern of local tumor progression was a single viable outgrowth from the side
of the ablated area when the ablative margin was less than 5 mm. Multiple
viable outgrowths were observed in one case despite the presence of an
ablative margin greater than 5 mm.
CONCLUSION. An ablation zone with an ablative margin of 5 mm or
greater was the most important factor for local control of hepatocellular
carcinoma.
Keywords: abdominal imaging • cancer • hepatocellular carcinoma • liver disease • radiofrequency ablation
Introduction
Hepatocellular carcinoma (HCC) is one of the most common malignant
tumors worldwide [1]. HCC
frequently recurs after curative treatment, leading to high mortality rates
[2,
3]. Surgical resection and
orthotopic hepatic transplantation are curative treatments of HCC but are
often not feasible. A shortage of donors limits the possibilities for
orthotopic hepatic transplantation, and surgical resection is frequently
precluded because of poor hepatic reserve due to liver cirrhosis.
Radiofrequency ablation is therefore widely used to control locoregional
disease. Good outcome has been obtained with respect to survival and local
control
[4-11].
Radiofrequency ablation with a percutaneously inserted electrode ablates
tumors more completely than other locoregional treatments, reducing the rate
of local recurrence [10,
11]. To further improve local
disease control and outcome, several studies have been conducted to analyze
risk factors and patterns of local recurrence after radiofrequency ablation of
HCC. The presence of vessels around HCC, a tumor size of 2 cm or greater, and
tumor location near the liver surface have been identified as risk factors for
local recurrence
[6-8].
Vessels around HCC are minimally affected by radiofrequency ablation,
increasing the risk of local recurrence
[12]. Other factors
potentially related to local control of HCC involve the ablation zone
[13].
Complete ablation of HCC is required for prevention of local recurrence and
a good prognosis [6,
14]. After complete ablation,
the ablation zone is completely surrounded by an avascular area with a
contrast defect identifiable on dynamic contrast-enhanced CT. Despite complete
ablation, however, outgrowths sometimes develop around ablated areas
[15], and the presence of
residual cancer cells can lead to regrowth of the tumor. Therefore, the term
"local tumor progression" is more accurate than the term
"local recurrence"
[16]. Ablation of appropriate
margins beyond the tumor is necessary to achieve complete tumor destruction,
and the term "ablative margin" is proposed to describe this 0.5-
to 1.0-cm-wide region [13,
16]. Ablative margin is one
possible determinant of local tumor progression after complete ablation.
In this study, we examined various factors, including ablative margin, that
may correlate with local progression of primary single HCC after complete
radiofrequency ablation. The pattern was assessed by imaging analysis in
patients with local tumor progression.
Materials and Methods
Clinical Features of Patients
Between October 1999 and December 2004, radiofrequency ablation was used to
treat 383 patients with HCC at Kitasato University East Hospital. Ninety-four
patients were included in the study on the basis of the inclusion criteria.
Inclusion criteria were adult patient with a single primary HCC smaller than 3
cm in diameter, no eligibility for surgical resection or refusal of surgery,
liver function classified as Child-Pugh class A or B, platelet count greater
than 30 x 103/µL, and prothrombin activity greater than
40%. Exclusion criteria were previous treatment of HCC, incomplete ablation of
HCC, presence of extrahepatic metastasis or vascular invasion, and follow-up
period of less than 6 months. Nine patients were excluded. In five of these
nine patients, tumor ablation was incomplete because HCC involved the lung,
gallbladder, liver surface, or a combination of these areas. In the other four
patients, the follow-up period was less than 6 months because of death from
rupture of esophageal varices or because the patient had moved and was lost to
follow-up. Eighty-five patients underwent technically successful complete
ablation with an ablative margin and were included in the study.
The diagnosis of HCC was established on the basis of radiologic features
compatible with HCC on contrast-enhanced multiphase helical CT scans or
dynamic contrast-enhanced MR images (n = 45) and histologic
confirmation (n = 36). The other four patients had tumors with a
serum 
-fetoprotein level > 20 ng/dL or a level of protein induced by
vitamin K absence or antagonism II (PIVKA-II) > 40 mAU/mL. Sixty-four (75%)
of the patients had positive results for anti-hepatitis C virus, and 13 (15%)
had positive results for hepatitis B surface antigen. Fifty-nine (69%) of the
patients had a serum -fetoprotein level > 20 ng/dL or PIVKA-II level
> 40 mAU/mL. The median diameter of the HCC nodules was 20 mm (range, 10-29
mm). Tumor location was described according to Couinaud segmental anatomic
classification. Eighty-two patients had liver cirrhosis, and three had chronic
hepatitis. Clinical stage was defined according to Child-Pugh classification
and Japan Integrated Staging score
[17]. Fifty (59%) and 35 (41%)
of the patients had disease in Child-Pugh classes A and B, respectively. The
Japan Integrated Staging score was 0 in 48 patients, 1 in 36 patients, and 2
in one patient. Our study was performed in accordance with the guidelines of
our institutional review board, and written informed consent was obtained from
all patients before treatment.
Radiofrequency Thermal Ablation
Eighty-two patients were treated by percutaneous radiofrequency ablation
under real-time sonographic guidance (model 6500, Aloka Medical Systems) with
a 3.75-MHz probe. Three patients were treated under CT guidance. Fifty-five
(65%) of the patients were treated with multitined expandable electrodes, and
30 (35%) were treated with internally cooled electrodes. Conscious sedation
with a combination of pethidine hydrochloride 35 mg (Opystan, Tanabe) and
fentanyl citrate 0.1 mg (Fentanest, Sankyo) was administered IV.
Radiofrequency ablation was performed with one of three devices.
Twenty-seven patients were treated with 25-cm-long, 15-gauge multitined
electrodes with a 1-cm-long tip expandable by four to seven hooks to a maximum
diameter of 3 cm (model 30 or 70, RITA Medical Systems). A 460-kHz
radiofrequency generator (model 500PA, RITA Medical Systems) was activated,
and the power needed to maintain a temperature of 90-120°C at the tip was
delivered for 8 minutes. After the first ablation, the hooks were retracted,
and the electrode was rotated 45°. The hooks were redeployed, and the
radiofrequency generator was reactivated for an additional 8 minutes.
Twenty-eight patients were treated with hooked, 25-cm-long, 15-gauge
multitined electrodes expandable by 10 hooks to a maximum dimension of 3 cm
(LeVeen needle electrode, RadioTherapeutics), and radiofrequency ablation was
applied with a 460-kHz radiofrequency generator (RTC 2000, Boston Scientific
Japan). Initial output was set to 40 W, and the output was increased 10 W
every 60 seconds until the peak power of 90 W was attained. Ablation was
maintained at peak power for at least 15 minutes.
Thirty patients were treated with 25-cm-long, 17-gauge internally cooled
electrodes with an exposed 2- to 3-cm metallic tip capable of producing 200 W
of power. These electrodes were attached to a 480-kHz radiofrequency generator
(CC1, Radionics). A peristaltic pump was used to deliver chilled saline
solution in a cannula sheath of internally cooled electrodes to maintain
electrode temperature below 15°C. Radiofrequency current was emitted for
12-15 minutes per needle electrode insertion with the generator set to deliver
the maximum power in the autocontrol mode. An impedance control mode gradually
increased the power until the impedance rose to 10 
above baseline
level. To avoid a further increase in tissue temperature that would likely
result in charring, the power was reduced automatically to 10 W for 15 seconds
and returned to maximal power until the impedance increased again.
The three types of electrodes were used in the order they were introduced
to our hospital. The electrodes were inserted in several sites to treat
overlapping zones and to enlarge the ablation zone. The initial treatment was
planned with one ablation for tumors less than 2 cm in diameter and two or
more ablations for tumors with the overlapping technique for tumors 2-3 cm in
diameter. When tumor ablation was complete, thermal ablation was performed
along the needle track. All patients were carefully observed for
treatment-related complications.
Image Analysis for HCC and Posttreatment Assessment
The following tumor characteristics were analyzed directly from CT scans
(n = 82) or MR images (n = 3): tumor size (
20 mm or
< 20 mm in diameter), location within liver, tumor type (simple round tumor
or not, subcapsular or nonsubcapsular), and presence of blood vessels (first
to third branches of the portal vein and first and second branches of the
hepatic veins) within 5 mm from the border of the HCC. A total of 120 mL of
nonionic contrast material (Omnipaque [iohexol], Daiichi Seiyaku) was
administered with an automatic power injector at a rate of 3-4.5 mL/s. Images
were obtained before and 30 and 180 seconds after initiation of injection of
IV contrast material, representing the unenhanced, hepatic arterial, and
equilibrium phases, respectively. Images were obtained in a craniocaudal
direction with 7-mm collimation and 7-mm/s table speed during a single
breath-hold helical acquisition of 25-30 seconds. The axial images were
reconstructed at intervals of 5 mm. For each patient the ablation zone was
examined on axial images in the craniocaudal direction in the same field of
view as on the hard copies obtained before and 3-5 days after treatment.
The goal of the treatment was to achieve complete ablation in the tumor
ablation zones, which were the hypoattenuating unenhanced areas visualized
during the arterial and the portal venous phases that were larger than the
tumor itself. Additional sessions were scheduled for ablation of residual
tumors when irregular peripheral enhancement was confirmed at the margin of
the ablation zone on images obtained 3-5 days after the first treatment. The
diagnosis and treatment procedures were repeated until complete ablation was
achieved during one hospital stay. The presence of an ablative margin of at
least 5 mm around the HCC (minimum measurement of ablative margin) was
examined on the final images used during the hospital stay to determine
whether ablation was complete. The ablative margin is diagrammatically shown
between the arrows in Figure
1A. All variables were assessed by one person and reviewed
retrospectively by a second person working independently. The observers
therefore were blinded with respect to patient characteristics and outcome.
Discrepancies were resolved by consensus. Subsequent diagnostic scans were
obtained 1 month after discharge. The follow-up protocol included measuring
-fetoprotein and PIVKA-II levels and acquisition of CT scans at 4-month
intervals to monitor for signs of recurrence.
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Fig. 1E —34-year-old man with hepatocellular carcinoma. Transverse
contrast-enhanced arterial phase helical CT scan shows area in D after
ablation. Lesion has been completely ablated. Ablation zone includes ablative
margin of more than 5 mm.
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Local Tumor Progression
Local tumor progression was defined as development of new tumor around the
ablation zone. It was diagnosed on the basis of tumor enhancement at the
margin of the ablation zone
[15]. The cases were analyzed
over time by image analysis to characterize patterns of local tumor
progression.
Statistical Analysis of Determinants for Local Tumor Progression
Clinical and biochemical features at the time of radiofrequency ablation,
tumor characteristics, radiofrequency ablation electrode type (multitined
expandable or internally cooled), tumor location, presence of contiguous
vessels, hepatic surface (portion of tumor located within 5 mm of the surface
of the liver), and Couinaud segment were analyzed. In addition, whether needle
biopsy was performed before ablation and whether there was a completely
ablated margin of at least 5 mm were analyzed for local tumor progression.
Data were expressed as mean ± SD. The Kaplan-Meier method was used to
estimate the interval from radiofrequency ablation treatment to local tumor
progression. The variables as determinants of local tumor progression were
analyzed with the use of the log-rank test. A Cox proportional hazards
regression model was used to analyze independent risk factors. All p
values were two-tailed. A p value < 0.05 was considered to
indicate statistical significance. Statistical analyses were performed with
the statistical package SPSS Base 11.0J (SPSS) for Windows (Microsoft).
Results
No patient had major complications after radiofrequency ablation. The
cumulative survival rate was 99% at 1 year and 87% at 3 years. The median
follow-up period was 30.3 months (range, 6.0-74.7 months). Forty-five (53%) of
the patients were treated in overlapping zones with several insertions. The
mean number of radiofrequency ablation treatment sessions needed for complete
ablation of HCC was 1.4 (range, 1-4 sessions) during one hospital stay. The
average hospital stay was 12 days. Eight patients died of hepatic failure, and
one patient died of esophageal varix rupture during follow-up. Local tumor
progression was found in 14 patients. The median period until detection of
tumor progression was 14.1 months (range, 6.6-41.2 months). The cumulative
rate of local tumor progression was 6.1% at 1 year and 19.5% at 3 years.
Table 1 shows determinants
of local tumor progression. Clinical laboratory data, HCC diameter, number of
treatment sessions, electrode device used, and results of tumor needle biopsy
were not significantly related to tumor progression. Presence of vessels
contiguous with HCC and an ablative margin of less than 5 mm were
significantly related to local tumor progression. The cumulative rate of local
tumor progression at 3 years was significantly higher for HCC with contiguous
vessels (32%) than for HCC without contiguous vessels (5%) (p =
0.0292) (Fig. 2A). The
cumulative rate of local tumor progression at 3 years was significantly lower
for HCC with an ablative margin of 5 mm or more (3.5%) than for HCC with an
ablative margin of less than 5 mm (28.3%) (p = 0.019)
(Fig. 2B). Cox regression
analysis showed that the presence of an ablative margin of less than 5 mm was
a significant independent risk factor for local tumor progression (p
= 0.04; relative risk = 8.475; 95% CI, 0.015-0.902). A difference between
multitined expandable and internally cooled electrodes in rate of development
of an ablative margin of 5 mm or more was not observed (35% vs 36%).
Figure 3 classifies the lesions
according to the presence or absence of contiguous vessels and whether the
ablative margin was at least 5 mm or less than 5 mm. The number of HCCs with
contiguous vessels and an ablative margin of at least 5 mm was significantly
lower than the number of HCCs without contiguous vessels (chi-square test,
p = 0.005).
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Fig. 2A —Curves of local tumor progression, calculated by Kaplan-Meier
method, according to presence or absence of contiguous vessels and presence or
absence of ablative margin 5 mm. Graph shows log-rank test result that
over time presence of contiguous vessels was associated with significantly
higher rate of local tumor progression (p = 0.0292).
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Fig. 2B —Curves of local tumor progression, calculated by Kaplan-Meier
method, according to presence or absence of contiguous vessels and presence or
absence of ablative margin 5 mm. Graph shows log-rank test result that
over time presence of ablative margin of 5 mm within ablation zone was
significantly related to freedom from local recurrence (p =
0.019).
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Fig. 3 —Chart shows association between local tumor progression and presence
of contiguous vessels and ablative margin of 5 mm within ablation zone in 85
patients with hepatocellular carcinoma (HCC). Number of cases of local tumor
progression was high for HCCs with contiguous vessels that did not have
ablative margin of 5 mm within ablation zone. Proportion of cases with
ablative margin of 5 mm was significantly lower in HCCs with contiguous
vessels than in those without contiguous vessels (p = 0.005,
chi-square test). Ablative margin was not associated with local tumor
progression in HCCs without contiguous vessels.
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The patterns of local tumor progression are shown in Figures
4A,
4B,
4C,
4D,
5A,
5B,
5C,
5D,
5E,
6A,
6B,
6C,
6D,
6E. Outgrowths emerged from
the sides of ablative margins less than 5 mm wide (Fig.
4A,
4B,
4C,
4D) and from the caudate or
cranial sides of ablated regions. In one patient, a recurrence developed on
the opposite side of a vessel adjacent to the ablation zone (Fig.
5A,
5B,
5C,
5D,
5E). Another patient had
multiple viable recurrent lesions around the ablation zone contiguous with its
border (Fig. 6A,
6B,
6C,
6D,
6E).
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Fig. 4A —72-year-old man with single outgrowth of hepatocellular carcinoma
detected 41 months after ablation with expandable multitined electrode.
Diagram shows ablation zone (shading) and local tumor progression
(hatching).
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Fig. 4B —72-year-old man with single outgrowth of hepatocellular carcinoma
detected 41 months after ablation with expandable multitined electrode.
Transverse contrast-enhanced arterial phase helical CT scan shows tumor
(arrowhead) before ablation.
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Fig. 4C —72-year-old man with single outgrowth of hepatocellular carcinoma
detected 41 months after ablation with expandable multitined electrode.
Transverse contrast-enhanced arterial phase helical CT scan 1 month after
ablation.
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Fig. 4D —72-year-old man with single outgrowth of hepatocellular carcinoma
detected 41 months after ablation with expandable multitined electrode.
Transverse contrast-enhanced arterial phase helical CT scan shows single
viable lesion (arrow) that developed 41 months after ablation.
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Fig. 5A —50-year-old man with recurrent hepatocellular carcinoma that emerged
on other side of vessel. Ablation was done with expandable electrode. Diagram
shows ablation zone (shading) and local tumor progression
(hatching).
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Fig. 5B —50-year-old man with recurrent hepatocellular carcinoma that emerged
on other side of vessel. Ablation was done with expandable electrode.
Transverse contrast-enhanced arterial phase helical CT scan shows lesion
(arrowhead) with contiguous vessels before ablation.
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Fig. 5C —50-year-old man with recurrent hepatocellular carcinoma that emerged
on other side of vessel. Ablation was done with expandable electrode.
Transverse contrast-enhanced arterial phase helical CT scan 1 month after
ablation shows ablation zone.
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Fig. 5D —50-year-old man with recurrent hepatocellular carcinoma that emerged
on other side of vessel. Ablation was done with expandable electrode. Dynamic
phase of transverse contrast-enhanced arterial phase helical CT scan 35 months
after ablation shows local tumor progression in ablation zone
(arrow).
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Fig. 5E —50-year-old man with recurrent hepatocellular carcinoma that emerged
on other side of vessel. Ablation was done with expandable electrode.
Equilibrium phase image corresponding to D shows local tumor
progression in ablation zone (arrow).
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Fig. 6A —63-year-old man with multiple viable recurrent lesions around
ablation zone after treatment of hepatocellular carcinoma with internally
cooled electrode. Diagram shows ablation zone (shading) and local
tumor progression (hatching).
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Fig. 6B —63-year-old man with multiple viable recurrent lesions around
ablation zone after treatment of hepatocellular carcinoma with internally
cooled electrode. Transverse contrast-enhanced arterial phase helical CT scan
shows lesion (arrowhead) before ablation.
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Fig. 6C —63-year-old man with multiple viable recurrent lesions around
ablation zone after treatment of hepatocellular carcinoma with internally
cooled electrode. Transverse contrast-enhanced arterial phase helical CT scan
1 month after ablation shows ablation zone.
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Fig. 6D —63-year-old man with multiple viable recurrent lesions around
ablation zone after treatment of hepatocellular carcinoma with internally
cooled electrode. Dynamic phase of transverse contrast-enhanced arterial phase
helical CT scan 9 months after ablation shows multiple recurrent lesions
(arrows). Ablation zone has ablative margin of more than 5 mm.
Therefore, multiple viable lesions probably involved intrahepatic metastasis
or iatrogenic spread.
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Fig. 6E —63-year-old man with multiple viable recurrent lesions around
ablation zone after treatment of hepatocellular carcinoma with internally
cooled electrode. Dynamic phase of transverse contrast-enhanced arterial phase
helical CT scan 9 months after ablation shows multiple recurrent lesions
(arrows). Ablation zone has ablative margin of more than 5 mm.
Therefore, multiple viable lesions probably involved intrahepatic metastasis
or iatrogenic spread.
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Discussion
Radiofrequency ablation is often performed instead of surgery in
percutaneous management of early HCC and metastatic hepatic tumors
[1]. It is useful for the
management of unresectable HCC in patients with insufficient hepatic reserve
and is less invasive than surgical resection. HCC is associated with a high
incidence of intrahepatic recurrence after treatment
[2,
3]. Studies
[5-8,
10,
11,
18] have shown that after
radiofrequency ablation of HCC, the rate of local tumor progression can range
from as low as 2% to as high as 53%. Previous studies have shown that tumors
exceeding 2 cm in diameter, subcapsular tumors, tumors situated at the liver
surface, and incompletely ablated tumors are associated with local tumor
progression after radiofrequency ablation
[7,
8,
18]. Whether the proximity of
a tumor to intrahepatic vessels is a risk factor for local tumor progression
after radiofrequency ablation remains controversial
[7,
8,
12,
19]. To achieve better local
control of HCC managed with radiofrequency ablation, analysis of ablation
zones with ablative margins is needed. Therefore, we examined small HCCs that
had easily comparable ablative margins within their ablation zones.
Unlike the findings of previous studies
[6-8],
our results showed that tumor size, capsular HCCs, and location of tumor at
the liver surface were not related to local tumor progression. Differences in
determinants of local tumor progression may be related to the smaller size of
HCCs in our study, the performance of more than two ablations with the
overlapping technique for tumors 2-3 cm in diameter, and the presence of
complete ablation zones with ablative margins of at least 5 mm from the tumor
border. Local tumor progression occurred more than 2 years (range, 26-41.2
months) after radiofrequency ablation in four of 14 patients, and the ablative
margins in those patients were less than 5 mm. Previous studies have shown
that local tumor progression generally develops within 2 years after local
ablation [15,
20,
21]. Thus, later local tumor
progression can occur after complete ablation without a sufficient ablative
margin.
Analysis by the log-rank test showed that an ablation zone including an
ablative margin less than 5 mm from the tumor border and the presence of blood
vessels contiguous with tumors were significantly related to local tumor
progression. Multivariate analysis showed that presence of an ablative margin
of at least 5 mm was a significant independent factor for local tumor
progression. An adequate ablative margin is required because most recurrent
lesions emerge from ablation zones within 5 mm from the tumor border, the area
most likely to contain viable tumor cells. We found that outgrowth emerged
from the side of an incompletely ablated margin, including the caudal and
cranial ends of the ablated areas, possibly where the ablative margin was
underestimated on single-section helical CT scans obtained after
radiofrequency ablation. Local tumor progression also occurs beyond vessels
adjacent to an ablation zone in cases of HCC with contiguous vessels (Fig.
5A,
5B,
5C,
5D,
5E). To inhibit local tumor
progression, both stricter evaluation of ablation zones with imaging
techniques such as MDCT and the use of radiofrequency techniques to enlarge
ablation zones are necessary.
Because techniques such as overlapping insertions of electrodes sometimes
produce small ablation zones relative to the number of ablations
[13], other tumor ablation
strategies, such as saline or ethanol injections before radiofrequency
ablation and the use of devices such as cooled-tip triple-cluster needles, are
effective for developing larger areas of ablation with adequate ablative
margins
[22-25].
Okusaka et al. [26] reported
that small single HCCs (3 cm or less in diameter) with no satellite lesions on
preoperative images had microscopic satellite lesions 0.5-1.0 cm from the main
tumor. These findings suggest the need for an ablative margin of 0.5-1.0 cm
around tumors treated with ablation. Because excessively large ablation zones
adjacent to blood vessels can cause intravascular thrombosis
[27], radiofrequency ablation
procedures must be carefully monitored.
Our findings suggest that it is difficult to develop an ablative margin of
at least 5 mm in the management of HCC with contiguous vessels
(Fig. 3). Blood flow reduces
the thermal effects of radiofrequency ablation, a phenomenon that increases
the likelihood of the presence of residual viable tumor cells
[24,
28,
29]. To avoid the heat-sink
effects of large vessels, radiofrequency ablation with balloon occlusion of
the hepatic vessels, a technique that achieves more extensive ablation than
standard radiofrequency ablation, can be used to manage HCC with contiguous
vessels [28,
30]. Thus, an ablative margin
of 5 mm or more should be required in the management of HCC, especially of
lesions with contiguous blood vessels.
In cases of HCC without contiguous vessels, local tumor progression was not
different in the ablation zones, as shown in
Figure 3. The absence of
contiguous blood vessels in HCC was significantly associated with location of
the tumor near the surface of the liver (n = 24) compared with the
presence of contiguous vessels (n = 13) (chisquare test, p =
0.012). The findings suggest that because there is less influence of blood
flow around the tumor, the absence of contiguous vessels in HCC allows
ablation of necrotic tissue that is closer than can be achieved when
contiguous vessels are present. In addition, radiofrequency ablation of tumors
at the hepatic surface can leave an area of scar contraction on the liver.
These factors might have contributed to the results related to width of
ablative margin and local tumor progression in the cases of HCC without
contiguous vessels.
The present study had several limitations. It was performed as a
retrospective singlecenter study, and three models of devices were used for
radiofrequency ablation under sonographic guidance, possibly leading to bias.
To reduce the effects of the other factors, we focused on patients who had
primary single small HCC that was completely ablated. These results must be
confirmed in larger prospective studies.
In conclusion, the presence of blood vessels contiguous to HCC is related
to local tumor progression after radiofrequency ablation. A margin of at least
5 mm around HCC should be completely ablated along with the tumor. This factor
is most important for local control. Because single or multiple lesions can
develop around ablation zones despite the presence of an ablative margin of
more than 5 mm, patients should be closely observed, and follow-up
examinations should be done at regular intervals. Further studies of the
mechanism of local tumor progression after radiofrequency ablation are
essential for defining the factors involved.
Acknowledgments
We thank Naomi Kakutani for assistance preparing the figures. We also thank
Robert E. Brandt for help editing the manuscript.
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Abstract
Introduction
