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DOI:10.2214/AJR.05.0350
AJR 2006; 186:S327-S333
© American Roentgen Ray Society

Original Research

Percutaneous Radiofrequency Ablation of Hepatocellular Carcinoma: Effect of Histologic Grade on Therapeutic Results

Seong Hyun Kim1, Hyo K. Lim1, Dongil Choi1, Won Jae Lee1, Seung Hoon Kim1, Min Ju Kim1, Chan Kyo Kim1, Yong Hwan Jeon1, Jong Mee Lee1 and Hyunchul Rhim1

1 All authors: Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul 135-710, South Korea.

Received March 1, 2005; accepted after revision June 2, 2005.

 
Address correspondence to H. K. Lim (hklim{at}smc.samsung.co.kr).


Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
OBJECTIVE. The purpose of our study was to assess the therapeutic results of radiofrequency ablation of hepatocellular carcinoma (HCC) based on the histologic grades of the tumors.

SUBJECTS AND METHODS. Between April 1999 and December 2003, 95 patients with nodular HCC were treated with percutaneous radiofrequency ablation. All tumors were histologically proven by sonography-guided percutaneous biopsy and were classified as Edmondson-Steiner grade I HCC (n = 38) (mean, 2.3 cm) (group 1), grade II HCC (n = 50) (mean, 2.4 cm) (group 2), or grade III HCC (n = 7) (mean, 2.8 cm) (group 3). All patients underwent contrast-enhanced three-phase helical CT examination before and after radiofrequency ablation. After retrospective review of the medical records and follow-up CT examinations, the rates of technique effectiveness, local tumor progression, cumulative survival, and cancer-free survival using a Kaplan-Meier method were calculated and compared among the groups.

RESULTS. Technique effectiveness rates in groups 1, 2, and 3 were 87% (27/31), 71% (30/42), and 43% (3/7), respectively, with statistical significance (p = 0.032). Local tumor progression rates in groups 1, 2, and 3 were 16% (5/31), 36% (15/42), and 71% (5/7), respectively, with statistical significance (p = 0.013). Five-year cumulative survival rates in groups 1, 2, and 3 were 71%, 44%, and 43%, respectively, with no statistical significance (p > 0.05). Four-year cancer-free survival rates in groups 1, 2, and 3 were 39%, 10%, and 0%, respectively (p < 0.05 for groups 1 vs 2; p > 0.05 for groups 1 vs 3 and groups 2 vs 3).

CONCLUSION. The histologic grade of HCC is an important factor influencing therapeutic results with survival after radiofrequency ablation.

Keywords: ablation • hepatocellular carcinoma • histologic grade • radiofrequency


Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
Radiofrequency ablation is a widely accepted alternative to surgical resection in the treatment of hepatic tumors, particularly hepatocellular carcinoma (HCC) [1-4]. The technique has been considered safe and promising, especially for the unresectable hepatic tumors that result from multifocal tumors and a limited hepatic functional reserve due to liver cirrhosis [1, 2, 4, 5]. The crucial advantage of radiofrequency ablation is its ability to reduce morbidity and mortality and to preserve more liver parenchymal volume. In addition, the procedure is less technically challenging than surgical resection of hepatic tumors [6].

The therapeutic results of radiofrequency ablation of hepatic tumors are influenced by a variety of factors such as the skill of the operator; the choice of technique; the generator power of the radiofrequency ablation device; and the size, location, and morphology of the tumor [1, 5, 7-10]. We hypothesized that the therapeutic results also could be influenced by the histologic grade of HCC. However, to our knowledge, no study has assessed the therapeutic efficacy of radiofrequency ablation according to the histologic grade of HCC. The purpose of this study was to conduct such an assessment.


Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Patient Selection
The study was performed with the approval of the institutional review board. Written informed consent was obtained from all patients included in the study. Between April 1999 and December 2003, 727 patients with nodular HCC were referred to our department for radiofrequency ablation because of poor hepatic functional reserve due to liver cirrhosis, multiple HCC tumors, expected liver cell loss due to resection, refusal of the patient to undergo liver transplantation, or cardiopulmonary dysfunction. Of these patients, 632 were excluded from the study; this excluded group included patients with a history of treatment by hepatic resection, transcatheter arterial chemoembolization (TACE), or percutaneous ethanol injection therapy (PEIT) for HCC (n = 330); patients without pathologic proof of HCC (n = 203); patients who were followed up for less than 1 month (n = 45); and patients proven to have a dysplastic nodule (n = 54). The remaining 95 patients, each with a pathologically proven single HCC nodule, were included in the study (68 men and 27 women; age range, 38-79 years; mean, 57 years). All patients in the study met the following criteria for percutaneous radiofrequency ablation: a single HCC nodule no greater than 5 cm in maximum diameter, no portal vein thrombosis or extrahepatic metastasis, liver cirrhosis classified as Child-Pugh class A or B, a prothrombin time ratio greater than 50% (prothrombin time with an international normalized ratio < 1.7), a platelet count greater than 50,000/mm3 (50 cells x 109/L), no prior treatment for HCC, and a visible tumor on sonography.

For the diagnosis of HCC, preprocedural imaging studies using combined sonography and CT or combined sonography, CT, and superparamagnetic iron oxide-enhanced MRI were performed on all patients, and then sonography-guided percutaneous biopsy of the tumor was performed using either a 19.5-gauge (AutoVac, Angiomed) or an 18-gauge (Hart Enterprises) automated biopsy gun. One experienced pathologist analyzed the histologic grade of the tumor according to the grading system of Edmondson and Steiner [11]. HCC tumors of more than one Edmondson-Steiner grade (n = 25) were classified according to the predominating histologic characteristics [12, 13]. The tumors measured 1.2-5.0 cm in maximum diameter (mean, 2.4 cm). Finally, we classified each patient into one of three groups: Edmondson-Steiner grade I HCC (n = 38) (range, 1.4-5.0 cm; mean, 2.3 ± 0.8 [SD] cm), Edmondson-Steiner grade II HCC (n = 50) (range, 1.2-4.5 cm; mean, 2.4 ± 0.8 cm), or Edmondson-Steiner grade III HCC (n = 7) (range, 1.6-4.0 cm; mean, 2.8 ± 1.0 cm). No patients in the study had Edmondson-Steiner grade IV HCC. The baseline characteristics of the three groups are shown in Table 1.


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  		TABLE 1: Baseline Characteristics of 95 Patients

 

Radiofrequency Ablation Procedure
Our descriptions of the radiofrequency ablation procedures and data are based on a proposed standardization of terms and reporting criteria [14]. Radiofrequency ablation was performed percutaneously on all patients under real-time sonographic guidance with a 2- to 5-MHz convex-array transducer (HDI 5000, Advanced Technology Laboratories) by one of four experienced radiologists. From April 1999 to June 2000, we used multitined expandable electrode systems exclusively (model 500 series and model 1500 series, RITA Medical Systems; or RF 2000 system, RadioTherapeutics). After this period, we usually used an internally cooled electrode system (Cool-tip, Valleylab). All patients were treated under IV conscious sedation with pethidine hydrochloride, 50 mg (Samsung Pharmaceutical). Local anesthesia was performed by injecting anesthetic (lidocaine, Kwang Myung Pharmaceutical) from the skin to the liver capsule along a predetermined insertion route. Our choice of radiofrequency device depended on the availability of the electrode and the size and location of the tumor. The internally cooled electrode system with the more powerful generator was used more often in groups 1 and 2 than in group 3 (Table 1). We usually prefer the internally cooled electrode system for the treatment of tumors near the large, central vessels close to the hepatic hilum and near organs—such as the gallbladder, colon, and stomach—that potentially can be damaged by the fully deployed tines of the multitined expandable electrode. Our strategy for complete tumor necrosis was to ablate a peripheral margin of 0.5-1.0 cm of normal hepatic tissue surrounding the tumor and the entire tumor itself. For 33 patients with tumors larger than 2.5 cm in diameter, we performed 2-6 (mean, 3) overlapping ablations to destroy the tumor completely in one session. The multiple overlapping ablations were made through the initial electrode tract. For tumors smaller than 2.5 cm, one ablation was usually enough to destroy the entire tumor.

Follow-Up Imaging
All patients underwent contrast-enhanced threephase CT before and after radiofrequency ablation according to our protocol. CT was performed using a helical scanner (HiSpeed Advantage, GE Healthcare) with a 5-mm slice thickness. A total of 120 mL of nonionic contrast material ([300 mg of iodine per milliliter] Ultravist 300, Schering) was administered with a power injector at a rate of 3 mL/sec (OP 100, Medrad). CT images were obtained at 30, 70, and 180 sec after the start of IV contrast material injection for imaging during the hepatic arterial, portal venous, and equilibrium phases, respectively.

For determination of early therapeutic efficacy, all patients underwent 1-month follow-up CT after radiofrequency ablation. Residual nonablated tumor was defined as any irregular, peripherally enhancing focus in the ablation zone. If residual nonablated tumor was found in the ablation zone, it was treated with additional radiofrequency ablation. If follow-up CT after the second session of radiofrequency ablation showed residual tumor in the ablation zone, the tumor was considered unresponsive to radiofrequency ablation and TACE was performed. If the tumor was treated completely by radiofrequency ablation and no new HCC nodules were found at 1-month follow-up CT using the same protocol, contrast-enhanced three-phase CT was repeated at 2- to 4-month intervals. The technique was considered effective if follow-up CT more than 1 year after the last radiofrequency ablation session showed no enhancing foci in the ablation zone, indicating that tumor necrosis had been complete. Local tumor progression was considered present if 1-month follow-up CT had shown no evidence of residual nonablated tumor but later follow-up CT showed a growing, enhancing tumor in the ablation zone. We tried to treat any local tumor progression found in the ablation zone with additional radiofrequency ablation. If additional radiofrequency ablation was not feasible because the local tumor progression was of a poor configuration, TACE was performed.

Except for 15 patients who were followed up by CT for less than 1 year, all patients were followed up by CT for 1-67 months (mean, 29 months). The three radiologists who did not perform radiofrequency ablation retrospectively reviewed all CT images obtained before and after radiofrequency ablation for the 95 patients. The final diagnostic decision was reached by consensus. After retrospective review of the medical records and follow-up CT examinations, we evaluated the rate of technique effectiveness, the rate of local tumor progression (and its time course in patients with follow-up CT of more than 1 year), and the cumulative and cancer-free survival rates for each group. We also evaluated needle track seeding associated with percutaneous biopsy or radiofrequency ablation and new liver tumors found farther than 2 cm from the ablation zone on follow-up CT.


Figure 1
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  		Fig. 1A —54-year-old man with Edmondson-Steiner grade I hepatocellular carcinoma (HCC) who had local tumor progression after radiofrequency ablation. Contrast-enhanced CT scan obtained during arterial phase before radiofrequency ablation shows 2.7-cm HCC (arrows) in liver segment VI.

 


Figure 2
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  		Fig. 1B —54-year-old man with Edmondson-Steiner grade I hepatocellular carcinoma (HCC) who had local tumor progression after radiofrequency ablation. Contrast-enhanced CT scan obtained during arterial phase 5 months after radiofrequency ablation shows no evidence of local tumor progression in radiofrequency ablation zone (arrows), with atrophy of hepatic parenchyma distal to ablation zone.

 


Figure 3
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  		Fig. 1C —54-year-old man with Edmondson-Steiner grade I hepatocellular carcinoma (HCC) who had local tumor progression after radiofrequency ablation. Contrast-enhanced CT scan obtained during arterial phase 7 months after radiofrequency ablation shows local tumor progression (arrows) in peripheral margin of radiofrequency ablation zone (asterisk).

 


Figure 4
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  		Fig. 2A —46-year-old-woman with Edmondson-Steiner grade II hepatocellular carcinoma (HCC) who had delayed local tumor progression after radiofrequency ablation. Contrast-enhanced CT scan obtained during arterial phase 3 months after radiofrequency ablation for 2.5-cm HCC in liver segment VII shows radiofrequency ablation zone (arrows) with no local tumor progression.

 


Figure 5
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  		Fig. 2B —46-year-old-woman with Edmondson-Steiner grade II hepatocellular carcinoma (HCC) who had delayed local tumor progression after radiofrequency ablation. Contrast-enhanced CT scan obtained during arterial phase 19 months after radiofrequency ablation shows decrease in size of radiofrequency ablation zone (arrows) with no local tumor progression.

 


Figure 6
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  		Fig. 2C —46-year-old-woman with Edmondson-Steiner grade II hepatocellular carcinoma (HCC) who had delayed local tumor progression after radiofrequency ablation. Contrast-enhanced CT scan obtained during arterial phase 26 months after radiofrequency ablation shows local tumor progression (arrow) in margin of radiofrequency ablation zone (asterisk).

 


Figure 7
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  		Fig. 3A —45-year-old-man with Edmondson-Steiner grade III hepatocellular carcinoma (HCC) who had delayed local tumor progression after radiofrequency ablation. Contrast-enhanced CT scan obtained during arterial phase before radiofrequency ablation shows 3.2-cm HCC tumor (arrows) in liver segment II.

 


Figure 8
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  		Fig. 3B —45-year-old-man with Edmondson-Steiner grade III hepatocellular carcinoma (HCC) who had delayed local tumor progression after radiofrequency ablation. Contrast-enhanced CT scan obtained during arterial phase 23 months after radiofrequency ablation shows small, enhancing nodule (arrow) in margin of radiofrequency ablation zone (asterisk), with substantial decrease in size of zone.

 


Figure 9
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  		Fig. 3C —45-year-old-man with Edmondson-Steiner grade III hepatocellular carcinoma (HCC) who had delayed local tumor progression after radiofrequency ablation. Contrast-enhanced CT scan obtained during arterial phase 26 months after radiofrequency ablation shows growth of enhancing nodule (arrow) and new enhancing nodule (arrowhead) in margin of radiofrequency ablation zone (asterisk).

 
Statistical Analysis
The baseline characteristics of the three groups were compared using the Kruskal-Wallis test for age, tumor size, and follow-up period; the chisquare test for sex; and Fisher's exact test for the histology of background liver and the type of radiofrequency device used. We tested differences in the rate of technique effectiveness and local tumor progression among the three groups using the chi-square test and Fisher's exact test, respectively. Differences in the time course of local tumor progression and the occurrence of new HCC tumors during follow-up among the three groups were analyzed using the Kruskal-Wallis test and Fisher's exact test, respectively. The length of survival from the time of the first radiofrequency ablation was calculated. We calculated the cumulative and cancer-free survival rates of the three groups using the Kaplan-Meier method, and differences between the curves were assessed using the log-rank test. A p value of less than 0.05 was considered to indicate statistical significance.


Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Baseline Characteristics of Groups
No statistically significant differences in baseline characteristics among the three groups were observed, except for the type of radiofrequency device used (Table 1).

Technique Effectiveness
Of the 95 patients, one (1%) in group 2 was unresponsive to radiofrequency ablation. For the 80 patients who were followed up for more than 1 year after radiofrequency ablation, follow-up CT showed that the rate of technique effectiveness was 75% (60/80 HCC tumors). The technique effectiveness rates were 87% (27/31) for group 1, 71% (30/42) for group 2, and 43% (3/7) for group 3, with statistical significance (p = 0.032) among the three groups.

Local Tumor Progression
On follow-up CT, local tumor progression was seen at the ablation margin in 25 (31%) of 80 patients. No needle track seeding was seen at follow-up CT. The local tumor progression rates were 16% (5/31) for group 1 (Figs. 1A, 1B, and 1C), 36% (15/42) for group 2 (Figs. 2A, 2B, and 2C), and 71% (5/7) for group 3 (Figs. 3A, 3B, and 3C), with statistical significance among the three groups (p = 0.013). Local tumor progression was seen on follow-up CT 3-26 months (mean, 10.4 months) after radiofrequency ablation. In 18 (72%) of 25 patients with local tumor progression, viable tumor started to appear on follow-up CT at less than 12 months (range, 3-11 months; mean, 6.7 months) after radiofrequency ablation (Figs. 1A, 1B, and 1C), and for the remaining seven patients (28%), viable tumor appeared at more than 12 months (range, 13-26 months; mean, 19.7 months) (Figs. 2A, 2B, 2C, 3A, 3B, and 3C). Local tumor progression appeared at 6-16 months (mean, 9.8 months) after radiofrequency ablation for group 1, at 4-26 months (mean, 10.0 months) for group 2, and at 3-26 months (mean, 12.2 months) for group 3, with no significant difference in time course among the three groups (p = 0.906).

Survival Rates
Of the 80 patients with follow-up CT of more than 1 year, new HCC tumors at liver sites different from the site treated by radiofrequency ablation occurred in 48% (15/31) in group 1, 79% (33/42) in group 2, and 86% (6/7) in group 3. New HCC tumors occurred more often with increasing histologic grade of HCC (p = 0.014). They were treated with radiofrequency ablation, TACE, or both.


Figure 10
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  		Fig. 4 —Curves indicate cumulative survival in three groups with different histologic grades after radiofrequency ablation. Cumulative survival rates at 1, 3, and 5 years were 97%, 79%, and 71%, respectively, for group 1; 92%, 56%, and 44%, respectively, for group 2; and 100%, 57%, and 43%, respectively, for group 3. Three- and 5-year cumulative survival rates in group 1 were higher than those of groups with higher histologic grades, but no statistically significant difference was found for cumulative survival rates between groups (p > 0.05). Number of patients followed up at 1, 3, and 5 years was 35, 14, and one, respectively, in group 1; 46, 23, and seven, respectively, in group 2; and seven, four, and two, respectively in group 3.

 


Figure 11
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  		Fig. 5 —Curves indicate cancer-free survival in three groups with different histologic grades after radiofrequency ablation. Cancer-free survival rates at 1, 2, 3, and 4 years were 74%, 44%, 39%, and 39%, respectively, for group 1; 53%, 23%, 13%, and 10%, respectively, for group 2; and 57%, 29%, 14%, and 0%, respectively, for group 3. Four-year cancer-free survival rate showed a trend to decrease with increasing histologic grade of hepatocellular carcinoma (p < 0.05 for groups 1 vs 2; p > 0.05 for groups 1 vs 3 and groups 2 vs 3 by Bonferroni correction). Number of patients followed up at 1, 2, 3, and 4 years was 25, 10, four, and two, respectively, in group 1; 24, seven, four, and two, respectively, in group 2; and four, two, one, and one, respectively, in group 3.

 
During follow-up, 36 (38%) of the 95 patients died. Eight (21%) of 38 patients died in group 1 (seven of hepatic failure due to advanced cirrhosis and one of variceal bleeding), 24 (48%) of 50 patients died in group 2 (12 of hepatic failure due to advanced cirrhosis and 12 of tumor progression), and four (57%) of seven patients died in group 3 (one of hepatic failure due to advanced cirrhosis, two of tumor progression, and one of variceal bleeding). The 1-, 3-, and 5-year cumulative survival rates for all patients with HCC treated with radiofrequency ablation were 95%, 64%, and 51%, respectively. The 1-, 3-, and 5-year cumulative survival rates were 97%, 79%, and 71%, respectively, for group 1; 92%, 56%, and 44%, respectively, for group 2; and 100%, 57%, and 43%, respectively, for group 3 (Fig. 4). The 3- and 5-year cumulative survival rates were higher in group 1 than in the groups having an increasing histologic grade, but no statistically significant difference was found among the groups (p > 0.05). The 1-, 2-, 3-, and 4-year cancer-free survival rates for all patients with HCC treated with radiofrequency ablation were 61%, 32%, 22%, and 16%, respectively. The 1-, 2-, 3-, and 4-year cancer-free survival rates were 74%, 44%, 39%, and 39%, respectively, for group 1; 53%, 23%, 13%, and 10%, respectively, for group 2; and 57%, 29%, 14%, and 0%, respectively, for group 3. The 4-year cancer-free survival rate showed a trend to decrease with increasing histologic grade of HCC (p < 0.05 for groups 1 vs 2; p > 0.05 for groups 1 vs 3 and groups 2 vs 3 by Bonferroni correction) (Fig. 5).


Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
Several studies have reported excellent local control after radiofrequency ablation, especially for patients with HCC [6, 15, 16]. Our results for the rate of technique effectiveness (75%) and the rate of local tumor progression (31%) after radiofrequency ablation of HCC were comparable to previously reported rates (65-100% for technique effectiveness [3, 17, 18] and 38% for local tumor progression [19]).

Today, hepatic tumors are histologically confirmed—and their treatment planned—on the basis of aspiration cytology or percutaneous needle biopsy instead of surgery, because of the development of state-of-the art imaging techniques for differentiating hepatic tumors and the introduction of various locoregional therapies for them. However, it is almost impossible to obtain pathologic proof for all suspected tumors in a cirrhotic liver, and the result has been a lack of studies on the therapeutic efficacy of radiofrequency ablation based on the histologic grade of HCC. We conducted such a study and found that the rate of technique effectiveness decreased and the rate of local tumor progression increased as the histologic grade increased. Histologic grade is one indicator of the biologic aggressiveness and progression of an HCC tumor [20, 21]. Therefore, HCC tumors of a higher histologic grade have a greater chance of producing early infiltration and of becoming surrounded by vascular tumor emboli than do tumors of a lower histologic grade, and incomplete ablation or local tumor progression often follows radiofrequency ablation of high-grade HCC. In our study, 28% of patients with local tumor progression after radiofrequency ablation of HCC did not show viable tumor on follow-up CT until more than 12 months after radiofrequency ablation. This delayed appearance of local tumor progression on follow-up CT may contribute to the variable doubling time of HCC. However, the mean time courses of local tumor progression according to histologic grade of HCC after radiofrequency ablation were not statistically different.

Several investigators [22-26] have reported 5-year survival rates for HCC patients after surgery and PEIT. These rates have ranged from 41% to 51% after surgery and from 32% to 47% after PEIT. In our study, the 5-year cumulative survival rate was 51%. However, a direct comparison of our 5-year cumulative survival rate with the rates of other studies is difficult because of differences in study populations or study designs. To the best of our knowledge, no substantial evidence exists that the survival rate after radiofrequency ablation is higher than that after other treatments such as surgical resection or PEIT for patients with HCC and cirrhosis, because no randomized, controlled trials have been reported.

The wide use of the Edmondson-Steiner classification system for predicting patient outcome is controversial. Several investigators [27, 28] have reported that the histologic grade of HCC was a significant factor affecting survival. In contrast, other investigators [29, 30] have reported no positive correlation between Edmondson-Steiner grade and outcome when the studies were based on surgical or biopsy specimens. Although no statistically significant difference was found in our study, the 3- and 5-year cumulative survival rates of group 1 were higher than those of the other groups. Cancer-free survival reflects local recurrence, including local tumor recurrence at the radiofrequency ablation zone, hepatocarcinogenesis in areas other than the ablation zone, and distant metastasis of HCC. In our study, the 4-year cancer-free survival rate showed a trend to decrease with increasing histologic grade of HCC. This result is similar to that of Lin et al. [31].

Goldberg [32] suggested that new HCC tumors and underlying liver disease, rather than small foci of potential residual tumor at the ablation zone, might be the most influential determinant of survival for HCC patients. At follow-up CT in our study, new HCC tumors were seen to occur more often with increasing histologic grade of HCC. Additional treatment given for these new HCC tumors, as well as the new tumors themselves, may influence the survival rate.

This study had some limitations. First, only a few patients had Edmondson-Steiner grade III HCC, and none had grade IV. We believe that this limitation is due to advances in technology and clinical surveillance programs for HCC, allowing it to be detected early and surgically resected before the tumors become large and poorly differentiated. Second, obtaining histologic proof of HCC by needle biopsy is not always sufficient to eliminate histologic examination of the entire tumor after resection. However, because radiofrequency ablation usually is performed on patients who have unresectable HCC, it is difficult for the tumors to be histologically confirmed by hepatic resection or even by needle biopsy. Third, the rates of technique effectiveness and local tumor progression may have been influenced by the type of radiofrequency device used because internally cooled electrodes with a more powerful generator were used more often in groups 1 and 2 than in group 3. However, we think that the type of radiofrequency device was minimally influential on therapeutic results because we ablated an adequate, 0.5- to 1.0-cm, tumor-free margin and the entire tumor regardless of the type of radiofrequency device used. In addition, we had the advantage of using expandable needles, which produce a more uniform and spheric ablation zone than do the internally cooled electrodes used in the study of de Baere et al. [33]. Fourth, although cumulative 3- and 5-year survival rates did not differ by more than 20% between group 1 and the other groups, this difference was not statistically significant. We believe that statistical significance was lacking because the number of patients analyzed at 3 and 5 years was much smaller than the overall population. Also, the follow-up period ranged widely, and thus our cumulative survival and cancer-free survival results should be considered with caution because they were determined using relatively few patients.

In summary, we found that after radiofrequency ablation, the rate of technique effectiveness decreased and the rate of local tumor progression increased with an increasing histologic grade of HCC. New HCC tumors were seen more frequently as the histologic grade of HCC increased. Also, cumulative and cancer-free survival was influenced by the histologic grade of HCC. Our results indicate that the histologic grade of HCC is an important factor influencing therapeutic results after radiofrequency ablation.


References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

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