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Vascular and Interventional Radiology |
1 From the Department of Radiology, Kyoto University Graduate School of Medicine, 54-Kawaharacho, Shogoin, Sakyoku, Kyoto 606-8507, Japan. Received October 28, 2004; revision requested December 20; revision received March 3, 2005; final version accepted March 23. Address correspondence to Toshiya Shibata (e-mail: ksj{at}kuhp.kyoto-u.ac.jp).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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3.0 cm) hepatocellular carcinomas (HCCs). Materials and Methods: The human subjects research review board at the study institution approved the protocol, and each patient provided informed consent. Seventy-four patients (58 men and 16 women; age range, 41–83 years) with 83 HCC nodules 3 cm or smaller were randomly divided into an internally cooled electrode group (38 patients with 41 nodules) and an expandable electrode group (36 patients with 42 nodules). RF ablation was performed by one individual. Primary technique effectiveness and rates of major complications were evaluated between the two groups with the Fisher exact test. Rates of local tumor progression, overall survival, local progression–free survival, and event-free survival were evaluated by using the Kaplan-Meier method.
Results: The primary technique effectiveness was 95% in the internally cooled electrode group and 93% in the expandable electrode group (P = .51); rates of major complications were 0% and 2.1% per session (P = .50) and 0% and 2.8% per patient (P = .49), respectively. Rates at 1, 2, and 3 years in the internally cooled electrode group versus the expandable electrode group were as follows: local tumor progression, 12% versus 17%, 20% versus 22%, and 20% versus 22% (P = .72, log-rank test); overall survival, 100% versus 94%, 94% versus 92%, and 94% versus 77% (P = .29, log-rank test); local progression–free survival, 87% versus 78%, 73% versus 66%, and 73% versus 46% (P = .27, log-rank test); and event-free survival, 47% versus 44%, 34% versus 22%, and 34% versus 22% (P = .40, log-rank test).
Conclusion: On the basis of the study findings, RF ablation with an internally cooled electrode needle and an expandable electrode needle has equivalent effectiveness for the treatment of small HCCs.
© RSNA, 2006
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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3.0 cm) HCC nodules. |
MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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The patients were randomly assigned to undergo RF ablation with an internally cooled electrode or with an expandable electrode, according to a weekly schedule. RF ablation with the internally cooled electrode was performed every Tuesday (38 patients with 41 HCC nodules) and that with the expandable electrode (36 patients with 42 HCC nodules) was performed every Friday.
Imaging and Confirmation of Diagnosis
Pretreatment imaging studies performed were abdominal ultrasonography (US) and dynamic computed tomography (CT). Abdominal US was performed with a real-time scanner and a 3.5-MHz transducer (SSD-550; Aloka, Tokyo, Japan) by one author (Toyomichi Shibata) who did not know the patients' treatment group. Dynamic CT was performed with a helical CT scanner (HiSpeed Advantage; GE Medical Systems, Milwaukee, Wis). Triple-phase contiguous CT scans with 7-mm-thick sections were obtained. First, nonenhanced CT scans were obtained. Then, early-phase CT scans were obtained 30 seconds after the initiation of the bolus injection of 100 mL of 65% iopamidol (Iopamiron 300; Nihon Schering, Osaka, Japan); late-phase CT scans were obtained 120 seconds after the initiation of the injection of contrast media. One author (Y.M.), who did not know the patients' treatment group, diagnosed the CT findings. The European Association for the Study of the Liver (19) demonstrated that HCC can be diagnosed by means of coincident findings with at least two of three modalities—US, CT, or magnetic resonance imaging—that show characteristic features in a focal lesion. In our study, the diagnosis of HCC was obtained according to characteristic image findings at both US and dynamic CT in 55 of 74 patients; HCC was confirmed with percutaneous needle biopsy in the remaining 19 patients, who had nodules that could not be diagnosed as HCC according to the image findings.
RF Ablation
One author (Toshiya Shibata), who had 18 years of experience in interventional radiology, performed the RF ablation.
Internally cooled electrode.—The Cool-tip RF system, produced by Radionics, was used (9). The RF system consists of a 480-kHz generator; a 20- or 15-cm-long, 17-gauge cooled-tip RF electrode with a 2- to 3-cm-long exposed metallic tip; and a dispersive pad applied to the patient's skin. Grounding was achieved by attaching a dispersive pad to each of the patient's thighs. Pentazocine (15 mg, Sosegon; Yamanouchi Pharmaceutical, Tokyo, Japan) was intramuscularly injected 10 minutes before therapy as premedication for sedation. After the skin surface was disinfected, induction of local anesthesia with 1% lidocaine (Xylocaine; AstraZeneca, Osaka, Japan) was performed.
For nodules that were up to 1.5 cm in diameter, an electrode with a 2-cm exposed metallic tip was introduced into the center of the nodules by using either US or CT guidance. An electrode with a 3-cm exposed metallic tip was introduced into the center of nodules that were 1.5–2.5 cm in diameter. For nodules greater than 2.5 cm in diameter, a multiple electrode insertion technique was applied. Two electrodes with a 3-cm exposed metallic tip were inserted in the peripheral parts of the tumor, with an interelectrode distance of 1.5–2.0 cm.
During RF ablation, a thermocouple embedded in the electrode tip continuously measured the local temperature. Tissue impedance was monitored continuously by means of circuitry incorporated in the generator. A peristaltic pump (Watson-Marlow, Wilmington, Mass) was used to infuse 0°C normal saline solution into the cooling lumen of the electrode at a rate sufficient to maintain a tip temperature of 20°C–25°C. RF energy was delivered in the following manner: After measurement of baseline tissue impedance, generator output was slowly increased to 1000–1400 mA, and this level was maintained until the end of the procedure. If an increase in impedance equal to or greater than 10 above baseline was observed, the current was reduced until stable impedance was observed and then increased again. The process of decreasing and increasing generator output was repeated for the remainder of the treatment session to prevent tissue charring, which leads to increased impedance and limited energy deposition. The length of these cycles of increased and decreased generator output varied according to tissue impedance; in general, however, decreased output was maintained for approximately 15 seconds. An analgesic (pentazocine, 15 mg) was administered intravenously for patients who experienced severe pain during or immediately after the treatments.
Expandable electrode.—The RF 2000 generator system, produced by RadioTherapeutics, was used (10). This system consists of a generator, a monopolar array needle electrode (LeVeen), and a dispersive electrode pad applied to the patient's skin. The RF generator has a 460-kHz frequency and features displays indicating tissue impedance value and procedure time. The needle electrode is a 15-gauge insulated cannula with eight or 10 expandable hook-shaped electrode tines, whose diameters are 2.0 or 3.0 cm at expansion. Grounding was achieved by attaching a dispersive pad to each of the patient's thighs. Pentazocine (15 mg) was intramuscularly injected 10 minutes before therapy as premedication for sedation. After the skin surface was disinfected, induction of local anesthesia with 1% lidocaine was performed.
For nodules up to 1.5 cm in diameter, an electrode with 2.0-cm expanded tines, which was connected to the RF generator with a soft cable, was introduced into the center of the nodules by using either US or CT guidance. Hooks were then deployed in situ in the nodule. An initial power of 30 W was applied and increased at a rate of 10 W/min to 90 W. RF energy was applied until either marked increases in impedance were achieved or 15 minutes had elapsed. The second treatment was then applied at the same position until either marked increases in impedance were achieved or 10 minutes had elapsed at the 75% of the maximum output of the first treatment. If the marked increases in impedance were not obtained after the second treatment within 10 minutes, the third treatment was initiated at the same power of the second treatment and increased at a rate of 10 W/min to 90 W maximum, until marked increases in impedance were obtained. During procedures, an analgesic (pentazocine, 15 mg) was administered intravenously for patients who experienced severe pain during or immediately after the treatments.
For nodules 1.5–2.5 cm in diameter, an electrode with 3.0-cm expanded tines was introduced into the center by using US guidance. An initial power of 40 W was applied and increased at a rate of 10 W/min to 90 W. RF energy was applied until either marked increases in impedance were achieved or 15 minutes had elapsed. The second treatment was then applied at the same position until either marked increases in impedance were achieved or 10 minutes had elapsed at the 75% of the maximum output of the first treatment. If the marked increases in impedance were not obtained after the second treatment during 10 minutes, the third treatment was initiated at the same power of the second treatment and increased at a rate of 10 W/min to 90 W maximum, until marked increases in impedance were obtained. During procedures, an analgesic (pentazocine, 15 mg) was administered intravenously for patients who experienced severe pain during or immediately after the treatments.
For nodules larger than 2.5 cm in diameter, a multiple-electrode insertion technique was applied. Two electrodes were inserted in the peripheral parts of the tumor, with an interelectrode distance of 1.5–2.0 cm. The electrode used in the multiple-electrode insertion technique was the same as that used with the 3.0-cm expanded tines.
Treatment Course and Follow-up
Treatment course.—One to 2 days after each treatment session, dynamic CT was performed with the same protocols as the pretreatment imaging studies to diagnose the spread of the coagulation areas. One author (Y.M.) evaluated the CT findings. When a nonenhancing area with a diameter greater than that of the treated nodule was depicted, the treatment was finished. When nodule enhancement was seen at dynamic CT, an additional RF treatment was performed for the residual enhanced lesion. We limited the total number of treatment sessions for each nodule to no more than three so that a treatment course included one to three RF sessions. The effectiveness of the RF ablation technique was evaluated with dynamic CT performed 3–4 weeks after the first RF ablation session was performed. When no enhancing lesion was seen at CT, the technique effectiveness was defined as complete. When nodule enhancement was still seen at CT, the technique effectiveness was defined as incomplete (19). The nodules showing incomplete technique effectiveness were not treated with additional RF ablation but rather with transcatheter arterial embolization. Primary technique effectiveness rates (19) were evaluated in our study.
Follow-up US and dynamic CT were performed at 3-month intervals with the same protocols as the pretreatment studies. Local tumor progression was defined as a newly appearing enhancing lesion in or near the treated nodule at dynamic CT (19). The occurrence of new lesions in the liver and tumor dissemination or tumor implantation along the electrode tract were evaluated with US and dynamic CT. One author (Toyomichi Shibata) performed US, and another author (Y.M.) assessed the dynamic CT findings. Follow-up periods after RF ablation were 10–41 months (mean, 27 months ± 6.8) overall, 10–41 months (mean, 28 months ± 7.9) in the expandable electrode group, and 16–40 months (mean, 21 months ± 5.7) in the internally cooled electrode group.
Comparison.—The following points were compared between the internally cooled electrode and expandable electrode groups:
1. Rates of primary technique effectiveness in each nodule.
2. Rates of major complications: In accordance with the complication definitions established by the Society of Interventional Radiology, specific complications of interventional procedures were assigned to major and minor categories (20). Major complications were defined as those that required therapy with hospitalization or involved permanent adverse sequelae, including death. Major complications occurring after percutaneous ablation therapy for liver tumors are hemorrhage requiring transfusion, liver abscess requiring percutaneous drainage, bile duct injury requiring biliary drainage, pleural effusion requiring thoracentesis, tumor dissemination, hepatic failure, and death. Each one of two authors (H.I. and M.H.) assessed the major complications.
3. Rates of local tumor progression in each nodule: The time from the beginning of RF ablation to last follow-up CT was used.
4. Rates of overall survival: The time from the beginning of RF ablation to last follow-up CT or death was used.
5. Rates of local tumor progression–free survival: The time from the beginning of RF ablation to last follow-up CT, local tumor progression, or death was used.
6. Rates of event-free survival: The time from the beginning of RF ablation to last follow-up CT, local tumor progression, occurrence of new lesions in the liver, distant metastasis, or death was used.
Statistical Analysis
The variables in the internally cooled electrode and expandable electrode groups were compared. Patient age and size of nodules were statistically evaluated by using the Student t test. Patient sex, positivity for hepatitis C virus antibody, positivity for hepatitis B surface antigen, and serum 
-fetoprotein level greater than 200 µg/L were evaluated by using 
2 analysis. Number of nodules and Child-Pugh classification were evaluated by using the Wilcoxon test. Rates of primary technique effectiveness and of major complications were evaluated by using the Fisher exact test. Rates of local tumor progression, overall survival, local tumor progression–free survival, and event-free survival were estimated by using the Kaplan–Meier method. We compared these rates between the two groups by performing the log-rank test. Prognostic value of baseline characteristics, such as patient age and sex, Child-Pugh class, positivity for hepatitis C virus antibody, positivity for hepatitis B surface antigen, serum -fetoprotein level greater than 200 µg/L, and number and size of nodules, was assessed by using Cox proportional hazards regression models. A P value < .05 was considered to indicate a significant difference. Data processing and analysis were performed by using commercially available software (SPSS for Windows, version 9.0; SPSS, Chicago, Ill).
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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-fetoprotein levels; number of nodules; or size of nodules (Table).
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Primary Technique Effectiveness
In the internally cooled electrode group of 41 nodules, 39 (95%) showed complete technique effectiveness and two (4.9%) had incomplete technique effectiveness; these two were deeply located in the caudate lobe. In the expandable electrode group of 42 nodules, 39 (93%) showed complete technique effectiveness and three (7.1%) showed incomplete technique effectiveness; two of these three were located near the hepatic veins and inferior vena cava. There was no significant difference with respect to the rates of primary technique effectiveness between the two groups (P = .51, Fisher exact test).
Major Complications
A major complication—tumor implantation along the electrode tract—occurred with one session (2.1% per session) in one patient (2.8% per patient) in the expandable electrode group. No major complication occurred in the internally cooled electrode group. There was no significant difference in the rates of major complications between the two groups (P = .50 for difference according to session and P = .49 for difference according to patient, Fisher exact test).
Local Tumor Progression Rates
During follow-up, local tumor progression developed in eight nodules in the internally cooled electrode group and in nine nodules in the expandable electrode group. Of the nodules with local tumor progression, one nodule in the internally cooled electrode group and three nodules in the expandable electrode group were located near the inferior vena cava and hepatic veins (Fig 1). Two nodules in the internally cooled electrode group were deeply located in the caudate lobe. According to the Kaplan-Meier method, local tumor progression rates (Fig 2) in the internally cooled electrode group versus the expandable electrode group at 1, 2, and 3 years were as follows: 12% versus 17%, 20% versus 22%, and 20% versus 22%. There was no significant difference in the rates of local tumor progression between the two groups (P = .72, log-rank test).
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By using Cox proportional hazards model, baseline variables (patient age and sex, Child-Pugh class, positivity for hepatitis C virus antibody, positivity for hepatitis B surface antigen, serum -fetoprotein level >200 µg/L, and number and size of nodules) were not prognostically relevant with respect to the rates of overall survival, local tumor progression–free survival, and event-free survival.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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With RF ablation, local control of tumors is very important for achieving good patient survival, and successful tumor ablation is achieved when the tumor is completely destroyed by heat. The ideal for RF ablation would be to create a larger coagulation area than the tumor area during one session. Currently, three main strategies have been developed to enlarge coagulation areas: perfusion, internally cooled straight electrodes, and multitined expandable electrodes. De Baere et al (17) reported that the internally cooled cluster electrode clearly induced significantly larger lesions than the expandable needle in explanted calf livers (P < .002) and in vivo in swine livers (P < .001). They discussed the higher delivery of power exceeding 100 W (up to 200 W) in the Cool-tip system and attributed it to a larger coagulation area than that obtained with the expandable electrode, in which the maximum power delivered was up to 50 W (model 500; RITA Medical Systems, Mountain View, Calif). Pereira et al (18) compared four commercially available devices (perfusion, internally cooled cluster, and nine- and 12-tine expandable electrodes) in pig livers and showed that the maximum coagulation volumes were obtained with the perfusion electrode, followed by the internally cooled cluster, the 12-tine expandable electrode, and the nine-tine expandable electrode. However, they reported that high power output was not of primary importance for obtaining large coagulation volumes because excessive power output leads to overheating and tissue desiccation.
In our study, the rates of complete technique effectiveness evaluated at early-stage CT after RF ablation were comparatively high in both the internally cooled electrode and expandable electrode groups at 95% and 93%, respectively. For small HCC nodules no greater than 3 cm, sufficient coagulation areas would be obtained with the expandable electrode, as well as with the internally cooled electrode. Although the Cool-tip system has high delivery up to 200 W, the maximum power used for each treated nodule was 80–130 W in our study. The delivery of power greater than 130 W induced a frequent increase in impedance and multiple automatic reduction of the current that might consequently diminish the total treated times. On the other hand, the newly designed RF 3000 system (RadioTherapeutics), with multitine expandable electrode needle, can deliver power up to 200 W, but we believe that delivery of higher power up to 200 W, when electrodes with 2.0- or 3.0-cm expanded tines are used, may induce tissue charring around the electrode. Arata et al (22) reported that roll-off—the sudden increase of impedance and reduction in the current—is a significant predictor of local control after RF ablation because the local recurrence rate of the liver tumors treated with expandable electrode needle was 43% without roll-off and 15% with roll-off (P = .024). In our study, roll-off was obtained in most nodules (43 of 47 [91.5%]) in the expandable electrode group by using maximum 90-W power of the RF generator 2000 system.
Even if apparent coagulation necrosis were noted at early-stage dynamic CT, residual microscopic nests of tumor would lead to local tumor progression in some patients. Several causes have been suggested for the unsatisfactory results: technical difficulties in localizing the tumor and accurately placing the ablation electrode, heterogeneous thermodynamic properties of tissue in the ablation field (eg, the heat-sink effects of blood vessels in close proximity), and the different volume and geometry of ablation achieved with different ablation devices (23). Rates of local tumor progression after RF ablation of HCC or metastatic liver tumor have been reported to vary from 1.8% to 34%–55% (10–11,24–26). In our study, the rates of local tumor progression of the internally cooled electrode group versus the expandable electrode group at 1, 2, and 3 years were 12% versus 17%, 20% versus 22%, and 20% versus 22% (P = .72). Although our rates of local tumor progression are not low, heat-sink effects would affect the unsatisfactory results in four nodules located near the inferior vena cava and hepatic veins (three in the expandable electrode group and one in the internally cooled electrode group), and difficulty in accurately placing the ablation electrode affected the results in two nodules in the internally cooled electrode group located in the caudate lobe.
No significant difference was noted between the two groups with regard to local tumor progression (P = .72) or tumor progression–free survival rates (P = .27). RF ablation with the two different electrodes showed the equivalent effectiveness of local control of small HCC. So, which electrode should we choose? With US guidance, precise depiction of the tip of the expanded tines may not be clear in some cases. We believe the expandable electrode should not be used for nodules just near the heart or gastrointestinal tract to avoid direct injury of the organs. The shape of the coagulation area produced with the expandable electrode has been more oval than that produced with the perfusion or internally cooled electrode (18). When the nodule's short axis vertical to the inserted electrode is long, we should choose an expandable electrode. Major complications rarely occurred: Rates were 0% in the internally cooled electrode group and 2.1% per session and 2.8% per patient in the expandable electrode group. We believe both RF techniques proved to be equally a safe technique.
Our study had some limitations in that RF ablation is currently undergoing major modifications so that newer techniques or refined treatment strategies may produce larger areas of tumor coagulation and result in better local tumor response rates. In our study, long-term follow-up was needed to compare the local control of tumor or patient survival between the internally cooled electrode and expandable electrode groups, and the RF generator with expandable electrode used in our study has been replaced by a newer device with higher power output (RF 3000 system).
In conclusion, the two RF ablation devices used in our study have equivalent primary technique effectiveness, rates of major complications, rates of local tumor progression, rates of overall survival, and rates of local tumor progression–free survival.
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FOOTNOTES |
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Abbreviations: HCC = hepatocellular carcinoma • RF = radiofrequency
Authors stated no financial relationship to disclose.
Author contributions: Guarantor of integrity of entire study, Toshiya Shibata; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, Toshiya Shibata, Y.M., H.I., M.H.; clinical studies, Toshiya Shibata, Toyomichi Shibata; experimental studies, H.I.; statistical analysis, Toshiya Shibata, Y.M.; and manuscript editing, Toshiya Shibata, Toyomichi Shibata, M.H.
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References |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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