(Radiology. 1999;210:655-661.)
© RSNA, 1999
Vascular and Interventional Radiology |
Small Hepatocellular Carcinoma: Treatment with Radio-frequency Ablation versus Ethanol Injection
Tito Livraghi, MD1,
S. Nahum Goldberg, MD2,
Sergio Lazzaroni, MD3,
Franca Meloni, MD1,
Luigi Solbiati, MD4 and
G. Scott Gazelle, MD, MPH2
1 Department of Radiology, Ospedale Civile, Via C. Battisti 23, 20059 Vimercate, Italy (T.L., F.M.)
2 Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Mass (S.N.G., G.S.G.)
3 Department of Internal Medicine, Ospedale San Biagio, Clusone, Italy (S.L.)
4 Department of Radiology, Ospedale Generale, Busto Arsizio, Italy (L.S.).
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Abstract
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PURPOSE: To compare the effectiveness of radio-frequency (RF) ablation with that of percutaneous ethanol injection in the treatment of small hepatocellular carcinoma (HCC).
MATERIALS AND METHODS: Eighty-six patients with 112 small (
3-cm-diameter) HCCs underwent RF ablation (42 patients with 52 tumors) or percutaneous ethanol injection (44 patients with 60 tumors). Therapeutic efficacy was evaluated with dual-phase spiral computed tomography performed at least 4 months after treatment.
RESULTS: Complete necrosis was achieved in 47 of 52 tumors with RF ablation (90%) and in 48 of 60 tumors with percutaneous ethanol injection (80%). These results were obtained with an average of 1.2 sessions per tumor with RF ablation and 4.8 sessions per tumor with percutaneous ethanol injection. One major complication (hemothorax that required drainage) and four minor complications (intraperitoneal bleeding, hemobilia, pleural effusion, cholecystitis) occurred in patients treated with RF ablation; no complications occurred in patients treated with percutaneous ethanol injection.
CONCLUSION: RF ablation results in a higher rate of complete necrosis and requires fewer treatment sessions than percutaneous ethanol injection. However, the complication rate is higher with RF ablation than with percutaneous ethanol injection. RF ablation is the treatment of choice for most patients with HCC.
Index terms: Alcohol, 761.1269 • Liver, interventional procedure, 761.1269 • Liver neoplasms, therapy, 761.1269, 761.323, 761.47 • Radiofrequency (RF) ablation, 761.1269, 761.47
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Introduction
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In patients with cirrhosis or chronic hepatitis, regular screening with ultrasonography (US) permits early detection of hepatocellular carcinoma (HCC) (1,2). In these patients, in whom the tumor is usually less than 5 cm in diameter, percutaneous ablation of neoplastic tissue with injected ethanol has become widely accepted due to the favorable results (roughly comparable with those of surgery), relative simplicity, low cost, and safety of the technique (3–6). Results of large series (5,7,8) have demonstrated that complete tumor necrosis can be achieved in approximately 70%–80% of cases. In the remaining tumors, nearly complete necrosis can generally be achieved.
To improve on the results that have been obtained with percutaneous ethanol injection and still maintain the principal advantages of this technique over surgery (ie, decreased invasiveness and cost, relative simplicity, repeatability), other percutaneous techniques have been developed. These include thermal methods such as the use of radio frequency (RF) (9), laser (10), or microwaves (11,12). However, to our knowledge, no comparative study of the results obtained with different techniques in similar patient groups has been performed.
We performed a prospective study in which two cohorts of otherwise similar patients with small HCCs were treated with percutaneous ethanol injection or RF ablation. To our knowledge, this study was the first prospective comparison of these two techniques. In addition, to our knowledge, our patient population was the first series of patients with HCC to be treated with internally cooled RF electrodes, a technique that to our knowledge has been used only in patients with hepatic metastases (13).
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MATERIALS AND METHODS
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Patients
The study was performed with approval from the institutional ethics committees at Vimercate and Busto Arsizio hospitals. Informed consent was obtained from all patients at the time of enrollment.
Between July 1995 and July 1997, 86 consecutive patients with cirrhosis or chronic hepatitis and HCC (112 lesions 3 cm in diameter) were treated with percutaneous ethanol injection (44 patients with 60 lesions) or RF ablation (42 patients with 52 lesions). The patients had been referred to our centers for treatment with percutaneous ethanol injection but agreed to enter a study in which percutaneous ethanol injection or RF ablation would be selected for them. They were told that results with the two techniques were expected to be roughly the same on the basis of our experience with RF ablation in hepatic metastases (13). However, they were not told which treatment would be performed before agreeing to participate in the study. Seven patients with lesions adjacent to the hepatic hilum or the confluence of the hepatic veins were excluded from RF therapy because of the unknown risk to these vital structures.
The choice of treatment was based solely on the location of the patient's residence relative to the hospital. Patients who lived more than 2 hours from the hospital underwent RF ablation; patients who lived within 2 hours underwent percutaneous ethanol injection. Treatment choice was based on patient location because of the greater number of sessions generally required for percutaneous ethanol injection and the difficulty in scheduling multiple return visits for patients who live a greater distance from the hospital. The two patient groups were otherwise comparable (P > .05) with respect to age, sex, type of cirrhosis, Child-Pugh class, number of lesions, lesion diameter, type of HCC (nodular, contiguous multinodular, or infiltrating), 
-fetoprotein level, and des-
-carboxy-prothrombin level. Thus, there is no reason to believe that this method of determining treatment type would lead to statistically significant bias in the results. The characteristics of both patient groups are reported in the Table.
The pretreatment work-up included US and unenhanced and dual-phase spiral computed tomography (CT). Dual-phase spiral CT was performed with injection of 150 mL of iopamidol (Iopamiro; Bracco, Milan, Italy) at a rate of 3 mL/sec. The entire liver was scanned twice: once beginning 22 seconds after the initiation of contrast material injection and a second time beginning 60 seconds after the initiation of contrast material injection. In 68 patients (36 who underwent percutaneous ethanol injection and 32 who underwent RF ablation), the diagnosis of HCC was confirmed with US-guided fine-needle biopsy. Biopsy was not performed in patients in whom US and CT findings consistently indicated HCC and -fetoprotein levels were more than 200 ng/mL (>200 µg/L) or des--carboxy-prothrombin levels were abnormal. In patients who underwent RF ablation, the following serologic values were measured before treatment and 24 hours, 48 hours, and 1 month after treatment: levels of transaminases, alkaline phosphatase, bilirubin, electrolytes, hemoglobin, fibrinogen, haptoglobin, and creatinine; prothrombin activity; and complete blood cell count. These values were not measured in the percutaneous ethanol injection group because no important changes in these values were observed in several previous studies (8,14–16).
Techniques
Both procedures were performed under real-time US guidance (model AU 4; Esaote, Genoa, Italy) with a 3.5-MHZ sector probe (model CAB411; Hitachi Medical, Tokyo, Japan). A guide device incorporated into the US probe was used for placement of the needle or RF electrode. Before the procedures, coagulation parameters were checked in all patients. Treatment was not performed in patients with a platelet count below 40,000/mm3 (<40 x 109/L) or less than 40% prothrombin activity. After cleansing of the skin with iodized alcohol (which also served as a contact medium), the most appropriate approach was chosen. For lesions located in the right lobe, an intercostal approach was often preferred; for lesions located in the left lobe, a subcostal approach was generally used.
Percutaneous ethanol injection.—The procedure was performed in the outpatient department by one radiologist (T.L., S.L., F.M., L.S.) and one nurse. No sedative or local anesthetic was given. To inject ethanol, a 20-cm-long, 21-gauge needle with a closed conical tip and three terminal side holes (PEIT needle; Hakko, Tokyo, Japan) was used. Only one needle was used in any one treatment session. Ethanol was injected in a dose of 1–4 mL per session according to the distribution of ethanol, patient compliance, and lesion size. The perfused area was clearly seen as a hyperechoic focus. The ethanol was injected slowly in small boluses (~0.1–0.2 mL), with the diffusion checked by means of real-time US.
If ethanol diffusion was not clearly seen or if most of the ethanol diffused outside the tumor, injection was suspended and the needle was withdrawn. The needle was then repositioned and the injection repeated. To prevent reflux of ethanol along the needle track and leakage into the peritoneum, the needle was left in place for 20–30 seconds after completion of the injection and then slowly withdrawn. The injection site was chosen before each session to ensure perfusion of areas considered not to have been treated. Treatment ended when the perfusion of the neoplastic tissue was considered to be total. We performed two to six sessions per lesion (one treatment cycle) according to lesion size. Treatments were performed two times per week. After each treatment, patients were observed in the waiting room for 1–2 hours.
RF ablation.—The procedure was performed in a hospital procedure room by two radiologists (T.L., S.L., F.M., L.S.) and one nurse. One hour before treatment, the patient received an orally administered sedative and an intravenously administered analgesic. The patient was monitored continuously before, during, and after the procedure. A 20-cm-long, 18-gauge, cooled-tip RF electrode with a 2–3-cm-long exposed metallic tip (Radionics, Burlington, Mass) was used to deliver RF energy. Grounding was achieved by attaching a dispersive pad with a surface area greater than 400 cm2 to each of the patient's thighs. The electrode was then attached to a 500-kHz RF generator (series 3; Radionics) capable of producing 150 W of power.
During lesion 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°–25°C. No more than 2 L of saline solution was required for any procedure. After induction of local anesthesia, a 14-gauge needle was inserted through the skin to facilitate introduction of the RF electrode. For each treatment session, a single RF electrode was positioned at the center of the tumor.
RF energy was delivered in the following manner: After measurement of baseline tissue impedance, generator output was slowly increased to 1,000–1,400 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.
During energy deposition, a hyperechoic patch due to vaporization and cavitation effects was observed around the electrode tip; the patch progressively increased to cover all of the neoplastic area or a larger area (Fig 1). Frequently, hyperechoic microbubbles were simultaneously seen in the hepatic veins; occasionally, microbubbles could also be seen in the right atrium. In some cases, the hyperechoic patch did not appear progressively but suddenly, at which time an audible "pop" came from the liver. Several minutes after the end of treatment, the hyperechoic patch cleared and was replaced by a hyperechoic ring, which was usually smaller. RF energy was applied for 10–12 minutes. Only one application of RF energy was used for each tumor (one treatment cycle).
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Figure 1a. (a) Intercostal oblique sonogram shows a 2.8-cm-diameter nodular HCC (arrows) in segment 5. The RF electrode has been placed in the lesion, and the electrode tip is recognizable as an echogenic area in the tumor. (b) Sonogram obtained after several minutes of energy deposition shows a hyperechoic patch (arrow) around the electrode tip. (c) Sonogram obtained at the end of the procedure shows that the patch has increased (arrow) and covers more than the neoplastic area.
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Figure 1b. (a) Intercostal oblique sonogram shows a 2.8-cm-diameter nodular HCC (arrows) in segment 5. The RF electrode has been placed in the lesion, and the electrode tip is recognizable as an echogenic area in the tumor. (b) Sonogram obtained after several minutes of energy deposition shows a hyperechoic patch (arrow) around the electrode tip. (c) Sonogram obtained at the end of the procedure shows that the patch has increased (arrow) and covers more than the neoplastic area.
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Figure 1c. (a) Intercostal oblique sonogram shows a 2.8-cm-diameter nodular HCC (arrows) in segment 5. The RF electrode has been placed in the lesion, and the electrode tip is recognizable as an echogenic area in the tumor. (b) Sonogram obtained after several minutes of energy deposition shows a hyperechoic patch (arrow) around the electrode tip. (c) Sonogram obtained at the end of the procedure shows that the patch has increased (arrow) and covers more than the neoplastic area.
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After the RF procedure, patients were hospitalized for 48 hours; if no complications occurred, the patients were then discharged. Patients were observed longer after RF ablation than after percutaneous ethanol injection due to limited experience with RF ablation in patients with cirrhosis and specifically due to concern about complications.
Assessment of Therapeutic Efficacy
To evaluate the response, contrast-enhanced CT scans were obtained 30–40 days after treatment with the parameters described earlier. In patients who underwent RF ablation, CT was also performed 1 day after treatment to evaluate the short-term effects of the procedure. Repeat CT was performed every 3–4 months. Follow-up ranged from 4 to 28 months (mean, 10 months). At this writing, only 39 of the 86 patients have undergone follow-up CT at 8 months or later. Thus, tumor necrosis was considered complete when no areas of enhancement were seen in the tumor or at the periphery on CT scans obtained 4 months after treatment (Fig 2).
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Figure 2a. (a) Arterial-phase CT scan obtained before RF ablation shows a nodular HCC (arrow) with peripheral vascularity. (b) CT scan obtained at 8-month follow-up shows complete necrosis, with no areas of enhancement detectable in the tumor. The size and shape of the area of necrosis (arrow) reproduce those of the tumor.
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Figure 2b. (a) Arterial-phase CT scan obtained before RF ablation shows a nodular HCC (arrow) with peripheral vascularity. (b) CT scan obtained at 8-month follow-up shows complete necrosis, with no areas of enhancement detectable in the tumor. The size and shape of the area of necrosis (arrow) reproduce those of the tumor.
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If CT scans obtained at 1 month showed persistence of residual tumor, an additional treatment cycle (ie, one session of RF ablation or multiple sessions of percutaneous ethanol injection) was performed (Fig 3). No more than two treatment cycles were performed in any patient. If follow-up CT scans obtained after the second treatment cycle demonstrated residual tumor, the case was considered a treatment failure. In these cases, treatment was abandoned or another treatment was used (eg, segmental chemoembolization, RF ablation in patients who underwent percutaneous ethanol injection, percutaneous ethanol injection in patients who underwent RF ablation). However, the analysis of results for each technique was based on the follow-up CT scans obtained 4 months after treatment (ie, before another treatment was used).
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Figure 3a. (a) CT scan obtained 1 month after RF ablation shows a semilunar area of residual neoplastic tissue (small arrows). The oval area of low attenuation (large arrow) is the necrotic thermolesion produced by the first treatment session. (b) CT scan obtained after a second treatment session shows complete ablation of the residual tumor. In this case, the 3-cm-long electrode tip was positioned 1 cm beyond the tumor in cirrhotic tissue. The amount of necrosis achieved in cirrhotic tissue (arrow) was less than that achieved in neoplastic tissue.
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Figure 3b. (a) CT scan obtained 1 month after RF ablation shows a semilunar area of residual neoplastic tissue (small arrows). The oval area of low attenuation (large arrow) is the necrotic thermolesion produced by the first treatment session. (b) CT scan obtained after a second treatment session shows complete ablation of the residual tumor. In this case, the 3-cm-long electrode tip was positioned 1 cm beyond the tumor in cirrhotic tissue. The amount of necrosis achieved in cirrhotic tissue (arrow) was less than that achieved in neoplastic tissue.
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The CT scans were interpreted by two radiologists (T.L., L.S.) who were experienced in abdominal imaging. These were the same radiologists who performed percutaneous ethanol injection and RF ablation. The CT scans were interpreted by means of consensus, and the readers were not blinded to the clinical history or the treatment used.
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RESULTS
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Percutaneous Ethanol Injection
A single treatment cycle was performed in 44 of 60 tumors (73%); in 16 tumors (27%), a second treatment cycle was performed because of residual foci of enhancement, which were thought to represent neoplastic tissue. When both the first and (when performed) second treatment cycles were taken into account, an average of 4.8 sessions per tumor was performed. Complete necrosis was achieved in 48 of 60 tumors (80%). These results are comparable with those reported in the literature (5,7,8). Of the 12 tumors (18%) in which necrosis was incomplete even after the second treatment cycle, six were infiltrating HCCs, four were contiguous multinodular HCCs, and two were nodular HCCs. Most patients experienced moderate pain during and/or immediately after the ethanol injection. Analgesics were required in only one patient, who experienced abdominal pain for 2 days. The mean total procedure time was approximately 30 minutes per session.
RF Ablation
A single treatment cycle was performed in 44 of 52 tumors (85%); in eight tumors (15%), a second treatment cycle was performed because of residual foci of enhancement, which were thought to represent neoplastic tissue. When both the first and (when performed) second treatment cycles were taken into account, an average of 1.2 sessions per tumor was performed. Complete necrosis was achieved in 47 of 52 tumors (90%). Of the five tumors (10%) in which necrosis was incomplete even after the second treatment cycle (ie, second session), three were nodular HCCs, one was a contiguous multinodular HCC, and one was an infiltrating HCC.
Most patients experienced mild to moderate pain during the procedure, especially when the tumor was superficially located. In five patients, treatment was interrupted due to severe pain; an anesthesiologist administered propofol (Diprivan 1%; Zeneca, Milan, Italy) and performed assisted ventilation for the duration of the procedure. Two patients with superficially located tumors (Fig 4) experienced pain for 3–4 days; the pain required administration of analgesics. In all patients, levels of transaminases increased by two to four times over baseline at 24 hours, with an observed decrease (trend to baseline) by 48 hours. No important changes in level of unconjugated bilirubin, complete blood cell count, or platelet count were observed. The mean total procedure time was approximately 45 minutes per session.
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Figure 4a. (a) Arterial-phase CT scan obtained before RF ablation shows a hyperattenuating, superficially located 2.1-cm-diameter nodular HCC in the right lobe (arrow). (b) CT scan obtained 1 day after RF ablation shows a 4.5 x 2.8-cm necrotic area (arrows), which is larger than the tumor. The Glisson capsule has been breached, and phlyctenae have formed. The "oven effect" (see "Discussion") did not occur because the patient had chronic hepatitis. (c) CT scan obtained at 8-month follow-up shows repair of the hepatic capsule (arrows) and complete necrosis of the tumor.
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Figure 4c. (a) Arterial-phase CT scan obtained before RF ablation shows a hyperattenuating, superficially located 2.1-cm-diameter nodular HCC in the right lobe (arrow). (b) CT scan obtained 1 day after RF ablation shows a 4.5 x 2.8-cm necrotic area (arrows), which is larger than the tumor. The Glisson capsule has been breached, and phlyctenae have formed. The "oven effect" (see "Discussion") did not occur because the patient had chronic hepatitis. (c) CT scan obtained at 8-month follow-up shows repair of the hepatic capsule (arrows) and complete necrosis of the tumor.
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Figure 4b. (a) Arterial-phase CT scan obtained before RF ablation shows a hyperattenuating, superficially located 2.1-cm-diameter nodular HCC in the right lobe (arrow). (b) CT scan obtained 1 day after RF ablation shows a 4.5 x 2.8-cm necrotic area (arrows), which is larger than the tumor. The Glisson capsule has been breached, and phlyctenae have formed. The "oven effect" (see "Discussion") did not occur because the patient had chronic hepatitis. (c) CT scan obtained at 8-month follow-up shows repair of the hepatic capsule (arrows) and complete necrosis of the tumor.
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One major complication occurred (2% of patients): hemothorax due to damage of an intercostal vessel located along the electrode track. This complication required surgical drainage after 3 days. Four minor complications occurred in four patients (8%): intraperitoneal bleeding (reduction of hemoglobin level by 4 g/dL [40 g/L]); hemobilia (indicated by the appearance of sludge in the gallbladder during the procedure); pleural effusion (after intercostal insertion of the electrode in a superficially located tumor), which resolved after 2 months; and mild cholecystitis (the tumor was located close to the gallbladder), which resolved in several days. None of these complications required treatment, although discharge from the hospital was delayed. All five complications occurred during the first 24 hours after the procedure.
On CT scans obtained 1 day after treatment, a hyperattenuating ring around the coagulated region was apparent in most cases. This ring was thought to be related to hyperemia and disappeared progressively during follow-up. The diameter of the hyperechoic patch seen during treatment was usually 5–10 mm larger than the diameter of the necrotic area on CT scans. However, the hyperechoic ring seen after the procedure was generally comparable in size with the necrotic area seen at CT.
The size and shape of the necrotic area were different in cirrhotic and neoplastic tissue. In cirrhotic tissue, the necrotic area was cylindric with a diameter of 1.7–2.0 cm; in neoplastic tissue of the most common type (ie, nodular), the size and shape of the necrotic area generally reproduced those of the tumor, as if a mold of the tumor had been made. This kind of response, which will be discussed later, was termed the oven effect (Figs 3b, 5). In infiltrating and contiguous multinodular tumors, the size and shape of the necrotic area were irregular and did not always conform to those of the tumor.
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Figure 5. CT scan obtained 1 day after RF ablation of a 2.4-cm-diameter nodular HCC shows the oven effect. In this case, the 3-cm-long electrode tip was positioned several millimeters before and beyond the tumor. The amount of necrosis achieved in cirrhotic tissue (small arrows) was less than that achieved in neoplastic tissue (large arrow).
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On CT scans obtained after 1 month, thickening of the hepatic surface was sometimes observed, particularly when the tumor was superficially located. This finding disappeared progressively during follow-up. US was not useful in evaluation of therapeutic efficacy because of the inhomogeneous, variable echogenicity observed after treatment. These changes, which furthermore resolved in a nonpredictable fashion, precluded accurate assessment of induced coagulation.
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DISCUSSION
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This study demonstrates that in similar patients with HCC, treatment with RF ablation can result in complete tumor necrosis in a greater percentage of patients than can treatment with percutaneous ethanol injection (90% vs 80%). This difference between treatments was not statistically significant (P = .127). However, in the three nodular HCCs in which complete necrosis was not achieved with RF ablation, treatment failure can be attributed, at least in retrospect, to improper placement of the electrode in the tumor due to the difficult approach. An additional and important advantage of RF ablation over percutaneous ethanol injection is that fewer treatment sessions (ie, 1.2 vs 4.8) were required to achieve this result. This is an advantage not only for patients but also for hospital staff.
Although a formal cost-effectiveness analysis was not performed as part of this study, we believe that the greater success in achieving a total response coupled with the need for fewer treatment sessions make RF ablation the preferred treatment for most patients with HCC. Nevertheless, given the well-established efficacy of percutaneous ethanol injection (confirmed in this study), percutaneous ethanol injection should remain the primary treatment option when RF ablation is not available. In addition, there was a difference between percutaneous ethanol injection and RF ablation related to the hospital stay associated with RF ablation in this study. This finding was the result of our conservative therapeutic regimen, which was due to the experimental nature of RF ablation. Indeed, we currently observe patients for only 24 hours. The occurrence of some adverse events suggests such a course of action until greater experience is obtained.
An interesting finding of this study was that the size and shape of the necrotic area generally conformed to the size and shape of the tumor, with a coagulation diameter larger than expected within the tumor and smaller than expected in surrounding cirrhotic tissue. According to previous experimental work in the liver in normal animals, the mean diameter of the necrotic area produced with the RF ablation technique used in this study should have been approximately 2.4 cm (17). In many cases, however, a necrotic area of up to 3.0 cm in diameter was seen in the tumor, whereas the necrotic area was generally limited to 1.7–2.0 cm in diameter in cirrhotic tissue (when the electrode extended beyond the tumor). We attribute this difference to the so-called oven effect. In essence, the cirrhotic tissue around the tumor might behave like a thermal insulator, increasing heat retention within the tumor and preventing heating outside the tumor.
The oven effect may also help explain the difference in results between tumor types. Both percutaneous ethanol injection and RF ablation demonstrated decreased efficacy in the treatment of contiguous multinodular HCC. For percutaneous ethanol injection, the decreased efficacy was likely due to the fibrosis surrounding the small neoplastic nodules, which limits ethanol diffusion and prevents homogeneous distribution throughout the tumor. This intratumoral fibrosis may also influence heat diffusion (the oven effect in reverse) and thereby limit the efficacy of RF ablation (Fig 6). Fortunately, the importance of this unfavorable occurrence is minimized by the low frequency of this type of HCC.
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Figure 6a. (a) CT scan obtained after one RF ablation treatment shows partial necrosis in a contiguous multinodular HCC. A cluster of small, hyperattenuating neoplastic nodules remains in the upper portion of the tumor (arrow). (b) CT scan obtained after a second treatment still shows a small viable nodule (arrow).
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Figure 6b. (a) CT scan obtained after one RF ablation treatment shows partial necrosis in a contiguous multinodular HCC. A cluster of small, hyperattenuating neoplastic nodules remains in the upper portion of the tumor (arrow). (b) CT scan obtained after a second treatment still shows a small viable nodule (arrow).
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The single unfavorable feature of RF ablation was the higher complication rate (major, 2%; minor, 8%) compared with the 0% complication rate of percutaneous ethanol injection. The complications may have been related, at least partly, to the lower gauge of the electrode used in RF ablation, as well as to heating of normal structures adjacent to the tumor (gallbladder wall, pleural layers). An additional explanation may be that RF ablation was relatively new to the operators in comparison with percutaneous ethanol injection, which has been used in hundreds of patients. Greater experience coupled with a better understanding of the technique may help limit complications.
The results of this study, along with ongoing advances in the techniques for in situ tumor ablation, may ultimately change the overall approach to management of nonadvanced HCC. For many years, surgical resection was considered the only curative option for HCC in cirrhosis because the neoplasm can be completely removed. More recently, however, it has been understood that HCC is a multifocal disease in due time (18,19). In other words, the first lesion to be detected is only the prelude to other neoplasms. For this reason and because of the relatively high complication rate associated with surgery, percutaneous ethanol injection has gained an increasing role in the treatment of HCC detected with screening US.
According to historic data, the mean 5-year survival rate for patients with Child-Pugh class A HCC and a single lesion 5 cm in diameter or smaller is 49% after surgery and 48% after percutaneous ethanol injection (20). The comparability of these results probably reflects a balance between the success of surgery in completely removing the tumor (vs the 70%–80% rate for percutaneous ethanol injection) and the repeatability (because of the tendency of HCC to recur), lack of liver damage (there is substantial loss of hepatic tissue in some resections), and absence of mortality (vs the mean mortality rate of 7% reported by experienced surgeons) associated with percutaneous ethanol injection (5). The most important predictors of a favorable result with surgery, as determined by the Liver Cancer Study Group of Japan (21), are young age, a single focus of disease, no portal involvement, compensated cirrhosis, and a low -fetoprotein level. Except for patients who are candidates for liver transplantation, surgical resection is likely to be the best choice for patients with only favorable prognostic factors; all other patients are generally better treated with percutaneous ethanol injection (5).
Because our study demonstrated that RF ablation enables complete tumor necrosis in more patients than does percutaneous ethanol injection (90% vs 80%), it is possible that the indications for surgery may be decreased even further. Accordingly, we believe that nodular HCC with favorable prognostic factors can be effectively treated with RF ablation, with surgery being reserved for those patients in whom RF ablation fails. However, surgery still remains the treatment of choice for contiguous multinodular HCC due to the unsatisfactory results of percutaneous ethanol injection or RF ablation in this tumor type.
In conclusion, in 86 patients who underwent percutaneous ethanol injection or RF ablation of HCC, RF ablation was more effective and enabled tumor necrosis in fewer treatment sessions, albeit with a higher rate of complications. On the basis of these results, we currently prefer to use RF ablation in the majority of patients, reserving percutaneous ethanol injection for HCCs that are difficult to approach or located in areas where RF ablation is considered unsafe. Use of RF ablation might decrease the indications for surgery. Improvements in the technique of RF ablation may further increase the efficacy and decrease the complications. Identification of the oven effect has persuaded us to treat tumors of increasingly larger size, and preliminary results encourage us to continue in this direction.
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Footnotes
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Address reprint requests to T.L.
Abbreviations: HCC = hepatocellular carcinoma
RF = radio frequency
Author contributions: Guarantors of integrity of entire study, T.L., G.S.G.; study concepts, T.L.; study design, T.L., S.L., L.S.; definition of intellectual content, T.L.; literature research, T.L.; clinical studies, T.L., S.L., F.M., L.S.; experimental studies, S.N.G., G.S.G.; data acquisition, T.L., S.L., F.M., L.S.; data analysis, T.L., G.S.G.; statistical analysis, G.S.G.; manuscript preparation, T.L., G.S.G., S.N.G., L.S.; manuscript editing, G.S.G., S.N.G.; manuscript review, T.L., G.S.G., S.N.G.
Received February 6, 1998;
revision requested April 14, 1998; revision received July 8, 1998;
accepted September 8, 1998.
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Abstract
Introduction
