Radiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rossi, S.
Right arrow Articles by Bartolozzi, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rossi, S.
Right arrow Articles by Bartolozzi, C.
(Radiology. 2000;217:119-126.)
© RSNA, 2000

Vascular and Interventional Radiology

Percutaneous Radio-frequency Thermal Ablation of Nonresectable Hepatocellular Carcinoma after Occlusion of Tumor Blood Supply1

Sandro Rossi, MD, Francesco Garbagnati, MD, Riccardo Lencioni, MD, Hans-Peter Allgaier, MD, Alfonso Marchianò, MD, Fabio Fornari, MD, Pietro Quaretti, MD, Giuseppe Di Tolla, MD, Claudia Ambrosi, MD, Vincenzo Mazzaferro, MD, Hubert E. Blum, MD and Carlo Bartolozzi, MD

1 From the Depts of Gastroenterology (S.R.), Emergency Medicine (F.F.), and Radiology (P.Q.), Public Hospital of Piacenza, Italy; Depts of Radiology (F.G., A.M., G.D.T., C.A.) and Surgery (V.M.), National Cancer Institute, via Venezian 1, 20133 Milan, Italy; Dept of Radiology, Univ of Pisa, Italy (R.L., C.B.); and Dept of Gastroenterology, Univ of Freiburg, Germany (H.P.A., H.E.B.). Received Aug 23, 1999; revision requested Oct 7; revision received Jan 4, 2000; accepted Feb 7. Address correspondence to F.G. (e-mail: garbagnatif@yahoo.com).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
PURPOSE: To evaluate the usefulness of percutaneous radio-frequency (RF) thermal ablation of nonresectable hepatocellular carcinoma (HCC) after occlusion of the tumor arterial supply.

MATERIALS AND METHODS: Sixty-two patients with cirrhosis and biopsy-proved HCC underwent RF ablation after interruption of the tumor arterial supply by means of occlusion of either the hepatic artery with a balloon catheter (40 patients) or the feeding arteries with gelatin sponge particles (22 patients).

RESULTS: After a single RF procedure in 56 patients and after two procedures in six patients, spiral computed tomography (CT) demonstrated a nonenhancing area corresponding in shape to the previously identified HCC, which was suggestive of complete necrosis. No major complications occurred. Two patients subsequently underwent surgical resection; the remaining 60 patients were followed up with spiral CT. During a mean follow-up of 12.1 months, 11 HCC nodules showed areas of local progression; 49 were identified as nonenhancing areas with a 40%–75% reduction in maximum diameter. The 1-year estimate of failure risk was 19% for local recurrence and 45% for overall intrahepatic recurrence. The estimated 1-year survival was 87%. Histopathologic analysis of one autopsy and two surgical specimens revealed more than 90% necrosis in one specimen and 100% necrosis in two.

CONCLUSION: HCC nodules 3.5–8.5 cm in diameter can be ablated in one or two RF sessions after occlusion of the tumor arterial supply.

Index terms: Liver, interventional procedures, 761.1264, 761.1269 • Liver neoplasms, 761.323 • Liver neoplasms, angiography, 761.1242 • Liver neoplasms, CT, 761.12112, 761.12114, 761.12115 • Liver neoplasms, MR, 761.121411, 761.121412, 761.12143 • Radiofrequency (RF) ablation, 761.1269


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Radio-frequency (RF) thermal ablation was used for the treatment of hepatocellular carcinoma (HCC) in 1993 (1) after extensive animal studies (2,3). The goal was to ablate tumor tissue percutaneously with RF energy delivered directly through a noninsulated electrode tip. Thermal lesions, which are areas of coagulative necrosis that evolve into fibrosis (2), are created in a core of tissue that adheres to the noninsulated electrode tip owing to the heat generated by molecular friction (4,5). The final size of the lesion depends on the total amount of heat deposition, the thermal conductivity of the tissue, and the heat lost due to convection through blood flow (2–5).

In early clinical trials, multiple electrode insertions were required to destroy even small tumor nodules because of the limited size of the thermal lesions created at each activation of the RF system (1,6,7). Consequently, efforts were directed at increasing the volume of RF thermal lesions to reduce the number of electrode insertions and simplify the procedure. To this end, various approaches have focused on maximizing heat deposition in the tissue and achieving larger thermal lesions by using powerful RF generators with expandable (8,9) or cooled electrodes (10,11) or a cluster of closely spaced electrodes (12).

In this study, rather than increase the heat deposition, we attempted to reduce it by means of convection by decreasing the blood flow during the RF procedure. The thermal lesions obtained in studies of in vitro livers have been larger than those in vivo because of the lack of heat loss by convection that is related to blood flow (10), and the reduction or elimination of blood flow during the RF procedure was known to increase the volume of the thermal lesions (13–15). Because HCCs are nourished almost exclusively by vessels arising from the hepatic artery (16), we performed the RF procedure in HCC nodules after the interruption of their arterial supply by means of occlusion of either the hepatic artery with a balloon catheter or the feeding arteries with gelatin sponge particles. Our purpose was to assess the usefulness of percutaneous RF thermal ablation of nonresectable HCC after occlusion of the tumor arterial blood supply.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Patients
Before the start of the study, the protocol design was approved by the Institutional Committee on Human Investigations of the National Cancer Institute of Milan, Italy. An informed consent form was signed by each patient at the time of enrollment after the nature of the procedure had been fully explained.

Between January 1997 and December 1998, 62 consecutive patients (48 men, 14 women; mean age, 68.1 years; age range, 45–78 years) with a single HCC accompanying cirrhosis underwent the RF procedure after occlusion of the tumor arterial supply. The underlying biopsy-proved cirrhosis was related to hepatitis C in 41 patients, related to hepatitis B in four, related to hepatitis B or C in 13, related to alcohol use in two, and cryptogenic in two. The Child-Pugh class of cirrhosis (17) was determined in each patient, and at the time of the ablation procedure, eight patients were judged to have Child-Pugh class A5 cirrhosis; 40, class A6; 10, class B7; and four, class B8. Pathologic proof of HCC was obtained in all cases by means of ultrasonographically (US) guided biopsy with a 21-gauge cutting needle (Surecut; HS Hospital Service, Cavezzo, Italy).

All the patients had been examined by an experienced surgical staff and were considered to be unsuitable for surgical intervention. Patients with coexistent morbidity–related poor life expectancy, multinodular or diffuse intrahepatic tumor, extrahepatic spread, portal thrombosis, Child-Pugh class C cirrhosis, refractory ascites, prothrombin activity less than 50%, or a platelet count lower than 50 cells x 109/L were excluded from this study.

Before enrollment, the stage of intrahepatic disease was determined by using US, contrast material–enhanced spiral computed tomography (CT), and selective hepatic angiography in all the patients. Magnetic resonance (MR) images were acquired in 15 patients. The US scans were obtained in the sagittal, transverse, and intercostal planes by using ATL HDI (Advanced Technology Laboratories, Bothell, Wash) and AU 590 (Esaote Biomedica, Genoa, Italy) units and a convex 3.5-MHz probe. CT was performed with model PQ 6000 (Picker International, Highland Heights, Ohio) and HiSpeed Advantage (GE Medical Systems, Milwaukee, Wis) spiral scanners.

Nonenhanced and biphasic contrast-enhanced CT images (5-mm-thick sections, 7-mm collimation, 1.50 pitch, 120 Kvp, 220–250 mAs) were acquired in all cases. For the contrast-enhanced studies, the patients received 150 mL of iopamidol (370 mg of iodine per milliliter) (Iopamiro 370; Bracco, Milano, Italy) by means of power injection at a rate of 3–4 mL/sec. CT began 25 seconds after the start of the contrast material injection to obtain arterial phase images and 70–75 seconds after the injection to obtain portal venous phase images. The liver was imaged in 20–30 seconds.

Selective hepatic angiography was conducted with a digital angiographic unit (Polytron 1000; Siemens, Erlangen, Germany). An 8.0-F valved sheath (Introducer II-long sheath; Terumo; Tokyo, Japan) was inserted into the femoral artery with the patient under local anesthesia, which was induced by injecting 10 mL of 1% lidocaine (Lidrian; Bieffe Medital, Modena, Italy). Celiac and superior mesenteric arteriography was performed with a prebent 5.0-F catheter (Glidecath; Terumo), which was advanced into the common hepatic artery by using a 0.038-inch gliding guide wire (Guide Wire M; Terumo). Selective hepatic angiographic data were recorded with a digital subtraction technique.

The nonenhanced MR images were obtained by using a 1.5-T Magnetom Vision unit (Siemens) and two pulse sequences: T2-weighted turbo spin echo (4,200/83 or 165 [repetition time msec/echo time msec], 7-mm section thickness, 128 x 256 matrix, 3-minute imaging time) and T1-weighted gradient echo with a fast low-angle shot technique (174.9/4.1, 80° flip angle, 7-mm section thickness, 128 x 256 matrix, 22-second imaging time). Contrast-enhanced MR images were acquired after the bolus injection of 0.1 mmol of gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany) per kilogram of body weight at a rate of 3 mL/sec. Three to four consecutive dynamic T1-weighted, fast low-angle shot sequences were performed in 30-second intervals.

The size and location of the HCC nodules were assessed with Couinaud nomenclature (18) by means of consensus between at least two observers who compared the images obtained with each of the radiologic techniques. Serum {alpha}-fetoprotein assays (normal value, <=20 µg/L) were performed just before the RF procedure in all patients.

Equipment and Procedure
The RF energy was delivered by using a 15-gauge, 25.0-cm-long electrode with a 1.0-cm-long exposed tip that was expandable by four hooks, each of which contained a thermistor on the tip, to a maximum diameter of 3.0 cm (8). The electrode was connected to a 460-KHz RF generator (Model 500 L; RITA Medical System, Mountain View, Calif), which supplied a maximum power output of 50 W. A computer (IBM ThinkPad 360; IBM-Asjstel, Milan, Italy) with dedicated software (Micro Interactive, New York, NY) connected to the generator recorded the power delivered, impedance values, thermistor temperatures, and timing of each procedure (Fig 1).



View larger version (39K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1. Graphs illustrate typical changes in temperature and impedance during the 8 minutes of RF ablation to create the last thermal lesion, performed along the major axis of the electrode with the pullback technique, and changes in temperatures during the following 2 minutes. TH = temperatures at the hook tips, TI = temperatures on the thermistor placed just inside the HCC nodule, TO = temperatures on the thermistor placed just outside the HCC nodule.

 
The RF ablation procedure was performed in inpatients who had fasted overnight, after the end of diagnostic selective hepatic angiography for the assessment of the hepatic vascular anatomy, tumor feeding arteries, and portal venous patency. No general anesthesia or conscious sedation was induced. A 13 x 21-cm grounding pad was fixed to the patient’s back and connected to the RF generator to close the electrical circuit. A guide wire was advanced into the proper hepatic artery, and the 5.0-F catheter was replaced with a 7.0-F catheter that had an 11.5-mm occlusion balloon at the tip (Medi-tech/Boston Scientific, Watertown, Mass). The RF electrode was then introduced with real-time US guidance into the HCC nodule with the patient under local anesthesia induced by using 10 mL of 1% lidocaine injected from the skin into the peritoneum along the predetermined puncture line. The electrode hooks were deployed at the deepest margin of the nodule, and the occlusion balloon in the hepatic artery was filled with a mixture of saline solution and contrast material. No anticoagulant agents were administered. The RF generator was activated, and the power needed to maintain a temperature of 90°C–115°C at the hook tips was delivered for 8 minutes.

After creation of the first thermal lesion, the hooks were retracted and the electrode was withdrawn 1.0 cm along its major axis; the hooks were then redeployed and the RF generator was reactivated (8). For each HCC nodule 5.5 cm or less in diameter, three to five thermal lesions were made by using the described pullback technique with a single electrode insertion through the nodule center. For each nodule larger than 5.5 cm in diameter, six to eight thermal lesions were made by inserting the electrode into two different points in the nodule that were chosen on the basis of the tumor shape. At the end of the procedure, the electrode was withdrawn, the occlusion balloon was deflated, and the immediate results were evaluated with angiography.

When occlusion of the HCC arterial supply could not be achieved by using a balloon catheter (eg, because of variant vascular anatomy, irregular shape, or stenosis of the hepatic artery), it was performed by injecting a mixture of gelatin sponge particles (Gelfoam; Upjohn, Kalamazoo, Mich) and contrast material into the feeding vessels through either the 5.0-F catheter, which was advanced into the segmental arteries, or a 3.0-F microcoaxial catheter preloaded with a core guide wire (Tracker-325 Vascular Access System; Medi-tech/Boston Scientific) that was inserted through the 5.0-F catheter. Electrode insertion and the RF procedure were performed as previously described.

In 10 patients, who had HCC nodules that ranged in size from 4.0 to 5.2 cm, additional remote thermometry studies were performed during the RF procedure. Occlusion of the HCC arterial supply was achieved by using the balloon catheter in seven of these 10 patients and by using gelatin sponge particle injection in three. With US guidance through a Chiba-type needle, an independent thermocouple was placed 2–5 mm inside the HCC margins at a mean distance of 2.0 cm (range, 1.8–2.4 cm) from the electrode, and another thermocouple was inserted 2–5 mm outside the HCC margins at a mean distance of 2.7 cm (range, 2.3–3.1 cm) from the electrode. Each thermocouple was connected to a display unit (Thermometer HD 8464H; Delta Ohm, Milan, Italy) for recording of the temperatures.

Pain during the RF procedure was graded as absent or slight discomfort not requiring therapy, mild to moderate pain requiring analgesia, or severe pain requiring sedation.

Posttreatment and Follow-up Studies
For evaluation of complications after RF ablation, all patients underwent hemoglobin, serum aminotransferase, and Child-Pugh–related liver tests within 24 hours after the procedure and US within 2–5 days after the procedure. Serum aminotransferase and Child-Pugh–related liver tests were repeated within 6–7 days and when suggested on the basis of clinical symptoms.

The efficacy of the RF ablation was assessed by using spiral CT within 2–5 days after the procedure and by using {alpha}-fetoprotein assays within 10–15 days after the procedure. Fifteen patients underwent additional MR imaging within 2–5 days. The presence of well-defined, nonenhancing tissue on images obtained during both phases of contrast-enhanced CT and of hypointense, nonenhancing tissue on gadolinium-enhanced T1-weighted MR images was indicative of tissue necrosis (6,8,9,11). The radiologic findings were used to define the response to treatment according to World Health Organization criteria (19)—that is, complete response, defined as no evidence of neoplastic disease; partial response, a greater than 50% reduction in total tumor load; no change, a less than 50% reduction in total tumor load; and progressive disease, a greater than 25% increase in tumor load. The response was measured soon after the treatment and throughout follow-up or until the time of disease progression. A second RF procedure was planned as soon as possible for patients who did not show a complete response after the first procedure.

Follow-up studies included serum {alpha}-fetoprotein assay and US every 3–4 months and spiral CT every 3–4 months in the 1st year and every 6 months thereafter. Additional MR images were obtained in the patients in whom pretreatment staging with both MR and CT was performed. If any radiologic study had findings that were suggestive of recurrence, multiple US-guided fine-needle core biopsy procedures were performed. HCC nodules that were seen in the same liver segment as the previously treated one were defined as local recurrences, and the others were defined as new intrahepatic recurrences. The results of the described radiologic procedures were later discussed jointly by all the authors.

Geometric means were computed for the {alpha}-fetoprotein values measured before and after the RF procedure and during follow-up. Statistical comparisons were performed by using the Student t test. Estimates of survival and failure risk for local and overall intrahepatic recurrences were calculated according to the Kaplan-Meier method.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Preprocedural Findings
The HCC nodules were 3.5–8.5 cm in diameter (mean, 4.7 cm): 15 were 3.5–4.0 cm; 24, 4.1–5.0 cm; 18, 5.1–6.0 cm; four, 6.1–7.0 cm; and one, about 8.5 cm. Four HCC nodules were in the left segments, and the remaining 58 were in the right; 12 were subcapsular deforming liver margins.

The serum {alpha}-fetoprotein levels were normal in 24 patients, between 20 and 500 µg/L in 24, and higher than 500 µg/L in 14. The mean {alpha}-fetoprotein level was 88 µg/L (95% CI: 50 µg/L, 154 µg/L) at baseline.

Intraprocedural Findings and Immediate Posttreatment Results
Of the 62 treated patients, 40 underwent the RF procedure at the time of balloon catheter occlusion of the hepatic artery, and 13 underwent RF ablation at the time of occlusion of the HCC feeding arteries with gelatin sponge particles. The remaining nine patients underwent RF ablation 2–5 days after occlusion with gelatin sponge particles because of organizational problems at one of the participating centers.

Sixty-two HCC nodules were treated in 62 RF ablation sessions—48 with a single electrode insertion and 14 with two insertions. The total RF application time for each HCC nodule ranged between 24 and 64 minutes (mean ± SD, 34.0 minutes ± 8.6). Temperatures of 95°C–115°C were achieved at the hook tips during thermal ablation of each lesion. To reach and maintain these temperatures, a power output ranging from 50 W at the start of the ablation to 20 W at the end of the ablation was needed. At the end of the RF procedure, temperatures higher than 50°C persisted for more than 2 minutes at the hook tips in all cases. During the RF procedures, stable impedance values between 30 and 41 {Omega} (mean, 34.4 {Omega}) were observed in all cases. Impedance ranged from 34 to 41 {Omega} (mean, 36.2 {Omega}) in the patients who underwent balloon catheter occlusion and from 30 to 37 {Omega} (mean, 31.1 {Omega}) in those who underwent gelatin sponge particle occlusion. In the patients in whom remote thermometry studies were performed, temperatures between 38°C and 42°C (mean, 40.8°C) were detected with the thermocouple placed just outside the HCC margins and between 50°C and 74°C (mean, 56.2°C) with the thermocouple just inside the margins. The latter recorded temperatures of higher than 45°C for almost 2 minutes after the end of the RF procedure. Temperatures did not differ between the patients who underwent balloon catheter occlusion and those who underwent gelatin sponge particle occlusion.

Real-time US during the RF procedure always depicted an expanding hyperechoic area with posterior acoustic shadowing involving the entire HCC nodule by the end of the procedure. Pretreatment US in the patients who underwent RF ablation 2–5 days after gelatin sponge particle occlusion showed a hyperechoic area with a peripheral hypoechoic rim at the site of the HCC. This whole area became hyperechoic after the RF procedure. The hyperechogenicity disappeared in a few days.

Hepatic angiography performed at the end of RF ablation in the 40 patients in whom HCC arterial flow was occluded by using a balloon catheter depicted complete disappearance of the tumor neovasculature and/or tumor stain in all cases (Fig 2). No hepatic arterial thrombosis occurred despite the lack of anticoagulation therapy.



View larger version (175K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2a. Single 5.4-cm-diameter HCC nodule accompanying cirrhosis in a 67-year-old man. (a) Transverse T1-weighted gradient-echo MR image (174.9/4.1, 80° flip angle) obtained with bolus injection of gadopentetate dimeglumine before RF ablation shows an enhancing HCC (short arrows) impressing on the right hepatic vein (long arrow) in hepatic segment 7. (b) Frontal hepatic angiogram obtained before RF ablation depicts the neovasculature (arrows) of the right hepatic lobe. (c) Frontal angiogram obtained during RF ablation shows the RF electrode (long arrows) inserted into the HCC nodule with the hooks deployed. The tip of the balloon catheter is positioned in the proper hepatic artery, and the balloon has been inflated with a mixture of saline solution and contrast material to occlude the hepatic artery (short arrow). Arrest of hepatic arterial flow was confirmed by injecting contrast material through the lumen of the balloon catheter. (d) On the frontal angiogram obtained at the end of RF ablation, after deflation of the balloon catheter, the HCC neovasculature is no longer visible. (e) Transverse T1-weighted gradient-echo MR image (174.9/4.1, 80° flip angle) obtained with bolus injection of gadopentetate dimeglumine 4 days after the RF procedure shows a completely nonenhancing area with a peripheral enhancing rim (arrow), due to reactive hyperemia, with the same diameter as that of the treated HCC nodule. (f) Transverse T1-weighted gradient-echo MR image (174.9/4.1, 80° flip angle) obtained with bolus injection of gadopentetate dimeglumine 1 year after the RF procedure shows a completely nonenhancing area (arrows) about 3.0 cm in diameter at the site of the treated HCC nodule. The peripheral enhancing rim is no longer visible, and the hepatic vein is no longer impressed.

 


View larger version (199K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2b. Single 5.4-cm-diameter HCC nodule accompanying cirrhosis in a 67-year-old man. (a) Transverse T1-weighted gradient-echo MR image (174.9/4.1, 80° flip angle) obtained with bolus injection of gadopentetate dimeglumine before RF ablation shows an enhancing HCC (short arrows) impressing on the right hepatic vein (long arrow) in hepatic segment 7. (b) Frontal hepatic angiogram obtained before RF ablation depicts the neovasculature (arrows) of the right hepatic lobe. (c) Frontal angiogram obtained during RF ablation shows the RF electrode (long arrows) inserted into the HCC nodule with the hooks deployed. The tip of the balloon catheter is positioned in the proper hepatic artery, and the balloon has been inflated with a mixture of saline solution and contrast material to occlude the hepatic artery (short arrow). Arrest of hepatic arterial flow was confirmed by injecting contrast material through the lumen of the balloon catheter. (d) On the frontal angiogram obtained at the end of RF ablation, after deflation of the balloon catheter, the HCC neovasculature is no longer visible. (e) Transverse T1-weighted gradient-echo MR image (174.9/4.1, 80° flip angle) obtained with bolus injection of gadopentetate dimeglumine 4 days after the RF procedure shows a completely nonenhancing area with a peripheral enhancing rim (arrow), due to reactive hyperemia, with the same diameter as that of the treated HCC nodule. (f) Transverse T1-weighted gradient-echo MR image (174.9/4.1, 80° flip angle) obtained with bolus injection of gadopentetate dimeglumine 1 year after the RF procedure shows a completely nonenhancing area (arrows) about 3.0 cm in diameter at the site of the treated HCC nodule. The peripheral enhancing rim is no longer visible, and the hepatic vein is no longer impressed.

 


View larger version (209K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2c. Single 5.4-cm-diameter HCC nodule accompanying cirrhosis in a 67-year-old man. (a) Transverse T1-weighted gradient-echo MR image (174.9/4.1, 80° flip angle) obtained with bolus injection of gadopentetate dimeglumine before RF ablation shows an enhancing HCC (short arrows) impressing on the right hepatic vein (long arrow) in hepatic segment 7. (b) Frontal hepatic angiogram obtained before RF ablation depicts the neovasculature (arrows) of the right hepatic lobe. (c) Frontal angiogram obtained during RF ablation shows the RF electrode (long arrows) inserted into the HCC nodule with the hooks deployed. The tip of the balloon catheter is positioned in the proper hepatic artery, and the balloon has been inflated with a mixture of saline solution and contrast material to occlude the hepatic artery (short arrow). Arrest of hepatic arterial flow was confirmed by injecting contrast material through the lumen of the balloon catheter. (d) On the frontal angiogram obtained at the end of RF ablation, after deflation of the balloon catheter, the HCC neovasculature is no longer visible. (e) Transverse T1-weighted gradient-echo MR image (174.9/4.1, 80° flip angle) obtained with bolus injection of gadopentetate dimeglumine 4 days after the RF procedure shows a completely nonenhancing area with a peripheral enhancing rim (arrow), due to reactive hyperemia, with the same diameter as that of the treated HCC nodule. (f) Transverse T1-weighted gradient-echo MR image (174.9/4.1, 80° flip angle) obtained with bolus injection of gadopentetate dimeglumine 1 year after the RF procedure shows a completely nonenhancing area (arrows) about 3.0 cm in diameter at the site of the treated HCC nodule. The peripheral enhancing rim is no longer visible, and the hepatic vein is no longer impressed.

 


View larger version (187K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2d. Single 5.4-cm-diameter HCC nodule accompanying cirrhosis in a 67-year-old man. (a) Transverse T1-weighted gradient-echo MR image (174.9/4.1, 80° flip angle) obtained with bolus injection of gadopentetate dimeglumine before RF ablation shows an enhancing HCC (short arrows) impressing on the right hepatic vein (long arrow) in hepatic segment 7. (b) Frontal hepatic angiogram obtained before RF ablation depicts the neovasculature (arrows) of the right hepatic lobe. (c) Frontal angiogram obtained during RF ablation shows the RF electrode (long arrows) inserted into the HCC nodule with the hooks deployed. The tip of the balloon catheter is positioned in the proper hepatic artery, and the balloon has been inflated with a mixture of saline solution and contrast material to occlude the hepatic artery (short arrow). Arrest of hepatic arterial flow was confirmed by injecting contrast material through the lumen of the balloon catheter. (d) On the frontal angiogram obtained at the end of RF ablation, after deflation of the balloon catheter, the HCC neovasculature is no longer visible. (e) Transverse T1-weighted gradient-echo MR image (174.9/4.1, 80° flip angle) obtained with bolus injection of gadopentetate dimeglumine 4 days after the RF procedure shows a completely nonenhancing area with a peripheral enhancing rim (arrow), due to reactive hyperemia, with the same diameter as that of the treated HCC nodule. (f) Transverse T1-weighted gradient-echo MR image (174.9/4.1, 80° flip angle) obtained with bolus injection of gadopentetate dimeglumine 1 year after the RF procedure shows a completely nonenhancing area (arrows) about 3.0 cm in diameter at the site of the treated HCC nodule. The peripheral enhancing rim is no longer visible, and the hepatic vein is no longer impressed.

 


View larger version (179K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2e. Single 5.4-cm-diameter HCC nodule accompanying cirrhosis in a 67-year-old man. (a) Transverse T1-weighted gradient-echo MR image (174.9/4.1, 80° flip angle) obtained with bolus injection of gadopentetate dimeglumine before RF ablation shows an enhancing HCC (short arrows) impressing on the right hepatic vein (long arrow) in hepatic segment 7. (b) Frontal hepatic angiogram obtained before RF ablation depicts the neovasculature (arrows) of the right hepatic lobe. (c) Frontal angiogram obtained during RF ablation shows the RF electrode (long arrows) inserted into the HCC nodule with the hooks deployed. The tip of the balloon catheter is positioned in the proper hepatic artery, and the balloon has been inflated with a mixture of saline solution and contrast material to occlude the hepatic artery (short arrow). Arrest of hepatic arterial flow was confirmed by injecting contrast material through the lumen of the balloon catheter. (d) On the frontal angiogram obtained at the end of RF ablation, after deflation of the balloon catheter, the HCC neovasculature is no longer visible. (e) Transverse T1-weighted gradient-echo MR image (174.9/4.1, 80° flip angle) obtained with bolus injection of gadopentetate dimeglumine 4 days after the RF procedure shows a completely nonenhancing area with a peripheral enhancing rim (arrow), due to reactive hyperemia, with the same diameter as that of the treated HCC nodule. (f) Transverse T1-weighted gradient-echo MR image (174.9/4.1, 80° flip angle) obtained with bolus injection of gadopentetate dimeglumine 1 year after the RF procedure shows a completely nonenhancing area (arrows) about 3.0 cm in diameter at the site of the treated HCC nodule. The peripheral enhancing rim is no longer visible, and the hepatic vein is no longer impressed.

 


View larger version (175K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2f. Single 5.4-cm-diameter HCC nodule accompanying cirrhosis in a 67-year-old man. (a) Transverse T1-weighted gradient-echo MR image (174.9/4.1, 80° flip angle) obtained with bolus injection of gadopentetate dimeglumine before RF ablation shows an enhancing HCC (short arrows) impressing on the right hepatic vein (long arrow) in hepatic segment 7. (b) Frontal hepatic angiogram obtained before RF ablation depicts the neovasculature (arrows) of the right hepatic lobe. (c) Frontal angiogram obtained during RF ablation shows the RF electrode (long arrows) inserted into the HCC nodule with the hooks deployed. The tip of the balloon catheter is positioned in the proper hepatic artery, and the balloon has been inflated with a mixture of saline solution and contrast material to occlude the hepatic artery (short arrow). Arrest of hepatic arterial flow was confirmed by injecting contrast material through the lumen of the balloon catheter. (d) On the frontal angiogram obtained at the end of RF ablation, after deflation of the balloon catheter, the HCC neovasculature is no longer visible. (e) Transverse T1-weighted gradient-echo MR image (174.9/4.1, 80° flip angle) obtained with bolus injection of gadopentetate dimeglumine 4 days after the RF procedure shows a completely nonenhancing area with a peripheral enhancing rim (arrow), due to reactive hyperemia, with the same diameter as that of the treated HCC nodule. (f) Transverse T1-weighted gradient-echo MR image (174.9/4.1, 80° flip angle) obtained with bolus injection of gadopentetate dimeglumine 1 year after the RF procedure shows a completely nonenhancing area (arrows) about 3.0 cm in diameter at the site of the treated HCC nodule. The peripheral enhancing rim is no longer visible, and the hepatic vein is no longer impressed.

 
Short-term Results
The mean hospital stay was 4 days (range, 2–9 days). In 56 of 62 patients, posttreatment dual-phase spiral CT depicted a well-defined nonenhancing area with a thin peripheral enhancing rim that had a shape roughly resembling that of the treated HCC nodule, for a complete response of 90% (Fig 3). In 15 of these 56 patients, complete response was confirmed at posttreatment T2-weighted MR imaging, which depicted a hypointense area with the same shape as the treated HCC nodule, which, with the exception of a thin peripheral enhancing rim, did not enhance during the gadolinium-enhanced dynamic study. The maximum diameters of these nonenhancing areas were equal to or larger than the maximum pretreatment diameters of the HCC nodules. Enhancing tissue within the nonenhanced area at the site of the treated HCC, which was indicative of partial response, persisted in six (10%) of the 62 patients, who had nodules larger than 5.5 cm in diameter. Three of these six patients underwent RF ablation after occlusion of the HCC arterial supply with a balloon catheter device; two, after gelatin sponge particle occlusion; and one, 3 days after gelatin sponge particle occlusion. In these six patients, complete response was achieved with a new RF procedure performed within 9 days after the first ablation. Therefore, in the final analysis, a total of 68 RF ablation sessions were needed to treat 62 HCC nodules. No differences in coagulative necrosis were noted between the patients who underwent balloon catheter occlusion and those who underwent gelatin sponge particle occlusion.



View larger version (164K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3a. Single 5.5-cm-diameter HCC nodule accompanying cirrhosis in a 62-year-old man. (a) Transverse, arterial phase, contrast-enhanced CT scan obtained before RF ablation shows a hyperattenuating HCC (arrows) in hepatic segment 7. (b) Transverse portal venous phase CT scan obtained before RF ablation shows a partially isoattenuating, partially hypoattenuating area (arrows) at the site of the HCC nodule. (c) Transverse arterial phase CT scan obtained 5 days after RF ablation shows a completely nonenhancing area (arrows) with the same diameter as that of the treated HCC nodule. (d) Findings on the transverse portal venous phase CT scan obtained 5 days after RF ablation confirm the completely nonenhancing area (arrows) at the site of the treated HCC nodule.

 


View larger version (147K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3b. Single 5.5-cm-diameter HCC nodule accompanying cirrhosis in a 62-year-old man. (a) Transverse, arterial phase, contrast-enhanced CT scan obtained before RF ablation shows a hyperattenuating HCC (arrows) in hepatic segment 7. (b) Transverse portal venous phase CT scan obtained before RF ablation shows a partially isoattenuating, partially hypoattenuating area (arrows) at the site of the HCC nodule. (c) Transverse arterial phase CT scan obtained 5 days after RF ablation shows a completely nonenhancing area (arrows) with the same diameter as that of the treated HCC nodule. (d) Findings on the transverse portal venous phase CT scan obtained 5 days after RF ablation confirm the completely nonenhancing area (arrows) at the site of the treated HCC nodule.

 


View larger version (152K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3c. Single 5.5-cm-diameter HCC nodule accompanying cirrhosis in a 62-year-old man. (a) Transverse, arterial phase, contrast-enhanced CT scan obtained before RF ablation shows a hyperattenuating HCC (arrows) in hepatic segment 7. (b) Transverse portal venous phase CT scan obtained before RF ablation shows a partially isoattenuating, partially hypoattenuating area (arrows) at the site of the HCC nodule. (c) Transverse arterial phase CT scan obtained 5 days after RF ablation shows a completely nonenhancing area (arrows) with the same diameter as that of the treated HCC nodule. (d) Findings on the transverse portal venous phase CT scan obtained 5 days after RF ablation confirm the completely nonenhancing area (arrows) at the site of the treated HCC nodule.

 


View larger version (134K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3d. Single 5.5-cm-diameter HCC nodule accompanying cirrhosis in a 62-year-old man. (a) Transverse, arterial phase, contrast-enhanced CT scan obtained before RF ablation shows a hyperattenuating HCC (arrows) in hepatic segment 7. (b) Transverse portal venous phase CT scan obtained before RF ablation shows a partially isoattenuating, partially hypoattenuating area (arrows) at the site of the HCC nodule. (c) Transverse arterial phase CT scan obtained 5 days after RF ablation shows a completely nonenhancing area (arrows) with the same diameter as that of the treated HCC nodule. (d) Findings on the transverse portal venous phase CT scan obtained 5 days after RF ablation confirm the completely nonenhancing area (arrows) at the site of the treated HCC nodule.

 
The {alpha}-fetoprotein levels decreased in all the patients who had elevated pretreatment values—to within the normal range in 22 patients, to 20–100 µg/L in 15, and from 1,528 to 975 µg/L in one. The mean posttreatment {alpha}-fetoprotein level was 16 µg/L (range, 12–20 µg/L), which was a significant decrease from the baseline values (P <.001).

Outcome and Long-term Follow-up
Two patients with HCC nodules measuring 4.2 cm and 5.2 cm in diameter underwent liver resection between 15 days and 3 months after RF thermal ablation; the remaining 60 patients were followed up for a mean of 12.1 months (range, 3.0–26.0 months) with radiologic procedures and {alpha}-fetoprotein assays. During the follow-up period, 49 (82%) of the 60 treated HCC nodules showed stable complete response, which manifested at contrast-enhanced spiral CT and/or MR imaging as a completely nonenhancing area with a 40%–75% reduction in maximum diameter compared with the lesion observed immediately after the RF procedure. The degree of reduction observed depended on the length of time since treatment. The remaining 11 (18%) nodules showed local progression, which manifested as enhancing tissue within or near the nonenhancing area at the site of the treated HCC; US-guided core biopsy of these nodules revealed viable cancer cells.

Of the 60 followed up patients who did not undergo liver resection, eight (13%) had local recurrence, three (5%) had both local and new intrahepatic recurrence, 18 (30%) showed new intrahepatic recurrence, and 31 (52%) remained apparently disease free. No cases of extrahepatic spread were observed. The 1-year estimate of failure risk was 19% (95% CI: 8%, 30%) for local recurrences and 45% (95% CI: 30%, 60%) for overall intrahepatic recurrences. No differences in local and new intrahepatic recurrence rates were found between the patients who underwent occlusion of the HCC arterial supply by means of a balloon catheter technique and those who underwent occlusion by means of a gelatin sponge particle technique. Histologic proof of intrahepatic recurrence was obtained in all cases with US-guided core-needle biopsy.

The serum {alpha}-fetoprotein levels rose above 500 µg/L again in three patients with local recurrence and in five patients with new intrahepatic recurrence, but the levels remained normal or between 20 and 100 µg/L in the other patients. The mean value was 28 µg/L (range, 18–44 µg/L) and remained significantly lower than the baseline values (P = .002).

Three (5%) patients died of advanced cancer, and three (5%) died of unrelated causes (ie, sudden death, heart failure, and respiratory failure). Autopsy was performed on the patient who died of respiratory failure 11 months after the RF procedure. Histopathologic examination did not demonstrate viable cancer cells in either the autopsy specimen or the surgical specimen from one of the patients who underwent liver resection, and it revealed more than 90% necrosis in the other case of resection (Fig 4). The estimated 1-year survival was 87% (95% CI: 76%, 98%).



View larger version (149K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 4. Cut surface of a resected left hepatic lobe shows massive necrosis of a 5.2-cm-diameter HCC nodule in a 52-year-old man 15 days after RF thermal ablation with a single electrode insertion following occlusion of the tumor feeding arteries by means of gelatin sponge particle injection. Five thermal lesions along the major axis of the electrode were created in 40 minutes. At the inferior margin of the treated HCC nodule (short arrows) is a small residual area of viable tumor (long arrow) infiltrating the capsule.

 
Complications
Generally, the patients tolerated the procedure well. No fatal or major complications related to the treatment occurred. Thirty-nine (63%) of the 62 patients experienced mild to moderate abdominal pain during the RF procedure; this was treated with 1,000 mg of intravenous pro-paracetamol (Pro-efferalgan; UPSA Medica, Milan, Italy). Fever (>38°C) was observed in 37 (70%) of 53 patients who underwent RF ablation after occlusion of arterial flow and treated with 500 mg of noramidopyrine (Novalgina; Hoechst Marion Roussel Spa, Milan, Italy). The nine patients who underwent a delayed RF procedure experienced fever after occlusion of the HCC feeding arteries with gelatin sponge particles but not after the RF procedure itself. Chemical acalculous cholecystitis developed in two patients who underwent the RF procedure after gelatin sponge particle occlusion and was successfully treated with antibiotics. Intimal dissection of the hepatic artery up to the celiac trunk without clinical sequelae was observed at posttreatment angiography in one patient who underwent balloon catheter occlusion.

Serum alanine transferase and serum aspartate transferase levels rose more than 50% in all patients but returned to baseline values within a week. The Child-Pugh grade of cirrhosis in five patients who underwent the RF procedure after gelatin sponge particle occlusion changed from A6 to B (four to B7 and one to B8), but it returned to the initial grade within 2 weeks. No late complications were observed.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
 
RF thermal ablation has proved to be safe and effective for the treatment of small hepatic tumors in patients who are considered to be unsuitable for surgical intervention (6–9,11,20) and recently has attracted much attention. It has some merits compared with the other percutaneous techniques: The treatment time is shorter than that with the more popular ethanol injection (21), the thermal lesions are larger than those obtained with a microwave electrode (8,11,22), and it is less expensive and easier to perform than interstitial laser photocoagulation, in which multiple fiber insertions are always required (23). However, the limited volume of coagulative necrosis obtained at each activation of the RF system and the sometimes irregular burn shape due to the proximity of large vessels that act as a heat sink have thus far prevented the wide use of RF thermal ablation for the treatment of hepatic tumors.

Results of the present study provide evidence that areas of coagulative necrosis that are much larger than those previously reported can be created if RF thermal ablation is performed in HCC nodules after occlusion of their arterial supply. The radiologic findings in the present study demonstrated that enhancing HCC ranging from 3.5 to 5.5 cm in diameter was replaced with nonenhancing tissue, indicating necrosis, after a single session with a single electrode insertion in all cases. In a previous study in which the same electrode and technique were used without occlusion of the HCC arterial supply, the maximum diameter of coagulative necrosis with a single electrode insertion was 2.5 cm (8). This 1.0–3.0-cm difference in diameter represents a dramatic increase in the volume of necrosis. In fact, with the thermal necrosis considered to be spherical (12), the volume increased from about 8.0 cm3 to 22.0–87.0 cm3; this permitted treatment, in a single session, of HCC nodules that were too large to be treated by using an RF procedure without occlusion of their arterial supply.

The considerable increase in the volume of coagulative necrosis was confirmed with histopathologic analysis, at which complete necrosis of two HCC nodules, 4.2 and 4.9 cm in diameter, and more than 90% necrosis in an HCC nodule 5.2 cm in diameter were detected. These findings were further supported by the dramatic decrease in {alpha}-fetoprotein levels, which either returned to normal or were no longer substantially elevated after treatment.

In all instances, the areas of coagulative necrosis reproduced the shape of the HCC nodules and spared the surrounding nontumorous tissue. This was observed for HCC nodules 3.5 cm in diameter, as well as for those larger than 5.0 cm and seemed to be related to the temperature gradient between the tumorous tissue and the surrounding nontumorous tissue during the RF procedure. In fact, killing temperatures were reached just inside the HCC nodule, whereas nonkilling temperatures were detected in the hepatic tissue immediately surrounding the nodule. This temperature distribution within and around the HCC nodule seems to be related to the difference in vascularization between HCC and the surrounding cirrhotic hepatic tissue. The latter has a dual blood supply and is nourished mainly by the portal vein, which provides about two-thirds of the blood flow; the hepatic artery provides the remaining one-third (24). HCC, however, is nourished mainly by the hepatic artery (16,25), with the portal vein providing a minor blood supply (25,26) and the main venous drainage (27).

Normally, blood enters through the branches of the hepatic artery into the sinusoid of the HCC nodule, and then, following a pressure gradient, it drains through rich vascular communications into the portal and/or hepatic veins (27,28). Acute occlusion of arterial flow is soon followed by a decrease in pressure within the HCC nodule, which continues to be perfused only by means of reversed portal flow and, in some cases, by small collateral arteries (25,26). Thus, although the blood flow supplying the HCC nodule is substantially impaired, changing from high to sluggish flow, the blood flow supplying the surrounding hepatic tissue is only marginally modified. This results in an almost complete lack of heat loss due to convection within the HCC nodule, whereas intact and perhaps even increased portal blood flow in the surrounding tissue acts as an efficient heat sink that prevents heat diffusion outside the HCC nodule. Therefore, the resultant necrosis selectively involves only the HCC nodule and reproduces the nodule’s shape. This phenomenon has the advantage of sparing the surrounding nonneoplastic tissue and the disadvantage of lacking control over extracapsular daughter nodules.

However, in our study, because areas of necrosis that reproduced the original tumor’s shape were obtained also in HCC nodules about 5.0 cm in diameter and killing temperatures were detected at their margins, factors in addition to the lack of convection within the HCC probably contributed to the thermal lesions being unexpectedly larger than those created by using the same parameters in vivo in completely devascularized porcine liver tissue and thus in the complete absence of convection (15). This might be explained by modifications in HCC tissue conductivity that occur after the sudden hemodynamic changes. This hypothesis is supported by the fact that during the RF procedure, after the occlusion of arterial flow, the mean impedance values in the HCC were unexpectedly substantially lower than those in the HCC tissue without occlusion of arterial blood flow (8) or in porcine liver in vivo with or without occlusion of hepatic blood flow (15). Therefore, low impedance during RF ablation may explain the unexpectedly large thermal lesions, because impedance is crucial to the size and evolution of a thermal lesion in that it reflects the tissue’s degree of hydration and ability to transfer heat (29). In fact, tissue with high impedance tends to produce smaller lesions, whereas tissue with low impedance tends to produce larger ones (29).

The persistent sluggish flow from the portal vein after arterial occlusion may ensure the persistent hydration of HCC tissue and therefore could be the cause of the low impedance detected during the RF procedure. This explanation was suggested also by the low impedance and larger-than-expected thermal lesions observed in porcine livers when the RF procedures were performed after subtotal occlusion of the hepatic veins, which lead to vascular stasis and tissue hyperhydration (15). However, the exact mechanism that underlies this finding needs further investigation, which is problematic mainly because of the lack of a suitable experimental model that can reproduce the described complex relationship between the HCC vasculature and that of the surrounding cirrhotic liver tissue.

The preferred method of occluding the HCC arterial supply was that with a balloon catheter, which helped avoid the complications related to gelatin sponge particle injection that are widely reported in the literature (30,31). Occlusion of HCC feeding arteries with gelatin sponge particles alone was the second choice when, for some reason, placement of the balloon catheter was not possible or did not completely occlude arterial flow. In these cases, the persistent ischemia induced by the gelatin sponge particle occlusion certainly may have contributed to the necrosis. However, we believe that the immediate massive necrosis observed was primarily related to the good diffusion of heat through the tissue due to the lack of heat loss with convection and to the change in tissue impedance during RF ablation. This is supported by the finding that during the RF procedure, killing temperatures were detected just inside the HCC nodule margins regardless of whether arterial supply occlusion was achieved by using a balloon catheter or gelatin sponge particles. Furthermore, complete response at imaging occurred after one ablation session in the majority of patients who underwent the RF procedure after occlusion of the HCC feeding arteries with gelatin sponge particles; this result was not achieved in HCCs by using transcatheter arterial embolization with gelatin sponge particles alone (30).

Follow-up study results confirm that RF thermal ablation after occlusion of the HCC arterial supply can result in debulking and/or complete necrosis of large tumor nodules. Drastic shrinkage of the nonenhancing area at the site of the treated HCC at repeated contrast-enhanced spiral CT and/or MR imaging, together with stable normal {alpha}-fetoprotein levels in patients with high pretreatment values have been considered to be indicative of complete necrosis (6–8,9,32). Local recurrence, the percentage of which was less than 20% in our study, might be due to the unsatisfactory diffusion of heat within the HCC nodule, as well as to the presence of extracapsular invasion or daughter nodules outside the nodule. However, most of the recurrences observed during follow-up in our study were due to new growths in hepatic segments other than the treated one. Similar findings related to probable underestimation of disease at study enrollment or to de novo carcinogenesis in the cirrhotic liver are common to all treatment modalities except liver transplantation (8,30,32–34).

RF thermal ablation after occlusion of the HCC arterial supply appears to be a safe procedure with virtually negligible side effects. In the current study, there was no lasting impairment of liver function, liver failure, or death directly caused by the procedure. However, we believe that this technique should be used to treat only HCCs larger than 3.0 cm in diameter, because the need for angiography adds to the complexity and cost of the procedure.

The RF thermal ablation procedure with an expandable electrode described in the present study could be performed equally well by using other commercially available electrodes, because the factors that lead to the creation of such large coagulative necrotic areas are primarily lack of convection and changes in tissue impedance related to occlusion of the HCC arterial supply.

The results achieved with this technique are promising for the local control of disease, but they must be evaluated with consideration of some important limitations. The lack of extensive pathologic correlations and the relatively short follow-up period could have caused an overestimation of the percentage of success and an underestimation of the rates of local recurrence, which can occur much later (6,8). In addition, the follow-up period was too short to allow meaningful differences in survival between the described RF ablation technique and other treatment modalities to emerge. Therefore, determining the real effect of this technique on survival will necessitate further studies with longer follow-up periods.

In conclusion, the lack of heat loss due to convection and the probable modifications in tumor tissue conductivity related to occlusion of the HCC arterial blood supply during a single RF ablation session with a single electrode insertion result in areas of coagulative necrosis that are larger than 5.0 cm in diameter and thus ablation of HCC that ranges from 3.5 to 5.5 cm in diameter. The nontumorous hepatic tissue surrounding the tumor was spared owing to a persistence of convection related to intact portal blood flow. For these reasons, this technique seems to be appropriate for patients with nonresectable HCC nodules accompanying cirrhosis in whom preservation of residual liver function is mandatory.


   ACKNOWLEDGMENTS
 
We thank Luigi Marini, PhD, of the Department of Medical Statistics and Biometrics of the National Cancer Institute, Milan, Italy, for the statistical analysis; Stephen T. Kee, MD, of the Department of Radiology at Stanford University Medical Center, Calif, for assistance in manuscript editing; Mary Trotter for assistance in preparing the manuscript; and Sauro Ceccarini for assistance in obtaining the images.


   FOOTNOTES
 
Abbreviations: HCC = hepatocellular carcinoma, RF = radio frequency

Author contributions: Guarantors of integrity of entire study, S.R., F.G., H.E.B., C.B.; study concepts, S.R.; study design, S.R., F.G., R.L., P.Q.; definition of intellectual content, S.R., F.G., H.E.B., C.B.; literature research, P.Q., G.D.T., A.M.; clinical studies, G.D.T., A.M., F.G., R.L., H.P.A., V.M.; data acquisition, G.D.T, A.M., C.A., F.G., R.L., H.P.A., V.M.; data analysis, S.R., F.G., R.L., H.P.A.; statistical analysis, H.P.A.; manuscript preparation and editing, S.R., R.L., H.P.A., F.F.; manuscript review, H.E.B., C.B., F.F.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 

  1. Rossi S, Fornari F, Buscarini L. Percutaneous ultrasound-guided radiofrequency electrocautery for the treatment of small hepatocellular carcinoma. J Interv Radiol 1993; 8:97-103.
  2. Rossi S, Fornari F, Paties C, Buscarini L. Thermal lesions induced by 480 KHz localized current field in guinea pig and pig livers. Tumori 1990; 76:54-57.[Medline]
  3. McGahan JP, Browning PD, Brock JM, Tesluk H. Hepatic ablation using radiofrequency electrocautery. Invest Radiol 1990; 25:267-272.[Medline]
  4. Organ LW. Electrophysiologic principles of radiofrequency lesion making. Appl Neurophysiol 1976; 39:69-76.[Medline]
  5. Cosman ER, Nashold BS, Badenbaugh P. Stereotactic radiofrequency lesion making. Appl Neurophysiol 1983; 46:160-166.[Medline]
  6. Rossi S, Di Stasi M, Buscarini E, et al. Percutaneous RF interstitial thermal ablation in the treatment of liver cancer. AJR Am J Roentgenol 1996; 167:759-768.[Abstract/Free Full Text]
  7. Solbiati L, Ierace T, Golberg SN, et al. Percutaneous US-guided radio-frequency tissue ablation of liver metastases: treatment and follow-up in 16 patients. Radiology 1997; 202:195-203.[Abstract/Free Full Text]
  8. Rossi S, Buscarini E, Garbagnati F, et al. Percutaneous treatment of small hepatic tumors by an expandable RF needle electrode. AJR Am J Roentgenol 1998; 170:1015-1022.[Abstract/Free Full Text]
  9. Curley SA, Izzo F, Delrio P, et al. Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies: results in 123 patients. Ann Surg 1999; 230:1-8.[Medline]
  10. Goldberg SN, Gazelle GS, Solbiati L, Rittman WJ, Muller PR. Radiofrequency tissue ablation: increase of lesion diameter with a perfusion electrode. Acad Radiol 1996; 3:636-644.[Medline]
  11. Solbiati L, Goldberg SN, Ierace T, et al. Hepatic metastases: percutaneous radio-frequency ablation with cooled-tip electrodes. Radiology 1997; 205:367-373.[Abstract/Free Full Text]
  12. Goldberg SN, Solbiati L, Hahn PF, et al. Large-volume tissue ablation with radio frequency by using a clustered, internally cooled electrode technique: laboratory and clinical experience in liver metastases. Radiology 1998; 209:371-379.[Abstract/Free Full Text]
  13. Goldberg SN, Hahn PF, Tanabe KK, et al. Percutaneous radiofrequency tissue ablation: does perfusion mediated tissue cooling limit coagulation necrosis?. J Vasc Interv Radiol 1998; 9:101-111.[Medline]
  14. Patterson E, Scudamore CH, Owen DA, Nagy AG, Buczkowsky AK. Radiofrequency ablation of porcine liver in vivo: effects of blood flow and treatment time on lesion size. Ann Surg 1998; 227:559-565.[Medline]
  15. Rossi S, Garbagnati F, De Francesco I, et al. Relationship between the shape and size of radiofrequency induced thermal lesions and hepatic vascularisation. Tumori 1999; 85:137-141.[Medline]
  16. Breedis C, Young G. The blood supply of neoplasms in the liver. Am J Pathol 1954; 30:969-985.
  17. Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973; 60:646-649.[Medline]
  18. Lafortune M, Madore F, Patriquin H, Breton G. Segmental anatomy of the liver: a US approach to the Couinaud nomenclature. Radiology 1991; 181:443-448.[Abstract/Free Full Text]
  19. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer 1981; 47:207-214.[Medline]
  20. Allgaier HP, Deibert P, Zuber I, Olshewski M, Blum HE. Percutaneous radiofrequency interstitial ablation of small hepatocellular carcinoma. Lancet 1999; 353:1676-1677.[Medline]
  21. Livraghi T, Goldberg SN, Lazzaroni S, Meloni F, Solbiati L, Gazelle GS. Small hepatocellular carcinoma: treatment with radio-frequency ablation versus ethanol injection. Radiology 1999; 210:655-661.[Abstract/Free Full Text]
  22. Seki T, Wakabayashi M, Nakagawa T, et al. Ultrasonically guided percutaneous microwave coagulation therapy for small hepatocellular carcinoma. Cancer 1994; 74:817-825.[Medline]
  23. Huang GT, Wang TH, Sheu JC, et al. Low-power laserthermia for the treatment of small hepatocellular carcinoma. Eur J Cancer 1991; 27:1622-1627.
  24. Lautt WW, Greenway CV. Conceptual review of the hepatic vascular bed. Hepatology 1987; 7:952-963.[Medline]
  25. Kan Z. Dynamic study of iodized oil in the liver and blood supply to hepatic tumors: an experimental investigation in several animal species. Acta Radiol Suppl 1996; 408:1-25.[Medline]
  26. Goseki N, Nosaka T, Endo M, Koike M. Nourishment of hepatocellular carcinoma though the portal blood flow with and without transcatheter arterial embolization. Cancer 1995; 76:736-742.[Medline]
  27. Ueda K, Matsui O, Kawamori Y, Nakanuma Y, Kadoya M, Yoshikawa J. Hypervascular hepatocellular carcinoma: evaluation of hemodynamics with dynamic CT during hepatic arteriography. Radiology 1998; 206:161-166.[Abstract/Free Full Text]
  28. Kanazawa S, Yasui K, Doke T, Mitogawa Y, Hiraki Y. Hepatic arteriography in patients with hepatocellular carcinoma: change in findings caused by balloon occlusion of tumor-draining hepatic veins. AJR Am J Roentgenol 1995; 165:1415-1419.[Abstract/Free Full Text]
  29. Djavan B, Zlotta A, Susani M, et al. Transperineal radiofrequency interstitial tumor ablation of the prostate: correlation of magnetic resonance imaging with histopathologic examination. Urology 1997; 50:986-993.[Medline]
  30. Bruix J, Llovet JM, Castells A, et al. Transarterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: results of a randomized trial in a single institution. Hepatology 1998; 27:1578-1583.[Medline]
  31. Bismuth H, Morino M, Sherlock D, et al. Primary treatment of hepatocellular carcinoma by arterial chemoembolization. Am J Surg 1992; 163:387-394.[Medline]
  32. Ebara M, Kita K, Sugiura N, et al. Therapeutic effect of percutaneous ethanol injection on small hepatocellular carcinoma: evaluation with CT. Radiology 1995; 195:371-377.[Abstract/Free Full Text]
  33. Belghiti J, Panis Y, Farges O, Benamou JP, Feketè F. Intrahepatic recurrences after resection of hepatocellular carcinoma complicating cirrhosis. Ann Surg 1991; 214:114-117.[Medline]
  34. Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996; 344:693-699.



This article has been cited by other articles:


Home page
 RadiologyHome page
C. T. Sofocleous, R. G. Nascimento, L. M. Petrovic, D. S. Klimstra, M. Gonen, K. T. Brown, L. A. Brody, A. M. Covey, R. H. Thornton, Y. Fong, et al.
Histopathologic and Immunohistochemical Features of Tissue Adherent to Multitined Electrodes after RF Ablation of Liver Malignancies Can Help Predict Local Tumor Progression: Initial Results
Radiology, October 1, 2008; 249(1): 364 - 374.
[Abstract] [Full Text] [PDF]

Home page
 RadiologyHome page
T. de Baere, F. Deschamps, P. Briggs, C. Dromain, V. Boige, L. Hechelhammer, M. Abdel-Rehim, A. Auperin, D. Goere, and D. Elias
Hepatic Malignancies: Percutaneous Radiofrequency Ablation during Percutaneous Portal or Hepatic Vein Occlusion
Radiology, September 1, 2008; 248(3): 1056 - 1066.
[Abstract] [Full Text] [PDF]

Home page
 RadiologyHome page
O. Seror, G. N'Kontchou, M. Ibraheem, Y. Ajavon, C. Barrucand, N. Ganne, E. Coderc, J. Claude Trinchet, M. Beaugrand, and N. Sellier
Large (>=5.0-cm) HCCs: Multipolar RF Ablation with Three Internally Cooled Bipolar Electrodes--Initial Experience in 26 Patients
Radiology, July 1, 2008; 248(1): 288 - 296.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
B.-Q. Cheng, C.-Q. Jia, C.-T. Liu, W. Fan, Q.-L. Wang, Z.-L. Zhang, and C.-H. Yi
Chemoembolization Combined With Radiofrequency Ablation for Patients With Hepatocellular Carcinoma Larger Than 3 cm: A Randomized Controlled Trial
JAMA, April 9, 2008; 299(14): 1669 - 1677.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Roentgenol.Home page
J. Lee, H. Rhim, Y. H. Jeon, H. K. Lim, W. J. Lee, D. Choi, and Y.-s. Kim
Radiofrequency Ablation of Liver Adjacent to Body of Gallbladder: Histopathologic Changes of Gallbladder Wall in a Pig Model
Am. J. Roentgenol., February 1, 2008; 190(2): 418 - 425.
[Abstract] [Full Text] [PDF]

Home page