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Vascular and Interventional Radiology |
1 From the Department of Radiology, Ospedale Civile, Via Cereda, 23, 20059 Vimercate, Italy (T.L., F.M.); the Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Mass (S.N.G.); the Department of Internal Medicine, Ospedale San Biagio, Clusone, Italy (S.L.); the Department of Radiology, Ospedale Generale, Busto Arsizio, Italy (T.I., L.S.); and the Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Mass (G.S.G.). From the 1998 RSNA scientific assembly. Received March 10, 1999; revision requested April 27; revision received June 17; accepted July 21. Supported in part by Radionics. Address reprint requests to T.L. (e-mail: lalivra@tin.it).
| Abstract |
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MATERIALS AND METHODS: One-hundred fourteen patients who were under conscious sedation or general anesthesia had 126 HCCs greater than 3.0 cm in diameter treated with RF by using an internally cooled electrode. Eighty tumors were medium (3.15.0 cm), and 46 were large (5.19.5 cm). The mean diameter for all tumors was 5.4 cm. At imaging, 75 tumors were considered noninfiltrating, and 51 were considered infiltrating.
RESULTS: Complete necrosis was attained in 60 lesions (47.6%), nearly complete (90%99%) necrosis in 40 lesions (31.7%), and partial (50%89%) necrosis in the remaining 26 lesions (20.6%). Medium and/or noninfiltrating tumors were treated successfully significantly more often than large and/or infiltrating tumors. Two major complications (death, hemorrhage requiring laparotomy) and five minor complications (self-limited hemorrhage, persistent pain) were observed. The single death was due to a break in sterile technique rather than to the RF procedure itself.
CONCLUSION: RF ablation appears to be an effective, safe, and relatively simple procedure for the treatment of medium and large HCCs.
Index terms: Hepatitis, 761.291 Liver, cirrhosis, 761.794 Liver, CT, 761.12112, 761.12115 Liver, interventional procedures, 761.1269, 761.47 Liver, US, 761.12983, 761.12985 Liver neoplasms, therapy, 761.1269, 761.323, 761.47 Radiofrequency (RF) ablation, 761.1269, 761.47
| Introduction |
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Results from a recent prospective study (9) in which PEI and RF ablation were compared in patients with small HCC demonstrated that RF resulted in a 10% increase in the number of completely ablated tumor nodules. Treatment with RF also required fewer treatment sessions than PEI. This study proposed the so-called oven effect, owing to improved heat retention during ablation of lesions surrounded by cirrhotic tissue, as an explanation for the success in achieving relatively larger amounts of induced necrosis than previously seen with other liver tumors.
On the basis of the favorable results attained in this initial study, and to take advantage of ongoing improvements in RF technique, including the development of internally cooled cluster electrodes and pulsed current application (10,11), we treated larger HCCs. The purpose of this study was to report the local therapeutic efficacy, side effects, and complications of RF ablation in the treatment of HCCs 3.1 cm or greater in diameter in patients with cirrhosis or chronic hepatitis.
| MATERIALS AND METHODS |
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Between May 1996 and August 1998, 126 HCC lesions 3.1 cm or greater in diameter in 114 consecutive patients (82 men, 32 women; mean age, 64.4 years; age range, 5386 years) with cirrhosis or chronic hepatitis were treated by using percutaneous RF therapy at two different institutions: 77 at Vimercate Hospital, Vimercate, Italy, and 37 at Busto Arsizio Hospital, Busto Arsizio, Italy. Both institutions are referral centers for percutaneous ablation procedures.
One hundred six patients were treated for a single tumor (92.9%), four for two tumors (3.5%), and four (3.5%) for three tumors (n = 126 tumors). Four patients had more than three tumors, but because tumor diameter was smaller than 3.1 cm, they were excluded from the results of this study.
One hundred patients had chronic hepatitis or Child-Pugh class A cirrhosis, and 14 had Child-Pugh class B cirrhosis. Hepatitis B surface antigen and antibody to hepatitis C were positive in 29 (25.4%) and 73 patients (64.0%), respectively. Six patients (5.3%) tested positive for both antigens. Four patients (3.5%) without evidence of viral hepatitis reported high alcohol consumption, and two (1.8%) had cirrhosis of unknown origin.
Patients with severe coagulation disorders (prothrombin activity < 40% [prothrombin time > 23 seconds], platelet count < 40,000/mL [0.04 x 109/L]), severe cirrhosis (Child-Pugh class C), or advanced neoplastic disease (ie, tumor diameter > 10 cm, extrahepatic malignancy, or lobar portal venous thrombosis) were excluded from this study. Thus, during this same time period, three patients were excluded owing to tumor location (adjacent to the hepatic hilum), 22 were excluded owing to advanced cirrhosis, and 20 were excluded owing to advanced neoplastic disease. No patients underwent cryotherapy or surgery.
Tumors were classified according to size and the appearance of tumor margins. The mean diameter for all tumors was 5.4 cm. Eighty tumors were 3.15.0 cm in diameter (medium), and 46 tumors were 5.19.5 cm in diameter (large). Seventy-five tumors had smooth, well-circumscribed margins or were surrounded by a capsule at imaging and were considered noninfiltrating. Fifty-one tumors had irregular margins, peripheral satellite tumors, local portal invasion, and/or appeared encapsulated but had extranodular growth; these tumors were classified as infiltrating.
The goal of RF therapy in patients with noninfiltrating tumors was curative (ie, complete ablation). Therefore, patients in this group who at follow-up imaging had residual areas of vital tissue deemed amenable to further treatment underwent additional RF therapy. Additional treatment was possible only when the residual vital tissue was detectable as a vascularized area at color Doppler ultrasonography (US) with or without enhancement with SH U 508A (Levovist; Schering, Berlin, Germany). The goal of RF therapy in patients with infiltrating HCC was palliative (ie, to attain the greatest amount of necrosis achievable to retard tumor growth). We recognize that the difference in treatment goals between the two types of tumors may have biased the results in favor of noninfiltrative lesions. This issue is further considered in the Discussion.
Pretreatment Diagnostic Work-up
For all patients, pretreatment work-up included gray-scale and color Doppler US examination (AU 5, Esaote, Genoa, Italy; Astro, Hitachi, Tokyo, Japan), as well as nonenhanced and dual-phase contrast materialenhanced helical computed tomography (CT; HiSpeed Advantage, GE Medical Systems, Milwaukee, Wis; Radix Turbo, Hitachi; Xpress, Toshiba Medical Systems, Tokyo, Japan). CT was performed during and after the injection of 150 mL of iopamidol (Iopamiro; Bracco, Milan, Italy) at a rate of 34 mL/sec. The entire liver was scanned twice: once beginning 20 seconds (arterial phase) and then again 60 seconds (portal phase) following the initiation of contrast material injection.
In addition, at Vimercate Hospital,
-fetoprotein and des-
-carboxy-prothrombin levels were measured before treatment in 77 patients. The diagnosis of HCC was established by means of either fine-needle biopsy or, in 56 patients, the combination of US and CT demonstrating classic imaging manifestations of this tumor and an abnormal
-fetoprotein level (>200 ng/mL [200 µg/L]) in 43 patients or des-
-carboxy-prothrombin level in 33 patients. In all patients, the following serum test results were checked before treatment and 24 and 48 hours, 7 days, and 1 month after treatment: transaminase, alkaline phosphatase, bilirubin, electrolyte, creatinine, hemoglobin, fibrinogen, and haptoglobin levels; prothrombin activity; and blood cell count.
Technique
Treatment was performed with the use of conscious sedation, analgesia with assisted ventilation (ie, oxygen given by mask with manual ventilation), or general anesthesia. In cases in which treatment was anticipated to require only one or two electrode insertions (ie, solitary lesions < 4.0 cm in diameter), treatment was performed with the use of conscious sedation with 0.5 mg of atropine sulfate (Atropina; SALF, Bergamo, Italy) administered intramuscularly, one-third drop of diazepam (Ansiolin; Doppel, Piacenza, Italy) administered orally per kilogram of body weight, 2.5 mg of droperidol (Sintodian; Farmitalia, Milan, Italy) administered intravenously, 30 mg of ketorolac tromethamine (Lixidol; Roche, Milan, Italy) administered intravenously 2 hours before treatment, and 200 mg of tramadol hydrochloride (Fortradol; Bayer, Milan, Italy) administered intravenously 30 minutes before treatment, or with administration of analgesia with assisted ventilation after the administration of propofol (Diprivan; Zeneca, Genoa, Italy). In patients treated with the use of either conscious sedation or analgesia with assisted ventilation, local anesthesia was achieved by using 5 mL of 2% xylocaine (Xilocaina, SALF).
Vital signs were continuously monitored during and for 1 hour following the procedure. When a tumor was more than 4.0 cm in diameter, multiple tumors were to be treated, or the patient was particularly anxious, treatment was performed with the use of general anesthesia with endotracheal intubation and mechanical ventilation. This had the additional advantage of allowing temporary suspension of respiration with controlled pulmonary inflation, as necessary, to facilitate electrode placement.
RF ablation was performed with real-time US guidance (AU 5) by using a 3.5-MHz probe (CA B411, Hitachi). A guide device incorporated into the US probe was used for electrode placement. After cleansing of the skin with iodized alcohol (Braunol; Braun Surgical, Milan, Italy), which also served as contact medium, the most appropriate approach for electrode insertion was selected. For lesions located in the right lobe, an intercostal approach with the patient in the left lateral decubitus position generally was preferred. For lesions located in the left lobe, a subcostal approach was used most often.
Two types of 20-cm-long, 18-gauge internally cooled RF electrodes (Radionics, Burlington, Mass) were used, depending on the size and location of the tumor. For all tumors 3.14.0 cm in diameter, a single electrode with 3.0 or 4.0 cm of exposed metallic tip was used. In these cases, we attempted to place the electrode into the center of the lesion. For tumors more than 4.0 cm in diameter, a triple electrode cluster with individual electrodes spaced 5 mm apart generally was used. However, in some cases the cluster electrode could not be inserted owing to a narrow intercostal space or because a very oblique subcostal approach was required. These tumors were treated with two to four insertions of a single electrode.
Grounding was achieved by attaching two dispersive pads, each with a surface area greater than 400 cm2, to the patient's thighs. The RF electrodes were attached to a 500-kHz RF generator (series CC-1; Radionics) capable of producing 200 W of power. During the procedure, a thermocouple embedded within the electrode tip continuously measured local tissue temperature. Tissue impedance was monitored by using circuitry incorporated within the generator. A peristaltic pump (Watson-Marlow, Medford, Mass) was used to infuse 0°C normal saline solution into the lumen of the electrodes at a rate sufficient to maintain a tip temperature of 20°25°C. No more than 3 L of saline solution was required for any patient.
During RF application, generator output was monitored constantly and adjusted to apply maximum current without causing impedance rises of more than approximately 10
. As RF energy was applied to the treatment probes, a hyperechoic focus developed around the uninsulated portion of the electrodes. This was attributed to tissue vaporization and cavitation. The area of increased echogenicity was round, most often progressively increased in size over the course of ablation, and generally enveloped the entire tumor with variable extension into the surrounding liver by the end of treatment. Hyperechoic microbubbles were often seen escaping into the hepatic veins during RF application. In some cases, the hyperechoic focus did not develop progressively but appeared rather suddenly and was accompanied with an audible popping sound emanating from the liver.
The appearance and progression of hyperechogenicity was used to guide the duration of therapy. RF was applied until the tumor appeared completely hyperechoic, the hyperechoic focus did not increase in size for several minutes, or both. Furthermore, in cases in which multiple electrode insertions were required, each subsequent electrode placement was directed to an area of the tumor where hyperechogenicity was not evident. In some cases, however, hyperechogenicity obscured the deeper portions of the tumor and made repositioning of the RF electrode difficult. Additional US imaging was not performed after the end of each treatment session.
Each application of RF energy lasted 812 minutes, and in all cases the entire treatment session was less than 1 hour. After RF therapy, patients were hospitalized for 2 days, unless complications necessitated longer hospitalization. Patients were hospitalized largely owing to the limited experience with the treatment of large tumors in patients with cirrhosis, in addition to conformity with established practice patterns at the two institutions where the procedures were performed. Similar procedures have been performed elsewhere with outpatients.
Assessment of Therapeutic Efficacy
To evaluate response to RF therapy, contrast-enhanced CT, with the same parameters as at pretreatment scanning, was performed on the day following treatment to check the short-term effects, at 1 month after the procedure, and every 45 months thereafter. All follow-up CT scans were interpreted by two investigators from each institution (T.L., F.M., T.I., L.S.) who were unaware of the details of subsequent follow-up imaging studies. In all cases, a consensus of the readers was used to judge treatment efficacy. Follow-up was 530 months (mean, 10.2 months).
Tumor necrosis was considered complete when no foci of enhancement were seen within the tumor or at its periphery on CT scans obtained at least 5 months after treatment. When residual tumor enhancement was detected at follow-up imaging, we attempted to estimate whether the volume of tumor necrosis was less than or greater than 90% of the original tumor volume. Results from prior studies (3,12) have confirmed the utility of CT imaging in distinguishing between adequately and incompletely treated tumor, as necrotic tissue does not enhance following administration of contrast material.
At Vimercate Hospital,
-fetoprotein and des-
-carboxy-prothrombin assays were performed 1 month and subsequently every 45 months after treatment. However,
-fetoprotein and des-
-carboxy-prothrombin levels were not used to assess treatment efficacy because they have been observed to normalize when CT scans demonstrate residual viable tissue, likely owing to nearly complete necrosis of tumor tissue, or they may rise when CT shows complete necrosis owing to intra- or extrahepatic lesions that are below the threshold for detection.
Statistical Analysis
To investigate the effect of both tumor size (medium vs large) and morphology (infiltrating vs noninfiltrating) on treatment efficacy, multidimensional contingency table analysis was performed by using the Cochran-Mantel-Haenszel test. The effect of tumor size on treatment efficacy, controlling for tumor morphology, and the effect of tumor morphology on treatment efficacy, controlling for tumor size, were each evaluated. The Breslow-Day statistic was used to test for homogeneity of effect across each of the controlling factors and thus permitted an analysis of the overall effect of tumor size and tumor morphology. Two sets of comparisons were performed: (a) 100% versus less than 100% necrosis and (b) necrosis of 90% or more versus necrosis less than 90%. For all comparisons, significance was at the .05 level.
| RESULTS |
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-fetoprotein levels normalized (<20 ng/mL [20 µg/L]) in 15 of 43 patients, decreased in 20 patients, and increased in eight patients. Des-
-carboxy-prothrombin levels normalized in 20 of 33 patients, decreased in 10 patients, and increased in three patients.
Imaging Findings
A rim of hyperattenuation surrounding the region of coagulated tumor was apparent in the majority of cases during the portal phase of contrast enhancement on CT scans obtained 24 hours after RF treatment (Fig 3b). This was attributed to reactive hyperemia rather than residual viable tumor and disappeared progressively on subsequent follow-up studies. Thickening of the hepatic capsule was sometimes observed on CT scans obtained 1 month after ablation and beyond, particularly when the tumor was located close to the surface of the liver. This finding also progressively disappeared on subsequent follow-up studies.
Immediately following RF therapy, treated areas of tumor appeared as areas of hypoattenuation relative to both surrounding liver and residual tumor, if present. However, tumor size was unchanged relative to pretreatment tumor size, regardless of treatment response. On subsequent follow-up CT scans, areas of successfully treated tumor either remained unchanged in size or diminished at unpredictable rates.
Although the diameter of the hyperechoic focus seen during treatment was used to guide the duration of RF application, and grossly corresponded to the diameter of necrosis demonstrated at CT, conventional US was not used for the evaluation of therapeutic response. This is principally because of the heterogeneous and variable extent of hyperechogenicity observed after treatment. An additional finding often detected was that of a hyperechoic line corresponding to the electrode track during treatment (Figs 1b, 3c).
Side Effects
The majority of patients treated with the use of sedation or analgesia had mild or moderate pain during the procedure. This disappeared immediately following the cessation of RF application. However, in three of 114 patients, RF application had to be interrupted temporarily because of severe pain. In these cases, propofol and additional analgesia with assisted ventilation were administered to complete the procedure. When multiple insertions were performed, some patients reported slight discomfort in the right hypochondrium for 12 days and hyperpyrexia for several days following treatment.
In the majority of patients, a small asymptomatic right pleural effusion that lasted for less than 1 month was observed. In two (1.8%) of 114 patients, a moderate-to-large pleural effusion was documented at 1 month; this resolved by the 56-month follow-up CT.
In the majority of patients, transaminase levels increased two to seven times over baseline during the first 3 days following therapy. Moreover, a slight increase in leukocytes and bilirubin and a decrease in platelets and haptoglobin were observed. All of these test results returned to baseline levels by 7 days following RF ablation. No significant changes in other test results were observed.
Complications
Major complications.One 55-year-old obese patient with diabetes and two infiltrating HCC tumors of 7.0- and 4.5-cm diameter died (0.8%). On day 3 after the procedure, this patient had shock without hyperpyrexia or leukocytosis. US documented a small amount of fluid, and paracentesis yielded purulent material due to Staphylococcus aureus peritonitis. During the following days, the patient developed multiorgan failure and subsequently died 8 days after the procedure, despite massive antibiotic treatment and intensive care.
Given a lack of evidence for infection in the liver and adequate treatment of the tumor, this complication was attributed to a break in sterile technique and not to the application of RF per se. As a result of this complication, however, antibiotic prophylaxis with 1,000 mg of ceftriaxone sodium (Rocephin, Roche) is currently administered to all patients.
One patient with a superficially located tumor had intraperitoneal hemorrhage on the day of the procedure and required laparotomy. This patient developed strong hiccups secondary to insufficient diaphragmatic paralysis during general anesthesia. As a result, the cluster electrode became malpositioned during the procedure. This, in turn, resulted in tearing of the tumor and the hepatic capsule.
Minor complications.Two (1.8%) of 114 patients developed self-limited intraperitoneal hemorrhage (the appearance of peritoneal effusion with an associated 34 g/dL decrease in serum hemoglobin). These patients did not require blood transfusion or other interventions.
Three (2.6%) of 114 patients, all with superficially located tumors, complained of pain and required nonsteroidal analgesics for 23 days following treatment. None of these complications required further treatment, although hospital discharge was delayed.
| DISCUSSION |
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Our success rate in achieving complete tumor necrosis was lower than has been reported with smaller HCC (ie, 90% [9]). Our data also suggest that tumor size, controlling for tumor morphology, and morphology, controlling for tumor size, are important determinants of treatment success. The greatest success rate was achieved in noninfiltrating tumors 3.15.0 cm in diameter; RF therapy resulted in complete necrosis in 71% of cases and nearly complete necrosis (90%99%) in 24%. Complete necrosis was achieved significantly less frequently in tumors that were more than 5.0 cm in diameter, infiltrating, or both. However, even in these lesions, complete or nearly complete necrosis was achieved in the majority of cases.
Furthermore, it is important to note that small residual foci of untreated or locally recurrent tumor were not targeted for repeat treatment when the tumor was infiltrating, whereas similar areas generally were re-treated when the tumor was noninfiltrating. This may have biased our results in favor of noninfiltrating tumors and likely accounts for some of the difference in local control rates. In the future, it may be possible to increase the rates of complete necrosis if small foci of residual tumor are either more readily detected or more aggressively re-treated. However, with respect to prognostic improvement, 100% and 90%99% necrosis are probably similar, and it is important to note that no other therapy is more effective than RF therapy for the treatment of large infiltrating HCC (3,6,8).
In comparison with the other currently available percutaneous thermal therapies for HCC, RF appears to have several advantages. RF can create larger volumes of tumor necrosis in a shorter period of time (68) than either laser or microwave therapy. In addition, equipment used for RF ablation is less expensive than either laser or microwave equipment.
The results of RF therapy appear to be roughly comparable to those of PEI, although it is difficult to compare the results of this series with those obtained with PEI. PEI has been reported to result in complete necrosis in 70%75% of HCC tumors 35 cm in diameter (1,12,13). However, treatment of these tumors with PEI generally requires multiple outpatient treatment sessions, whereas RF ablation usually can be accomplished in a single treatment session during a short hospitalization. In a series of HCC tumors larger than 5 cm that were treated with single-session PEI performed with the use of general anesthesia (3), complete necrosis was achieved in 58% of noninfiltrating tumors but in no infiltrating tumors. In these patients, treatment duration is similar to that required for RF, but side effects, complications, and length of hospitalization are greater (3).
An additional advantage of RF therapy over PEI relates to procedural complexity. To destroy medium-sized tumors by using PEI, the physician must carefully plan multiple treatment sessions and needle insertions to ensure that ethanol has been distributed throughout the entire volume of tumor to be treated (1). On the other hand, RF therapy needs only one or two insertions. Furthermore, our success rates may be somewhat conservative, since at the beginning of the study we attempted to treat all lesions by using only one RF probe insertion. This generally was insufficient in tumors larger than 5.0 cm.
RF therapy also appears to be more effective than conventional transarterial chemoembolization. In multiple lesions, when conventional nonsegmental transarterial chemoembolization is used, complete necrosis can be achieved in 15%35% (14,15). This is considerably lower than results attained with RF. Moreover, the side effects and the long-term impairment of liver function associated with transarterial chemoembolization (16,17) further support the use of RF therapy. In medium-sized tumor, the results of RF therapy appear to be roughly comparable to those of segmental transarterial chemoembolization (18).
On the basis of prior experience treating small HCC, we described the "oven effect" (9), whereby cirrhotic liver surrounding individual HCC nodules acts as a thermal insulator that increases tissue heating during RF therapy. The results of this study further support the importance of this effect. In several cases, we were able to treat noninfiltrating tumors in a single treatment session. These tumors, if located in normal liver, ordinarily would be difficult to treat without using multiple electrodes, multiple treatment sessions, or both.
The oven effect may also partially explain our limited success in treating satellite lesions (Fig 4). These nodules remain a limitation for RF ablation, despite continued technical improvements. We believe that peritumoral fibrotic tissue that is interposed between the main tumor and satellite lesions may limit heat diffusion from the tumor center to the satellites. Regardless of the mechanism, however, these lesions are much more difficult to treat successfully with RF. Longer follow-up will be required to determine the prognostic improvement, if any, that results from treatment of the central tumor alone.
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The other major complication, massive bleeding from the liver capsule, was related to insufficient anesthesia. This patient had severe hiccups that led to erratic diaphragmatic movement during electrode placement. As a result, the tumor and liver capsule were lacerated. In retrospect, the procedure should have been temporarily halted until the patient's hiccups were better controlled.
The rate of minor complications and side effects was also acceptably low, especially given the size of the lesions treated and the overall medical condition of the patients. Leukocytosis can be attributed to inflammatory phenomena connected with repair of the tissue. Increase in bilirubin and decrease in haptoglobin and platelets probably are attributable to initial intravascular hemolysis and microhemorrhage. Transient pleural effusions are likely related to irritation of the liver capsule and diaphragm.
It is important to point out that several tumors near the hepatic capsule, gallbladder, and major blood vessels were successfully treated without complications. Previously, we and others have suggested that hepatic metastases in close proximity to these structures either should not or could not be treated successfully (19). It is possible that differences in heat conduction between cirrhotic liver and normal liver generally seen in patients with metastases also accounts for these differences. Thus, the oven effect not only promotes complete tumor destruction but also may protect surrounding structures. In addition, unlike metastases, in which a 510-mm rim of normal liver around the tumor must be treated, with HCC it is generally sufficient to treat just the tumor itself.
In conclusion, percutaneous RF ablation appears to be an effective, safe, and relatively simple procedure for the treatment of HCC lesions 3.1 cm or greater in diameter in patients with cirrhosis or chronic hepatitis. In comparison with PEI, the principal alternative, RF appears easier to perform and capable of achieving complete tumor necrosis in fewer treatment sessions compared with multisession PEI or with fewer complications compared with single-session PEI. We currently prefer to use RF rather than PEI when treating infiltrating and noninfiltrating medium HCC, infiltrating large HCC, and noninfiltrating large HCC in patients with risk factors for complications with single-session PEI (ie, marked portal hypertension, esophageal varices at risk of bleeding, Child-Pugh class B cirrhosis, chronic renal insufficiency). In noninfiltrating large HCC in patients without these risk factors, a higher rate of complete ablation probably will be achieved by performing more insertions than used in this study.
| Footnotes |
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Author contributions: Guarantors of integrity of entire study, T.L., G.S.G., L.S.; study concepts, T.L.; study design, T.L., S.L., F.M., L.S.; definition of intellectual content, T.L.; literature research, T.L.; clinical studies, T.L., S.L., F.M., L.S., T.I.; 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.
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V. W.-T. Lam, K. K. Ng, K. S.-H. Chok, T.-T. Cheung, J. Yuen, H. Tung, W.-K. Tso, S.-T. Fan, and R. T. P. Poon Incomplete Ablation After Radiofrequency Ablation of Hepatocellular Carcinoma: Analysis of Risk Factors and Prognostic Factors Ann. Surg. Oncol., March 1, 2008; 15(3): 782 - 790. [Abstract] [Full Text] [PDF] |
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K. Numata, M. Morimoto, T. Ogura, K. Sugimori, S. Takebayashi, M. Okada, and K. Tanaka Ablation Therapy Guided by Contrast-Enhanced Sonography with Sonazoid for Hepatocellular Carcinoma Lesions Not Detected by Conventional Sonography J. Ultrasound Med., March 1, 2008; 27(3): 395 - 406. [Abstract] [Full Text] [PDF] |
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S. N. Wong, C.-J. Lin, C.-C. Lin, W.-T. Chen, I. H. Y. Cua, and S.-M. Lin Combined Percutaneous Radiofrequency Ablation and Ethanol Injection for Hepatocellular Carcinoma in High-Risk Locations Am. J. Roentgenol., March 1, 2008; 190(3): W187 - W195. [Abstract] [Full Text] [PDF] |
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M NOMURA, K YAMAKADO, Y NOMOTO, A NAKATSUKA, N II, H TAKAKI, Y YAMASHITA, and K TAKEDA Complications after lung radiofrequency ablation: risk factors for lung inflammation Br. J. Radiol., March 1, 2008; 81(963): 244 - 249. [Abstract] [Full Text] [PDF] |
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M.-h. Park, H. Rhim, Y.-s. Kim, D. Choi, H. K. Lim, and W. J. Lee Spectrum of CT Findings after Radiofrequency Ablation of Hepatic Tumors RadioGraphics, March 1, 2008; 28(2): 379 - 390. [Abstract] [Full Text] [PDF] |
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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] |
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M. R. Khan, R. T. P. Poon, K. K. Ng, A. C. Chan, J. Yuen, H. Tung, J. Tsang, and S. T. Fan Comparison of Percutaneous and Surgical Approaches for Radiofrequency Ablation of Small and Medium Hepatocellular Carcinoma Arch Surg, December 1, 2007; 142(12): 1136 - 1143. [Abstract] [Full Text] [PDF] |
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D. Pandey, K.-H. Lee, C.-T. Wai, G. Wagholikar, and K.-C. Tan Long Term Outcome and Prognostic Factors for Large Hepatocellular Carcinoma (10 cm or more) after Surgical Resection Ann. Surg. Oncol., October 1, 2007; 14(10): 2817 - 2823. [Abstract] [Full Text] [PDF] |
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C. T. Sofocleous, R. G. Nascimento, M. Gonen, M. Theodoulou, A. M. Covey, L. A. Brody, S. M. Solomon, R. Thornton, Y. Fong, G. I. Getrajdman, et al. Radiofrequency Ablation in the Management of Liver Metastases from Breast Cancer Am. J. Roentgenol., October 1, 2007; 189(4): 883 - 889. [Abstract] [Full Text] [PDF] |
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A. Hakime, A. Hines-Peralta, H. Peddi, M. B. Atkins, V. P. Sukhatme, S. Signoretti, M. Regan, and S. N. Goldberg Combination of Radiofrequency Ablation with Antiangiogenic Therapy for Tumor Ablation Efficacy: Study in Mice Radiology, August 1, 2007; 244(2): 464 - 470. [Abstract] [Full Text] [PDF] |
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Y.-J. Zhang, H.-H. Liang, M.-S. Chen, R.-P. Guo, J.-Q. Li, Y. Zheng, Y.-Q. Zhang, and W. Y. Lau Hepatocellular Carcinoma Treated with Radiofrequency Ablation with or without Ethanol Injection: A Prospective Randomized Trial Radiology, August 1, 2007; 244(2): 599 - 607. [Abstract] [Full Text] [PDF] |
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H. W. Head, G. D. Dodd III, N. C. Dalrymple, S. R. Prasad, F. M. El-Merhi, M. W. Freckleton, and L. G. Hubbard Percutaneous Radiofrequency Ablation of Hepatic Tumors against the Diaphragm: Frequency of Diaphragmatic Injury Radiology, June 1, 2007; 243(3): 877 - 884. [Abstract] [Full Text] [PDF] |
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S.-Y. Chiou, J.-B. Liu, and L. Needleman Current Status of Sonographically Guided Radiofrequency Ablation Techniques J. Ultrasound Med., April 1, 2007; 26(4): 487 - 499. [Abstract] [Full Text] [PDF] |
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C. J. Simon, D. E. Dupuy, T. A. DiPetrillo, H. P. Safran, C. A. Grieco, T. Ng, and W. W. Mayo-Smith Pulmonary Radiofrequency Ablation: Long-term Safety and Efficacy in 153 Patients Radiology, April 1, 2007; 243(1): 268 - 275. [Abstract] [Full Text] [PDF] |
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M. Kuang, M. D. Lu, X. Y. Xie, H. X. Xu, L. Q. Mo, G. J. Liu, Z. F. Xu, Y. L. Zheng, and J. Y. Liang Liver Cancer: Increased Microwave Delivery to Ablation Zone with Cooled-Shaft Antenna--Experimental and Clinical Studies Radiology, March 1, 2007; 242(3): 914 - 924. [Abstract] [Full Text] [PDF] |
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S. A. Solazzo, M. Ahmed, Z. Liu, A. U. Hines-Peralta, and S. N. Goldberg High-Power Generator for Radiofrequency Ablation: Larger Electrodes and Pulsing Algorithms in Bovine ex Vivo and Porcine in Vivo Settings Radiology, March 1, 2007; 242(3): 743 - 750. [Abstract] [Full Text] [PDF] |
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T. Nakazawa, S. Kokubu, A. Shibuya, K. Ono, M. Watanabe, H. Hidaka, T. Tsuchihashi, and K. Saigenji Radiofrequency Ablation of Hepatocellular Carcinoma: Correlation Between Local Tumor Progression After Ablation and Ablative Margin Am. J. Roentgenol., February 1, 2007; 188(2): 480 - 488. [Abstract] [Full Text] [PDF] |
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Y. Minami, M. Kudo, H. Chung, T. Kawasaki, Y. Yagyu, T. Shimono, and H. Shiozaki Contrast Harmonic Sonography-Guided Radiofrequency Ablation Therapy Versus B-Mode Sonography in Hepatocellular Carcinoma: Prospective Randomized Controlled Trial Am. J. Roentgenol., February 1, 2007; 188(2): 489 - 494. [Abstract] [Full Text] [PDF] |
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C. J. Simon, D. E. Dupuy, D. A. Iannitti, D. S. K. Lu, N. C. Yu, B. I. Aswad, R. W. Busuttil, and C. Lassman Intraoperative Triple Antenna Hepatic Microwave Ablation Am. J. Roentgenol., October 1, 2006; 187(4): W333 - W340. [Abstract] [Full Text] [PDF] |
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A. Hines-Peralta, V. Sukhatme, M. Regan, S. Signoretti, Z.-j. Liu, and S. N. Goldberg Improved Tumor Destruction with Arsenic Trioxide and Radiofrequency Ablation in Three Animal Models Radiology, July 1, 2006; 240(1): 82 - 89. [Abstract] [Full Text] [PDF] |
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F. F. Amersi, A. McElrath-Garza, A. Ahmad, T. Zogakis, D. P. Allegra, R. Krasne, and A. J. Bilchik Long-term Survival After Radiofrequency Ablation of Complex Unresectable Liver Tumors Arch Surg, June 1, 2006; 141(6): 581 - 588. [Abstract] [Full Text] [PDF] |
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P. F. Laeseke, L. A. Sampson, C. L. Brace, T. C. Winter III, J. P. Fine, and F. T. Lee Jr. Unintended thermal injuries from radiofrequency ablation: protection with 5% dextrose in water. Am. J. Roentgenol., May 1, 2006; 186(5 Suppl): S249 - S254. [Abstract] [Full Text] [PDF] |
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Y. K. Kim, C. S. Kim, G. H. Chung, Y. M. Han, S. Y. Lee, G. Y. Jin, and J. M. Lee Radiofrequency ablation of hepatocellular carcinoma in patients with decompensated cirrhosis: evaluation of therapeutic efficacy and safety. Am. J. Roentgenol., May 1, 2006; 186(5 Suppl): S261 - S268. [Abstract] [Full Text] [PDF] |
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Y. K. Cho, H. Rhim, Y. S. Ahn, M. Y. Kim, and H. K. Lim Percutaneous radiofrequency ablation therapy of hepatocellular carcinoma using multitined expandable electrodes: comparison of subcapsular and nonsubcapsular tumors. Am. J. Roentgenol., May 1, 2006; 186(5 Suppl): S269 - S274. [Abstract] [Full Text] [PDF] |
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W. Yang, M. H. Chen, S. S. Yin, K. Yan, W. Gao, Y. B. Wang, L. Huo, X. P. Zhang, and B. C. Xing Radiofrequency ablation of recurrent hepatocellular carcinoma after hepatectomy: therapeutic efficacy on early- and late-phase recurrence. Am. J. Roentgenol., May 1, 2006; 186(5 Suppl): S275 - S283. [Abstract] [Full Text] [PDF] |
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P. Cabassa, F. Donato, F. Simeone, L. Grazioli, and L. Romanini Radiofrequency ablation of hepatocellular carcinoma: long-term experience with expandable needle electrodes. Am. J. Roentgenol., May 1, 2006; 186(5 Suppl): S316 - S321. [Abstract] [Full Text] [PDF] |
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S. H. Kim, H. K. Lim, D. Choi, W. J. Lee, S. H. Kim, M. J. Kim, C. K. Kim, Y. H. Jeon, J. M. Lee, and H. Rhim Percutaneous radiofrequency ablation of hepatocellular carcinoma: effect of histologic grade on therapeutic results. Am. J. Roentgenol., May 1, 2006; 186(5 Suppl): S327 - S333. [Abstract] [Full Text] [PDF] |
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A. U. Hines-Peralta, N. Pirani, P. Clegg, N. Cronin, T. P. Ryan, Z. Liu, and S. N. Goldberg Microwave Ablation: Results with a 2.45-GHz Applicator in ex Vivo Bovine and in Vivo Porcine Liver Radiology, April 1, 2006; 239(1): 94 - 102. [Abstract] [Full Text] [PDF] |
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N. C. Yu, D. S. K. Lu, S. S. Raman, D. E. Dupuy, C. J. Simon, C. Lassman, B. I. Aswad, D. Ianniti, and R. W. Busuttil Hepatocellular Carcinoma: Microwave Ablation with Multiple Straight and Loop Antenna Clusters--Pilot Comparison with Pathologic Findings Radiology, April 1, 2006; 239(1): 269 - 275. [Abstract] [Full Text] [PDF] |
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S. Clasen, D. Schmidt, A. Boss, K. Dietz, S. M. Krober, C. D. Claussen, and P. L. Pereira Multipolar Radiofrequency Ablation with Internally Cooled Electrodes: Experimental Study in ex Vivo Bovine Liver with Mathematic Modeling Radiology, March 1, 2006; 238(3): 881 - 890. [Abstract] [Full Text] [PDF] |
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T. Shibata, T. Shibata, Y. Maetani, H. Isoda, and M. Hiraoka Radiofrequency Ablation for Small Hepatocellular Carcinoma: Prospective Comparison of Internally Cooled Electrode and Expandable Electrode Radiology, January 1, 2006; 238(1): 346 - 353. [Abstract] [Full Text] [PDF] |
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J. R. Haaga, A. A. Exner, Y. Wang, N. T. Stowe, and P. J. Tarcha Combined Tumor Therapy by Using Radiofrequency Ablation and 5-FU-Laden Polymer Implants: Evaluation in Rats and Rabbits Radiology, December 1, 2005; 237(3): 911 - 918. [Abstract] [Full Text] [PDF] |
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H. P. Clark, W. F. Carson, P. V. Kavanagh, C. P. H. Ho, P. Shen, and R. J. Zagoria Staging and Current Treatment of Hepatocellular Carcinoma RadioGraphics, October 1, 2005; 25(suppl_1): S3 - S23. [Abstract] [Full Text] [PDF] |
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M. Akahane, H. Koga, N. Kato, H. Yamada, K. Uozumi, R. Tateishi, T. Teratani, S. Shiina, and K. Ohtomo Complications of Percutaneous Radiofrequency Ablation for Hepato-cellular Carcinoma: Imaging Spectrum and Management RadioGraphics, October 1, 2005; 25(suppl_1): S57 - S68. [Abstract] [Full Text] [PDF] |
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S. A. Solazzo, Z. Liu, S. M. Lobo, M. Ahmed, A. U. Hines-Peralta, R. E. Lenkinski, and S. N. Goldberg Radiofrequency Ablation: Importance of Background Tissue Electrical Conductivity--An Agar Phantom and Computer Modeling Study Radiology, August 1, 2005; 236(2): 495 - 502. [Abstract] [Full Text] [PDF] |
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G. D. Dodd III, D. Napier, J. D. Schoolfield, and L. Hubbard Percutaneous Radiofrequency Ablation of Hepatic Tumors: Postablation Syndrome Am. J. Roentgenol., July 1, 2005; 185(1): 51 - 57. [Abstract] [Full Text] [PDF] |
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M. Ahmed, Z. Liu, A. N. Lukyanov, S. Signoretti, C. Horkan, W. L. Monsky, V. P. Torchilin, and S. N. Goldberg Combination Radiofrequency Ablation with Intratumoral Liposomal Doxorubicin: Effect on Drug Accumulation and Coagulation in Multiple Tissues and Tumor Types in Animals Radiology, May 1, 2005; 235(2): 469 - 477. [Abstract] [Full Text] [PDF] |
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C. Horkan, K. Dalal, J. A. Coderre, J. L. Kiger, D. E. Dupuy, S. Signoretti, E. F. Halpern, and S. N. Goldberg Reduced Tumor Growth with Combined Radiofrequency Ablation and Radiation Therapy in a Rat Breast Tumor Model Radiology, April 1, 2005; 235(1): 81 - 88. [Abstract] [Full Text] [PDF] |
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P. Liang, B. Dong, X. Yu, D. Yu, Y. Wang, L. Feng, and Q. Xiao Prognostic Factors for Survival in Patients with Hepatocellular Carcinoma after Percutaneous Microwave Ablation Radiology, April 1, 2005; 235(1): 299 - 307. [Abstract] [Full Text] [PDF] |
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H. Dossing, F. N. Bennedbaek, and L. Hegedus Effect of ultrasound-guided interstitial laser photocoagulation on benign solitary solid cold thyroid nodules - a randomised study Eur. J. Endocrinol., March 1, 2005; 152(3): 341 - 345. [Abstract] [Full Text] [PDF] |
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M. Morimoto, A. Nozawa, K. Numata, K. Shirato, K. Sugimori, A. Kokawa, N. Tomita, T. Saitou, Y. Nakatani, T. Imada, et al. Evaluation Using Contrast-Enhanced Harmonic Gray Scale Sonography After Radio Frequency Ablation of Small Hepatocellular Carcinoma: Sonographic-Histopathologic Correlation J. Ultrasound Med., March 1, 2005; 24(3): 273 - 283. [Abstract] [Full Text] [PDF] |
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A Grieco, M Pompili, G Caminiti, L Miele, M Covino, B Alfei, G L Rapaccini, and G Gasbarrini Prognostic factors for survival in patients with early-intermediate hepatocellular carcinoma undergoing non-surgical therapy: comparison of Okuda, CLIP, and BCLC staging systems in a single Italian centre Gut, March 1, 2005; 54(3): 411 - 418. [Abstract] [Full Text] [PDF] |
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T. D. Atwell, D. J. Brandhagen, J. W. Charboneau, D. M. Nagorney, M. R. Callstrom, and M. A. Farrell Successful Treatment of Hepatocellular Adenoma with Percutaneous Radiofrequency Ablation Am. J. Roentgenol., March 1, 2005; 184(3): 828 - 831. [Abstract] [Full Text] [PDF] |
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D. S. K. Lu, N. C. Yu, S. S. Raman, P. Limanond, C. Lassman, K. Murray, M. J. Tong, R. G. Amado, and R. W. Busuttil Radiofrequency Ablation of Hepatocellular Carcinoma: Treatment Success as Defined by Histologic Examination of the Explanted Liver Radiology, March 1, 2005; 234(3): 954 - 960. [Abstract] [Full Text] [PDF] |
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A. Giorgio, L. Tarantino, G. de Stefano, C. Coppola, and G. Ferraioli Complications After Percutaneous Saline-Enhanced Radiofrequency Ablation of Liver Tumors: 3-Year Experience with 336 Patients at a Single Center Am. J. Roentgenol., January 1, 2005; 184(1): 207 - 211. [Abstract] [Full Text] [PDF] |
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O. Seror, G. N'Kontchou, D. Haddar, M. Dordea, Y. Ajavon, N. Ganne, J. C. Trinchet, M. Beaugrand, and N. Sellier Large Infiltrative Hepatocellular Carcinomas: Treatment with Percutaneous Intraarterial Ethanol Injection Alone or in Combination with Conventional Percutaneous Ethanol Injection Radiology, January 1, 2005; 234(1): 299 - 309. [Abstract] [Full Text] [PDF] |
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G. S. Gazelle, P. M. McMahon, M. T. Beinfeld, E. F. Halpern, and M. C. Weinstein Metastatic Colorectal Carcinoma: Cost-effectiveness of Percutaneous Radiofrequency Ablation versus That of Hepatic Resection Radiology, December 1, 2004; 233(3): 729 - 739. [Abstract] [Full Text] [PDF] |
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S. H. Kim, H. K. Lim, D. Choi, W. J. Lee, S. H. Kim, M. J. Kim, S. J. Lee, and J. H. Lim Changes in Bile Ducts after Radiofrequency Ablation of Hepatocellular Carcinoma: Frequency and Clinical Significance Am. J. Roentgenol., December 1, 2004; 183(6): 1611 - 1617. [Abstract] [Full Text] [PDF] |
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J M Lee, J K Han, S H Kim, J Y Lee, S H Choi, and B I Choi Hepatic bipolar radiofrequency ablation using perfused-cooled electrodes: a comparative study in the ex vivo bovine liver Br. J. Radiol., November 1, 2004; 77(923): 944 - 949. [Abstract] [Full Text] [PDF] |
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G. Y. Jin, J. M. Lee, Y. C. Lee, Y. M. Han, and Y. S. Lim Primary and Secondary Lung Malignancies Treated with Percutaneous Radiofrequency Ablation: Evaluation with Follow-Up Helical CT Am. J. Roentgenol., October 1, 2004; 183(4): 1013 - 1020. [Abstract] [Full Text] [PDF] |
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A. Hines-Peralta and S. N. Goldberg Review of Radiofrequency Ablation for Renal Cell Carcinoma Clin. Cancer Res., September 15, 2004; 10(18): 6328S - 6334S. [Abstract] [Full Text] [PDF] |
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A R Gillams Liver ablation therapy Br. J. Radiol., September 1, 2004; 77(921): 713 - 723. [Full Text] [PDF] |
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M. Koda, M. Ueki, Y. Maeda, K.-i. Mimura, K. Okamoto, Y. Matsunaga, M. Kawakami, K. Hosho, and Y. Murawaki Percutaneous Sonographically Guided Radiofrequency Ablation with Artificial Pleural Effusion for Hepatocellular Carcinoma Located Under the Diaphragm Am. J. Roentgenol., September 1, 2004; 183(3): 583 - 588. [Abstract] [Full Text] [PDF] |
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K. Steinke, J. King, D. W. Glenn, and D. L. Morris Percutaneous Radiofrequency Ablation of Lung Tumors with Expandable Needle Electrodes: Tips from Preliminary Experience Am. J. Roentgenol., September 1, 2004; 183(3): 605 - 611. [Full Text] [PDF] |
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C. Gadaleta, V. Mattioli, G. Colucci, A. Cramarossa, V. Lorusso, E. Canniello, A. Timurian, G. Ranieri, G. Fiorentini, M. De Lena, et al. Radiofrequency Ablation of 40 Lung Neoplasms: Preliminary Results Am. J. Roentgenol., August 1, 2004; 183(2): 361 - 368. [Abstract] [Full Text] [PDF] |
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Y. Minami, M. Kudo, T. Kawasaki, H. Chung, C. Ogawa, and H. Shiozaki Treatment of Hepatocellular Carcinoma with Percutaneous Radiofrequency Ablation: Usefulness of Contrast Harmonic Sonography for Lesions Poorly Defined with B-Mode Sonography Am. J. Roentgenol., July 1, 2004; 183(1): 153 - 156. [Abstract] [Full Text] [PDF] |
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M.-H. Chen, W. Yang, K. Yan, M.-W. Zou, L. Solbiati, J.-B. Liu, and Y. Dai Large Liver Tumors: Protocol for Radiofrequency Ablation and Its Clinical Application in 110 Patients--Mathematic Model, Overlapping Mode, and Electrode Placement Process Radiology, July 1, 2004; 232(1): 260 - 271. [Abstract] [Full Text] [PDF] |
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K. Yasui, S. Kanazawa, Y. Sano, T. Fujiwara, S. Kagawa, H. Mimura, S. Dendo, T. Mukai, H. Fujiwara, T. Iguchi, et al. Thoracic Tumors Treated with CT-guided Radiofrequency Ablation: Initial Experience Radiology, June 1, 2004; 231(3): 850 - 857. [Abstract] [Full Text] [PDF] |
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R. T. P. Poon, K. K. C. Ng, C.-M. Lam, V. Ai, J. Yuen, and S.-T. Fan Effectiveness of Radiofrequency Ablation for Hepatocellular Carcinomas Larger Than 3 cm in Diameter Arch Surg, March 1, 2004; 139(3): 281 - 287. [Abstract] [Full Text] [PDF] |
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M. Ahmed, Z. Liu, K. S. Afzal, D. Weeks, S. M. Lobo, J. B. Kruskal, R. E. Lenkinski, and S. N. Goldberg Radiofrequency Ablation: Effect of Surrounding Tissue Composition on Coagulation Necrosis in a Canine Tumor Model Radiology, March 1, 2004; 230(3): 761 - 767. [Abstract] [Full Text] [PDF] |
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S. M. Lobo, K. S. Afzal, M. Ahmed, J. B. Kruskal, R. E. Lenkinski, and S. N. Goldberg Radiofrequency Ablation: Modeling the Enhanced Temperature Response to Adjuvant NaCl Pretreatment Radiology, January 1, 2004; 230(1): 175 - 182. [Abstract] [Full Text] [PDF] |
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H. Rhim, G. D. Dodd III, K. N. Chintapalli, B. J. Wood, D. E. Dupuy, J. L. Hvizda, P. E. Sewell, and S. N. Goldberg Radiofrequency Thermal Ablation of Abdominal Tumors: Lessons Learned from Complications RadioGraphics, January 1, 2004; 24(1): 41 - 52. [Abstract] [Full Text] [PDF] |
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J. M. Lee, G. Y. Jin, S. N. Goldberg, Y. C. Lee, G. H. Chung, Y. M. Han, S. Y. Lee, and C. S. Kim Percutaneous Radiofrequency Ablation for Inoperable Non-Small Cell Lung Cancer and Metastases: Preliminary Report Radiology, January 1, 2004; 230(1): 125 - 134. [Abstract] [Full Text] [PDF] |
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S. Sumie, F. Yamashita, E. Ando, M. Tanaka, Y. Yano, K. Fukumori, and M. Sata Interventional Radiology for Advanced Hepatocellular Carcinoma: Comparison of Hepatic Artery Infusion Chemotherapy and Transcatheter Arterial Lipiodol Chemoembolization Am. J. Roentgenol., November 1, 2003; 181(5): 1327 - 1334. [Abstract] [Full Text] [PDF] |
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K Steinke, D Glenn, J King, and D L Morris Percutaneous pulmonary radiofrequency ablation: difficulty achieving complete ablations in big lung lesions Br. J. Radiol., October 1, 2003; 76(910): 742 - 745. [Abstract] [Full Text] [PDF] |
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M. P. Rao and R. Bell Pulmonary Hemorrhage After Radioablation of Liver Metastases Anesth. Analg., September 1, 2003; 97(3): 684 - 686. [Abstract] [Full Text] [PDF] |
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