Young-sun Kim

Ten-year outcomes of percutaneous radiofrequency ablation as first-line therapy of early hepatocellular carcinoma: Analysis of prognostic factors

BACKGROUND & AIMS The aim was to assess 10-year outcomes of radiofrequency ablation as a first-line therapy of early-stage hepatocellular carcinoma with an analysis of prognostic factors. METHODS From April 1999 to April 2011, 1305 patients (male:female=993:312; mean age, 58.4 years) with 1502 early-stage hepatocellular carcinomas (mean size, 2.2 cm) were treated with percutaneous radiofrequency ablation as a first-line option. Follow-up period ranged from 0.4 to 146.6 months (median, 33.4 months). We assessed the 10-year follow-up results of recurrences and survival with the analyses of prognostic factors. RESULTS Recurrences occurred in 795 patients (1-17 times), which were managed with various therapeutic modalities. The cumulative local tumor progression rates were 27.0% and 36.9% at 5 and 10 years, respectively, for which the only significant risk factor was large tumor size (B=0.584, p=0.001). Cumulative intrahepatic distant and extrahepatic recurrence rates were 73.1% and 88.5%, and 19.1% and 38.2% at 5 and 10 years, respectively. Corresponding overall survival rates were 59.7% and 32.3%, respectively. Poor survival was associated with old age (B=0.043, p=0.010), Child-Pugh class B (B=-1.054, p<0.001), absence of antiviral therapy during follow-up (B=-0.699, p=0.034), and presence of extrahepatic recurrence (B=0.971, p=0.007). CONCLUSIONS Ten-year survival outcomes after percutaneous radiofrequency ablation as a first-line therapy of hepatocellular carcinoma were excellent despite frequent tumor recurrences. Overall survival was influenced by age, Child-Pugh class, antiviral therapy, or extrahepatic recurrence.

The Minimal Ablative Margin of Radiofrequency Ablation of Hepatocellular Carcinoma (> 2 and < 5 cm) Needed to Prevent Local Tumor Progression: 3D Quantitative Assessment Using CT Image Fusion

OBJECTIVE The aim of this study was to elucidate the minimal ablative margin for percutaneous radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) (> 2 and < 5 cm) needed to prevent local tumor progression using CT image fusion and a 3D quantitative method. MATERIALS AND METHODS From April 2005 to March 2007, we performed percutaneous RFA for the treatment of 382 HCCs larger than 2 cm and smaller than 5 cm. A total of 110 tumors in 103 patients (77 men and 26 women; mean age, 59.7 years) that were previously untreated and were monitored for at least 1 year were retrospectively enrolled. A 5-mm safety margin was attempted in all cases, and a CT finding of complete replacement of the index tumor by RFA zone was defined as technical success. We constructed fusion images of CT images obtained before and after RFA and performed radial multiplanar reformation with the rotation axis at the center of the tumor to analyze the ablative margin quantitatively. Risk factors for local tumor progression (the thinnest ablative margin, tumor size, and the effect of hepatic vessels) were assessed by multivariate analysis. RESULTS Patients underwent follow-up for 12.9-46.6 months (median, 28.1 months). The tumors were 2.1-4.8 cm (mean +/- SD, 2.7 +/- 0.6 cm) in diameter. The thinnest ablative margins ranged from 0 to 6 mm (1.0 +/- 1.4 mm). A 5-mm safety margin was achieved in only 2.7% (3/110) of cases. In 47.3% (52/110) of cases, vessel-induced indentation of the ablation zone contributed to the thinnest ablative margins. Local tumor progression was detected in 27.3% (30/110) of cases. Concordance between local tumor progression and the thinnest margin was observed in 83.3% (25/30) of cases. The incidence of concordant local tumor progression was 22.7% (25/110), 18.9% (10/53), 5.9% (2/34), and 0% (0/15) in tumors with the thinnest ablative margin of > or = 0, > or = 1, > or = 2, and > or = 3 mm, respectively. An insufficient ablative margin was the sole significant factor associated with local tumor progression. CONCLUSION When the thickness of the ablative margin is evaluated by CT image fusion, a margin of 3 mm or more appears to be associated with a lower rate of local tumor progression after percutaneous RFA of HCC.

Small Hepatocellular Carcinomas: Improved Sensitivity by Combining Gadoxetic Acid–enhanced and Diffusion-weighted MR Imaging Patterns

PURPOSE To determine if the combination of gadoxetic acid-enhanced magnetic resonance (MR) imaging and diffusion-weighted (DW) imaging helps to increase accuracy and sensitivity in the diagnosis of small hepatocellular carcinomas (HCCs) compared with those achieved by using each MR imaging technique alone. MATERIALS AND METHODS The institutional review board approved this retrospective study and waived the requirement for informed consent. The study included 130 patients (95 men, 35 women) with 179 surgically confirmed small HCCs (≤2.0 cm) and 130 patients with cirrhosis (90 men, 40 women) without HCC who underwent gadoxetic acid-enhanced MR imaging and DW imaging at 3.0 T between May 2009 and July 2010. Three sets of images were analyzed independently by three observers to detect HCC: a gadoxetic acid set (unenhanced, early dynamic, and hepatobiliary phases), a DW imaging set, and a combined set. Data were analyzed by using alternative-free response receiver operating characteristic analysis. Diagnostic accuracy (area under the receiver operating characteristic curve [A(z)]), sensitivity, specificity, and positive predictive value were calculated. RESULTS The mean A(z) values for the combined set (0.952) were significantly higher than those for the gadoxetic acid set (A(z) = 0.902) or the DW imaging set alone (A(z) = 0.871) (P ≤ .008). On a per-lesion basis, observers showed higher sensitivity in their analyses of the combined set (range, 91.1%-93.3% [163-167 of 179]) than in those of the gadoxetic acid set (range, 80.5%-82.1% [144-147 of 179]) or the DW imaging set alone (range, 77.7%-79.9% [139-143 of 179]) (P ≤ .003). Positive predictive values and specificity for all observers were equivalent for the three imaging sets. CONCLUSION The combination of gadoxetic acid-enhanced MR imaging and DW imaging yielded better diagnostic accuracy and sensitivity in the detection of small HCCs than each MR imaging technique alone.

Percutaneous Radiofrequency Ablation with Artificial Ascites for Hepatocellular Carcinoma in the Hepatic Dome: Initial Experience

OBJECTIVE Our objective was to assess the feasibility, safety, and efficacy of percutaneous radiofrequency ablation with artificial ascites for hepatocellular carcinoma (HCC) in the hepatic dome. MATERIALS AND METHODS Sonographically guided percutaneous radiofrequency ablation with artificial ascites was performed in 25 patients with 34 HCCs using an internally cooled electrode radiofrequency system. At least one hepatic dome tumor in each patient was considered difficult to treat percutaneously because of partially visible tumor (n = 16) or poor electrode path (n = 9) on planning sonography. We artificially induced ascites before radiofrequency ablation by dripping 5% dextrose in water (D/W) solution to improve tumor visibility or electrode path and to separate the radiofrequency ablation zone from the diaphragm. We assessed the technical feasibility, safety, and efficacy of this technique with clinical and CT follow-up for at least 4 months (mean, 281.4 days) RESULTS Artificial ascites was successfully achieved in 22 (88%) of 25 patients with the administration of a mean of 348 mL of D/W solution for an additional mean time of 9.3 minutes. There was substantial improvement in the visibility in 93.4% (15/16) of the partially visible tumors and in achieving a better path in 77.8% (7/9) of the tumors with a poor electrode path. The primary technique effectiveness rate for hepatic dome tumors was 96% (24/25) at 1-month follow-up CT. There was no diaphragmatic thermal injury in all but one case. No complication related to artificial ascites occurred during the follow-up period. CONCLUSION Percutaneous radiofrequency ablation with artificial ascites appears a feasible, safe, and effective technique for treating HCC of the hepatic dome.

Spectrum of CT Findings after Radiofrequency Ablation of Hepatic Tumors

Image-guided radiofrequency (RF) ablation has been used to treat both resectable and nonresectable hepatic tumors. A precise imaging assessment of the therapeutic response and of any complications is mandatory after ablation. Contrast material-enhanced ultrasonography, computed tomography (CT), and magnetic resonance imaging all may be useful for this assessment. At most institutions, a three-phase contrast-enhanced CT examination is performed immediately or within 1 month after RF ablation to assess the technical success of treatment. If ablation was technically successful, three-phase CT may be repeated at 3-month intervals for evaluation of tumor recurrence. The typical CT finding in the zone subjected to RF ablation is an area of low attenuation that encompasses the tumor and an ablative margin. However, the appearance of the ablative zone may vary greatly, depending on the success of treatment and the time elapsed after the procedure. Ringlike enhancement representing benign reactive hyperemia around the ablation zone, central high-attenuation areas representing greater cellular disruption, and tiny air bubbles frequently are seen at immediate follow-up CT but usually have disappeared by the first or second follow-up examination. The successfully ablated zone gradually involutes. The appearance of the zone differs when residual tumor tissue or local tumor progression is present. Immediate or delayed complications also may be seen at follow-up CT. Radiologists must be familiar with both typical and atypical CT findings and their clinical significance. (c) RSNA, 2008.

Novel temperature-triggered liposome with high stability: formulation, in vitro evaluation, and in vivo study combined with high-intensity focused ultrasound (HIFU).

We developed a novel temperature-sensitive liposome, STL composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG-2000), cholesterol, and a fatty acid conjugated elastin-like polypeptide (ELP). The STL had a unilamellar spherical shape with a mean diameter of 160 nm. Doxorubicin (DOX) was encapsulated by the STL using an ammonium sulfate gradient method with a lipid to drug ratio of 1:0.2 (w/w), resulting in 95% loading efficiency. The STL exhibited better stability than conventional low temperature sensitive liposome (LTSL-lysolipid-based temperature sensitive liposomes; DPPC:MSPC:DSPE-PEG-2000=90:10:4) at 37 °C in the presence of serum; there was rapid release of doxorubicin in the range of 39-42 °C (≥95% release at 42 °C within 10s). A confocal microscope revealed that DOX encapsulated in STL (STL-DOX) was taken up much better by cell nuclei at 42 °C than at 37 °C. The difference in cell viability between 37 and 42 °C was 63% relative to STL-DOX and 18% for LTSL-DOX. The pharmacokinetics (PK) and antitumor effect of STL-DOX combined with high-intensity focused ultrasound (HIFU) were studied, and compared with LTSL. An in vivo study demonstrated that STL-DOX is highly stable, with a long circulating property (half life=2.03±0.77 h) in HIFU-untreated mice, and resulted in significant tumor regression for 2 days after intravenous injection of STL-DOX at 5 mg DOX/kg in combination with HIFU. These results are better than conventional LTSL, for which the blood circulation time is short (0.92±0.17 h) and inhibition of tumor growth is weak. These results indicate that the properties of stability at 37 °C and burst release at 42 °C of STL-DOX act synergistically against tumors.

Percutaneous Radiofrequency Ablation of Hepatocellular Carcinoma: Fusion Imaging Guidance for Management of Lesions With Poor Conspicuity at Conventional Sonography

OBJECTIVE The purpose of this study was to determine whether fusion imaging-guided percutaneous radiofrequency ablation (RFA) is effective in the management of hepatocellular carcinoma (HCC) that has poor conspicuity at conventional sonography. SUBJECTS AND METHODS Percutaneous RFA of HCC with poor conspicuity was performed under fusion imaging guidance. The time needed for image fusion between the ultrasound and CT or MR images was recorded. The quality of image fusion and the degree of operator confidence in identifying the index tumor were graded on 4-point scales. Technical success and procedure-related complications were evaluated with liver CT immediately after RFA. RESULTS Thirty patients with HCC (1.0 ± 0.3 cm) were enrolled. Twenty-seven of the 30 lesions detected at planning ultrasound were identified with fusion imaging. Of the 30 HCC candidate lesions detected with ultrasound, five were found to be pseudolesions close to the index tumor. The time needed for image fusion for the 27 lesions was 3.7 ± 2.1 minutes (range, 1.3-9.0 minutes). The quality of image fusion was graded 3.4 ± 0.6, and the degree of operator confidence in identifying the 30 HCCs, 3.3 ± 0.9. The technical success rate was 90% (27/30) in intention-to-treat analysis and 100% in analysis of actually treated lesions. There were no major RFA-related complications. CONCLUSION Fusion imaging-guided percutaneous RFA is effective in the management of HCC that has poor ultrasound conspicuity.

Local Tumor Progression After Radiofrequency Ablation of Liver Tumors: Analysis of Morphologic Pattern and Site of Recurrence

OBJECTIVE The purpose of our study was to assess the morphologic pattern and exact site of local tumor progression with relation to various risk factors after radiofrequency ablation of liver tumors. CONCLUSION Local tumor progression after radiofrequency ablation shows mostly the peripheral nodular type. The site of local tumor progression shows a higher concordance rate with insufficient ablative margin than contiguous vessel and subcapsular location.

Diagnostic accuracy and sensitivity of diffusion-weighted and of gadoxetic acid-enhanced 3-T MR imaging alone or in combination in the detection of small liver metastasis (≤ 1.5 cm in diameter).

Purpose:To compare the diagnostic accuracy and sensitivity of combined gadoxetic acid-enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) with each imaging approach alone for detecting small hepatic metastases (⩽1.5 cm). Materials and Methods:Institutional review board approved this retrospective study and waived informed patient consent. Eighty-six patients with 179 liver metastases underwent liver MRI including unenhanced and gadoxetic acid-enhanced imaging and DWI at 3.0 T. Three image sets including unenhanced images—gadoxetic acid set (early dynamic and hepatocyte phase), DWI set, and the combined set—were analyzed independently and in consensus by 2 observers for detecting liver metastases using receiver operating characteristic analysis. Results:There was a tendency toward an increased diagnostic accuracy for the combined set (mean, 0.965) compared with that for each image set alone (mean, 0.911 for gadoxetic acid set; 0.926 for DWI set). The combined set showed better sensitivity (mean, 97.47%/95.0%: values on per-lesion/per-patient basis) than each imaging set alone (mean, 90.7%/83.7% for gadoxetic acid set; 91.6%/83.0% for DWI set) (P < 0.05) on both per-lesion basis and per-patient basis. All image sets showed similar positive predictive values. Conclusions:The combination of gadoxetic acid-enhanced MRI and DWI yielded better diagnostic accuracy and sensitivity in the detection of small liver metastasis than each magnetic resonance scan sequence alone.

Volumetric MR-HIFU ablation of uterine fibroids: Role of treatment cell size in the improvement of energy efficiency

PURPOSE To evaluate the energy efficiency of differently sized volumetric ablations in MR-guided high-intensity focused ultrasound (MR-HIFU) treatment of uterine fibroids. MATERIALS AND METHODS This study was approved by the institutional review board and informed consent was obtained from all participants. Ten symptomatic uterine fibroids (mean diameter 8.9 cm) in 10 women (mean age 42.2) were treated by volumetric MR-HIFU ablation under binary feedback control. The energy efficiency (mm3/J) of each sonication was calculated as the volume of lethal thermal dose (240 equivalent minutes at 43 °C) per unit acoustic energy applied. Operator-controllable parameters and signal intensity ratio of uterine fibroid to skeletal muscle on T2-weighted MR images were tested with univariate and multivariate analyses to discern which parameters significantly correlated with the ablation energy efficiency. RESULTS We analyzed a total of 236 sonications. The energy efficiency of the ablations was 0.42±0.25 mm3/J (range 0.004-1.18) with energy efficiency improving with the treatment cell size (4 mm, 0.06±0.06 mm3/J; 8 mm, 0.29±0.12 mm3/J; 12 mm, 0.58±0.18 mm3/J; 16 mm, 0.91±0.17 mm3/J). Treatment cell size (r=0.814, p<0.001), distance of ultrasound propagation (r=-0.151, p=0.020), sonication frequency (1.2 or 1.45 MHz; p<0.001), and signal intensity ratio (r=-0.205, p=0.002) proved to be significant by univariate analysis, while multivariate analysis revealed treatment cell size (B=0.075, p<0.001), US propagation distance (B=-6.928, p<0.001), and signal intensity ratio (B=-0.024, p=0.001) to be independently significant. CONCLUSION Energy efficiency in volumetric MR-HIFU ablation of uterine fibroids improves with increased treatment cell size, independent of other significant contributors such as distance of ultrasound propagation or signal intensity of the tumor on T2-weighted MR imaging.