Lack of response after initial chemoembolization for hepatocellular carcinoma: does it predict failure of subsequent treatment?

PURPOSE: To (a) evaluate the response of hepatocellular carcinoma (HCC) to chemoembolization after initial nonresponse, as determined with European Association for the Study of the Liver (EASL) criteria and modified Response Evaluation Criteria in Solid Tumors (mRECIST), and (b) compare posttreatment survival of initial nonresponders versus that of initial responders. MATERIALS AND METHODS: The institutional review board approved this retrospective study, which was compliant with HIPAA. A total of 116 consecutive patients (96 men, 20 women; mean age, 63 years) with unresectable HCC who underwent at least two chemoembolization procedures were included. The chemoembolization mixture consisted of 100 mg of cisplatin, 50 mg of doxorubicin, and 10 mg of mitomycin C mixed 1:1 with iodized oil. Tumor response at magnetic resonance imaging was evaluated after each chemoembolization procedure according to EASL criteria and mRECIST. The survival rate in each subgroup was calculated and correlated with response. The Wilcoxon test was used to test group comparability. Kaplan-Meier estimators were used to generate survival curves and compared by using the log-rank test. RESULTS: No response to initial chemoembolization was seen in 43% and 50% of patients according to EASL criteria and mRECIST, respectively. After a second chemoembolization procedure, 44% (EASL) and 47% (mRECIST) of initial nonresponders showed a significant response. With EASL criteria, the 1-, 2-, and 3-year survival rates (±standard error of the mean) after two chemoembolization procedures were 39%±10, 14%±7, and 0%, respectively, for nonresponders and 68%±10, 50%±11, and 37%±11 for responders (P=.036, P=.006, and P<.005 at 1, 2, and 3 years). With mRECIST, the 1-, 2-, and 3-year survival rates after two chemoembolization procedures were 49%±9, 20%±8, and 7%±6 for nonresponders and 67%±9, 44%±10, and 36%±9 for responders (P=.174, P=.046, and P=.011 at 1, 2, and 3 years). CONCLUSION: Patients who underwent chemoembolization for HCC showed a response (with both EASL criteria and mRECIST) and improved survival after the second chemoembolization treatment. At least two chemoembolization procedures should be performed in the same targeted lesions before further treatment is abandoned.

DNA synthesis and neuronal apoptosis caused by familial Alzheimer disease mutants of the amyloid precursor protein are mediated by the p21 activated kinase PAK3.

Apoptotic pathways and DNA synthesis are activated in neurons in the brains of individuals with Alzheimer disease (AD). However, the signaling mechanisms that mediate these events have not been defined. We show that expression of familial AD (FAD) mutants of the amyloid precursor protein (APP) in primary neurons in culture causes apoptosis and DNA synthesis. Both the apoptosis and the DNA synthesis are mediated by the p21 activated kinase PAK3, a serine-threonine kinase that interacts with APP. A dominant-negative kinase mutant of PAK3 inhibits the neuronal apoptosis and DNA synthesis; this effect is abolished by deletion of the PAK3 APP-binding domain or by coexpression of a peptide representing this binding domain. The involvement of PAK3 specifically in FAD APP-mediated apoptosis rather than in general apoptotic pathways is suggested by the facts that a dominant-positive mutant of PAK3 does not alone cause neuronal apoptosis and that the dominant-negative mutant of PAK3 does not inhibit chemically induced apoptosis. Pertussis toxin, which inactivates the heterotrimeric G-proteins Go and Gi, inhibits the apoptosis and DNA synthesis caused by FAD APP mutants; the apoptosis and DNA synthesis are rescued by coexpression of a pertussis toxin-insensitive Go. FAD APP-mediated DNA synthesis precedes FAD APP-mediated apoptosis in neurons, and inhibition of neuronal entry into the cell cycle inhibits the apoptosis. These data suggest that a normal signaling pathway mediated by the interaction of APP, PAK3, and Go is constitutively activated in neurons by FAD mutations in APP and that this activation causes cell cycle entry and consequent apoptosis.

Review of radiofrequency ablation for renal cell carcinoma.

This review will discuss how minimally invasive, image-guided radiofrequency (RF) tumor ablation [i.e., coagulating tumor using short-duration heating (<15 minutes) by directly applying temperatures >50 degrees C via needle electrodes] is being incorporated as a clinical tool for the treatment of renal cell carcinoma. RF ablation has been used to treat focal liver tumors. Potential benefits of this thermal therapy include reduced morbidity and mortality compared with standard surgical resection and the ability to treat nonsurgical patients. More recently, this technique has been introduced to treat focal renal tumors, particularly incidental lesions smaller than 3 cm in elderly patients and those with comorbid conditions. Other uses have included treatment in patients with von Hippel-Lindau syndrome and other diseases that predispose patients to multiple renal carcinomas, where renal parenchymal preservation is desired. Techniques, complications, and results will be discussed. Additionally, strategies that we are currently studying to improve RF outcomes and enable the potential treatment of larger tumors will be addressed. Most notably, recent data on increased coagulation achieved by combining RF ablation with antivascular/antiangiogenic therapies, such as arsenic trioxide, that reduce blood flow and promote heat retention are provided.

Implementation of screen-capture video recordings of resident conferences in an academic radiology department: pilot experience.

RATIONALE AND OBJECTIVES: Didactic lectures are an integral component of resident education, but many are missed because of postcall or away rotation status. The authors describe their pilot experience implementing an audiovisual recording program for didactic lectures and report residents' and faculty members' perceptions of this experience. MATERIALS AND METHODS: From July to October 2008, resident conference didactic lectures were recorded on a voluntary faculty basis and posted to a secure Web site using affordable ($500) commercially available equipment. After the trial period, surveys were administered to residents and faculty members. Questions addressed residents' use of the system and its perceived usefulness, as well as its impact on conference attendance, lecture quality, and preparation time. RESULTS: The survey was completed by 32 of 37 residents (86%) and by 24 of 68 (35%) faculty. Median rankings of perceived usefulness of the system (1 = not useful, 5 = extremely useful) were 5 for residents and 3 for faculty members (P < .01, Wilcoxon's rank-sum test). The mean numbers of lectures viewed were 1.7 per week during regular rotations and 3.93 per week during away rotations or night float (P = .02, t test). A majority (21 of 32 [66%]) of residents stated that lecture quality had improved. A majority (21 of 24 [88%]) of faculty members reported no increases in lecture preparation time compared to before the pilot program. CONCLUSIONS: On the basis of its affordability, perceived usefulness by residents, and minimal impact on faculty members' preparation time, a recording system for didactic lectures has the potential to enhance residents' learning at only minimal costs to radiology departments.

Radiofrequency ablation: variability in heat sensitivity in tumors and tissues.

PURPOSE: To characterize the thermal dosimetry (ie, heating profile) of radiofrequency ablation (RFA) in multiple ex vivo tissues and in vivo tumor models. MATERIALS AND METHODS: RFA was performed for 3-24 minutes in ex vivo bovine livers (n=20), porcine kidneys (n=20), and turkey muscles (n=20) and in vivo canine venereal sarcomas (n=8). RFA was performed by using 1 and 3-cm long tips internally cooled electrodes. In addition, RFA was performed in in vivo R3220 rat mammary adenocarcinomas (n=36) and human renal cell carcinomas in nude mice (n=6) by using 1-cm monopolar electrodes. Continuous temperature monitoring was performed at multiple depths to calculate thermal dosimetry, reported as the area under the curve (AUC). Cumulative equivalent minutes at 43 degrees C (CEM43) were used for the critical ablation margin. Data were compared with analysis of variance and regression analysis. RESULTS: For each tissue and/or tumor type, statistically significant temperature differences (up to 14 degrees) were observed at the ablation margin (P<.01). Temperature was dependent on the procedure duration. For 10-minute treatments, temperatures were significantly higher in the kidney compared with the R3230 tumor (72 degrees C+/-2.2) (P<.01) and lower in R3230 tumor (41.6 degrees C+/-1.4) (P<.05) but were similar for liver and muscle (51.6 degrees C+/-1.6 and 54.1 degrees C+/-1.8, respectively). Thus, a wide range of ablative temperatures were observed (41.0 degrees C+/-0.7 to 76.7 degrees C+/-1.9), with coagulation diameter correlating logarithmically with radiofrequency duration and AUC (R2=0.85-0.95). The CEM43 demonstrated an extreme range of values (10(11)). CONCLUSION: The results of the study demonstrate a wide range of thermal sensitivity to RFA among commonly investigated tissues and tumor models, suggesting that further characterization of tissue-specific end points (ie, the duration and end temperature of ablation) is likely warranted. The AUC showed good correlation with ablation sizes, but the CEM43 proved unworkable given an extreme range of values for RFA.

High-power generator for radiofrequency ablation: larger electrodes and pulsing algorithms in bovine ex vivo and porcine in vivo settings.

PURPOSE: To prospectively maximize the extent of tissue coagulation by using a high-power (1000-W, 4000-mA) radiofrequency (RF) generator to optimize pulsing algorithms. MATERIALS AND METHODS: The institutional animal care and use committee approved the use of the animal model in the in vivo portion of this study. RF ablations (n = 258) were performed in ex vivo bovine livers by using a 500-kHz high-power generator. Through internally cooled 3.0-cm single and 2.5- and 4.0-cm cluster electrodes, RF energy was applied for 12 minutes. For each electrode, simplex optimization was used to determine the pulsing algorithms to be used (ie, 5-50-second "on" [energy application] and 10-50-second "off" [cooling without RF heating] periods). Three-dimensional contour maps expressing the relationship between pulsing parameters and resultant coagulation were constructed. Then, 31 RF ablations were performed with optimal settings in vivo in porcine livers, and the results were compared with those obtained in control ablations performed by using a 2000-mA commercial generator. Finally, in 108 experiments, RF energy was applied in ex vivo livers for 6, 12, and 20 minutes with maximum current settings (1000-4000 mA) by using the optimal on and off settings for all three electrodes, and the results were analyzed with multivariate analysis of variance (MANOVA). RESULTS: For all three electrodes, a relationship between the on and off times during the pulsing cycle and the resultant coagulation was established (P < .01). With 3.0-cm single electrodes, maximum coagulation (mean, 5.2 cm +/- 0.1 [standard deviation] ex vivo and 3.6 cm +/- 0.2 in vivo) was achieved with pulse settings of 10-18 seconds on and 11-20 seconds off. With cluster electrodes, greater coagulation was achieved (mean, 6.5 cm +/- 0.6 ex vivo and 3.9 cm +/- 0.3 in vivo with 2.5-cm tip; 8.3 cm +/- 0.3 ex vivo and 5.2 cm +/- 0.8 in vivo with 4.0-cm tip) with optimal pulse settings. Thus, use of the high-power generator yielded substantially increased tissue coagulation in vivo compared with the coagulation achieved with the standard generator. MANOVA revealed that increased maximum current and RF ablation durations of up to 20 minutes were associated with greater coagulation, the size of which also varied according to electrode type (P < .01). CONCLUSION: Markedly larger coagulation zones can be achieved with optimized high-power RF ablation. This may require longer pulsing intervals compared with those previously used.

Combination of radiofrequency ablation with antiangiogenic therapy for tumor ablation efficacy: study in mice.

PURPOSE: To prospectively determine whether modulation of renal cell carcinoma (RCC) tumor microvasculature by using the antiangiogenic drug sorafenib could increase the extent of radiofrequency (RF)-induced coagulation in an RCC animal tumor model. MATERIALS AND METHODS: All investigations received animal care and utilization committee approval. RCC (human 786-0) was implanted subcutaneously into 27 nude mice. Sixteen mice were randomly assigned into one of three groups when tumors reached 12 mm in diameter: Six mice received 80 mg of sorafenib, a Raf kinase and vascular endothelial growth factor receptor inhibitor, per kilogram of body weight; five mice received 20 mg/kg sorafenib; and five mice received a control carrier vehicle alone. Antiangiogenic therapy was administered until a mean 1-mm reduction in tumor diameter was noted in one group. These 16 mice received a standard dose of RF ablation. Ablation size was visualized by using 2% triphenyltetrazolium chloride. An additional 11 tumors in mice treated with sorafenib alone were stained with CD31 to determine microvascular density (MVD). Resultant size of ablation was compared among groups; statistical significance was determined with analysis of variance. Differences in MVD were assessed with the Kruskal-Wallis test. RESULTS: Over the 9-day administration of sorafenib, mean tumor size in the control group reached 15.2 mm +/- 0.8 (standard deviation). Tumors in mice receiving 20 mg/kg and 80 mg/kg sorafenib measured 12.2 mm +/- 0.6 and 11.1 mm +/- 0.5, respectively (P < .05). RF-induced coagulation diameter was 8.5 mm +/- 0.4 and 11.1 mm +/- 0.3 in the 20 mg/kg and 80 mg/kg sorafenib groups, respectively, but was only 6.7 mm +/- 0.7 for animals that underwent RF ablation alone (P < .01). Likewise, significant decreases in MVD were noted in the sorafenib-treated animals (P < .01). CONCLUSION: Treatment of RCC in nude mice with the antiangiogenic agent sorafenib resulted in markedly decreased MVD and significantly larger zones of RF-induced coagulation necrosis.

CT perfusion for determination of pharmacologically mediated blood flow changes in an animal tumor model.

PURPOSE: To prospectively compare single- and multisection computed tomographic (CT) perfusion for tumor blood flow determination in an animal model. MATERIALS AND METHODS: All animal protocols and experiments were approved by the institutional animal care and use committee before the study was initiated. R3230 mammary adenocarcinoma was implanted in 11 rats. Tumors (18-20 mm) were scanned with dynamic 16-section CT at baseline and after administration of arsenic trioxide, which is known to cause acute reduction in blood flow. The concentration of arsenic was titrated (0-6 mg of arsenic per kilogram of body weight) to achieve a defined blood flow reduction (0%-75%) from baseline levels at 60 minutes, as determined with correlative laser Doppler flowmetry. The mean blood flow was calculated for each of four 5-mm sections that covered the entire tumor, as well as for the entire tumor after multiple sections were processed. Measurements obtained with both methods were correlated with laser Doppler flowmetry measurements. Interobserver agreement was determined for two blinded radiologists, who calculated the percentage of blood flow reduction for the "most representative" single sections at baseline and after arsenic administration. These results were compared with the interobserver variability of the same radiologists obtained by summing blood flow changes for the entire tumor volume. RESULTS: Overall correlations for acute blood flow reduction were demonstrated between laser Doppler flowmetry and the two CT perfusion approaches (single-section CT, r=0.85 and r(2)=0.73; multisection CT, r=0.93 and r(2)=0.87; pooled data, P=.01). CT perfusion disclosed marked heterogeneity of blood flow, with variations of 36% +/- 13 between adjacent 5-mm sections. Given these marked differences, interobserver agreement was much lower for single-section CT (standard deviation, 0.22) than for multisection CT (standard deviation, 0.10; P=.01). CONCLUSION: Multisection CT perfusion techniques may provide an accurate and more reproducible method of tumor perfusion surveillance than comparison of single representative tumor sections.

Improved tumor destruction with arsenic trioxide and radiofrequency ablation in three animal models.

PURPOSE: To assess the extent of tumor blood flow reduction that is achievable with arsenic trioxide (As2O3) and the effect of As2O3 on radiofrequency (RF)-induced coagulation. MATERIALS AND METHODS: All animal protocols and experiments were approved by an institutional animal care and use committee before the start of the study. Experiments were conducted in three tumor models: intrarenal VX2 sarcoma in 27 rabbits, RCC 786-0 human renal cell carcinoma in 24 nude mice, and R3230 mammary adenocarcinoma in 40 rats. One dose (0-7.5 mg per kilogram of body weight) of As2O3 was administered (intraperitoneally in rodents, intravenously in rabbits) 1, 6, or 24 hours before standardized RF ablation, which was performed by using a 1-cm active tip, with mean temperatures of 70 degrees C +/- 2 (standard deviation) for 5 minutes in rodents and 90 degrees C +/- 2 for 6 minutes in rabbits. Laser Doppler flowmetry was used to quantify changes in blood flow, which were compared with diameters of induced tumor coagulation. Comparisons between groups were performed by using Student t tests or analysis of variance. The strengths of correlations between As2O3, tumor blood flow, and RF-induced coagulation were assessed by using linear and higher-order regression models and reported as R2 computations. RESULTS: Administration of As2O3 significantly (P < .05) reduced blood flow and increased tumor destruction in all tumor models. In VX2 sarcoma tumors, 1 mg/kg As2O3 reduced mean tumor blood flow to 46% +/- 13 of the normal value. The mean resultant coagulation (1.1 cm +/- 0.1) was significantly greater than that achieved with RF ablation alone (0.6 cm +/- 0.1, P < .01). In RCC 786-0 and R3230 tumors, 5 mg/kg As2O3 reduced mean tumor blood flow to 57% +/- 6 and 46% +/- 6 of normal, respectively, increasing mean ablation extent to 0.8 cm +/- 0.1 for both models, compared with those achieved with the control treatment (0.6 cm +/- 0.1 and 0.5 cm +/- 0.1, respectively; P < .05 for both comparisons). Dose studies revealed correlations between drug dose, tumor blood flow, and RF-induced coagulation in all three tumor models (R2 = 0.60-0.79). Maximal RF synergy was observed 1 hour after As2O3 administration. CONCLUSION: As2O3 administration represents a transient noninvasive method of reducing tumor blood flow during RF ablation, enabling larger zones of tumor destruction in multiple tumor models.

Chemical tumor ablation with use of a novel multiple-tine infusion system in a canine sarcoma model.

PURPOSE: To determine whether larger confluent zones of ablation can be achieved in chemical ablation with use of a multiple-tine infusion device compared with standard needle infusion in a solid tumor model. MATERIALS AND METHODS: Multiple canine venereal sarcomas (N=42) were implanted in nine mildly immunosuppressed dogs (treated with 10 mg/kg cyclosporin A twice daily). Tumors incubated for 8-12 weeks grew to a diameter of 5.4 cm+/-1.0. With ultrasound guidance, 8-56 mL of 100% ethanol or 15% acetic acid (diluted in saturated saline solution) were injected in aliquots (2-8 mL) at multiple distances (radius of 0-2 cm) from the needle axis with use of a multiple-tine infusion device. Presence of fluid reflux at the needle puncture site and resultant coagulation diameters were measured within 1 hour and compared with the results of infusion with a standard 18-gauge needle. RESULTS: Multiple-tine infusion enabled greater fluid infusion (15 mL+/-3 to 53 mL+/-3 depending on protocol) than standard needle injection (8 mL+/-1) before reflux was observed at the puncture site (P<.01). Additionally, progressive gains in contiguous tumor coagulation were achieved because acetic acid was infused as far as 2 cm from the needle axis with the multiple-tine device (P<.01; R(2)=0.59; y=0.5x+2.9). Optimal coagulation was achieved with the infusion of 4-mL aliquots at 0.5 cm and 1.0 cm from the needle, followed by three 4-mL or 8-mL aliquots (40 degrees rotation between infusions) at 1.5 cm and 2.0 cm from the needle (32 mL+/-0 and 53 mL+/-3 total, respectively). This yielded confluent short-axis coagulation diameters of 4.9 cm+/-1.0 and 5.4 cm+/-1.0, respectively, which were significantly greater than the measurement of 3.1 cm+/-0.4 achieved with standard needle infusion (P<.01). Smaller and noncontiguous foci of coagulation foci (1.7 cm+- 0.5) were seen with the use of ethanol for standard needle and multiple-tine infusions. CONCLUSIONS: Chemical ablation with 15% acetic acid with use of a multiple-tine infusion device resulted in larger diameters of contiguous tumor coagulation and enabled greater volumes of infusion than standard needle infusion or ethanol ablation. This suggests that chemical ablation with acetic acid infused with use of a multiple-tine device may overcome some of the difficulties seen with the use of conventional needle chemical ablation injection alone, such as irregular ablation and fluid reflux up the needle tract.

Microwave ablation: results with a 2.45-GHz applicator in ex vivo bovine and in vivo porcine liver.

PURPOSE: To characterize the relationship between applied power and treatment duration in their effect on extent of coagulation produced with a 2.45-GHz microwave applicator in both an ex vivo and a perfused in vivo liver model. MATERIALS AND METHODS: All experimentation was approved by the Institute of Animal Care and Use Committee. Multiple tissue ablations were performed in ex vivo bovine liver (120 ablations) and in vivo porcine liver (45 ablations) with a 5.7-mm-diameter 2.45-GHz microwave applicator. The applied power was varied from 50 to 150 W (in 25-W increments ex vivo and 50-W increments in vivo), while treatment duration varied from 2 to 20 minutes (in eight time increments for ex vivo and five for in vivo liver). Three-dimensional contour maps of the resultant short- and long-axis coagulation diameters were constructed to identify the optimal parameters to achieve maximum coagulation in both ex vivo and in vivo models. Multivariate analysis was performed to characterize the relationship between applied power and treatment duration. RESULTS: Power and treatment duration were both associated with coagulation diameter in a sigmoidal fashion (ex vivo, R(2) = 0.78; in vivo, R(2) = 0.74). For ex vivo liver, the maximum short-axis coagulation diameter (7.6 cm +/- 0.2 [standard deviation] by 12.3 cm +/- 0.8) was achieved at greatest power (150 W) and duration (20 minutes). In vivo studies revealed a sigmoidal relationship between duration and coagulation size, with a relative plateau in coagulation size achieved within 8 minutes duration at all power levels. After 8 minutes of treatment at 150 W, the mean short-axis coagulation diameter for in vivo liver was 5.7 cm +/- 0.2 by 6.5 cm +/- 1.7, which was significantly larger than the corresponding result for ex vivo liver (P < .05). CONCLUSION: Large zones of ablation can be achieved with the 2.45-GHz microwave applicator used by the authors. For higher-power ablations, larger zones of coagulation were achieved for in vivo liver than for ex vivo liver with short energy applications, a finding previously not seen with other ablation devices, to the authors' knowledge.

Radiofrequency tumor ablation: insight into improved efficacy using computer modeling.

OBJECTIVE: To use computer modeling of the Bio-Heat equation to demonstrate factors influencing RF ablation tissue heating. CONCLUSION: Computer modeling demonstrates the importance of energy deposition, tumor and background tissue electrical and thermal conductivity, and perfusion on RF ablation outcomes.

Radiofrequency ablation: importance of background tissue electrical conductivity--an agar phantom and computer modeling study.

PURPOSE: To determine whether radiofrequency (RF)-induced heating can be correlated with background electrical conductivity in a controlled experimental phantom environment mimicking different background tissue electrical conductivities and to determine the potential electrical and physical basis for such a correlation by using computer modeling. MATERIALS AND METHODS: The effect of background tissue electrical conductivity on RF-induced heating was studied in a controlled system of 80 two-compartment agar phantoms (with inner wells of 0.3%, 1.0%, or 36.0% NaCl) with background conductivity that varied from 0.6% to 5.0% NaCl. Mathematical modeling of the relationship between electrical conductivity and temperatures 2 cm from the electrode (T2cm) was performed. Next, computer simulation of RF heating by using two-dimensional finite-element analysis (ETherm) was performed with parameters selected to approximate the agar phantoms. Resultant heating, in terms of both the T2cm and the distance of defined thermal isotherms from the electrode surface, was calculated and compared with the phantom data. Additionally, electrical and thermal profiles were determined by using the computer modeling data and correlated by using linear regression analysis. RESULTS: For each inner compartment NaCl concentration, a negative exponential relationship was established between increased background NaCl concentration and the T2cm (R2= 0.64-0.78). Similar negative exponential relationships (r2 > 0.97%) were observed for the computer modeling. Correlation values (R2) between the computer and experimental data were 0.9, 0.9, and 0.55 for the 0.3%, 1.0%, and 36.0% inner NaCl concentrations, respectively. Plotting of the electrical field generated around the RF electrode identified the potential for a dramatic local change in electrical field distribution (ie, a second electrical peak ["E-peak"]) occurring at the interface between the two compartments of varied electrical background conductivity. Linear correlations between the E-peak and heating at T2cm (R2= 0.98-1.00) and the 50 degrees C isotherm (R2= 0.99-1.00) were established. CONCLUSION: These results demonstrate the strong relationship between background tissue conductivity and RF heating and further explain electrical phenomena that occur in a two-compartment system.

Hybrid radiofrequency and cryoablation device: preliminary results in an animal model.

PURPOSE: To determine whether the simultaneous application of combined bipolar radiofrequency (RF) ablation and cryoablation in a hybrid system produces larger ablation zones than RF or cryoablation alone. MATERIALS AND METHODS: Multiple 15-minute ablations were performed in ex vivo bovine liver (n = 167) with a hybrid applicator system with RF ablation alone (0.3-0.7 A), cryoablation alone (3,500 psi, two freeze/thaw cycles), and combined RF/cryoablation (0.4-0.7 A, 1,000-3,500 psi) with use of a novel applicator consisting of two 2.5-cm active bipolar RF poles located on the same 18-gauge needle separated by two embedded cryoablation nozzles. Resultant coagulation diameters were compared with use of analysis of variance for more than three groups or Student t tests for two groups. Confirmation of the optimal parameters of combination RF/cryoablation was performed by reassessing a range of argon pressure (1,000-3,500 psi) and RF current (0.4-0.7 A) in in vivo porcine liver (n = 36). Arrays of two to four RF/cryoablation applicators were also assessed in ex vivo (n = 54) and in vivo (n = 12) liver. RESULTS: In ex vivo liver, simultaneous RF/cryoablation (0.6 A, 3,000 psi) produced 3.6 cm +/- 0.4 of short-axis coagulation. This was significantly larger than that achieved with optimal RF alone or cryoablation alone (1.5 cm +/- 0.3 and 1.6 cm +/- 0.3, respectively; F = 95; P < .01). The coagulation diameter with simultaneous combination RF/cryoablation was related in parabolic fashion to argon pressure and current with a multivariate r(2) of 0.68. For in vivo liver, optimal combination RF/cryoablation achieved 3.3 cm +/- 0.2 of coagulation, which was significantly larger than that achieved with RF alone (1.1 cm +/- 0.1; P < .01) or cryoablation alone (1.1 cm +/- 0.1 and 1.3 cm +/- 0.1; F = 203; P < .01). The greatest contiguous coagulation was achieved with multiple-applicator arrays. For ex vivo liver, short-axis coagulation measured 5.3 cm +/- 0.1, 6.4 cm +/- 0.1, and 7.6 cm +/- 0.1 for two-, three-, and four-applicator arrays, respectively. For in vivo liver, two-, three-, and four-applicator arrays produced 5.1 cm +/- 0.2, 5.8 cm +/- 0.5, and 7.0 cm +/- 0.5 of confluent coagulation, respectively. CONCLUSION: Simultaneous combination RF and cryoablation with use of a novel applicator design yielded significantly larger zones of coagulation than either modality alone. The large ablation diameters achieved warrant further investigation of the device.