Image-guided percutaneous chemical and radiofrequency tumor ablation in an animal model

PURPOSE: To determine whether combining acetic acid instillation before radiofrequency (RF) ablation can improve local tissue electrical conductivity, RF energy deposition, intratumoral heating, and tumor necrosis in a large animal model. MATERIALS AND METHODS: Multiple hypovascular canine venereal sarcomas were implanted in 11 mildly immunosuppressed dogs (25 mg/kg cyclosporin A twice daily). Tumors were incubated for 8-12 weeks to 4.2 cm +/- 0.6 in diameter. Treatment strategies included 10% and 15% acetic acid diluted in distilled water, 10% and 15% acetic acid diluted in saturated NaCl solution, 50% acetic acid, and 100% ethanol, with 6 mL of each injected alone or in combination with RF ablation (internally cooled, 1-cm tip; 12 minutes). Two additional control groups were studied in which tumors received either RF alone or distilled water injected alone. Comparisons were also made with groups treated with 36% NaCl with and without RF ablation. Resultant coagulation for these ablative strategies, along with local temperatures and RF parameters such as impedance, current, and power, were compared. RESULTS: Increasing coagulation was observed with increasing acetic acid concentrations (1.7 cm +/- 0.4, 2.8 cm +/- 0.6, and 3.5 cm +/- 0.3 for 10%, 15%, and 50% acetic acid alone, respectively; P <.01). The combination of RF ablation with acetic acid resulted in greater coagulation than with either therapy alone (P <.05). However, maximum heating and coagulation were observed with 10% acetic acid diluted in NaCl, with which the entire tumor (diameter, 4.5 cm +/- 0.4) was completely ablated in every case. This was equivalent to results for tumors treated with 36% NaCl combined with RF. RF with a 50% acetic acid concentration resulted in coagulation measuring only 3.7 cm +/- 0.3 (P <.01). Significantly greater RF heating (89.7 degrees C +/- 12.3 at 10 mm) was observed when the tumors were pretreated with 10% or 15% acetic acid in saturated NaCl, compared with 67.9 degrees C +/- 13.7 observed when acetic acid was diluted in water (P <.02). RF combined with ethanol produced less coagulation (2.8 cm +/- 0.3) than combinations with acetic acid because rapid and irreversible impedance increases were observed. CONCLUSION: Addition of acetic acid injections to RF ablation substantially increases tumor destruction compared with RF or injection therapy alone. However, lower acetic acid concentrations in saturated NaCl produced greater tumor coagulation, suggesting that, in this hypovascular tumor model, alterations in electrical conductivity play a more important role in increasing tumor ablation efficiency than do the additional ablative effects of acetic acid.     

Radio-frequency thermal ablation with NaCl solution injection: effect of electrical conductivity on tissue heating and coagulation-phantom and porcine liver study

PURPOSE: To characterize the effects of NaCl concentration on tissue electrical conductivity, radio-frequency (RF) deposition, and heating in phantoms and optimize adjunctive NaCl solution injection for RF ablation in an in vivo model. MATERIALS AND METHODS: RF was applied for 12-15 minutes with internally cooled electrodes. For phantom experiments (n = 51), the NaCl concentration in standardized 5% agar was varied (0%-25.0%). A nonlinear simplex optimization strategy was then used in normal porcine liver (n = 44) to determine optimal pre-RF NaCl solution injection parameters (concentration, 0%-38.5%; volume, 0-25 mL). NaCl concentration and tissue conductivity were correlated with RF energy deposition, tissue heating, and induced coagulation. RESULTS: NaCl concentration had significant but nonlinear effects on electrical conductivity, RF deposition, and heating of agar phantoms (P<.01). Progressively greater heating was observed to 5.0% NaCl, with reduced temperatures at higher concentrations. For in vivo liver, NaCl solution volume and concentration significantly influenced both tissue heating and coagulation (P<.001). Maximum heating 20 mm from the electrode (102.9 degrees C +/- 4.3 [SD]) and coagulation (7.1 cm +/- 1.1) occurred with injection of 6 mL of 38.5% (saturated) NaCl solution. CONCLUSION: Injection of NaCl solution before RF ablation can increase energy deposition, tissue heating, and induced coagulation, which will likely benefit clinical RF ablation. In normal well-perfused liver, maximum coagulation (7.0 cm) occurs with injection of small volumes of saturated NaCl solution.     

Percutaneous tumor ablation: increased coagulation by combining radio-frequency ablation and ethanol instillation in a rat breast tumor model

PURPOSE: To determine if percutaneously applied radio frequency (RF) combined with percutaneous ethanol instillation (PEI) can increase the extent of ablation in rat breast tumors. MATERIALS AND METHODS: R3230 mammary adenocarcinoma was implanted bilaterally in the mammary fat pads of 18 female rats. The tumor nodules measured 1. 2-1.5 cm. Eight tumors each were treated with (a) conventional, monopolar RF (96 mA +/- 28; 70 degrees C for 5 minutes); (b) PEI (250 microL of ethanol infused over 1 minute); (c) combined therapy of PEI immediately followed by RF ablation; or (d) combined therapy of RF ablation immediately followed by PEI. Four tumors were not treated and served as controls. Histopathologic examination included staining for mitochondrial enzyme activity. Resultant coagulation necrosis was compared between treatment groups. RESULTS: Coagulation necrosis was observed only within treated tumors. Tumors treated with RF alone had 6.7 mm +/- 0.6 of coagulation surrounding the electrode, and those treated with PEI alone had 6.4 mm +/- 0.6 of coagulation around the instillation needle (not significant). Significantly increased coagulation of 10.1 mm +/- 0.9 (P: <.001) was observed with the combined therapy of PEI followed by RF. RF followed by PEI did not increase coagulation (6.4 mm +/- 0.8 around the needle; not significant). CONCLUSION: PEI followed by RF ablation therapy increases the extent of induced coagulation necrosis in rat breast tumors, as compared with either therapy alone.     

Injectable polymer depot combined with radiofrequency ablation for treatment of experimental carcinoma in rat

OBJECTIVE: The purpose of this study was to investigate whether an intralesional chemotherapy depot with or without a chemosensitizer could improve the efficacy of radiofrequency (RF) ablation in treatment of experimental carcinoma in rats. MATERIALS AND METHODS: Eighteen BD-IX rats were inoculated with bilateral subcutaneous tumors via injection of DHD/K12TRb rat colorectal carcinoma cells in suspension. Four weeks after inoculation, one tumor in each rat was treated with RF ablation at 80 degrees C for 2 minutes and the other with RF ablation followed by intralesional chemotherapy with carboplatin. The drug was administered via 2 different in situ-forming poly(D,L-lactide-coglycolide) (PLGA) depot formulations either with or without a chemosensitizer. Treatment efficacy was assessed by comparing the change in tumor diameter compared with control, percent of coagulation necrosis and a rating of treatment completeness. RESULTS: Tumors treated with ablation and carboplatin + sensitizer (n = 9) showed a diameter decrease of 49.4 +/- 24.5% at the end point relative to ablation control, while those treated with ablation and carboplatin only (n = 8) showed a 7.1 +/- 12.6% decrease. Use of sensitizer also showed increased tissue necrosis (81.9 +/- 9.7% compared with 68.7 +/- 26.7% for ablation only) and double the number of complete treatments (6/9 or 66.7%) compared with ablation control (3/9 or 33.3%). CONCLUSIONS: From these results, we conclude that intralesional administration of a carboplatin and sensitizer-loaded polymer depot after RF ablation has the potential to improve the outcome of ablation by increasing effectiveness of local adjuvant chemotherapy in preventing progression of tumor unaffected by the ablation treatment.     

Combination radiofrequency ablation with intratumoral liposomal doxorubicin: effect on drug accumulation and coagulation in multiple tissues and tumor types in animals

PURPOSE: To determine whether use of radiofrequency (RF) ablation combined with intravenously (IV) administered liposomal doxorubicin, as compared with use of RF ablation or doxorubicin alone, facilitates increased tissue coagulation and interstitial drug accumulation in animal models. MATERIALS AND METHODS: The institutional animal care and use committee approved this study. In experiment 1, multiple canine sarcomas were implanted in seven mildly immunosuppressed dogs and grown to a mean diameter of 4.8 cm. Tumors were assigned to three treatment groups: internally cooled RF ablation (12 minutes, 2000-mA pulsed technique) followed by IV liposomal doxorubicin (10 mg per animal) (n = 6), RF ablation alone (n = 6), and liposomal doxorubicin alone (n = 4). In experiment 2, the livers and kidneys of 10 rabbits and the thigh muscles of 10 rats were randomly assigned to one of two treatment groups: conventional RF ablation (90 degrees C +/- 2, 5 minutes) followed by IV liposomal doxorubicin (5 mg per rabbit, 1 mg per rat) or RF ablation alone (n = 5, each). Coagulation diameter and interstitial doxorubicin concentration (tissues were homogenized in acid alcohol, with doxorubicin extracted for 24 hours at 5 degrees C and quantified with fluorimetry) were measured 48 hours after treatment and compared. Multivariate analysis of variance and subsequent pairwise t tests (alpha = .05, two-tailed test) were performed. RESULTS: Data are means +/- standard errors of the mean. A larger diameter of tumor destruction was observed in canine sarcomas treated with RF ablation-liposomal doxorubicin (3.7 cm +/- 0.6) compared with that in tumors treated with RF ablation (2.3 cm +/- 0.1) or liposomal doxorubicin (0.0 cm +/- 0.0) alone (P < .01). A new finding was a completely necrotic red zone (1.6 cm +/- 0.7) surrounding the central RF ablation-induced white coagulation zone. Greater but nonuniform drug uptake was observed particularly in this red zone (77.0 ng/g +/- 18.2) compared with uptake in the central zone (15.1 ng/g +/- 3.2), peripheral area of untreated tumor (38.9 ng/g +/- 8.0), and tumors treated with liposomal doxorubicin alone (43.9 ng/g +/- 6.7 for all regions) (P < .01 for all individual comparisons). In experiment 2, use of combined therapy led to increased coagulation in all tissues (liver: 17.6 mm +/- 3.1, P = .03; kidney: 11.0 mm +/- 3.1, P = .03; muscle: 13.1 mm +/- 1.3, P < .01) compared with use of RF ablation alone (liver, 13.4 mm +/- 1.5; kidney, 7.9 mm +/- 0.7; muscle, 8.6 mm +/- 0.5). Combined therapy, as compared with liposomal doxorubicin therapy alone, was also associated with increased doxorubicin accumulation in liver, kidney, and muscle (1.56 microg/g +/- 0.34, 4.36 microg/g +/- 1.78, and 3.63 microg/g +/- 1.43, respectively, vs 1.00 microg/g +/- 0.18, 1.23 microg/g +/- 0.32, and 0.87 microg/g +/- 0.53, respectively) (P < or = .01 for all individual comparisons). CONCLUSION: Use of RF ablation combined with liposomal doxorubicin facilitates increased tissue coagulation and interstitial doxorubicin accumulation in multiple tissues and tumor types and may be useful for treatment of large tumors and achieving an ablative margin within the untreated tissue surrounding RF ablation-treated tumors.     

Percutaneous tumor ablation: reduced tumor growth with combined radio-frequency ablation and liposomal doxorubicin in a rat breast tumor model

PURPOSE: To determine whether combined intravenous liposomal doxorubicin and radio-frequency (RF) ablation decreases tumor growth and increases endpoint survival over those with RF or liposomal doxorubicin alone in an animal tumor model. MATERIALS AND METHODS: Subcutaneous R3230 mammary adenocarcinoma (1.1-1.4 cm) was implanted in female Fischer rats. Initially, 35 tumors were randomized into four experimental groups: (a) conventional monopolar RF (70 degrees C for 5 minutes) alone, (b) liposomal doxorubicin (1 mg) alone, (c) RF ablation followed by liposomal doxorubicin, and (d) no treatment. Ten additional tumors were randomized into two groups that received a 90 degrees C RF dose either with or without liposomal doxorubicin. Tumor growth rates and the defined survival endpoint, the time at which the tumor reached 3.0 cm in diameter, were recorded. The effect of treatments on endpoint survival and tumor doubling time were analyzed by means of the Kaplan-Meier method and analysis of variance statistics. RESULTS: Differences in endpoint survival and tumor doubling time in the six groups were highly significant (P <.001). Endpoint survivals were 9.1 days +/- 2.5 for the control group, 16 days +/- 3.7 for tumors treated with 70 degrees C RF alone, 16.5 days +/- 3.2 for tumors treated with liposomal doxorubicin alone, and 26.6 +/- 5.3 days with combined treatment. For 90 degrees C RF ablation, endpoint survivals were 16.6 days +/- 1.2 and 31.5 days +/- 3.0 without and with liposomal doxorubicin (P <.01). Mean endpoint survival and tumor doubling times for the three RF levels (0, 70 degrees C, and 90 degrees C) were all significantly different (P =.01). Additionally, animals that received combined liposomal doxorubicin and 90 degrees C RF ablation survived longer than did animals that received combined liposomal doxorubicin and 70 degrees C RF ablation (P <.01). CONCLUSION: Combined RF ablation and liposomal doxorubicin retards tumor growth and may increase animal survival compared with that with either therapy alone or no therapy.     

Radiofrequency ablation: effect of surrounding tissue composition on coagulation necrosis in a canine tumor model

PURPOSE: To determine the effect of surrounding tissue type on coagulation necrosis from radiofrequency (RF) ablation in a homogeneous animal tumor model. MATERIALS AND METHODS: Thirty canine venereal sarcomas were implanted in three tissue sites (subcutaneous, kidney, and lung) in 13 mildly immunosuppressed dogs. Five of 25 tumors, which were 19 mm +/- 3 (mean +/- SD) in diameter, were allocated to each of five groups: (a) subcutaneous tumors, (b) kidney tumors, (c) lung tumors with blood flow, and (d) subcutaneous and (e) renal tumors without blood flow, which was achieved by sacrificing the animal to eliminate tumor perfusion. A sixth group comprised larger subcutaneous tumors (mean diameter, 46 mm +/- 4) that were also treated. RF ablation was performed with a 1-cm tip and 5 minutes of ablation at 90 degrees C +/- 1. Impedance, temperature, and resultant coagulation diameter were recorded and compared. Data were analyzed statistically, including one-way analysis of variance to determine the effect of tissue conductivity (ie, systemic impedance) on necrosis size and tissue temperatures. Linear regression analysis was used to compare changes in impedance between the control and experimental groups. RESULTS: Increasing linear correlation was observed between tumor coagulation diameter and overall baseline system impedance (R(2) = 0.65). RF ablation of lung tumors resulted in the greatest coagulation diameter (13.0 mm +/- 3.5) compared with that in the other groups (P <.01). The smallest coagulation diameter was observed in kidney tumors in the presence of blood flow (7.3 mm +/- 0.6) compared with that in the other groups (P <.01). Elimination of blood flow in kidney tumors increased coagulation diameter to 10.3 mm +/- 0.6 (P <.01). After RF ablation, coagulation diameter in the subcutaneous tumor groups was the same (mean, 9.8 mm +/- 1.0) (difference not significant), regardless of tumor size or presence of blood flow. CONCLUSION: The characteristics of tissue that surrounds tumor, including vascularity and electric conductivity, affect ablation outcome. Predominance of tissue-specific characteristics will likely result in site-specific differences in RF-induced coagulation necrosis.     

Radiofrequency ablation: Effect of pharmacologic modulation of hepatic and renal blood flow on coagulation diameter in a VX2 tumor model

PURPOSE: To determine whether pharmacologic agents can be used to modulate blood flow in hepatic and renal tumors sufficiently to alter the extent of radiofrequency (RF)-induced coagulation. MATERIALS AND METHODS: VX2 tumors (8-15 mm) were implanted in the liver (n = 25) or kidney (n = 8) of 33 New Zealand White rabbits. RF was applied to tumors for 6 minutes with use of conventional electrodes (125 mA +/- 35; 90 degrees C +/- 2 degrees C tip temperature). In the hepatic model, blood flow was modulated with use of halothane, epinephrine, or arsenic trioxide (2-6 mg/kg). Laser Doppler flowmetry was used to quantify changes in hepatic blood flow. Correlation of blood flow with induced coagulation diameter was performed. RF ablation was then performed in a renal model with and without arsenic trioxide. RESULTS: For liver tumors, halothane and arsenic trioxide reduced blood flow to 40.3% +/- 17.8% and 29% +/- 15% of normal, respectively, whereas epinephrine increased blood flow to 207.8% +/- 97.9%. Correlation of blood flow to coagulation diameter was demonstrated (R(2) = 0.40). Coagulation measured 7 mm +/- 1 with epinephrine, 10 mm +/- 1 with normal blood flow, 12 mm +/- 3 with halothane, and 13 mm +/- 3 with arsenic trioxide (P <.04 compared with controls). In the renal model, arsenic trioxide decreased blood flow (44% +/- 16%) and increased coagulation diameter (10.9 mm +/- 1) compared with controls (84% +/- 11% and 7.6 mm +/- 1; P <.01, both comparisons). CONCLUSIONS: RF-induced coagulation necrosis in rabbit hepatic and renal tumors is affected by tumor blood flow. Pharmacologic modulation of tumor blood flow may provide a noninvasive way to decrease blood flow during thermally mediated ablation therapy, potentially enabling the creation of larger zones of coagulation necrosis.     

Percutaneous tumor ablation: increased necrosis with combined radio-frequency ablation and intravenous liposomal doxorubicin in a rat breast tumor model

PURPOSE: To determine whether a combination of intravenous liposomal doxorubicin and radio-frequency (RF) ablation increases tumor destruction compared with RF alone in an animal tumor model. MATERIALS AND METHODS: R3230 mammary adenocarcinoma 1.4-1.8-cm- diameter nodules were implanted subcutaneously in 132 female Fischer rats. Initially, tumors were treated with (a) conventional, monopolar RF (mean, 250 mA +/- 25 [SD] at 70 degrees C +/- 1 for 5 minutes) ablation alone, (b) RF ablation followed by intravenous administration of 1 mg of liposomal doxorubicin, (c) RF ablation followed by intravenous administration of 1 mg of empty liposomes, (d) RF ablation and direct intratumoral administration of liposomal doxorubicin, or (e) no treatment. Subsequently, the dose (0.06-2.00 mg) of liposomal doxorubicin, the timing of administration (3 days before to 3 days after RF ablation), and the time of pathologic examination (0-72 hours after treatment) were varied. RESULTS: Mean coagulation diameter for treated tumors follows: 6.7 mm +/- 0.6, RF ablation alone; 11.1 mm +/- 1.5, RF ablation and intravenous administration of empty liposomes (P <.05, compared with RF ablation alone); and 8.4 mm +/- 1.1, RF ablation with intratumoral administration of liposomal doxorubicin (P <.05, compared with RF ablation alone). Maximal increased mean coagulation diameter (13.1 mm +/- 1.5) was observed with a combination of liposomal doxorubicin and RF ablation (P <.001, for all comparisons). The increased coagulation for combination therapy developed over 48 hours after therapy. Coagulation diameter did not vary with the doxorubicin concentration range and was not dependent on the timing of administration of liposomal doxorubicin from 3 days before to 24 hours after RF ablation. CONCLUSION: Intravenous administration of liposomal doxorubicin can improve RF ablation, since it increases coagulation diameter in solid tumors compared with RF ablation alone or a combination of RF ablation with administration of empty liposomes.     

Radiofrequency ablation of the porcine liver in vivo: increased coagulation with an internally cooled perfusion electrode

RATIONALE AND OBJECTIVES: A major limitation of radiofrequency (RF) ablation is its inability to produce a large enough diameter of coagulation necrosis to encompass hepatic tumors with an appropriate ablative margin at a single RF application. We evaluated the in vivo efficiency of RF ablation (RFA) using an internally cooled perfusion (ICP) electrode with hypertonic saline infusion to induce coagulation necrosis compared with that of RFA using single needle electrode types. MATERIALS AND METHODS: RF was applied to a porcine liver in monopolar mode using a 200 W generator and an internally cooled electrode (group A) or an ICP electrode (group B) at 200 W for 12 minutes or using a 60 W generator with a perfusion electrode at 40 W for 20 minutes (group C). In total, 36 (3 x 12) ablation zones were created using the three different regimens. In group B, 14.6% NaCl solution was infused at 1 mL/minute and in group C, 0.9% NaCl solution was infused at 1.5 mL/minute. The three groups were compared in terms of amount of delivered RF energy and dimensions and the coefficients of variation of the ablation zones. RESULTS: The mean energies applied in the three groups were 52.3 +/- 10.3 kJ for group A, 115.4 +/- 10.5 kJ for group B, and 38.5 +/- 11.5 kJ for group C, respectively (P < .05). The mean ablation volumes in groups A, B and C were 13.1 +/- 4.7 cm3 in group A, 43.7 +/- 17.5 cm3 in group B, and 26.3 +/- 20.2 cm3 in group C, respectively (P < .05). In addition, the coefficients of variation of the volumes of the ablation zones in groups A, B, and C were 0.36, 0.4, and 0.78, respectively. CONCLUSIONS: RFA using the ICP electrode showed better performance in terms of creating a larger ablation zone than RFA using an internally cooled or a perfusion electrode.     

Thoracic tumors treated with CT-guided radiofrequency ablation: initial experience

PURPOSE: To determine the effectiveness of computed tomography (CT)-guided radiofrequency (RF) ablation of malignant thoracic tumors. MATERIALS AND METHODS: CT-guided RF ablations of 99 malignant thoracic tumors (3-80 mm in largest diameter; mean, 19.5 mm) were performed in 35 patients in 54 sessions. Ablation was performed with an RF generator by using a single internally cooled electrode. Tumors were both primary (three lesions) and secondary (pulmonary or pleural metastases, 96 lesions). Follow-up was 1-17 months (mean, 7.1 months). Follow-up CT and histopathologic examinations were evaluated. Univariate analysis was performed with the Fisher exact test, and Welch t test was used to evaluate differences between group means. P <.05 represented a significant difference. The maximal diameter of each residual tumor or local recurrence or the proportion of primary lesions of pulmonary metastatic tumors with recurrence after RF ablation were analyzed. Complications, management, and outcomes of the complications were recorded. RESULTS: The appearance of each ablation zone, including the target tumor and surrounding normal lung parenchyma, showed involution at follow-up CT. Local recurrence was demonstrated histopathologically or radiologically in nine tumors. The other 90 tumors showed no growth progression at follow-up CT. Probable complete coagulation necrosis obtained with initial RF ablation was achieved in 91% (90 of 99) of the tumors. The mean maximal diameter of the nine tumors (19.6 mm +/- 7.7 [SD]) was not significantly different (P =.994) from that of the other 90 tumors (19.5 mm +/- 13.0). Primary lesions of those nine metastatic tumors varied and did not demonstrate a specific tendency. Complications included pneumothorax, fever higher than 37.5 degrees C, hemoptysis, cough, pleural effusion, abscess formation, and hemothorax. The overall complication rate was 76% (41 of 54 sessions). CONCLUSION: RF ablation seems to be a promising treatment for malignant thoracic tumors.     

Radiofrequency ablation in pig lungs: in vivo comparison of internally cooled, perfusion and multitined expandable electrodes

The purpose of this study was to compare the amounts of in vivo coagulation obtained by radiofrequency (RF) ablation in porcine lung, using three types of electrodes. 15 in vivo ablation procedures were performed in the lungs of five pigs using three kinds of currently available RF devices under CT guidance. After placing an electrode in the lung, three ablation zones were created at each of three different regimens: Group A: RF ablation with an internally cooled electrode; Group B: RF ablation with a perfusion electrode, with instillation of 0.9% NaCl solution at a rate of 1.5 ml min(-1); Group C: RF ablation with a multitined expandable electrode. According to the manufacturer's recommendations, RF application times were 12 min in group A and 20 min in group B. In group C, RF energy was delivered for 7 min after a mean temperature of 110 degrees C was reached at 5 cm deployment. 36 min after the procedures, contrast-enhanced CT scans were obtained to evaluate the volume of zone of coagulation, and lungs were harvested for gross measurements. After macroscopic and histopathological analyses of 5 mm-thick lung sections, diameters, volumes and variation coefficients of regions of central coagulation were assessed. During RF ablation, the perfusion electrode allowed a larger energy delivery than the internally cooled or the multitined expandable electrodes, i.e. 33.6+/-4.7 kJ in group A, 40.0+/-8.2 kJ in group B and 23.5+/-6.1 kJ in group C (p<0.05). On gross observation, the cut surface of the gross specimen containing RF-induced coagulation showed that the ablated tissue appeared to be a central, firm, dark-brown area surrounded by an irregular outer margin (approximately 3-10 mm thick) of bright red tissue. In vivo studies showed that RF ablation using the perfusion electrode achieved larger coagulation volume than RF ablation using the other electrodes (p<0.05): 7.2+/-4.1 cm3 in group A; 16.9+/-5.5 cm3 in group B; 7.5+/-3.3 cm3 in group C. The corresponding variation coefficients were 0.55, 0.31, and 0.45, respectively. Our study shows that RF ablation using a perfusion electrode achieves a larger coagulation volume with an irregular margin than RF ablation using internally cooled or multitined expandable electrodes in the porcine lung.     

Radio-frequency ablation increases intratumoral liposomal doxorubicin accumulation in a rat breast tumor model

PURPOSE: To determine whether intratumoral accumulation of liposomal doxorubicin or free unencapsulated doxorubicin is increased when combined with radio-frequency (RF) ablation. MATERIALS AND METHODS: Two 1.2-1.5-cm R3230 mammary adenocarcinomas were grown within the mammary fat pads of 19 female Fischer rats. One tumor of each pair was treated with RF ablation (tip temperature, 70 degrees C +/- 2 [SD]; 120 mA +/- 75) for 5 minutes, whereas the other tumor was a control. Intravenous liposomal doxorubicin (1 mg in 500 micro L, n = 6) or intravenous free unencapsulated doxorubicin (n = 7) was administered immediately following RF ablation. Doxorubicin was extracted in acid alcohol from tumors 24 hours following RF ablation, and fluorescent spectrophotometry was used to quantify extracted doxorubicin. Comparisons of intratumoral doxorubicin accumulation in tumors treated with RF ablation and in untreated tumors were analyzed with parametric (paired Student t test) and nonparametric (Wilcoxon rank sum test) statistics. Findings at autoradiography with densitometry (six additional tumors) demonstrated the spatial distribution of the intratumoral accumulation of liposomal doxorubicin. RESULTS: When RF ablation preceded administration of liposomal doxorubicin, mean intratumoral doxorubicin concentration was 5.6 micro g/g +/- 2.1 (range, 1.9-7.7 micro g/g), whereas 1.0 micro g/g +/- 0.4 (range, 0.5-1.5 micro g/g) was present in control tumors not treated with RF ablation (P <.05). Thus, there was a mean 7.1-fold +/- 4.9 increase in intratumoral doxorubicin accumulation following RF ablation (range, 2.1-14.5-fold) compared with the amount without RF pretreatment (P <.05). Increased intratumoral accumulation was not seen in animals receiving free doxorubicin with (mean, 0.4 micro g/g +/- 0.1) or without (mean, 0.8 micro g/g +/- 0.4) RF pretreatment (P =.07). Autoradiographic findings demonstrated accumulation of liposomal doxorubicin in a peripheral rim of tumor adjacent to the zone of coagulation. CONCLUSION: RF ablation augments the delivery of systemic antineoplastic agents such as liposomal doxorubicin.     

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.     

Risk factors for occurrence of local tumor progression after percutaneous radiofrequency ablation for lung neoplasms

PURPOSE: To examine the characteristics of lung tumors for which radiofrequency (RF) ablation therapy is effective, and to determine what RF ablation parameters are effective for obtaining complete coagulation of the entire ablation zone with a single RF ablation session. MATERIALS AND METHODS: Computed tomography (CT)-guided RF ablation of lung tumors was performed on 82 lesions in 34 patients between April 2003 and May 2005. Tumor characteristics and ablation parameters, including tumor size, location, and depth, and ablation duration, power deployed during ablation, and temperatures achieved were analyzed with regard to local tumor progression. RESULTS: In all, 103 RF ablation sessions were performed on 82 tumors. As a procedure-related complication, pneumothorax occurred in 27 procedures. During the mean follow-up period of 10 months (range, 6-28 months), local tumor progression occurred in 18 (22.0%) of the 82 ablated tumors (3 months after RF ablation in 10, 6 months after RF ablation in 5, 9 months after RF ablation in 1, and 12 months after RF ablation in 2). Mean local progression-free duration was 8.7 +/- 4.5 months (range, 3-28 months). The frequency of local tumor progression was significantly correlated with size, whereas other variables had no statistical association. In tumors with a diameter > or =2.5 cm, only the period of ablation during the initial session was significantly correlated with subsequent local tumor progression (P = 0.000002, chi-square test). CONCLUSION: A long duration of RF ablation is desirable for large lung tumors. The success of RF ablation is dependent upon tumor size. RF ablation treatment is most effective for lesions < 2.5 cm.     

Reduced tumor growth with combined radiofrequency ablation and radiation therapy in a rat breast tumor model

PURPOSE: To determine whether use of combined radiofrequency (RF) ablation and external-beam radiation therapy increases end-point survival beyond that with either RF ablation or radiation therapy alone in an animal tumor model. MATERIALS AND METHODS: With a protocol approved by the institutional animal care and use committee, R3230 mammary adenocarcinoma (12.5 mm +/- 0.6 [standard deviation]) was implanted subcutaneously into 107 female Fischer 344 rats. Initially, 42 tumors were randomized into four treatment groups: (a) RF ablation (70 degrees C for 5 minutes) alone, (b) RF ablation followed by radiation therapy with a total dose of 20 Gy, (c) 20-Gy radiation alone, and (d) no treatment. Another 19 tumors were randomized to receive (e) RF ablation (70 degrees C for 5 minutes) followed by 5-Gy radiation, (f) 5-Gy radiation alone, or (g) no treatment. Animals were followed up until survival end point (either until tumor growth to 30 mm in diameter, or for 120 days if no tumor was seen in mammary fat pad or chest wall). Results were analyzed with the Kaplan-Meier method. Histopathologic analysis was performed in 15 additional tumors at survival end point and 18 other representative tumors at other specified end points. RESULTS: Combined RF ablation and 20-Gy radiation resulted in complete local control in nine (82%) of 11 tumors, compared with one (9%) of 11 tumors treated with RF ablation alone and one (17%) of six treated with RF ablation and 5-Gy radiation (P < .001). No local control was achieved in rats with radiation therapy alone or in controls. Median end-point survival was 12 days for controls, 20 days with RF ablation or 5-Gy radiation alone, 30 days with RF ablation plus 5-Gy radiation, 40 days with 20-Gy radiation alone, and 120 days with RF ablation plus 20-Gy radiation. Mean end-point survival was 13 days +/- 5 (standard deviation) for the control group, 34 days +/- 31 with RF ablation alone, and 43 days +/- 16 with 20-Gy radiation alone. Mean survival was significantly greater with 20-Gy radiation and RF ablation combined: 94 days +/- 34 (P < .001 compared with all other groups). Mean survival for rats that received 5-Gy radiation with RF ablation versus without was 46 days +/- 37 versus 24 days +/- 11, respectively. CONCLUSION: Combined RF ablation and external-beam radiation therapy increased animal survival compared with that with either of the treatments alone or with no treatment.     

Percutaneous radiofrequency ablation of renal cell carcinoma: preliminary results

PURPOSE: To report early results in percutaneous radiofrequency ablation (RFA) of renal cell carcinoma with an expandable RF probe. MATERIAL AND METHODS: In 14 patients (9 male, mean age 67.9 +/- 9.9 years) CT-guided percutaneous radiofrequency ablation of 15 renal cell carcinomas was performed using an expandable LeVeen probe (diameter 2-4 cm) and a 200-watt generator under general anesthesia and CT control. Tumors exceeding a diameter of 3 cm (n=6) were embolized within 24 h prior to RFA. Average tumor size was 3.0 +/- 1.0 cm. RESULTS: RFA was technically successful in all patients, resulting in a mean size of necrosis of 3.7 +/- 0.7 cm. With the exception of one reno-cutaneous fistula, which was successfully treated conservatively, no major complications were observed. No local recurrence was observed (follow-up: 13.9 +/- 12.4 months) while extrarenal tumor progression occurred in four patients. CONCLUSION: Our preliminary data suggest that nephron sparing percutaneous RFA of renal tumors with an expandable RF probe is safe and effective.     

Percutaneous radiofrequency ablation of renal tumors: midterm results in 16 patients

PURPOSE: To evaluate the outcome of 16 patients after percutaneous radiofrequency ablation of renal tumors. MATERIALS AND METHODS: Sixteen patients (nine women, seven men; mean age, 61+/-9 years) with 24 unresectable renal tumors (mean volume, 4.3+/-4.3 cm3) underwent CT-guided (n=20) or MR imaging-guided (n=4) percutaneous radiofrequency ablation using an expandable electrode (Starburst XL, RITA Medical Systems, Mountain View, CA) with a 150-W generator. The initial follow-up imaging was performed within 1-30 days after RF ablation, then at 3-6 month intervals using either CT or MRI. Residual tumor volume and coagulation necrosis was assessed, and statistical correlation tests were obtained to determine the strength of the relationship between necrosis volume and number of ablations. RESULTS: Overall, 97 overlapping RF ablations were performed (mean, 3.5+/-1.5 ablations per tumor) during 24 sessions. Five or more RF ablations per tumor created significant larger necrosis volumes than 1-2 (p=.034) or 3-4 ablations (p=.020). A complete ablation was achieved in 20/24 tumors (primary technical success, 83%; mean volume of coagulation necrosis: 10.2+/-7.2 cm3). Three of four residual tumors were retreated and showed complete necrosis thereafter. Three major complications (one percuatneous urinary fistula and two ureteral strictures) were observed after RF ablation. No further clinically relevant complications were observed and renal function remained stable. During a mean follow-up of 11.2 months (range, 0.2-31.5), 15/16 patients (94%) were alive. Only one patient had evidence of local recurrent tumor. CONCLUSION: The midterm results of percutaneous RF ablation for renal tumors are promising and show that RF ablation is well-suited to preserve renal function.     

Comparison of expandable electrodes in percutaneous radiofrequency ablation of renal cell carcinoma

OBJECTIVE: To compare two different expandable electrodes in radiofrequency ablation of renal cell carcinoma. METHODS: Percutaneous ablation was performed at two centers using either an expandable 7F umbrella-shaped LeVeen probe (diameter 2-4 cm) and a 200-W generator (group A), or an expandable Starburst XL electrode with a 150-W generator (group B). From each center, eight patients with one tumor each were matched retrospectively with regard to tumor volume, which was 9.71+/-6.43 cm3 for group A and 8.74+/-4.35 cm3 for group B (mean tumor diameter: 2.47+/-0.9 cm versus 2.50+/-0.4 cm, respectively). An unpaired t-test showed no significant difference in tumor volume between the two groups (p=0.820). RESULTS: Sixteen patients with 16 tumors were treated. The primary technical success of radiofrequency ablation was 94% (15 of 16 patients). After retreatment of residual tumor in one patient from group B, secondary technical success was 100%. No major complications were observed. The resulting mean volume of the almost spherical necroses was 21.1+/-9.1 cm3 versus 14.6+/-6.7 cm3 for groups A and B (diameter of necrosis: 3.5+/-0.7 cm versus 3.1+/-0.6 cm, respectively). A Mann-Whitney U-test showed no significant difference in necrosis volume between the two groups (CI [-0.215; 0.471]; p=0.2892). The calculated shape value of S (ratio of length to height of the coagulation necrosis) was 0.9+/-0.1 and 1.0+/-0.1 for groups A and B, respectively. No local recurrence was observed during a mean follow-up of 14.8+/-11.6 months, while extrarenal tumor progression occurred in three patients. CONCLUSIONS: No significant differences in coagulation volume and shape were found after RF ablation of renal cell carcinoma using two different expandable electrodes. To avoid local recurrence, however, accurate placement of probes and appropriate expansion of the electrode is necessary.     

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.