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.     

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.     

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.     

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.     

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.     

Improved coagulation with saline solution pretreatment during radiofrequency tumor ablation in a canine model

PURPOSE: To determine whether pretreatment with local NaCl injection can increase radiofrequency (RF)-induced coagulation in a large animal model. MATERIAL AND METHODS: Multiple canine venereal sarcomas (n = 25) were implanted subcutaneously in eight mildly immunosuppressed dogs (25 mg/kg cyclosporin A twice daily). Tumors were incubated for 8-12 weeks to a diameter of 4.2-6.3 cm (5.1 cm +/- 0.7). Internally cooled RF ablation (1-cm tip; 12 min; pulsed technique; 2,000-mA maximum) was performed. Tumors were pretreated with 6 mL of 18%, 24%, or 36% NaCl injected intratumorally under direct ultrasound guidance after RF electrode insertion, and this treatment was compared to RF treatment without NaCl injection and to 36% NaCl injection without RF ablation. Impedance measurements and remote thermometry were performed. These measurements and resultant coagulation were compared. RESULTS: Significantly greater RF heating (73 degrees C +/- 11 degrees C at 20 mm) was observed when the tumors were treated with 24% or 36% NaCl pretreatment, compared to the 47 degrees C +/- 5 degrees C observed when 18% or no NaCl was injected (P <.02). In the 36% NaCl group, the entire tumor (5.2 cm +/- 0.8 diameter) was completely ablated in every case, with coagulation extending several centimeters into the surrounding tissues. By comparison, control tumors (without NaCl injection) contained coagulation measuring 3.1 cm +/- 0.2, surrounded by viable, well-perfused tumor (P <.01), and 36% NaCl alone produced 2.7 cm +/- 0.6 of patchy necrosis. CONCLUSIONS: Pretreatment with intratumoral injection of small volumes of highly concentrated NaCl markedly increases RF heating and coagulation in a large animal tumor model. The complete destruction of tumors 5 cm in diameter or larger suggests that this substantial increase may be achieved for tumor ablation in clinical practice.     

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.     

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.     

Combined radiofrequency ablation and adjuvant liposomal chemotherapy: effect of chemotherapeutic agent, nanoparticle size, and circulation time

PURPOSE: To evaluate the effects of liposomal chemotherapeutic agent, nanoparticle size, and liposome circulation time on tissue coagulation and intratumoral drug uptake when radiofrequency (RF) ablation is combined with adjuvant intravenous liposomal chemotherapy in an animal breast tumor model. MATERIALS AND METHODS: Ninety-one R3230 mammary adenocarcinoma nodules were implanted in 48 Fischer rats. First, standardized RF ablation was combined with intravenous liposomal doxorubicin, cisplatin, or 5-fluorouracil (35 tumors each). Second, three different-sized doxorubicin-containing nanoparticle preparations were combined with standardized RF ablation. Last, two doxorubicin-containing liposome preparations with different blood elimination half-lives were combined with RF ablation. Coagulation diameter and interstitial doxorubicin concentration were measured 48 hours after treatment and compared with use of statistical analysis. RESULTS: All combinations of RF with liposomal chemotherapy caused significantly greater tumor necrosis than RF alone (P<.05). Significantly increased necrosis was observed with intravenous liposomal RF/doxorubicin and RF/cisplatin compared with intravenous liposomal RF/5-fluorouracil (P<.01). Greater coagulation was observed with RF combined with 100-nm nanoparticles compared with 20-nm or 250-nm nanoparticles (P=.01 and P=.04, respectively). Additionally, greater intratumoral doxorubicin uptake was observed in the group treated with 20-nm nanoparticles compared with those treated with other sizes of nanoparticles (P<.05). RF plus liposomal doxorubicin produced greater coagulation and intratumoral doxorubicin uptake than RF plus 1,2-dipalmitoyl-sn-glycero-3-phosphatidic acid (P<.05). CONCLUSION: When combined with RF ablation, modification of adjuvant intravenous liposomal chemotherapy, including nanoparticle size, circulation time, and chemotherapeutic agent, can influence intratumoral drug accumulation and tissue coagulation.     

Dual-probe radiofrequency ablation: an in vitro experimental study in bovine liver

OBJECTIVE: To determine whether alternative radiofrequency (RF) application with dual probes has advantages over sequential or simultaneous RF application for creating larger coagulation necrosis. MATERIALS AND METHODS: Using 2 17-gauge internally cooled electrodes and a 200-watt generator (CC-3 model, Radionics), RF energy was applied sequentially (group A, n = 20), simultaneously (group B, n = 20), or alternately (group C, n = 20) to explanted bovine liver. After preliminary experiments with a probe distance of 2-5 cm, a distance of 2 cm and 3 cm were chosen for main experiments. Total duration of the RF application was 10 minutes. In the alternative mode, the energy was applied alternately to both RF electrodes in 2-second intervals. Changes occurring in tissue impedance, current, power output, and temperature at the midpoint between the 2 electrodes were measured. The technical parameters, temperatures, and dimension of the ablated area were compared in the 3 groups using analysis of variance or Kruskal-Wallis test. RESULTS: In the groups B and C, the impedance was gradually decreased during RF application and the mean current flow of both groups was 1550 +/- 130 mA and 1375 +/- 175 mA, respectively. However, in the group A, the impedance was markedly increased during RF application, and the mean current was 940 +/- 484 mA (P < 0.05, between groups A and B, and groups A and C). With 3-cm spacing, the alternative RF application created oval-shaped ablation zones with larger shortest axis diameter at the midpoint than either the sequential or simultaneous RF application: 12.0 +/- 7.1 mm in group A; 27.0 +/- 3.1 mm in group B; 34.9 +/- 3.4 mm in group C (P < 0.05). With 2 cm spacing, the corresponding figures were 25.3 +/- 7.8 mm in group A; 34.9 +/- 7.8 mm in group B; 41.5 +/- 1.8 mm in group C (P < 0.05): the differences between groups A and B, and between groups A and C were statistically significant (P < 0.05). With 3-cm spacing, the temperature at the midpoint between the 2 probes was higher in group C (102 degrees C) than in either the group A (62 degrees C) or the group B (78 degrees C; P < 0.05). With 2-cm spacing, groups B and C showed higher temperature than group A (P < 0.05), but the difference between groups B and C was not significant (P > 0.05). CONCLUSION: The alternative RF application creates larger, more regular ablation zones than either the sequential or simultaneous RF application. This result suggests that use of an alternating RF power application will improve the results of RF ablation for the treatment of larger tumors.     

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.     

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.     

Effects of perfusion on radiofrequency ablation in swine kidneys

PURPOSE: To evaluate the effect of vascular occlusion on the size of radiofrequency (RF) ablation lesions and to evaluate embolization as an occlusion method. MATERIALS AND METHODS: The kidneys of six swine were surgically exposed. Fifteen RF ablation lesions were created in nine kidneys by using a 2-cm-tip single-needle ablation probe in varying conditions: Seven lesions were created with normal blood flow and eight were created with blood flow obstructed by means of vascular clamping (n = 5) or renal artery embolization (n = 3). The temperature, applied voltage, current, and impedance were recorded during RF ablation. Tissue-cooling curves acquired for 2 minutes immediately after the ablation were compared by using regression analysis. Lesions were bisected, and their maximum diameters were measured and compared by using analysis of variance. RESULTS: The mean diameter of ablation lesions created when blood flow was obstructed was 60% greater than that of lesions created when blood flow was normal (1.38 cm +/- 0.05 [standard error of mean] vs 0.86 cm +/- 0.07, P <.001). The two methods of flow obstruction yielded lesions of similar mean sizes: 1.40 cm +/- 0.06 with vascular clamping and 1.33 cm +/- 0.07 with embolization. The temperature at the probe tip when lesions were ablated with normal blood flow decreased more rapidly than did the temperature when lesions were ablated after flow obstruction (P <.001), but no significant differences in tissue-cooling curves between the two flow obstruction methods were observed. CONCLUSION: Obstruction of renal blood flow before and during RF ablation resulted in larger thermal lesions with potentially less variation in size compared with the lesions created with normal nonobstructed blood flow. Selective arterial embolization of the kidney vessels may be a useful adjunct to RF ablation of kidney 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.     

Hepatic bipolar radiofrequency ablation using perfused-cooled electrodes: a comparative study in the ex vivo bovine liver

The purpose of this paper was to demonstrate the efficacy of the dual probe bipolar radiofrequency (RF) system with the perfused-cooled electrodes inducing coagulation necrosis in the ex vivo bovine liver. The perfused-cooled electrode that allows simultaneous internal cooling and interstitial hypertonic saline perfusion has been developed for RF ablation (RFA). RF was applied to excised bovine liver in a bipolar mode at 150 W using a 200 W generator with two perfused-cooled electrodes for 10 min. After placing the electrodes at 3 cm spacing in the explanted liver, 45 ablation zones were created with three different regimens: Group A, using both intraelectrode cooling and interstitial perfusion; group B, using only the intraelectrode cooling; and group C, using only interstitial perfusion. In groups A and C, RFA was performed with the infusion of 6% hypertonic saline at the rate of 2 ml min(-1). During RFA, we measured the tissue temperature at the midpoint between the two electrodes. The dimensions of the ablation zones and the changes in impedance, currents and liver temperature during RFA were compared in these three groups. The mean tissue impedance during RFA in group A (56.7+/-21.7 Omega) and group C (56.9+/-20.6 Omega) was significantly lower than group B (112+/-19.7 Omega) (p<0.001). The mean current was higher in group A (1765+/-128 mA) than groups B (760+/-321 mA) and C (1298+/-349 mA) (p<0.05). In addition, the shortest vertical diameter of coagulation necrosis was greater in groups A (4.9+/-0.5 cm) and C (4.6+/-0.7 cm) than in group B (3.5+/-0.4 cm) (p<0.05). The temperature at the mid-point between the two probes was higher in group A than other groups: 99 degrees C in group A, 88.9 degrees C in group B, and 94.3 degrees C in group C (p>0.05). The ratios of the diameter of the long-axis to the diameter of the vertical-axis of groups A, B and C were 1.1+/-0.1, 1.2+/-0.1, and 1.1+/-0.2, respectively (p<0.05). Bipolar RFA using intraelectrode cooling and the interstitial saline perfusion simultaneously produced ablation zones significantly larger than the area produced by only one measure.     

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.     

Percutaneous radiofrequency (RF) thermal ablation of rabbit tumors embedded in fat: a model for RF ablation of breast tumors

RATIONALE AND OBJECTIVES: To develop an experimental tumor model for RF ablation of breast tumors surrounded by fat and to investigate the minimally invasive treatment of such tumors by saline-enhanced RF ablation monitored by ultrasound (US). METHODS: Twenty-eight VX2 tumors were implanted into the retroperitoneum of 14 rabbits and monitored by B-mode US at regular intervals of 2 to 3 days. Saline-enhanced RF ablation (25-mm tip length) was performed 16 days after tumor implantation (10-minute treatment time, 28 W, 15 mL/h infusion of 0.9% NaCl, which was increased to 30 mL/h in cases of an impedance increase). Thermal lesion growth was monitored by B-mode US. Treatment was considered complete if no relapse was detectable histopathologically after a follow-up period of up to 3 weeks. RESULTS: All tumor implantations were successful, reaching sizes from 5 to 38 mm 16 days after implantation. Tumors >20 mm showed central necrosis on US. Smaller tumors without signs of necrosis required greater needle perfusion to maintain constant needle-to-tissue impedance. Local relapses occurred in 14 of 27 tumors (51.8%), all with tumors >20 mm. In 12 cases, they were already detected sonographically. In 2 cases, "islands" of vital tumor were detected only during histopathological assessment. CONCLUSIONS: VX2 tumors are implantable into hypovascular adipose tissue with a high success rate and may be used as a model for RF ablation of breast tumors. B-mode US is not suitable for guiding RF ablation of tumors embedded in fat. The method appears to be more successful with smaller tumors.     

Radio-frequency-induced coagulation necrosis in rabbits: immediate detection at US with a synthetic microsphere contrast agent.

PURPOSE: To determine whether a synthetic ultrasonographic (US) contrast agent can be used to differentiate coagulation necrosis from untreated tumor immediately after radio-frequency ablative therapy. MATERIALS AND METHODS: VX2 (adenocarcinoma) tumors (0.8-1.5-cm diameter) were implanted into 12 rabbits. Gray-scale and color Doppler US were performed with or without intravenous injection of a US contrast agent composed of poly-lactide-co-glycolic acid polymeric (PLGA) microspheres (2-micron diameter) filled with perfluorocarbon gas. Radio frequency was applied to each nodule for 6 minutes at 127 mA +/- 33 (mean +/- SD) (tip temperature, 92 degrees C +/- 2). Repeat US with a second dose of the contrast agent was performed immediately after ablation. In four animals, a third dose was administered 30-120 minutes after ablation. Radiologic-histopathologic correlation was performed and included in vivo staining and studies of mitochondrial function. RESULTS: Intense contrast agent enhancement was seen throughout the tumor prior to ablation. At gray-scale US, ablation produced hyperechoic foci, which were within 1 mm of the foci identified at histopathologic examination in seven of 12 animals (58%). After the administration of contrast material, foci devoid of previously visualized enhancement, which measured 7.3-15.0 mm, were identified. These were within 1 mm of the size of the foci identified at histopathologic examination in 11 of 12 animals (92%, P < .01). In two animals, enhancement depicted viable tumor, which appeared hyperechoic, on nonenhanced images. On delayed images, hyperechoic areas decreased in size, whereas the nonenhanced region remained unchanged. CONCLUSION: A PLGA microspherical US contrast agent enabled the immediate detection of coagulation necrosis as a region devoid of contrast enhancement after radio-frequency ablation in rabbit hepatic tumors. Therefore, this agent could provide real-time guidance during complex ablative procedures and may provide an efficient technique for postprocedural assessment.     

Radio-frequency ablation of VX2 rabbit tumors: assessment of completeness of treatment by using contrast-enhanced harmonic power Doppler US

PURPOSE: To assess contrast material-enhanced harmonic power Doppler and fundamental color Doppler ultrasonography (US) in the detection of residual viable tumor tissue after radio-frequency (RF) ablation in tumors embedded in fat. MATERIALS AND METHODS: Twenty-eight VX2 tumors were implanted into the retroperitoneum of 14 rabbits. Tumors were examined with contrast-enhanced fundamental color Doppler US and harmonic power Doppler US before and 10 minutes after RF ablation. Saline-enhanced RF ablation (30 mL/h) was performed over 10 minutes with 28-W RF power. Follow-up included repeat US examinations. Necropsies and histopathologic assessment were performed after detection of residual untreated tumor at US or 3 weeks after ablation. RESULTS: VX2 tumors reached a mean size of 21 mm +/- 9 (SD) (size range, 6-43 mm) 25 days after implantation. All tumors larger than 31 mm showed signs of central necrosis at US. Before ablation, intense vascularity was detected in all tumors with both contrast-enhanced US modes. Histopathologic assessment at the end of the follow-up period revealed local relapses due to incomplete ablation in 14 (50%) of 28 cases. Detection of residual tumor was missed in all cases with contrast-enhanced color Doppler US. Contrast-enhanced harmonic power Doppler US depicted residual flow in 12 of the 14 cases (sensitivity, 86%) in which local relapses occurred. There was a significant (P <.005, McNemar test) improvement in detection of residual tumor when the harmonic power Doppler mode was used. CONCLUSION: Contrast-enhanced harmonic power Doppler US has greater sensitivity than contrast-enhanced color Doppler US for detecting residual VX2 tumor following ablation. Therefore, contrast-enhanced harmonic power Doppler US may be a useful additional method for the detection of residual tumors after RF ablation.