Percutaneous saline-enhanced radiofrequency ablation of unresectable hepatic tumors: initial experience in 26 patients

OBJECTIVE: The purpose of our study was to evaluate the safety and efficacy of percutaneous saline-enhanced radiofrequency ablation for unresectable primary or metastatic hepatic tumors. SUBJECTS AND METHODS: Twenty-six patients with 15 hepatocellular carcinomas and 33 hepatic metastases (maximum diameter < or = 8.6 cm) were treated; of these, seven tumors in five patients were treated twice. Thus, 44 radiofrequency treatments were performed. Saline-enhanced and impedance-controlled radiofrequency ablation (0.5-1.1 mL/min of saline, 15-mm conductive portion of the electrode tip, 25-60 W, 5-43 min) was performed using MR imaging guidance. Coagulation necrosis, volume indexes, morbidity, and complications were assessed. RESULTS: The volume of coagulation necrosis 1-7 days after radiofrequency ablation was 1.6-126.6 cm(3) (median, 18.9 cm(3)), corresponding to coagulation diameters of 1.5-6.2 cm (median, 3.2 cm). The coagulation volume was significantly larger if there were more than four radiofrequency applications (p = 0.006). Tumors of 3 cm or less in diameter were eight times as likely to be successfully completely ablated (p = 0.01) and volume indexes of lesions treated with the patient under general anesthesia were significantly larger than those treated with the patient under conscious sedation (p < 0.001). Major complications occurred in four patients (15%). Incomplete ablation in 19 (35%) of 54 radiofrequency lesions was due to cooling by a large vessel nearby (n = 2) or to low power applied in painful (n = 11) or critical (n = 6) locations. Residual tumor was observed in 14 (58%) of 24 tumors evaluated 6-8 months after radiofrequency ablation. CONCLUSION: Percutaneous saline-enhanced and impedance-controlled radiofrequency ablation can be effective in the treatment of unresectable hepatic tumors and minimizes potential carbonization. A greater number of radiofrequency applications, general anesthesia, and increasing experience provide significantly better results.     

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.     

Radiofrequency ablation of hepatic tumors: variability of lesion size using a single ablation device

OBJECTIVE: In this study, we examined the variability of lesion sizes produced by a single radiofrequency ablation using the same device and algorithm in patients with small malignant hepatic tumors. MATERIALS AND METHODS: A review of the clinical records of 208 patients who underwent radiofrequency ablation of malignant hepatic tumors during a 6-year period revealed 31 patients with small tumors that were treated with a single ablation. Clinical data were recorded using standardized work sheets. Tumor and lesion sizes after ablation were measured from CT scans. The influences of tumor size, tumor type, presence or absence of cirrhosis, and tissue temperature on the ablation size were analyzed. RESULTS: The size of tumor before treatment ranged from 0.8 to 4.0 cm (mean diameter [+/- SD] = 1.8 +/- 0.9 cm) with corresponding volumes of 0.27-30.24 mL (mean volume = 27.1 +/- 15.9 mL). The lesion sizes after ablation ranged from 1.7 to 5.3 cm (mean diameter = 3.6 +/- 0.7 cm) with corresponding volumes of 2.29-75.87 mL (mean volume = 4.9 +/- 7.1 mL). Tumor type (p > 0.25), presence or absence of cirrhosis (p > 0.45), and tissue temperature (p = 0.055) had no relationship to ablation size. Tumor size had a statistically significant influence on ablation lesion size (p < 0.04). Ablation of small tumors (diameter < or = 2.25 cm, n = 32) produced random lesion sizes whereas ablation of large tumors (diameter > 2.25 cm, n = 11) produced larger lesions (mean diameter = 4.0 +/- 0.8 cm). CONCLUSION: Significant variation occurs in the lesion size produced using the same ablation device and algorithm. These findings must be considered when planning ablation strategies.     

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.     

Radiofrequency ablation in the treatment of small hepatocellular carcinomas: comparison of the radiofrequency effect with and without chemoembolization

OBJECTIVE: The purpose of this study was to determine whether a combination of transcatheter arterial chemoembolization using doxorubicin and radiofrequency ablation can increase tumor destruction compared with radiofrequency alone in the treatment for hepatocellular carcinoma. SUBJECTS AND METHODS. Twenty-one patients with 26 nodules smaller than 3 cm in diameter were treated with radiofrequency ablation. Of these, 10 nodules were treated with a combination of radiofrequency ablation and chemoembolization using doxorubicin. All nodules were evaluated for size of induced coagulation, local recurrence, and complication. RESULTS: The therapeutic areas averaged 27.6 x 22.3 mm using an electrode with a 2-cm tip and 37.2 x 29.1 mm using an electrode with a 3-cm tip. With respect to the results for 14 nodules treated using an electrode with a 3-cm tip with or without chemoembolization, the greatest dimension of the area coagulated by combined therapy was significantly larger (longest axis dimension, 39.9 +/- 4.4 mm; shortest axis dimension, 32.3 +/- 5.2 mm; n = 7 nodules) than areas without chemoembolization (longest axis dimension, 34.6 +/- 2.6 mm; shortest axis dimension, 26.0 +/- 3.3 mm; n = 7 nodules) (longest and shortest axis dimensions, p < 0.05). No recurrence occurred in the nodules smaller than 2 cm in diameter. Among the nodules larger than 2 cm in diameter, one local recurrence was observed in seven nodules treated by combined therapy, while two local recurrences were observed in seven nodules treated by radiofrequency alone. Minor complications developed in three patients, two with persistent high fever and one with biliary stenosis. CONCLUSION: The combination of radiofrequency ablation and transcatheter arterial chemoembolization using doxorubicin markedly increased the extent of induced coagulation compared with radiofrequency alone, despite a small number of patients and the preliminary nature of this study.     

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 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.     

Using multidetector CT for preoperative vascular evaluation of liver neoplasms: technique and results

OBJECTIVE: We evaluated the feasibility, tolerance, and efficacy of percutaneous hepatic vein or segmental portal branch balloon occlusion during radiofrequency ablation of hepatic malignancies. SUBJECTS AND METHODS: Ten tumors were treated by percutaneous radiofrequency ablation during balloon occlusion of a hepatic vein (n = 8) or a segmental portal branch (n = 2). Venous occlusion was undertaken because the tumor was in contact with a hepatic vein (n = 3) or a portal branch (n = 1); because the tumor exceeded 35 mm in width (mean, 44 mm), which was considered the maximum size amenable to ablation in a single session (n = 2); or because of both large size and contact with a hepatic vein (n = 3) or a portal branch (n = 1). RESULTS: Vascular occlusion was always technically possible. Radiofrequency was delivered to one to three locations (mean, 1.9 locations) with a cluster electrode. The largest axis of radiofrequency-induced lesions after ablation with the cluster needle-between 42 and 51 mm (mean, 49 mm)-was always larger than the targeted tumor. These sizes were statistically larger than in a matched control group of patients who underwent radiofrequency ablation without vascular occlusion (p < 0.0003). After a mean follow-up of 12.6 months, CT and MR imaging revealed complete destruction of nine tumors after a single radiofrequency ablation treatment; one tumor required three treatments to achieve ablation. Five patients are tumor-free 12-18 months (mean, 14.4 months) after the first radiofrequency ablation treatment, and five developed new liver metastases. CONCLUSION: Temporary hepatic vein or portal branch occlusion during radiofrequency ablation can safely facilitate the treatment of large tumors or tumors in contact with the walls of large vessels.     

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.     

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.     

Image-guided radiofrequency ablation of Bosniak category III or IV cystic renal tumors: initial clinical experience

The purpose of this study was to assess the efficacy of image-guided radiofrequency (RF) ablation of cystic renal tumors. Between November 2005 and August 2007, computed tomography (CT) or ultrasound-guided RF ablation was performed in nine patients with 14 Bosniak category III (n = 5) or IV (n = 9) cystic renal tumors using an internally cooled RF ablation system. We evaluated the number of sessions, cycles and duration of energy application, treatment results, lesion size change, and complications. Together the cystic renal tumors required 15 sessions and 23 cycles of energy application. The duration of energy application per one tumor ablation ranged from 1 to 12 min (mean 6 min). The last follow-up CT indicated complete coagulation of 14/14 (100%) lesions. None of these tumors had recurred within 1-19 months (mean 8 months). The maximum diameter of the cystic renal tumors was significantly reduced from 2.5 +/- 0.6 cm before ablation to 1.7 +/- 0.7 cm at the last follow-up CT (P < 0.01). Complications were pneumothorax (n = 2), inguinal paresthesia (n = 1), and arteriovenous fistula (n = 1). Image-guided RF ablation is an effective treatment for Bosniak category III or IV cystic renal tumors, which might need relatively shorter duration of energy application than purely solid renal tumors of the same size.     

Intrahepatic tumor recurrence after partial hepatectomy: value of percutaneous radiofrequency ablation

PURPOSE: To determine the risks and benefits of percutaneous radiofrequency (RF) ablation of recurrent hepatic tumors in patients who have undergone hepatic resection. MATERIALS AND METHODS: Retrospective review of the institutional RF ablation database yielded 35 patients with recurrent hepatic tumor after hepatectomy. Sixty-one recurrent hepatic tumors (mean diameter +/- SD, 1.7 +/- 1.1 cm; range, 0.5-5.3 cm) were ablated percutaneously under sonographic guidance or combined guidance with sonographic and fluoroscopic computed tomography (CT). Follow-up CT, magnetic resonance imaging, or both were used for assessment of the primary and secondary therapeutic effectiveness rate and failure of RF ablation. Patients' survival status was determined by contacting the primary care physician or searching the Social Security Death Index. RESULTS: Complete ablation was accomplished in 54 of 61 hepatic tumors (primary therapeutic effectiveness rate, 88.5%). During a mean follow-up time of 18 months (range, 1-65 months), 14.8% of the tumors (n = 9) were incompletely ablated. Three of the nine incompletely ablated tumors were treated with a second RF ablation, all three of which failed (secondary therapeutic effectiveness rate, 0%). Distant intrahepatic tumor progression appeared in 23 of 35 patients (65.7%). One major complication (2.1%, one of 48 sessions) and eight minor complications (16.7%, eight of 48 sessions) were reported. The major complication was hepatic abscess formation. The overall survival rates for all patients at 1, 2, and 3 years were 76%, 68%, and 45%, respectively. For patients with metastases from colorectal cancer (n = 14), the overall survival rates were 72%, 60%, and 60% at 1, 2, and 3 years, respectively; and for patients with hepatocellular carcinoma (n = 8), the overall survival rates were 72%, 58%, and 44% at 1, 2, and 3 years, respectively. CONCLUSION: Percutaneous RF ablation offers a safe and effective treatment option for recurrent hepatic tumors after previous partial hepatectomy.     

Combined radiofrequency and alcohol injection for percutaneous hepatic tumor ablation

OBJECTIVE: We sought to determine if alcohol potentiates radiofrequency energy by obtaining larger ablative volumes in 30 liver tumors in human patients. SUBJECTS AND METHODS: We compared two groups of patients: one group treated with radiofrequency ablation alone (radiofrequency-alone group), and a second group treated with radiofrequency ablation and immediate prior injection of alcohol (combined group). The radiofrequency-alone group comprised 20 ablations (mean diameter, 8.4 cm; colorectal cancer metastases [n = 15]; other metastases [n = 5]). The combined group consisted of 30 radiofrequency ablations (mean diameter, 8.8 cm; metastatic colorectal cancer [n = 17]; other metastases [n = 8]; and hepatocellular carcinoma [n = 5]) treated with alcohol injection immediately before radiofrequency ablation. The amount of alcohol injected was determined by the size and location of tumors. Preprocedural laboratory tests (complete blood cell count with differential, liver function tests, and coagulation parameters) were performed in all patients, along with pre- and postprocedural CT, MRI, and PET. Measurements of tissue necrosis were obtained on the postprocedural CT scans and MR images. Volumes of necrosis calculated in each group were corrected for the number of radiofrequency applications and were statistically compared using the Student's t test. In addition, tissue impedances obtained during the radiofrequency ablation procedure were compared between the two groups. RESULTS: The mean ablation volumes for the radiofrequency-alone group were 32.3 cm(2) (median, 28.6 cm(2); range, 14.4-61.8 cm(2)) and for the combined group, 84.6 cm(2) (median, 78.3 cm(2); range, 34.6-149 cm(2)). The difference in the necrosis volumes was significantly larger (p < 0.0001) in the combined group. Overall, the combined treatment group underwent fewer radiofrequency applications per session. Tissue impedance during radiofrequency ablation was higher in the combined group (mean, 62.7 vs 57.3 Omega in the radiofrequency alone group; p = 0.0005) at comparable times during the ablations. No major complications were seen in either group. CONCLUSION: Percutaneous radiofrequency ablation appears to be potentiated by immediate prior alcohol injection into the tumor. Consistently larger lesions are obtainable in fewer sessions, without any increase of complications, using the combined method.     

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.     

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.     

Comparison of renal ablation with monopolar radiofrequency and hypertonic-saline-augmented bipolar radiofrequency: in vitro and in vivo experimental studies

OBJECTIVE: We sought to determine whether hypertonic-saline (HS)-augmented bipolar radiofrequency ablation has advantages over monopolar radiofrequency ablation for creating larger areas of coagulation necrosis in the kidney. MATERIALS AND METHODS: Using a 200-W generator and bipolar perfused-cooled electrodes or a monopolar cooled-tip electrode, we performed 14 radiofrequency ablations in explanted bovine kidneys. Radiofrequency was applied in standard monopolar (n = 7) or bipolar (n = 7) modes at 100 W for 10 min. In the bipolar mode, the perfused-cooled electrodes were placed at interelectrode distances of 3 cm, and a 6% sodium chloride solution was instilled into tissue at a rate of 2 mL/min through the electrodes. For in vivo experiments, either monopolar (n = 7) or HS-augmented bipolar (n = 7) radiofrequency ablation was performed in the lower pole of canine kidneys. Three days after the procedure, contrast-enhanced CT scans were obtained to evaluate the volumes of the ablation regions, and the kidneys were harvested for gross measurements. Technical parameters such as changes in impedance and current during radiofrequency ablation and dimensions of the thermal ablation zones were compared between the two groups. RESULTS: In ex vivo and in vivo experiments, the frequency of the pulsed radiofrequency application caused by rises in impedance was higher in the monopolar mode than in the bipolar mode during the application of radiofrequency energy. The in vivo study showed that the bipolar radiofrequency ablation allowed larger mean current flows than the monopolar radiofrequency ablation (i.e., mean +/- SD, 1,654 +/- 144 mA vs 967 +/- 597 mA) (p < 0.05). Ex vivo studies revealed that the volumes of bipolar radiofrequency-induced ablation regions were substantially larger than those of monopolar radiofrequency-induced ablation regions (26.1 +/- 10.5 cm(3) vs 10.2 +/- 4.2 cm(3)). In vivo studies showed bipolar radiofrequency ablation achieved larger coagulation necrosis than monopolar radiofrequency (3.2 +/- 0.3 cm vs 2.4 +/-0.4 cm) (p < 0.05). This was confirmed by the measured volume of nonenhancing area on contrast-enhanced CT (20.4 +/- 6.4 cm(3) vs 13.5 +/- 6.0 cm(3)). CONCLUSION: HS-augmented bipolar radiofrequency ablation using perfused-cooled electrodes shows better performance in creating coagulation necrosis than monopolar radiofrequency ablation in the kidney of an animal model.     

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.     

Effect of vascular occlusion on radiofrequency ablation of the liver: results in a porcine model

OBJECTIVE: This study determined the effect of vascular occlusion on radiofrequency lesion shape, volume, and temperature in a porcine liver model. SUBJECTS AND METHODS: Radiofrequency lesions (n = 33) were created in the livers of six domestic pigs in vivo using a multiprong radiofrequency electrode. Lesions were randomly assigned to one of four vascular occlusion groups: portal vein, hepatic artery, Pringle maneuver (both hepatic artery and portal vein), or no occlusion. Radiofrequency parameters were time, 7 min; power, 50 W; and target temperature, 100 degrees C. Temperatures were measured 5, 10, and 15 mm from the electrode. After the animals were sacrificed, the lesions were excised. Lesion volume, diameter, and shape; maximum temperature; and time exposed to lethal temperatures (42-60 degrees C) were determined. RESULTS: Lesion volume was greatest with the Pringle maneuver lesions (12.6 +/- 4.8 cm(3)), followed by occlusion of the portal vein (8.6 +/- 3.8 cm(3)), occlusion of the hepatic artery (7.6 +/- 2.9 cm(3)), and no occlusion (4.3 +/- 1.0 cm(3)) (p < 0.05). Maximum lesion diameter was similar with the Pringle maneuver (3.3 +/- 0.3 cm), the portal vein (3.3 +/- 0.2 cm), and the hepatic artery (3.2 +/- 0.2 cm) groups compared with no occlusion (2.6 +/- 1.0 cm) (p < 0.05). Minimum lesion diameter ranged from 2.9 cm for Pringle maneuver lesions to 1.0 cm for lesions with no occlusion (p < 0.05). Vascular occlusion increased the time tissue was exposed to lethal temperatures (> 42-60 degrees C) and created more spherical lesions than no occlusion. CONCLUSION: Vascular occlusion combined with radiofrequency ablation increases the volume of necrosis, creates a more spherical lesion, and increases the time tissue is exposed to lethal temperatures when compared with radiofrequency alone. Most of this vascular occlusion effect could be accomplished with hepatic artery occlusion alone.     

Percutaneous image-guided thermal ablation and radiation therapy: outcomes of combined treatment for 41 patients with inoperable stage I/II non-small-cell lung cancer

PURPOSE: To evaluate the clinical outcomes in patients with early-stage non-small-cell lung cancer (NSCLC) after combined treatment with thermal ablation and radiation therapy (RT). MATERIALS AND METHODS: Forty-one patients with inoperable stage I/II NSCLC tumors underwent thermal ablation and RT at our institution between 1998 and 2005. Thirty-seven radiofrequency (RF) ablation procedures and four microwave ablation procedures were performed. Ablations were followed by standard-fraction external-beam RT within 90 days (n = 27) or postprocedural brachytherapy (n = 14). Survival and local recurrence were the primary endpoints evaluated by Kaplan-Meier analysis. RESULTS: The median follow-up was 19.5 months. The overall survival rates were 97.6% at 6 months, 86.8% at 1 year, 70.4% at 2 years, and 57.1% at 3 years. Patients with tumors smaller than 3 cm (n = 17) had an average survival time of 44.4 +/- 5.4 months (SE). Patients with tumors 3 cm or larger (n = 24) had an average survival time of 34.6 +/- 7.0 months (P = .08). Local recurrence occurred in 11.8% of tumors smaller than 3 cm after an average of 45.6 +/- 4.1 months and in 33.3% of the larger tumors after an average of 34.0 +/- 7.8 months (P = .03). Outcomes in the brachytherapy and RT groups did not differ significantly. Nine of 15 pneumothoraces required chest tube drainage (22.0%). CONCLUSIONS: Thermal ablation followed by RT for inoperable stage I/II NSCLC has a relatively low rate of complications that are easily managed. Combined therapy may result in an improved survival compared with either modality alone.     

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.