Coagulation Diameter Research Articles

Ablative effect of the interstitial laser setting in the human placental model.

To assess the impact of laser power and time on interstitial ablation generated by neodymium-doped yttrium aluminium garnet (Nd:YAG) and diode laser in the human placental model. The experiment was carried out in a simulation model of interstitial laser ablation on ex-vivo placental tissue. One-hundred and forty-four pieces of fresh placentae were interstitially ablated with Nd:YAG or diode laser at various power (15, 20, 25, 30 W)-time (5, 10, 15 s) combinations. The ablation tissues were evaluated using both sonographic and histopathologic measurements. Laser generator, power, and time significantly affected the ablation size (p < 0.001). The coagulation zone continuously increased with extending time at the power of 15, 20, and 25 W. When adjusting to the power of 30 W, increased time from 10to 15 s did not induce the larger coagulation diameter. The maximal diameter was obtained at the laser power of 20 W for 15 s. The ablation from the diode laser was greater than that from Nd:YAG laser. The sonographic evaluation overestimated the ablation size by an average of 24%. Diode laser destroys greater tissue than Nd:YAG laser. Different power settings of interstitial laser ablation produce diverse patterns of correlation between laser time and coagulation size.

Percutaneous radiofrequency ablation of HCC: reduced ablation duration and increased ablation size using single, internally cooled electrodes with an optimized pulsing algorithm

Purpose To assess the use of optimized radiofrequency (RF) to achieve larger, spherical ablation volumes with short application duration for hepatocellular carcinoma (HCC). Materials and methods Twenty-two patients (M:F = 17:5, median age 69.6 year, range 63–88) with 28 HCCs due to HCV + liver cirrhosis underwent RFA. 20/28 (71.4%) were tumors ≤3cm diameter, and 8/28 (28.6%) ranged from 3.2 to 4.2 cm. RF was applied using up to 2500mA via an optimized pulsing algorithm with real-time ultrasound monitoring to detect hyperechogenic changes. Single insertions of an internally cooled electrode were performed using exposed tips of 2 or 3 cm for 13 HCCs and 4 cm for 15 HCCs. All patients were followed-up for a minimum of 5 years with contrast-enhanced computed tomography (CECT). Results Technical success was achieved without adverse events in all cases. The mean ablation time was 8.5 ± 2.6 min. In 21/28 (75%), ablation duration ranged from 3 to 9 min, with 12 min duration applied in only 7/28 (25%). Mean coagulation diameters were 2.4 ± 0.14, 3.3 ± 0.62, and 4.4 ± 1.0, for 2, 3 and 4 cm electrodes, respectively (p < 0.01). The sphericity index was 74.9 ± 12.8 for 4 cm electrodes and 81.9 ± 8.0 for shorter electrodes (p = 0.091). At 5-year follow-up, no tumor ≤3 cm had recurrence and only 2/8 (25%) >3 cm tumors developed local progression. One patient had multifocal disease with no local progression. Conclusion Efficient delivery of RF energy can considerably decrease the ablation time in many instances while achieving larger, relatively spherical, and reproducible areas of ablation with extremely low rates of local tumor progression and adverse events.

Hepatic Microwave Ablation-Induced Tumor Destruction and Animal End Point Survival Can Be Improved by Suppression of Heat Shock Protein 90.

To investigate the effect of heat shock protein 90 (HSP90) modulation on tumor necrosis, apoptosis, tumor growth delay, and end point survival by combining microwave ablation (MWA) with an HSP90 inhibitor in a nude mouse model. This study was approved by the Ethics Committee. Forty mice with HepG2 subcutaneous xenograft tumors (10 ± 1 mm) were randomized into 4 groups: (1) no treatment, (2) MWA only, (3) the HSP90 inhibitor ganetespib only, and (4) ganetespib combined with MWA. Tumors were harvested 24 hours after treatment, and gross coagulation diameters were measured. The effect of ganetespib on HSP90 and caspase 3 expression in the periablational rim was assessed. Another 40 mice with the same tumors and groupings were observed after treatment. Tumor growth curve and Kaplan-Meier survival analyses were performed with a tumor diameter of 2.2 cm and 40 days of survival as the defined survival end points. Combination treatment significantly increased the coagulation size compared to tumors treated with MWA or ganetespib alone (P < 0.05). The combination of MWA and ganetespib decreased HSP90 expression and increased cleaved caspase 3 expression 24 hours after treatment. Compared with MWA or ganetespib only, combination treatment could lengthen the end point survival and reduce the tumor growth rate. Modulation of HSP production can improve MWA-induced tumor apoptosis and destruction, reduce residual tumor growth rates, and prolong end point survival.

Prediction of laser-induced thermal damage with artificial neural networks

Laser-induced thermotherapy (LITT) has been widely studied since it is a minimally invasive technique for focal destruction of liver tumors without side effects. However, there are still some concerns about the treatment and monitoring thermal effects during operation. Although real-time imaging modalities are available, like magnetic resonance imaging, they are not cost-effective and not applicable to all conditions. This paper presents artificial neural network (ANN) modeling of laser-induced thermal damages on ex vivo liver tissue. In this work three laser sources, i.e. a diode pumped laser with a wavelength of 980 nm, a 1070 nm yttrium lithium fluoride fiber laser, and a 1940 nm thulium fiber laser, were used in order to thermally damage tissues by applying the laser until coagulation observed. The diameter and depth of coagulation were empirically measured and used to train the ANN model by finding the correlation between laser parameters (application time, power, penetration depth, wavelength, and spot size) and thermal damages. Thermal damage can be determined by observing coagulation diameter and coagulation depth. The prediction ability and accuracy of the trained ANN model were tested by comparing the actual and simulated results. Our result showed that the ANN successfully predicts LITT damage in terms of coagulation diameter and coagulation depth, with a very high accuracy. The trained ANN model was compared with two mathematical models. In terms of performance, the ANN is a very useful and practical tool for determining LITT damage.

Microwave ablation of ex vivo human undifferentiated pleomorphic sarcoma

Background: Many undifferentiated pleomorphic sarcoma (UPS) patients had lost the opportunity of surgical therapy. Microwave (MW) ablation of UPS can be an effective method for achieving local tumor control while preserving the relative function. We report for the first time the size of the ablation zone and temperature distribution of MW ablation on ex vivo human UPS specimens. Methods: Twenty UPS patients’ specimens were recruited into present experimental study (11 men, 9 women, average age 52±14.7 years). A commercial 2,450 MHz MW ablation apparatus was used throughout this experiment. MW ablations were performed immediately after resection of tissue specimens by using powers of 40, 60, 80 and 100 W for 10 min, and each power setting was performed in five specimens. Coagulation shape, lesion size, and temperature distributions were recorded. Histological examination was performed to assess the pathological changes of the ablation issue. Results: All coagulation geometries were ellipsoidal under the four power settings (40, 60, 80 and 100 W for 10 min) with a ratio of short-axis/long-axis range from 0.80 to 0.88. The short-axis diameters of the coagulation at 40, 60, 80 and 100 W groups were 28.2±1.1, 35.6±1.3, 40.6±1.6, and 46.4±1.7 mm, respectively; and the corresponding long-axis were 33.4±1.5, 41.4±1.7, 47.6±1.8, and 54.2±2.1 mm, respectively. Overall, temperatures at 3 points of distance 10, 20, and 30 mm from antenna increased along with ablation time. Routine histological analysis using haematoxylin-eosin (H&E) showed tissue fixation within the ablation area. Conclusions: The present ex vivo experiment showed that MW ablation by single 2,450 MHz antennae could generate an ellipsoidal coagulation geometry and large ablation zone, which increases with increasing power and time. This initial study provides experimental evidence for clinical MW ablation of UPS.

Ex Vivo Liver Experiment of Hydrochloric Acid-Infused and Saline-Infused Monopolar Radiofrequency Ablation: Better Outcomes in Temperature, Energy, and Coagulation.

To compare temperature, energy, and coagulation between hydrochloric acid-infused radiofrequency ablation (HAIRFA) and normal saline-infused radiofrequency ablation (NSIRFA) in ex vivo porcine liver model. 30 fresh porcine livers were excised in 60 lesions, 30 with HAIRFA and the other 30 with NSIRFA. Both modalities used monopolar perfusion electrode connected to a RF generator set at 103 °C and 30 W. In each group, ablation time was set at 10, 20, or 30 min (10 lesions from each group at each time). We compared tissue temperatures (at 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 cm away from the electrode tip), average power, deposited energy, deposited energy per coagulation volume (DEV), coagulation diameters, coagulative volume, and spherical ratio between the two groups. Temperature-time curves showed that HAIRFA provided progressively greater heating than that of NSIRFA. At 30 min, mean average power, deposited energy, coagulation volumes (113.67 vs. 12.28 cm(3)) and diameters, and increasing in tissue temperature were much greater with HAIRFA (P < 0.001 for all), except DEV was lower (456 vs. 1396 J/cm(3), P < 0.001). The spherical ratio was closer to 1 with HAIRFA (1.23 vs. 1.46). Coagulation diameters, volume, and average power of HAIRFA increased significantly with longer ablation times. While with NSIRFA, these characteristics were stable till later 20 min, except the power decreased with longer ablation times. HAIRFA creates much larger and more spherical lesions by increasing overall energy deposition, modulating thermal conductivity, and transferring heat during ablation.

Radiofrequency ablation combined with transcatheter therapy in rabbit VX2 liver tumors: effects and histopathological characteristics

Transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) treatment (TACE-RFA) has been confirmed superior to TACE or RFA alone in animal liver tumors. TACE before RFA was shown to increase hepatocellular damage. Further optimization of the combination strategy for transcatheter arterial embolization (TAE) or TACE combined with RFA is warranted. To determine the optimal strategy for radiofrequency ablation combined with transcatheter therapies in VX2 liver tumors in a rabbit model. Twenty-four Japanese White rabbits with VX2 liver tumors were randomly divided into four groups: TACE-RFA (TACE-RFA group), transcatheter arterial embolization (TAE) combined with RFA treatment (TAE-RFA group), RFA only group, and TACE only group. Blood samples were collected 1 day before the operation and at 3 and 7 days postoperatively. Seven days after the operation, maximal diameters of coagulation or infarcted zones in the gross specimens, CT images, histopathological characteristics, tumor necrotic rate, and growth rate were compared. Significantly larger mean long-axis (P < 0.05) and short-axis (P < 0.05) diameters of coagulation and infarction were observed in the TACE-RFA group compared with the TAE-RFA, RFA, and TACE groups on day 7; and the TAE-RFA group showed a significant (P < 0.05) increase versus the RFA and TACE groups on day 7. There were no significant differences in tumor growth rate (109.3 ± 37.5 vs. 119.0 ± 43.1%, P = 0.45) and necrotic rate (89.5 ± 12.0 vs. 83.5 ± 9.3%, P = 0.73) between the TACE-RFA and TAE-RFA groups. TACE-RFA was more effective for achieving tumor destruction than the other treatment strategies, but led to increased rabbits discomfort and more severe liver dysfunction compared with TAE-RFA. TAE-RFA appears to be a beneficial therapeutic modality for treating VX2 liver tumors in a rabbit model.

Combined Radiofrequency Ablation and Double Anti-Angiogenic Protein Therapy to Increase Coagulation Efficacy: An Experimental Study in a Murine Renal Carcinoma Model.

ObjectiveTo evaluate whether suppression of tumor microvasculature by double anti-angiogenic protein (DAAP) treatment could increase the extent of radiofrequency ablation (RFA)-induced coagulation in a murine renal cell carcinoma model.Materials and MethodsRenal cell carcinoma cell lines were implanted subcutaneously into 10 nude mice. Four mice received adenoviral DAAP treatment and 6 mice received sterile 0.9% saline solution as DAAP-untreated group. The effect of DAAP was evaluated according to the vascularity by contrast-enhanced ultrasound (CEUS) using microbubbles. Four DAAP-treated mice and 4 DAAP-untreated mice were then treated with RFA, resulting in 3 groups: no-therapy (n = 2), RFA only (n = 4), and RFA combined with DAAP treatment (n = 4). Immediately after RFA, the size of coagulation necrosis and mitochondrial enzyme activity were compared between the groups using analysis of variance (ANOVA) and post hoc test.ResultsThe contrast enhancement ratio for tumor vascularization on CEUS was significantly lower in the DAAP treated group than in DAAP-untreated group (30.2 ± 9.9% vs. 77.4 ± 17.3%; p = 0.021). After RFA, the mean coagulation diameter was 0 mm for no-therapy group, 6.7 ± 0.7 mm for the RFA only group and 8.5 ± 0.4 mm for the RFA with DAAP group (ANOVA, p < 0.001). The area of viable mitochondria within the tumor was 27.9 ± 3.9% in no-therapy group, 10.3 ± 4.5% in the RFA only group, and 2.1 ± 0.7% in the RFA with DAAP group (ANOVA, p < 0.001).ConclusionOur results suggest the potential value of combining RFA with anti-angiogenic therapy.

Optimisation of the coagulation zone for thermal ablation procedures: A theoretical approach with considerations for practical use

Purpose: This paper outlines a theoretical approach for optimisation of the coagulation zone for thermal ablation procedures and considerations for its practical application. Methods: The theoretical approach is outlined in the Cartesian coordinate system. Considerations for practical application are implemented. The optimised coagulation zone is defined as the bare coverage of tumour mass plus a safety margin. The eccentricity of coagulation centre (ECC) is defined as the distance between the coagulation centre and the tumour centre. The direction of the applicator shaft is determined based on the x-axis direction. The tumour centre and coagulation centre are defined within the x/y-plane. The distance between coagulation margin (applicator tip) and tumour margin is called parallel offset (PAO). Results: For spherical coagulation shapes, a linear relationship exists between optimised coagulation diameter and ECC. An exponential relationship exists between optimised coagulation volume and ECC. A complex relationship was found between PAO and determinants of ECC, which are ex and ey. PAO is an extremely important parameter, which allows for determination of the optimal applicator tip position in relation to the tumour margin. It can be calculated in such a manner that the optimised coagulation zone is minimised by neutralising dislocation of the coagulation centre in applicator shaft direction. The latter can be realised by withdrawing or further inserting the applicator shaft. Conclusions: The presented concept can be used to optimise the extent of the coagulation zone for thermal ablation procedures after positioning of the applicator. Its inherent advantage is the simple adjustment of the applicator shaft, which obviates the need for a repuncture.

Tm:Fiber laser ablation with real‐time temperature monitoring for minimizing collateral thermal damage: ex vivo dosimetry for ovine brain

The thermal damage of the surrounding tissue can be an unwanted result of continuous-wave laser irradiations. In order to propose an effective alternative to conventional surgical techniques, photothermal damage must be taken under control by a detailed dose study. Real-time temperature monitoring can be also an effective way to get rid of these negative effects. The aim of the present study is to investigate the potential of a new laser-thermoprobe, which consists of a continuous-wave 1,940-nm Tm:fiber laser and a thermocouple measurement system for brain surgery in an ex vivo study. A laser-thermoprobe was designed for using the near-by tissue temperature as a real-time reference for the applicator. Fresh lamb brain tissues were used for experiments. 320 laser shots were performed on both cortical and subcortical tissue. The relationship between laser parameters, temperature changes, and ablation (removal of tissue) efficiency was determined. The correlation between rate of temperature change and ablation efficiency was calculated. Laser-thermoprobe leads us to understand the basic laser-tissue interaction mechanism in a very cheap and easy way, without making a change in the experimental design. It was also shown that the ablation and coagulation (thermally irreversible damage) diameters could be predicted, and carbonization can be avoided by temperature monitoring.

Microwave Ablation in Porcine Livers Applying 5-minute Protocols: Influence of Deployed Energy on Extent and Shape of Coagulation

PurposeTo evaluate the influence of deployed energy on extent and shape of microwave (MW)-induced coagulation in porcine livers applying 5-minute protocols. Materials and MethodsMW ablations (n = 25) were performed in ex vivo porcine livers (n = 8). Ablation time was 5 minutes. Five study groups were defined, each with different power output: I, 20 W (n = 5); II, 40 W (n = 5); III, 60 W (n = 5); IV, 80 W (n = 5); and V, 105 W (n = 5). Extent and shape of white coagulation was evaluated macroscopically, including short diameter, volume, front margin, coagulation center (distance between center of short diameter of coagulation and applicator tip), and ellipticity index (short diameter/long diameter). Deployed energy was also analyzed. ResultsShort diameter and volume were significantly different (P<.001 and P<.001) between the groups: I, 23.0 mm and 11.1 cm3; II, 12.4 mm and 12.4 cm3; III, 27.0 mm and 17.6 cm3; IV, 31.0 mm and 29.2 cm3; and V, 35.0 mm and 42.3 cm3. Front margin and coagulation center were also significantly different (P<.05 and P<.001): I, 6.0 mm and 13.0 mm; II, 8.0 mm and 11.0 mm; III, 8.0 mm and 14.0 mm; IV, 8.0 mm and 18.0 mm; and V, 10.0 mm and 19.0 mm. Ellipticity index was not significantly different. Deployed energy was significantly different (P<.001): I, 5.7 kJ; II, 11.0 kJ; III, 15.5 kJ; IV, 21.6 kJ; and V, 26.6 kJ. ConclusionsExtent, but not shape, of MW-induced coagulation depends on the deployed energy. Applying the protocols described in this study, significantly different coagulation volumes can be created with an ablation time of 5 minutes but different power output.

Radiofrequency ablation in a porcine kidney model: effect of occlusion of the arterial blood supply on ablation temperature, coagulation diameter, and histology

Radiofrequency ablation (RFA) is susceptible to the cooling effect of flowing blood. The reduced efficacy of RFA in large tumors reflects the in vivo biophysiological limitations imposed by perfusion-mediated vascular cooling. To compare the effects of RFA alone and of RFA combined with occlusion of the arterial blood supply on the tissue temperature, coagulation diameter, and histological changes in the acute phase. The temperature at roll-off, the coagulated tissue diameter, and histologic tissue changes were compared in normal porcine kidneys subjected in situ to two pigs each were subjected to RFA alone (four kidneys) or to RFA plus balloon occlusion of the renal artery (four kidneys). The tissue temperature was measured at three sites: area I, the center of the RFA field; area II, the ischemic field 1 cm distant from the edge of the RFA field; and area III, the normal kidney. Tissue samples were stained with hematoxylin and eosin (H&E). Cell viability in the ablated zone was determined by nicotinamide adenine dinucleotide (NADH) staining of frozen sections. The tissue temperatures achieved by RFA in areas I, II, and III were 101°C, 58°C, and 40°C with and 92°C, 44°C, and 38°C without balloon occlusion, respectively. The maximal coagulation diameter was 31 mm with and 23 mm without occlusion. The coagulation diameter was significantly larger and the temperature in area II was significantly higher in kidneys subjected to RFA with renal artery occlusion. H&E staining showed preservation of the normal renal parenchymal structure outside the thermal lesion and an increase in eosinophilic cells with indistinct cell borders and nuclei within the thermal lesion. H&E and NADH staining demonstrated a sharp demarcation between the ablation and normal tissue area and showed that in area II the addition of balloon occlusion did not produce histologic changes different from those in kidneys subjected to RFA alone. A technique that combines RFA and partial renal artery occlusion may be useful in treatment of the non-resectable renal tumors with sizes appropriate for RF ablation.

Efficacy of microwave versus radiofrequency ablation for treatment of small hepatocellular carcinoma: experimental and clinical studies

To prospectively compare microwave (MW) ablation using a modified internal cooled-shaft antenna with radiofrequency (RF) ablation in in vivo porcine liver and in patients with small hepatocellular carcinoma (sHCC). In an animal study, MW and RF ablations using a cooled-shaft antenna or internally cooled electrode were performed in in vivo porcine liver. Coagulation diameters of both ablations were compared. For clinical study, 42 patients with sHCC were treated with MW or RF ablation. Complete ablation (CA) and local tumour progression (LTP) were compared. MW ablation produced significantly larger ablation zones than RF ablation in both porcine liver and sHCC with an ablated volume of 33.3 ± 15.6 cm(3) vs. 18.9 ± 9.1 cm(3) and 109.3 ± 58.3 cm(3) vs. 48.7 ± 30.5 cm(3), respectively. The CA rate was 95.5 % (21/22) for MW ablation and 95.0 % (19/20) for RF ablation. In a 5.1-month follow-up, the LTP rate was 18.2 % (4/22) in the MW ablation group and 15.0 % (3/20) in the RF ablation group. MW ablation using a modified cooled-shaft antenna produces a larger ablation zone than RF ablation, with an efficacy similar to RF ablation in local tumour control. MW ablation is a safe and promising treatment of sHCC.

Radiofrequency Ablation: Effect of Tumor- and Organ-specific Pharmacologic Modulation of Arterial and Portal Venous Blood Flow on Coagulation Diameter in an N1-S1 Tumor Model

PurposeTo investigate inherent differences in vasculature of tumors versus normal parenchyma and efficacy of radiofrequency (RF) ablation with glucagon, adenosine, and a combination of the two compared with normal saline solution (NS) controls in an N1-S1 tumor model implanted in Sprague–Dawley rat livers. Materials and MethodsA total of 17 tumors were established in the left lobes of rats. Tumor perfusion relative to surrounding liver parenchyma was evaluated with contrast-enhanced ultrasound with intermittent-bolus technique before and after administration of glucagon, adenosine, a combination of the two, or NS. Tumors were ablated with a 22-gauge RF probe with 1 cm of exposed tip at 80 °C for 2 min. Tumor size, zone of necrosis, and viable tumor were measured in tumors after 2,3,5-triphenyltetrazolium chloride staining. Results were compared with degree of tumor perfusion. ResultsThe normalized tumor perfusion ratio did not significantly change with administration of NS (1.38% ± 3.93). Vasomodulation resulted in significant decreases in normalized tumor perfusion ratio: 66.22% ± 24.57 (P < .01) with glucagon, 71.45% ± 22.72 (P < .01) with adenosine, and 74.98% ± 16.58 (P < .01) with glucagon plus adenosine. After tumor ablation, there was an increase in size of the ablated area by 100%–165% in the three treatment groups compared with NS controls. Differences among treatment groups were not statistically significant. ConclusionsTumor blood flow may be significantly altered by using systemic injection of appropriate medications. This tumor- and organ-specific approach to tumor vasomodulation may be used to enhance current therapeutic options.

Abstract No. 13: Radiofrequency ablation: effect of tumor and organ-specific pharmacologic modulation of arterial and portal venous blood flow on coagulation diameter in a N1-S1 tumor model

To investigate the inherent differences in the vasculature of tumors versus normal parenchyma and the efficacy of RF ablation using glucagon (GN), adneosine (AD), and a combination of AD + GN as compared with normal saline (NS) controls using an N1-S1 tumor model implanted in Sprague-Dawley rat livers. Specifically, we evaluated pharmacologic agents and doses that yielded the greatest amount of decreased tumor perfusion and resulted in a greater percentage of tumor coagulative necrosis.

Microwave ablation: results in ex vivo and in vivo porcine livers with 2450-MHz cooled-shaft antenna.

Imaging-guided thermal ablation using different energy sources continues to gain favor as a minimally invasive technique for the treatment of primary and metastatic hepatic malignant tumors. This study aimed to evaluate the performance of microwave ablation with 2450-MHz internally cooled-shaft antenna in ex vivo and in vivo porcine livers. All studies were animal care and ethics committee approved. Microwave ablation was performed using a noncooled or cooled-shaft antenna in 23 ex vivo (92 ablations) and eight in vivo (36 ablations) porcine livers. Diameters of the coagulation zone were observed on gross specimens. The coagulation diameters achieved in different microwave ablation parameter groups were compared. Curve estimation analysis was performed to characterize the relationship between applied power and treatment duration and coagulation diameter (including short-axis and long-axis diameter). Coagulation zones were elliptical and an arrowed-shaped carbonization zone around the shaft was observed in all groups. But the antenna track was also coagulated in the noncooled-shaft antenna groups. In ex vivo livers, the short-axis diameter correlated with the power output in a quadratic curve fashion (R(2) = 0.95) by fixing ablation duration to 10 minutes, and correlated with the ablation duration in a logarithmic curve fashion (R(2) = 0.98) by fixing power output to 80 W. The short-axis reached a relative plateau within 25 minutes. In in vivo livers, short-axis diameter correlated with the coagulation duration in a sigmoidal curve fashion (60 W group R(2) = 0.76, 80 W group R(2) = 0.87), with a relative plateau achieved within 10 minutes for power settings of 60 W and 80 W. The internally cooled microwave antenna may be advantageous to minimize collateral damage. The short-axis diameter enlargement has a plateau by fixing power output.

Radiofrequency ablation combined with liposomal quercetin to increase tumour destruction by modulation of heat shock protein production in a small animal model

Purpose: To investigate the effect of heat shock protein (HSP) modulation on tumour coagulation by combining radiofrequency (RF) ablation with adjuvant liposomal quercetin and/or doxorubicin in a rat tumour model.Methods: Sixty R3230 breast adenocarcinoma tumours/animals were used in this IACUC-approved study. Initially, 60 tumours (n = 6, each subgroup) were randomised into five groups: (1) RF alone, (2) intravenous (IV) liposomal quercetin alone (1 mg/kg), (3) IV liposomal quercetin followed 24 h later with RF, (4) RF followed 15 min later by IV liposomal doxorubicin (8 mg/kg), (5) IV liposomal quercetin 24 h before RF followed by IV liposomal doxorubicin 15 min post-ablation. Animals were sacrificed 4 or 24 h post-treatment and gross coagulation diameters were compared. Next, immunohistochemistry staining was performed for Hsp70 and cleaved caspase-3 expression. Comparisons were performed by using Student t-tests or ANOVA.Results: Combination RF-quercetin significantly increased coagulation size compared with either RF or liposomal quercetin alone (13.1 ± 0.7 mm vs. 8.8 ± 1.2 mm or 2.3 ± 1.3 mm, respectively, P < 0.001 for all comparisons). Triple therapy (quercetin-RF-doxorubicin) showed larger coagulation diameter (14.5 ± 1.0 mm) at 24 h than quercetin-RF (P = 0.016) or RF-doxorubicin (13.2 ± 1.3 mm, P = 0.042). Combination quercetin-RF decreased Hsp70 expression compared with RF alone at both 4 h (percentage of stained cells/hpf 22.4 ± 13.9% vs. 38.8 ± 16.1%, P < 0.03) and 24 h (45.2 ± 10.5% vs. 81.1 ± 3.6%, P < 0.001). Quercetin-RF increased cleaved caspase-3 expression at both 4 h (percentage of stained cells/hpf 50.7 ± 13.4% vs. 41.9 ± 15.1%, P < 0.03) and 24 h (37.4 ± 7.8% vs. 33.2 ± 6.5%, P = 0.045); with, triple therapy (quercetin-RF-doxorubicin) resulting in the highest levels of apoptosis (45.1 ± 10.7%) at 24 h. Similar trends were observed for rim thickness.Conclusions: Suppression of HSP production using adjuvant liposomal quercetin can increase apoptosis and improve RF ablation-induced tumour destruction. Further increases in tumour coagulation can be seen including an additional anti-tumour adjuvant agent such as liposomal doxorubicin.

Sustained Growth of the Ex Vivo Ablation Zones’ Critical Short Axis Using Gas-cooled Radiofrequency Applicators

To evaluate the ablation zones created with a gas-cooled bipolar radiofrequency applicator performed on ex vivo bovine liver tissue. A total of 320 ablations with an internally gas-cooled bipolar radiofrequency applicator were performed on fresh ex vivo bovine liver tissue, varying the ablation time (5, 10, 15, and 20min), power (20, 30, 40, and 50W), and gas pressure of the CO(2) used for cooling (585, 600, 615, 630, 645 psi), leading to a total of 80 different parameter combinations. Size and shape of the white coagulation zone were assessed. The largest complete ablation zone was achieved after 20min of implementing 50W and 645 psi, resulting in a short axis of mean 46±1mm and a long axis of 56±2mm (mean±standard deviation). Short-axis diameters increased between 5 and 20min of ablation time at 585 psi (increase of the short axis was 45% at 30W, 29% at 40W, and 39% at 50W). This increase was larger at 645 psi (113% at 30W, 67% at 40W, and 70% at 50W). Macroscopic assessment and NADH (nicotinamide adenine dinucleotide) staining revealed incompletely ablated tissue along the needle track in 18 parameter combinations including low-power settings (20 and 30W) and different cooling levels and ablation times. Gas-cooled radiofrequency applicators increase the short-axis diameter of coagulation in an ex vivo setting if appropriate parameters are selected.

Percutaneous microwave coagulation therapy for hepatocellular carcinoma: Increased coagulation diameter using a new electrode and microwave generator

We performed percutaneous microwave co-agulation therapy (PMCT) using a new microwave electrode and microwave generator to lessen the number of microwave electrode insertions for hepatocellular carcinoma (HCC) measuring <or=3.0 cm in diameter. In this study, we assessed the efficacy of this new system. Fifty-two patients with liver cirrhosis and HCC measuring <or=3.0 cm in diameter (tumor size: <or=2 cm, 27 patients; >2 to <or=2.5 cm, 13 patients; >2.5 to <or=3 cm, 12 patients) underwent PMCT using a new microwave coagulation system under ultrasonographic guidance. Forty-two of 52 patients showed complete necrosis of the tumor lesion with a treated margin >or=5 mm on dynamic computed tomography. Necrosis of HCC and the non-cancerous area surrounding the tumor was obtained by a single needle insertion in 23 patients (tumor size: <or=2 cm, 23 patients), by two needle insertions in 11 patients (tumor size: <or=2 cm, 4 patients; >2 to <or=2.5 cm, 5 patients; >2.5 to <or=3 cm, 2 patients), and by three needle insertions in 8 patients (tumor size: >2 to <or=2.5 cm, 5 patients; >2.5 to <or=3 cm, 3 patients). During the follow-up period of 5-34 months, all patients remained alive. Among the patients showing complete necrosis of HCC with a treated margin >or=5 mm, we have not detected local recurrences. On the other hand, 4 of the 10 patients who could not obtain the treated margin of >or=5 mm, experienced a local recurrence. No fatal complications were observed. However, bile duct stricture was observed in 2 patients. The new microwave coagulation system can induce extensive necrosis with a small number of microwave electrode insertions. This system may enhance the efficacy of PMCT for HCC measuring <3.0 cm in diameter.

Renal Artery Embolization Combined With Radiofrequency Ablation in a Porcine Kidney Model: Effect of Small and Narrowly Calibrated Microparticles as Embolization Material on Coagulation Diameter, Volume, and Shape

The purpose of this study was to evaluate the effect of renal artery embolization with small and narrowly calibrated microparticles on the coagulation diameter, volume, and shape of radiofrequency ablations (RFAs) in porcine kidneys. Forty-eight RFAs were performed in 24 kidneys of 12 pigs. In 6 animals, bilateral renal artery embolization was performed with small and narrowly calibrated microparticles. Upper and lower kidney poles were ablated with identical system parameters. Applying three-dimensional segmentation software, RFAs were segmented on registered 2mm-thin macroscopic slices. Length, depth, width, volume_segmented, and volume_calculated were determined to describe the size of the RFAs. To evaluate the shape of the RFAs, depth-to-width ratio (perfect symmetry-to-lesion length was indicated by a ratio of 1), sphericity ratio (perfect sphere was indicated by a sphericity ratio of 1), eccentricity (perfect sphere was indicated by an eccentricity of 0), and circularity (perfect circle was indicated by a circularity of 1) were determined. Embolized compared with nonembolized RFAs showed significantly greater depth (23.4±3.6 vs. 17.2±1.8mm; p<0.001) and width (20.1±2.9 vs. 12.6±3.7mm; p<0.001); significantly larger volume_segmented (8.6±3.2 vs. 3.0±0.7ml; p<0.001) and volume_calculated (8.4±3.0ml vs. 3.3±1.1ml; p<0.001); significantly lower depth-to-width (1.17±0.10 vs. 1.48±0.44; p<0.05), sphericity (1.55±0.44 vs. 1.96±0.43; p<0.01), and eccentricity (0.84±0.61 vs. 1.73±0.91; p<0.01) ratios; and significantly greater circularity (0.62±0.14 vs. 0.45±0.16; p<0.01). Renal artery embolization with small and narrowly calibrated microparticles affected the coagulation diameter, volume, and shape of RFAs in porcine kidneys. Embolized RFAs were significantly larger and more spherical compared with nonembolized RFAs.