Tumor location on electroporation therapies by means of multi-electrode structures and machine learning.

Electroporation is a phenomenon produced in the cell membrane when it is exposed to high pulsed electric fields that increases its permeability. Among other application fields, this phenomenon can be exploited in a clinical environment for tumor ablation therapies. In this context to achieve optimum results, it is convenient to focus the treatment on the tumor tissue to minimize side effects. In this work, a pre-treatment tumor location method is developed, with the purpose of being able to precisely target the therapy. This is done by taking different impedance measurements with a multi-output electroporation generator in conjunction with a multi-electrode structure. Data are processed by means of a vector of independent artificial neural networks, trained and tested with simulation data, and validated with phantom gels. This algorithm proved to provide suitable accuracy in spite of the low electrode count compared to the number of electrodes of a standard electrical impedance tomography device.

Histopathological and Ultrastructural Changes after Electroporation in Pig Liver Using Parallel-Plate Electrodes and High-Performance Generator.

Irreversible electroporation (IRE) has gained attention as a new non-thermal therapy for ablation with important benefits in terms of homogeneous treatment and fast recovery. In this study, a new concept of high voltage generator is used, enabling irreversible electroporation treatment in large tissue volume using parallel plates. Unlike currently available generators, the proposed versatile structure enables delivering high-voltage high-current pulses. To obtain homogeneous results, 3-cm parallel-plates electrodes have also been designed and implemented. IRE ablation was performed on six female pigs at 2000 V/cm electric field, and the results were analysed after sacrifice three hours, three days and seven days after ablation. Histopathological and ultrastructural studies, including transmission and scanning electron microscopy, were carried out. The developed high-voltage generator has proved to be effective for homogeneous IRE treatment using parallel plates. The destruction of the membrane of the hepatocytes and the alterations of the membranes of the cellular organelles seem incompatible with cell death by apoptosis. Although endothelial cells also die with electroporation, the maintenance of vascular scaffold allows repairing processes to begin from the third day after IRE as long as the blood flow has not been interrupted. This study has opened new direction for IRE using high performance generators and highlighted the importance of taking into account ultrastructural changes after IRE by using electron microscopy analysis.

Long-term effectiveness of irreversible electroporation in a murine model of colorectal liver metastasis.

Irreversible electroporation (IRE) has recently gained in popularity as an ablative technique, however little is known about its oncological long-term outcomes. To determine the long-time survival of animals treated with a high dose of IRE and which histological changes it induces in tumoral tissue, IRE ablation was performed in forty-six athymic-nude mice with KM12C tumors implanted in the liver by applying electric current with different voltages (2000 V/cm, 1000 V/cm). The tumors were allowed to continue to grow until the animals reached the end-point criteria. Histology was harvested and the extent of tumor necrosis was semi-quantitatively assessed. IRE treatment with the 2000 V/cm protocol significantly prolonged median mouse survival from 74.3 ± 6.9 days in the sham group to 112.5 ± 15.2 days in the 2000 V/cm group. No differences were observed between the mean survival of the 1000 V/cm and the sham group (83.2 ± 16.4 days, p = 0.62). Histology revealed 63.05% ± 23.12 of tumor necrosis in animals of the 2000 V/cm group as compared to 17.50% ± 2.50 in the 1000 V/cm group and 25.6% ± 22.1 in the Sham group (p = 0.001). IRE prolonged the survival of animals treated with the highest electric field (2000 V/cm). The animals in this group showed significantly higher rate of tumoral necrosis.

Irreversible electroporation of the liver: is there a safe limit to the ablation volume?

Irreversible electroporation is a fast-growing liver ablation technique. Although safety has been well documented in small ablations, our aim is to assess its safety and feasibility when a large portion of liver is ablated. Eighty-seven mice were subjected to high voltage pulses directly delivered across parallel plate electrodes comprising around 40% of mouse liver. One group consisted in 55 athymic-nude, in which a tumor from the KM12C cell line was grown and the other thirty-two C57-Bl6 non-tumoral mice. Both groups were subsequently divided into subsets according to the delivered field strength (1000 V/cm, 2000 V/cm) and whether or not they received anti-hyperkalemia therapy. Early mortality (less than 24 hours post-IRE) in the 2000 V/cm group was observed and revealed considerably higher mean potassium levels. In contrast, the animals subjected to a 2000 V/cm field treated with the anti-hyperkalemia therapy had higher survival rates (OR = 0.1, 95%CI = 0.02-0.32, p < 0.001). Early mortality also depended on the electric field magnitude of the IRE protocol, as mice given 1000 V/cm survived longer than those given 2000 V/cm (OR = 4.7, 95%CI = 1.8-11.8, p = 0.001). Our findings suggest that ionic disturbances, mainly due to potassium alterations, should be warned and envisioned when large volume ablations are performed by IRE.

Radiofrequency hepatic ablation with internally cooled electrodes and hybrid applicators with distant saline infusion using an in vivo porcine model.

AIMS: Radiofrequency ablation (RFA) of tumors by means of internally cooled (ICE) or multitined expandable electrodes combined with infusion of saline into the tissue may improve results. Our aim was to determine the efficacy of a previously optimized hybrid ICE system (ICE combined with infusion of saline into the tissue at a distance of 2mm) in comparison with a conventional ICE cluster electrode in porcine liver in vivo. METHODS: A total of 32 RFA were performed on a total of 10 farm pigs using two RFA systems: Group A (n=16): Cluster electrode. Group B (n=16): Hybrid system (with continuous infusion of 100ml/h of 20% NaCl at 2mm distance from the electrode shaft by an independent isolated needle). Livers were removed for macroscopic and histological assessment after the procedure. Coagulation volume, coagulation diameters, coefficient of variability (CV) of coagulation volume, sphericity ratio (SR), deposited power (DP), deposited energy (DE), deposited energy per coagulation volume (DEV) and rise of animal temperature during the procedure were compared and correlated among groups. Additionally, linear regression analysis was modeled to study the relationship between deposited energy and either coagulation volume and rise of animal temperature during the procedure in both groups. RESULTS: Both coagulation volume and short diameter of coagulation were significantly greater (p<0.05) in group B compared to group A (22.7+/-11.0 cm(3) and 3.1+/-0.7 cm vs. 13.5+/-7.7 cm(3) and 2.5+/-0.5 cm, respectively). A similar CV and SR was observed among groups (57.1% and 1.4+/-0.3 vs. 48.6% and 1.3+/-0.2 for groups B and A, respectively). In group B, DE and DP were more than double group A, but DEV was nearly twice as high (9782 J/cm(3) vs. 5342 J/cm(3), for groups B and A, respectively). No significant relationship between DE and coagulation volume was encountered. CONCLUSION: Efficacy of a single ICE may be improved with continuous infusion of saline at around 2 mm from the electrode shaft. Coagulation volume obtained with this improved system may be even greater than that obtained with a cluster electrode.

A radiofrequency-assisted device for bloodless rapid transection of the liver: a comparative study in a pig liver model.

BACKGROUND: Efficient and safe liver parenchymal transection is dependent on the ability to address both parenchymal division and hemostasis simultaneously. In this article we describe and compare with a saline-linked instrument a new radiofrequency (RF)-assisted device specifically designed for tissue thermocoagulation and division of the liver used on an in vivo pig liver model. METHODS: In total, 20 partial hepatectomies were performed on pigs through laparotomy. Two groups were studied: group A (n=8) with hepatectomy performed using only the proposed RF-assisted device and group B (n=8) with hepatectomy performed using only a saline-linked device. Main outcome measures were: transection time, blood loss during transection, transection area, transection speed and blood loss per transection area. Secondary measures were: risk of biliary leakage, tissue coagulation depth and the need for hemostatic stitches. Tissue viability was evaluated in selected samples by staining of tissue NADH. RESULTS: In group A both blood loss and blood loss per transection area were lower (p=0.001) than in group B (70+/-74 ml and 2+/-2 ml/cm(2) vs. 527+/-273 ml and 13+/-6 ml/cm(2), for groups A and B, respectively). An increase in mean transection speed when using the proposed device over the saline-linked device group was also demonstrated (3+/-0 and 2+/-1cm(2)/min for group A and B, respectively) (p=0.002). Tissue coagulation depth was greater (p=0.005) in group A than in group B (6+/-2 mm and 3+/-1 mm, for groups A and B, respectively). Neither macroscopic nor microscopic differences were encountered in transection surfaces between both groups. CONCLUSIONS: The proposed RF-assisted device was shown to address parenchymal division and hemostasis simultaneously, with less blood loss and faster transection time than saline-linked technology in this experimental model.

Tecnologías emergentes en ablación por radiofrecuencia de tumores hepáticos / No disponible

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Hepatic lesion ablation with bipolar saline-enhanced radiofrequency in the audible spectrum.

RATIONALE AND OBJECTIVES: The authors' purpose was to create larger and more regular liver lesions in vitro by testing a new hyperthermia approach that uses a bipolar saline-enhanced electrode for radiofrequency (RF) in the audible spectrum and a greater power supply. MATERIALS AND METHODS: The authors' hyperthermia approach (group A, n = 23) was used in excised porcine livers, and the results were compared with those of a previously described monopolar saline-enhanced electrode procedure (group B, n = 23). In each set of experiments, RF in the audible spectrum current (50 Hz) was provided for 15 minutes with a similar ablation protocol. Electrical variables (impedance, current, voltage, power, and energy), temperatures in the lesions, volume size, regularity ratio of the lesion, and microscopic findings were measured. RESULTS: In group A, the mean volume size and the mean regularity ratio values were 144.8 cm3 +/- 59.8 and 0.78 +/- 0.1, respectively. In group B, the mean volume size and regularity ratio values were 62.1 cm3 +/- 36.4 and 0.62 +/- 0.1, respectively. The values in group B were thus significantly lower than those in group A (P < .01). The lesions in group A were also more homogeneous. No significant differences were found in electrical variables. CONCLUSION: The new bipolar saline-enhanced electrode produced larger, more regular, and more homogeneous lesions ex vivo than the previously used monopolar saline-enhanced electrode method. Using a greater power supply increased the amount of coagulative necrosis.