The role of anti-tumor immunity of focused ultrasound for the malignancies: depended on the different ablation categories.

Improving anti-tumor immunity has promising outcomes in eradicating malignant tumors. Tumor cells can escape from immune surveillance and killing; therefore, various strategies are continuously developing to inhibit immune escape. Focused ultrasound (FUS) has recently emerged to play an important role in immune modulation. After FUS therapy, various tumor antigens and related signals are released. The non-thermal effect of FUS strengthens the blood and lymph circulation, increases cell permeability, and helps in crossing the physical barrier like the blood-brain barrier and blood-tumor barrier. However, the different ablation of FUS is proposed to have a different anti-tumor immune effect. Therefore, we categorized the FUS ablation into thermal and non-thermal ablation and summarized possible anti-tumor immunity mechanisms.

Investigation of safety for electrochemotherapy and irreversible electroporation ablation therapies in patients with cardiac pacemakers.

BACKGROUND: The effectiveness of electrochemotherapy of tumors (ECT) and of irreversible electroporation ablation (IRE) depends on different mechanisms and delivery protocols. Both therapies exploit the phenomenon of electroporation of the cell membrane achieved by the exposure of the cells to a series of high-voltage electric pulses. Electroporation can be fine-tuned to be either reversible or irreversible, causing the cells to either survive the exposure (in ECT) or not (in IRE), respectively. For treatment of tissues located close to the heart (e.g., in the liver), the safety of electroporation-based therapies is ensured by synchronizing the electric pulses with the electrocardiogram. However, the use of ECT and IRE remains contraindicated for patients with implanted cardiac pacemakers if the treated tissues are located close to the heart or the pacemaker. In this study, two questions are addressed: can the electroporation pulses interfere with the pacemaker; and, can the metallic housing of the pacemaker modify the distribution of electric field in the tissue sufficiently to affect the effectiveness and safety of the therapy? RESULTS: The electroporation pulses induced significant changes in the pacemaker ventricular pacing pulse only for the electroporation pulses delivered during the pacing pulse itself. No residual effects were observed on the pacing pulses following the electroporation pulses for all tested experimental conditions. The results of numerical modeling indicate that the presence of metal-encased pacemaker in immediate vicinity of the treatment zone should not impair the intended effectiveness of ECT or IRE even when the casing is in direct contact with one of the active electrodes. Nevertheless, the contact between the casing and the active electrode should be avoided due to significant tissue heating at the site of the other active electrode for the IRE protocol and may cause the pulse generator to fail to deliver the pulses due to excessive current draw. CONCLUSIONS: The observed effects of electroporation pulses delivered in close vicinity of the pacemaker or its electrodes do not indicate adverse consequences for either the function of the pacemaker or the treatment outcome. These findings should contribute to making electroporation-based treatments accessible also to patients with implanted cardiac pacemakers.

Implications and considerations of thermal effects when applying irreversible electroporation tissue ablation therapy.

Irreversible electroporation (IRE) describes a cellular response to electric field exposure, resulting in the formation of nanoscale defects that can lead to cell death. While this behavior occurs independently of thermally-induced processes, therapeutic ablation of targeted tissues with IRE uses a series of brief electric pulses, whose parameters result in secondary Joule heating of the tissue. Where contemporary clinical pulse protocols use aggressive energy regimes, additional evidence is supplementing original studies that assert care must be taken in clinical ablation protocols to ensure the cumulative thermal effects do not induce damage that will alter outcomes for therapies using the IRE non-thermal cell death process for tissue ablation. In this letter, we seek to clarify the nomenclature regarding IRE as a non-thermal ablation technique, as well as identify existing literature that uses experimental, clinical, and numerical results to discretely address and evaluate the thermal considerations relevant when applying IRE in clinical scenarios, including several approaches for reducing these effects. Existing evidence in the literature describes cell response to electric fields, suggesting cell death from IRE is a unique process, independent from traditional thermal damage. Numerical simulations, as well as preclinical and clinical findings demonstrate the ability to deliver therapeutic IRE ablation without occurrence of morbidity associated with thermal therapies. Clinical IRE therapy generates thermal effects, which may moderate the non-thermal aspects of IRE ablation. Appropriate protocol development, utilization, and pulse delivery devices may be implemented to restrain these effects and maintain IRE as the vastly predominant tissue death modality, reducing therapy-mitigating thermal damage. Clinical applications of IRE should consider thermal effects and employ protocols to ensure safe and effective therapy delivery.

Pulsed electric field performance calculator tool based on an in vitro human cardiac model.

Introduction: Pulsed Field Ablation (PFA) is a novel non-thermal method for cardiac ablation, relying on irreversible electroporation induced by high-energy pulsed electric fields (PEFs) to create localized lesions in the heart atria. A significant challenge in optimizing PFA treatments is determining the lethal electric field threshold (EFT), which governs ablation volume and varies with PEF waveform parameters. However, the proprietary nature of device developer's waveform characteristics and the lack of standardized nonclinical testing methods have left optimal EFTs for cardiac ablation uncertain. Methods: To address this gap, we introduced a laboratory protocol employing human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in monolayer format to evaluate the impact of a range of clinically relevant biphasic pulse parameters on lethal EFT and adiabatic heating (AH). Cell death areas were assessed using fluorescent dyes and confocal microscopy, while lethal EFTs were quantified through comparison with electric field numerical simulations. Results and conclusion: Our study confirmed a strong correlation between cell death in hiPSC-CMs and the number and duration of pulses in each train, with pulse repetition frequency exerting a comparatively weaker influence. Fitting of these results through machine learning algorithms were used to develop an open-source online calculator. By estimating lethal EFT and associated temperature increases for diverse pulse parameter combinations, this tool, once validated, has the potential to significantly reduce reliance on animal models during early-stage device de-risking and performance assessment. This tool also offers a promising avenue for advancing PFA technology for cardiac ablation medical devices to enhance patient outcomes.

A Multi-centre, Single Arm, Non-randomized, Prospective European Trial to Evaluate the Safety and Efficacy of the HistoSonics System in the Treatment of Primary and Metastatic Liver Cancers (#HOPE4LIVER).

PURPOSE: Image-guided thermal ablation are established treatment options for non-surgical patients with primary and metastatic liver cancers. However, there are limitations with nonuniformity of cancer tissue destruction, heat sink effect and the risk of thermal ablative injury. The current non-thermal ablative techniques have high risk of local recurrence and are not widely adopted. Histotripsy is a treatment technology that destroys targeted tissue under ultrasound visualization via mechanical destruction through the precise application of acoustic cavitation and can offer the potential of non-invasive, non-thermal and non-ionizing radiation cancer treatment. The aim of this multi-centre non-randomized phase I/II trial is to assess the initial safety and efficacy of the prototype investigational 'System' in the treatment of primary and metastatic liver cancers. METHODS/DESIGN: All non-surgical patients with primary/metastatic liver cancers having had previous liver directed therapy, radiation therapy or image-guided ablation may be offered image-guided Histotripsy as per trial protocol. The co-primary endpoints are technical success and procedural safety. Technical success is determined, at ≤ 36 h post procedure, by evaluating the histotripsy treatment size and coverage. The procedural safety is defined by procedure related major complications, defined as Common Terminology Criteria for Adverse Events (CTCAE version 5) grade 3 or higher toxicities, up to 30 days post procedure. This phase I/II trial has intended to recruit up to 45 patients to show safety and efficacy of image-guided histotripsy in liver cancers. TRAIL REGISTRATION: Clinicaltrials.gov identifier-NCT04573881; NIHR CRN CPMS-ID 47572.

Mechanical Characteristics of the Flebogrif System-The New System of Mechano-Chemical Endovenous Ablation.

Non-thermal endovenous ablations, due to the lowest probability of complications, are the new method of treating chronic venous insufficiency-one of the most common diseases globally. The Flebogrif system (Balton Sp. z o.o., Warsaw, Poland) is a new mechano-chemical ablation system causing the mechanical damage of endothelium that allows for better sclerosant penetration into its wall. The purpose of the article is to provide mechanical characteristics in the form of force-displacement dependence for a single cutting element, and a bundle of cutting elements of Flebogrif as a whole for different levels of protrusion of the bundle of cutting elements. A TA.HD plus (Stable Micro Systems, Godalming, UK) analyzer equipped with special handles, was used for characteristics testing. The head movement speed used was 5 mm·s-1. The Flebogrif system was tested for three cutting element protrusion levels: L = Lmax, L = 0.9·Lmax, and L = 0.8·Lmax. Before testing, geometric measurement of the spacing of the cutting elements for three proposed protrusions was performed. It was established that decreasing the working length of the cutting elements will increase their rigidity, and, as a result, increase the force exerted on the internal surface of the vein wall. The obtained characteristics will allow for specifying contact force variability ranges and the corresponding diameter ranges of operated veins.

Modeling of a single bipolar electrode with tines for irreversible electroporation delivery.

Irreversible electroporation (IRE) is a non-thermal tumor ablation technology employed to treat solid tumors not amenable to resection or thermal ablation. The IRE systems currently in clinical use deliver electrical pulses via multiple monopolar electrodes. This approach can present significant technical challenges due to the requirement for accurate placement of multiple electrodes and maintenance of parallel electrode alignment during pulse delivery. In this study, we sought to evaluate a novel IRE electrode configuration consisting of a single bipolar electrode with deployable tines. Using commercial finite element software predicted ablation outcomes, thermal damage, ablation sphericity, and energy delivery were calculated for existing monopolar and bipolar electrodes, and bipolar electrodes with either 4 or 8 deployable tines. The bipolar electrodes with tines generated larger predicted ablations compared to existing monopolar (>100%) and bipolar (>10%) arrangements, and the ablation shape using bipolar electrodes with tines were more spherical than those modeled for bipolar electrodes. Thermal damage modeled for bipolar electrodes and bipolar electrodes with tines was less than that of monopolar electrodes (using identical pulse parameters), and bipolar electrodes with tines delivered less energy than monopolar or bipolar electrodes. These studies using a single point of device insertion suggest the potential for developing alternative IRE delivery techniques, and may simplify clinical use and increase the predicted ablation shape/volume.

A pre-clinical animal study of a novel mechanical-only ablation device treatment for superficial venous disease.

OBJECTIVE: Current minimally invasive techniques for ablation in superficial venous reflux are limited to thermal based systems requiring tumescent anesthesia, non-thermal chemical sclerosants and permanent glue implantation. The aim of this feasibility study was to determine the safety and efficacy of a novel mechanical-only ablation (MOA) device called EnVena, in a recognised large animal model with chronic follow up. METHODS: Venous ablation of six lateral saphenous veins in three sheep was performed using the EnVena device. Luminal patency and vein wall fibrosis were evaluated by histologic analysis at 51 and 89 days. RESULTS: All treated veins demonstrated fibrotic occlusion in contiguous segments at 51 and 89 days on histological analysis. From 45 consecutive segments spanning the treatment length across the six treated veins, 26 (57%) were fully occluded, 7 (16%) were impinged or partially occluded and 12 (27%) were open. There were no device related complications during the follow up period. CONCLUSIONS: A purely mechanical approach to superficial venous ablation demonstrated safety and efficacy in a recognized large animal model based on histological findings.

Ultrasound-guided interventional radiology procedures on veins.

Although ultrasound-guided interventional procedures have resulted in great advances in many fields of medicine, this approach has revolutionized endovascular procedures. This paper aims to review the basic principles to develop a strategy to follow in ultrasound-guided treatments of varices in the lower limbs, as well as to provide a brief overview of the main endovenous techniques available nowadays. We divide these techniques into those that use catheters to occlude straight saphenous axes (thermal / non-thermal ablation) and other options, such as foam sclerotherapy, which can be used in all types of varices, even in those originating in the pelvis.

Two-Year Follow-Up after Endovenous Closure with Short-Chain Cyanoacrylate versus Laser Ablation in Venous Insufficiency.

BACKGROUND: The current treatment of venous disease is focused on the minimally invasive exclusion of the affected vein. Besides widely used thermal ablation, chemical ablation with cyanoacrylate, reported as safe and highly effective, has been gaining increasing interest. PATIENTS AND METHODS: In the current report, we present data from a two-year observation in 89 patients (61 female/28 male, mean age 44.3 ± 13.5) suffering from venous insufficiency (C2-C4), treated either using short-chain cyanoacrylate, the VenaBlock system (n = 43) or laser thermoablation with ELVeS 1470 (n = 46). The assessment comprised the occurrence of venous disease-related symptoms and the ultrasound examination of the leg venous system. RESULTS: The frequency of recanalization after 2 years from the VenaBlock procedure was significantly higher than after laser treatment (37.2 vs. 8.7%). Apart from recanalization, in some individuals from both groups, the symptoms of recurrence and/or disease progression, including the development of insufficiency in other veins of treated or contralateral legs (9.3 vs. 15.2% and 9.3 vs. 17.4%, respectively), were observed. Unexpectedly, the general prevalence of the disease progression did not differ significantly between the VenaBlock and ELVeS groups (44.2 vs. 34.8%, respectively). CONCLUSIONS: Despite the higher recanalization rate of VenaBlock compared to ELVeS, the overall effectiveness of cyanoacrylate and laser thermoablation after two years was similar. Therefore, both methods similarly failed to prevent recurrence and disease progression, which seem to be method-independent.

Stereotactic Percutaneous Electrochemotherapy as Primary Approach for Unresectable Large HCC at the Hepatic Hilum.

Electrochemotherapy (ECT) is a novel non-thermal ablative technique that combines chemotherapy and the application of electric pulses for reversible cell membrane electroporation. This method was recently performed in the treatment of deep-seated liver tumors during open surgery but experience about percutaneous ECT is rare and further developments like combination of percutaneous ECT with stereotactic navigated devices may be very promising. We report on a case of a 4.7 × 4.5 × 3.5 cm unresectable HCC at the hepatic hilum adjacent to the major vessels and the bile duct that was successfully treated using percutaneous ECT in combination with stereotactic navigation. Follow-up imaging 6 weeks and 6 months after ECT showed complete response.

Serie interventional ultrasound: Ultrasound-guided interventional radiology procedures on veins. / Serie de ecografía intervencionista: Intervencionismo venoso guiado por ecografía.

Although ultrasound-guided interventional procedures have resulted in great advances in many fields of medicine, this approach has revolutionized endovascular procedures. This paper aims to review the basic principles to develop a strategy to follow in ultrasound-guided treatments of varices in the lower limbs, as well as to provide a brief overview of the main endovenous techniques available nowadays. We divide these techniques into those that use catheters to occlude straight saphenous axes (thermal / non-thermal ablation) and other options, such as foam sclerotherapy, which can be used in all types of varices, even in those originating in the pelvis.

Intracranial Non-thermal Ablation Mediated by Transcranial Focused Ultrasound and Phase-Shift Nanoemulsions.

High intensity focused ultrasound (HIFU) mechanical ablation is an emerging technique for non-invasive transcranial surgery. Lesions are created by driving inertial cavitation in tissue, which requires significantly less peak pressure and time-averaged power compared with traditional thermal ablation. The utility of mechanical ablation could be extended to the brain provided the pressure threshold for inertial cavitation can be reduced. In this study, the utility of perfluorobutane (PFB)-based phase-shift nanoemulsions (PSNEs) for lowering the inertial cavitation threshold and enabling focal mechanical ablation in the brain was investigated. We successfully achieved vaporization of PFB-based PSNEs at 1.8 MPa with a 740 kHz focused transducer with a pulsed sonication protocol (duty cycle = 1.5%, 10 min sonication) within intact CD-1 mice brains. Evidence is provided showing that a single bolus injection of PSNEs could be used to initiate and sustain inertial cavitation in cerebrovasculature for at least 10 min. Histologic analysis of brain slices after HIFU exposure revealed ischemic and hemorrhagic lesions with dimensions that were comparable to the focal zone of the transducer. These results suggest that PFB-based PSNEs may be used to significantly reduce the inertial cavitation threshold in the cerebrovasculature and, when combined with transcranial focused ultrasound, enable focal intracranial mechanical ablation.

Intervencionismo venoso guiado por ecografía / Serie interventional ultrasound: Ultrasound-guided interventional radiology procedures on veins

Si en muchos campos de la medicina el intervencionismo ecográfico ha aportado grandes avances, sin duda en lo que respecta a las terapias endovenosas ha supuesto una revolución. El presente artículo pretende repasar los principios básicos para desarrollar una estrategia a seguir en los tratamientos ecoguiados de varices en los miembros inferiores. Así mismo, busca transmitir una breve perspectiva sobre las principales técnicas endovenosas disponibles en la actualidad. Dichas técnicas las dividiremos principalmente en aquellas que se sirven de un catéter con el fin de ocluir los ejes safenos rectos (ablación térmica/no térmica) y aquellas otras opciones, como es la esclerosis con espuma, que permite su uso en todo tipo de varices, incluso las de origen pélvico.(AU)

Although ultrasound-guided interventional procedures have resulted in great advances in many fields of medicine, this approach has revolutionized endovascular procedures. This paper aims to review the basic principles to develop a strategy to follow in ultrasound-guided treatments of varices in the lower limbs, as well as to provide a brief overview of the main endovenous techniques available nowadays. We divide these techniques into those that use catheters to occlude straight saphenous axes (thermal / non-thermal ablation) and other options, such as foam sclerotherapy, which can be used in all types of varices, even in those originating in the pelvis.(AU)

Irreversible electroporation for the treatment of pancreatic neuroendocrine tumors.

BACKGROUNDS/AIMS: Resection or enucleation is currently the treatment of choice for small pancreatic neuroendocrine tumors (NETs). Irreversible electroporation is a novel ablative method that is used for locally advanced pancreatic adenocarcinoma, but little data exists for its use for pancreatic NETs. We report an early experience of IRE for early pancreatic NETs. METHODS: Between April 2014 and March 2015, 3 patients with small (<2 cm) pancreatic NETs were treated with percutaneous IRE. RESULTS: There were no adverse effects during the procedure. Mean hospital stay was 2.6 days. All patients remained disease free on 12-19 months follow up. One patient developed recurrent pancreatitis with pseudocyst formation. CONCLUSIONS: IRE for small tumors of the pancreas is practical and may offer advantages over other thermal ablative techniques, since it preserves vital structures such as blood vessels, bile and pancreatic ducts. Further data regarding the long term disease free interval is required to establish efficacy.

Irreversible electroporation for the treatment of pancreatic neuroendocrine tumors

BACKGROUNDS/AIMS: Resection or enucleation is currently the treatment of choice for small pancreatic neuroendocrine tumors (NETs). Irreversible electroporation is a novel ablative method that is used for locally advanced pancreatic adenocarcinoma, but little data exists for its use for pancreatic NETs. We report an early experience of IRE for early pancreatic NETs. METHODS: Between April 2014 and March 2015, 3 patients with small (<2 cm) pancreatic NETs were treated with percutaneous IRE. RESULTS: There were no adverse effects during the procedure. Mean hospital stay was 2.6 days. All patients remained disease free on 12-19 months follow up. One patient developed recurrent pancreatitis with pseudocyst formation. CONCLUSIONS: IRE for small tumors of the pancreas is practical and may offer advantages over other thermal ablative techniques, since it preserves vital structures such as blood vessels, bile and pancreatic ducts. Further data regarding the long term disease free interval is required to establish efficacy.