Incomplete Ablation Research Articles

Dual-Synergistic Nanomodulator Alleviates Exosomal PD-L1 Expression Enabling Exhausted Cytotoxic T Lymphocytes Rejuvenation for Potentiated iRFA-Treated Hepatocellular Carcinoma Immunotherapy.

The tumor immunosuppressive microenvironment (TME) induced by incomplete radiofrequency ablation (iRFA) in hepatocellular carcinoma (HCC) is a critical driver of tumor progression and metastasis. Herein, we proposed a therapeutic strategy aimed at remodeling the post-iRFA TME by targeting exosome biogenesis, secretion, and PD-L1 expression, thereby rejuvenating cytotoxic T lymphocyte function to mitigate the progression and metastasis of HCC. Leveraging the versatile properties of polydopamine nanomodulators, we have engineered a tailored delivery platform for GW4869 and amlodipine (AM), enabling precise and tumor-specific release of these therapeutic agents. Initially, GW4869, a neutral sphingomyelinase inhibitor, synergized with AM, an intracellular calcium modulator, to suppress exosome biogenesis and secretion. Subsequently, AM triggered the autophagic degradation of PD-L1. In vitro and in vivo experiments demonstrated that this synergistic approach significantly enhanced the robust activation and proliferation of various functional T-cell subsets following iRFA, particularly CD8+T cells, IFN-γ+ CD8+ cytotoxic T cells, natural killer cells, and innate lymphoid cells. Concurrently, it effectively reduced the infiltration of immunosuppressive cell types, including regulatory T cells and myeloid-derived suppressor cells. This favorable remodeling of the TME substantially inhibited the progression and metastasis of HCC post-iRFA. Collectively, our study presented a promising paradigm for enhancing HCC treatment efficacy by integrating radiofrequency ablation with advanced immune modulation strategies.

INNV-32. LASER INTERSTITIAL THERMAL THERAPY FOLLOWED BY CONSOLIDATION STEREOTACTIC RADIOSURGERY (LITT-CSRS) IN PATIENTS WITH NEWLY DIAGNOSED BRAIN METASTASIS

Abstract INTRODUCTION The efficacy and safety of laser interstitial thermal therapy followed by consolidation radiosurgery (LITT-cSRS) was previously studied in brain metastasis that recurs locally after initial radiosurgery (BMRS). Here, we characterize the clinical outcome of LITT-cSRS in patients with newly diagnosed brain metastasis. METHODS Between 2017 and 2023, ten consecutive cancer patients with newly diagnosed brain mass of unclear etiology who underwent stereotactic needle biopsy (SNB) and LITT in the same setting followed by consolidation SRS (cSRS) with > 6 months follow-up were identified retrospectively. Clinical and imaging outcomes were collected. RESULTS The histology of the BM were: breast cancer (n=3), melanoma (n=3), non-cell cell lung cancer (n=3), colon (n=1). There were no wound or procedural complications. All patients were discharged home, with a median one-day hospital stay (range: 1-2 days). All patients were off corticosteroid therapy by the one-month follow-up. cSRS were carried out 12-27 days (median of 19 days) after SNB+LITT. There were no subsequent emergency room presentation, 30-day or 90-day re-admission. The Karnofsky Performance Score (KPS) remains stable or improved at the 3 months-follow-up. With a median follow-up of 416 days (13.8 mo; range: 199-1,096 days), there was one local recurrence at 384 days (12.8 mo) post-LITT-cSRS. Of note, this is the only patient who underwent incomplete ablation with LITT and the location of the recurrence corresponded to the residual tumor that was not treated with LITT. With exception of this patient with local recurrence, all patients showed decreased FLAIR volume surrounding the LITT-cSRS treated BMRS by the six-month follow-up. CONCLUSIONS To our awareness, this case series represent the first to describe LITT-cSRS in the setting of newly diagnosed BM. The results presented here provide pilot data to support the safety and efficacy of LITT-cSRS and lay the foundation for future studies.

Surgical microwave ablation of 397 neuroendocrine liver metastases: a retrospective cohort analysis of 16 years of experience.

Neuroendocrine tumors (NET) constitute a heterogeneous group of malignancies whose incidence has been on the rise over the past two decades, currently documented at 5.25 per 100,000. Liver metastasis develops in over 60% of NET patients. Even after resection recurrence rates are high, underscoring the importance of parenchymal-sparing interventions. In this study, we conducted 105 surgical microwave ablations and examined outcomes related to survival and local recurrence. Retrospective review of patients who underwent a surgical microwave ablation (MWA) at a single-center, high-volume institution from September 2007 through December 2022 using a prospective database. Primary outcome was overall survival. A total of 105 operations were performed on 94 patients, with 397 tumors undergoing MWA. Median tumor size was 1.3cm (range 0.3-8.0), and the median number of tumors ablated was 2 (range 1-12). Laparoscopic approach was utilized 69.5% of the time. The most common concomitant procedure performed was hepatectomy (33.3%) and cholecystectomy (23.8%). Clavien-Dindo grade III or IV complications occurred in 9 patients (9.6%). Mortality within 30days occurred in 1 patient (1.1%). The rate of incomplete ablation was 0.3% per tumor. Local recurrence occurred in 2.8% of tumors. Median OS was 9.43years [95% CI 4.23-14.63years], with a 5- and 10-year survival probability of 70.2% and 48.2%, respectively. Surgical MWA offers an efficacious, parenchymal-sparing treatment of hepatic metastasis of NET, with low rates of incomplete ablation and local recurrence per tumor.

Incomplete Thermal Ablation-Induced FOXP4-Mediated Promotion of Malignant Progression in Liver Cancer via NDST2.

The explosive progression of residual hepatocellular carcinoma (HCC) following incomplete thermal ablation is challenging, and the underlying mechanisms require further exploration. We investigated the mechanism by which Forkhead box P4 (FOXP4) promotes the malignant transformation of residual HCC cells through N-deacetylase and N-sulfotransferase 2 (NDST2) after incomplete thermal ablation. The clinical significance of FOXP4 and NDST2 in HCC was evaluated using big data analysis. FOXP4 expression was detected in clinical samples of HCC. The gene expression levels in an in vitro heat-stressed HCC cell model were determined using quantitative real-time PCR (RT-qPCR) and Western blotting. The effects of the genes on heat-stressed HCC cells were investigated using Cell Counting Kit-8 (CCK-8), scratch, Transwell migration, and invasion assays. Additionally, the regulatory relationship between FOXP4 and NDST2 was validated using the Cleavage Under Targets and Tagmentation (CUT&Tag) experiments and phenotypic assays. High FOXP4 expression was correlated with liver cancer occurrence and development. In the heat-stressed HCC cell model, downregulating FOXP4 inhibited cancer cell progression. Besides, there was a positive association between FOXP4 and NDST2 in liver cancer. Suppressing FOXP4 reduced NDST2 expression in the heat-stressed HCC cells. Furthermore, reducing NDST2 expression weakened the biological behavior of heat-stressed HCC cells. FOXP4 and NDST2 are crucial in the incomplete thermal ablation of residual cancer. FOXP4 might regulate the biological progression of residual HCC after incomplete thermal ablation through NDST2.

A Closed-Loop Nanosystem Based on Piezoelectric Sensor and Pd-Nanoshell Photothermal Ablation for Renal Denervation to Treat Hypertension.

Renal sympathetic nerves play a crucial role in the pathogenesis of hypertension, and renal denervation (RDN) is a new solution for patients with refractory hypertension. However, current RDN techniques show inconsistent results in clinical application probably owing to incomplete endovascular ablation of the sympathetic nerves and a lack of measures to localize and assess efficacy. In this study, a closed-loop RDN system consisting of a sensing unit with a piezoelectric thin-film sensor (PTFS) and a treatment unit with a hollow Pd nanoparticle shell (PdNPS) with a diameter of 202.0nm for photothermal neural ablation is constructed. The PTFS can monitor and collect arterial pulsation and blood pressure (BP) and direct PdNPS to maximize RDN. PdNPS maintains a local temperature of 58-62°C under near-infrared-II irradiation (1,064nm) to achieve effective RDN within a range of 90-120s treatment window. Photothermal ablation significantly inhibits the activities of renal sympathetic nerves post-procedure and after one month and reduces the elevation of BP by > 50%. The novel closed-loop system enables safe and efficient targeting, dynamic monitoring, and ablation of the renal sympathetic nerves. This closed-loop system provides a new strategy for RDN technology and even for treating sympathetic nerve-related chronic diseases.

Multi‐Hierarchical Fe Single Atom Nanozymes with Axially‐Coordinated O‐Fe‐N4 Active Centers Reshape Macrophage Epigenetics Against Immunosuppression

AbstractImmunosuppression is ubiquitous in solid tumors, characterized by few cytotoxic T infiltrations, abundant inflammation enrichment, immunosuppressive cell recruitment, etc., which is especially potentiated by incomplete tumor resection. In this report, multi‐hierarchical Fe single‐atom nanozymes (SAzymes) featuring axially‐coordinated O‐Fe‐N4 active centers are constructed to reshape tumor‐associated macrophages (TAMs) epigenetics via repolarizing their phenotypes, which is highly profitable for mitigating tumor immunosuppression after incomplete radiofrequency ablation (iRFA). Therein, a nitrogen‐doped bamboo‐like carbon nanotube (N‐BCNT) is engineered to coordinatively immobilize Fe atoms, wherein another axial coordination (O) is introduced to further switch non‐polar Fe‐N4 to polar O‐Fe‐N4. The polarization switching of active centers synergies with N doping‐encouraged electron transport, low‐temperature synthesis‐discouraged N loss and large surface area‐unlocked O‐Fe‐N4 enrichment to confer tetra‐enzymic catalysis activities including peroxidase, oxidase, catalase, and glutathione oxidase, maximumly favoring reactive oxygen species (ROS) production and hypoxia reversal. After delivering TAMs polarization‐encouraged drug, toosendanin, TAMs epigenetics are altered and their phenotypes are repolarized to relieve immunosuppression and magnify immune responses, which suppress residual tumor progression after iRFA. Such a comprehensive structure optimization strategy provides a versatile route to design and construct SAzymes‐like drugs with multi‐enzymatical catalysis activities.

Ruthenium Complex Suppresses Proliferation of Residual Hepatocellular Carcinoma after Incomplete Radiofrequency Ablation Therapy.

Radiofrequency ablation (RFA) is an effective therapy for hepatocellular carcinoma (HCC). However, incomplete radiofrequency ablation (IRFA) can promote the progression of residual cancer cells, which is a serious problem in the clinical application of RFA. Therefore, it is of great significance to explore the mechanism and countermeasures of the progression of residual tumors after IRFA. Our previous study confirmed that IRFA can activate the hypoxia/ autophagy pathway of residual tumors in mice and then induce the proliferation of residual tumor cells. Additionally, we found a metal ruthenium complex [Ru(bpy)2(ipad)](ClO4)2 (Ru, where bpy = 2,2'-bipyridine and ipad = 2-(anthracene-9,10-dione-2-yl)imidazo[4,5-f][1,10]phenanthroline) can effectively inhibit hypoxia-inducible factor (HIF-1α) and has good anti-tumor effect in a hypoxic environment; however, whether Ru could suppress the proliferation of residual tumor cells after IRFA is unknown. This study intends to evaluate the effect of Ru in suppressing the proliferation of residual hepatocellular carcinoma after IRFA in a mice model. The Hepa1-6 xenograft mouse model was established in C57BL/6 mice to simulate clinical IRFA. H&E staining was used to evaluate the biosafety of major organs in the treated mice. TUNEL assay was employed to assess the antitumor effect. Immunohistochemically and immunofluorescence staining was performed to detect the expression of HIF-1α and autophagy-related proteins. The ELISA assay was used to examine the cytokines of interferon-gamma (IFN-γ) and interleukin 10 (IL-10). Our findings revealed that the residual tumor relapsed via the HIF-1α/LC3B/P62 autophagy- related pathway after IRFA, while Ru could suppress this process. In addition, it was demonstrated that Ru could effectively activate the immune system of the mice and reverse the tumor immune suppression microenvironment after IRFA. The ruthenium complex Ru could suppress the proliferation of residual hepatocellular carcinoma cells after IRFA in the mice model. This study introduces a novel approach that combines the use of ruthenium complexes with IRFA, offering a potential solution to address the reoccurrence of residual liver cancer following IRFA in clinical settings.

Incomplete ablation of thyroid cancer: Achilles’ Heel?

BackgroundIn recent years, the incidence of thyroid nodules has increased significantly. There are various ways to treat thyroid nodules, and ablation therapy is one of the important ways to treat thyroid nodules. However, there are many complications and deficiencies in the current ablation treatment of thyroid nodules, especially the incomplete ablation of thyroid cancer nodules, which limits the further application of ablation technology.Case SummaryIn this paper, we report two cases of incomplete ablation of thyroid nodules, one of which underwent surgical treatment due to anxiety after ablation, and the postoperative pathology confirmed that there was still residual papillary thyroid carcinoma, and the other patient underwent an operation after ablation, but visited our medical institution again due to cervical lymph node metastasis in a short period of time, and after radical cervical lymph node dissection, pathology confirmed multiple cervical lymph node metastasis. Radionuclide therapy was performed after surgery, and two patients are currently receiving endocrine suppression therapy, and their condition is stable with no signs of recurrence.ConclusionThe incomplete ablation of thyroid cancer nodules limits the development of ablation therapy, making ablation treatment a double-edged sword. Guidelines and expert consensus can guide their development, but they need to evolve with the times, and a multidisciplinary diagnostic team can help screen the most suitable patients. Only by using this technology more standardly, using the most appropriate technology, and treating the most suitable patients, can benefit more and more patients.

Five-year follow-up after a single US-guided high intensity focused ultrasound treatment of breast fibroadenoma

The aim of this study was to evaluate the long-term efficacy of a single ultrasound-guided high-intensity focused ultrasound (US-HIFU) treatment in patients with breast fibroadenoma (FA) in terms of volume and pain reduction as well as palpation findings. From december 2013 until november 2014 27 women with a symptomatic FA were treated in one HIFU-session. Follow-up visits were performed after 7 days, 6 months and 1, 2, 3 and 5 years with clinical examination and ultrasound. One year after the procedure, a core needle biopsy of the residual lesion was offered. There was a significant volume reduction 6 months after HIFU from 1083.10 to 347.13 mm3 (p < 0.0001) with a mean volume reduction ratio (VRR) of 61.63%. Thereafter the FAs showed a further, but no longer significant decrease in size. One patient with an initial incomplete ablation and histologically confirmed persistent vital cells after 1 year showed a strong regrowth after 3 years. Excluding this patient from analysis, the mean VRR at months 12, 24, 36, and 60 was 86.44%, 94.44%, 94.90%, and 97.85%, respectively. Before HIFU, 59.26% of the patients had pain (22.33/100 VAS) which decreased to 6.56/100 after 12 months and remained reduced over the 5 year follow up period. A decrease in palpability from 85.19 to 7.69% was observed within 24 months. A single HIFU intervention let to a substantial reduction in size, pain, and palpability with its most potential effect during the first 12 months. Subsequently, the observed effect remained stable over a 5 year follow up period. Incomplete initial treatment was associated with the risk of regrowth.

A Bioinspired Photosensitizer Performs Tumor Thermoresistance Reversion to Optimize the Atraumatic Mild-Hyperthermia Photothermal Therapy for Breast Cancer.

Mild-hyperthermia photothermal therapy (mPTT) has therapeutic potential with minimized damage to normal tissues. However, the poorly vascularized tumor area severely hampers the penetration of photothermal agents (PTAs), resulting in their heterogeneous distribution and the subsequent heterogeneous local temperature during mPTT. The presence of regions below the therapeutic 42 °C threshold can lead to incomplete tumor ablation and potential recurrence. Additionally, tumor anti-apoptosis and cytoprotection pathways, particularly activated thermoresistance, can nullify mild hyperthermia-induced tumor damage. Therefore, a bioinspired photosensitizer decorated with leucine to form biomimetic nanoclusters (CP-PLeu nanoparticles (NPs)) aimed at achieving rapid and homogeneous accumulation in tumors, is introduced. Moreover, CP-PLeu exhibits photodynamic effects that reverse tumor thermoresistance and physiological repair mechanisms, thereby inhibiting tumor resistance to hyperthermia. With the addition of NIR-II laser irradiation, CP-PLeu optimizes the therapeutic efficacy of mPTT and contributes to a minimally invasive therapeutic process for breast cancer. This therapeutic strategy, utilizing a biomimetic photosensitizer for homogeneous distribution of therapeutic temperature and photoactivated reversal of tumor thermoresistance, successfully achieves efficient breast tumor inhibition through an atraumatic mPTT process.

Analysis of technical failure after 1,613 surgical microwave ablations: A propensity score–matched analysis

BackgroundMicrowave ablation is becoming increasingly common for the treatment of liver tumors. Despite numerous studies aimed at identifying risk factors for local recurrence after microwave ablation, a consensus on modifiable risk factors for failure remains elusive, partly because of the limited statistical power of these studies. This study investigated the incidence of technical failure after microwave ablation, encompassing both incomplete ablation and local recurrence, and aimed to identify modifiable factors that reduce technical failure. MethodsThis retrospective review included patients who underwent surgical microwave ablation at a high-volume institution between October 2006 and March 2023. Univariate analysis, multivariate analysis, and propensity score matching were performed to identify risk factors for technical failure. ResultsA total of 1,613 surgical microwave ablations were performed on 3,035 tumors, with 226 instances (14% per procedure, 7.4% per tumor) of technical failure. Incomplete ablation occurred at a rate of 1.7% per tumor, whereas local recurrence was identified in 6.5% of ablations in per-tumor analysis. Body mass index >25 was significant for failure (odds ratio, 1.50; 95% confidence interval, 1.07–2.11; P < .05), suggesting that more difficult targeting may lead to increased technical failure rates. African American race (odds ratio, 1.62; 95% confidence interval, 1.16–2.27; P < .05), pre–microwave ablation transarterial chemoembolization (odds ratio, 1.54; 95% confidence interval, 1.08–2.21; P < .05), and previous ablation (odds ratio, 1.58; 95% confidence interval, 1.09–2.29; P < .05) were found to be statistically significant. ConclusionOn the basis of the largest microwave ablation database available to date, this study identified novel modifiable and nonmodifiable risk factors of microwave ablation failure. These results can lead to decreasing technical failure rates after microwave ablation.

Blocking TGFβR synergistically enhances anti-tumor effects of anti-PD-1 antibody in a mouse model of incomplete thermal ablation

The mechanism of early tumor recurrence after incomplete microwave ablation (iMWA) is poorly understood. The anti-programmed cell death protein 1 (anti-PD-1) monotherapy is reported to be ineffective to prevent the progression of residual tumor resulted from iMWA. Transforming growth factor-β (TGFβ) signaling pathway plays an important role in tumorigenesis and development. We assume blocking transforming growth factor-β receptor (TGFβR) after incomplete iMWA may synergistically enhance the effect of anti-PD-1 antibody to prevent the progression of residual tumor. We construct an iMWA model with mice harboring Hepa1-6 derived xenograft. The Tgfb1 expression and phosphorylated-Smad3 protein expression is upregulated in the residual tumor after iMWA. With the application of TGFβR inhibitor SB431542, the cell proliferation potential, the tumor growth, the mRNA expression of epithelial mesenchymal transition (EMT) markers including Cdh2, and Vim, and cancer stem cell marker Epcam, and the infiltrating Treg cells are reduced in the residual tumor tissue. In addition, iMWA combined with TGFβR blocker and anti-PD-1 antibody further decreases the cell proliferation, tumor growth, expression of EMT markers and cancer stem cell marker, and the infiltrating Treg cells in the residual tumor tissue. Blocking TGFβR may alleviate the pro-tumoral effect of tumor microenvironment thereby significantly prevents the progression of residual tumor tissue. Our study indicates that blocking TGFβR may be a novel therapeutic strategy to enhance the effect of anti-PD-1 antibody to prevent residual hepatocellular carcinoma (HCC) progression after iMWA.

Particle swarm optimization solution for roll-off control in radiofrequency ablation of liver tumors: Optimal search for PID controller tuning.

The study investigates the efficacy of a bioinspired Particle Swarm Optimization (PSO) approach for PID controller tuning in Radiofrequency Ablation (RFA) for liver tumors. Ex-vivo experiments were conducted, yielding a 9th order continuous-time transfer function. PSO was applied to optimize PID parameters, achieving outstanding simulation results: 0.605% overshoot, 0.314 seconds rise time, and 2.87 seconds settling time for a unit step input. Statistical analysis of 19 simulations revealed PID gains: Kp (mean: 5.86, variance: 4.22, standard deviation: 2.05), Ki (mean: 9.89, variance: 0.048, standard deviation: 0.22), Kd (mean: 0.57, variance: 0.021, standard deviation: 0.14) and ANOVA analysis for the 19 experiments yielded a p-value ≪ 0.05. The bioinspired PSO-based PID controller demonstrated remarkable potential in mitigating roll-off effects during RFA, reducing the risk of incomplete tumor ablation. These findings have significant implications for improving clinical outcomes in hepatocellular carcinoma management, including reduced recurrence rates and minimized collateral damage. The PSO-based PID tuning strategy offers a practical solution to enhance RFA effectiveness, contributing to the advancement of radiofrequency ablation techniques.

Potentiating dual-directional immunometabolic regulation with nanomedicine to enhance anti-tumor immunotherapy following incomplete photothermal ablation

Photothermal therapy (PTT) is a promising cancer treatment method due to its ability to induce tumor-specific T cell responses and enhance therapeutic outcomes. However, incomplete PTT can leave residual tumors that often lead to new metastases and decreased patient survival in clinical scenarios. This is primarily due to the release of ATP, a damage-associated molecular pattern that quickly transforms into the immunosuppressive metabolite adenosine by CD39, prevalent in the tumor microenvironment, thus promoting tumor immune evasion. This study presents a photothermal nanomedicine fabricated by electrostatic adsorption among the Fe-doped polydiaminopyridine (Fe-PDAP), indocyanine green (ICG), and CD39 inhibitor sodium polyoxotungstate (POM-1). The constructed Fe-PDAP@ICG@POM-1 (FIP) can induce tumor PTT and immunogenic cell death when exposed to a near-infrared laser. Significantly, it can inhibit the ATP-adenosine pathway by dual-directional immunometabolic regulation, resulting in increased ATP levels and decreased adenosine synthesis, which ultimately reverses the immunosuppressive microenvironment and increases the susceptibility of immune checkpoint blockade (aPD-1) therapy. With the aid of aPD-1, the dual-directional immunometabolic regulation strategy mediated by FIP can effectively suppress/eradicate primary and distant tumors and evoke long-term solid immunological memory. This study presents an immunometabolic control strategy to offer a salvage option for treating residual tumors following incomplete PTT.

Harnessing bimetallic iMWA nanosensitizer to unleash ferroptosis and calcium overload: Unlocking tumor vulnerability for potentiated iMWA therapy against hepatocellular carcinoma

Microwave ablation (MWA) holds promise as a tumor treatment modality, yet incomplete ablation with low-frequency MWA (iMWA) remains a significant obstacle to survival, while the high-frequency MWA poses safety concerns. To address these challenges, we introduce a novel bimetallic iMWA nanosensitizer, CFT-NPs, constructed via metal-coordination interactions between tannic acid (TA) and iron/calcium dual metal ions (Fe3+/Ca2+). The Fe3+/Ca2+ in CFT-NPs work in harmony to convert electromagnetic energy into heat, thereby bolstering the effectiveness of iMWA while maintaining good biosafety. Furthermore, the pH-triggered rupture of CFT-NPs release TA, Fe3+, and Ca2+. The liberated Fe3+ undergoes reduction by TA, and when combined with Ca2+, they trigger ferroptosis and Ca2+ overload respectively, significantly amplifying the therapeutic effects of iMWA. Utilization iMWA with CFT-NPs results in lipid oxidation, mitochondrial dysfunction, and disruption of redox balance, both in vitro and in vivo. Notably, this nanosensitizer exerts a robust antitumor effect, effectively inhibiting tumor growth and downregulating the expression of matrix metalloproteinases, which is associated with tumor metastasis. Collectively, this innovative study offers a promising approach to overcome the challenges of incomplete ablation and biological safety, enhancing the antitumor efficacy of iMWA..

Transbronchial cryoablation in peripheral lung parenchyma with a novel thin cryoprobe and initial clinical testing

BackgroundTransbronchial cryoablation shows potential as a local therapy for inoperable peripheral lung cancer. However, its clinical application for peripheral pulmonary lesions has not been reported yet.MethodsAn improved cryoprobe with an...

Magneto-Acoustic Theranostic Approach: Integration of Magnetomotive Ultrasound Shear Wave Elastography and Magnetic Hyperthermia.

Although magnetically induced hyperthermia has shown great efficiency in the treatment of solid tumors, it is still a challenge to avoid incomplete ablation or overtreatment. In this study, we applied magnetomotive ultrasound shear wave elastography (MMUS-SWE) as a tool for real-time image guidance and feedback in the magnetic hyperthermia (MH) process. We called this new method as magneto-acoustic theranostic approach (MATA). In MATA, a ferromagnetic particle (fMP) was simultaneously used as a thermoseed for MH and a shear wave source for MMUS-SWE. The fMP was excited by a high-frequency magnetic field to induce the heating effect for MH. Meanwhile, the fMP was stimulated by a pulsed magnetic field to generate shear wave propagation for MMUS-SWE. Thus, the changes in elastic modulus surrounding fMP can be used to estimate the therapy effect of MH. The phantom and in vitro experiments were conducted to verify the feasibility of MATA, which has good performance in magnetothermal conversion and treatment efficacy feedback. The shear wave speed of the isolated pork liver changed significantly after the MH process, which varied from about 1.36 to 4.85 m/s. Preliminary results proved that changes in elastic modulus could be useful to estimate the therapy effect of MH. We expect that MATA, which is the integration of MMUS-SWE and MH, will be a novel theranostic method for clinical translation.

DNA Framework-Enabled 3D Organization of Antiarrhythmic Drugs for Radiofrequency Catheter Ablation.

Preorganizing molecular drugs within a microenvironment is crucial for the development of efficient and controllable therapeutic systems. Here, the use of tetrahedral DNA framework (TDF) is reported to preorganize antiarrhythmic drugs (herein doxorubicin, Dox) in 3D for catheter ablation, a minimally invasive treatment for fast heartbeats, aiming to address potential complications linked to collateral tissue damage and the post-ablation atrial fibrillation (AF) recurrence resulting from incomplete ablation. Dox preorganization within TDF transforms its random distribution into a confined, regular spatial arrangement governed by DNA. This, combined with the high affinity between Dox and DNA, significantly increases local Dox concentration. The exceptional capacity of TDF for cellular internalization leads to a 5.5-fold increase in intracellular Dox amount within cardiomyocytes, effectively promoting cellular apoptosis. In vivo investigations demonstrate that administering TDF-Dox reduces the recurrence rate of electrical conduction after radiofrequency catheter ablation (RFCA) to 37.5%, compared with the 77.8% recurrence rate in the free Dox-treated group. Notably, the employed Dox dosage exhibits negligible adverse effects in vivo. This study presents a promising treatment paradigm that strengthens the efficacy of catheter ablation and opens a new avenue for reconciling the paradox of ablation efficacy and collateral damage.

TOP-510 Incomplete thermal ablation plus programmed cell death protein 1 monoclonal antibodies increase the incidence of hyperprogressive disease in hepatocellular carcinoma

TOP-510 Incomplete thermal ablation plus programmed cell death protein 1 monoclonal antibodies increase the incidence of hyperprogressive disease in hepatocellular carcinoma

Localization of ganglionated plexi by high density mapping: an atropine-response analysis

Abstract Introduction Growing interest has emerged around cardiac autonomic nervous system driven by ablation approaches for the treatment of neurally-mediated syncope (NMS). Ganglionated-plexi (GPs) located in the epicardial fat pads are the main target of ablative therapies, but little is known about the finest method to track their location from the endocardium. Most current techniques rely on empirical research of signal fragmentation and/or vagal response at anatomical landmarks. A poor accuracy in targeting GPs may lead to the risk of incomplete or over-extensive ablation. Purpose We analyzed the atrial electrograms (EGMs) in healty subjects and their response to atropine to describe physiological fragmentation and the relationship with vagal output. Methods Study partecipants were selected from young patients without structural heart desease who underwent electrophysiological study (EPS) for standard indications. High-density mapping of right atrium was performed before and after administration of 2 mg atropine at the end of the planned procedure. Offline analyses were performed comparing the two maps of each patient focusing on the fragmentation of the atrial EGMs. Results The study cohort comprised 10 patients (mean age of 39±11 years, 6 males). The indication for EPS was: supraventricular tachycardia (SVT) ablation in 9 patients, syncope in 1 patient. High density three-dimensional electro-anatomic maps (EAM) were all obtained with a multipolar catheter during sinus rhythm (number of points: 8794±937 in basal maps and 9007±1296 after atropine, p=0,87). The response to atropine was documented by an increase in heart rate (mean increase 59 ± 19% of basal cycle length). All basal maps showed a similar pattern of fragmentation in the posterior-septal wall reflecting the anatomical distribution of right GPs. In particular, three main stations were identified in the supero-, mid- and infero-posterior regions. Fragmentation of EGMs was found to progress from the edge to the core of each area. After administration of atropine, a reduction in fractionated area was observed in all patients. Filtering the maps according to a cut-off of fragmentation ≥ 6 peaks allowed identification of the nucleus with the highest degree of variation after atropine injection (mean basal area = 0,89 ± 0,81 cm2 ; mean atropine area = 0,44 ± 0,56 cm2 p&amp;lt;0,001). Conclusion Fragmentation of atrial electrograms is a dynamic property related to vagal output. High density mapping with a high pass filter of 6 peaks allows to identify the smallest vagal sensitive area in the anatomical stations of the GPs.