BACKGROUND:Pulsed electric field (PEF) ablation is a promising nonthermal tumor treatment for liver cancer, recognized for its ability to induce immune responses. However, the field has lacked a comprehensive bibliometric evaluation. This study aimed to provide an in-depth analysis of the research landscape. METHODS:In total, 691 English-language articles on PEF-based liver cancer therapy, published between 1989 and 2025, were identified from the Scopus and Web of Science databases. Bibliometric tools, including VOSviewer, CiteSpace, Scimago Graphica, and Bibliometrix, were applied to perform coauthorship, cocitation, and keyword cooccurrence analyses, focusing on contributions from countries, institutions, authors, and journals. RESULTS:Research on PEF therapy in liver cancer has grown steadily, showing an annual increase of 9.7%. The United States and China were the most influential contributors, with the former leading in both total publications and citations. Major contributing institutions included Zhejiang University, Zhongshan University, and Northwestern University, with Leen Edward, Nuccitelli Richard, and Davalos Rafael V. the most frequently cocited authors. Journal of Vascular and Interventional Radiology was the most productive journal in the field. Radiology showed the highest total link strength in cocitation analysis. Co-occurrence analyses of keywords and cocited references highlighted the tumor microenvironment and immunotherapy as emerging research priorities. CONCLUSIONS:PEF therapy for liver cancer is advancing rapidly and holds strong clinical promise. Future research will likely focus on the tumor microenvironment, immune mechanisms, and field parameter optimization. Strengthened international collaboration is essential to foster innovation and expand clinical applications.
To evaluate the incidence and risk factors of complications following percutaneous pulsed electric field (PEF) ablation for hepatocellular carcinoma (HCC) in high-risk anatomical locations based on a 10-year multicenter experience. This retrospective multicenter study enrolled patients with HCC who underwent microsecond PEF (μsPEF) or nanosecond PEF (nsPEF) ablation across seven medical centers between July 2015 and July 2025. Complications were categorized into minor or major according to the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) modified classification system. Propensity score matching (PSM) was employed to compare the safety profiles between the μsPEF and nsPEF cohorts, and exploratory oncologic outcomes were assessed in patients with available follow-up data. A total of 304 patients (mean age, 58.0 ± 11.0 years; 241 males) with 338 tumors were included. The overall complication rate was 7.6
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy, primarily attributable to its immunosuppressive tumor microenvironment and limited responsiveness to conventional therapies. Irreversible electroporation (IRE), a non-thermal ablation technique, holds significant promise as it preserves critical peritumoral structures and can induce immunogenic cell death. However, the immunostimulatory effects elicited by IRE are typically transient, which constrains durable therapeutic benefit. To address this limitation, we developed an electro-responsive nanoadjuvant system (PSFC) composed of peptide-modified, superparamagnetic iron oxide (SPIO)-encapsulated nanoparticles engineered to synergize with IRE. Upon IRE application, the PSFC nanoparticles undergo electro-triggered disassembly, releasing CpG oligodeoxynucleotides (CpG ODNs) to amplify both innate and adaptive immune responses. This approach promotes antigen-presenting cells' activation and macrophage polarization toward an M1 phenotype, while enhancing intratumoral T cell activation and pro-inflammatory cytokine secretion. By enabling spatiotemporal control of immune activation, this combined electro-immunotherapeutic strategy effectively overcomes the inherent immuno-resistance of PDAC and yields significantly improved treatment outcomes.
BACKGROUND:To investigate the ultrasonographic features and clinical characteristics of TFE3-rearranged renal cell carcinoma (TFE3-rRCC) in adults. MATERIALS AND METHODS:Ultrasound images and clinical records of 28 adult patients with TFE3-rRCC confirmed by immunohistochemical and fluorescence in situ hybridization were retrospectively analyzed. RESULTS:Patients (22 females, 6 males) were aged 19-70 years (mean age, 43.9 ± 15.8 years). The size of tumors ranged from 1.5 to 17.0 cm (mean diameter, 5.5 ± 3.5 cm). Seven patients (mean diameters, 9.7 ± 3.6 cm) had symptoms and 21 patients (mean diameters, 4.0 ± 2.0 cm) were asymptomatic. Most of the patients (20/28) had no metastasis and they haven't experienced recurrence. TFE3-rRCC presented as well-defined (26/28) lumps with regular shapes (27/28). Solid lumps (hyperechoic 15, isoechoic 8, hypoechoic 1) accounted for 85.7% (24/28). Cystic components (14/24), punctate or circular calcifications (8/24), and color Doppler signals (19/24) can be observed in the solid lumps. Few tumors (4/28) are cystic lumps with varying thickness internal septations (4/4), calcifications (4/4), irregular walls (2/4), and solid protrusions (2/4). CONCLUSION:Most of the TFE3-rRCC were hyperechoic or isoechoic lumps, often accompanied by cystic components and calcifications. Few cases were cystic masses with internal septations, calcifications, irregular wall, and solid protrusions. These features may have potential value in the diagnosis of TFE3-rRCC.
ABSTRACT Irreversible electroporation (IRE) is an emerging tumor ablation technique that induces permanent damage to cellular membranes through the application of high‐intensity short‐duration electrical pulses. This process results in the formation of nanoscale pores within the cell membrane, and when the electric field exceeds a critical threshold, these pores become permanent, leading to the disruption of cellular homeostasis and ultimately initiating programmed cell death. The ability of IRE to selectively target tumor cells while preserving the adjacent neural and vascular structures makes it a promising approach to the treatment of solid tumors, including those of the liver, pancreas, and prostate. In this review, we provide a comprehensive overview of the foundational research and clinical translation of IRE‐based tumor ablation technologies, with a particular focus on electrode optimization. In addition, we explore the potential for the use of IRE in combination with immunotherapy or other emerging treatment modalities. It is anticipated that the integration of technological advancements in IRE devices with personalized treatment strategies will enhance the precision and efficacy of tumor ablation.
Sonodynamic therapy (SDT) represents a promising modality for oncological treatment; however, its application in glioma management is hindered by several critical barriers, including inadequate penetration of the blood-brain barrier (BBB), the inability to monitor intracranial targeting in real time, and the lack of image guidance for treatment localization. To address these challenges, we developed an integrated theranostic nanoplatform, iRGD-LP-DM, comprising iRGD peptide-modified liposomes loaded with a manganese-chelated porphyrin sonosensitizer. The system leverages iRGD-mediated active targeting to traverse the BBB while simultaneously serving as a T1-weighted MRI contrast agent. Upon tumor accumulation, ultrasound irradiation activates the sonosensitizer, triggering localized reactive oxygen species (ROS) generation and apoptotic cell death. In vitro and in vivo evaluations confirmed the enhanced glioma-targeting and deeper tissue penetration of iRGD-LP-DM, which was effectively tracked in real time via MRI. When combined with ultrasound irradiation, iRGD-LP-DM elicited significantly stronger antitumor efficacy and prolonged survival in orthotopic glioma-bearing mice compared with all control groups. This work presents a multifunctional nanotheranostic platform that synchronizes active tumor targeting, real-time MRI guidance, and localized SDT, offering a compelling strategy for precision, image-guided treatment of glioma.
Preoperative risk stratification for cervical lymph node metastasis (LNM) is challenging in papillary thyroid carcinoma (PTC), metabolic disturbances may contribute to tumor progression and metastasis. This large retrospective cohort study investigated clinical and metabolic profiles to identify independent metabolic correlates associated with cervical LNM, which may complement preoperative risk assessment. A retrospective cohort analysis of 1,003 PTC patients was performed. Preoperative variables (demographics, clinicopathological features, serum biochemical markers) were profiled; univariate and multivariable logistic regression analyses were utilized to identify independent metabolic factors associated with central (CLNM) and lateral LNM (LLNM). Among 1,003 patients, 35.19
Early detection of focal liver lesions (FLLs) is crucial for clinical practice, but ultrasound performance heavily depends on operator experience. We developed Auto-DFLLs, an automated deep learning model based on ResNet and FPN architectures to detect FLLs in ultrasound videos. It was trained and validated on 5258 prospectively collected videos from three hospitals. On internal validation, Auto-DFLLs achieved an AP50 (average precision at IoU = 50%) of 0.7772, Pr70 (precision at 70% recall) of 0.7967, and FP70 (false positives at 70% recall) of 3.4688. Validation study showed that Auto-DFLLs significantly improved junior sonographers’ detection (AFROC-AUC: 79.52 vs. 71.55, P = 0.021) and enhanced senior sonographers’ performance (AFROC-AUC: 78.64 vs. 74.57, P = 0.0366), especially for small lesions (< 10 mm, P = 0.034). Auto-DFLLs maintained stable detection across different lesion size, echogenicity, location, and ultrasound equipment from different manufacturers. Auto-DFLLs reduces operator-dependent variability and offers a reliable assistive tool for real-time FLLs screening, particularly valuable in resource-limited areas.
In patients at high risk for hepatocellular carcinoma (HCC), perfluorobutane-enhanced US incorporating Kupffer-phase findings by using modified Liver Imaging Reporting and Data System criteria was effective for diagnosing HCC in liver nodules (≤20 mm), and diagnostic performance was similar to that of MRI.
Background & Aims: Irreversible electroporation (IRE) and stereotactic body radiotherapy (SBRT) are important therapeutic alternatives for hepatocellular carcinoma (HCC) unsuitable for thermal ablation, but comparative outcome data remain limited. We compared the efficacy and safety of IRE vs. SBRT for solitary HCC ≤5.0 cm. Methods: Between January 2019 and December 2024, this multicenter retrospective cohort study at five centers included 315 patients with solitary HCC ≤5.0 cm (IRE, n = 180; SBRT, n = 135). To reduce confounding, propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and restricted cubic splines (RCS) were applied. The primary endpoint was cumulative recurrence rate (CRR), comprising cumulative local recurrence (CLRR) and cumulative distant recurrence (CDRR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results: After a median follow-up of 36 months, matched cohorts showed no significant differences in CRR (hazard ratio [HR]: 0.83; p = 0.332), PFS (HR: 0.77; p = 0.171), or OS (HR: 0.76; p = 0.529). However, in the matched cohort, IRE achieved superior local control, with a lower 3-year CLRR (14.2% vs. 30.5%; HR: 0.31; p = 0.001). SBRT local control was lower than in some previous studies, possibly reflecting anatomically complex tumors requiring risk-adapted planning. This CLRR benefit was consistent across tumor sizes and in perivascular HCC. CDRR was comparable (HR: 0.92; p = 0.685). Overall AE rates were similar (33.3% vs. 38.5%; p = 0.266), although profiles differed (transaminase elevations with IRE vs. gastrointestinal disturbances with SBRT). Conclusions: IRE and SBRT yielded comparable OS and PFS for solitary HCC ≤5.0 cm. However, IRE offered significantly superior local tumor control, especially for tumors adjacent to major vessels. Impact and implications: This multicenter study addresses the limited comparative evidence between IRE and SBRT for HCC unsuitable for thermal ablation. The findings indicate that, although survival outcomes were comparable, IRE demonstrated superior local tumor control, particularly for perivascular lesions. These results support IRE as a strategic therapeutic option for anatomically complex tumors, aiding clinicians in optimizing treatment selection based on specific tumor location and vascular proximity. Future prospective trials are warranted to validate these findings and refine patient selection.
OBJECTIVE:This study aimed to investigate the contrast-enhanced ultrasound (CEUS) imaging features of renal hemangiomas and to evaluate their potential role in improving preoperative diagnosis and differential diagnosis. METHODS:In this retrospective study, clinical and ultrasound data from 20 patients with surgically confirmed renal hemangiomas (22 lesions) were analyzed. All patients underwent preoperative conventional ultrasound. Among them, 6 patients (7 lesions) additionally underwent CEUS examination within one month before surgery. Standardized ultrasound techniques and equipment were employed, with focused analysis on the enhancement patterns and hemodynamic characteristics observed on CEUS. RESULTS:The cohort comprised 10 men and 10 women (mean age 50 years). Most lesions (13/22) were located in the renal medulla. On conventional ultrasound, lesions typically appeared as well-defined, round, hypoechoic nodules, with most showing no significant internal flow on color Doppler imaging. In the 6 patients who underwent CEUS, a characteristic pattern of peripheral nodular enhancement in the arterial phase, followed by progressive centripetal filling, was observed. Peak enhancement intensity was generally comparable to that of the surrounding renal parenchyma. Pathologically, anastomosing hemangioma and capillary hemangioma were the most common subtypes (9 cases each), with immunohistochemical profiles (CD31/CD34 positive, low Ki-67) consistent with benign behavior. CONCLUSION:The combination of conventional ultrasound and CEUS may enhance the preoperative evaluation of renal hemangiomas. CEUS demonstrates distinctive enhancement patterns that can aid in differentiating these rare benign tumors from other renal malignancies. However, these findings are preliminary and require validation in larger-scale studies.
Background: Radiofrequency ablation (RFA) is a curative therapy for early-stage hepatocellular carcinoma (HCC), yet recurrence remains a major challenge. Current predictive tools are limited by small sample sizes, linear assumptions, and lack of rigorous validation. Materials and Methods: In this multi-center bidirectional cohort study, we enrolled 2,602 HCC patients who underwent RFA across four hospitals (2012–2024). Eighteen predictors were selected via adaptive Elastic-Net regression. We developed and internally-externally validated twelve machine learning (ML) algorithms for recurrence prediction. The optimal model was interpreted using SHapley Additive exPlanations (SHAP). Mediation analysis explored the causal pathway between tumor location and recurrence. Results: Over 8,377 person-years, 3,653 recurrence events occurred. The Gradient Boosting Classifier (GBC) achieved superior discrimination, with AUROCs of 0.987 (training) and 0.963, 0.966, and 0.862 in three independent external validation cohorts. SHAP analysis revealed that ablation technical difficulty mediated 47.3% of the effect of tumor location on recurrence. Importantly, we identified a non-linear “proficiency curve” for surgeon experience, with optimal outcomes observed at 5~15 years of experience. The model maintained robust performance across temporal and subgroup analyses. Conclusions: The GBC model provides highly accurate, interpretable predictions of post-RFA recurrence using readily available clinical parameters. The mediation insights offer actionable targets, such as technical optimization, to potentially improve outcomes beyond simple risk stratification.
Liver malignancies are frequently evaluated on contrast-enhanced computed tomography (CE-CT), but missed or delayed diagnoses remain a clinically important challenge in high-volume, real-world radiology workflows, highlighting the need for scalable diagnostic safety net approaches. To address this, we developed the Liver DiagnOsis Network (LiON), a CE-CT-based artificial intelligence (AI) system that supports flexible multiphase processing, clinical data integration and workflow-compatible liver malignancy diagnosis. LiON was trained on 6,443 patients and retrospectively validated across 22,251 patients from multicenter and real-world cohorts. LiON achieved high performance for malignancy diagnosis, with an area under the receiver operating characteristic curve (AUC) of 0.975 (95% confidence interval (CI): 0.971-0.979), and maintained robust performance in real-world cohorts and among patients with hepatic steatosis (AUC 0.971, 95% CI: 0.952-0.985) and cirrhosis (AUC 0.924, 95% CI: 0.901-0.946). We then conducted a single-arm trial in 10,333 patients in routine clinical practice, in which LiON functioned as an additional AI reader within the existing clinical workflow. The trial met its primary endpoint, defined as an AUC for malignancy diagnosis with the lower bound of the 95% CI exceeding 0.900, achieving an AUC of 0.952 (95% CI: 0.942-0.961). Secondary outcomes demonstrated that AI-human collaboration identified 51 previously overlooked lesions (15 malignancies) and triggered 37 amended radiology reports, 22 multidisciplinary team escalations and clinical management changes in a subset of patients. These findings suggest that AI, when deployed as a workflow-compatible diagnostic support, may help reduce missed or delayed diagnoses and guide clinical interventions. Nevertheless, further evidence from prospective comparative studies across diverse healthcare systems is warranted to assess effects on clinical outcomes. ClinicalTrials.gov identifier: NCT07153783 .
Serous effusions, including pleural effusion and ascites, commonly occur in advanced cancers like lung and ovarian carcinomas. Detecting tumor cells in these effusions is crucial for assessing cancer metastasis. However, clinical methods mainly include cytological examination, which has limited sensitivity, and complex cell block technology that requires large volumes of serous effusion. Surface-enhanced Raman spectroscopy (SERS), with its high sensitivity and noninvasive nature, has emerged as a crucial tool for liquid biopsies. Building on this technology, a novel SERS bioprobe was specifically designed for the precise identification and capture of tumor cells in serous effusions, utilizing a composite material. The SERS bioprobes offer strong SERS enhancement, excellent spectral reproducibility, and molecular targeting, thereby enhancing detection specificity. Furthermore, SERS classification models were established to categorize samples based on tumor cell concentrations in serous effusions, enabling semiquantitative diagnostic capability. Notably, machine learning-assisted analysis enables rapid processing and classification of numerous Raman spectra and thorough feature extraction and greatly improves the SERS bioprobe's diagnostic accuracy. Consequently, the combination of SERS bioprobes and machine learning provides a rapid and effective detection method that overcomes the low sensitivity of conventional cytological detection in serous effusions and enables assessment of tumor cell concentration ranges within these fluids.
Objective: To assess the efficacy of this approach and establish the criteria that identify patients with locally advanced pancreatic cancer (LAPC) who may achieve survival benefits from radical resection combined with intestinal autotransplantation (RRCIA).Background: Surgical resection for LAPC remains challenging and is associated with high morbidity and mortality, especially for surgery with major arterial reconstruction. We previously showed the feasibility and safety of RRCIA after systemic treatment.Methods: A retrospectively observational and prospectively validated study with 3 cohorts was conducted using multiple treatments. Overall survival (OS) and progression-free survival (PFS) were compared for both analyses. Propensity-score matching (PSM) and stabilized inverse probability of treatment weighting (IPTW) were performed to adjust for potential confounders.Results: Among 208 patients with LAPC, we identified 48 who underwent systemic treatment followed by RRCIA. Using PSM and stabilized IPTW analyses, we observed that patients who underwent RRCIA had better overall and PFS compared with patients who did not have surgery (PSM cohort: median OS: 25.8 vs 14.2 months, P = 0.0031, and IPTW cohort: median OS: 23.2 vs 15.4 months, P = 0.0069) and PFS (PSM cohort: median PFS: 13.3 vs 7.0 months, P = 0.0246, and IPTW cohort: median OS: 13.3 vs 8.8 months, P = 0.002). Further prospective analysis showed that patients who received systemic treatment, followed by RRCIA, were associated with improved OS and PFS compared with patients who were eligible but did not receive RRCIA (median OS: 22.6 vs 18.2 months, P = 0.035; median PFS: 13.2 vs 10.3 months, P = 0.0412). Moreover, the stratified and multivariable analysis demonstrated that preoperative carbohydrate antigen 19-9 normalization and duration of initial treatment over 8 cycles were predictors for the precise selection of patients who would benefit from RRCIA. Meanwhile, adjuvant therapy after RRCIA was a significant factor in improving survival.Conclusions: This study suggests that RRCIA appears to be effective and associated with improved outcomes for patients with LAPC with favorable responses to systemic treatment. Patients with LAPC Should have at least 8 cycles of systemic treatment and carbohydrate antigen 19-9 normalization to be considered for RRCIA.
Papillary thyroid carcinoma (PTC) exhibits a high incidence and a strong propensity for lymph node metastasis (LNM). Accurate preoperative assessment of LNM is crucial for guiding surgical approaches, but conventional ultrasound exhibits suboptimal sensitivity. In this study, we developed a deep learning-based multimodal model to predict LNM in PTC patients. We retrospectively collected fine needle aspiration (FNA) liquid-based cytology specimens (N = 1095) and corresponding ultrasound images (N = 2190). A ResNet-101 architecture was trained using five-fold cross-validation and validated on external datasets from two independent centers. The multimodal model achieved strong predictive performance on the internal validation set (area under the curve, AUC: 0.891; accuracy: 0.821) and external validation set (AUC: 0.875; accuracy: 0.808). It outperformed models based solely on ultrasound or cytology images. Gradient-weighted class activation mapping revealed that nuclear features in FNA images were the most influential for LNM prediction. Our model achieved promising predictive performance and has the potential to guide clinical decision-making, potentially reducing unnecessary lymph node dissections in PTC patients.
Although irreversible electroporation (IRE) is an approved ablation therapy for liver cancer, the border of the IRE-induced inflammatory margin (IM) remains poorly defined, posing a challenge for investigating IRE-specific immune and metabolic alterations within this area. To address this, we employed a male C57BL/6 orthotopic liver cancer model and integrated spatial transcriptomics, spatial metabolomics, single-cell RNA sequencing, and cytometry by time-of-flight (CyTOF). This multiomics approach enabled precise spatial mapping of the IM and revealed a pronounced infiltration of Ly6ClowPD-L1hi that phenotypically resemble lipid-associated macrophages (LAMs). Further analysis uncovered profound lipid metabolic reprogramming within the IM, including biosynthesis of unsaturated fatty acids, arachidonic acid and sphingolipid metabolism, which appears to sustain the immunosuppressive phenotype of LAMs. Collectively, our study uncovers an IRE-specific immunosuppressive microenvironment in the IM and propose potential metabolic targets that might be effectively combined with IRE to improve therapeutic outcomes.
Sonodynamic immunotherapy represents a promising strategy for cervical cancer treatment by stimulating antitumor immune responses. However, therapy-induced prosurvival autophagy may attenuate therapeutic efficacy. To address this limitation, we constructed multifunctional nanoparticles (poly[lactic-co-glycolic acid]-b-poly[ethylene glycol] [PLGA-PEG2,000]-based nanoparticles coloaded with hematoporphyrin monomethyl ether and SAR405 [PHS NPs]) codelivering the sonosensitizer hematoporphyrin monomethyl ether and the selective vacuolar protein sorting 34 inhibitor SAR405. Upon low-intensity focused ultrasound irradiation, PHS NPs generated reactive oxygen species that induced mitochondrial stress while concurrently modulating autophagic flux through VPS34 inhibition. This coordinated intervention was associated with microtubule-associated protein 1A/1B-light chain 3-II and p62 coaccumulation and the presence of undegraded autolysosomal structures, suggesting impairment of lysosome-associated autophagic degradation. Enhanced oxidative stress, together with modulation of autophagic flux, was accompanied by lysosomal dysfunction and reduced degradative capacity. These alterations were associated with sustained intracellular stress and amplified oxidative injury in tumor cells. Functionally, the combined treatment suppressed tumor growth, promoted immunogenic cell death, and was accompanied by macrophage polarization toward an M1-like phenotype and increased CD8+ T cell infiltration. Validated in HPV-associated tumor models, this nanoparticle-based strategy provides a rational and potentially translatable platform to mitigate autophagy-associated adaptive responses and enhance the therapeutic potential of sonodynamic immunotherapy in solid tumors.
Breast cancer (BC) is a serious health threat to women worldwide and is on the steady rise in morbidity and mortality, of which estrogen receptor α (ERα)-positive cases account for nearly 70%. ERα is highly expressed in ERα-positive (ERα+) BC, and it is involved in tumorigenesis and metastasis, making it a compelling target for BC theranostics. Herein, we developed and evaluated an ERα-targeted fluorescent probe (IRDye800-4OHT) by conjugating ERα targeting ligand 4-hydroxytamoxifen with near-infrared fluorescence dye IRDye800CW for ERα+ BC detection via imaging ERα. The probe demonstrated a second near-infrared (NIR-II) imaging capability (λem = 950 nm), high binding affinity (RBA = 2.3) toward ERα, and excellent biocompatibility. In vitro cellular uptake further confirmed that IRDye800-4OHT could specifically target the ERα. Moreover, in vivo NIR-II imaging clearly revealed that IRDye800-4OHT enabled real-time imaging of ERα, specifically illuminated tumor tissue, and successfully guided breast tumor resection. Therefore, we postulate that IRDye800-4OHT can serve as a valuable tool for the precise diagnosis and surgical excision of ERα-positive tumors.