INTRODUCTION:Primary liver cancers, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, are one of the leading causes of cancer-related mortality. Transarterial chemoembolisation (TACE) and radioembolisation (TARE) are established palliative treatments yet they are traditionally performed during inpatient hospitalisation. Recent technical and organisational advances allow for safe same-day ambulatory procedures. In particular, the extent to which ambulatory intra-arterial therapy aligns with patients' expectations, comfort and quality of life remains poorly documented. The Care pathway for Hepatic intra-arterial Oncology in an ambulatory Context study (CHOC) trial aims to evaluate the implementation and effectiveness from both patient-centred and clinical perspectives of an ambulatory care pathway for intra-arterial treatment of primary liver cancer in a multicentre randomised hybrid type 1 trial. METHODS AND ANALYSIS:CHOC is a pragmatic, multicentre, randomised controlled hybrid type 1 trial comparing ambulatory versus conventional inpatient care for patients undergoing TACE or TARE for primary liver cancer. A total of 206 patients (103 per arm) will be randomised 1:1 and followed for 7 months. The primary outcome is the patient's global satisfaction score, measured 3 days post-procedure using the EORTC PATSAT-C33 questionnaire. Secondary outcomes include quality of life, safety, clinical outcomes, cost analysis and an embedded qualitative implementation study assessing acceptability, adoption, feasibility and sustainability across centres. Economic analyses will estimate both per-patient costs and the 5-year budget impact for the French national health insurance. ETHICS AND DISSEMINATION:The study has received ethical approval from the Protection of Persons Committee and adheres to the Declaration of Helsinki, good clinical practice and French regulatory requirements. Findings will be disseminated through peer-reviewed publications, conferences and participating centres to guide broader implementation of ambulatory interventional radiology care. TRIAL REGISTRATION NUMBER:NCT06990659.

BACKGROUND & AIMS:We aim to analyze the impact on oncological outcomes of extrahepatic metastases (EM) in patients with unresectable hepatocellular carcinoma (HCC) treated by atezolizumab/bevacizumab (Atezo/Bev). METHODS:We retrospectively included patients with HCC treated with Atezo/Bev as first-line systemic treatment in 6 centers. EM patterns were assessed using the following definitions: 1) presence of EM, 2) number of EM sites (none, 1, 2, ≥3), 3) EM burden (total number of metastases) and 4) oligometastasis status (ESMO definition). We used cox and logistic regression to evaluate the associations between variables and overall survival (OS), progression free survival (PFS) and radiological progression (RECIST v1.1). RESULTS:647 patients were enrolled with a median age of 67 years, 86% male and 74% of cirrhosis. Among the 197 patients with EM (30%), the most common metastatic sites were lymph nodes (49%), lung (39%), peritoneal (19%), and bone (19%) and 71% had a unique EM, 29% had ≥ 2 EM sites and 8.1% ≥ 3 EM sites. EM was not associated with OS but was associated with shorter PFS (adjusted hazard ratio [aHR]:1.23, 95%CI:1.01-1.49, p = 0.036) and lower disease control rate (DCR) (adjusted odds ratio [aOR]:0.62, 95%CI:0.44-0.89, p = 0.009). Three or more EM sites were associated with poorer OS (aHR: 2.44, 95%CI: 1.39-4.29, p = 0.02), PFS (aHR:2.22, 95%CI: 1.31-3.75, p < 0.01), and DCR (aOR: 0.28, 95%CI: 0.08-0.85, p = 0.035). Patients with oligometastasis have the same OS and PFS than patients without metastasis whereas patients with multiple metastasis have a shorter OS (P = 0.026) and PFS (P < 0.001). CONCLUSION:Presence of high metastatic burden negatively affects the prognosis of patients with HCC under Atezo/Bev whereas patients with oligometastasis have the same oncological outcomes than patients without EM.

To assess the safety and efficacy of an irreversible electroporation (IRE) system integrating real-time electrical and thermal monitoring for liver tumor ablation. This bicentric retrospective study included all consecutive patients treated with this device for primary or secondary liver tumors between April 2022 and August 2024. IRE was selected when surgery or thermal ablation was unsuitable. Patient, tumor and procedure characteristics—including voltage, amperage, interprobe distance, and maximal needle tip temperature—were recorded. Procedures were guided by CT, cone-beam CT or ultrasound. The protocol aimed for a “plateau-current” ≥30 A per needle pair while maintaining probe-tip temperature <50 °C near at-risk structures. Complications were classified using the CIRSE classification. Local tumor progression-free survival (LTPFS) was assessed by MRI every 3 months. 27 patients with 31 liver tumors (15 primary, 16 metastatic; mean diameter 17.9 mm) were treated using 3–6 electrodes. No grade ≥3 complications occurred. Median follow-up was 18.4 months; 6- and 12-month LTPFS rates were 87

Electrochemotherapy (ECT) combines the administration of cytotoxic agents with high-voltage electric pulses that transiently permeabilize tumor cell membranes and enhance intracellular drug uptake. This minimally invasive, nonthermal technique is particularly suitable for tumors located near critical structures, where surgery, radiotherapy, or percutaneous thermal ablation may be limited. In the spine, ECT can provide pain relief, neural decompression, and local tumor control while preserving neural structures. However, its implementation remains challenging due to complex vertebral anatomy, limited understanding of electric field distribution, the absence of dedicated planning tools, and the risk of neural injury. This protocol describes a reproducible workflow for patient-specific electric field simulation in spinal ECT. Multimodal imaging combining CT and MRI enables reconstruction of tumoral, vertebral, neural, and soft-tissue anatomy using semi-automatic and manual segmentations performed within the open-source 3D Slicer platform. Tissue conductivities are assigned according to the IT'IS database, and linear finite-element simulations (constant conductivity) are performed with AI4DEEP, a dedicated 3D Slicer module, to compute 3D electric field maps across multiple isodose thresholds. Follow-up contrast-enhanced MRI is used for validation through Dice similarity coefficients comparing simulated isoelectric field volumes with post-ECT necrotic tumoral areas. Qualitative comparison of simulated electric field maps, follow-up MRI, and clinical outcomes was performed by expert interventional radiologists to evaluate the ability of the software to predict undertreated and overtreated regions. Nine ECT procedures were processed to assess the workflow. The highest concordance between simulated electric field and post-ECT necrosis was observed in the 160-200 V/cm range in this specific clinical and numerical setting. The workflow also identified regions of insufficient or excessive treatment, consistent with clinical and imaging follow-up. The described workflow lays the groundwork for reproducible ECT planning, supporting optimized electrode placement and parameter adjustment to improve safety and efficacy in complex spinal ECT procedures.

BACKGROUND & AIMS:We compared multibipolar radiofrequency ablation (mbpRFA) with open liver resection (OLR) or laparoscopic liver resection (LLR) in patients with HCCs within Milan. METHODS:This multicenter cohort study included patients treated by mbpRFA, OLR or LLR for HCC within the Milan Criteria, developed on advanced fibrosis in nine French centres between 2008 and 2018. Adjustments on HCC size/number, gender, age, ASA, HCV, HBV, metabolic syndrome, chronic alcohol intake, MELD score, serum AFP level, APRI score, cirrhosis, significant portal hypertension and HCC localization were performed using multivariable regressions with centre-robust variance and propensity score-based matching (3:1 nearest-neighbour with calliper < 0.1; effective ratios 2.18:1 and 2.43:1). RESULTS:1040 patients were included (median age: 64 years; male 82.9%), with 606, 266 and 168 treated by mbpRFA, LLR and OLR. Most HCCs were solitary (84.8%) and on cirrhosis (89.2%). In months, the follow-up was 50.2 (95% CI: 45.3, 54.3), 43.3 (95% CI: 40.0, 48.6) and 47.4 (95% CI: 40.8, 58.7) for mbpRFA, LLR and OLR patients. After matching, OLR patients had similar overall survival (OS) (HR = 1.05 [CI 95% = 0.65, 1.69], p = 0.853), transplant-free survival (TFS) (HR = 0.91 [CI 95% = 0.56, 1.47]; p = 0.690) or recurrence-free survival (RFS) (HR = 0.99 [CI 95% = 0.69, 1.43]; p = 0.968) compared to mbpRFA patients but with more severe adverse events (RR = 2.58 [CI 95% = 1.16, 5.71]; p = 0.02) and mortality (RR = 4.51 [CI 95% = 1.16, 17.59]; p = 0.03). After matching, LLR patients had better OS (HR = 0.57 [CI 95% = 0.38, 0.88], p = 0.01) but similar TFS (HR = 0.77 [CI 95% = 0.55, 1.1]; p = 0.152) and more severe adverse events (RR = 2.61 [CI 95% = 1.15, 5.96]; p = 0.022) compared to mbpRFA patients. LLR patients had a better RFS (HR = 0.7 [CI 95% = 0.53, 0.91]; p = 0.009) than mbpRFA patients. When distant-only recurrences were considered in the mbpRFA patients, there was no significant difference in RFS (p = 0.087). The LLR survival benefit was consistent across pre-specified subgroups, with no interaction surviving correction for multiple testing. CONCLUSIONS:Minimally invasive modalities (LLR or mbpRFA) should be prioritized when treating early HCC. LLR maximizes oncological outcomes, but mbpRFA maintains optimal TFS with less morbidity.

BACKGROUND & AIMS:In hepatocellular carcinoma (HCC) with cirrhosis, portal hypertension worsens outcomes. Esophagogastroduodenoscopy (EGD), the current screening method for esophageal varices (EVs), is invasive and may delay therapy. We aimed to develop and externally validate non-invasive models to detect EVs and predict hepatic decompensation (bleeding, ascites or hepatic encephalopathy), a major cause of mortality in patients with HCC, using routine contrast-enhanced CT and clinical data. METHODS:This multicenter retrospective study included 489 patients with unresectable HCC treated with atezolizumab-bevacizumab (AtezoBev) from five French centers, divided into a development cohort (n = 279) and an external validation cohort (n = 210). Arterial-phase contrast-enhanced CTs were processed through a Deep Learning pipeline using a foundation model (HepatoSageCT). Logistic and Cox models generated clinical models and combined models integrating the HepatoSageCT scores with key clinical variables for EVs and hepatic decompensation. Performance was assessed using AUROC, sensitivity, specificity, C-index and cause-specific hazard ratios. RESULTS:Portosystemic shunts (PSS) at imaging identified EVs with an AUROC of 0.78, increasing to 0.84 when combined with HepatoSageCT. A decision algorithm incorporating PSS and HepatoSageCT missed 4.2% of varices needing treatment, compared to 8.4% when using only PSS, while missing 0% of large EVs. HepatoSageCT predicted hepatic decompensation in the validation cohort (C-index: 0.73, hazard ratio: 3.17) with significant stratification (p <0.001), comparable to a composite score of ascites, splenomegaly and HepatoSageCT risk (C-index: 0.73, hazard ratio: 3.48). Patients stratified at higher risk of decompensation by HepatoSageCT also exhibited significantly lower overall survival (p <0.001). CONCLUSIONS:HepatoSageCT scores, supplemented with clinical data, enable accurate non-invasive detection of EV in AtezoBev-treated unresectable HCC and stratify patients according to their risk of hepatic decompensation. This approach may reduce unnecessary endoscopies and improve prognostic assessment. IMPACT AND IMPLICATIONS:The present study demonstrates that foundation models applied to routine CT imaging, when combined with routinely collected features such as the presence of portosystemic shunts, can accurately predict the presence of esophageal varices and the risk of first or further hepatic decompensation in patients with AtezoBev-treated unresectable hepatocellular carcinoma. These findings are particularly relevant for hepatologists and oncologists, as they highlight a promising non-invasive tool for timely risk assessment in a time-sensitive patient population. While prospective validation is warranted, this approach could support more personalized management and care of patients with unresectable hepatocellular carcinoma.

BACKGROUND AND AIMS:Irreversible electroporation (IRE) is a non-thermal ablation technique suited for difficult-to-treat hepatocellular carcinoma (HCC) with 1-year local recurrence (LR) rates above 50%. We hypothesized that peri-procedural immunotherapy could synergize with IRE to decrease local recurrence. APPROACH AND RESULTS:NIVOLEP is a multicenter phase 2 trial evaluating nivolumab combined with IRE in patients with BCLC A HCC. Patients received 2 neoadjuvant nivolumab infusions, IRE with curative intent, and 12 monthly adjuvant nivolumab infusions. Tumor biopsies were performed at baseline and during IRE. The primary endpoint was 1-year local recurrence-free survival (LRFS). In all, 62 HCC nodules (mean size: 30.0 mm) from 43 patients (mean age: 71 y, 88% male, 81% cirrhosis) were considered. All patients received neoadjuvant nivolumab; 35 underwent curative IRE (8 others: 4 IRE failures, 3 HCC progressions, 1 death). After neoadjuvant nivolumab, radiological or pathological response was observed in 24.2% and 26.3% nodules, respectively. One-year LRFS was 70.6% (95% CI: 55.3-85.9), and 2-year overall survival was 74.2% in the intention-to-treat analysis. Grade 3 or 4 adverse events related to nivolumab occurred in 2 patients; 1 patient died due to nivolumab. RNA-sequencing analysis of the tumor after neoadjuvant nivolumab showed an enrichment of pathways associated with leukocyte migration, T cell activation, and CD8+ T and B-cell infiltration associated with pathological response. Circulating protein variations were associated with pathological or radiological responses and local recurrence. CONCLUSIONS:Neoadjuvant and adjuvant nivolumab in BCLC A HCC patients eligible for IRE lead to pathological response related to immune activation and show anti-tumoral effect.

Cholangiocarcinoma (CCA) is the second most common primary liver cancer and is being diagnosed with increasing frequency worldwide. We performed a systematic review on radiofrequency (RFA), microwave (MWA), irreversible electroporation (IRE), trans-arterial chemoembolization (TACE) and selective internal radiation therapy (SIRT) in CCA. Thirty-one ablation studies (1526 patients), 21 TACE studies (1594 patients), and 38 SIRT studies (1954 patients) were included; most cohorts involved intrahepatic CCA (iCCA) and originated from Asia. For RFA/MWA, overall survival (OS) typically exceeded 25 months and recurrence-free survival (RFS) 7-9 months. The ideal candidate profile for percutaneous ablation was an uninodular iCCA measuring ≤ 2-3 cm developed on cirrhosis. For TACE, median objective response rate (ORR) was 35%, with median OS 11.7 months and RFS of 4 months. Hypervascularity, low tumour burden (< 30%-50% of liver involvement), and preserved liver function were associated with better outcomes and may be used to identify suitable candidates for TACE in case of unresectable iCCA. For SIRT, median ORR was 36.3%, OS 14.5 months, and RFS 8.7 months. A large unilobar tumour with personalised dosimetry appears the best candidate for SIRT in unresectable iCCA, with potential for downstaging to surgery in some cases. However, the literature regarding locoregional treatment is predominantly retrospective and heterogeneous, with inconsistent reporting of staging, cirrhosis, and endpoints, and almost no randomised trials. Locoregional radiological therapies remain viable options for carefully selected, liver-dominant iCCA, but prospective multicenter studies are needed to define indications, and to optimise sequencing and combination strategy with systemic treatments.

Background and Objectives: Electroporation ablation is a promising nonsurgical and minimally invasive technique for tumor ablation; however, no monitoring is currently available. In this article, we present recent advances in the numerical workflow toward a peroperative numerical evaluation of clinical irreversible electroporation (IRE) procedures of liver tumors. The objective of this study is to propose an updated numerical workflow for the digital twin of electroporation ablation, to provide relevant information to physicians performing IRE for hepatocellular carcinoma (HCC). Methods: The workflow consists of four main steps: (1) an image registration algorithm to align the contrast-enhanced cone beam computed tomography (CBCT), where the region of interest are visible, with the lower-quality CBCT acquired after needle insertion; (2) extraction of needles position by manual selection directly on the CBCT containing the needles; (3) accurate and efficient numerical computation of the electric field (EF) distribution, using a static linear model and the finite difference method to simulate the EF at the maximum voltage applied between each electrode pair; and (4) numerical assessment of the tumor coverage by the 3D EF. Results: We propose a criterion for electrical heterogeneity of the medium near the electrode thanks to the measurements provided by the Nanoknife IRE device. The full protocol was tested on three representative patients with nodular HCCs <5 cm. The complete numerical workflow, from image registration and needle detection to the computation, requires at most less than 15 min following image acquisitions, making it suitable for clinical use. Interestingly, the number of finite difference computations increases linearly with the number of needles N, despite the number of electrode pairs increasing as N ( N - 1 ) / 2 . In addition, the pulse amplitude can be modified without the need for full recomputation, enabling online adjustment of the treatment plan.

Electroporation ablation is a promising non-surgical and minimally invasive tumor ablation technique. The objective of this paper is to propose a deep learning strategy for fast and accurate 3D computation of the electric field distribution during the ablation procedure. The computation of the electrostatic potential is accelerated using a well-designed convolutional neural network, which serves to initialize the iterative solver for matrix inversion The proposed approach, which combine deep learning and more standard numerical strategies, is compared with state-of-the-art numerical schemes, evaluating its performance in terms of error on the solution, residuals of the numerical scheme, and computation time. As a proof of concept, we demonstrate its potential on a clinical case of electroporation ablation of a liver tumor, showing that the proposed approach can be advantageously combined with clinical data to provide real-time insights into the effective electroporation ablation.

Accurate electric dosimetry is essential for predicting treatment outcomes in Irreversible Electroporation (IRE), a promising non-thermal tumor ablation technique. However, real-time 3D electric field computation remains computationally expensive, limiting its practical use in clinical settings. In this study, we propose a hybrid approach combining deep learning (DL)-based initialization with an iterative numerical solver to accelerate dose map calculation. The novelty of our approach is to combine CNN and numerical discretization of the partial differential equation to compute fastly and accurately the electric potential. We evaluate our method on data from 10 patients undergoing IRE liver ablation under real-time clinical conditions. Our results demonstrate a 10-fold speedup compared with conventional solvers while maintaining comparable accuracy. This hybrid method offers a promising pathway toward fast and reliable electric dosimetry for on-line IRE procedures.

Objective.To correlate numerical simulations of the electric dose distribution with early post-operative MRI following irreversible electroporation (IRE) treatment of hepatocellular carcinoma (HCC).Approach.A standard linear electrostatic model was employed to simulate the three-dimensional electric field (EF) distribution using real electric pulses and geometrical characteristics and intraoperative cone-beam CT (CBCT) data. Spatial registration between intraoperative CBCT and post-operative MRI was performed using both rigid and deformable methods, ranging from simple global translations based on anatomical landmarks to advanced deformable image registration (DIR) techniques accounting for elastic tissue deformations.Main results.The proposed approach was retrospectively evaluated using data from 22 patients who underwent IRE liver ablation (one patient underwent two distinct IRE procedures), resulting in a total of 23 procedures. The most accurate correspondence between predicted and observed ablation zones was achieved using a dose threshold of approximately 350 V cm-1, yielding a median dice similarity coefficient around 0.74, indicative of substantial spatial overlap. Although elastic DIR approaches applied to segmented liver regions provided the highest registration accuracy, the simpler translational registration based on manually selected landmarks demonstrated surprisingly robust performance in localizing the simulated EF within the actual ablation zone.Significance.These findings contribute to the standardization of IRE efficacy assessment on MRI and highlight the significant potential EF simulations to predict the extent of tissue ablation in IRE procedures for HCC. This approach may offer a valuable tool for improving intraoperative decision-making and post-operative assessment.

IntroductionProlonged or recurrent cough is a common reason for referral to pediatric pulmonologists, yet few studies have assessed its causes. We examined records of children visiting respiratory outpatient clinics in Switzerland and assessed how diagnoses vary by age.MethodsWe analyzed data from the multicenter Swiss Paediatric Airway Cohort study. We included 363 children (median age 6 years, range 0-16) referred for prolonged or recurrent cough. From outpatient records, we extracted information on diagnostic investigations, final diagnoses proposed by pediatric pulmonologists, and treatments prescribed.ResultsAsthma and asthma-like conditions (cough variant asthma, episodic viral wheeze, and recurrent obstructive bronchitis) were diagnosed in 132 (36%) of 363 children, respiratory tract infections (RTI) including protracted bacterial bronchitis (PBB) in 51 (14%), upper airway cough syndrome (UACS) in 48 (13%), and postinfectious cough in 36 (10%); other diagnoses including gastroesophageal reflux disease (GERD) and somatic cough syndrome or tic cough were found in 23 (6%). No etiology was found in 73 children (20%). Asthma was diagnosed 3.5 times more often in schoolchildren while RTI including PBB was diagnosed three times more often in preschoolers. Inhaled corticosteroids were prescribed for 84% of children diagnosed with asthma and asthma-like conditions, antibiotics for 43% of children with RTI, and nasal corticosteroids for 83% of those with UACS.ConclusionCoughing children received a wide spectrum of diagnoses that differed between preschool and schoolchildren. Asthma accounted for 36% of diagnoses, which emphasizes the importance of comprehensive investigation beyond asthma in children with prolonged or recurrent cough.

BACKGROUND:Irreversible electroporation (IRE) in hepatocellular carcinoma (HCC) triggers apoptosis instead of thermal coagulation, resulting in specific modifications within ablation zones. Aim of this study is to evaluate the diagnostic value of MRI performed three days post-IRE (D3MRI). METHODS:This single-institution retrospective study examined patients with HCC treated by IRE from 2012-2017. Criteria included no prior HCC treatment, available D3MRI and one-month MRI (M1MRI) without residual tumor and at least one follow-up MRI after 3 months. We measured the peripheral hyperemia (IREPZ) and central necrotic zone (IRECZ) in the ablation area along with the minimum thickness of IREPZ (min.Th/IREPZ) on both D3MRI and M1MRI. The duration of follow-up and instances of local tumor progression (LTP) were recorded. RESULTS:Forty-eight patients (median age: 68 years) with 65 treated nodules (median diameter: 19 mm) were included. The median follow-up was 37 months. D3MRI median dimensions were 67 mm for IREPZ, 19 mm for IRECZ, and 5 mm for min.Th/IREPZ. LTP occurred in 25 nodules after 18 months. 52% had LTP at min.Th/IREPZ. A min.Th/IREPZ ≤ 5 mm on D3MRI indicated a 24-fold higher risk of LTP (95% CI [2.25-255.95], p < .01), conversely, the min.Th/IREPZ on M1MRI had no predictive value. CONCLUSION:D3MRI appears to be a valuable tool for assessing the true ablation margins in HCC nodules treated with IRE and for identifying potential sites of local recurrence. It may, therefore, be considered for integration into the follow-up protocol for patients undergoing IRE treatment for HCC.