To explore factors associated with overall survival (OS) and progression-free survival (PFS) of intrahepatic cholangiocarcinoma (iCCA) after ultrasound-guided ablation and establish a model for survival risk evaluation. Data from 54 patients with 86 iCCAs between August 2008 and October 2022 were retrospectively analyzed. Cox regression were used to analyze the effects of clinical features on OS and PFS. Based on the variables screened by multivariable analysis, a model was established to predict the survival of the patients. Time-dependent receiver operating characteristic (timeROC) curve was constructed to evaluate the performance of this model. The model was further verified by bootstrap validation. The clinical usefulness of the model was evaluated by the decision curve analysis (DCA). During follow up, 39 patients died and 49 patients developed recurrence. Pre-ablation CA199 level > 140 U/ml was the only independent predictor of poor PFS. Age > 70 years, early recurrence, maximal diameter of tumor size > 1.5 cm and pre-ablation CA199 level > 140 U/ml were significantly associated with poor OS. Then a model was established based on the above four variables. The areas under the timeROC curve (AUC) for 1-year, 2-year, 3-year, 5-year were 0.767, 0.854, 0.791 and 0.848, respectively. After bootstrapping for 1000 repetitions, the AUCs were similar to the initial model. DCA also demonstrated that the model had good positive net benefits. The established model in this study could predict the survival outcomes of the patients with iCCA after thermal ablation, but further research was needed to validate the results.

Purpose To investigate the value of three-dimensional ultrasound fusion imaging (3DUS FI) technique for guiding needle placement in hepatocellular carcinoma (HCC) thermal ablation. Methods A total of 57 patients with 60 HCCs with 3DUS FI-guided thermal ablation were retrospectively included in the study. 3DUS volume data of liver were acquired preoperatively by freehand scanning with the tumor and predetermined 5 mm ablative margin automatically segmented. Plan of needle placement was made through a predetermined simulated ablation zone to ensure a 5 mm ablative margin with the coverage rate toward tumor and ablative margin. With real-time ultrasound and 3DUS fusion imaging, ablation needles were placed according to the plan. After ablation, the ablative margin was immediately evaluated by contrast-enhanced ultrasound and 3DUS fusion imaging. The rate of adequate ablative margin, complete response (CR), local tumor progression (LTP), disease-free survival (DFS), and overall survival (OS) was evaluated. Results According to postoperative contrast-enhanced CT or MR imaging, the complete response rate was 100% (60/60), and 83% of tumors (30/36) achieved adequate ablative margin (>5 mm) three-dimensionally. During the follow-up period of 6.0-42.6 months, LTP occurred in 5 lesions, with 1- and 2-year LTP rates being 7.0% and 9.4%. The 1- and 2-year DFS rates were 76.1% and 65.6%, and 1- and 2-year OS rates were 98.1% and 94.0%. No major complications or ablation-related deaths were observed in any patients. Conclusions Three-dimensional ultrasound fusion imaging technique may improve the needle placement of thermal ablation for HCC and reduce the rate of LTP.

The purpose of this study is to establish microvascular invasion (MVI) prediction models based on preoperative contrast-enhanced ultrasound (CEUS) and ethoxybenzyl-enhanced magnetic resonance imaging (EOB-MRI) in patients with a single hepatocellular carcinoma (HCC) ≤ 5 cm. Patients with a single HCC ≤ 5 cm and accepting CEUS and EOB-MRI before surgery were enrolled in this study. Totally, 85 patients were randomly divided into the training and validation cohorts in a ratio of 7:3. Non-radiomics imaging features, the CEUS and EOB-MRI radiomics scores were extracted from the arterial phase, portal phase and delayed phase images of CEUS and the hepatobiliary phase images of EOB-MRI. Different MVI predicting models based on CEUS and EOB-MRI were constructed and their predictive values were evaluated. Since univariate analysis revealed that arterial peritumoral enhancement on the CEUS image, CEUS radiomics score, and EOB-MRI radiomics score were significantly associated with MVI, three prediction models, namely the CEUS model, the EOB-MRI model, and the CEUS-EOB model, were developed. In the validation cohort, the areas under the receiver operating characteristic curve of the CEUS model, the EOB-MRI model, and the CEUS-EOB model were 0.73, 0.79, and 0.86, respectively. Radiomics scores based on CEUS and EOB-MRI, combined with arterial peritumoral enhancement on CEUS, show a satisfying performance of MVI predicting. There was no significant difference in the efficacy of MVI risk evaluation between radiomics models based on CEUS and EOB-MRI in patients with a single HCC ≤ 5 cm. Radiomics models based on CEUS and EOB-MRI are effective for MVI predicting and conducive to pretreatment decision-making in patients with a single HCC within 5 cm. • Radiomics scores based on CEUS and EOB-MRI, combined with arterial peritumoral enhancement on CEUS, show a satisfying performance of MVI predicting. • There was no significant difference in the efficacy of MVI risk evaluation between radiomics models based on CEUS and EOB-MRI in patients with a single HCC ≤ 5 cm.

Objective: The aim of the work described here was to explore the value of contrast -enhanced ultrasound (CEUS) quantitative parameters in predicting the response of combined immune checkpoint inhibitor (ICI) and antiangiogenesis therapies for unresectable hepatocellular carcinoma (HCC). Methods: Sixty-six HCC patients who underwent combined ICI and anti-angiogenesis therapies were prospectively enrolled. A CEUS examination was performed at baseline, and tumor perfusion parameters were obtained with perfusion quantification software. The differences in CEUS quantitative parameters between the responder and non -responder groups were compared, and the correlations between CEUS parameters and progression -free survival (PFS) was evaluated. Results: The objective response rate (ORR) was 21.2%. The values of rising time (RT) ratio, time to peak ratio, fall time ratio, peak enhancement ratio, wash -in rate ratio, wash -in perfusion index ratio and wash -out rate ratio differed significantly differed between the responder and non -responder groups (all p values < 0.05). Multivariable logistic regression analysis revealed that the RT ratio was the only independent factor associated with the ORR (odds ratio = 0.007, 95% confidence interval: 0.000-0.307, p = 0.010). The median RT ratios of the responder and non -responder groups were 36.9 and 58.9, respectively (p = 0.006). The appropriate cutoff point of the RT ratio was 80.1, determined with the X -tile program. Survival analysis indicated high PFS for the patients with a lower RT ratio (high RT ratio vs. low RT ratio = 4.4 mo vs. not reached, p = 0.001). Conclusion: CEUS quantitative parameters may predict the efficacy of ICI and anti-angiogenesis combined therapies for HCC.

Background: Immune checkpoint inhibitors (ICIs) have been increasingly used to treat hepatocellular carcinoma (HCC). Prognostic biomarkers are an unmet need. We aimed to develop a prognostic nomogram for patients with unresectable HCC receiving ICIs therapy. Methods: A total of 120 patients with unresectable HCC receiving ICIs treatment were enrolled in this study. Patients were randomly divided into a training set (n = 84) and a validation set (n = 36) in a 7:3 ratio. Clinical characteristics were retrospectively analyzed. Serum α-fetoprotein protein (AFP) response was defined as a decline of ≥20% in AFP levels within the initial eight weeks of treatment. Univariable and multivariable Cox analyses were used to select relevant variables and construct the nomogram. The areas under the receiver operating characteristic curves (AUCs) were used to determine the performance of the model. Kaplan–Meier analysis with the log-rank test was used to compare different risk groups. Results: The median progression-free survival (PFS) was 7.7 months. In the multivariate Cox analysis, the presence of extrahepatic metastasis (hazard ratio [HR] = 2.08, 95% confidence interval [CI]: 1.02–4.27, p < 0.05), white blood cell count (HR = 3.48, 95% CI: 1.02–11.88, p < 0.05) and AFP response (HR = 0.41, 95% CI: 0.18–0.95, p < 0.05) independently predicted PFS. A nomogram for PFS was established with AUCs of 0.79 and 0.70 in the training and validation sets, respectively. The median PFS of the high- and low-risk subgroups was 3.5 and 11.7 months, respectively (p < 0.05). Conclusion: The nomogram could predict PFS in patients with unresectable HCC receiving ICIs treatment and further help decision making in daily clinical practice.

BACKGROUND:Registration of three-dimensional contrast-enhanced ultrasound fusion imaging (3DCEUS-FI) is time-consuming to obtain high success rate.OBJECTIVE:To investigate the influence factors on registration success rate of 3DCEUS-FI.METHODS:Water tank phantoms were made to obtain mimicked pre- and post- radiofrequency ablation three-dimensional contrast-enhanced ultrasound (3DCEUS) and CT images. Orthogonal trials were designed according to factors including size, depth, enhancement level of mimicked tumor, diameter and number of mimicked adjacent vessels. Mimicked pre- and post-RFA 3DCEUS images of 72 trials were fused to assess ablative margin (AM) by two radiologists. With CT images as standard, 3DCEUS-FI accuracy was considered as the consistency of AM evaluation. The inter-observer agreement and the influence factors on registration success rates were analyzed.RESULTS:The intraclass correlation coefficient (ICC) for the consistency of AM evaluation between CT and 3DCEUS-FI in x-axis, y-axis or z-axis was 0.840∼0.948 (P < 0.001). The ICC for inter-observer agreement was 0.840∼0.948 (P < 0.001). The success rates of registration within mimicked vessels with diameter of 2 mm were significantly lower than those with diameter of 3 mm and 4 mm.CONCLUSIONS:The mimicked AM measured by 3DCEUS-FI had high accuracy and inter-observer agreement. Diameter of the mimicked adjacent vessels was significantly related to success rate of registration.

Background To explore the pathologic basis and prognostic value of tumor and liver stiffness measured pre-operatively by two-dimensional shear wave elastography (2D-SWE) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients who undergo hepatic resection. Methods A total of 191 HBV-infected patients with solitary resectable HCC were prospectively enrolled. The stiffness of intratumoral tissue, peritumoral tissue, adjacent liver tissue, and distant liver tissue was evaluated by 2D-SWE. The correlations between stiffness and pathological characteristics were analyzed in 114 patients. The predictive value of stiffness for recurrence-free survival (RFS) was evaluated, and Cutoff Finder was used for determining optimal cut-off stiffness values. Cox proportional hazards analysis was used to identify independent predictors of RFS. Results Pathologically, intratumoral stiffness was associated with stroma proportion and microvascular invasion (MVI) while peritumoral stiffness was associated with tumor size, capsule, and MVI. Adjacent liver stiffness was correlated with capsule and liver fibrosis stage while distant liver stiffness was correlated with liver fibrosis stage. Peritumoral stiffness, adjacent liver stiffness, and distant liver stiffness were all correlated to RFS (all p < 0.05). Higher peritumoral stiffness (> 49.4 kPa) (HR = 1.822, p = 0.023) and higher adjacent liver stiffness (> 24.1 kPa) (HR = 1.792, p = 0.048) were significant independent predictors of worse RFS, along with tumor size and MVI. The nomogram based on these variables showed a C-index of 0.77 for RFS prediction. Conclusions Stiffness measured by 2D-SWE could be a tumor microenvironment and tumor invasiveness biomarker. Peritumoral stiffness and adjacent liver stiffness showed important values in predicting tumor recurrence after curative resection in HBV-related HCC. Clinical relevance statement Tumor and liver stiffness measured by two-dimensional shear wave elastography serve as imaging biomarkers for predicting hepatocellular carcinoma recurrence, reflecting biological behavior and tumor microenvironment. Key points • Stiffness measured by two-dimensional shear wave elastography is a useful biomarker of tumor microenvironment and invasiveness. • Higher stiffness indicated more aggressive behavior of hepatocellular carcinoma. • The study showed the prognostic value of peritumoral stiffness and adjacent liver stiffness for recurrence-free survival. • The nomogram integrating peritumoral stiffness, adjacent liver stiffness, tumor size, and microvascular invasion showed a C-index of 0.77. Graphical Abstract

To explore the pathologic basis, the influencing factors and potential prognostic value of the stiff rim sign in two-dimensional shear wave elastography (2D-SWE) of hepatocellular carcinoma (HCC). HCC patients who underwent tumor 2D-SWE examination before resection were prospectively enrolled. The stiff rim sign was defined as increased stiffness in the peritumoral region. Interobserver and intraobserver variability of the stiff rim sign was assessed. The correlation between the stiff rim sign and pathological characteristics was analyzed. Multivariate analysis was performed to examine clinical and radiological factors influencing the appearance of stiff rim sign. The Kaplan–Meier method was used to analyze the relationship between recurrence-free survival (RFS) and the stiff rim sign. The stiff rim sign on 2D-SWE was present in 44.7

To assess the methodological quality and to evaluate the predictive performance of radiomics studies for preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Publications between 2017 and 2021 on radiomic MVI prediction in HCC based on CT, MR, ultrasound, and PET/CT were included. The risk of bias was assessed using the prediction model risk of bias assessment tool (PROBAST). Methodological quality was assessed through the radiomics quality score (RQS). Fourteen studies classified as TRIPOD Type 2a or above were used for meta-analysis using random-effects model. Further analyses were performed to investigate the technical factors influencing the predictive performance of radiomics models. Twenty-three studies including 4947 patients were included. The risk of bias was mainly related to analysis domain. The RQS reached an average of (37.7 ± 11.4)% with main methodological insufficiencies of scientific study design, external validation, and open science. The pooled areas under the receiver operating curve (AUC) were 0.85 (95% CI 0.82–0.89), 0.87 (95% CI 0.83–0.92), and 0.74 (95% CI 0.67–0.80), respectively, for CT, MR, and ultrasound radiomics models. The pooled AUC of ultrasound radiomics model was significantly lower than that of CT (p = 0.002) and MR (p < 0.001). Portal venous phase for CT and hepatobiliary phase for MR were superior to other imaging sequences for radiomic MVI prediction. Segmentation of both tumor and peritumor regions showed better performance than tumor region. Radiomics models show promising prediction performance for predicting MVI in HCC. However, improvements in standardization of methodology are required for feasibility confirmation and clinical translation.