Hepatocellular Carcinoma Nodules Research Articles

Trim21 deficiency in mice increases HCC carcinogenesis in a NASH context and is associated with immune checkpoint upregulation.

The global pandemic of metabolic diseases has increased the incidence of hepatocellular carcinoma (HCC) in the context of non-alcoholic steatohepatitis (NASH). The downregulation of the E3 ubiquitin ligase TRIM21 has been linked to poor prognosis in different cancers including HCC. In order to investigate the role of TRIM21 in liver cancer progression on NASH, Trim21+/+ and Trim21-/- male mice were injected with streptozotocin at the neonatal stage. The hypoinsulinemic mice were then fed with a high-fat high-cholesterol diet (HFHCD) for 4, 8 or 12 weeks. All mice developed NASH which systematically resulted in HCC progression. Interestingly, compared to the Trim21+/+ control mice, liver damage was worsened in Trim21-/- mice, with more HCC nodules found after 12 weeks on HFHCD. Immune population analysis in the spleen and liver revealed a higher proportion of CD4+PD-1+ and CD8+PD-1+ T cells in Trim21-/- mice. The liver and HCC tumors of Trim21-/- mice also exhibited an increase in the number of PD-L1+ and CD68+ PD-L1+ cells. Thus, TRIM21 limits the emergence of HCC nodules in mice with NASH by potentially restricting the expression of PD-1 in lymphocytes and PD-L1 in tumors.

Evaluation of the Time Difference Method in Identifying Hepatocellular Carcinoma in Current CEUS LR-M Category Nodules

ObjectiveTo explore a potential method for improving the diagnostic detection hepatocellular carcinoma (HCC) based on the contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) version 2017. MethodsWe retrospectively evaluated 585 liver nodules in 427 patients with HCC risk from December 2020 to March 2023. The nodules were categorized as LR-1 to LR-M based on CEUS LI-RADS version 2017 and were randomly subclassified into a developmental cohort (DC) and a validation cohort (VC) at 3:1. In the DC, the cutoff value of the time difference (∆T) for differentiating HCC from other malignancies in LR-M was calculated, which was used to reclassify nodules in the VC. The diagnostic effect on HCC detection before and after reclassification was further assessed. ResultsAccording to the current CEUS LI-RADS, 140 of 426 (32.9%) confirmed HCC nodules were misclassified as LR-M. In the DC (439 nodules), the receiver operating characteristic (ROC) curve showed that the cutoff value of ∆T (washout onset time minus contrast arrival time) recommended for HCC diagnosis was greater than 21 s. In the VC (146 nodules), 34 HCCs were correctly categorized as LR-5 according to the cutoff value and after reclassification LR-5 had higher accuracy (67.1% vs. 89.0%, p < 0.001) and sensitivity (56.0% vs. 87.2%, p < 0.001) for HCC diagnosis with high specificity (100% vs. 94.6%, p = 0.500) remained. ConclusionUsing the time difference method could identify HCC nodules misdiagnosed as LR-M and improve the diagnostic performance for current CEUS LI-RADS.

A case of secondary immune thrombocytopenia induced by atezolizumab plus bevacizumab therapy for hepatocellular carcinoma resulting in death from intracranial hemorrhage

An 84-year-old woman underwent laparoscopic partial hepatectomy for a single 3.0-cm-diameter nodule of hepatocellular carcinoma at segment 5. Although the postoperative condition was uneventful, multiple recurrences were observed six months after hepatic resection. Transcatheter arterial chemoembolization (TACE) was the second-line therapy. However, she was later diagnosed as TACE refractory due to residual tumor and presence of portal vein tumor thrombus. Third-line therapy was the combination of atezolizumab and bevacizumab, which was discontinued after 22 courses due to disease progression. Two months after the conclusion of chemotherapy, sudden onset of purpura was observed around her eyes and on her lower legs. Laboratory tests revealed severe thrombocytopenia, and she was diagnosed with secondary immune thrombocytopenic purpura. Steroids and immunoglobulin therapy were then administered. Although the immature platelet fraction increased after treatment, the platelet count did not. The patient died of intracranial hemorrhage 10 days after initiation of steroid and immunoglobulin therapy.

Overall Survival Prediction by Tumor Microenvironment Lymphocyte Distribution in Hepatocellular Carcinoma After Liver Transplantation

IntroductionOur previous research demonstrated that CD8+ cell density profiling using a hexagonal grid-based digital image analysis method provides predictors of patient outcomes after liver resection due to hepatocellular carcinoma (HCC). Continuing our study, we have further investigated the applicability of the methodology to patients receiving a liver transplant for HCC. MethodsThe retrospective study enrolled patients with HCC who underwent liver transplantation (LT) at the Vilnius University Hospital Santaros Clinics between 2007 and 2020. We determined the density profiles of CD8+ lymphocytes at the interface between HCC and stroma and the interface between the perineoplastic liver parenchyma and stroma. Both digital image analysis and the hexagonal grid-based immunogradient method were applied to CD8+ immunohistochemistry images. Survival statistics based on clinicopathological, peripheral blood analysis, and surgical data determined the prognostic value of these indicators. ResultsUnivariate clinicopathological predictors of worse OS after LT included: patient's age at the time of the transplantation, a higher number of HCC nodules, lower platelet count, longer activated thromboplastin time, lower serum albumin, higher serum total bilirubin, and lower serum creatinine levels. The two independent predictors of overall survival were mean CD8+ cell density at the epithelial edge of the explanted liver parenchyma-stroma interface and peripheral blood platelet count. ConclusionsOur model discloses that preoperative peripheral blood platelet count and mean CD8+ cell density at the epithelial edge of nonmalignant interface in the explanted liver parenchyma are independent predictors of OS for HCC after LT.

Intratumoral perfusion may affect microwave ablation area of hepatocellular carcinoma

Objectives We aimed to evaluate the effect of intratumoral perfusion on microwave ablation (MWA) area in hepatocellular carcinoma (HCC). Methods Patients who underwent curative MWA for HCC between October 2013 and May 2015 were enrolled. Three days before MWA, contrast-enhanced ultrasound (CEUS) was performed to illustrate the perfusion characteristics of the target lesion. Using the Sonoliver quantification software, time-intensity curves of dynamic CEUS were obtained, and quantitative parameters were extracted. Two microwave antennae were inserted into the center of the tumor and MWA was performed with a continuous power output of 50 W for 5 min. A second CEUS was performed to measure the size of the ablated region. Thereafter, an additional MWA procedure was performed until complete ablation with a 5–10-mm safety margin was achieved. Results A total of 38 patients who underwent curative MWA for 39 HCC nodules were enrolled. The mean age was 57 years (34–80 years), and the median maximum diameter of the HCC was 3.4 cm (interquartile range, 2–6.8 cm). Time-intensity curves were obtained and the area under the curve (AUC) was selected as a parameter for intratumoral perfusion. The AUC was inversely and linearly correlated with the size of the MWA area, including long- and short-axis diameters and ablation volume. A 1,000-dB·s change in the AUC produced an average change of 1.17 ± 0.44 mm, 0.725 ± 0.355 mm, and 2.4995 ± 0.6575 cm³ in the long- and short-axis diameters and ablation volume, respectively. Conclusions The intratumoral perfusion of HCC was inversely correlated with MWA area size.

Machine Learning-Based CEMRI Radiomics Integrating LI-RADS Features Achieves Optimal Evaluation of Hepatocellular Carcinoma Differentiation.

To develop and compare various machine learning (ML) classifiers that employ radiomics extracted from contrast-enhanced magnetic resonance imaging (CEMRI) for diagnosing pathological differentiation of hepatocellular carcinoma (HCC), and validate the performance of the best model. A total of 251 patients with HCCs (n = 262) were assigned to a training (n = 200) cohort and a validation (n = 62) cohort. A collectionof 5502 radiomics signatures were extracted from the CEMRI images for each HCC nodule. To reduce redundancy and dimensionality, Spearman rank correlation, minimum redundancy maximum relevance (mRMR), and the least absolute shrinkage and selection operator (LASSO) approach were employed. Eight ML classifiers were trained to obtain the best radiomics model. The performance of each model was evaluated based on the area under the receiver operating characteristic curve (AUC). The radiomics model was integrated with liver imaging reporting and data system (LI-RADS) features to design a combined model. The eXtreme Gradient Boosting (XGBoost)-based radiomics model outperformed other ML classifiers in evaluating pHCC, achieving an AUC of 1.00 and accuracy of 1.00 in the training cohort. The LI-RADS model demonstrated an AUC value of 0.77 and 0.82 in the training and validation cohorts. The combined model exhibited best performance in both the training and validation cohorts, with AUCs of 1.00 and 0.86 for evaluating HCC differentiation, respectively. CEMRI radiomics integrating LI-RADS features demonstrated excellent performance in evaluating HCC differentiation, suggesting an optimal clinical decision tool for individualized diagnosis of HCC differentiation.

Assessment of LI-RADS efficacy in classification of hepatocellular carcinoma and benign liver nodules using DCE-MRI features and machine learning

PurposeThe current study aimed to evaluate the efficiency of dynamic contrast-enhanced (DCE) MRI visual features in classifying benign liver nodules and hepatocellular carcinoma (HCC) using a machine learning model. Methods115 LI-RADS3, 137 LI-RADS4, and 140 LI-RADS5 nodules were included (392 nodules from 245 patients), which were evaluated by follow-up imaging for LR-3 and pathology results for LR-4 and LR-5 nodules. Data was collected retrospectively from 3 T and 1.5 T MRI scanners. All the lesions were categorized into 124 benign and 268 HCC lesions. Visual features included tumor size, arterial-phase hyper-enhancement (APHE), washout, lesion segment, mass/mass-like, and capsule presence. Gini-importance method extracted the most important features to prevent over-fitting. Final dataset was split into training(70%), validation(10%), and test dataset(20%). The SVM model was used to train the classifying algorithm. For model validation, 5-fold cross-validation was utilized, and the test data set was used to assess the final accuracy. The area under the curve and receiver operating characteristic curves were used to assess the performance of the classifier model. ResultsFor test dataset, the accuracy, sensitivity, and specificity values for classifying benign and HCC lesions were 82%,84%, and 81%, respectively. APHE, washout, tumor size, and mass/mass-like features significantly differentiated benign and HCC lesions with p-value < .001. ConclusionsThe developed classification model employing DCE-MRI features showed significant performance of visual features in classifying benign and HCC lesions. Our study also highlighted the significance of mass and mass-like features in addition to LI-RADS categorization. For future work, this study suggests developing a deep-learning algorithm for automatic lesion segmentation and feature assessment to reduce lesion categorization errors.

Can absolute arterial phase hyperenhancement improve sensitivity of detection of hepatocellular carcinoma in indeterminate nodules on CT?

To determine if quantitative assessment of relative (R) and absolute (A) arterial phase hyperenhancement (APHE) and washout (WO) applied to indeterminate nodules on CT would improve the overall sensitivity of detection of hepatocellular carcinoma (HCC). One-hundred and fourteen patients (90 male; mean age, 65years) with 210 treatment-naïve HCC nodules (190 HCCs, 20 benign) who underwent 4-phase CT were included in this retrospective study. Four radiologists independently assigned a qualitative LR (LI-RADS) category per nodule. LR-3/4 nodules were then quantitatively analyzed by the 4 readers, placing ROIs within nodules and adjacent liver parenchyma. A/R-APHE and WO were calculated, and per-reader sensitivity and specificity updated. Interobserver agreement and AUCs were calculated per reader. Qualitative readers 1-4 categorized 57, 69, 57, and 63 nodules as LR-3/4 respectively with moderate to substantial agreement in LR category (kappa 0.56-0.69, p < 0.0001); their diagnostic performances in the detection of HCC were 80%, 73.2%, 77.4%, and 77.4% sensitivity, and 100%, 95%, 70%, and 100% specificity, respectively. A threshold of ≥ 20 HU for A-APHE increased overall sensitivity of HCC detection by 0.5-3.1% without changing specificity for the subset of nodules APHE - /WO + on qualitative read, with 2, 6, 6, and 1 additional HCC detected by readers 1-4. Relative and various A-WO formulae and thresholds all increased sensitivity, but with a drop in specificity for some/all readers. Quantitatively assessed A-APHE showed potential to increase sensitivity and maintain specificity of HCC diagnosis when selectively applied to indeterminate nodules demonstrating WO without subjective APHE. Quantitatively assessed R and A-WO increased sensitivity, however reduced specificity. A workflow using selective quantification of absolute arterial enhancement is routinely employed in the CT assessment of renal and adrenal nodules. Quantitatively assessed absolute arterial enhancement is a simple tool which may be used as an adjunct to help increase sensitivity and maintain specificity of HCC diagnosis in indeterminate nodules demonstrating WO without subjective APHE. • In indeterminate nodules categorized as LI-RADS 3/4 due to absent subjective arterial phase hyperenhancement, a cut-off for absolute arterial phase hyperenhancement of ≥ 20 HU may increase the overall sensitivity of detection of HCC by 0.5-3.1% without affecting specificity. • Relative and various absolute washout formulae and cut-offs increased sensitivity of HCC detection, but with a drop in specificity for some/all readers.

Imaging Investigation of Hepatocellular Carcinoma Progress via Monitoring γ-Glutamyltranspeptidase Level with a Near-Infrared Fluorescence/Photoacoustic Bimodal Probe.

Hepatocellular carcinoma (HCC) is one of the main principal causes of cancer death, and the late definite diagnosis limits therapeutic approaches in time. The early diagnosis of HCC is essential, and the previous investigations on the biomarkers inferred that the γ-glutamyltranspeptidase (GGT) level could indicate the HCC process. Herein, a near-infrared fluorescence/photoacoustic (NIRF/PA) bimodal probe, CySO3-GGT, was developed for monitoring the GGT level and thus to image the HCC process. After the in-solution tests, the bimodal response was convinced. The various HCC processes were imaged by CySO3-GGT at the cellular level. Then, the CCl4-induced HCC (both induction and treatment) and the subcutaneous and orthotopic xenograft mice models were selected. All throughout the tests, CySO3-GGT achieved NIRF and PA bimodal imaging of the HCC process. In particular, CySO3-GGT could effectively realize 3D imaging of the HCC nodule by visualizing the boundary between the tumor and the normal tissue. The information here might offer significant guidance for the dynamic monitoring of HCC in the near future.

Single or multiple treatments with lusutrombopag in subjects with thrombocytopenia and chronic liver disease needing an invasive procedure

Thrombocytopenia is one of the most frequent implications of liver cirrhosis. This condition, when present in the severe form [platelet count (PLT) less than 50 × 109/L] correlates, with an increased risk of bleeding during the main diagnostic-therapeutic procedures which cirrhotic patients usually undergone. In these cases, generally, an infusion of platelets is performed, albeit in recent years has been replaced by a cycle of second generation thrombopoietin receptor (TpoR) agonists. This article reports two different cases concerning respectively an 83-year-old female patient suffering from arterial hypertension, aneurysm of the sub-renal aorta, hepatitis C virus (HCV)-positive liver cirrhosis responsive to treatment with antiviral drugs, and a 2.0 cm diameter hepatocellular carcinoma (HCC) nodule localized in the hepatic segment III and a 53-year-old female patient with HCV-positive liver cirrhosis complicated by portal hypertension with splenomegaly, thrombocytopenia, and F3 esophageal varices at high risk of bleeding. Both of them, eligible for invasive procedures such as HCC transarterial chemoembolization (TACE) and for esophageal variceal band ligation, were prescribed prophylaxis with TpoR agonists due to their severe and persistent thrombocytopenia. These two cases show how a short course of lusutrombopag allows to safely perform one or more invasive procedures and how the administration of the drug can be repeated without losing efficacy. Furthermore, this drug shows an excellent safety profile and avoids the risks of platelet transfusion. In conclusion, second generation TpoR agonists can be considered the prophylactic treatment of choice to reduce the risk of bleeding in patients with liver cirrhosis and severe thrombocytopenia.

Efficacy of the Combination of Systemic Sequential Therapy and Locoregional Therapy in the Long-Term Survival of Patients with BCLC Stage C Hepatocellular Carcinoma.

The aim of this study was to evaluate the clinical impact of a combination of systemic sequential therapy and locoregional therapy on the long-term survival of patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC). Sixty-four consecutive patients with intrahepatic target nodules who had initially received systemic therapy (lenvatinib and atezolizumab plus bevacizumab) were reviewed. The clinical impact of the combined use of systemic sequential therapy and locoregional therapy was evaluated by determining overall survival (OS). The combined use of systemic sequential therapy with more than two agents and locoregional treatment was defined as multidisciplinary combination therapy (MCT), while only systemic sequential therapy and repeated locoregional-treatment was defined as a single treatment procedure (STP). R0 resection, MCT, and STP resulted in significantly better OS compared with no additional treatment (median OS, not reached vs. 18.2 months and 12.6 vs. 8.1 months, respectively; p = 0.002). Multivariate analysis confirmed that the use of R0 resection and MCT were associated with better OS (hazard ratio [HR]; 0.053, p = 0.006 and 0.189, p < 0.001, respectively) compared with that for STP (HR; 0.279, p = 0.003). MCT is may effective in patients with BCLC stage C HCC and intrahepatic target nodules who have previously received systemic therapy-based treatment.

Imaging biomarkers on Angio-CT for predicting the efficacy of transarterial chemoembolization in hepatocellular carcinoma.

This study aimed to evaluate whether the lipiodol deposition pattern on intraprocedural Angio-CT could predict tumor treatment response in hepatocellular carcinoma (HCC) patients treated with conventional transarterial chemoembolization (c-TACE). This retrospective study enrolled intermediated and advanced HCC nodules treated with c-TACE and Angio-CT from June 2021 to June 2022. The therapeutic efficacy was evaluated according to the mRECIST standards. First, Angio-CT was used to determine lipiodol deposition at the end of c-TACE, redefined as complete, partial-complete, and incomplete groups. Second, the mean CT value of lipiodol deposition and its association with therapeutic efficacy were calculated in the complete model. Finally, the relationship between imaging biomarkers and efficacy was evaluated. A total of 45 patients with 72 HCC nodules were enrolled with 28 nodules in the complete group, 31 nodules in the partial-complete group, and 13 nodules in the incomplete group. The complete response (CR) proportion was significantly higher in patients with good lipiodol deposition compared with patients with poor lipiodol deposition (P<0.0001). There was no significantly different CR rate between CT value ≥800 and <800 HU (P=0.119) in the complete group. Meanwhile, the non-CR rate in cases with hepatic vein development was significantly higher than that in cases with no hepatic vein development in the arterial phase (P<0.0001). Complete lipiodol deposition on Angio-CT during c-TACE was a predictive factor for therapeutic response to TACE. For HCC nodules with well-deposited lipiodol, hepatic vein development on Angio-CT in the arterial phase was strongly associated with poor efficacy of TACE.

Risk of Treatment Failure and Death after Ablation in Hepatocellular Carcinoma Patients-A Multiparametric Prediction.

Ablation is a first-line treatment for Barcelona Clinic Liver Cancer (BCLC)-0/A hepatocellular carcinoma (HCC). However, there are scarce data about patients' outcomes after recurrence. The present study evaluates the impact of patient and tumor characteristics at baseline and at recurrence on the Clinical Decision-Making process. We evaluated BCLC-0/A patients treated with percutaneous ablation from January 2010 to November 2018. Clinical and radiological data such as age, tumor location at ablation, pattern of recurrence/progression, and comorbidities during follow-up were registered. Tumor location was divided into 'suboptimal' vs. 'optimal' locations for ablation. The Clinical Decision-Making was based on tumor burden, liver dysfunction, or comorbidities. The statistical analysis included the time-to-recurrence/progression, censoring at time of death, date of last follow-up or liver transplantation, and time-to-event was estimated by the Kaplan-Meier method and Cox regression models to evaluate the risk of an event of death and change of treatment strategy. A total of 225 patients [39.1% BCLC-0 and 60.9% BCLC-A] were included, 190 had unifocal HCC and 82.6% were ≤3 cm. The complete response rate and median overall survival were 96% and 60.7 months. The HCC nodules number (Hazard Ratio-HR 3.1), Child-Pugh (HR 2.4), and Albumin-Bilirubin score (HR 3.2) were associated with increased risk of death during follow-up. HCC in 'suboptimal location' presented a shorter time to recurrence. When comorbidities prevented further loco-regional or systemic treatment, the risk of death was significantly increased (HR 2.0, p = 0.0369) in comparison to those who received treatment. These results expose the impact of non-liver comorbidities when considering treatment for recurrence after ablation in the real-world setting and in research trials. Ultimately, we identified an orphan population for which effective interventions are needed.

PPM1H is down-regulated by ATF6 and dephosphorylates p-RPS6KB1 to inhibit progression of hepatocellular carcinoma

We have shown previously that polymorphism of activating transcription factor 6 (ATF6) is associated with susceptibility to hepatocellular carcinoma (HCC). Therefore, genes down-regulated by ATF6 might play a tumor-suppressing role. In the present study, we identified that expression of protein phosphatase magnesium- or manganous-dependent 1H (PPM1H) mRNA and protein can be inhibited by ATF6 in hepatoma cells and mice with liver Atf6 knockdown. Tumor tissues from 134 HCC patients were analyzed by immunohistochemistry, andPPM1H exhibited higher expression levels in adjacent para-cancer tissues than in HCC tissues. Therefore, patients with higher expression of PPM1H had a better prognosis. PPM1H inhibited proliferation, migration, and invasion of hepatoma cells. In addition, PPM1H inhibited induced HCC nodule formation as well as tumor xenograft growth in diethylnitrosamine/CCl4-induced HCC mouse model and nude mouse tumorigenicity assay, respectively. A 3D model of PPM1H was obtained by homology multi-template modeling, and ribosomal protein S6 kinase B1 (RPS6KB1) in the bone morphogenetic protein (BMP)/transforming growth factor β (TGF-β) pathway was screened out as the potential substrate of PPM1H by Rosetta. PPM1H could directly dephosphorylate p-RPS6KB1. To conclude, we discovered RPS6KB1 as a new PPM1H dephosphorylation substrate. PPM1H exhibited a suppressive effect on HCC progression by dephosphorylating p-RPS6KB1.

A gadoxetic-acid enhancement flux analysis of small liver nodules (≤2 cm) in patients at high risk of hepatocellular carcinoma

PurposeTo discriminate between benignities and hepatocellular carcinomas (HCCs) in patients at high risk of HCC using a novel enhancement flux analysis for gadoxetic-acid enhanced MRI. MethodThis study retrospectively collected 181 liver nodules in 156 patients at high risk of HCC who underwent gadoxetic acid-enhanced MRI examinations with following surgical resection from 1st August 2017 to 31st December 2021 as the training set; another 42 liver nodules in 36 patients were prospectively collected from 1st January 2022 to 1st October 2022 as the test set. The time-intensity curves (TICs) of liver nodules were formed with consecutive time points: 0 s, 20 s, 1 min, 2 min, 5 min, 10 min, 15 min, and 20 min since contrast injection. A novel enhancement flux analysis was applied by using a biexponential function fitting to distinguish benignities and HCC. Besides, previously published models including maximum enhancement ratio (ERmax), percentage signal ratio (PSR), and ERmax+PSR were compared. The areas under the receiver operating characteristic curves (AUCs) were compared among these methods. ResultsThe novel enhancement flux analysis showed the highest AUCs in the training set (0.897, 95%CI: 0.833–0.960) and the test set (0.859, 95%CI: 0.747–0.970) among all models. The AUCs of PSR, ERmax and ERmax+PSR were 0.801 (95%CI: 0.710–0.891), 0.620 (95%CI: 0.510–0.729), and 0.799 (95%CI: 0.709–0.889) in the training set, and were 0.701 (95%CI: 0.539–0.863), 0.529 (95%CI: 0.342–0.717), and 0.708 (95%CI: 0.549–0.867) in the test set. ConclusionsThe biexponential flux analysis for gadoxetic-acid enhanced MRI presents a better potential in accurate diagnosis of small HCC nodules.

Gastric Perforation After Microwave Ablation to Adjacent Hepatocellular Lesion

ABSTRACT Locoregional treatment modalities for hepatocellular carcinoma are generally effective and safe and benefit the subset of patients who are not eligible for surgery or have marginal hepatic function. This case report discusses a 77-year-old patient with cirrhosis who underwent microwave lesion ablation for 3 hepatocellular carcinoma nodules. On the 12th day after ablation, the patient was diagnosed with a perforation of the anterior wall of the stomach near one of the target ablation sites on the left side of the liver. The patient underwent surgical therapy with clinical improvement. This report highlights the potential risks associated with microwave ablation for hepatocellular carcinoma.

Gadoxetic Acid-Enhanced Liver MRI: Everything You Need to Know.

Since its introduction in the worldwide medical market, gadoxetic acid has attracted considerable interest. The year 2023 marks the 15th anniversary of the introduction of gadoxetic acid in Japan. Gadoxetic acid-enhanced magnetic resonance imaging (GA-MRI) is the predominantly performed contrast MRI examination for the liver. Its most essential characteristic, namely, the hepatobiliary phase, revolutionized the clinical management of liver disease. Gadoxetic acid-enhanced MRI is currently the most efficient method for focal liver lesion detection and analysis. Meta-analyses demonstrated its excellent effectiveness for the diagnosis of hepatocellular carcinoma and liver metastases. Owing to the extensive usage of gadoxetic acid, a hepatobiliary phase hypointense nodule without arterial phase hyperenhancement is well documented. The existence of such nodules may be a sign of hypervascular hepatocellular carcinoma in nodules and other areas in the liver. Apart from its role in tumor identification and characterization, GA-MRI can help assess response to therapy and liver fibrosis. Therefore, it is proposed to use gadoxetic acid as the first option for MRI of the liver in the majority of patients. The efficacy of gadoxetic acid surpasses its disadvantages, rendering this contrast agent the preferred choice for routine MRI of the liver. The clinical use of GA-MRI is discussed in this review article.

P53 expression is associated with tumor stage, grade and subtype in patients with hepatocellular carcinoma.

The present study aimed to determine the expression levels of p53 in patients with hepatocellular carcinoma (HCC) and to evaluate its association with several HCC-related prognostic factors and in particular, with tumor stage, grade and subtype. Therefore, a cross-sectional study, involving 41 patients with HCC, who underwent surgical resection between January, 2013 and December, 2020 was conducted. To assess the expression levels of p53 in all patients with HCC, immunohistochemical staining was performed. In addition, the association between p53 expression and the clinicopathological characteristics of patients with HCC, including prognostic factors, was evaluated by applying the appropriate statistical analysis methods. The results revealed that among the 41 patients enrolled, 35 patients (85.4%) were positive for p53 expression. A higher percentage of positive p53 expression was observed in male patients >60 years old, with single HCC nodules >5 cm in diameter and vascular invasion, compared with their counterparts. A positive p53 expression was associated with well- and poorly differentiated HCC, but not with tumor stage and subtype. No differences in p53 expression were observed across different tumor stages and subtypes. Additionally, patients with moderately and poorly differentiated HCC exhibited significantly higher p53 expression levels compared with those suffering from well-differentiated HCC. Overall, the results demonstrated that the rate of p53 immuno-positive cells was increased in patients with HCC. In addition, p53 expression was associated with well- and poorly differentiated HCC, thus suggesting its association with a poorer prognosis.

Liver resection versus transarterial chemoembolisation for the treatment of intermediate hepatocellular carcinoma: a systematic review and meta-analysis.

Transarterial chemoembolisation (TACE) is the primary treatment for intermediate-stage hepatocellular carcinoma (HCC), according to the updated Barcelona Clinic Liver Cancer (BCLC) staging system. Although growing evidence favours liver resection (LR) over TACE for intermediate-stage HCC, the best treatment option remains controversial. This meta-analysis aimed to compare the overall survival (OS) after LR versus TACE for intermediate-stage HCC. A comprehensive literature review of PubMed, Embase, Cochrane Library, and Web of Science was performed. Studies that compared the efficacy of LR and TACE in patients with intermediate (BCLC stage B) HCC were selected. According to the recent updated BCLC classification, intermediate stage of HCC was defined as follows: (a) four or more HCC nodules of any size, or (b) two or three nodules, but if at least one tumour is larger than 3cm. The main outcome was OS, expressed as the hazard ratio. Nine eligible studies of 3355 patients were included in the review. The OS of patients who underwent LR was significantly longer than that of patients who underwent TACE (hazard ratio=0.52; 95% CI: 0.39-0.69; I2=79%). Prolonged survival following LR was confirmed after sensitivity analysis of five studies using propensity score matching (HR=0.45; 95% CI: 0.34-0.59; I2=55%). Patients with intermediate-stage HCC who underwent LR had a longer OS that those who underwent TACE. The role of LR in patients with BCLC stage B should be clarified in future randomised controlled trials.

Contrast-enhanced ultrasound liver imaging reporting and data system v2017: patient outcomes after treatment for early-stage hepatocellular carcinoma nodules with category 3-5 and category M.

To evaluate correlation between contrast-enhanced ultrasonography Liver Imaging Reporting and Data System (CEUS LI-RADS; v. 2017) categories (LR 3-5 vs LR-M) and outcomes in patients with early-stage hepatocellular carcinoma (HCC) after initial therapy. In this retrospective study, 272 patients with high risks for HCC and solitary clinically or pathologically confirmed HCC were identified between January 2010 and December 2015. Patients were initially treated by resection and radiofrequency ablation (RFA) according to the Barcelona Clinic Liver Cancer staging system and were followed up until December 31, 2018. Recurrence-free survival (RFS) and overall survival (OS) were compared between nodules assigned as LR 3-5 or LR M according to CEUS LI-RADS v. 2017 by using the Kaplan-Meier curve, log-rank test, and Cox proportional hazard model. Early washout is the key determinating whether a nodule is classed as LR-M. Treatment procedures and LI-RADS category showed an independent correlation with OS and RFS (p < 0.05). LR 3-5 category were more correlated with better OS (88.6 months and 74.2 months, respectively; p = 0.017) compared with LR-M. Surgical resection demonstrated longer OS and RFS than RFA in LR-M patients and longer OS in LR 3-5 patients (p < 0.05). Besides, there was no significantly difference in OS and RFS between two categories in resection (p > 0.05), while for patients treated with RFA, LR 3-5 patients showed significant longer OS and RFS than LR-M patients (p < 0.05). Patients with HCC assigned as LR-M showed worse RFS and OS and surgical resection tended to be a more effective treatment for these patients. Putting forward a theory that CEUS LI-RADS categories could independently predict the outcome for patients with solitary HCC at early-stage after initial treatment.