Hepatocellular Carcinoma Lesions Research Articles

Potential for contrast-enhanced intraoperative ultrasonography with the Kupffer phase to improve and guide therapeutic strategies for hepatocellular carcinoma.

Not all malignant tumors, especially in hepatocellular carcinoma (HCC) patients with cirrhosis, can be detected by preoperative imaging methods. Therefore, it is urgently necessary to improve the intraoperative detectability of HCCs. Contrast-enhanced intraoperative ultrasonography (CE-IOUS) is an effective technique for detecting and characterizing occulting HCC lesions. We aimed to evaluate the performance of CE-IOUS with the Kupffer phase in the detection and diagnosis of HCC tumors. From November 2019 to July 2022, we retrospectively enrolled 25 consecutive patients in the Department of General Surgery of Beijing Hospital who had HCC and were scheduled to undergo hepatic surgery. Preoperative magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) were performed pre-operatively. During laparoscopic or open surgery, intraoperative ultrasound (IOUS) and CE-IOUS with Sonazoid were scheduled, and the Kupffer phase was used to detect lesions. Each pathological diagnosis of neoplasm was compared with image information. Among the total of 25 patients included in this study, there were 72 lesions including 57 HCCs and 15 others. The receiver operating characteristic (ROC) analysis of the four imaging methods was statistically significant. Based on the pairwise comparison of ROC curves, CE-IOUS showed the highest (96.5%) sensitivity, which did not differ significantly from MRI and CEUS (CE-IOUS vs. MRI P=0.946, CE-IOU vs. CEUS P=0.649, all P>0.05). The four imaging methods showed significantly different sensitivities in detecting HCC lesions (Cochran's Q 27.826, P<0.05). CE-IOUS may be superior to other imaging methods in detecting potentially additional HCC lesions to be removed at the time of surgery. Thus, it can be used as an essential tool for patients with HCC to guide and modify surgical strategies.

Molecular MR Imaging of T-Cell Immune Response to Cryoablation in Immunologically Hot vs. Cold Hepatocellular Carcinoma.

Background and aimsThe increasing enthusiasm for integrating locoregional therapy in primary liver cancer with systemic immunotherapy underscores the need for non-invasive imaging biomarkers. This study aims to establish advanced molecular magnetic resonance imaging (MRI) tools for monitoring T-cell responses to cryoablation in murine models, distinguishing between immunologically "hot" and "cold" hepatocellular carcinoma (HCC). Materials and methodsImmunocompetent 7-10-weeks-old C57BL/6J and BALB/cJ mice (n = 18 each) received carbon tetrachloride for 12 weeks to induce liver cirrhosis. Intrinsically immunogenic Hepa1-6 (“hot”) and non-immunogenic TiB75 (“cold”) cells were orthotopically implanted in C57BL/6 or BALB/c mice, respectively, to generate focal HCC lesions. After one week, animals were randomly assigned to (A) partial cryoablation (pCryo) (1.2 mm cryoprobe, -40°C) or (B) no treatment groups (n=8 per group and tumor type). Gadolinium 160 (160Gd)-labeled CD8+ antibody was administered intravenously either one week after tumor induction (control) or one-week post (pCryo) (treatment). T1-weighted MRI scans were performed using a 9.4 Tesla MRI scanner. Radiological-pathological correlation included imaging mass cytometry (IMC) and immunohistochemistry. ResultsPCryo-treated Hepa1-6 tumors displayed peritumoral ring enhancement on T1-weighted MRI with 160Gd-CD8, correlating with IMC signal patterns. Untreated Hepa1-6 tumors lacked such enhancement. Radiological-pathological correlation confirmed significantly increased tumor-infiltrating CD8+ T-lymphocytes in pCryo Hepa1-6 tumors compared with untreated tumors (p < 0.001), and a stronger local response compared with systemic lymph nodes (p=0.0415). Increased T-lymphocyte infiltration was not observed in TiB75 tumors, as indicated by MRI and histopathology. ConclusionPCryo induced increased T-cell infiltration in Hepa1-6 tumors compared to TiB75 tumors. T1-weighted MRI, following 160Gd-CD8 antibody administration, reproducibly detected the ablation-induced changes. These findings encourage further investigation of MR-based molecular imaging biomarkers to assess immune responses in local tumor therapies. Impact and implicationsThis study successfully established reliable MR-based molecular imaging tools to visualize CD8+ anti-tumor specific T-cell infiltration following partial cryoablation (pCryo) in murine tumor models. The study's significance lies in advancing our understanding of immune responses within induced cirrhosis and distinguishing between "hot" and "cold" tumor phenotypes. The findings not only build upon previous proof-of-principle data but also extend this technology to include different immune cell types in hepatocellular carcinoma (HCC). The study reveals that pCryo may exert specific effects on the tumor microenvironment, augmenting the anti-tumor immune response in immunogenic tumors while displaying a weaker local effect in non-immunogenic tumors.

Prostate-Specific Membrane Antigen (PSMA) PET/CT in the Detection and Diagnosis of Hepatocellular Carcinoma (HCC): A Systematic Review and Meta-Analysis.

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is widely used in prostate cancer. Recent studies indicate hepatocellular carcinoma (HCC) demonstrates PSMA PET uptake. The diagnostic accuracy of PSMA PET for HCC is not known. We conducted a systematic review and meta-analysis of studies assessing 68Ga-PSMA-11 in HCC. Nine studies were included, with 196 patients and a total of 491 HCC lesions. Per-patient analysis yielded a pooled sensitivity of 89.8% (95% CI 78.5-95.5). Specificity was poorly reported, with insufficient data. When per-lesion level analysis was performed on seven studies, the pooled sensitivity was 94.5% (95% CI 82.9-98.4), and specificity was again poorly reported with insufficient data. Among the three studies with adequate data for full per-lesion meta-analysis, 115 lesions in 41 patients demonstrated sensitivity of 97.1% (95% CI 87.8-99.4), while specificity was 42.2% (95% CI 0.3-99.4). Two studies provided sufficient data for meta-analysis on a per-patient level (n = 50 patients), demonstrating a sensitivity of 92.5% (95% CI 64.0-98.9) and specificity of 72.4% (95% CI 1.3-99.8). PSMA PET demonstrates a high sensitivity for HCC and shows promise as an imaging modality for diagnosis and staging of HCC. However, the existing literature does not provide enough data to confidently evaluate its specificity and, therefore, accuracy. Further prospective studies are necessary, with a focus on the accurate reporting of benign lesions and inclusion of patients with an intermediate probability of HCC.

Enhancing deep-seated hepatocellular carcinoma detection: assessing the added value of high mechanical index setting in sonazoid-based contrast-enhanced ultrasound during post-vascular phase.

This retrospective study aimed to investigate the role of an additional high mechanical index (MI) setting scan during the post-vascular phase (PVP) in detecting deep-seated hepatocellular carcinoma (HCC) lesions. A total of 805 confirmed HCCs, which underwent Sonazoid-based contrast-enhanced ultrasound (CEUS) between January 2014 and October 2021, were included. Low MI scan was initially employed for lesion detection during the PVP, followed by high MI scan. Propensity score matching (PSM) was utilized to address confounding variables. Of the 805 study lesions, 668 were detected as perfusion defects at the initial low MI setting, while 137 remained undetected. Among these 137 undetected lesions, 77 were identified at the subsequent high MI setting, whereas 60 remained undetected. Lesions that were larger (18.69±11.27mm vs. 16.55±7.42mm, p = 0.006), more superficial (6.06±2.41cm vs. 7.40±2.74cm, p < 0.001), and hypoechoic (482/668 vs. 62/137, p < 0.001) were detectable at the initial low MI setting. Male patients benefited more from the additional high MI scan (63/97 vs. 14/40, p < 0.001). Lesions identified with additional high MI were larger (18.30±8.76mm vs. 14.30±4.34mm, p < 0.001) and deeper than undetected ones (8.48±2.48cm vs. 6.02±2.43cm, p < 0.001). After PSM, depth was shown to be an independent predictor in multivariate analysis (odds ratio: 1.557, 95% confidence interval: 1.249-1.941). The depth cutoff was 7.75 cm, with a sensitivity of 0.681, specificity of 0.851, and area under the curve of 0.774. The additional high MI setting scan during the PVP of Sonazoid-based CEUS leads to enhanced detection of deep-seated HCCs.

Single cell-spatial transcriptomics and bulk multi-omics analysis of heterogeneity and ecosystems in hepatocellular carcinoma

This study profiled global single cell-spatial-bulk transcriptome landscapes of hepatocellular carcinoma (HCC) ecosystem from six HCC cases and a non-carcinoma liver control donor. We discovered that intratumoral heterogeneity mainly derived from HCC cells diversity and pervaded the genome-transcriptome-proteome-metabolome network. HCC cells are the core driving force of taming tumor-associated macrophages (TAMs) with pro-tumorigenic phenotypes for favor its dominant growth. Remarkably, M1-types TAMs had been characterized by disturbance of metabolism, poor antigen-presentation and immune-killing abilities. Besides, we found simultaneous cirrhotic and HCC lesions in an individual patient shared common origin and displayed parallel clone evolution via driving disparate immune reprograms for better environmental adaptation. Moreover, endothelial cells exhibited phenotypically conserved but executed differential functions in a space-dependent manner. Further, the spatiotemporal traits of rapid recurrence niche genes were identified and validated by immunohistochemistry. Our data unravels the great significance of HCC cells in shaping vibrant tumor ecosystems corresponding to clinical scenarios.

Mac-2 binding protein glycosylation isomer as a potential biomarker of hepatocellular carcinoma in HCV-cured patients

ObjectiveMac-2 binding protein glycosylation isomer (M2BPGi) is produced in the extracellular matrix and serves as an indicator of hepatic stellate cell activation. Assessing M2BPGi levels could aid in predicting hepatocellular carcinoma (HCC) in individuals with hepatitis C virus (HCV). The objective of this study was to evaluate the usefulness of M2BPGi as a biomarker for HCC in HCV patients and its association with disease severity and progression.MethodsThis study included patients who were cured of chronic hepatitis C virus. The patients were divided into three subgroups: HCV without cirrhosis, HCV with cirrhosis, and HCV with HCC. These subgroups were then compared to a subgroup of healthy volunteers. In addition to routine laboratory investigations, M2BPGi levels were measured in all the enrolled subjects.ResultsThe level of serum M2BPGi was significantly greater in the HCV with cirrhosis and HCC groups than in the control group (P < 0.001). Additionally, it was significantly greater in multifocal HCC than in those with unifocal HCC (P < 0.001), and it was directly proportional to the size of the focal lesion of HCC (P = 0.001). The cutoff for serum M2BPGi in diagnosing HCC was ≥ 0.869 (C.O.I), with an AUC of 0.762, a sensitivity of 78.6%, and a specificity of 61.9% (P = 0.004). Furthermore, the cutoff for predicting multifocality was > 0.93 (C.O.I), with an AUC of 0.73, sensitivity of 66.7%, and specificity of 63.8% (P = 0.03). Although the AFP level was still superior in predicting cirrhosis and HCC, the M2BPGi level was better at predicting the size and diagnostic value of HCC when the AFP level was normal. The cutoff for M2BPGi in this case was 0.903(C.O.I), with a sensitivity of 80%, specificity of 75%, and an accuracy of 76.25%. M2BPGi was independently associated with the CRP level (β = 0.484, P = 0.001) and the size of the HCC focal lesion (β = 1.422, P = 0.001).ConclusionM2BPGi can be used as an effective marker to assess the biological behavior and aggressiveness of HCC. Further studies are warranted on a large scale of patients to confirm our findings.

Improving Image Quality and Visualization of Hepatocellular Carcinoma in Arterial Phase Imaging Using Contrast Enhancement-Boost Technique.

This study aimed to evaluate the image quality and visualization of hepatocellular carcinoma (HCC) on arterial phase computed tomography (CT) using the contrast enhancement (CE)-boost technique. This retrospective study included 527 consecutive patients who underwent dynamic liver CT between June 2021 and February 2022. Quantitative and qualitative image analyses were performed on 486 patients after excluding 41 patients. HCC conspicuity was evaluated in 40 of the 486 patients with at least one HCC in the liver. Iodinated images obtained by subtracting nonenhanced images from arterial phase images were combined to generate CE-boost images. For quantitative image analysis, image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured for the liver, pancreas, muscles, and aorta. For qualitative analysis, the overall image quality and noise were graded using a 3-point scale. Artifact, sharpness, and HCC lesion conspicuity were assessed using a 5-point scale. The paired-sample t test was used to compare quantitative measures, whereas the Wilcoxon signed-rank test was used to compare qualitative measures. The mean SNR and CNR of the aorta, liver, pancreas, and muscle were significantly higher, and the image noise was significantly lower in the CE-boost images than in the conventional images (P < 0.001). The mean CNR of HCC was also significantly higher in the CE-boost images than in the conventional images (P < 0.001). In the qualitative analysis, CE-boost images showed higher scores for HCC lesion conspicuity than conventional images (P < 0.001). The overall image quality and visibility of HCC were improved using the CE-boost technique.

Non-Invasive Ultrasound Diagnostic Techniques for Steatotic Liver Disease and Focal Liver Lesions: 2D, Colour Doppler, 3D, Two-Dimensional Shear Wave Elastography (2D-SWE), and Ultrasound-Guided Attenuation Parameter (UGAP).

We conducted a comprehensive literature review to evaluate the efficacy of combining two-dimensional shear wave elastography (2D-SWE) and ultrasound-guided attenuation parameter (UGAP) in assessing the risk of progressive metabolic dysfunction-associated steatohepatitis (MASH). This narrative review explores the applications of liver ultrasound in diagnosing metabolic liver diseases, focusing on recent advancements in diagnostic techniques for steatotic liver disease (SLD). Liver ultrasound can detect a spectrum of SLD manifestations, from metabolic dysfunction-associated liver disease (MASLD) to fibrosis and cirrhosis. It is also possible to identify inflammation, hepatitis, hepatocellular carcinoma (HCC), and various other liver lesions. Innovative ultrasound applications, including elastography and UGAP, can significantly enhance the diagnostic capabilities of ultrasound in accurately interpreting liver diseases. Understanding the pathogenesis of liver diseases requires a thorough analysis of their etiology and progression in order to develop sound diagnostic and therapeutic approaches. Chronic liver diseases (CLD) vary in origin, with MASLD affecting approximately 20-25% of the general population. The insidious progression of CLD from inflammation to fibrosis and cirrhosis underscores the need for effective early detection methods. This review aims to highlight the evolving role of non-invasive ultrasound-based diagnostic tests in the early detection and staging of liver diseases. By synthesizing current evidence, we aim to provide an updated perspective on the utility of advanced ultrasound techniques in redefining the diagnostic landscape for metabolic liver diseases.

Cross-institutional evaluation of deep learning and radiomics models in predicting microvascular invasion in hepatocellular carcinoma: validity, robustness, and ultrasound modality efficacy comparison

PurposeTo conduct a head-to-head comparison between deep learning (DL) and radiomics models across institutions for predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC) and to investigate the model robustness and generalizability through rigorous internal and external validation.MethodsThis retrospective study included 2304 preoperative images of 576 HCC lesions from two centers, with MVI status determined by postoperative histopathology. We developed DL and radiomics models for predicting the presence of MVI using B-mode ultrasound, contrast-enhanced ultrasound (CEUS) at the arterial, portal, and delayed phases, and a combined modality (B + CEUS). For radiomics, we constructed models with enlarged vs. original regions of interest (ROIs). A cross-validation approach was performed by training models on one center’s dataset and validating the other, and vice versa. This allowed assessment of the validity of different ultrasound modalities and the cross-center robustness of the models. The optimal model combined with alpha-fetoprotein (AFP) was also validated. The head-to-head comparison was based on the area under the receiver operating characteristic curve (AUC).ResultsThirteen DL models and 25 radiomics models using different ultrasound modalities were constructed and compared. B + CEUS was the optimal modality for both DL and radiomics models. The DL model achieved AUCs of 0.802–0.818 internally and 0.667–0.688 externally across the two centers, whereas radiomics achieved AUCs of 0.749–0.869 internally and 0.646–0.697 externally. The radiomics models showed overall improvement with enlarged ROIs (P < 0.05 for both CEUS and B + CEUS modalities). The DL models showed good cross-institutional robustness (P > 0.05 for all modalities, 1.6–2.1% differences in AUC for the optimal modality), whereas the radiomics models had relatively limited robustness across the two centers (12% drop-off in AUC for the optimal modality). Adding AFP improved the DL models (P < 0.05 externally) and well maintained the robustness, but did not benefit the radiomics model (P > 0.05).ConclusionCross-institutional validation indicated that DL demonstrated better robustness than radiomics for preoperative MVI prediction in patients with HCC, representing a promising solution to non-standardized ultrasound examination procedures.

Correspondence on Editorial regarding "Genetically modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcinoma lesions in a clinical setting".

Correspondence on Editorial regarding "Genetically modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcinoma lesions in a clinical setting".

Reply to: Correspondence on Editorial regarding "Genetically modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcinoma lesions in a clinical setting".

Reply to: Correspondence on Editorial regarding "Genetically modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcinoma lesions in a clinical setting".

Machine learning model based on dynamic contrast-enhanced ultrasound assisting LI-RADS diagnosis of HCC: A multicenter diagnostic study

BackgroundTo enhance the accuracy of hepatocellular carcinoma (HCC) diagnosis using contrast-enhanced (CE) US, the American College of Radiology developed the CEUS Liver Imaging Reporting and Data System (LI-RADS). However, the system still exhibits limitations in distinguishing between HCC and non-HCC lesions. PurposeTo investigate the viability of employing machine learning methods based on quantitative parameters of contrast-enhanced ultrasound for distinguishing HCC within LR-M nodules. Materials and methodsThis retrospective analysis was conducted on pre-treatment CEUS data from liver nodule patients across multiple centers between January 2013 and June 2022. Quantitative analysis was performed using CEUS images, and the machine learning diagnostic models based on quantitative parameters were utilized for the classification diagnosis of LR-M nodules. The performance of the model was assessed using the area under the receiver operating characteristic curve (AUC) and compared with the performance of four radiologists. ResultsThe training and internal testing datasets comprised 168 patients (median age, 53 years [IQR, 18 years]), while the external testing datasets from two other centers included 110 patients (median age, 54 years [IQR, 16 years]). In the internal independent test set, the top-performing Random Forest model achieved an AUC of 0.796 (95%CI: 0.729–0.853) for diagnosing HCC. This model exhibited a sensitivity of 0.752 (95%CI: 0.750–0.755) and a specificity of 0.761 (95%CI: 0.758–0.764), outperforming junior radiologists who achieved an AUC of 0.619 (95%CI: 0.543–0.691, p < .01) with sensitivity and specificity of 0.716 (95%CI: 0.713–0.718) and 0.522 (95%CI: 0.519–0.526), respectively. ConclusionSignificant differences in contrast-enhanced ultrasound quantitative parameters are observed between HCC and non-HCC lesions. Machine learning models leveraging these parameters effectively distinguish HCC categorized as LR-M, offering a valuable adjunct for the accurate classification of liver nodules within the CEUS LI-RADS framework.

A combined model based on radiomics features of Sonazoid contrast-enhanced ultrasound in the Kupffer phase for the diagnosis of well-differentiated hepatocellular carcinoma and atypical focal liver lesions: a prospective, multicenter study.

The objective of this study was to develop a combined model based on radiomics features of Sonazoid contrast-enhanced ultrasound (CEUS) during the Kupffer phase and to evaluate its value in differentiating well-differentiated hepatocellular carcinoma (w-HCC) from atypical benign focal liver lesions (FLLs). A total of 116 patients with preoperatively Sonazoid-CEUS confirmed w-HCC or benign FLL were selected from a prospective multiple study on the clinical application of Sonazoid in FLLs conducted from August 2020 to March 2021. According to the randomization principle, the patients were divided into a training cohort and a test cohort in a 7:3 ratio. Seventy-nine patients were used for establishing and training the radiomics model and combined model. In comparison, 37 patients were used for validating and comparing the performance of the models. The diagnostic efficacy of the models for w-HCC and atypical benign FLLs was evaluated using ROCs curves and decision curves. A combined model nomogram was created to assess its value in reducing unnecessary biopsies. Among the patients, there were 55 cases of w-HCC and 61 cases of atypical benign FLLs, including 28 cases of early liver abscess, 16 cases of atypical hepatic hemangioma, 8 cases of hepatocellular dysplastic nodules (DN), and 9 cases of focal nodular hyperplasia (FNH). The radiomics model and combined model we established had AUCs of 0.905 and 0.951, respectively, in the training cohort, and the AUCs of the two models in the test cohort were 0.826 and 0.912, respectively. The combined model outperformed the radiomics feature model significantly. Decision curve analysis demonstrated that the combined model achieved a higher net benefit within a specific threshold probability range (0.25 to 1.00). A nomogram of the combined model was developed. The combined model based on the radiomics features of Sonazoid-CEUS in the Kupffer phase showed satisfactory performance in diagnosing w-HCC and atypical benign FLLs. It can assist clinicians in timely detecting malignant FLLs and reducing unnecessary biopsies for benign diseases.

Effect of Transarterial Chemoembolization on Portal Venous Pressure in Patients with Hepatocellular Carcinoma

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and has a poor prognosis unless treated. Transarterial chemoembolization of HCC lesions is a promising treatment option for patients who are not eligible for surgery. Objective To study the short term effect of TACE on portal venous pressure by assessing it indirectly through measuring hepatic venous pressure gradient before and after TACE procedure. Patients and Methods Our study was a Prospective cohort analysis of patients who were been referred to our IR unit (in our university hospital) diagnosed with HCC for performance of TACE at the period between January 2022 and December 2022. (21 patients). Results Our study showed that there is no short term effect of TACE on HVPG (which reflects the portal pressure). We also recommend doing a follow up measurement of HVPG after 6 months and compare it with the baseline measurements to assess the long term effect of TACE on the portal pressure. Conclusion Our study is in agreement with previous studies that there is no short term effect of TACE on HVPG (which reflects the portal pressure).

Predictive Factors for Hepatic Decompensation after Transarterial Chemoembolization for Hepatocellular Carcinoma

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and has a poor prognosis unless treated. Transarterial chemoembolization (TACE) of HCC lesions is a promising treatment option for patients who are not eligible for surgery. There are various risk factors that can contribute to the development of hepatic decompensation such as liver function status, HCC morphology and patient’s comorbidities. Aim of the Work to analyse the different predictive parameters for hepatic decompensation after transarterial chemoembolisation (TACE) for hepatocellular carcinoma (HCC). Patients and Methods Our study included 50 patients who underwent TACE for HCC, mostly males (72%) with HCV being the most common cause (86%) of HCC in our sample. Results The results showed that 44% of patients developed hepatic decompensation after TACE. Comparison was done between the compensated and decompensated patients as regards different epidemiologic, laboratory and tumor morphology variables. Regarding the pre-TACE laboratory data, the decompensated group had significantly lower levels of albumin and higher levels of bilirubin, ALT, AST and INR. There was no statistically significant difference in the levels of AFP and creatinine between the two groups. Regarding the tumor characteristics in our study groups, the size and number of nodules were significantly higher in the decompensated group. However, the location and the distribution of the tumor between the two groups were not statistically significant. Multivariate analysis revealed that serum bilirubin level (p = 0.007 at 95% CI), MELD score (p value=0.011 at 95% CI) and ALBI score (p = 0.021 at 95% CI) were the statistically significant independent factors predictive of decompensation after TACE. Conclusion There is significant hepatic decompensation after TACE for patients with HCC. Serum bilirubin level with the ALBI and MELD scores were the independent predictors of decompensation after TACE. Patients should be cautiously selected for TACE and prioritized in post-operative management to early identify the signs of hepatic decompensation. This would allow prioritized treatment and improve the chances of survival.

Retrospective Analysis of Radiofrequency Ablation in Patients with Small Solitary Hepatocellular Carcinoma: Survival Outcomes and Development of a Machine Learning Prognostic Model.

The effectiveness of radiofrequency ablation (RFA) in improving long-term survival outcomes for patients with a solitary hepatocellular carcinoma (HCC) measuring 5 cm or less remains uncertain. This study was designed to elucidate the impact of RFA therapy on the survival outcomes of these patients and to construct a prognostic model for patients following RFA. This study was performed using the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2017, focusing on patients diagnosed with a solitary HCC lesion ≤5 cm in size. We compared the overall survival (OS) and cancer-specific survival (CSS) rates of these patients with those of patients who received hepatectomy, radiotherapy, or chemotherapy or who were part of a blank control group. To enhance the reliability of our findings, we employed stabilized inverse probability treatment weighting (sIPTW) and stratified analyses. Additionally, we conducted a Cox regression analysis to identify prognostic factors. XGBoost models were developed to predict 1-, 3-, and 5-year CSS. The XGBoost models were evaluated via receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA) curves and so on. Regardless of whether the data were unadjusted or adjusted for the use of sIPTWs, the 5-year OS (46.7%) and CSS (58.9%) rates were greater in the RFA group than in the radiotherapy (27.1%/35.8%), chemotherapy (32.9%/43.7%), and blank control (18.6%/30.7%) groups, but these rates were lower than those in the hepatectomy group (69.4%/78.9%). Stratified analysis based on age and cirrhosis status revealed that RFA and hepatectomy yielded similar OS and CSS outcomes for patients with cirrhosis aged over 65 years. Age, race, marital status, grade, cirrhosis status, tumor size, and AFP level were selected to construct the XGBoost models based on the training cohort. The areas under the curve (AUCs) for 1, 3, and 5 years in the validation cohort were 0.88, 0.81, and 0.79, respectively. Calibration plots further demonstrated the consistency between the predicted and actual values in both the training and validation cohorts. RFA can improve the survival of patients diagnosed with a solitary HCC lesion ≤5 cm. In certain clinical scenarios, RFA achieves survival outcomes comparable to those of hepatectomy. The XGBoost models developed in this study performed admirably in predicting the CSS of patients with solitary HCC tumors smaller than 5 cm following RFA.

A Nomogram Based on Features of Ultrasonography and Contrast-Enhanced CT to Predict Vessels Encapsulating Tumor Clusters Pattern of Hepatocellular Carcinoma

ObjectiveThis study aimed to establish a clinical prediction model for vessels encapsulating tumor clusters (VETC) based on preoperative ultrasonography (US) and contrast-enhanced computed tomography (CECT) imaging in patients with hepatocellular carcinoma (HCC). MethodsData were retrospectively collected from 215 patients who underwent hepatectomy for solitary HCC lesions. They were divided into training and validation cohorts at a ratio of 6:4. Preoperative imaging features were extracted (seven from US and nine from CECT imaging) to explore their relationship with VETC. A VETC prediction model was constructed and graphically depicted as a nomogram. Its performance was evaluated via the receiver operating characteristic (ROC) curve, the calibration curve, and decision curve analysis (DCA). ResultsThe VETC incidence for all the lesions was 37.7%. The final variables included in the nomogram were “peritumoral enhancement in CECT”, “alpha-fetoprotein level > 200 ng/Ml,” “halo in US,” “capsule enhancement in CECT,” and “posterior acoustic enhancement in US.” The area under the curve (AUC) values for the training and validation cohorts were 0.824 and 0.725, respectively. The Hosmer–Lemeshow fit test showed no statistical difference (p = 0.369 and p = 0.067 for the training and validation cohorts, respectively). DCA demonstrated that our nomogram provided clinical benefits to a wide range of patients. According to the nomogram score, the VETC-positive and -negative groups demonstrated significant differences in both the training (p < 0.001) and validation (p = 0.001) cohorts. ConclusionOur prediction model based on US and CECT imaging features can accurately predict VETC in HCC.

68Ga]Ga-RAYZ-8009: A Glypican-3-Targeted Diagnostic Radiopharmaceutical for Hepatocellular Carcinoma Molecular Imaging-A First-in-Human Case Series.

To date, the imaging and diagnosis of hepatocellular carcinoma (HCC) rely on CT/MRI, which have well-known limitations. Glypican-3 (GPC3) is a cell surface receptor highly expressed by HCC but not by normal or cirrhotic liver tissue. Here we report initial clinical results of GPC3-targeted PET imaging with [68Ga]Ga-DOTA-RYZ-GPC3 (RAYZ-8009), a peptide-based GPC3 ligand in patients with known or suspected HCC. Methods: [68Ga]Ga-RAYZ-8009 was obtained after labeling the peptide precursor with 68Ga from a 68Ge/68Ga generator and heating at 90°C for 10 min followed by sterile filtration. After administration of [68Ga]Ga-RAYZ-8009, a dynamic or static PET/CT scan was acquired between 45 min and 4 h after administration. Radiotracer uptake was measured by SUVs for the following tissues: suspected or actual HCC or hepatoblastoma lesions, non-tumor-bearing liver, renal cortex, blood pool in the left ventricle, and gastric fundus. Additionally, tumor-to-healthy-liver ratios (TLRs) were calculated. Results: Twenty-four patients (5 patients in the dynamic protocol; 19 patients in the static protocol) were scanned. No adverse events occurred. Two patients had no lesion detected and did not have HCC during follow-up. In total, 50 lesions were detected and analyzed. The mean SUVmax of these lesions was 19.6 (range, 2.7-95.3), and the mean SUVmean was 10.1 (range, 1.0-49.2) at approximately 60 min after administration. Uptake in non-tumor-bearing liver and blood pool rapidly decreased over time and became negligible 45 min after administration (mean SUVmean, <1.6), with a continuous decline to 4 h after administration (mean SUVmean, 1.0). The opposite was observed for HCC lesions, for which SUVs and TLRs continuously increased for up to 4 h after administration. In individual lesion analysis, TLR was the highest between 60 and 120 min after administration. Uptake in the gastric fundus gradually increased for up to 45 min (to an SUVmax of 31.3) and decreased gradually afterward. Conclusion: [68Ga]Ga-RAYZ-8009 is safe and allows for high-contrast imaging of GPC3-positive HCC, with rapid clearance from most normal organs. Thereby, [68Ga]Ga-RAYZ-8009 is promising for HCC diagnosis and staging. Further research is warranted.

CD36-mediated accumulation of MDSCs exerts abscopal immunosuppressive responses in hepatocellular carcinoma after insufficient microwave ablation

The immune landscape of distant unablated tumors following insufficient microwave ablation (iMWA) in hepatocellular carcinoma (HCC) remains to be clarified. The objective of this study is to define the abscopal immune landscape in distant unablated tumor before and after iMWA for HCC. Two treatment-naive patients were recruited for tumor tissue sampling, of each with two HCC lesions. Tumor samples were obtained at before and after microwave ablation in distant unablated sites for single-cell RNA sequencing (scRNA-seq). Mouse model with bilateral hepatoma tumors were developed, and distant unablated tumors were analyzed using multicolor immunofluorescence, RNA sequencing and flow cytometry. The scRNA-seq revealed that a reduced proportion of CD8+ T cells and an increased proportion of myeloid-derived suppressor cells (MDSCs) were observed in the distant unablated tumor microenvironment (TME). A notable disruption was observed in the lipid metabolism of tumor-associated immune cells, accompanied by an upregulated expression of CD36 in tumor-infiltrating immune cells in distant unablated tumor. The administration of a CD36 inhibitor has been demonstrated to ameliorate the adverse effects induced by iMWA, primarily by reinstating the anti-tumor responses of T cells in distant unablated tumor. These findings explain the recurrence and progression of tumors after iMWA and provide a new target of immunotherapy for HCC.

Value of hepatic artery digital subtraction angiography in the detection of small hepatocellular carcinoma lesions.

To compare the detection rates of hepatic artery digital subtraction angiography (HA-DSA) and magnetic resonance imaging (MRI) gadolinium diethylenetriaminepentaacetic acid (MRI-Gd-DTPA) and MRI gadolinium diethylenetriaminepentaacetic acid (MRI-Gd-EOB-DTPA) for small (diameter ≤2 cm) hepatocellular carcinoma (HCC) lesions. A prospective analysis of patients admitted to the Tumor Hospital of Guangxi Medical University between January 1, 2015, and December 30, 2016, was conducted. The detection rates of the three methods were analyzed. The diameter of small HCC lesions detected using HA-DSA and MRI-Gd-EOB-DTPA were evaluated. The diagnostic value of HCC Barcelona staging for HA-DSA was analyzed. For 107 small lesions detected in 57 patients, the detection rates of HA-DSA and MRI-Gd-DTPA were 86.0% (92/107) and 71.0% (76/107), respectively (p < .05). Of 77 small lesions detected in 42 patients using MRI-Gd-EOB-DTPA and HA-DSA, 67 were detected using HA-DSA, all of which had a rich blood supply, and 72 were detected using MRI-Gd-EOB-DTPA. The minimum diameter of lesions detected using MRI-Gd-EOB-DTPA was approximately 0.4 cm, whereas that of lesions detected using HA-DSA was approximately 0.5 cm. After HA-DSA, a change in the Barcelona staging occurred in 33.3% (62/186) of cases but not after MRI-Gd-DTPA; HA-DSA was significantly better than MRI-Gd-DTPA for staging (p = .03). HA-DSA and MRI-Gd-EOB-DTPA have high diagnostic values for the detection of small HCC lesions, which is helpful for accurate staging of HCC and provides the most valuable information for patient treatment and prognosis.