This study aims to compare the efficacy and safety of radiotherapy (RT) and transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) with inferior vena cava/right atrium tumor thrombus (IVC/RATT) treated with lenvatinib and camrelizumab.

HCC with IVC/RATT from four hospitals were enrolled in this retrospective study. The patients were divided into RT group and TACE group. Stabilized inverse probability of treatment weighting (sIPTW) was used to minimize bias. The primary endpoints were overall survival (OS) and progression free survival (PFS). The second endpoints were objective response rate (ORR) and disease control rate (DCR). In addition, safety was assessed by treatment-related adverse events (TRAEs) between the two groups.

Among 108 patients included in this study, 48 patients in TACE group and 60 patients in RT group. The median follow-up time was 24.8 months. After the application of sIPTW, baseline characteristics were well-balanced between the two groups. Before and after sITPW, the median OS and median PFS in the RT group were significantly longer than in the TACE group. Multivariate Cox analysis showed that RT was an independent prognosis factor of both OS and PFS. There was no significant difference between two groups in overall response, while IVC/RATT response rate of RT group was significantly higher than TACE group. Incidence rate of TRAEs in two groups were similar.

In combination with lenvatinib and camrelizumab, RT significantly improves the prognosis of HCC with IVC/RATT compared to TACE, with a comparable safety profile.

Intraoperative intraperitoneal lavage with lobaplatin is widely used in the treatment of colorectal and gastric cancers. This study aimed to explore the efficacy of lobaplatin lavage in patients with ruptured hepatocellular carcinoma (HCC) administered radical hepatectomy.

Ruptured HCC patients who underwent hepatectomy between September 2007 and March 2022 were divided into the distilled water lavage and lobaplatin lavage groups. Survival curves for RFS and OS were generated by the Kaplan-Meier method and compared by the log-rank test using Propensity Score Matching (PSM). Cox regression analysis was conducted to identify independent prognostic factors of RFS and OS.

This study included 201 patients, with 114 cases (89.1%) in the distilled water lavage group and 55 cases (75.3%) in the lobaplatin lavage group experiencing recurrence, and 95 (74.2%) and 44 (60.3%) patients died in the distilled water lavage and lobaplatin lavage groups, respectively during the follow-up period. After PSM, 1-, 2-, 3-year RFS rates were 38.6%, 21.1%, 10.5% and 57.9%, 40.4%, 26.3% in the distilled water lavage and lobaplatin lavage groups, respectively (P = 0.001). 1-, 2-, 3-year OS rates were 56.1%, 40.4%, 33.3% and 89.5%, 63.2%, 43.9% in the distilled water lavage and lobaplatin lavage groups, respectively (P = 0.001). Multivariable Cox regression indicated that lobaplatin lavage may improve RFS (HR = 0.524, 95% CI: 0.354-0.775;P = 0.001) and OS (HR = 0.524, 95% CI: 0.350-0.783;P = 0.002).

Intraoperative lobaplatin lavage improves RFS and OS in patients with ruptured HCC after hepatectomy.

TJ-IRB202403002, 2024-04-26, retrospectively registered.

Despite advances in surgical treatment, high recurrence after surgery remains a challenge for patients with hepatocellular carcinoma (HCC). This study aimed to investigate the association between compliance to regular follow-up and long-term oncological outcomes among patients undergoing curative resection for HCC.

This multicenter study included patients who underwent curative resection for early-stage HCC between January 2012 and December 2021 at 12 liver surgery centers. Patients were stratified into a regular follow-up group (follow-up every 2-3 months for the first 2 years and every 3-6 months thereafter) and an irregular/no follow-up group. Overall survival (OS), time to recurrence (TTR), and post-recurrence survival (PRS) were compared between the two groups.

Among 1544 patients, 786 (50.9 %) underwent regular follow-up during postoperative follow-up. The regular follow-up group had better OS (median: 113.4 vs. 94.5 months, P = 0.010) and PRS (median: 37.9 vs. 16.3 months, P < 0.001) than the irregular/no follow-up group, although TTR was comparable (median: 61.4 vs. 66.2 months, P = 0.161). Furthermore, patients in the regular follow-up group had a lower incidence of tumor beyond the Milan criteria at recurrence (41.6 % vs. 50.4 %, P = 0.013) and were more likely to receive curative treatments for recurrence (56.1 % vs. 49.3 %, P = 0.061). On multivariate analysis, compliance to regular follow-up was an independent factor associated with better OS [hazard ratio (HR) = 0.777, 95 % confidence interval (CI): 0.663-0.910, P = 0.002] and PRS (HR = 0.523, 95 % CI: 0.428-0.638, P < 0.001).

Compliance to regular follow-up improved OS and PRS after curative resection for HCC, highlighting the importance of postoperative regular follow-up for early detection of recurrence and timely intervention.

Hepatocellular carcinoma (HCC) surveillance is crucial for patients with compensated cirrhosis (CC) and decompensated cirrhosis (DC). Increasing evidence has revealed a connection between thyroid hormone (TH) and HCC, although this relationship remains contentious. Complements and immunoglobulin (Ig), which serve as surrogates of cirrhosis-associated immune dysfunction, are associated with the severity and outcomes of liver cirrhosis (LC). To date, there is a lack of evidence supporting the recommendation of TH, Ig, and complement tests in patients at high risk of HCC.

To assess the predictive value of TH, Ig, and complements for HCC development.

Data from 142 patients, comprising 72 patients with CC and 70 patients with DC, were analysed as a training set. Among them, 100 patients who underwent complement and Ig tests were considered for internal validation. Logistic regression was employed to identify independent risk factors for HCC development.

The median follow-up duration was 32 (24-37 months) months. The incidence of HCC was significantly higher in the DC group (16/70, 22.9%) compared to the CC group (3/72, 4.2%) (χ² = 10.698, P < 0.01). Patients with DC exhibited lower total tetraiodothyronine (TT4), total triiodothyronine (TT3), free triiodothyronine, complement C3, and C4 (all P < 0.01), and higher IgA and IgG (both P < 0.01). In both CC and DC patients, TT3 and TT4 positively correlated with alanine transaminase (ALT), aspartate transaminase (AST), and gamma-glutamyl transpeptidase (GGT). IgG positively correlated with IgM, IgA, ALT, and AST, while it negatively correlated with C3 and C4. Multivariable analysis indicated that age, DC status, and GGT were independent risk factors for HCC development.

The predictive value of TH, Ig, and complements for HCC development is suboptimal. Age, DC, and GGT emerge as more significant factors during HCC surveillance in hepatitis B virus-related LC.

We aimed to develop a convenient nomogram to predict preoperative MVI in patients with hepatocellular carcinoma (HCC). Patients who underwent surgical resection due to HCC from June 2018 to June 2023 at the Third Affiliated Hospital of Sun Yat-sen University were retrospectively reviewed. Univariate and multivariable logistic linear regression analyses were used to investigate potential risk factors for MVI. A nomogram was plotted based on these risk factors. The tumor diameter (≥ 5 cm), BCLC stage, PLT (>127.50 × 109/L), AST (>29.50 U/L) and AFP (>10.07 ng/ml) were identified as independent preoperative risk factors for MVI by univariate and multivariable logistic analysis. The nomogram demonstrated decent accuracy in estimating the presence of MVI, with an AUC of 0.69 (95%CI: 0.64-0.73). The calibration curves exhibited a close match between the predicted probabilities and the actual estimates of MVI in the nomogram (p = 0.947). Decision curve analysis (DCA) revealed that the prediction model had a high net benefit if the threshold probability>20%. High platelet counts were strongly associated with the presence of MVI in HCC patients. Our convenient nomogram demonstrated decent accuracy in estimating the presence of MVI and had notable clinical application.

Transarterial chemoembolization (TACE) refractoriness is a significant challenge in treating intermediate to advanced-stage hepatocellular carcinoma (HCC). A few studies suggest that liver cancer stem cells (LCSCs) may be associated with TACE refractoriness. This study aims to explore the potential correlation between TACE refractoriness and HCC stemness, highlighting its clinical significance.

This research encompassed the analysis of diverse HCC datasets, including RNA-sequencing, microarray, single-cell RNA-sequencing, and clinical cohorts. We identified common genes between TACE refractoriness and tumor stemness (TSGs). Unsupervised clustering was employed to classify HCC patients into different clusters based on TSGs (TRS clusters). The study explored the differences in clinical prognosis, biological characteristics, genomic variations, immune landscapes, and treatment responses among the TRS clusters.

Patients with TACE-refractoriness demonstrated significantly higher tumor stemness. Our study identified 33 TSGs and established two TRS clusters, including C1 and C2. C1 was associated with TACE refractoriness, elevated tumor stemness, and poorer prognosis. Genomic alterations were found to be significantly different between the TRS clusters. The C1 exhibited signs of immunosuppression and lower activity of immune effector cells, while the C2 had a more robust immune response and higher level of immune cell presence. Single-cell RNA-seq revealed distinct cell type characteristics in each subtypes, with the C1 showing a higher proportion of stem cells and malignant cells.

Our findings establish a connection between TACE refractoriness and tumor stemness in HCC, proposing a novel subtype classification to guide personalized treatment. Insights gained may facilitate overcoming TACE refractoriness and the development of innovative therapies.

Hepatocellular carcinosarcoma (HCS) is a rare and aggressive liver tumor with limited clinical evidence due to its infrequency. This case series aimed to enrich the existing knowledge on the diagnosis and clinical management of HCS.

Four patients with HCS were evaluated, focusing on their symptoms, diagnoses, treatments, and outcomes. The imaging characteristics and tumorigenesis of HCS were also investigated, highlighting the role of p53 mutations.

This case series found that timely surgery and localized chemotherapy are crucial in managing HCS. Despite the promising results of targeted therapy, its limitations were observed in some patients. The onset and progression of HCS were found to be significantly correlated with the presence of p53 mutations.

This case series underscores the need for further research to improve the diagnosis and treatment of HCS and emphasizes the importance of timely surgery and localized chemotherapy in mitigating tumor side effects and potentially prolonging survival.

In recent years, it has been discovered that the expression of long non-coding RNAs is highly deregulated in several types of cancer and contributes to its progression and development. Recently, it has been described that in tumors of the digestive system, such as colorectal cancer, pancreatic cancer, and gastric cancer, DNA damage-activated lncRNA (NORAD) was frequently up-regulated. The purpose of this review is to elucidate the functions of NORAD in tumors of the digestive system, emphasizing its involvement in important cellular processes such as invasion, metastasis, proliferation, and apoptosis. NORAD acts as a ceRNA (competitive endogenous RNA) that sponges microRNAs and regulates the expression of target genes involved in tumorigenesis. Thus, the mechanisms underlying the effects of NORAD are complex and involve multiple signaling pathways. This review consolidates current knowledge on the role of NORAD in digestive cancers and highlights the need for further research to explore its potential as a therapeutic target. Understanding the intricate functions of NORAD could elucidate the way for innovative approaches to cancer treatment.

Hepatocellular carcinoma (HCC) is a highly immunogenic tumor and the third leading cause of cancer-related deaths worldwide with an increasing incidence. Therefore, the combination of immunotherapy with other approaches, such as anti-angiogenic agents and local area therapy, has become a new strategy for HCC treatment.

We searched PubMed and Web of Science and extracted publications relating to the radiofrequency ablation (RFA) and immunotherapy. The search terms were: "radiofrequency ablation", "immunotherapy" and "hepatocellular carcinoma", and manual searches of eligible articles from literature reference lists were performed. We then thoroughly reviewed the literature on ablation combined with immunotherapy for HCC, analyzed the relevant mechanism, and explored the safety and effectiveness of this form of combination therapy.

RFA combined with immunotherapy in HCC is reported to have good efficacy and controllable safety. On the one hand, RFA can induce the immunogenic substances including Ficolin-3, IL-1 and heat shock protein and regulate the immune cells by mediating the Th1/Th2 ratio, increasing Th17 cells, etc. On the other hand, RFA treatment can lead to tumor immune microenvironment reconstruction, increasing the proportion of functional T cells and upregulate PD-1 in T cells in distant tumors without RFA. This combined strategy has the ability to enhance the anti-tumor immune response through synergies, significantly reduce the risk of recurrence and improve survival.

RFA combined with immunotherapy yields a good synergistic effect: it can further strengthen anti-tumor response, delay distant tumor growth, reduce tumor recurrence and metastasis, providing new options for HCC systemic treatment.

Various conversion therapy options have become available to patients with unresectable HCC, but which conversion therapy is optimal for which type of patient is controversial. This study compared the efficacy and safety of TACE alone or combined with immune checkpoint and tyrosine kinase inhibitors.

Data were retrospectively compared for patients with initially unresectable HCC who underwent conversion therapy consisting of TACE alone (n=459) or combined with immune checkpoint and tyrosine kinase inhibitors (n=343). Compared to the group that received TACE alone, the group that received triple conversion therapy showed significantly higher rates of overall survival (HR 0.43, 95%CI 0.35-0.53). In addition, triple therapy was associated with significantly longer median progression-free survival (15.9 vs. 8.0 mo, p <0.001). These results were confirmed in matched subsets of patients from each group. However, subgroup analysis confirmed the results only for patients with HCC in intermediate or advanced stages, not in an early stage. Those who received triple conversion therapy had a significantly higher rate of hepatectomy after conversion therapy (36.4 vs. 23.5%, p <0.001). Among those who underwent hepatectomy after conversion therapy, triple therapy was associated with a significantly higher rate of complete tumor response (32.1 vs. 11.1%, p <0.001). However, it was also associated with a significantly higher frequency of serious adverse events (35.6 vs. 27.0%, p =0.009).

Combining TACE with immune checkpoint and tyrosine kinase inhibitors was associated with significantly better survival and conversion efficacy than TACE alone among patients with intermediate or advanced unresectable HCC.

The prognosis for patients with hepatocellular carcinoma (HCC) depends on tumor stage and remnant liver function. However, it often includes tumor morphology, which is usually assessed with imaging studies or pathologic analysis, leading to limited predictive performance. Therefore, the aim of this study was to develop a simple and low-cost prognostic score for HCC based on serum biomarkers in routine clinical practice. A total of 3,100 patients were recruited. The least absolute shrinkage and selector operation (LASSO) algorithm was used to select the significant factors for overall survival. The prognostic score was devised based on multivariate Cox regression of the training cohort. Model performance was assessed by discrimination and calibration. Albumin (ALB), alkaline phosphatase (ALP), and alpha-fetoprotein (AFP) were selected by the LASSO algorithm. The three variables were incorporated into multivariate Cox regression to create the risk score (APP score = 0.390* ln (ALP) + 0.063* ln(AFP) - 0.033*ALB). The C-index, K-index, and time-dependent AUC of the score displayed significantly better predictive performance than 5 other models and 5 other staging systems. The model was able to stratify patients into three different risk groups. In conclusion, the APP score was developed to estimate survival probability and was used to stratify three strata with significantly different outcomes, outperforming other models in training and validation cohorts as well as different subgroups. This simple and low-cost model could help guide individualized follow-up.

Recent research has highlighted lactate's crucial role in epigenetic regulation, particularly by influencing histone modifications that drive the initiation and progression of hepatocellular carcinoma (HCC). While mitochondria are known to regulate tumor behavior, the interaction between lactate metabolism and mitochondrial function in cancer tissues remains underexplored. Understanding this relationship may provide deeper insights into tumor metabolic reprogramming and reveal novel therapeutic targets for HCC and other malignancies.

We conducted a comprehensive screening of lactylation- and mitochondria-associated genes (LMRGs) in HCC patients, followed by clustering based on these genes. Prognostic outcomes and pathway enrichment were analyzed across the identified clusters. Additionally, we developed a prognostic model based on LMRGs, examining its implications for survival, immune response, and drug sensitivity. In vitro experiments were performed to validate the expression patterns and functional role of MRPL3 in HCC.

We developed a prognostic model, named the LMRG model, incorporating three key genes: ACACA, MRPL3, and MRPS23. This model revealed significant differences in survival outcomes, immune responses, and drug sensitivity between patients with high and low LMRG scores. MRPL3 was found to be overexpressed in HCC, playing a critical role in tumor growth and metastasis. These results were further validated through in vitro experiments, confirming MRPL3's role in HCC cell proliferation and invasion.

We created a predictive model, LMRG, and identified MRPL3 as a key biomarker. Our findings suggest that MRPL3 has significant potential as a reliable predictive biomarker for clinical applications in HCC diagnosis and treatment.

Large hepatocellular carcinoma (HCC) is difficult to resect and accompanied by poor outcome. The aim was to evaluate the short-term and long-term outcomes of patients who underwent liver resection for large HCC, eventually drawing prediction models for short-term and long-term outcomes.

1710 large HCC patients were recruited and randomly divided into the training (n = 1140) and validation (n = 570) cohorts in a 2:1 ratio. Independent risk factors were identified by regression model and used to establish three nomograms for surgical risk, overall survival (OS), and recurrence-free survival (RFS) in the training cohort. Model performances were assessed by discrimination and calibration. The three models were also compared with six other staging systems.

Platelet (PLT), gamma-glutamyl transpeptidase (GGT), albumin-bilirubin (ALBI) grade, blood transfusion and loss, resection margin, tumor size, and tumor number were established in a nomogram to evaluate surgical risk ( https://largehcc.shinyapps.io/largehcc-morbidity/ ). The model had a good prediction capability with a C-index of 0.764 and 0.773 in the training and validation cohorts. Alpha-fetoprotein (AFP), resection margin, tumor size, tumor number, microvascular invasion, Edmondson-Steiner grade, tumor capsular, and satellite nodules were considered to construct a prognostic nomogram to predict the 1-, 3- and 5-year OS ( https://largehcc.shinyapps.io/largehcc-os/ ). The C-index of the model was 0.709 and 0.702 for the training and validation cohorts. Liver cirrhosis, albumin (ALB), total bilirubin (TBIL), AFP, tumor size, tumor number, microvascular invasion, and tumor capsular were used to draw a prognostic nomogram to predict the 1-, 3- and 5-year RFS ( https://largehcc.shinyapps.io/largehcc-rfs/ ). The C-index of the model was 0.695 and 0.675 in the training and validation cohorts. The discrimination showed that the models had significantly better predictive performances than six other staging systems.

Three novel nomograms were developed to predict short-term and long-term outcomes in patients with large HCC who underwent curative resection with adequate performance. These predictive models could help to design therapeutic interventions and surveillance for patients with large HCC.

Hepatocellular carcinoma (HCC) is one of the most common cancers occurring worldwide, including Mongolia. Although alpha-fetoprotein (AFP) is a widely used marker for HCC, conflicting studies have been published regarding its specificity and sensitivity towards HCC. Glypican-3 (GPC3) is a different promising biomarker for HCC, and there is some evidence to suggest that this protein may be a more specific marker compared with AFP. GPC3 has been shown to fulfill important roles in cell proliferation and division during embryogenesis, and is rarely found in the tissues of healthy adults. The aim of the present study was to investigate the levels of serum GPC3 (sGPC3) and tissue GPC3 in Mongolian patients with HCC. Serum samples from a total of 270 individuals [HCC group, 90 patients; risk group (RG), 90 subjects; and control group, 90 subjects] were evaluated using enzyme-linked immunosorbent assay to identify the sGPC3 levels. In addition, immunohistochemical analysis of the GPC3 was performed on tissue samples from 50 patients with HCC to evaluate the expression of GPC3. sGPC3 level was found to be significantly increased in the HCC group compared with the RG and the control group, with the area under the curve=0.85 (P<0.001). sGPC3 was found to be significantly associated with hepatitis C virus status and cirrhosis (P<0.05). In addition, the tissue expression of GPC3 was associated with the serum AFP (sAFP) level. Finally, positive staining of GPC3 was observed when the sAFP level of the patient was >20 ng/ml. In conclusion, the results from the present study have supported that GPC3 may be a promising marker for HCC, and can be used as a diagnostic marker alongside AFP.

Hepatocellular carcinoma (HCC) circulating tumor cells (CTCs) exhibit significant phenotypic heterogeneity and diverse gene expression profiles due to epithelial-mesenchymal transition (EMT). However, current detection methods lack the capacity for simultaneous quantification of multidimensional biomarkers, impeding a comprehensive understanding of tumor biology and dynamic changes. Here, the CTC Digital Simultaneous Cross-dimensional Output and Unified Tracking (d-SCOUT) technology is introduced, which enables simultaneous quantification and detailed interpretation of HCC transcriptional and phenotypic biomarkers. Based on self-developed multi-real-time digital PCR (MRT-dPCR) and algorithms, d-SCOUT allows for the unified quantification of Asialoglycoprotein Receptor (ASGPR), Glypican-3 (GPC-3), and Epithelial Cell Adhesion Molecule (EpCAM) proteins, as well as Programmed Death Ligand 1 (PD-L1), GPC-3, and EpCAM mRNA in HCC CTCs, with good sensitivity (LOD of 3.2 CTCs per mL of blood) and reproducibility (mean %CV = 1.80-6.05%). In a study of 99 clinical samples, molecular signatures derived from HCC CTCs demonstrated strong diagnostic potential (AUC = 0.950, sensitivity = 90.6%, specificity = 87.5%). Importantly, by integrating machine learning, d-SCOUT allows clustering of CTC characteristics at the mRNA and protein levels, mapping normalized heterogeneous 2D molecular profiles to assess HCC metastatic risk. Dynamic digital tracking of eight HCC patients undergoing different treatments visually illustrated the therapeutic effects, validating this technology's capability to quantify the treatment efficacy. CTC d-SCOUT enhances understanding of tumor biology and HCC management.

The number of focal liver lesions (FLLs) detected by imaging has increased worldwide, highlighting the need to develop a robust, objective system for automatically detecting FLLs.

To assess the performance of the deep learning-based artificial intelligence (AI) software in identifying and measuring lesions on contrast-enhanced magnetic resonance imaging (MRI) images in patients with FLLs.

Retrospective.

395 patients with 1149 FLLs.

The 1.5 T and 3 T scanners, including T1-, T2-, diffusion-weighted imaging, in/out-phase imaging, and dynamic contrast-enhanced imaging.

The diagnostic performance of AI, radiologist, and their combination was compared. Using 20 mm as the cut-off value, the lesions were divided into two groups, and then divided into four subgroups: <10, 10-20, 20-40, and ≥40 mm, to evaluate the sensitivity of radiologists and AI in the detection of lesions of different sizes. We compared the pathologic sizes of 122 surgically resected lesions with measurements obtained using AI and those made by radiologists.

McNemar test, Bland-Altman analyses, Friedman test, Pearson's chi-squared test, Fisher's exact test, Dice coefficient, and intraclass correlation coefficients. A P-value <0.05 was considered statistically significant.

The average Dice coefficient of AI in segmentation of liver lesions was 0.62. The combination of AI and radiologist outperformed the radiologist alone, with a significantly higher detection rate (0.894 vs. 0.825) and sensitivity (0.883 vs. 0.806). The AI showed significantly sensitivity than radiologists in detecting all lesions <20 mm (0.848 vs. 0.788). Both AI and radiologists achieved excellent detection performance for lesions ≥20 mm (0.867 vs. 0.881, P = 0.671). A remarkable agreement existed in the average tumor sizes among the three measurements (P = 0.174).

AI software based on deep learning exhibited practical value in automatically identifying and measuring liver lesions.

Stage 2.

Given the crucial role of imaging in HCC diagnosis, LI-RADS CT/MRI was developed to standardize the imaging interpretation and reporting of HCC in patients at risk for HCC and categorize hepatic observations on an ordinal scale according to the likelihood of HCC. LI-RADS has since been expanded to include 5 algorithms: LI-RADS US Surveillance, contrast-enhanced US (CEUS) LI-RADS, LI-RADS CT/MRI, and LI-RADS Treatment Response Assessment. LI-RADS has been adopted broadly in North America, however with less ubiquitous adoption outside of North America. Further elucidation of the perceived strengths and weakness of the LI-RADS algorithm, as it pertains to various geographic regions, will continue to inform a future system that may be more readily adopted globally. Therefore, the aim of this article is to summarize HCC risk factors and imaging guidelines in select geographically disparate regions, and to solicit feedback from liver imaging experts on the limitations and barriers to adoption of LI-RADS algorithms in their patient populations.

The management of hepatocellular carcinoma (HCC) with high tumor burden and major portal vein tumor thrombosis (PVTT) remains a great challenge. The authors aimed to investigate the efficacy and safety of lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, fluorouracil and leucovorin (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for HCC greater than 7.0 cm accompanied with major PVTT.

This multicenter retrospective cohort study evaluated consecutive patients with HCC (> 7.0 cm) and major PVTT who received Len+DEB-TACE+HAIC (Len+DEB-TACE+HAIC group) or Len+DEB-TACE (Len+DEB-TACE group) between July 2019 and June 2021 from eight institutions in China. Objective response rate (ORR), time to progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were compared between the two groups by propensity score matching (PSM).

A total of 205 patients were included. After PSM, 85-paired patients remained in the study cohorts. Patients in the Len+DEB-TACE+HAIC group had higher ORR (61.2% vs. 34.1%, P < 0.001), longer TTP (median, 9.8 vs. 5.9 months, P < 0.001), and prolonged OS (median, 16.7 vs. 12.5 months, P < 0.001) than those in the Len+DEB-TACE group. The ORR and TTP of both intrahepatic tumor (ORR: 64.7% vs. 36.5%, P < 0.001; median TTP: 10.7 vs. 7.0 months, P < 0.001) and PVTT (ORR: 74.1% vs. 47.1%, P < 0.001; median TTP: 17.4 vs. 7.6 months, P < 0.001) were better in the Len+DEB-TACE+HAIC group than the Len+DEB-TACE group. The frequency of grade 3-4 TRAEs in the Len+DEB-TACE+HAIC group were comparable to those in the Len+DEB-TACE group (38.8% vs. 34.1%, P = 0.524).

The addition of HAIC to Len+DEB-TACE significantly improved ORR, TTP, and OS over Len+DEB-TACE with an acceptable safety profile for large HCC with major PVTT.

This study aimed at ascertaining the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with donafenib versus HAIC alone in the treatment of unresectable hepatocellular carcinoma (HCC).

Seventy HCC patients were enrolled for our study, and they were randomized by simple randomization using computer-generated random numbers into two groups: control group and observation group. Regular follow-up reviews were conducted to assess the efficacy of treatments. The levels of apoptotic factors, the levels of hepatic fibrosis indices, the levels of serum tumor vascular factors and tumor markers, and the occurrence of adverse reactions in the two groups were recorded and compared.

Disease control rate, objective response rate, and progression-free survival (PFS) of patients in the observation group were higher in contrast to the control group. After 12 weeks of treatment, lower mRNA expression of c-mesenchymal-epithelial transition factor, telomerase, and Fas Ligand and higher mRNA expression of Fas and Caspase-3 were observed in HCC tissues of the observation group versus the control group (p < 0.05); lower detection values of serum laminin, hyaluronic acid, collage type IV, vascular endothelial growth factor receptor 2, and alpha-fetal protein (AFP) were noted in HCC patients of the observation group in comparison to the control group (p < 0.05); there was no difference in the incidence of adverse reactions between the two groups.

Donafenib combined with HAIC in the treatment of unresectable HCC patients can notably reduce serum AFP levels, improve hepatic fibrosis, enhance short-term efficacy, prolong PFS, and have a favorable safety profile.

We report a case of patient with Stage IIIa Hepatocellular Carcinoma Complicated by Early Gastric Cancer. Although Stage IIIa liver cancer can be treated with surgery, the overall prognosis of surgery is not ideal. Alternatively, conversion therapy is reported with different effectiveness towards stage IIIa liver cancer. Herein, this study shared the successful conversion of a patient with stage IIIa liver cancer and with early gastric cancer at Lanzhou University First Hospital, which is hoped to engage clinicians in evaluation and discussion.

Liver cancer stem cells (LCSCs) are thought to drive the metastasis and recurrence, however, the heterogeneity of molecular markers of LCSCs has hindered the development of effective methods to isolate them.

This study introduced an effective approach to isolate and culture LCSCs from human primary liver cancer (HPLC), leveraging mouse embryonic fibroblasts (MEFs) as feeder cells in conjunction with using defined medium. Isolated LCSCs were further characterized by multiple approaches. Transcriptome sequencing data analysis was conducted to identify highly expressed genes in LCSCs and classify different subtypes of liver cancers.

Total sixteen cell strains were directly isolated from 24 tissues of three types of HPLC without sorting, seven of which could be maintained long-term culture as colony growth on MEFs, which is unique characteristics of stem cells. Even 10 of cloned cells formed the tumors in immunodeficient mice, indicating that those cloned cells were tumorgenic. The histologies and gene expression pattern of human xenografts were very similar to those of HPLC where these cloned cells were isolated. Moreover, putative markers of LCSCs were further verified to all express in cloned cells, confirming that these cells were LCSCs. These cloned LCSCs could be cryopreserved, and still maintained the feature of colony growth on MEFs after the recovery. Compared to suspension culture as conventional approach to culture LCSCs, our approach much better maintained stemness of LCSCs for a long time. To date, these cloned cells could be cultured on MEFs over 12 passages. Moreover, bioinformatics analysis of sequencing data revealed the gene expression profiles in LCSCs, and liver cancers were classified into two subtypes C1 and C2 based on genes associated with the prognosis of LCSCs. Patients of the C2 subtype, which is closely related to the extracellular matrix, were found to be sensitive to treatments such as Cisplatin, Axitinib, JAK1 inhibitors, WNT-c59, Sorafenib, and RO-3306.

In summary, this effective approach offers new insights into the molecular landscape of human liver cancers, and the identification of the C2 subtype and its unique response to the treatment pave the way for the creation of more effective, personalized therapeutic strategies.

This randomized, prospective, multicenter (12 centers in China) phase III trial (Chinese Clinical Trial Registry #ChiCTR2000041170) compared drug-eluting bead transarterial chemoembolization (DEB-TACE) combined with apatinib and DEB-TACE monotherapy for patients with unresectable hepatocellular carcinoma (uHCC). Progression-free survival (PFS) was the primary endpoint. Overall survival (OS), mRECIST-based objective response rates (ORR) and disease control rates (DCR), and treatment-related adverse events (TRAEs) were secondary endpoints. Totally 243 cases were randomized, with 122 and 121 in the DEB-TACE + apatinib and DEB-TACE groups, respectively. Cases administered DEB-TACE + apatinib displayed markedly improved median PFS (7.1 months [95%CI 6.6-8.3] vs. 5.2 months [95%CI 5.0-5.9]) and OS (23.3 months [95%CI 20.7-29.6] vs. 18.9 months [95%CI 17.9-20.1] compared with those treated with DEB-TACE (both p < 0.001). Additionally, patients administered DEB-TACE + apatinib had elevated ORR (56.6% vs. 38.8%) and DCR (89.3% vs. 80.2%) versus the DEB-TACE group (both p < 0.001). Majority of TRAEs were mild and manageable. Regarding DEB-TACE-related TRAEs, the rates of hepatic artery thinning and spasms were elevated during the second DEB-TACE in cases administered DEB-TACE + apatinib vs. DEB-TACE. The commonest apatinib-related TRAEs in the DEB-TACE + apatinib group included hypertension, hand-foot syndrome, fatigue, and diarrhea. In conclusion, DEB-TACE plus apatinib demonstrates superior PFS versus DEB-TACE monotherapy in uHCC cases, maintaining a favorable safety profile with similar occurrences of AEs.

In China, transarterial chemoembolization (TACE) and systemic therapy are the primary treatment for patients with advanced hepatocellular carcinoma (HCC). Hepatic arterial infusion chemotherapy (HAIC) is more effective than TACE in treating large HCC (largest diameter ≥7 cm) without macrovascular invasion or extrahepatic spread. Additionally, HAIC in combination with camrelizumab and apatinib has shown promising efficacy and safety in the Barcelona Clinic Liver Cancer stage C (BCLC-C) HCC. The efficacy and safety of the modality of HAIC followed by TACE combined with camrelizumab and apatinib for the treatment of large HCC remains unknown. We present the first case of long-term survival after short-course HAIC followed by TACE combined with camrelizumab and apatinib in large HCC.

In April 2020, a 50-year-old Chinese woman was diagnosed with BCLC-C HCC. Magnetic resonance imaging (MRI) showed intrahepatic lesions involving the right and left lobes, with a total lesion size of 19 cm × 9 cm. After 3 cycles of HAIC with oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) plus camrelizumab and apatinib, followed by 2 cycles of TACE plus camrelizumab and apatinib, the efficacy was evaluated as a partial response (PR), with a total lesion size of 6.7 cm × 4.6 cm. The patient continued to take apatinib orally for 1.5 months after the last cycle of TACE but discontinued any antitumor therapy for financial reasons. Subsequent imaging consultation showed an efficacy evaluation of complete response (CR) per the modified Response Evaluation Criteria in Solid Tumors (mRECIST). The patient did not experience any serious adverse events during treatment. As of September 2024, the patient's progression-free survival (PFS) has reached 53 months.

The treatment modality of short-course HAIC followed by TACE combined with camrelizumab and apatinib for large HCC is safe and effective, and long-term survival may be expected in patients who achieve a CR.

Hepatocellular carcinoma (HCC) is currently one of the most common malignant tumors with the highest mortality rates in the world. Most patients with HCC have lost the opportunity for surgery at the time of initial diagnosis. This study aims to introduce a new conversion strategy: trans-arterial chemo-emobilization (TACE) combined with laparoscopic portal vein ligation (PVL) and terminal branches portal vein embolization (PVE).

From November 2018 to February 2023, patients with HCC and insufficient future liver remnant (FLR) were included for this novel treatment strategy. At first, TACE was performed. Then, these patients underwent laparoscopic PVL and terminal branches PVE. After hypertrophy of FLR, these patients underwent the second stage of liver resection. All patients were followed up regularly postoperatively.

A total of 13 patients with HCC were included. All patients underwent the TACE and the first stage of laparoscopic PVL and terminal branches PVE. After a mean of 28.7 days after the first stage of operation, the FLR increased by a mean of 183.4 cm3, equivalent to 49%. All patients underwent the second stage of liver resection. There was no surgical mortality. The mean postoperative hospital stay was 9.1 days. The median survival was 24.5 months.

The treatment strategy of preoperative TACE combined with laparoscopic PVL and terminal branches PVE and second stage of liver resection is a preliminarily feasible and relatively safe new strategy which deserves further exploration in the future.

Reliable differentiation of uveal melanoma and choroidal nevi is crucial to guide appropriate treatment, preventing unnecessary procedures for benign lesions and ensuring timely treatment for potentially malignant cases. The purpose of this study is to validate deep learning classification of uveal melanoma and choroidal nevi, and to evaluate the effect of colour fusion options on the classification performance.

A total of 798 ultra-widefield retinal images of 438 patients were included in this retrospective study, comprising 157 patients diagnosed with UM and 281 patients diagnosed with choroidal naevus. Colour fusion options, including early fusion, intermediate fusion and late fusion, were tested for deep learning image classification with a convolutional neural network (CNN). F1-score, accuracy and the area under the curve (AUC) of a receiver operating characteristic (ROC) were used to evaluate the classification performance.

Colour fusion options were observed to affect the deep learning performance significantly. For single-colour learning, the red colour image was observed to have superior performance compared to green and blue channels. For multi-colour learning, the intermediate fusion is better than early and late fusion options.

Deep learning is a promising approach for automated classification of uveal melanoma and choroidal nevi. Colour fusion options can significantly affect the classification performance.

To identify the risk factors and construct a predictive model for early recurrence of hepatitis B virus(HBV-)- related hepatocellular carcinomas(HCCs) after radical resection.

A total of 465 HBV-related HCC patients underwent radical resections between January 1, 2012 and August 31, 2018.Their data were collected through the inpatient information management system of the First Affiliated Hospital of University of Science and Technology of China. Survival and subgroup analyses of early recurrence among male and female patients were performed using Kaplan-Meier curves. The independent risk factors associated with early postoperative tumor recurrence were analyzed using multivariate Cox proportional hazards regression model. Based on these independent risk factors, a risk function model for early recurrence was fitted, and a column chart for the prediction model was drawn for internal and external validation.

A total of 181 patients developed early recurrences, including 156 males and 25 females. There was no difference in the early recurrence rates between males and females. Tumor diameters>5cm, microvascular invasion and albumin level<35 g/L were independent risk factors for early recurrence. A nomogram for the early recurrence prediction model was drawn; the areas under the curve for the model and for external verification were 0.638 and 0.655, respectively.

Tumor diameter>5 cm, microvascular invasion, and albumin level<35 g/L were independent risk factors for early recurrence. The prediction model based on three clinical indicators could predict early recurrence, with good discrimination, calibration, and extrapolation.

The advances in deep learning-based pathological image analysis have invoked tremendous insights into cancer prognostication. Still, lack of interpretability remains a significant barrier to clinical application.

We established an integrative prognostic neural network for intrahepatic cholangiocarcinoma (iCCA), towards a comprehensive evaluation of both architectural and fine-grained information from whole-slide images. Then, leveraging on multi-modal data, we conducted extensive interrogative approaches to the models, to extract and visualize the morphological features that most correlated with clinical outcome and underlying molecular alterations.

The models were developed and optimized on 373 iCCA patients from our center and demonstrated consistent accuracy and robustness on both internal (n = 213) and external (n = 168) cohorts. The occlusion sensitivity map revealed that the distribution of tertiary lymphoid structures, the geometric traits of the invasive margin, the relative composition of tumor parenchyma and stroma, the extent of necrosis, the presence of the disseminated foci, and the tumor-adjacent micro-vessels were the determining architectural features that impacted on prognosis. Quantifiable morphological vector extracted by CellProfiler demonstrated that tumor nuclei from high-risk patients exhibited significant larger size, more distorted shape, with less prominent nuclear envelope and textural contrast. The multi-omics data (n = 187) further revealed key molecular alterations left morphological imprints that could be attended by the network, including glycolysis, hypoxia, apical junction, mTORC1 signaling, and immune infiltration.

We proposed an interpretable deep-learning framework to gain insights into the biological behavior of iCCA. Most of the significant morphological prognosticators perceived by the network are comprehensible to human minds.

Coptisine (COP) has been shown to exhibit a wide range of anticancer properties, including in hepatocellular carcinoma (HCC). Nevertheless, the precise mechanism of COP in the treatment of HCC remains elusive. This study aims to investigate the potential mechanism of action of COP against HCC. By evaluating the anti-HCC activity of COP in different HCC cells lines and in xenografted nude mice, it was found that COP inhibited HCC in vitro and in vivo. Through RNA-Seq analysis, E2F7 was identified as a potential target of COP against HCC, as well as the cell cycle as a possible pathway. The overexpression of E2F7 and the inhibition of CHK1 demonstrated that COP inhibits the activity of HCC and induces G2/M phase arrest of HCC cells by down-regulating E2F7 and influencing the CHK1/CDC25A pathway. Finally, the promoter fragmentation experiments and chromatin immunoprecipitation revealed that COP down-regulated E2F7 by inhibiting the E2F4/NFYA/NFYB transcription factors. In conclusion, our study demonstrated that COP downregulates E2F7 by affecting key transcription factors, thereby inducing cell cycle arrest and inhibits HCC cell growth. This provides further evidence of the efficacy of COP in the treatment of tumors.

The metastatic vascular patterns of hepatocellular carcinoma (HCC) are mainly microvascular invasion (MVI) and vessels encapsulating tumor clusters (VETC). However, most existing VETC-related radiological studies still focus on the prediction of VETC status.

This study aimed to build and compare VETC-MVI related models (clinical, radiomics, and deep learning) associated with recurrence-free survival of HCC patients.

Retrospective.

398 HCC patients (349 male, 49 female; median age 51.7 years, and age range: 22-80 years) who underwent resection from five hospitals in China. The patients were randomly divided into training cohort (n = 358) and test cohort (n = 40).

3-T, pre-contrast T1-weighted imaging spoiled gradient recalled echo (T1WI SPGR), T2-weighted imaging fast spin echo (T2WI FSE), and contrast enhanced arterial phase (AP), delay phase (DP).

Two radiologists performed the segmentation of HCC on T1WI, T2WI, AP, and DP images, from which radiomic features were extracted. The RFS related clinical characteristics (VETC, MVI, Barcelona stage, tumor maximum diameter, and alpha fetoprotein) and radiomic features were used to build the clinical model, clinical-radiomic (CR) nomogram, deep learning model. The follow-up process was done 1 month after resection, and every 3 months subsequently. The RFS was defined as the date of resection to the date of recurrence confirmed by radiology or the last follow-up. Patients were followed up until December 31, 2022.

Univariate COX regression, least absolute shrinkage and selection operator (LASSO), Kaplan-Meier curves, log-rank test, C-index, and area under the curve (AUC). P < 0.05 was considered statistically significant.

The C-index of deep learning model achieved 0.830 in test cohort compared with CR nomogram (0.731), radiomic signature (0.707), and clinical model (0.702). The average RFS of the overall patients was 26.77 months (range 1-80 months).

MR deep learning model based on VETC and MVI provides a potential tool for survival assessment.

3 TECHNICAL EFFICACY: Stage 3.

Postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) can achieve longer overall survival (OS) and disease-free survival (DFS) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). We investigated whether this treatment strategy could benefit these patients by mediating the dysfunctional immunological status. Therefore, a retrospective cohort study was conducted to investigate the effect of early PA-TACE in HCC patients with MVI by measuring the levels of T helper cell 17 (Th17) and regulatory T cell (Treg).

This study retrospectively included 472 patients with HCC undergoing hepatectomy between December 2015 and December 2018, and 115 patients with MVI confirmed by postoperative pathology were enrolled and divided into two groups of TACE group and non-TACE group according to whether TACE was performed. HCC patients with MVI. The proportion of Treg and Th17 cells in peripheral blood was measured one day before and four weeks after TACE. All patients in the two groups were followed up until death or until the study ended in December 2023. The rates of OS and progression-free survival (PFS) in patients with MVI were compared between those who received hepatectomy alone and those who underwent early PA-TACE.

Among 115 HCC patients with MVI from 472 patients, the study enrolled 51 patients with PA-TACE into the TACE group and 42 patients without TACE into the non-TACE group. There were no statistical differences in baseline data between the two groups (all P>0.05). The frequency of Treg among CD4+ T cells in HCC patients with PA-TACE was significantly lower than baseline (7.34%±3.61% vs. 5.82%±2.76%, P<0.001), and the frequency of Th17 among CD4+ T cells in these patients was significantly higher than baseline (0.49%±0.28% vs. 0.50%±0.25%, P<0.001). Among all the patients, the median OS was 61.8 months. The OS rate and PFS rate at 12, 36, and 60 months in the TACE group were significantly higher than those in the non-TACE group (all P<0.05).

PA-TACE may have roles in improving survival outcomes, and restoring immune homeostasis in HCC patients with MVI after hepatectomy.

To evaluate the benefit-risk of 3 commonly used Chinese medicine injections, Aidi Injection (ADI), Cinobufagin Injection (CINI) and Compound Kushen Injection (CKI), in the treatment of primary liver cancer (PLC), so as to provide a reference for clinical decision-making.

Randomized controlled trials (RCTs) of ADI, CINI and CKI in the treatment of PLC published in the databases of China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, SinoMed, PubMed, Cochrane Library, and Web of Science were retrieved from January 2020 to October 2022. The data of benefit and risk indicators were combined to obtain the effect value. The multi-criteria decision analysis (MCDA) model was applied to build the decision tree. The benefit value, risk value and benefit risk value of the 3 injections in PLC treatment were calculated. Monte Carlo simulation was carried out to calculate the 95% confidence interval and probability of differences among the 3 injections, so as to optimize the evaluation results.

A total of 71 RCTs were included. The benefit values of ADI, CINI and CKI combined with transcatheter arterial chemoembolization (TACE) were 42, 38 and 36, respectively. The risk values were 42, 25 and 37, respectively. The benefit risk values were 42, 31 and 37, respectively. The benefit risk differences of ADI vs. CINI, ADI vs. CKI, and CKI vs. CINI were 11 (-0.86, 17.75), 5 (-5.01, 11.09), and 6 (-1.87, 12.63), respectively. The probability that ADI superior to CINI, ADI superior to CKI, and CKI superior to CINI was 96.26%, 77.27%, and 92.62%, respectively.

Based on the results of MCDA model, CINI combined with TACE has the greatest risk in the treatment of the PLC. Considering the efficacy and safety, the possible priority of the 3 Chinese medicine injections combined with TACE in the treatment of PLC is ADI, CKI and CINI.

The Albumin-Bilirubin (ALBI) score, widely used in predicting long-term prognosis for patients with hepatocellular carcinoma (HCC), has limitations due to serum albumin variability. This study aimed to develop and validate the Prealbumin-Bilirubin (preALBI) score as a reliable alternative.

A multicenter cohort of HCC patients who underwent hepatectomy was randomly divided into the training and validation cohorts. The preALBI score was developed using Cox regression models within the training cohort, incorporating serum prealbumin and bilirubin levels as crucial determinants. The survival predictive accuracy was evaluated and compared between the preALBI score with two other staging systems, including the ALBI score and the Child-Pugh grade.

A total of 2409 patients were enrolled. In the training cohort, the preALBI score demonstrated superior performance in predicting long-term survival after hepatectomy. The preALBI score was associated with the best monotonicity of gradients (linear trend χ2: 72.84) and homogeneity (likelihood ratio χ2: 74.69), and the highest discriminatory ability (the areas under curves for 1-, 3-, and 5-year mortality: 0.663, 0.654, and 0.644, respectively). In addition, the preALBI was the most informative staging system in predicting survival (Akaike information criterion: 11325.65).The results remained consistent in both training and validation cohorts, indicating its reliable performance across different populations.

The preALBI score, leveraging the stability of prealbumin, represents a promising tool for better patient stratification, providing more accurate prognostic predictions than the ALBI score and the Child-Pugh grade.

The application of Pringle maneuver (PM) during hepatectomy reduces intraoperative blood loss and the need for perioperative transfusion, but its effect on long-term recurrence and survival for patients with hepatocellular carcinoma (HCC) remains controversial. We sought to determine the association between the application of PM and post-hepatectomy oncologic outcomes for patients with HCC.

Patients who underwent curative hepatectomy for HCC at 9 Chinese hospitals from January 2010 to December 2018 were identified. Using two propensity score methods [propensity score matching (PSM) and inverse probability of treatment weight (IPTW)], cumulative recurrence rate and cancer-specific mortality (CSM) were compared between the patients in the PM and non-PM groups. Multivariate competing-risks regression models were performed to adjust for the effect of non-cancer-specific mortality and other prognostic risk factors.

Of the 2,798 included patients, 2,404 and 394 did and did not adopt PM (the PM and non-PM groups), respectively. The rates of intraoperative blood transfusion, postoperative 30-day mortality and morbidity were comparable between the two groups (all P>0.05). In the PSM cohort by the 1:3 ratio, compared to 382 patients in the non-PM group, 1,146 patients in the PM group also had the higher cumulative 5-year recurrence rate and CSM (63.9% and 39.1% vs. 55.3% and 31.6%, both P<0.05). Similar results were also yielded in the entire cohort and the IPTW cohort. Multivariate competing-risks regression analyses demonstrated that no application of the PM was independently associated with lower recurrence rate and CSM based on various analytical cohorts [hazard ratio (HR), 0.82 and 0.77 in the adjusted entire cohort, HR 0.80 and 0.73 in the PSM cohort, and HR 0.80 and 0.76 in the IPTW cohort, respectively].

The findings suggested that no application of PM during hepatectomy for patients with HCC reduced the risk of postoperative recurrence and cancer-specific death by approximately 20-25%.