Abstract Background Patients with hepatocellular carcinoma (HCC) have an unmet need for new therapies that improve survival. This phase II trial investigated the efficacy and safety of ociperlimab and tislelizumab plus BAT1706 (a bevacizumab biosimilar) in patients with first-line HCC. Methods In this phase II, multicenter, randomized, multi-arm, open-label trial, patients with advanced HCC received ociperlimab and tislelizumab plus BAT1706 (Arm A) or tislelizumab plus BAT1706 (Arm B). The primary objective was to evaluate efficacy using objective response rate (ORR) assessed by the investigator per RESIST v1.1 for Arms A and B. Results 94 patients were randomized to Arm A (N = 62) and Arm B (N = 32). Confirmed ORR (95% confidence interval) was 37.1% (25.2–50.3) for Arm A and 40.6% (23.7–59.4) for Arm B. In Arms A and B, respectively, 90.3% and 80.6% of patients experienced treatment-related treatment-emergent adverse events (TEAEs), 59.7% and 32.3% experienced Grade ≥ 3 treatment-related TEAEs and 22.6% and 9.7% experienced treatment-related TEAEs leading to treatment discontinuation. Immune-mediated adverse events were reported in 50.0% of patients in Arm A and 45.2% of patients in Arm B. Infusion-related reactions occurred in a single patient in Arm A. Conclusion In patients with advanced HCC, tislelizumab plus BAT1706 demonstrated promising ORR, while adding ociperlimab was not associated with improved efficacy. The safety profile of ociperlimab and tislelizumab plus BAT1706 was tolerable and manageable, with no new safety signals identified. Trial registration ClinicalTrials.gov: NCT04948697 (September 20, 2021).

4148 Background: Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have demonstrated efficacy in aHCC. Despite improved outcomes with PD-1/PD-L1 inhibitor-based regimens, prognosis remains poor and there is a continued unmet need for alternative therapies with long-term survival benefits. This study aimed to evaluate the effectiveness and safety of IBI310 (anti-CTLA-4 antibody) combined with sintilimab (anti-PD-1 antibody) in the first-line treatment of aHCC. Methods: Pts were randomized in a 2:1 ratio to IBI310+sintilimab group or sorafenib group. The experimental group received IBI310 3mg/kg intravenously (IV) and sintilimab 200 mg IV on day 1 of every 3 weeks. The control group received sorafenib 400 mg orally twice daily (BID) continuously until disease progression, intolerable toxicity, death or other protocol-specified discontinuation criteria. During the study, the IBI310 dose was adjusted to 1 mg/kg every 6 weeks. Primary end points included overall survival (OS) and objective response rate (ORR)assessed by the independent radiology review committee (IRRC) per RECIST v1.1. Secondary endpoint included progression-free survival (PFS), disease control rate (DCR), safety, etc. Results: As of August 2022, 344 patients were enrolled and allocated to Group 1 (G1, IBI310 3mg/kg + sintilimab, n=84), Group 2 (G2, modified-dose IBI310 1mg/kg + sintilimab, n=145) and Group 3 (G3, sorafenib, n=115). Overall, PFS and ORR improved with IBI310+sintilimab vs Sorafenib. The median OS in the primary endpoint was 44.0 months(G1), 36.1 months(G2) and 22.9 months(G3), respectively. Confirmed ORRs were significantly higher in the combination therapy groups (G1: 41.7%; G2: 22.1%) versus the control group (2.6%). Median PFS of three groups were 13.5 months(G1), 6.1 months(G2) and 2.8 months(G3), respectively. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 60.7% (G1), 34.7% (G2), and 35.1% (G3) of patients. Conclusions: Compared with sorafenib group, combination treatment of IBI310 + sintilimab as first-line treatment demonstrated survival benefits and a manageable safety profile in aHCC. Clinical trial information: NCT04720716 . Survival data. IBI310(3mg/kg)+Sintilimab(N=84) IBI310(1mg/kg)+Sintilimab(N=145) Sorafenib(N=115) mOS, m 44.0 36.1 22.9 Confirmed ORR, n(%) 35(41.7) 32(22.1) 3(2.6) mPFS, m 13.5 6.1 2.8

Background: A significant portion of primary liver cancer patients in China are diagnosed at intermediate-to-advanced stages, often making them ineligible for curative surgery. Furthermore, high postoperative recurrence rates, reaching up to 70%, pose a major challenge for long-term survival. The emergence of novel systemic treatments, such as immune checkpoint inhibitor combinations, and advancements in locoregional therapies have created new opportunities for conversion and perioperative strategies. This updated consensus aims to standardize the clinical application of these therapies based on the latest evidence, with the objective of improving patient prognosis. Methods: A multidisciplinary committee of 97 experts was convened to revise previous guidelines. The process involved a comprehensive search of medical databases and conference proceedings, with evidence graded according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Consensus statements were finalized through a formal electronic voting process, requiring at least 80% agreement for approval, resulting in 18 updated statements. Results: The consensus provides refined definitions for conversion and perioperative therapy. It recommends various strategies for oncological conversion, including systemic therapy with anti-angiogenic drugs plus immunotherapy, and locoregional approaches like precision transarterial chemoembolization (TACE) and hepatic artery infusion chemotherapy (HAIC). The document strongly affirms surgical resection as a crucial step for achieving long-term survival after successful conversion and offers guidance on surgical timing and adjuvant therapy. For resectable patients with high-risk features, neoadjuvant and adjuvant treatments are outlined to mitigate recurrence. The consensus also advocates for using dynamic enhanced magnetic resonance imaging ( MRI) and the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria for efficacy assessment and underscores the essential role of a multidisciplinary team in management. Conclusions: This updated consensus offers standardized, evidence-based guidance for clinicians on implementing conversion and perioperative strategies to optimize patient-centered care and highlights the need for continued research to further refine these promising approaches.

Hepatocellular carcinoma (HCC), which accounts for approximately 75–85% of primary liver cancers, ranks 4th in newly diagnosed cases among various types of cancer in China, and is the 2nd leading cause of cancer-related mortality, thereby posing a significant threat to the life and health of the Chinese population. Since the publication of the “Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China” in June 2017, which were updated by the China’s National Health Commission in December 2019 and December 2021, additional high-quality evidence from researchers worldwide regarding the diagnosis, staging, and treatment of HCC has emerged, necessitating another update to the guidelines. The new edition (2024 Edition) was written by more than 120 multidisciplinary experts in the field of HCC in China, which not only reflects the real-world situation in China but also may reshape the nationwide diagnosis and treatment of HCC. The new guideline aims to encourage the implementation of evidence-based practice and improve the national average 5-year survival rate for patients with HCC, as proposed in the “Healthy China 2030: A Vision for Health Care.”

4093 Background: Combination of an anti-PD-1/L1 antibody with an anti-angiogenic agent is currently the preferred 1L treatment for aHCC. Addition of a CTLA-4 inhibitor may further improve anti-tumor activity, with complementary immunostimulatory effects from CTLA-4 and PD-1/L1 blockade. We conducted a multicenter, open-label, phase 1b/2 trial (NCT05444088) to assess SHR-8068, a novel anti-CTLA-4 monoclonal antibody (mAb), combined with adebrelimab (A, anti-PD-L1 mAb) and bevacizumab (B) in patients (pts) with aHCC. Methods: Pts with or without prior treatment were enrolled (phase 1b: failed or refused standard therapy; phase 2: ≤1L systemic therapy, no immunotherapy [IO]). SHR-8068 was evaluated in 2 dosing regimens with AB: 1 mg/kg Q6W (Combo 1) or 4 mg/kg priming dose (Combo 2). An additional cohort evaluated AB alone (Combo 3). A was dosed at 20 mg/kg Q3W and B at 15 mg/kg Q3W for all regimens. Results: As of Oct 31, 2024, a total of 27, 53 and 21 pts received Combo 1, 2, and 3, respectively, across 2 study phases (overall: IO naïve, 97.0%; prior anti-angiogenic therapy, 32.7%); median follow-up was 16.7, 11.1 and 11.3 mo, respectively. In pts treated with Combo 2, the objective response rate (ORR) was 47.2% (25/53; 95% CI 33.3%–61.4%), with a median duration of response (DoR) of 12.7 mo (95% CI 5.8–NR). The median progression-free survival (PFS) was 8.7 mo (95% CI 5.5–11.6); median overall survival (OS) was not reached, with a 12-mo OS rate of 76.0% (95% CI 59.3%–86.6%). Numerically improved ORR and survival outcomes were seen with Combo 2 vs Combo 1 and 3 (Table 1). Overall, grade ≥3 treatment-related adverse events (TRAEs) occurred in 55.6%, 41.5% and 42.9% of pts with Combo 1, 2 and 3. The most common grade ≥3 TRAEs (incidence ≥10% for any Combo) were decreased platelet count (22.2%, 5.7%, and 4.8% for Combo 1, 2, and 3) and hypertension (18.5%, 7.5%, and 9.5%, respectively). TRAE led to discontinuation of any study agent in 11.1%, 1.9% and 9.5% of pts, respectively. There was 1 treatment-related death (Combo 3). Conclusions: SHR-8068 combined with adebrelimab and bevacizumab showed promising efficacy and manageable safety in aHCC. A more favorable benefit-risk profile was observed for SHR-8068 given as a priming dose. A phase 3 trial (NCT06618664) is currently underway to further assess the combination as 1L treatment for aHCC. Clinical trial information: NCT05444088 . Efficacy outcomes. Combo 1 (n=27) Combo 2 (n=53) Combo 3 (n=21) ORR, % (95% CI) 29.6 (13.8–50.2) 47.2 (33.3–61.4) 19.0 (5.5–41.9) Median DoR * , mo (95% CI) NR (9.4–NR) 12.7 (5.8–NR) NR (7.0–NR) 9-mo DoR rate * , % (95% CI) 100.0 (NR–NR) 69.8 (41.7–86.3) 66.7 (5.4–94.5) DCR, % (95% CI) 77.8 (57.7–91.4) 77.4 (63.8–87.7) 81.0 (58.1–94.6) Median PFS * , mo (95% CI) 6.9 (2.7–NR) 8.7 (5.5–11.6) 6.7 (2.8–9.5) 12-mo OS rate * , % (95% CI) 70.4 (49.4–83.9) 76.0 (59.3–86.6) 70.8 (46.2–85.7) Tumor response was assessed by investigator per RECIST v1.1. * Kaplan-Meier method. NR, not reached.

ABSTRACT Background Hepatocellular carcinoma (HCC) is the second leading cause of cancer‐related death in China. The rapid progress in systemic therapies has led to the approval of many therapeutic methods that have quickly changed clinical guidelines and practices. Because of the high heterogeneity of HCC, there are still some gaps between the guidelines and real‐world clinical practice. The present study surveyed experts in China to investigate the current treatment concepts and clinical practice regarding HCC. Methods A questionnaire survey on the treatment concepts and clinical practice of HCC was administered to 310 experts with senior professional titles in 2020 and 312 experts in 2021. The results were analyzed and compared. Results For treating patients with resectable HCC, 28% of hepatobiliary surgeons indicated neoadjuvant therapy, and 7% chose systemic therapy ± locoregional therapy as 1 L therapy in 2021 compared with 20% and 1% in 2020. More experts chose adjuvant treatment within 1 month in 2021 compared with 2020, and 6 months and 12 months were the leading choices for the duration of adjuvant treatment. In 2021, 79% of surgeons and 19% of interventionalists were willing to conduct downstaging/conversion therapy for patients with potentially resectable HCC, and 78% chose tyrosine kinase inhibitors (TKI) + immunotherapy (IO) + locoregional therapy for cases in which R0 resection could not be achieved. For completely unresectable HCC, more experts preferred TKI + IO‐based therapy as 1 L therapy in 2021 compared with 2020 (78% vs. 55%). The proportion of experts who indicated TKI + IO‐based therapy as 2 L therapy increased from 32% in 2020 to 40% in 2021. Conclusion The survey results indicated that in 2021, compared with 2020, more experts opted to administer IO + TKI for the treatment of liver cancer, and more experts and patients were willing to participate in clinical research.

Background: We aimed to evaluate ability of a novel scoring system that combines fluorodeoxyglucose-uptake parameters and systemic inflammatory response indicators to predict hepatocellular carcinoma (HCC) prognosis. Methods: Clinical data were collected from patients with HCC who underwent hepatectomy at our hospital in 2014-2022. The tumor-to-liver ratio (TLR) was adopted as a positron emission tomography/computed tomography (PET/CT) standardized uptake value (SUV)-related indicator and calculated as the ratio of the SUVmax of tumor tissue to the SUVmean of normal liver tissue. The patients' immune microenvironment reflected the NLR. Postoperative overall survival (OS)- and disease-free survival (DFS)-related independent prognostic factors were analyzed using Cox proportional hazards regression modeling. Results: Eighty-nine patients were included. TLR, NLR, and alpha-fetoprotein levels were independently associated with OS and DFS. The OS and DFS in the zero-point group were significantly longer than those in the one- and two-point groups. Time-dependent ROC curve analyses revealed area under the curve values of 0.830 and 0.752 for 5-year OS and DFS, respectively, for the scoring system, outperforming single evaluation indices. Conclusions: The proposed scoring system, which incorporates both TLR and NLR, simultaneously reflects metabolic tumor characteristics and the host's immune microenvironment, enabling more accurate patients with early to intermediate-stage HCC undergoing hepatectomy classification and better prognostic evaluation.

PURPOSE:This study aimed to develop and validate a novel prognostic index, the Weighted Alpha-Fetoprotein Tumor Burden Score (WATS), for predicting outcomes in hepatocellular carcinoma (HCC) patients undergoing resection. MATERIALS AND METHODS:A total of 772 resected HCC patients were included. WATS was developed and validated using an 8:2 cohort split. The score was derived from multivariate Cox regression, resulting in the formula: WATS = 0.73 × tumor number +0.17 × tumor size +0.1 × ln AFP. The time-dependent ROC curve assessed the score's predictive ability, while restricted cubic splines evaluated the dose-response relationship between WATS and prognostic outcomes. Kaplan-Meier curves and multivariate Cox regression further validated the prognostic accuracy. RESULTS:In the training cohort, AUCs for progression-free survival (PFS) at 1, 2, 3, 4, and 5 years were 0.683, 0.664, 0.661, 0.633, and 0.620, respectively; for overall survival (OS), they were 0.757, 0.732, 0.703, 0.672, and 0.670, respectively. In the validation cohort, AUCs for PFS were 0.711, 0.654, 0.671, 0.662, and 0.684, respectively; for OS, they were 0.724, 0.688, 0.642, 0.698, and 0.721, respectively. WATS outperformed other complex indicators and staging systems. RCS analysis showed a linear relationship between WATS and outcomes. The nomogram based on WATS demonstrated excellent discrimination, calibration, and clinical benefit. CONCLUSION:WATS is a novel, reliable prognostic tool for HCC post-resection, offering enhanced patient stratification and risk assessment, thereby improving clinical management.

Hepatocellular carcinoma (HCC) stands as one of the most malignant tumors characterized by poor prognosis and high mortality rates. Emerging evidence underscores the crucial role of the B7 protein family in various cancers, including HCC. However, the involvement of the human endogenous retrovirus H long-terminal repeat-associated protein 2 (HHLA2, or B7-H5) in HCC remains unclear. Immunohistochemistry was employed to assess the differential expression of HHLA2 between HCC and normal liver tissues. A battery of assays, including CCK8, EdU, tablet clone-forming, Transwell, and wound healing assays, were conducted to elucidate the function and potential mechanisms of HHLA2 in the malignant biological behaviors of HCC. Additionally, a xenograft mouse model was established to evaluate the tumorigenicity of hepatoma cell lines exhibiting different HHLA2 expression levels in vivo. Western blot analysis was used to analyze HHLA2, secretory phosphoprotein 1 (SPP1), and PI3K/AKT/mTOR levels. HHLA2 exhibited elevated expression in HCC tissues, correlating with poor tumor differentiation and shortened overall survival in HCC patients. In vitro experiments demonstrated that HHLA2 overexpression (OE) promoted the proliferation, migration, and invasion of hepatoma cells, while in vivo experiments revealed that HHLA2 OE enhanced HCC tumor growth. Conversely, inhibition of HHLA2 expression yielded the opposite effect. Downregulation of SPP1 inhibited the proliferation, migration, and invasion induced by HHLA2 OE, and this effect was linked to the PI3K/AKT/mTOR signaling pathway. Our findings indicate that HHLA2 promotes the proliferation, migration, and invasion of hepatoma cells via the SPP1/PI3K/AKT signaling pathway, establishing it as a potential therapeutic target for HCC.

Background: Three-dimensional reconstruction visualization technology (3D-RVT) is an important tool in the preoperative assessment of patients undergoing liver resection. However, it is not clear whether this technique can improve short-term and long-term outcomes in patients with hepatocellular carcinoma (HCC) compared with two-dimensional (2D) imaging. Method: A total of 3402 patients from five centers were consecutively enrolled from January 2016 to December 2020, and grouped based on the use of 3D-RVT or 2D imaging for preoperative assessment. Baseline characteristics were balanced using propensity score matching (PSM, 1:1) and stabilized inverse probability of treatment-weighting (IPTW) to reduce potential selection bias. The perioperative outcomes, long-term overall survival (OS), and recurrence-free survival (RFS) were compared between the two groups. Cox-regression analysis was used to identify the risk factors associated with RFS. Results: A total of 1681 patients underwent 3D-RVT assessment before hepatectomy (3D group), while 1721 patients used 2D assessment (2D group). The PSM cohort included 892 patient pairs. In the IPTW cohort, there were 1608.3 patients in the 3D group and 1777.9 patients in the 2D group. In both cohorts, the 3D group had shorter operation times, lower morbidity and liver failure rates, as well as shorter postoperative hospital stays. The 3D group had more margins >= 10 mm and better RFS than the 2D group. The presence of tumors with a diameter >= 5 cm, intraoperative blood transfusion and multiple tumors were identified as independent risk factors for RFS, while 3D assessment and anatomical resection were independent protective factors. Conclusion: In this multicenter study, perioperative outcomes and RFS of HCC patients following 3D-RVT assessment were significantly different from those following 2D imaging assessment. Thus, 3D-RVT may be a feasible alternative assessment method before hepatectomy for these patients.

PurposeThis study aims to compare the prognostic outcome of resection (RES) and microwave ablation (MWA) in different tumor burden score (TBS) cohorts.Patients and MethodsWe retrospectively analyzed 479 patients with primary hepatocellular carcinoma (HCC) who underwent RES (n = 329) or MWA (n = 150) with curative intent at our institution. We assessed their overall survival (OS) and progression-free survival (PFS) using the Kaplan–Meier curve. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to minimize selection and confounding biases. Multivariate Cox regression was used to define the association between surgical modalities and outcomes.ResultsFollowing PSM, in the TBS ≤3 cohort, the cumulative 1-, 3-, 5- year OS in the RES and MWA groups were 92.5% vs. 98.8%, 82.7% vs. 90.0%, and 82.7% vs. 83.2% (P = 0.366), respectively. The corresponding PFS rates in the RES and MWA groups were 82.7% vs. 88.0%, 63.6% vs. 68.3% and 55.2% vs. 56.3, respectively (P = 0.218). In the TBS >3 cohort, the cumulative 1-, 3-, 5- year OS between the RES and MWA groups were 92.5% vs. 95.0%, 82.8% vs. 73.2% and 76.3% vs. 55.1%, (P = 0.034), respectively. The corresponding PFS rates in the RES and MWA groups were 78.0% vs. 67.5%, 63.6% vs. 37.5% and 55.2% vs. 37.1%, respectively (P = 0.044). The IPTW analysis showed similar results as shown in PSM analysis. The multivariate Cox regression indicated that the type of surgical modality was not associated with a poorer prognostic outcome in the TBS ≤3 cohort, unlike in the TBS >3 cohort.ConclusionTBS, as a discriminator, might help guide treatment decision-making for HCC within the Milan criteria.

Up to half of hepatocellular carcinoma (HCC) cases are diagnosed at an advanced stage, for which effective treatment options are lacking, resulting in a poor prognosis. Over the past few years, the combination of immune checkpoint inhibitors and anti-angiogenic targeted therapy has proven highly efficacious in treating advanced HCC, significantly extending patients' survival and providing a potential for sequential curative surgery. After sequential curative hepatectomy or liver transplantation following conversion therapy, patients can receive long-term survival benefits. In order to improve the long-term survival rate of the overall population with liver cancer and achieve the goal of a 15% increase in the overall 5-year survival rate outlined in the Healthy China 2030 blueprint, the Professional Committee for Prevention and Control of Hepatobiliary and Pancreatic Diseases of Chinese Preventive Medicine Association, Chinese Society of Liver Cancer, and the Liver Study Group of Surgery Committee of Beijing Medical Association organized in-depth discussions among relevant domestic experts in the field. These discussions focused on the latest progress since the release of the Chinese expert consensus on conversion therapy of immune checkpoint inhibitors combined antiangiogenic targeted drugs for advanced hepatocellular carcinoma (2021 Edition) and resulted in a new consensus on the modifications and supplements to related key points. This consensus aims to further guide clinical practice, standardize medical care, and promote the development of the discipline.

Background and ObjectivesHepatocellular carcinoma (HCC) is a major global health concern, and emerging evidence suggests that TIGIT and NKG2A are potential immune checkpoints with implications for HCC progression. This study aimed to evaluate the prognostic significance of TIGIT and NKG2A expression in HCC patients who underwent radical liver resection.MethodsWe conducted a retrospective analysis of 144 HCC patients who underwent radical liver resection. TIGIT and NKG2A expression levels were assessed using the immunoreactive score. Cox proportional hazards models were utilized to analyze the association between TIGIT/NKG2A expression and clinical characteristics, relapse-free survival (RFS), and overall survival (OS). Prognostic models for OS and RFS was developed and validated using concordance index and calibration curves. Additionally, the random forest algorithm was employed to identify independent risk factors for OS and RFS and their correlation with predicted survival.ResultsTIGIT and NKG2A expression were identified as independent risk factors for RFS, while TIGIT expression alone significantly impacted OS. The prognostic models showed good discriminative ability, with concordance indices exceeding 0.7 for predicting 1-, 3-, and 5-year OS or RFS. Calibration curves confirmed the reliability of the nomograms for OS and RFS prediction. The areas under the ROC curve consistently exceeded 0.7 for predicting OS and RFS. Elevated levels of TIGIT and NKG2A expression were associated with diminished RFS, highlighting their importance as prognostic factors.ConclusionsOur study establishes the prognostic significance of TIGIT and NKG2A expression in predicting OS and RFS following radical liver resection for HCC patients. The developed prognostic models incorporating TIGIT and NKG2A expression hold promise for improving risk stratification and clinical management of HCC patients.

The incidence of colorectal neuroendocrine tumors is increasing every year with poor prognosis. Members of Chromogranin family proteins have been shown to be associated with cancer metastasis; however, the role of chromogranin B in colonic neuroendocrine carcinoma (NEC) is unknown. In this study, we investigated the expression and function of CgB in colonic NEC. Using RNA-seq data from GSE 9576 and GSE 142720 datasets, we analyzed the differentially expressed genes between the normal and NEC samples, which protein levels were further validated using the Human Protein Atlas (HPA) databases. Moreover, immunohistochemistry staining and biological experiments were conducted to examine the expression and function of CgB in colonic NEC. Western blot was also performed to confirm the effect of CgB on epithelial mesenchymal transition (EMT) and its related pathways. We found that the expression level of CgB was significantly higher in colonic NEC tissues than in the adjacent tissues. The upregulation of CgB promoted cell invasion and migration as well as activated EMT and stemness. Mechanistically, both pathway enrichment analysis and Western blot analysis confirmed that CgB overexpression activated p38 MAPK and ERK pathways, while silencing CgB showed the opposite effects. Collectively, our results suggested that CgB activated p38 MAPK and ERK pathways, thereby contributing to the development of colonic NEC.

Objective:To evaluate the ability of preoperative alkaline phosphatase to prealbumin ratio (APR) as a predictive factor for the prognosis of hepatocellular carcinoma (HCC), and to guide the clinical prognosis evaluation.Methods:A total of 184 HCC patients who underwent radical surgical treatment in Shengjing Hospital of China Medical University from April 2012 to November 2019 were retrospectively analyzed. Non-parametric Mann-Whitney U test, Chi-square test, and rank-sum test were used for comparison. Restricted cubic spline (RCS) was used for checking whether APR was linearly related to the prognoses. The best cut-off value was obtained by X-tile software. Kaplan-Meier curve and Log-rank test was used for the survival analysis. A multiple Cox regression model was set for univariate analysis and multiple analysis.Results:The result of RCS showed that APR was linear correlation with both prognoses. The best cut-off value of APR was 628.38. According to the cut-off value, the patients were divided into the APR≤628.38 group (131 cases) and the APR>628.38 group (53 cases). There were significant differences in gender, Child-Pugh, tumor size, and transfusion between the two groups (P<0.05), the median recurrence free survival (RFS) was 43 months in the APR≤628.38 group and 22 months in the APR>628.38 group respectively, and the median overall survival (OS) was not achieved in the APR≤628.38 group and 48 months in the APR>628.38 group respectively, with statistically significant differences (P<0.01). Univariate analysis and Cox multivariate analysis suggested that APR>628.38 and tumor size >5 cm were independent variables of RFS (P<0.01). Analogously, APR>628.38 and alpha fetoprotein >400 μg/L were independent predictors of OS (P=0.001). The results of simplified score showed that for patients with APR≤628.38, 74.05% were low-risk population of RFS and 77.10% were low-risk population of OS, and that patients with APR>628.38 were all at high risk RFS and OS.Conclusion:Preoperation APR has a good predictive value for the prognosis of HCC patients, and APR>628.38 is an independent risk factor for the RFS and OS of patients.

Liver cancer is highly malignant, has a low sensitivity to chemotherapy, and is associated with poor patient prognosis.The last 3 years have seen the emergence of promising targeted therapies for the treatment of hepatocellular carcinoma (HCC).For over 10 years, before the discovery of lenvatinib, sorafenib was only first-line therapeutic agent available for the treatment of advanced HCC.However, several clinical studies have shown that a considerable proportion liver cancer patients are insensitive to sorafenib.Very few patients actually substantially benefit from treatment with sorafenib, and the overall efficacy of the drug has not been satisfactory; therefore, sorafenib has attracted considerable research attention.This study, which is based on previous studies and reports, reviews the potential mechanisms underlying sorafenib resistance and summarizes combination therapies and potential drugs that can be used to sensitize HCC cells to sorafenib.

Background: Primary liver cancer, of which around 75–85% is hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China in June 2017, which were updated by the National Health Commission in December 2019, additional high-quality evidence has emerged from researchers worldwide regarding the diagnosis, staging, and treatment of liver cancer, that requires the guidelines to be updated again. The new edition (2022 Edition) was written by more than 100 experts in the field of liver cancer in China, which not only reflects the real-world situation in China but also may reshape the nationwide diagnosis and treatment of liver cancer. Key Messages: The new guideline aims to encourage the implementation of evidence-based practice and improve the national average 5-year survival rate for patients with liver cancer, as proposed in the “Health China 2030 Blueprint.”

The highly conserved ribosomal protein L34 (RPL34) has been reported to play an essential role in the progression of diverse malignancies. RPL34 is aberrantly expressed in multiple cancers, although its significant in colorectal cancer (CRC) is currently unclear. Here, we demonstrated that RPL34 expression was higher in CRC tissues than in normal tissues. Upon RPL34 overexpression, the ability of proliferation, migration, invasion, and metastasis of CRC cells were significantly enhanced in vitro and in vivo. Furthermore, high expression of RPL34 accelerated cell cycle progression, activated the JAK2/STAT3 signaling pathway, and induced the epithelial-to-mesenchymal transition (EMT) program. Conversely, RPL34 silencing inhibited the CRC malignant progression. Utilizing immunoprecipitation assays, we identified the RPL34 interactor, the cullin-associated NEDD8-dissociated protein 1 (CAND1), which is a negative regulator of cullin-RING ligases. CAND1 overexpression reduced the ubiquitin level of RPL34 and stabilized RPL34 protein. CAND1 silencing in CRC cells resulted in a decrease in the ability of proliferation, migration, and invasion. CAND1 overexpression promoted CRC malignant phenotypes and induced EMT, and RPL34 knockdown rescued CAND1-induced CRC progression. In summary, our study indicates that RPL34 acts as a mediator, is stabilized by CAND1, and promotes proliferation and metastasis, in part, through the activation of the JAK2/STAT3 signaling pathway and induction of EMT in CRC.

Since the laparoscopic liver resection（LLR）had been first published for nearly 30 years，it has gradually developed into one of the standard radical operation for hepatocellular carcinoma（HCC）. In selected patients，LLR has achieved oncological curative effect that is not inferior to open liver resection，and its advantages are increasingly recognized. LLR could be divided into anatomic and non-anatomic liver resection，depending on whether the liver is pre-dissected or blocked from inflow and /or outflow. They have their own scope of application，advantages and disadvantages. How to choose laparoscopic anatomic liver resection or laparoscopic non-anatomic liver resection for HCC remain controversial．Combined with relevant literature and personal experience，this paper briefly discusses the selection and standardization of laparoscopic radical liver resection for HCC.