Abstract Background and objective Conversion or downstaging therapy for intermediate and advanced unresectable hepatocellular carcinoma (HCC) has emerged as a major focus of clinical practice and research in recent years. This study aims to investigate the current clinical application of conversion therapy in China and determine the factors that physicians consider when selecting eligible patients for conversion therapy and choosing the appropriate conversion modality. Methods Physicians who met predefined inclusion criteria were invited to complete an online questionnaire between January and July 2024. The collected data were subsequently pooled and analyzed descriptively. Results A total of 120 valid questionnaires were gathered, mainly from surgical (n = 83, 69.2%) and interventional (n = 37, 30.8%) departments. The survey revealed that approximately 51% of CNLC stage Ib-IIIa patients were selected for conversion or downstaging treatment. Three primary factors were prioritized by physicians for the determination of conversion therapy: portal vein tumor thrombus (PVTT) type (116/120, 97%), future liver volume (108/120, 90%), and Child–Pugh classification (108/120, 90%). Currently, the predominant conversion therapy approach involves a combination of local and systemic therapies, which is utilized in approximately 73% of cases. Among systemic treatments, the combination of lenvatinib and immunotherapy is the most widely adopted. Besides, a higher objective response rate (ORR) was the foremost consideration for 83% (99/120) of physicians, followed by rapid response (82/120, 68%), adherence to guidelines and consensus (76/120, 63%), and lower tumor progression rate (70/120, 58%). Conclusion This survey demonstrated the current status of conversion therapy for HCC in China. Over half of the newly diagnosed HCC patients were eligible for treatment modalities aimed at achieving surgical resection through conversion therapy, and the most popular indications were the presence of PVTT, insufficient FLR and Child–Pugh classification.

Background Biliary tract cancer (BTC) is an aggressive malignancy with limited treatment options and a poor prognosis. Although immune checkpoint inhibitors combined with chemotherapy have improved patient outcomes, their toxicity remains concerning. This phase II multicenter trial evaluated the efficacy and safety of pembrolizumab plus lenvatinib with a reduced-dose gemcitabine and oxaliplatin (GEMOX) regimen as a first-line therapy for advanced BTC.Methods 60 patients with unresectable or metastatic BTC were enrolled from five centers in China. Patients received pembrolizumab (200 mg, every 3 weeks), lenvatinib (8 or 12 mg daily), and modified GEMOX (gemcitabine 1000 mg/m² and oxaliplatin 85 mg/m² on day 1 of each 3-week cycle) for 6–8 cycles, followed by maintenance with pembrolizumab and lenvatinib. The primary endpoint was objective response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.Results At a median follow-up of 16.0 months, the ORR (complete response 5.0%, partial response (PR) 50.0%) and disease control rate were 55.0% and 93.3%, respectively. The median PFS and OS were 12.5 months (95% CI 7.93 to 16.3), and 19.5 months (95% CI 17.97 to not estimable), respectively. Elevated baseline CA19-9 (>37 U/mL) and carcinoembryonic antigen levels (>5 ng/mL) were independently associated with poor OS and PFS, respectively. The regimen showed manageable toxicity, with 95% of patients experiencing treatment-emergent adverse events (AEs), mostly grades 1–2; grade 3–4 AEs occurred in 65% of patients, with no treatment-related deaths. Immune-related AEs occurred in 11.7% of the patients and were predominantly mild.Conclusions Pembrolizumab plus lenvatinib with reduced-dose GEMOX demonstrated promising efficacy and a favorable safety profile in advanced BTC, suggesting that chemotherapy de-escalation may optimize the efficacy–toxicity balance. Further randomized studies are warranted to confirm these findings and refine biomarker-based treatment selections.

BACKGROUND:Hepatitis B virus (HBV) infection is the main cause of cirrhosis and hepatocellular carcinoma (HCC) in China. Microvascular invasion (MVI) is a key pathological indicator of tumor invasiveness associated with HCC prognosis. This study aimed to investigate the association of cirrhosis with MVI incidence and postoperative prognosis in patients with HBV-related HCC. METHODS:Patients with HBV-related HCC who underwent resection in 13 centers in China between February 2011 and June 2023 were included in this study. Risk factors of MVI were analyzed using logistic regression analysis. A propensity score matching (PSM) was performed to eliminate confounders between the groups. Recurrence-free survival (RFS) and overall survival (OS) were estimated based on the Kaplan-Meier method and compared using the log-rank test. Independent risk factors for RFS and OS were identified using Cox regression analysis. RESULTS:Of 3048 patients with HBV-related HCC, 2271 (74.5%) had cirrhosis. Compared to patients without cirrhosis, the incidence of MVI was higher in patients with cirrhosis (47.8% vs. 41.2%, P = 0.001). Cirrhosis was independently associated with MVI (odds ratio = 1.41, P < 0.001). In patients with MVI, RFS and OS were significantly shorter in patients with cirrhosis than those without cirrhosis (after PSM, median RFS: 13.90 vs. 33.37 months, P < 0.001; median OS: 42.07 vs. 63.67 months, P < 0.001). Cirrhosis was an independent risk factor for RFS and OS in patients with MVI [RFS: hazard ratio (HR) = 1.62, P < 0.001; OS: HR = 1.56, P < 0.001]. CONCLUSIONS:Among patients with HBV-related HCC, cirrhosis was associated with the presence of MVI. Cirrhosis was an indicator of worse RFS and OS in patients with MVI.

Background: The differences in the prognostic value of microvascular invasion (MVI) and satellite nodules (S) for patients with hepatocellular carcinoma (HCC) remain unclear. We aimed to evaluate the effect of MVI and/or S on recurrence patterns and long-term prognosis of patients with HCC after hepatectomy. Methods: Patients with HCC who underwent hepatectomy in 23 cancer centers in China between 2012 and 2022 were included in this study. Patients were divided into four groups based on the histopathological diagnosis of MVI and/or S. Data were analyzed retrospectively. Results: The 3,145 enrolled patients were divided into four groups: No MVI or S, MVI-only, S-only, and MVI and S groups, comprising 1,495, 806, 245, and 599 patients, respectively. Patients in the S-only group exhibited a higher early recurrence (ER) rate compared to those in the MVI-only group (P=0.03). Patients in the MVI and S group had shorter median overall survival (OS) (30.2 vs. 72.5 vs. 53.8 vs. 47.8 months, P<0.001) and recurrence-free survival (RFS) (8.4 vs. 63.0 vs. 28.4 vs. 25.0 months, P<0.001) compared to those in the No MVI or S, MVI-only, and S-only groups, respectively. Multivariate analyses showed that MVI and S were both independent risk factors for OS, RFS, aggressive recurrence (AR), ER, and early aggressive recurrence (EAR). Conclusions: MVI and S were both independently associated with AR, ER, EAR, and poor long-term prognosis in patients with HCC after hepatectomy. Distinguishing between MVI and S is necessary for postoperative prognostic stratification and management in patients with HCC after hepatectomy.

The epidemiological shift toward non-B non-C hepatocellular carcinoma (NBNC-HCC) highlights the need for identifying prognostic markers in this population. While microvascular invasion (MVI) has been established in hepatitis virus-related HCC (HV-HCC), its role in NBNC-HCC remains unclear. This multicenter retrospective study analyzed 3308 patients with HCC undergoing curative resection (2012–2023). Risk factors for MVI were identified using logistic regression in the overall cohort. From this cohort, 439 patients with NBNC-HCC were stratified based on the MVI status and balanced using propensity score matching (PSM). Cox regression models and Kaplan–Meier analysis with log-rank test were employed to compare recurrence-free survival (RFS) and overall survival (OS) between MVI-positive and MVI-negative subgroups. The incidence of MVI was lower in the NBNC-HCC group compared to the HV-HCC group (31.44

This consensus by the CSCO Pancreatic Cancer Expert Committee establishes evidence-based guidelines for molecular testing in pancreatic ductal adenocarcinoma. It details recommendations for biomarkers (e.g., KRAS, BRCA, MSI), liquid biopsy, and precision imaging to direct targeted therapies and immunotherapy, aiming to standardize diagnosis and optimize individualized patient care. Pancreatic ductal adenocarcinoma (PDAC) is the most common pathological type of primary pancreatic malignancy, accounting for ~95% of cases and generally referred to as pancreatic cancer [1]. Its prognosis is extremely poor and its incidence continues to rise [2]. According to the most recent global cancer statistics, the incidence of pancreatic cancer ranks 12th among all cancers, and its mortality ranks 6th, making it one of the deadliest malignancies worldwide [3]. Approximately 57% of patients have metastatic disease at diagnosis and require systemic therapy, for which chemotherapy remains the standard first-line option [1]. However, the overall response rate to currently available systemic regimens is low, and the 5-year survival rate for patients with metastatic disease remains below 5% [3]. Although most pancreatic cancers harbor canonical driver mutations, they exhibit marked heterogeneity at the molecular level. Whole-genome sequencing (WGS) and integrative genomic analyses have identified molecular subtypes of PDAC with potential clinical relevance [4-9]. With the increasing implementation of precision oncology, the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Pancreatic Cancer give a level 1 recommendation to perform genetic and other molecular testing on tissue or cytologic specimens as part of the pathological diagnostic work-up, in order to guide individualized treatment, including targeted therapy and immunotherapy [10]. To further promote the use of genetic and molecular testing in the precision treatment of pancreatic cancer, the CSCO Pancreatic Cancer Expert Committee convened a multidisciplinary panel to develop the present Chinese Expert Consensus on Precision Testing and Molecular Diagnosis of Pancreatic Cancer (2025), aiming to provide clinicians with an authoritative reference for precision diagnostics and treatment decision-making.

4132 Background: Patients with advanced hepatocellular carcinoma (HCC) characterized by high tumor burden (beyond up-to-seven criteria) and portal vein tumor thrombus (PVTT) have a median overall survival (OS) of lower than 4 months without intervention. Global guidelines rely on Phase III trials that often under-represented this high-risk subgroup, creating a therapeutic gap. While systemic combinations are standard, they may lack the rapid cytoreductive potency required to prevent liver failure in this subgroup. We emulated a target trial to evaluate if adding hepatic arterial infusion chemotherapy (HAIC) to lenvatinib and PD-1 inhibitors (H+L+P) improves outcomes compared to lenvatinib and PD-1 inhibitors (L+P) alone. Methods: Using multicenter data from 22 centers in the Chinese Liver Cancer Clinical Study Alliance (CHANCE) registry, we compared first-line H+L+P (n = 127) vs. L+P (n = 117) in patients with advanced HCC (BCLC stage C without extrahepatic spread) and PVTT (Vp1-4). To minimize selection and immortal time biases, we employed stabilized inverse probability of treatment weighting (sIPTW) and a cloning-censoring-weighting framework. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS), site-specific PFS, objective response rate (ORR), and safety. Results: Baseline covariates were well-balanced after weighting (SMD < 0.1). After sIPTW adjustment, H+L+P demonstrated a significant survival benefit: median OS was 25.6 months (95% CI: 22.0–33.7) vs. 15.9 months (95% CI: 12.6–21.3) for L+P (adjusted HR, 0.60; 95% CI: 0.43–0.82; p = 0.0015). Crucially, a favorable survival trend was preserved even in the high-risk Vp3-4 subgroup (HR 0.77). Median PFS (RECIST v1.1) was 13.0 vs. 6.8 months (adjusted HR, 0.58; p = 0.0002). H+L+P significantly delayed progression in intrahepatic lesions (median 14.8 vs. 7.8 months; p = 0.0006) and PVTT (median 24.9 vs. 15.5 months; p = 0.0183). Intrahepatic ORR (mRECIST) was 87.4% for H+L+P vs. 28.9% for L+P (p < 0.0001), with a PVTT response rate of 81.6% vs. 22.1% (p < 0.0001). Grade ≥3 adverse events (AEs) occurred in 37.0% of the H+L+P group vs. 9.4% in the L+P group. Common Grade ≥3 AEs in the H+L+P arm included abdominal pain (20.5%) and leukopenia (5.5%); no treatment-related deaths occurred in the H+L+P group. Conclusions: In this target trial emulation, adding HAIC to lenvatinib and PD-1 inhibitors significantly improved OS and PFS in patients with high-risk HCC and PVTT. The survival advantage was driven by rapid and profound locoregional control, particularly of the tumor thrombus, with a manageable safety profile. Clinical trial information: NCT06631326 .

Pancreatic ductal adenocarcinoma (PDAC) ranks among the most lethal malignant tumours, characterised by an immunosuppressive tumour microenvironment and resistance to conventional therapies. Increasing evidence indicates that mitochondrial genes correlate with tumour progression, immune evasion, and treatment response. This study integrated transcriptomic data from multiple databases (GEO, TCGA, ICGC) to identify mitochondrial-related differentially expressed genes (MRGs) between tumour and normal tissues. Concurrently, a prognostic model for mitochondrial genes was constructed using 100 machine learning methods. The risk score from the optimal model, termed the MRGs score, effectively stratified patients into high-risk and low-risk groups. The model demonstrated robust predictive performance across training and validation cohorts, with patients in the high MRG score group exhibiting significantly poorer overall survival. Functional analysis revealed strong associations between MRG scores and cellular processes, including cell cycle regulation, immune cell infiltration, and metabolism. Computational deconvolution analysis revealed that high MRG scores correlate with increased infiltration of immunosuppressive cells and altered immune checkpoint expression. The existing MRGs score has the important property of predicting prognosis while at the same time capturing tumour microenvironment heterogeneity, genomic instability, and computationally predicted chemotherapy response variability, thus providing genuinely new avenues for developing risk stratification hypotheses and designing personalised treatment strategies for pancreatic cancer patients. However, the validity of these results must be confirmed by future clinical and laboratory studies.

Purpose:Targeting neddylation offers a potential therapeutic strategy for hepatocellular carcinoma (HCC). This retrospective study aims to identify genes linked to HCC prognosis associated with neddylation through bioinformatics. Patients and Methods:The research used publicly available datasets. Neddylation-related genes and survival-associated differentially expressed genes (DEGs) were intersected to identify key genes, which underwent enrichment analysis. Least absolute selection and shrinkage operator (LASSO)-Cox and multivariate Cox regression analyses were performed to identify prognostic genes and build a risk model. Potential mechanisms were explored via immune microenvironment and single-cell analysis. Finally, prognostic gene expression was validated in clinical tumor samples using real-time quantitative PCR (RT-qPCR). Results:Through methodical investigation, 62 intersection genes were found, mainly enriched in "DNA duplex unwinding" and "p53 signaling pathway". Six prognostic genes were further determined (SOCS2, DIRAS2, LPL, KRT17, BFSP1, and POF1B). RT-qPCR results confirmed the downregulation of SOCS2 and the upregulation of DIRAS2, LPL, KRT17, BFSP1, and POF1B in HCC. Risk prediction model based on these genes exhibited high predictive accuracy. Subsequently, analysis of the immunological microenvironment showed that the infiltration levels of 8 immune cell types varied significantly among risk categories. M0 macrophages had the highest negative correlation with SOCS2 and the strongest positive association with DIRAS2. Single-cell analysis showed that SOCS2 had higher expression levels in endothelial cells and significant differential expression in most cellular classifications. Conclusion:Six prognosis-associated genes (SOCS2, DIRAS2, LPL, KRT17, BFSP1, and POF1B) as predictive biomarkers for HCC were identified, and a high-accuracy risk model was developed, providing predictive and prognostic references for HCC risk stratification and clinical management.

Background/Objectives: Lenvatinib combined with anti-PD-1 therapy has shown promise in the treatment of hepatocellular carcinoma (HCC). The study evaluates changes in gut microbiota (GM) and metabolites during HCC treatment with lenvatinib combined with anti-PD-1. Methods: An HCC mouse model was established via diethylnitrosamine (DEN) injection, and the mice were then treated with lenvatinib, anti-PD-1, or their combination. GM composition and structural changes were assessed by 16S rDNA sequencing, and metabolite abundance by liquid chromatography-mass spectrometry (LC-MS). Results: Significant alterations in GM and metabolites were observed in the HCC group compared to the control group, and compared with the HCC group, both monotherapy and combination therapy resulted in varying degrees of GM and metabolites rebalancing. Specifically, compared to the HCC group, lenvatinib combined with anti-PD-1 therapy decreased the abundance of GM, including p_Patescibacteria, g_Lactobacillus, g_Clostridium_sensu_stricto_1, g_Eubacterium_siraeum_group, and g_Desulfovibrio, while the abundance of g_Prevotella_7 increased. Metabolite changes included increased 4-pyridoxic acid, deoxycholic acid, and taurochenodesoxycholic acid, and decreased myristic acid, oleic acid, riboflavin, and uric acid. Conclusions: HCC induces substantial alterations in the GM and metabolic profile of mice. Lenvatinib combined with anti-PD-1 treatment partially modulates these dysregulations. The relevant GM and metabolites may be associated with the efficacy of combined therapy and could serve as potential markers for further investigation.

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.

585 Background: Conversion or downstaging therapy for intermediate and advanced unresectable hepatocellular carcinoma (HCC) has emerged as a significant exploring area of clinical practice and research in recent years. Nonetheless, there exists considerable variability in both the selection criteria for patients undergoing conversion therapy and the regimens selected for conversion across different regions and medical institutions. The present study aims to elucidate the current clinical application of conversion therapy in China, as well as to identify the considerations that physicians take into account when selecting eligible patients for conversion therapy and determining the appropriate conversion modality. Methods: Physicians meeting predefined inclusion criteria were invited to complete an online questionnaire from January to July, 2024. The collected data were subsequently pooled and analyzed descriptively. Results: A total of 120 valid questionnaires were retrieved, mainly form surgical (69.2%, n=83) and interventional (30.8%, n=37) departments. Generally, the study showed that approximately 51% of stage Ib-IIIa patients will be selected for the treatment goal of conversion or downstaging, and the overall successful rate as meeting criteria for surgical resection after treatment was 36%. Three primary factors were prioritized by physicians for determination of conversion therapy: the type of portal vein tumor thrombus (PVTT) (97%, 116/120), the future liver volume (90%, 108/120), and Child-Pugh classification (90%,108/120). In the specific physician group who selected the following attributes, patients classified as Child-Pugh A (82%, 89/108) or Child-Pugh B7 (66%, 71/108), those with tumor diameter exceeding 5 cm (92%, 98/106) and Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1 (89%, 76/85) were most frequently selected for conversion therapy. Additionally, study showed that patients presenting with Vp1-2 (72%, 83/116) and Vp3 (71%, 82/116) could also be considered for conversion therapy. Currently, the prevalent treatment approach of conversion therapy involves a combination of local and systemic therapies, which is utilized in approximately 73% of cases. Among systemic treatment methodologies, the combination of Lenvatinib and immunotherapy is the most widely adopted by physicians. Besides, higher ORR was the foremost consideration for 83% (99/120) of physicians, followed by rapid response (68%, 82/120), adherence to guidelines and consensus (63%, 76/120), and lower tumor progression rate (58%, 70/120). Conclusions: This study elucidates the current status of conversion therapy for HCC in China. The findings underscore the necessity for optimizing conversion modalities and advancing standardized practices in the application of conversion therapy.

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.”

BACKGROUND:Surgical resection is the preferred curative approach for patients with early-stage hepatocellular carcinoma, but recurrence remains a major challenge. Consequently, neoadjuvant and adjuvant therapies have been proposed to reduce tumour burden and mitigate the risk of recurrence. The CARES-009 trial aimed to evaluate perioperative camrelizumab plus rivoceranib in patients with resectable hepatocellular carcinoma at intermediate or high risk of recurrence. METHODS:This multicentre, open-label, randomised, phase 2/3 trial enrolled patients with hepatocellular carcinoma classified as China Liver Cancer Staging (CNLC) stage Ib-IIIa without Vp4 portal vein tumour thrombosis (corresponding to Barcelona Clinic Liver Cancer stage A with tumour >5 cm, stage B, or stage C without Vp4 involvement or extrahepatic metastasis) at 16 hospitals in China. Patients were randomly assigned (1:1) to receive perioperative therapy or surgery alone and were stratified by CNLC stage and hepatitis B virus (HBV) infection status. The perioperative group received two cycles of neoadjuvant camrelizumab plus rivoceranib, followed by surgery and adjuvant camrelizumab plus rivoceranib. The primary endpoint was event-free survival (EFS) and was assessed by investigators (who were not masked to group assignment) in the intention-to-treat population. Safety was evaluated in the as-treated population. This trial is registered with ClinicalTrials.gov (NCT04521153) and is ongoing. FINDINGS:Between March 25, 2021, and Jan 29, 2024, 294 patients (87% male; 99% Han Chinese) were randomly assigned to the perioperative group (n=148) or surgery alone group (n=146). At a prespecified interim analysis, with a median follow-up of 21·3 months, median EFS was 42·1 months (95% CI 23·2-not estimable [NE]) in the perioperative group versus 19·4 months (14·9-NE) in the surgery alone group (hazard ratio 0·59, 95% CI 0·41-0·85; p=0·0040). Grade 3 or worse treatment-related adverse events occurred in 53 (38%) patients in the perioperative group and no patients in the surgery alone group. Two treatment-related deaths occurred during neoadjuvant therapy in the perioperative group: one due to hepatic failure, assessed as possibly related to treatment, and one due to combined hepatic and renal failure, with the causality deemed indeterminate. INTERPRETATION:Perioperative camrelizumab plus rivoceranib significantly improved EFS compared with surgery alone in patients with resectable hepatocellular carcinoma at intermediate or high risk of recurrence. FUNDING:Shanghai Hospital Development Center and Jiangsu Hengrui Pharmaceuticals.

Background:Patients with hepatocellular carcinoma (HCC) and microvascular invasion (MVI) are susceptible to early recurrence (ER) after hepatectomy. The use of postoperative adjuvant transcatheter arterial chemoembolization (TACE) for patients with HCC and MVI remains a subject of debate. Methods:A total of 1,191 patients with HCC and MVI from 16 participating centers were retrospectively analyzed. A nomogram for predicting ER was developed using risk factors via multivariate logistic regression in the training cohort, with performance validated in the internal and external validation cohorts. Patients were categorized into high- and low-risk groups based on maximum Jordon index, which was used to continue exploring the long-term prognosis and the impact of adjuvant TACE therapy. Results:In total, 217 (43.1%), 115 (45.6%), and 189 (43.4%) patients with ER were found in the training, internal validation and external validation cohort, respectively. The DCDAM score, which incorporates diameter, cirrhosis, differentiation, α-fetoprotein (AFP), and MVI grade, demonstrated superior net benefit and accuracy in predicting ER compared to traditional models across three cohorts. The high-risk group (DCDAM score >169) had higher cumulative recurrence rates and worse overall survival (OS) (median OS: 22.0 vs. 38.3, 17.5 vs. 41.7, and 23.6 vs. 45.2 months, all P<0.001) compared to the low-risk group (DCDAM score ≤169) in all cohorts. TACE-adjuvant therapy improved OS in the high-risk group but not in the low-risk group. Conclusions:DCDAM score achieved an optimal postoperative prediction of ER among patients with HCC and MVI. This model can help screen subjects who can benefit more from postoperative adjuvant TACE.

A few studies focus on the long-term outcomes and surveillance strategies for patients with hepatocellular carcinoma (HCC) and microvascular invasion (MVI) who experience postoperative recurrence. The aim of this study was to explore the patterns and prognosis of early and late recurrence (ER and LR) after hepatectomy of such patients. Consecutive patients with HCC and MVI after hepatectomy from 26 centers in China from 2009 to 2020 were included. Overall survival (OS) and post-recurrence survival (PRS) were compared using the Kaplan–Meier method and log-rank test. Of 2828 included patients, 1200 patients developed ER and 607 patients developed LR. Among patients with recurrence, 1166 patients had intra-hepatic recurrence as the primary site of first recurrence. The median OS times for the ER, LR, and non-recurrence groups were 20.2, 52.6, and 58.9 months, respectively. Besides, patients with ER had shorter PRS (14.3 vs. 18.9 months, p < 0.001) than LR. Compared to extra-hepatic and both intra- and extra-hepatic recurrence, intra-hepatic recurrence had better OS and PRS (p < 0.001). Recurrence patients who underwent regular postoperative surveillance had longer OS (37.1 vs. 23.4 months, p < 0.001) and PRS (21.2 vs. 11.9 months, p < 0.001) compared to those with irregular surveillance. Patients with HCC and MVI are more likely to develop ER within 1 year, and ER has a worse prognosis compared to LR. Intra-hepatic is the predominant recurrence site in ER and LR. Postoperative surveillance can improve survival outcomes in patients with recurrence.

Background: Primary liver cancer (PLC) ranks third in terms of fatality rate among all malignant tumors worldwide. Proteomics and metabolomics have become widely utilized in identifying causes and diagnostic indicators of PLC. Nevertheless, in studies aiming to identify proteins/metabolites that experienced significant changes before PLC, the potential impact of reverse causation and confounding variables still needs to be fully addressed. Methods: This study thoroughly investigated the causal relationship between 4719 blood proteins, 21 amino acids, and the risk of PLC using the Mendelian randomization (MR) method. In addition, through a comprehensive analysis of the TCGA-LIHC cohort and GEO databases, we evaluated the differentially expressed genes (DEGs) related to serine metabolism in diagnosing and predicting the prognosis of patients with PLC. Results: A total of 63 proteins have been identified as connected to the risk of PLC. Additionally, there has been confirmation of a positive cause–effect between PLC and the concentration of serine. The integration of findings from both MR analyses determined that the protein associated with PLC risk exhibited a significant correlation with serine metabolism. Upon careful analysis of the TCGA-LIHC cohort, it was found that eight DEGs are linked to serine metabolism. After thoroughly validating the GEO database, two DEGs, TDO2 and MICB, emerged as potential biomarkers for diagnosing PLC. Conclusions: Two proteins involved in serine metabolism, MICB and TDO2, are causally linked to the risk of PLC and could potentially be used as diagnostic indicators.

Abstract Background To investigate the risk factors for pancreatitis and their variability after endoscopic retrograde cholangiopancreatography (ERCP) in patients with biliary tract diseases. Methods The clinical data of a total of 234 patients who underwent ERCP for biliary tract diseases at the First Affiliated Hospital of Dalian Medical University from June 2023 to November 2023 were retrospectively analyzed, and a total of 149 patients were enrolled after inclusion and exclusion criteria were applied.This study has been approved by the Ethics Committee of the First Affiliated Hospital of Dalian Medical University, and the relevant guidelines and regulations have been strictly followed. This study has been approved by the Ethics Committee of the First Affiliated Hospital of Dalian Medical University, and the relevant guidelines and regulations have been strictly followed.According to the morphology of Oddi type sphincter of duodenal papilla, patients were classified as normal papillary muscle morphology and normal sphincter. According to the Oddi sphincter morphology of the duodenal papilla, the patients were divided into two layers: normal papillary muscle morphology and abnormal papillary muscle morphology, retrieved their baseline data, and then divided into the PEP group and non-PEP group according to the occurrence of PEP, based on the different stratification and grouping of the clinical baseline data, and the statistically significant results of the difference in the analysis of the difference in the relevant visualization. Patients were divided into study group (n=34, with PEP) and control group (n=115, without PEP) according to whether they had post-ERCP pancreatitis (PEP) or not, and their clinical baseline data were retrieved and compared. Their statistically significant risk factors for PEP were analyzed based on Lasso regression and logistic regression. Results In the DPS=0 group, the factors significantly associated with PEP are SA,PH,PS,IT,OSD,PAP,PI,NRG,PAG,PLG.In the DPS=1 group, the risk factors are BMI,SA,PH,IT,OSD,PAP,APG,PAG and PLG. The risk factors that are common between the groups for the occurrence of PEP are SA,PH,IT,OSD,PAP,PAG,PLG. OSD, PAP, PAG, PLG. In the between-group comparison analysis of variance, the most significant differences between groups are IT (t: 2.449, P: 0.0220) and OSD (t: -3.647, P: 0.0012). In the Lasso regression analysis and logistic regression analysis, it has been found that: gender, C, PS, IT, PI, OSD, PAP, PAR, NRG (2), TBG (2), PG, PAG, PLG (1), and ET are independent risk factors for the promotion of PEP as its occurrence. Conclusion According to DPS=0 and DPS=1 stratified intergroup correlation comparison variability analysis we have found that the common risk factors associated with PEP are SA,PH,IT,OSD,PAP,PAG,PLG, and the risk factors with the most significant intergroup variability are IT and OSD.Gender, C, PS, IT, PI, OSD, PAP, PAR, NRG (2), TBG(2), PG, PAG, PLG(1), and ET are independent risk factors for PEP. This study can assist clinicians to make a comprehensive and reasonable assessment of patients who are about to undergo ERCP, and to make relevant clinical interventions in a timely manner, so as to improve the prognosis of the patients.

Abstract High‐coverage mass spectrometry analysis of single‐cell metabolomics remains challenging due to the extremely low abundance and wide polarity of metabolites and ultra‐small volume in single cells. Herein, a novel concentric hybrid ionization source, nanoelectrospray ionization‐atmospheric pressure chemical ionization (nanoESI‐APCI), is ingeniously designed to detect polar and nonpolar metabolites simultaneously in single cells. The source is constructed by inserting a pulled glass capillary coaxially into a glass tube that acts as a dielectric barrier layer. Benefitting from the integrated advantages of nanoESI and APCI, its limit of detection is improved by one order of magnitude to 10 pg mL−1. After the operational parameter optimization, 254 metabolites detected in nanoESI‐APCI are tentatively identified from a single cell, and 82 more than those in nanoESI. The developed nanoESI‐APCI is successively applied to study the metabolic heterogeneity of human hepatocellular carcinoma tissue microenvironment united with laser capture microdissection (LCM), the discrimination of cancer cell types and subtypes, the metabolic perturbations to glucose starvation in MCF7 cells and the metabolic regulation of cancer stem cells. These results demonstrated that the nanoESI‐APCI not only opens a new avenue for high‐coverage and high‐sensitivity metabolomics analysis of single cell, but also facilitates spatially resolved metabolomics study coupled with LCM.