Our previous findings demonstrated the promising antitumor activity and manageable safety of sintilimab-lenvatinib conversion therapy. The current study aimed to evaluate long-term survival outcomes in patients with unresectable hepatocellular carcinoma (HCC) who underwent sequential surgical resection after successful conversion therapy. In this prospective, single-arm, expansion, phase II trial, patients with unresectable HCC received lenvatinib plus sintilimab conversion therapy. Hepatectomy was performed in consenting patients after successful conversion therapy. The primary endpoint was the conversion rate; secondary endpoints included median overall survival (OS), 5-year survival rates, and recurrence-free survival (RFS). Successful conversion was achieved in 67 of 120 patients (56%, 67/120). Independent imaging review per mRECIST and RECIST v1.1 criteria demonstrated objective response rates of 58.3% (70/120) and 45.8% (55/120), respectively. With a median follow-up of 41.0 months (95% confidence interval [CI], 39.5-42.5) for the entire cohort, the median OS was 36.0 months (95% CI, 25.0 to not estimable [NE]), with a 5-year OS rate of 42.6% (95% CI, 34.0-53.0). Following multidisciplinary team evaluation and consideration of patient preferences, 60 patients underwent surgical resection, achieving a median RFS of 40.0 months (95% CI, 24.0 to NE) and a 5-year survival rate of 73.9% (95% CI, 62.7-87.1). Grade ≥3 treatment-related adverse events occurred in 37 patients (31%). Approximately half of the patients with unresectable HCC achieved successful conversion after sintilimab plus lenvatinib therapy. Among those who achieved successful conversion, subsequent curative surgery demonstrated not only a favorable safety profile but also significant survival benefits. Trial registration number: ChiCTR1900023914.

PURPOSE:This exploratory study aimed to evaluate the value of PERCIST based on 18F-FDG PET/CT, in conjunction with contrast-enhanced MRI, for assessing pathological response in patients with advanced hepatocellular carcinoma (HCC) treated with neoadjuvant tyrosine kinase inhibitor (TKI) plus anti-PD-1 therapy followed by surgery. METHODS:Patients were prospectively recruited between June 2019 and June 2023 in a clinical trial registered in the Chinese Clinical Trial Registry (ChiCTR1900023914). All patients underwent 18F-FDG PET/CT and contrast-enhanced MRI at baseline and before surgery. PET/CT parameters included tumor size, SUVmax, SUVmean, SULpeak, total lesion glycolysis (TLG), metabolic tumor volume (MTV), and total tumor volume (TTV). Changes in these parameters after treatment were analyzed. Histopathology served as the reference standard. Exploratory diagnostic performance was assessed using the area under the receiver operating characteristic curve (AUC) for PERCIST, mRECIST, and RECIST 1.1. RESULTS:Thirty patients were included. Significant differences between the major pathological response (MPR) and non-MPR groups were observed for ΔSUVmax, ΔTLG, ΔMTV, ΔMTV/TTV, and ΔSULpeak. PERCIST also differed significantly between the two groups. ROC analysis demonstrated that the AUCs were 0.8839 for both PERCIST and ΔMTV/TTV, 0.8170 for mRECIST, and 0.5357 for RECIST 1.1. CONCLUSIONS:PERCIST and ΔMTV/TTV showed promising performance for assessing response to neoadjuvant TKI plus anti-PD-1 therapy in advanced HCC. These preliminary findings suggest that PERCIST may provide complementary information to conventional morphologic criteria.

Background: Immunotherapy has revolutionized hepatocellular carcinoma (HCC) treatment, increasingly being incorporated into various stages of treatment, including preoperative therapy. However, preoperative immunotherapy alters both physiological status and tumor biology, potentially impacting the perioperative risk. We aimed to explore the association between the implementation details of preoperative immunotherapy and perioperative risk. Methods: This study retrospectively enrolled HCC patients who received immune checkpoint inhibitor (ICI)-based immunotherapy prior to radical surgery. A comprehensive dataset encompassing baseline characteristics and immunotherapy-specific parameters was collected. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors, followed by validation through machine learning algorithms to evaluate the predictive performance of the derived determinants. Results: This multicenter retrospective study enrolled 303 HCC patients who received preoperative immunotherapy across 26 participating centers. Based on specified perioperative risk stratification criteria, 182 patients (60.07%) were stratified into the low-risk cohort, while 121 patients (39.93%) constituted the high-risk cohort. Multivariate logistic regression analysis identified several independent risk factors of elevated perioperative risk: ICI duration exceeding four cycles [odds ratio (OR), 2.00; 95% confidence interval (CI) 1.20-3.32]; the occurrence of grade >= 3 immune-related adverse events (irAEs) (OR, 2.36; 95% CI: 1.13-4.92); the presence of major vein thrombus (OR, 2.05; 95% CI: 1.25-3.38); multiple tumor nodules (OR, 1.74; 95% CI: 1.02-2.98); and maximal tumor diameter >5 cm (OR, 2.02; 95% CI: 1.10-3.73). Subgroup analyses consistently demonstrated these associations. Machine learning algorithms quantified feature importance for perioperative risk predictors, with extended ICIs duration (mean importance rank =2.88) and grade >= 3 irAEs (mean importance rank =2.38) emerging as top-ranked variables. Conclusions: This multicenter retrospective study reveals ICIs duration and high-grade irAEs were associated with elevated perioperative risk in HCC patients undergoing preoperative immunotherapy, providing actionable insights for optimizing perioperative management protocols.

Portal vein tumor thrombus (PVTT) occurs in more than half of patients with hepatocellular carcinoma (HCC) and is associated with markedly shortened survival and a poor prognosis. Historically, management relied mainly on locoregional therapies or upfront surgical resection, but outcomes remained unsatisfactory. In recent years, immune checkpoint inhibitors (ICIs) combined with antiangiogenic targeted therapy have substantially changed the systemic treatment landscape for advanced HCC and created new opportunities for patients with unresectable or borderline-resectable HCC with PVTT to undergo conversion therapy followed by sequential surgery (CT-S). This review summarizes conventional treatment strategies for HCC with PVTT; the biologic rationale and clinical evidence for the conversion therapy based on the combination of immune checkpoint inhibitors (ICIs) and anti-angiogenic targeted drugs; patient selection and response assessment for CT-S; surgical timing and perioperative management; modified techniques for portal vein management; imaging assessment. Available evidence suggests that CT-S may improve oncologic outcomes in carefully selected patients. However, the evidence is derived predominantly from single-arm studies, retrospective cohorts, and real-world investigations. Multicenter prospective studies are therefore required to define criteria for successful conversion, establish the optimal washout interval, clarify postoperative adjuvant strategies, and determine the generalizability of this approach.

Background: Although emerging evidence has reported the efficacy and safety of sequential surgery following targeted and immunotherapy conversion treatment for patients with initially unresectable hepatocellular carcinoma (HCC), these studies have been limited by small sample sizes and short follow-up periods. Moreover, whether such patients can achieve comparable survival outcomes to those undergoing upfront surgery for early-stage resectable HCC remains unreported. This study aims to compare long-term survival between patients with initially unresectable HCC who underwent sequential surgery after conversion therapy and those with early-stage HCC who received direct surgery. Methods: The retrospective cohort study was conducted from December 2018 through December 2023, with follow-up ending in June 2024. Ninety-nine patients with initially unresectable HCC underwent conversion therapy based on immune checkpoint inhibitors and anti-angiogenic targeted drugs, with a median duration of five cycles, followed by radical hepatectomy. One hundred and eleven patients with Barcelona Clinical Liver Cancer (BCLC) stage A HCC only underwent direct hepatectomy. Clinical characters, surgical features and survival outcomes of the two groups were compared. Results: In this cohort study of 210 patients, the 1-, 3-, and 5-year overall survival (OS) rates of initially unresectable HCC patients who underwent radical hepatectomy after achieving either partial response (PR) or complete response (CR) were comparable to those of early-stage (BCLC-A) HCC patients who received Conclusions: For patients with initially unresectable HCC, radical hepatectomy after effective conversion therapy (defined as achieving either PR or CR by mRECIST) brings a satisfying long-term outcome that is comparable to BCLC-A HCC patients undergoing direct surgery.

Background:Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) face a very poor prognosis. And it remains unclear whether sequential surgery following conversion therapy based on immunotherapy combined with targeted therapy can yield long‑term survival benefits. This study aims to evaluate the long-term efficacy and safety of hepatocellular carcinoma patients with portal vein tumor thrombus receiving sequential surgery following conversion therapy with a combination of targeted therapy and immunotherapy, thereby demonstrating the therapeutic potential of this regimen. Methods:Data from 76 HCC patients with PVTT treated with programmed death-1 (PD-1) inhibitors and tyrosine kinase inhibitors (TKIs) followed by surgical treatment at Chinese People's Liberation Army General Hospital (June 2019 to June 2024) were analyzed. Recurrence-free survival (RFS) and overall survival (OS) were primary endpoints. Results:The median RFS was 21 months; the median OS was 62 months. RFS rates at 6 months, 1 year, 2 years, and 3 years were 76.2%, 59.7%, 48.1%, and 42.5%, respectively. OS rates at 6 months, 1 year, 2 years, 3 years, and 5 years were 98.7%, 93.4%, 78.1%, 72.4%, and 45.5%, respectively. Cox regression showed that preoperative alpha-fetoprotein (AFP) ≥20 ng/mL was an independent mortality factor, while non-major-pathological-response (non-mPR) and tumor size >50 mm were independent recurrence factors. Adverse events and surgical complications were evaluated, with no patient deaths resulting from conversion therapy or sequential radical surgery. Conclusions:For HCC patients with PVTT who achieve successful conversion and undergo radical surgery, sequential surgery following conversion therapy based on combination of immune checkpoint inhibitors (ICIs) and anti-angiogenic targeted drugs (AATDs) is associated with favorable RFS and OS, and appears safe and effective. These findings suggest that this regimen may represent a promising option for these patients.

Conversion therapy with a combination of tyrosine kinase inhibitor and anti-programmed death-1 antibody sequential surgery and postoperative adjuvant therapy has shown improved survival benefits in patients with Barcelona C stage (BCLC-C) hepatocellular carcinoma (HCC). We aimed to compare the survival benefits in a retrospective cohort of patients with BCLC-C HCC who underwent surgery after conversion therapy with adjuvant therapy and surgery alone. The conversion therapy group was derived from a prospective clinical study, and from January 2015 to September 2023, we selected patients diagnosed with BCLC-C HCC who underwent liver resection at Chinese PLA General Hospital as the surgical group. The primary endpoint in the comparison of survival benefits between conversion therapy and surgery-alone groups was recurrence-free survival. Propensity score matching was applied to reduce any potential bias in the study. By the end of follow-up, the conversion therapy group mRFS was 37.8 months, with postoperative 1-, 2- and 3-year RFS rates of 66.8%, 54.6%, and 48.3%. In the surgery group, the mRFS was 3.0 months, and postoperative 1- , 2- and 3-year RFS rates of 22.4%, 17.5%, and 15.0%, respectively. On multivariable Cox regression analyses, conversion therapy significantly reduced HCC-related mortality and HCC recurrence rates compared with surgery alone. For BCLC-C HCC patients, conversion therapy with adjuvant therapy is in relationship with increased survival in comparison with surgery alone.

Immune checkpoint inhibitors (ICIs) combined with anti-angiogenic agents manifest improved survival in advanced hepatocellular carcinoma (HCC), but responses remain heterogeneous. Although high PIVKA-II expression correlates with advanced disease stage, early recurrence, shorter survival, and may predict resistance to anti-PD-1 plus lenvatinib therapy, the tumor microenvironment (TME) and resistance mechanisms in HCC with high PIVKA-II expression remain unclear. Clinical data from 156 resected HCC patients and 104 patients treated with anti-PD-1 plus lenvatinib are analyzed to correlate PIVKA-II expression with clinical features and outcomes. Single-cell RNA sequencing (scRNA-seq) is performed on tumors from 15 untreated and 7 treated patients. Mechanistic findings are validated in vitro and in vivo. High PIVKA-II expression is associated with advanced disease stage, increased microvascular invasion (MVI), early recurrence, and poor response to therapy. ScRNA-seq revealed an immunosuppressive TME enriched with regulatory T cells (Tregs), exhausted CD8⁺ T cells, and SPP1⁺ tumor-associated macrophages (TAMs). Mechanistically, tumors with high PIVKA-II expression upregulated NQO1, which stabilized p65 by inhibiting ubiquitination, activating the NF-κB/CXCL12 axis, and recruiting Tregs. This pathway mediated therapeutic resistance. Plerixafor, a CXCL12 inhibitor, disrupted this axis and significantly enhanced anti-tumor efficacy when combined with anti-PD-1 plus lenvatinib in vivo. PIVKA-II is a potentially effective biomarker for predicting resistance to anti-PD-1 plus lenvatinib therapy. Its high expression denotes an immunosuppressive TME. Targeting the NQO1/CXCL12/Tregs axis with Plerixafor may restore sensitivity and improve outcomes.

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.”

BackgroundTumor-associated macrophages (TAMs) shape the tumor microenvironment and drive hepatocellular carcinoma (HCC) progression. However, the prognostic significance of TAM polarity-related genes, particularly based on the CXCL9:SPP1 signature, remains unclear.MethodsWe identified 372 TAM polarity-related genes in the TCGA-LIHC dataset. Prognostic candidates were selected using univariate Cox regression, bootstrap resampling, and the Boruta algorithm. Seven machine learning models were compared, and XGBoost was selected to construct a TAM polarity-related signature (TPS) consisting of 17 genes. TPS was validated in two external cohorts. Associations with clinical features, biological pathways, immune status, and drug sensitivity were explored. scRNA-seq and qRT-PCR were performed to investigate cellular expression and functional relevance.ResultsTPS markedly different patients into high- and low-risk groups with significantly different survival outcomes (TCGA 1-, 3-, 5-year AUCs: 0.91, 0.89, 0.88). High-risk patients showed enrichment in glycan metabolism, DNA repair, and oncogenic pathways, whereas low-risk patients displayed elevated lipid and amino acid metabolism. Immune profiling revealed greater infiltration of immunosuppressive cells and higher expression of immune checkpoints in high-risk patients. Drug sensitivity analysis identified potential therapeutic targets and candidate compounds, including CDK1, PLK1, and statins. scRNA-seq analysis highlighted disrupted macrophage-immune interactions and identified SPP1 as a key signaling mediator. Silencing of TTC1 and G6PD suppressed HCC cell proliferation.ConclusionWe developed and validated a robust TAM polarity-related signature that effectively stratifies HCC patients by prognosis. TPS provides insights into tumor immunity, metabolism, and drug response, and may serve as a valuable tool for precision medicine in HCC.

Combination of anti-PD-1 with lenvatinib showed clinical efficacy in multiple cancers, yet the underlying immunological mechanisms are unclear. Here, we compared T cells in hepatocellular carcinoma (HCC) patients before and after combination treatment using single-cell transcriptomics and T cell receptor (scTCR) clonotype analyses. We found that tumor-infiltrating GZMK+ CD8+ effector/effector memory T (Teff/Tem) cells, showing a favorable response to combination therapy, comprise progenitor exhausted T (Tpex) cells and also unappreciated circulating Tem (cTem) cells enriched with hepatitis B virus (HBV) specificity. Further integrated analyses revealed that cTem cells are specifically associated with responsiveness to the combination therapy, whereas Tpex cells contribute to responses in both combination therapy and anti-PD-1 monotherapy. Notably, an underexplored KIR+ CD8+ T cell subset in the tumor and FOXP3+ CD4+ regulatory T cells are specifically enriched in non-responders after the combination therapy. Our study thus elucidated T cell subsets associated with clinical benefits and resistance in cancer immunotherapy.

Introduction:It is challenging to diagnose liver masses in the context of a rough liver background using computed tomography and magnetic resonance imaging. Perfluorobutane CEUS microbubble, an ultrasound (US) contrast agent, has a unique phase called the Kupffer phase. This study aimed to explore whether the diagnostic ability of Kupffer-CEUS is affected by the rough liver background. Methods:A prospective analysis was conducted on patients with access to histological pathology of FLLs and liver parenchyma from 23 centers between August 2020 and March 2021. Kupffer-CEUS was performed on 552 patients, who were divided into two groups (normal and abnormal) based on the pathological results of liver parenchyma, and the abnormal group was further divided into four groups (sight liver fibrosis, serious liver fibrosis, fatty liver, mixed). Kupffer-CEUS was divided into vascular phase and vascular and Kupffer phase. Results:In Kupffer-CEUS, differences in diagnostic efficiency of FLLs between normal and abnormal liver backgrounds were not statistically significant. However, in patients with abnormal liver backgrounds, the specificity (57.45% vs. 74.47%, p = 0.008) and accuracy (89.81% vs. 96.92%, p < 0.001) of the vascular phase in distinguishing malignant from benign lesions were statistically lower than those of the vascular and Kupffer phase (V&KP). Subgroup analysis revealed that the sensitivity, specificity, and accuracy of V&KP in screening FLLs were all higher than those of vascular phase, except for the accuracy in patients with serious liver fibrosis (98.51% vs. 94.06, p < 0.001). Conclusion:This study indicated that although there is no obvious restriction on the choice of Kupffer-CEUS methods when diagnosing liver masses in patients with normal or abnormal liver backgrounds, Kupffer phase CEUS can effectively reduce the misdiagnosis of FLLs. Particularly for patients with serious liver fibrosis, contrast-enhanced US combined with the Kupffer phase can provide a more accurate diagnosis than conventional contrast-enhanced ultrasonography.

Precision medicine increasingly relies on molecular subtyping to guide individualized therapy for hepatocellular carcinoma (HCC), yet conventional tissue biopsies have limited capacity to capture tumor heterogeneity and temporal changes. This study utilized patient-derived xenograft (PDX) models to isolate authentic tumor-derived exosomal proteins, which were profiled to classify HCC patients into molecular subtypes. Differential expression analysis combined with survival association screening and a bootstrap strategy was used to identify robust prognostic candidates, followed by Boruta feature selection to refine the list to 14 key proteins. These were integrated into a machine learning model (TSExs) to predict patient survival and treatment response. Immune-related pathway enrichment was performed to characterize the immune microenvironment of each subtype. Two robust subtypes, S1 and S2, were identified. S1 tumors demonstrated heightened antigen presentation and T-cell activation but impaired immune clearance, whereas S2 tumors exhibited lower immune infiltration yet more efficient immune-mediated tumor elimination. The TSExs model achieved high prognostic accuracy and reliably predicted responses to chemotherapy and immunotherapy across independent cohorts. By integrating exosomal proteomics with machine learning, this study establishes a non-invasive, biologically informed framework for immune profiling and therapeutic prediction in HCC, supporting the clinical potential of exosomal proteins as precision oncology biomarkers.

Contrast-enhanced US demonstrated a sensitivity and area under the receiver operating characteristic curve noninferior to contrast-enhanced MRI in the detection of residual hepatocellular carcinoma after lenvatinib and anti–programmed cell death protein-1 antibody therapy.

Background & Aims: Only a minority of patients could benefit from systemic therapy owing to the high heterogeneity of HCC. Therefore, a deeper understanding of the pathogenesis of HCC is essential for precision therapy. Genomic and proteomic studies of HCC have enhanced our understanding of HCC. However, phosphoproteomic characterization of HCC remains poorly understood. Approach & Results: We conducted an in-depth analysis of a clinical cohort of HCC using high-coverage phosphoproteomic. Effective therapeutic targets were validated using liver cancer cell lines and HCC patient-derived xenograft (PDX) mouse models that correspond to the phosphoproteomic subtypes of HCC. Phosphoproteomic analysis classified HCC into three subtypes, A, B, and C, with increasing malignancy and correlation with clinical features, including patient prognosis, tumor staging, serum alpha fetoprotein (AFP) levels, tumor thrombus, and tumor size. Phosphoproteomic subtyping deeply reflected the biological characteristics and clinical features of HCC patients. The profiles of HCC dysregulated kinase activities inferred from the different phosphoproteomic subtypes, consistently identifying increased kinase activity related to cell proliferation. Subtype-C HCC patients showed the most significant dysregulation, indicating a potential therapeutic target. The corresponding drug, bosutinib, demonstrated efficacy in inhibiting the growth of subtype C tumors in liver cancer cell lines and HCC patient-derived xenograft (PDX) mouse models representative of the phosphoproteomic HCC subtypes. Conclusions: Our study provides a comprehensive exploration of the phosphoproteomic landscape of HCC, establishing new subtypes that match clinical features and identifying potential therapeutic targets for the most malignant C subtype.

Intrahepatic bile duct stone disease has a high morbidity in China, with a high rate of additional surgery, a high rate of cancer development, and a high disease burden. Activation of the MAPK pathway leading to up-regulation of MUC5AC expression is an important factor in the formation of intrahepatic bile duct stones. Exosomes or extracellular vesicles (EVs) can be used as therapeutic vectors to encapsulate and carry drugs into diseased cells to achieve a therapeutic effect. The current study alleviated intrahepatic bile duct stone disease by preparing EVs carrying miR-141-3p. First, the researchers loaded mesenchymal stem cell (ESC)-derived EVs with miR-141-3p (miR-141-3p-EVs) and verified the phenotypes and characteristics of miR-141-3p-EVs. miR-141- 3p-EVs successfully reduced the inflammatory level of human biliary epithelial cells (HIBEC) and lowered, via the MAPK pathway, MUC5AC expression. In an experiment involving an animal model of intrahepatic bile duct stones, miR-141-3p-EVs effectively alleviated stone formation, and the intrinsic mechanism was associated with the decreased level of MAPK pathway expression. In conclusion, results suggested that the EV-based strategy of miR- 141-3p delivery to intrahepatic bile duct epithelial cells has value and provides a new approach for the treatment of intrahepatic biliary stone disease.

Robotic-assisted hepatopancreatobiliary (HPB) surgery is increasingly adopted in high-volume centers. This study evaluated the feasibility, safety, and technical characteristics of the Toumai® robotic system in HPB surgery. We retrospectively analyzed 160 consecutive patients who underwent HBP surgery using the Toumai® system at the Chinese People’s Liberation Army General Hospital between November 2024 and June 2025. Procedures included liver resection (92 cases: 32 lobectomies/segmentectomies and 60 local resections), pancreatic surgery (23 cases: 2 pancreaticoduodenectomies, 9 distal pancreatectomies, 11 tumor resections, 1 pancreatic duct incision and pancreaticojejunostomy), and biliary surgery (37 cases: 3 radical resections for hilar cholangiocarcinoma, 23 biliary explorations and stone removals, 6 gallbladder cancer resections, 3 choledochojejunostomies, and 2 cholecystectomies). Of the cohort, 46 patients (28.8

Systemic therapy is typically the primary treatment choice for hepatocellular carcinoma (HCC) patients with extrahepatic metastases. Some patients may achieve partial response (PR) or complete response (CR) with systemic treatment, leading to the possibility of their primary tumor becoming resectable. This study aimed to investigate whether these patients could achieve longer survival through surgical resection of their primary tumor. We retrospectively collected data from 150 HCC patients with extrahepatic metastases treated at 15 different centers from January 1st, 2015, to November 30th, 2022. We evaluated their overall survival (OS) and progress-free survival (PFS) and analyzed risk factors impacting both OS and PFS were analyzed. Patients who received surgical treatment had longer OS compared to those who did not (median OS 16.5 months vs. 11.3 months). However, there was no significant difference in progression-free survival between the two groups. Portal vein invasion (P = 0.025) was identified as a risk factor for poor prognosis in patients, while effective first-line treatment (P = 0.039) and surgical treatment (P = 0.005) were protective factors. No factors showed statistical significance in the analysis of PFS. Effective first-line treatment (P = 0.027) and surgical treatment (P = 0.006) were both independent protective factors for prolonging patient prognosis, while portal vein invasion was an independent risk factor (P = 0.044). HCC patients with extrahepatic metastases who achieve PR/CR with conversion therapy may experience longer OS through surgical treatment. This study is the first to analyze the clinical outcomes of patients receiving surgical treatment for HCC with extrahepatic metastases.

Background: Microvascular invasion (MVI) is associated with an unfavorable prognosis and early recurrence of hepatocellular carcinoma (HCC), which is the crucial pathological hallmark of immunotherapy. While microvascular invasion (MVI) in hepatocellular carcinoma (HCC) currently lacks a detailed single-cell analysis of the tumor microenvironment (TME), it holds significant promise for immunotherapy using immune checkpoint inhibitors (ICI). Methods: We performed single-cell RNA sequencing (scRNA-seq) on 3 MVI positive (MVIP) and 14 MVI-negative (MVIN) tumor tissues, as well as their paired adjacent non-tumoral tissues. Results: We identified SPP1+ macrophages and CD4+ proliferative T cells as intertumoral populations critical for the formation of cold tumors and immunosuppressive environments in MVI-positive patients and verified their prognostic value in correlation with MVIP HCC patients. Additionally, we identified SPP1+ dominated interactions between SPP1+ macrophages and the immunosuppressive T population as contributors to MVI destruction and tumorigenesis. Conclusions: We provide a comprehensive single-cell atlas of HCC patients with MVI, shedding light on the immunosuppressive ecosystem and upregulated signaling associated with MVI. These findings demonstrate that intercellular mechanisms drive MVI and provide a potential immunotherapeutic target for HCC patients with HCC and underlying MVI.