BACKGROUND:Dual-phenotype hepatocellular carcinoma (DPHCC) is a recently defined subtype of hepatocellular carcinoma (HCC) characterized by the simultaneous hepatocellular and biliary epithelial marker expression. This study aimed to elucidate the clinicopathological features of DPHCC following curative liver resection and its relationship with prognosis. METHODS:We analyzed 1493 patients with HCC who underwent curative liver resection at the Peking Union Medical College Hospital from January 2013 to December 2023. All patients were divided into two groups according to immunohistochemical marker expression, with 487 and 1006 cases in the DPHCC and non-DPHCC groups, respectively. Propensity score matching was performed to reduce the deviation caused by baseline characteristics. RESULTS:After 1:2 matching (DPHCC/non-DPHCC group = 453/771), patients were comparable regarding all baseline characteristics. Compared to patients with non-DPHCC, those with DPHCC were significantly associated with poorer differentiation, microvascular invasion, satellite nodules, and bile duct tumor thrombus (P < 0.05). Patients with DPHCC also exhibited significantly worse recurrence-free survival (P = 0.009) and overall survival (P = 0.021). Furthermore, multivariate analysis revealed that DPHCC was an independent risk factor for recurrence-free survival (HR = 1.28, 95% CI: 1.05-1.52, P = 0.019) and overall survival (HR = 1.33, 95% CI: 1.15-1.51, P = 0.023). CONCLUSIONS:DPHCC, a newly proposed subtype of HCC, is associated with poorer clinicopathological features and adverse prognosis, providing important clinical guidance.

e16251 Background: Postoperative recurrence remains a major challenge in hepatocellular carcinoma (HCC), particularly among patients with high-risk pathological features. Currently, no globally accepted standard adjuvant therapy exists after curative resection. This study reports an interim analysis evaluating the efficacy and safety of adjuvant donafenib combined with transarterial chemoembolization (TACE) in patients with high-risk HCC following surgery. Methods: This prospective, single-arm, single-center study enrolled patients with hepatocellular carcinoma who underwent curative resection and had predefined high-risk recurrence features, including tumor size > 5 cm, microvascular invasion, satellite lesions, or portal vein tumor thrombus. Patients received donafenib (200 mg BID) combined with a fixed single session of postoperative transarterial chemoembolization for a planned duration of 6 months. The primary endpoint was 12-month recurrence-free survival rate, with secondary endpoints including recurrence-free survival, overall survival, time to recurrence, and safety. This study was registered at ClinicalTrials.gov (NCT05161143). Results: As of December 10, 2025, 25 patients were enrolled, with a median follow-up of 9.7 months. High-risk features included tumor size ≥5 cm (56.0%), MVI (56.0%), satellite lesions (20.0%), and multiple concurrent high-risk factors (36.0%), and notably, the inclusion of patients with concomitant PVTT (n = 2). At data cut-off, 4 patients experienced recurrence, including one death. The 6-month RFS rate was 95.2% (95% CI, 86.6-100), and the estimated 12-month RFS rate was 74.9% (95% CI, 56.0-100); median RFS was not reached. In subgroup analyses, 12-month RFS rates were 81.5% and 66.7% in patients with tumor size ≥5 cm and < 5 cm, respectively. Patients without MVI showed a numerically higher 12-month rate than those with MVI (80.8% vs 66.7%). No stable subgroup-specific differences were observed according to satellite lesions or PVTT. Overall survival data remain immature. Treatment-emergent adverse events (TEAEs) occurred in 84.0% of patients, with grade ≥3 TEAEs reported in 36.0%. No grade 4 or 5 treatment-related adverse events were observed. ALBI scores remained stable during treatment, with no significant difference between baseline and end of treatment (median −3.12 vs −3.14, p = 0.68), indicating preserved liver function. Conclusions: This interim analysis suggests that adjuvant donafenib combined with a single session of postoperative TACE demonstrates encouraging antitumor activity and a manageable safety profile in patients with high-risk HCC after curative resection. Longer follow-up and larger studies are warranted to confirm the durability of benefit. Clinical trial information: NCT05161143 .

Chemotherapy, alone or combined with immune checkpoint inhibitors (ICIs), remains the standard first-line treatment for advanced intrahepatic cholangiocarcinoma (ICC), but survival gains are modest. Triple-combination strategies integrating targeted therapy, ICIs, and locoregional treatment have shown promise in biliary tract cancer, yet sintilimab-based regimens have not been systematically evaluated. This study assessed the efficacy and safety of sintilimab plus lenvatinib and locoregional therapy (triple-regimen) in advanced ICC. In this multicenter retrospective study, 169 patients with advanced ICC received triple-regimen, ICIs plus chemotherapy (ICIs-chemo), or chemotherapy alone between October 2019 and June 2025. Locoregional modalities included external beam radiation therapy, hepatic arterial infusion chemotherapy, and transarterial chemoembolization. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (AEs). The triple-regimen was associated with improved survival versus both comparators. Median PFS was 11.9 months with triple-regimen versus 6.0 months with ICIs-chemo (P < 0.001) and 5.2 months with chemotherapy (P = 0.007); median OS was 18.7 versus 14.4 and 13.4 months (P = 0.044 and 0.036), respectively. ORR was higher with triple-regimen (53.3

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy with a dismal prognosis, and pronounced interpatient heterogeneity severely limits the efficacy of systemic therapies, underscoring the need for rapid and accurate functional platforms to guide individualized drug selection. Here, we develop a clinically oriented, patient-derived, 3D bioprinted in vitro model for personalized drug sensitivity assessment in ICC. Using a compositionally defined and cost-effective GelMA/HAMA composite hydrogel, we reconstruct a tumor microenvironment that supports rapid self-organization and sustained viability of primary ICC cells. Histological analyses, marker expression profiling, and bright-field imaging demonstrate close similarity to matched patient tumor tissues. Genomic and transcriptomic fidelity are further confirmed by whole-exome and RNA sequencing, revealing preserved driver mutations and transcriptional programs. Drug sensitivity testing was performed on tumor samples from 21 ICC patients using clinically relevant agents. Notably, in patients receiving neoadjuvant therapy, in vitro drug responses were fully consistent with clinical outcomes. Longitudinal follow-up further showed that recurrence occurred exclusively in patients who did not receive the predicted sensitive therapies. Importantly, clinically actionable drug response profiles were generated within 10 days. Collectively, this platform provides a rapid, reproducible, and patient-specific functional drug testing strategy with strong potential for clinical translation.

Background and Objective:Pulmonary nodules are commonly identified in clinical practice, frequently as incidental findings during imaging performed for unrelated indications. Their management poses significant clinical challenges, as accurate risk stratification and timely diagnosis are essential to distinguish benign from malignant lesions. However, variability in clinician expertise often results in inconsistent decision-making. Artificial intelligence (AI) offers promising solutions for standardizing pulmonary nodule assessment and enhancing clinician training. This narrative review systematically compiles the current status and research progress of the application of AI technology in the field of medical education, especially in the teaching of pulmonary nodule management, and further discusses its future development trend. Methods:A narrative literature review was conducted using electronic databases, including PubMed and Google Scholar, to identify relevant peer-reviewed studies published in recent years. Literature retrieval was conducted in major research areas such as AI, medical education, pulmonary nodules, and clinical decision support. Articles were selected based on their relevance to AI-based educational tools, decision support systems, and diagnostic applications in pulmonary nodule evaluation. Key Content and Findings:The review reveals a growing integration of AI technologies in medical education and clinical training related to pulmonary nodule management. AI-driven educational platforms, including virtual simulation environments and intelligent tutoring systems, have demonstrated effectiveness in improving learners' skills in imaging interpretation and clinical risk assessment. Moreover, AI-enhanced decision support tools have the capacity to reduce diagnostic variability, particularly among trainees and early-career clinicians. In view of this, the medical education system urgently needs to introduce AI-related courses and build an interdisciplinary talent cultivation framework to promote the teaching of lung nodule management towards intelligence and precision. Conclusions:AI is the link between medical education and the clinical management of lung nodules, and is a transformative force driving its development. Its integration into training programs can facilitate more interactive, personalized, and effective learning experiences, ultimately contributing to improved diagnostic precision and patient outcomes. Future research should focus on validating AI-assisted educational interventions, addressing challenges in implementation, and ensuring their ethical and equitable use across diverse healthcare settings. Broader adoption of such technologies may significantly advance both clinician preparedness and the quality of care delivered to patients with pulmonary nodules.

Urine, a rich biological resource containing diverse metabolites, proteins, exfoliated cells, and cell-free DNA, provides valuable insights into physiological and pathological states. Its noninvasive nature and ease of collection have established urinary biomarkers as promising tools for detecting urological cancers, particularly bladder, prostate, and cervical malignancies. Advances in multi-omics technologies, including genomics, proteomics, and metabolomics, have significantly enhanced analytical sensitivity and specificity, improving diagnostic accuracy and disease monitoring. This comprehensive review systematically examines recent progress in biomarker discovery and clinical applications across various cancers, critically evaluating their diagnostic potential while addressing current limitations and challenges. The insights provided in this study aim to facilitate the optimization of urinary biomarker-based strategies and promote their broader integration into clinical practice for improved cancer detection and management.

Background:Hepatocellular carcinoma (HCC) with microvascular invasion (MVI) is associated with high recurrence and poor survival outcomes. Although adjuvant therapies such as transcatheter arterial chemoembolization (TACE), targeted therapy, and immunotherapy show potential in improving outcomes, the optimal postoperative treatment strategy remains undetermined. This study evaluates the efficacy of different adjuvant treatments on disease-free survival (DFS) and overall survival (OS) in HCC patients with MVI following curative resection. Methods:A retrospective cohort of 409 HCC patients with MVI who underwent curative resection from three clinical centers between 2017 and 2024 was analyzed. Patients were stratified into three groups: TACE alone (n=132), TACE + targeted therapy (n=58), and TACE + targeted immunotherapy (n=68). Propensity score matching (PSM) was employed to balance confounding factors. Kaplan-Meier survival curves and Cox regression models were used to assess DFS and OS. A nomogram was constructed for individualized DFS prediction. Results:After PSM, both the TACE + targeted therapy and TACE + targeted immunotherapy groups exhibited significantly prolonged DFS compared to TACE alone (median DFS: 16 vs 22 and 21 months, respectively; p=0.027). No significant differences were observed in OS across the groups. The nomogram for DFS demonstrated robust predictive performance, with a C-index of 0.709 and 0.645 in the training and validation cohorts, respectively, supporting its utility in clinical decision-making. Conclusion:In HCC patients with MVI, adjuvant TACE combined with targeted therapy or targeted immunotherapy significantly enhances DFS, though no OS benefit was observed. The developed nomogram provides a reliable tool for risk stratification and personalized postoperative management in this high-risk patient population.

Background and Aims:Dual-phenotype hepatocellular carcinoma (DPHCC) is an uncommon, highly aggressive form of liver cancer defined by the concurrent expression of both hepatocellular and cholangiocytic markers. This biphenotypic nature contributes to early recurrence and significantly worse survival compared to classic HCC. The benefit of adjuvant transarterial chemoembolization (TACE) after resection for DPHCC is unclear. We aimed to evaluate whether postoperative TACE improves outcomes in patients with resected DPHCC. Methods:We retrospectively evaluated 436 patients with confirmed DPHCC who underwent curative resection from 2013-2023 at a single center. Among them, 276 received adjuvant TACE and 160 had surgery alone. To minimize selection bias, we performed 1:2 propensity score matching, yielding a balanced cohort of 210 TACE-treated patients and 134 observation-only patients. Recurrence-free survival (RFS) and overall survival (OS) were assessed with Kaplan-Meier and Cox analyses (median follow-up 58 months). Results:Adjuvant TACE significantly prolonged RFS and OS compared to observation. In the matched cohort, TACE reduced the hazard of recurrence by 32% (HR 0.678, P = 0.032) and the hazard of death by 47% (HR 0.533, P = 0.026). Multivariate analysis confirmed adjuvant TACE as an independent protective factor for RFS and OS. Toxicities were mostly mild (11.4% Grade 3-4; no treatment-related deaths). Conclusion:In patients with DPHCC, the addition of adjuvant TACE after curative resection substantially lowers recurrence rates and prolongs long-term survival. These findings support incorporating TACE into postoperative management for this high-risk HCC subtype, warranting confirmation in prospective trials. Clinical Trial Registration:This study has been registered with the Chinese Clinical Trial Registry Center (ChiCTR2500103222).

Gallbladder cancer (GBC) is a highly aggressive malignancy, with limited survival profiles after curative surgeries. This study aimed to develop a practical model for predicting the postoperative overall survival (OS) in GBC patients. Patients from three hospitals were included. Two centers (N = 102 and 100) were adopted for model development and internal validation, and the third center (N = 85) was used for external testing. Univariate and stepwise multivariate Cox regression were used for feature selection. A nomogram for 1-, 3-, and 5-year postoperative survival rates was constructed accordingly. Performance assessment included Harrell's concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves. Kaplan-Meier curves were utilized to evaluate the risk stratification results of the nomogram. Decision curves were used to reflect the net benefit. Eight factors, TNM stage, age-adjusted Charlson Comorbidity Index (aCCI), body mass index (BMI), R0 resection, blood platelet count, and serum levels of albumin, CA125, CA199 were incorporated in the nomogram. The time-dependent C-index consistently exceeded 0.70 from 6 months to 5 years, and time-dependent ROC revealed an area under the curve (AUC) of over 75

AbstractThe influence of liver fibrosis on the rate of liver regeneration and complications following ALPPS has yet to be fully understood. This study aimed to scrutinize the effects of liver fibrosis on the postoperative complications, and prognosis subsequent to ALPPS. Clinical data were collected from patients with primary liver cancer who underwent ALPPS at Peking Union Medical College Hospital between May 2014 and October 2022. The degree of liver fibrosis was assessed using haematoxylin–eosin staining and Sirius red staining. This study encompassed thirty patients who underwent ALPPS for primary liver cancer, and there were 23 patients with hepatocellular carcinoma, 5 with cholangiocarcinoma, and 2 with combined hepatocellular-cholangiocarcinoma. The impact of severe liver fibrosis on the rate of liver regeneration was not statistically significant (P = 0.892). All patients with severe complications belonged to the severe liver fibrosis group. Severe liver fibrosis exhibited a significant association with 90 days mortality (P = 0.014) and overall survival (P = 0.012). Severe liver fibrosis emerges as a crucial risk factor for liver failure and perioperative mortality following the second step of ALPPS. Preoperative liver function impairment is an important predictive factor for postoperative liver failure.

Transarterial chemoembolization (TACE) is one of the predominant locoregional therapeutic modalities for addressing hepatocellular carcinoma (HCC). However, achieving precise prognostic predictions and effective patient selection remains a challenging pursuit. The primary objective of this systematic review and meta-analysis is to evaluate the efficacy of radiomics in forecasting the prognosis associated with TACE treatment. A comprehensive exploration of pertinent original studies was undertaken, encompassing databases of PubMed, Web of Science and Embase. The studies' quality was meticulously evaluated employing the quality assessment of diagnostic accuracy studies 2 (QUADAS-2), the radiomics quality score (RQS) and the METhodological RadiomICs Score (METRICS). Pooled statistics, along with 95

Abstract Introduction: Hepatocellular Carcinoma (HCC) is a highly malignant and challenging-to-treat tumor, with early recurrence affecting up to 35-50% of patients within two years after surgery, significantly impacting prognosis. Identifying high-risk patients for recurrence is critical for guiding postoperative adjuvant therapy. The rapidly advancing field of single-cell RNA sequencing technology offers an unprecedented opportunity to discover clinically relevant cell subpopulations. Here, we harnessed single-cell techniques to unveil a cell subpopulation closely linked with HCC recurrence, highlighting its clinical significance. Methods and Results: We conducted single-cell RNA sequencing on four HCC samples and harmonized data from three public datasets (GSE112271, GSE125449, CNP0000650) to elucidate the heterogeneity of malignant cells in HCC. Our investigation revealed a distinctive HCC subpopulation enriched in patients with early recurrence (11.4% vs. 3.8%, P=0.02). This subpopulation exhibited up-regulated STMN1 and EZH2, signifying high proliferative potential and a propensity for epithelial-mesenchymal transition (EMT). Applying the CIBERSORTx algorithm to the TCGA-LIHC dataset (N=323 patients), we inferred the proportion of this recurrence subpopulation among all malignant cells. Notably, patients with a higher proportion of this subpopulation (N=160) demonstrated significantly shorter recurrence-free survival (31.2 vs. 42.9 months, P=0.002), reduced median survival (45.9 vs 55.7 months, P=0.03) and a higher rate of microvascular invasion (35% vs. 23%, P=0.01). To validate this recurrence-related subpopulation in clinical samples, we conducted multiplex immunohistochemistry staining on paraffin-embedded (FFPE) HCC samples (including CD45, CD31, ARG1, STMN1, EZH2) and used machine learning for its identification. Our findings revealed that patients with a higher proportion of this recurrence subpopulation (N=40) experienced significantly shorter median survival (38.5 vs. 51.0 months, P<0.005) and progression-free survival (25.1 vs. 33.4 months, P=0.01) compared to a lower proportion (N=40). Multivariate Cox regression analysis confirmed that the proportion of this recurrence subpopulation is an independent predictor of worse prognosis (P=0.003). Conclusion: Through the power of single-cell RNA sequencing technology, we have unearthed and characterized a malignant cell subpopulation intricately connected with HCC recurrence. Importantly, this subpopulation can be identified in FFPE tissue samples and correlates robustly with patient prognosis. Our study underscores the transformative possibility of single-cell techniques in developing cell subpopulation-based biomarkers, emphasizing their clinical relevance and potential utility in guiding postoperative adjuvant therapy for HCC patients. Citation Format: Yucheng Dong, Xin Guo, Xuezhu Wang, Fan Yang, Yongchang Zheng, Yang Chen. Single-cell sequencing identification of malignant cell subpopulations linked to recurrence in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 865.

Large-scale transcriptomic data are crucial for understanding the molecular features of hepatocellular carcinoma (HCC). Integrated 15 transcriptomic datasets of HCC clinical samples, the first version of HCC database (HCCDB v1.0) was released in 2018. Through the meta-analysis of differentially expressed genes and prognosis-related genes across multiple datasets, it provides a systematic view of the altered biological processes and the inter-patient heterogeneities of HCC with high reproducibility and robustness. With four years having passed, the database now needs integration of recently published datasets. Furthermore, the latest single-cell and spatial transcriptomics have provided a great opportunity to decipher complex gene expression variations at the cellular level with spatial architecture. Here, we present HCCDB v2.0, an updated version that combines bulk, single-cell, and spatial transcriptomic data of HCC clinical samples. It dramatically expands the bulk sample size by adding 1656 new samples from 11 datasets to the existing 3917 samples, thereby enhancing the reliability of transcriptomic meta-analysis. A total of 182,832 cells and 69,352 spatial spots are added to the single-cell and spatial transcriptomics sections, respectively. A novel single-cell level and 2-dimension (sc-2D) metric is proposed as well to summarize cell type-specific and dysregulated gene expression patterns. Results are all graphically visualized in our online portal, allowing users to easily retrieve data through a user-friendly interface and navigate between different views. With extensive clinical phenotypes and transcriptomic data in the database, we show two applications for identifying prognosis-associated cells and tumor microenvironment. HCCDB v2.0 is available at http://lifeome.net/database/hccdb2.

Background2D CT image-guided radiofrequency ablation (RFA) is an exciting minimally invasive treatment that can destroy liver tumors without removing them. However, CT images can only provide limited static information, and the tumor will move with the patient's respiratory movement. Therefore, how to accurately locate tumors under free conditions is an urgent problem to be solved at present.PurposeThe purpose of this study is to propose a respiratory correlation prediction model for mixed reality surgical assistance system, Riemannian and Multivariate Feature Enhanced Temporal Convolutional Network (R-MFE-TCN), and to achieve accurate respiratory correlation prediction.MethodsThe model adopts a respiration-oriented Riemannian information enhancement strategy to expand the diversity of the dataset. A new Multivariate Feature Enhancement module (MFE) is proposed to retain respiratory data information, so that the network can fully explore the correlation of internal and external data information, the dual-channel is used to retain multivariate respiratory feature, and the Multi-headed Self-attention obtains respiratory peak-to-valley value periodic information. This information significantly improves the prediction performance of the network. At the same time, the PSO algorithm is used for hyperparameter optimization. In the experiment, a total of seven patients' internal and external respiratory motion trajectories were obtained from the dataset, and the first six patients were selected as the training set. The respiratory signal collection frequency was 21 Hz.ResultsA large number of experiments on the dataset prove the good performance of this method, which improves the prediction accuracy while also having strong robustness. This method can reduce the delay deviation under long window prediction and achieve good performance. In the case of 400 ms, the average RMSE and MAE are 0.0453 and 0.0361 mm, respectively, which is better than other research methods.ConclusionThe R-MFE-TCN can be extended to respiratory correlation prediction in different clinical situations, meeting the accuracy requirements for respiratory delay prediction in surgical assistance.

BackgroundLong noncoding RNAs (lncRNAs) have emerged as critical regulators of colorectal cancer (CRC) progression, but their roles and underlying mechanisms in colorectal cancer liver metastases (CRLMs) remain poorly understood.MethodsTo explore the expression patterns and functions of lncRNAs in CRLMs, we analyzed the expression profiles of lncRNAs in CRC tissues using the TCGA database and examined the expression patterns of lncRNAs in matched normal, CRC, and CRLM tissues using clinical samples. We further investigated the biological roles of LINC02257 in CRLM using in vitro and in vivo assays, and verified its therapeutic potential in a mouse model of CRLM.ResultsOur findings showed that LINC02257 was highly expressed in metastatic CRC tissues and its expression was negatively associated with overall survival. Functionally, LINC02257 promoted CRC cell growth, migration, metastasis, and inhibited cell apoptosis in vitro, and enhanced liver metastasis in vivo. Mechanistically, LINC02257 up-regulated phosphorylated c-Jun N-terminal kinase (JNK) to promote CRLM.ConclusionsOur study revealed that LINC02257 played a key role in the proliferation and metastasis of CRC cells through the LINC02257/JNK axis. Targeting this axis may represent a promising therapeutic strategy for the treatment of liver metastases in patients with CRC.

The authors regret that an error was made in the detail for affiliation c. The correct affiliation is: Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. The authors would like to apologise for any inconvenience caused. Re: Pathologic complete responses, long-term outcomes, and recurrence patterns in HER2-low vs. HER2-zero breast cancer after neoadjuvant chemotherapy: Several issues about HER2 expression and neoadjuvant chemotherapy in breast cancerEuropean Journal of CancerVol. 180PreviewWe followed with interest the report by Sora Kang et al. that pathological complete response (pCR) rate and disease-free survival (DFS) in patients with HER2-low as well as HER2-0 breast cancers who have undergone neoadjuvant chemotherapy [1]. There are many complex factors influencing condition of response and survival of breast cancer after neoadjuvant therapy by the changes of HER2 and hormone receptor (HR) status. We appreciated the authors' work in comparing the prognosis of patients with breast cancer after neoadjuvant chemotherapy in different HER2 status and providing new therapeutic ideas. Full-Text PDF

Clinical Imapct This article showed images of a patient with idiopathic serial right internal mammary artery true aneurysms treated by endovascular embolization, which is a rare diagnosis and should be considered in differential diagnosis of paratracheal mass.

Iron is essential to organisms, the liver plays a vital role in its storage. Under pathological conditions, iron uptake by the intestine or hepatocytes increases, allowing excess iron to accumulate in liver cells. When the expression of hepcidin is abnormal, iron homeostasis in humans cannot be regulated, and resulting in iron overload. Hepcidin also regulates the release of iron from siderophores, thereby regulating the concentration of iron in plasma. Important factors related to hepcidin and systemic iron homeostasis include plasma iron concentration, body iron storage, infection, inflammation, and erythropoietin. This review summarizes the mechanism and regulation of iron overload caused by hepcidin, as well as related liver diseases caused by iron overload and treatment.