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1
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Pescatori LC, Dessain M, N'Kontchou G, Petit A, Diallo A, Blaise L, Rols MP, Poignard C, Nault JC, Ganne-Carrié N, Nahon P, Sutter O, Seror O. The role of early MRI in assessing the risk of local tumor progression following irreversible electroporation for hepatocellular carcinoma treatment. Int J Hyperthermia 2025; 42:2505595. [PMID: 40436745 DOI: 10.1080/02656736.2025.2505595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 04/22/2025] [Accepted: 05/08/2025] [Indexed: 06/11/2025] Open
Abstract
BACKGROUND Irreversible electroporation (IRE) in hepatocellular carcinoma (HCC) triggers apoptosis instead of thermal coagulation, resulting in specific modifications within ablation zones. Aim of this study is to evaluate the diagnostic value of MRI performed three days post-IRE (D3MRI). METHODS This single-institution retrospective study examined patients with HCC treated by IRE from 2012-2017. Criteria included no prior HCC treatment, available D3MRI and one-month MRI (M1MRI) without residual tumor and at least one follow-up MRI after 3 months. We measured the peripheral hyperemia (IREPZ) and central necrotic zone (IRECZ) in the ablation area along with the minimum thickness of IREPZ (min.Th/IREPZ) on both D3MRI and M1MRI. The duration of follow-up and instances of local tumor progression (LTP) were recorded. RESULTS Forty-eight patients (median age: 68 years) with 65 treated nodules (median diameter: 19 mm) were included. The median follow-up was 37 months. D3MRI median dimensions were 67 mm for IREPZ, 19 mm for IRECZ, and 5 mm for min.Th/IREPZ. LTP occurred in 25 nodules after 18 months. 52% had LTP at min.Th/IREPZ. A min.Th/IREPZ ≤ 5 mm on D3MRI indicated a 24-fold higher risk of LTP (95% CI [2.25-255.95], p < .01), conversely, the min.Th/IREPZ on M1MRI had no predictive value. CONCLUSION D3MRI appears to be a valuable tool for assessing the true ablation margins in HCC nodules treated with IRE and for identifying potential sites of local recurrence. It may, therefore, be considered for integration into the follow-up protocol for patients undergoing IRE treatment for HCC.
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Affiliation(s)
| | - Mathilde Dessain
- Interventional Radiology Department, Avicenne Hospital (APHP), Bobigny, France
| | | | - Arthur Petit
- Interventional Radiology Department, Avicenne Hospital (APHP), Bobigny, France
| | - Abou Diallo
- Department of Medical Informatics, Avicenne Hospital (APHP), Bobigny, France
| | - Lorraine Blaise
- Hepatology Department, Avicenne Hospital (APHP), Bobigny, France
| | - Marie-Pierre Rols
- Pharmacology and Biology Department, Toulouse University, CNRS, UPS, Toulouse, France
| | | | | | | | - Pierre Nahon
- Hepatology Department, Avicenne Hospital (APHP), Bobigny, France
| | - Olivier Sutter
- Interventional Radiology Department, Avicenne Hospital (APHP), Bobigny, France
| | - Olivier Seror
- Interventional Radiology Department, Avicenne Hospital (APHP), Bobigny, France
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Buttler L, Velázquez-Ramírez DA, Tiede A, Conradi AM, Woltemate S, Geffers R, Bremer B, Spielmann V, Kahlhöfer J, Kraft AR, Schlüter D, Wedemeyer H, Cornberg M, Falk C, Vital M, Maasoumy B. Distinct clusters of bacterial and fungal microbiota in end-stage liver cirrhosis correlate with antibiotic treatment, intestinal barrier impairment, and systemic inflammation. Gut Microbes 2025; 17:2487209. [PMID: 40255076 PMCID: PMC12054929 DOI: 10.1080/19490976.2025.2487209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 01/22/2025] [Accepted: 03/25/2025] [Indexed: 04/22/2025] Open
Abstract
Decompensated liver cirrhosis (dLC) is associated with intestinal dysbiosis, however, underlying reasons and clinical consequences remain largely unexplored. We investigated bacterial and fungal microbiota, their relation with gut barrier integrity, inflammation, and cirrhosis-specific complications in dLC-patients. Competing-risk analyses were performed to investigate clinical outcomes within 90 days. Samples were prospectively collected from 95 dLC-patients between 2017 and 2022. Quantitative metagenomic analyses clustered patients into three groups (G1-G3) showing distinct microbial patterns. G1 (n = 39) displayed lowest diversity and highest Enterococcus abundance, G2 (n = 24) was dominated by Bifidobacteria, G3 (n = 29) was most diverse and clustered most closely with healthy controls (HC). Of note, bacterial concentrations were significantly lower in cirrhosis compared with HC, especially for G1 that also showed the lowest capacity to produce short chain fatty acids and secondary bile acids. Consequently, fungal overgrowth, dominated by Candida spp. (51.63%), was observed in G1. Moreover, G1-patients most frequently received antibiotics (n = 33; 86.8%), had highest plasma-levels of Zonulin (p = 0.044) and a proinflammatory cytokine profile along with numerically higher incidences of subsequent infections (p = 0.09). In conclusion, distinct bacterial clusters were observed at qualitative and quantitative levels and correlated with fungal abundances. Antibiotic treatment significantly contributed to dysbiosis, which translated into intestinal barrier impairment and systemic inflammation.
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Affiliation(s)
- Laura Buttler
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - David A. Velázquez-Ramírez
- Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
| | - Anja Tiede
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
| | - Anna M. Conradi
- Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
| | - Sabrina Woltemate
- Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany
| | - Robert Geffers
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
- Genome Analytics Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany
| | - Birgit Bremer
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Vera Spielmann
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Center for Infectious Disease Research (DZIF), HepNet Study-House/German Liver Foundation, Hannover, Germany
| | - Julia Kahlhöfer
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Center for Infectious Disease Research (DZIF), HepNet Study-House/German Liver Foundation, Hannover, Germany
| | - Anke R.M Kraft
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
- Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
- Centre for Experimental and Clinical Infection Research, A Joint Venture Between Helmholtz-Centre for Infection Research and Hannover Medical School, TWINCORE, Hannover, Germany
- Center for Individualized Infection Medicine (CiiM), Hannover, Germany
| | - Dirk Schlüter
- Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
- Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
- Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
- Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
- Centre for Experimental and Clinical Infection Research, A Joint Venture Between Helmholtz-Centre for Infection Research and Hannover Medical School, TWINCORE, Hannover, Germany
- Center for Individualized Infection Medicine (CiiM), Hannover, Germany
| | - Christine Falk
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
- Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
- Institute of Transplant Immunology, Hannover Medical School, Hannover, Germany
| | - Marius Vital
- Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
| | - Benjamin Maasoumy
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
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Zhou G, Sun B, Zhang F, Ji H, Kan X, Yang X. Radiofrequency hyperthermia enhances the antitumor efficacy of oncolytic peptide LTX-315 in liver cancer cells by activating of cGAS-STING pathway. Int J Hyperthermia 2025; 42:2511031. [PMID: 40485182 DOI: 10.1080/02656736.2025.2511031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 04/26/2025] [Accepted: 05/20/2025] [Indexed: 06/11/2025] Open
Abstract
PURPOSE This study evaluated whether radiofrequency hyperthermia (RFH) could enhance the effects of LTX-315, an oncolytic peptide, for hepatic cancer. METHODS In vitro experiments using rat hepatocellular carcinoma (HCC) cells and in vivo experiments with HCC rat models were conducted. Treatments included (1) phosphate buffered saline, (2) RFH at 42 °C for 30 min, (3) LTX-315 alone, and (4) a combination of RFH with LTX-315. Cell viability and apoptosis were measured using MTS assay, flow cytometry, and fluorescence microscopy. Tumor growth was monitored for two weeks using ultrasound and optical imaging. The western blotting, enzyme-linked immunoassay, real-time polymerase chain reaction, were performed to detect the activation of cGAS-STING pathway. The immunohistochemistry, enzyme-linked immunoassay, real-time polymerase chain reaction, and flow cytometry analysis were performed to evaluate changes of immune cells in tumors, and changes of cytokines in plasma and tumors after the treatment. RESULTS The combination treatment (RFH + LTX-315) resulted in the highest level of apoptosis and the lowest cell viability, along with the smallest tumor volume and strongest reduction in bioluminescence signal compared to other groups (p < 0.001). LTX-315 activated the cGAS-STING pathway, with RFH further enhancing this activation. After combination therapy, significant increases in CD8+ T cells, CD8+/IFN-γ+ T cells, CD8+/TNF-α+ T cells, and natural killer cells, along with a decrease in Tregs, were observed in tumors (p < 0.001). CONCLUSION RFH significantly enhanced the effects of LTX-315 on orthotopic HCC by activating the cGAS-STING pathway.
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Affiliation(s)
- Guanhui Zhou
- Image-Guided Bio-Molecular Intervention Research and Section of Vascular and Interventional Radiology, Department of Radiology, University of Washington School of Medicine, Seattle, WA, USA
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Bo Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Feng Zhang
- Image-Guided Bio-Molecular Intervention Research and Section of Vascular and Interventional Radiology, Department of Radiology, University of Washington School of Medicine, Seattle, WA, USA
| | - Hongxiu Ji
- Image-Guided Bio-Molecular Intervention Research and Section of Vascular and Interventional Radiology, Department of Radiology, University of Washington School of Medicine, Seattle, WA, USA
- Department of Pathology, Overlake Medical Center and Incyte Diagnostics, Bellevue, WA, USA
| | - Xuefeng Kan
- Image-Guided Bio-Molecular Intervention Research and Section of Vascular and Interventional Radiology, Department of Radiology, University of Washington School of Medicine, Seattle, WA, USA
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaoming Yang
- Image-Guided Bio-Molecular Intervention Research and Section of Vascular and Interventional Radiology, Department of Radiology, University of Washington School of Medicine, Seattle, WA, USA
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Vrtělka O, Králová K, Fousková M, Setnička V. Comprehensive assessment of the role of spectral data pre-processing in spectroscopy-based liquid biopsy. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2025; 339:126261. [PMID: 40273765 DOI: 10.1016/j.saa.2025.126261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Revised: 04/05/2025] [Accepted: 04/16/2025] [Indexed: 04/26/2025]
Abstract
Spectroscopic data often contain artifacts or noise related to the sample characteristics, instrumental variations, or experimental design flaws. Therefore, classifying the raw data is not recommended and might lead to biased results. Nevertheless, most issues may be addressed through appropriate data pre-processing. Effective pre-processing is particularly crucial in critical applications like liquid biopsy for disease detection, where even minor performance improvements may impact patient outcomes. Unfortunately, there is no consensus regarding optimal pre-processing, complicating cross-study comparisons. This study presents a comprehensive evaluation of various pre-processing methods and their combinations to assess their influence on classification results. The goal was to identify whether some pre-processing methods are associated with higher classification outcomes and find an optimal strategy for the given data. Data from Raman optical activity and infrared and Raman spectroscopy were processed, applying tens of thousands of possible pre-processing pipelines. The resulting data were classified using three algorithms to distinguish between subjects with liver cirrhosis and those who had developed hepatocellular carcinoma. Results highlighted that some specific pre-processing methods often ranked among the best classification results, such as the Rolling Ball for correcting the baseline of Raman spectra or the Doubly Reweighted Penalized Least Squares and Mixture model in the case of Raman optical activity. On the other hand, the selection of filtering and/or normalization approach usually did not have a significant impact. Nonetheless, the pre-processing of top-scoring pipelines also depended on the classifier utilized. The best pipelines yielded an AUROC of 0.775-0.823, varying with the evaluated spectroscopic data and classifier.
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Affiliation(s)
- Ondřej Vrtělka
- Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague 6, Czech Republic.
| | - Kateřina Králová
- Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague 6, Czech Republic
| | - Markéta Fousková
- Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague 6, Czech Republic
| | - Vladimír Setnička
- Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague 6, Czech Republic.
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Shui Y, Dai D, Yang Y, Yang J, Xuan F, Chen H, Liu L, Yu Q, Guo Y, Yu R, Lou J, Wei Q. The Role of Stereotactic Body Radiation Therapy in the Outcomes of Intrahepatic Recurrent Small Hepatocellular Carcinoma. J Clin Exp Hepatol 2025; 15:102561. [PMID: 40292335 PMCID: PMC12023874 DOI: 10.1016/j.jceh.2025.102561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Accepted: 03/26/2025] [Indexed: 04/30/2025] Open
Abstract
Background and aim To retrospectively evaluate the role of stereotactic body radiation therapy (SBRT) played for the outcomes of intrahepatic recurrent small hepatocellular carcinoma (HCC). Methods We collected 51 intrahepatic recurrent ≤5 cm small HCC patients between January 2016 and December 2021. SBRT was given as 4-5 fractions with 32.5-50Gy. The baseline data of the patients and the radiotherapy strategy data were collected and survival analyses were performed among these factors. The outcomes comprised overall survival (OS), freedom from local progression (FFLP), and progression-free survival (PFS), with the 95% confidence interval (95%CI). The follow-up time was calculated from the date of the SBRT to the date of the last follow-up communication, hospitalization, or death. Survival analysis was conducted by the Kaplan-Meier methods and log-rank test. Results The median follow-up time was 48 months (range: 4.8-90). The 1-year, 3-year, and 5-year OS rates of the overall cohort were 95.9% (95%CI: 0.905-1.000), 84.9% (95%CI: 0.751-0.959) and 69.1% (95%CI: 0.553-0.862), respectively. The 1-year, 3-year, and 5-year FFLP rates of the overall cohort were 97.5% (95%CI: 0.928-1.000), 82.0% (95%CI: 0.697-0.965), and 72.8% (95%CI: 0.578-0.918), respectively. The 1-year, 3-year, and 5-year PFS rates of the overall cohort were 85.7% (95%CI: 0.758-0.970), 43.4% (95%CI: 0.296-0.635), and 27.3% (95%CI: 0.149-0.498), respectively. The 5-year FFLP rate of lesions less than 2 cm [72.5% (95%CI: 0.52-1)] and those 2-5 cm [71.9% (95%CI: 0.514-0.976)] were similar. We suggested that the lesions received 45Gy/50Gy with 5 fractions were associated with a higher 5-year FFLP rate [74.6% (95%CI: 0.57-0.976)] than 40Gy/5F [40.0% (95%CI: 0.137-1)]. Conclusion We found SBRT was effective in patients with lesion size of 2-5 cm, with similar results in those with tumor size of 0-2 cm. We suggested that the lesions received over 85.5Gy of biological effective dose with α/β = 10Gy were associated with a higher FFLP.
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Affiliation(s)
- Yongjie Shui
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Dongjun Dai
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yang Yang
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jia Yang
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Feng Xuan
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Haiyan Chen
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lihong Liu
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qianqian Yu
- Department of Radiation Oncology, Wushan Campus of Hangzhou First People's Hospital, Hangzhou, China
| | - Yinglu Guo
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Risheng Yu
- Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jianying Lou
- Department of Hepatobiliary Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qichun Wei
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Zhao KF, Xie CB, Wu Y. Prediction of the efficacy of first transarterial chemoembolization for advanced hepatocellular carcinoma via a clinical-radiomics model. World J Clin Cases 2025; 13:101742. [DOI: 10.12998/wjcc.v13.i23.101742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 03/09/2025] [Accepted: 04/25/2025] [Indexed: 06/04/2025] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a common tumor with a poor prognosis. Early intervention is essential; thus, good prognostic markers to identify patients who benefit from first transarterial chemoembolization (TACE) are needed.
AIM To investigate the efficacy of computed tomography (CT) radiomics in predicting the success of the first TACE in patients with advanced HCC and to develop an early prediction model based on clinical radiomics features.
METHODS Data from 122 patients with advanced HCC treated with TACE were analyzed. Intratumoral and peritumoral areas on arterial and venous CT images were selected to extract radiomic features, which were screened in the training cohort using the minimum redundancy maximum correlation. Then, support vector machines were used to construct the model. To construct a receiver operating characteristic curve, the predictive efficacy of each model was evaluated on the basis of the area under the curve (AUC).
RESULTS Among the 122 patients, 72 patients were effectively treated via TACE, and in 50 patients, this treatment was ineffective. In the radiomics model, the areas under the curve of the venous phase model were 0.867 (95%CI: 0.790-0.940) in the training cohort and 0.755 (0.600-0.910) in the validation cohort, indicating good predictive efficacy. The multivariate logistic regression results indicated that preoperative alpha-fetoprotein levels (P = 0.01) were a risk factor for TACE. The screened clinical features were combined with the radiomic features to construct a combined model. This combined model had an AUC of 0.92 (0.87-0.95) in the training cohort and 0.815 (0.67-0.95) in the validation cohort.
CONCLUSION CT radiomics has good value in predicting the efficacy of the first TACE treatment in patients with HCC. The combined model was a better tool for predicting the first TACE efficacy in patients with advanced HCC and could provide an efficient predictive tool to help with the selection of patients for TACE.
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Affiliation(s)
- Kai-Fei Zhao
- Department of Radiology, The Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
| | - Chao-Bang Xie
- Department of Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang 563000, Guizhou Province, China
| | - Yang Wu
- Department of Intervention, The Second Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
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Fang Z, Pan Y, Lu Z, Wang L, Hu X, Ma Y, Li S. LncRNA SNHG1: A novel biomarker and therapeutic target in hepatocellular carcinoma. Gene 2025; 958:149462. [PMID: 40187618 DOI: 10.1016/j.gene.2025.149462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 03/24/2025] [Accepted: 03/28/2025] [Indexed: 04/07/2025]
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality globally. Increasing evidence suggests that long non-coding RNAs play a critical role in cancer development, with the small nucleolar RNA host gene family being a key participant in multiple types of carcinogenesis, including HCC. Small nucleolar RNA host gene 1 (SNHG1) is a significant member of the SNHG family. SNHG1 expression consistently increases in various HCC-associated processes, such as cell proliferation, apoptosis, angiogenesis, migration, invasion, and treatment resistance. Higher SNHG1 expression levels predict worse prognosis by positively correlating with clinicopathological features, including larger tumour size, poor differentiation, and advanced stages in patients with HCC. Nevertheless, the precise role of SNHG1 in the initiation and progression of HCC remains unclear. Therefore, this review aims to summarise the current investigations on the pathogenesis of SNHG1 in HCC, highlighting its potential as a molecular marker for early prediction and prognostic assessment. As a multifunctional modulator, SNHG1 is extensively involved in molecular signalling pathways in HCC progression and is valuable for therapeutic targeting.
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Affiliation(s)
- Zhou Fang
- Department of Infectious Diseases, Zhoushan Hospital, Wenzhou Medical University, No.739 Dingshen Road, Zhoushan 316021 Zhejiang Province, China
| | - Yong Pan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of Zhejiang University, Hangzhou 31003, China
| | - Zhengmei Lu
- Department of Infectious Diseases, Zhoushan Hospital, Wenzhou Medical University, No.739 Dingshen Road, Zhoushan 316021 Zhejiang Province, China
| | - Lingyun Wang
- Department of Infectious Diseases, Zhoushan Hospital, Zhejiang University, No.739 Dingshen Road, Zhoushan 316021 Zhejiang Province, China
| | - Xiaodan Hu
- Department of Infectious Diseases, Zhoushan Hospital, Wenzhou Medical University, No.739 Dingshen Road, Zhoushan 316021 Zhejiang Province, China
| | - Yingqiu Ma
- Department of Infectious Diseases, Zhoushan Hospital, Wenzhou Medical University, No.739 Dingshen Road, Zhoushan 316021 Zhejiang Province, China
| | - Shibo Li
- Department of Infectious Diseases, Zhoushan Hospital, Wenzhou Medical University, No.739 Dingshen Road, Zhoushan 316021 Zhejiang Province, China.
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8
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Mukund A, Kumar N, Srivastava A, Baby A. Transarterial Chemoembolization: A Consistent and Continuously Evolving Therapy for Hepatocellular Carcinoma. J Clin Exp Hepatol 2025; 15:102538. [PMID: 40226387 PMCID: PMC11985049 DOI: 10.1016/j.jceh.2025.102538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 02/25/2025] [Indexed: 04/15/2025] Open
Abstract
Since its introduction in 1977, transarterial chemoembolization (TACE) has widely been accepted treatment for unresectable intermediate stage hepatocellular carcinoma (HCC). Conventional TACE (c-TACE) uses an emulsion of chemotherapeutic agent and ethiodized oil with subsequent embolization of the feeding artery using gelatin sponge. Drug eluting beads (DEB) were introduced in clinical practice in the 2000s and have since been used as an alternative to c-TACE with better outcomes, especially in larger tumors. Considering the widespread use of TACE in HCC, it is important to revisit the current knowledge and the advances that have developed for better safety and efficacy. This article aims to emphasize on the current knowledge and importance of TACE, touch upon the technical aspects including post-TACE care, response assessment, and discontinuation strategies and highlight the recent advances in the technology, catheters, and embolization particles. Thus, despite a rapid change in treatment algorithms and availability of newer drugs for HCC, TACE will remain an integral part of HCC treatment alone or in combination with other therapies.
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Affiliation(s)
- Amar Mukund
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, 110070, India
| | - Niraj Kumar
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, 110070, India
| | - Amol Srivastava
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, 110070, India
| | - Akhil Baby
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, 110070, India
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Kawashima J, Akabane M, Khalil M, Woldesenbet S, Endo Y, Sahara K, Ruzzenente A, Ratti F, Marques HP, Oliveira S, Balaia J, Cauchy F, Lam V, Poultsides GA, Kitago M, Popescu I, Martel G, Gleisner A, Hugh T, Weiss M, Aucejo F, Aldrighetti L, Endo I, Pawlik TM. Model of End-Stage Liver Disease-alpha-fetoprotein-tumor burden (MELD-AFP-TBS) score to stratify prognosis after liver resection for hepatocellular carcinoma. Surgery 2025; 183:109388. [PMID: 40311416 DOI: 10.1016/j.surg.2025.109388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2025] [Revised: 03/06/2025] [Accepted: 03/31/2025] [Indexed: 05/03/2025]
Abstract
INTRODUCTION Morphologic criteria, such as the Barcelona Clinic Liver Cancer staging system often fail to accurately predict long-term survival among patients undergoing liver resection for hepatocellular carcinoma. We sought to develop a continuous risk score that incorporates established markers of tumor biology and liver function to improve the prediction of overall survival. METHODS Data from a multi-institutional database were used to identify patients who underwent curative-intent hepatectomy for hepatocellular carcinoma. A predictive score for overall survival was developed using weighted beta-coefficients from a multivariable Cox regression model. RESULTS Among 850 patients, 595 (70.0%) were assigned to the training cohort, and 255 (30.0%) to the test cohort. In the training cohort, multivariable analysis identified the Model of End-Stage Liver Disease (hazard ratio, 1.04; 95% confidence interval, 1.01-1.07), log-transformed alpha-fetoprotein (hazard ratio, 1.07; 95% confidence interval, 1.02-1.13), and tumor burden score (hazard ratio, 1.07; 95% confidence interval, 1.03-1.11) as independent predictors of worse overall survival. The Model of End-Stage Liver Disease-alpha-fetoprotein-tumor burden score, based on the Cox model, stratified patients into low-risk (n = 466, 78.3%) with a 5-year OS of 70.5% and high-risk (n = 129, 21.7%) with a 5-year OS of 47.0% (P < .001). In the test cohort, the Model of End-Stage Liver Disease-alpha-fetoprotein-tumor burden score demonstrated superior discriminative accuracy (C-index: 0.72, time-dependent area under the curve 1-year: 0.80, 3-year 0.76, 5-year 0.70) compared with the Barcelona Clinic Liver Cancer staging system (C-index: 0.53, time-dependent area under the curve 1-year: 0.61, 3-year 0.55, 5-year 0.56). An online tool was made accessible at https://jk-osu.shinyapps.io/MELD_AFP_TBS/. CONCLUSION The Model of End-Stage Liver Disease-alpha-fetoprotein-tumor burden score provides a novel, accurate tool for prognostic stratification of patients with hepatocellular carcinoma, identifying high-risk patients who may benefit from alternative treatments to improve outcomes.
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Affiliation(s)
- Jun Kawashima
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH; Department of Gastroenterological Surgery, Yokohama City University, Yokohama, Japan
| | - Miho Akabane
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Mujtaba Khalil
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Selamawit Woldesenbet
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Yutaka Endo
- Department of Transplant Surgery, University of Rochester Medical Center, Rochester, NY
| | - Kota Sahara
- Department of Gastroenterological Surgery, Yokohama City University, Yokohama, Japan
| | - Andrea Ruzzenente
- Division of General and Hepatobiliary Surgery, University of Verona, Verona, Italy
| | | | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - Sara Oliveira
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - Jorge Balaia
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - François Cauchy
- Department of HPB Surgery and Liver Transplantation, Beaujon Hospital, Clichy, France
| | - Vincent Lam
- Department of Surgery, Westmead Hospital, Westmead, New South Wales, Australia
| | | | - Minoru Kitago
- Department of Surgery, Keio University, Tokyo, Japan
| | - Irinel Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | | | - Ana Gleisner
- Department of Surgery, University of Colorado Denver, Denver, CO
| | - Tom Hugh
- Department of Surgery, The University of Sydney, Sydney, New South Wales, Australia
| | - Matthew Weiss
- Department of Surgery, Cancer Institute, Northwell Health, New Hyde Park, NY
| | - Federico Aucejo
- Department of Hepato-pancreato-biliary & Liver Transplant Surgery, Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Cleveland, OH
| | | | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University, Yokohama, Japan
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH.
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Cheng Z, Yang X, Ren Y, Wang H, Zhang Q, Lin S, Wu W, Yang X, Zheng J, Liu X, Tao X, Chen X, Qian Y, Li X. Investigating the molecular mechanisms and clinical potential of APO+ endothelial cells associated with PANoptosis in the tumor microenvironment of hepatocellular carcinoma using single-cell sequencing data. Transl Oncol 2025; 57:102402. [PMID: 40318262 PMCID: PMC12123355 DOI: 10.1016/j.tranon.2025.102402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2025] [Revised: 03/27/2025] [Accepted: 04/19/2025] [Indexed: 05/07/2025] Open
Abstract
INTRODUCTION PANoptosis is a newly identified form of programmed cell death that integrates elements of pyroptosis, apoptosis, and necroptosis. It plays a pivotal role in shaping the tumor immune microenvironment. Despite its significance, the specific functions and mechanisms of PANoptosis within the tumor microenvironment (TME) of hepatocellular carcinoma (HCC) remain unclear. This study aims to investigate these mechanisms using single-cell RNA sequencing data. METHODS Single-cell RNA sequencing data from HCC patients were obtained from the GEO database. The AUCell algorithm was used to quantify PANoptosis activity across various cell types in the TME. Cell populations with high PANoptosis scores were further analyzed using CytoTRACE and scMetabolism to assess their differentiation states and metabolic profiles. Associations between these high-score cell subsets and patient prognosis, tumor stage, and response to immunotherapy were examined. Cell-cell communication analysis was performed to explore how PANoptosis-related APO+ endothelial cells (ECs) may influence HCC progression. Immunofluorescence staining was used to assess the spatial distribution of APO+ ECs in tumor and adjacent tissues. Finally, a CCK8 assay was conducted to evaluate the effect of APOH+ HUVECs on HCC cell proliferation. RESULTS A total of 16 HCC patient samples with single-cell RNA sequencing data were included in the study. By calculating the PANoptosis scores of different cell types, we found that ECs, macrophages, hepatocytes, and fibroblasts exhibited higher PANoptosis scores. The PANoptosis scores, differentiation trajectories, intercellular communication, and metabolic characteristics of these four cell subpopulations with high PANoptosis scores were visualized. Among all subpopulations, APO+ ECs demonstrated the most significant clinical relevance, showing a positive correlation with better clinical staging, prognosis, and response to immunotherapy in HCC patients. Cellular communication analysis further revealed that APO+ ECs might regulate the expression of HLA molecules, thereby influencing T cell proliferation and differentiation, potentially contributing to improved prognosis in HCC patients. Immunofluorescence staining results indicated that APO+ ECs were primarily located in the adjacent tissues of HCC patients, with lower expression in tumor tissues. The results of cellular experiments showed that APOH+ HUVECs significantly inhibited the proliferation of HCC cells. CONCLUSIONS This study systematically mapped the cellular landscape of the TME in HCC patients and explored the differences in differentiation trajectories, metabolic pathways, and other aspects of subpopulations with high PANoptosis scores. Additionally, the study elucidated the potential molecular mechanisms through which APO+ ECs inhibit HCC cell proliferation and improve prognosis and immunotherapeutic efficacy in HCC patients. This research provides new insights for clinical prognosis evaluation and immunotherapy strategies in HCC.
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Affiliation(s)
- Zhaorui Cheng
- Department of Emergency, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China; Department of Urology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China.
| | - Xiangyu Yang
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, China.
| | - Yi Ren
- Southern University of Science and Technology, Shenzhen, Guangdong, China.
| | - Huimin Wang
- Department of Traditional Chinese Medicine, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China
| | - Qi Zhang
- Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, China
| | - Sailing Lin
- Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, China
| | - Wenhao Wu
- Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, China
| | - Xiaolu Yang
- Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, China
| | - Jiahan Zheng
- The First Clinical College, Gannan Medical University, Ganzhou, Jiangxi, China
| | - Xinzhu Liu
- Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, China
| | - Xin Tao
- Department of Pathology, Second Affiliated Hospital of Nanchang University, Nanchang, JiangXi, China
| | - Xiaoyong Chen
- Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, China.
| | - Yuxin Qian
- Department of Emergency, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China; Department of Urology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China.
| | - Xiushen Li
- Department of Traditional Chinese Medicine, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China; Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, China.
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11
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Malthiery C, Hossu G, Ayav A, Laurent V. Characterization of hepatocellular carcinoma with CT with deep learning reconstruction compared with iterative reconstruction and 3-Tesla MRI. Eur Radiol 2025; 35:4354-4361. [PMID: 39775897 DOI: 10.1007/s00330-024-11314-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 11/02/2024] [Accepted: 11/19/2024] [Indexed: 01/11/2025]
Abstract
OBJECTIVES This study compared the characteristics of lesions suspicious for hepatocellular carcinoma (HCC) and their LI-RADS classifications in adaptive statistical iterative reconstruction (ASIR) and deep learning reconstruction (DLR) to those of MR images, along with radiologist confidence. MATERIALS AND METHODS This prospective single-center trial included patients who underwent four-phase liver CT and multiphasic contrast-enhanced MRI within 7 days from February to August 2023. The lesion characteristics, LI-RADS classifications and confidence scores according to two radiologists on the ASIR, DLR and MRI techniques were compared. If the patient had at least one lesion, he was included in the HCC group, otherwise in the non-HCC group. MRI being the technique with the best sensitivity, concordance of lesions characteristics and LI-RADS classifications were calculated by weighted kappa between the ASIR and MRI and between the DLR and MRI. The confidence scores are expressed as the means and standard deviations. RESULTS Eighty-nine patients were enrolled, 52 in the HCC group (67 years ± 9 [mean ± SD], 46 men) and 37 in the non-HCC group (68 years ± 9, 33 men). The concordance coefficient between the LI-RADS classification by ASIR and MRI was 0.64 [0.52; 0.76], showing good agreement, that by DLR and MRI was 0.83 [0.73; 0.92], showing excellent agreement. The diagnostic confidence in ASIR was 3.31 ± 0.95 (mean ± SD) and 3.0 ± 1.11, that in the DLR was 3.9 ± 0.88 and 4.11 ± 0.75, that in the MRI was 4.46 ± 0.80 and 4.57 ± 0.80. CONCLUSION DLR provided excellent LI-RADS classification concordance with MRI, whereas ASIR provided good concordance. The radiologists' confidence was greater in the DLR than in the ASIR but remained highest in the MR group. KEY POINTS Question Does the use of deep learning reconstructions (DLR) improve LI-RADS classification of suspicious hepatocellular carcinoma lesions compared to adaptive statistical iterative reconstructions (ASIR)? Findings DLR demonstrated superior concordance of LI-RADS classification with MRI compared to ASIR. It also provided greater diagnostic confidence than ASIR. Clinical relevance The use of DLR enhances radiologists' ability to visualize and characterize lesions suspected of being HCC, as well as their LI-RADS classification. Moreover, it also boosts their confidence in interpreting these images.
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Affiliation(s)
- Clément Malthiery
- Department of Adult Radiology, CHRU de Nancy, Vandoeuvre-lès-Nancy, France.
| | - Gabriela Hossu
- Clinical Investigation Center Technological Innovation of Nancy, Inserm, CHRU de Nancy, Vandoeuvre-lès-Nancy, France
| | - Ahmet Ayav
- Department of HPB Surgery, CHRU de Nancy, Vandoeuvre-lès-Nancy, France
| | - Valérie Laurent
- Adaptive Diagnostic and Interventional Imaging, Inserm, CHRU de Nancy, Vandoeuvre-lès-Nancy, France
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Xu K, Wu T, Li X, Zhang X, Liu X, Ma S, Dong W, Yang J, Liu Y, Fang W, Ju Y, Chen Y, Dai C, Gong Z, He W, Huang Z, Chang L, Ma W, Xia P, Chen X, Yuan Y. ADH1C maintains the homeostasis of metabolic microenvironment to inhibit steatotic hepatocellular carcinoma. Metabolism 2025; 168:156267. [PMID: 40233847 DOI: 10.1016/j.metabol.2025.156267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 04/07/2025] [Accepted: 04/11/2025] [Indexed: 04/17/2025]
Abstract
Steatotic hepatocellular carcinoma (HCC) has emerged as a significant subtype of HCC. Understanding the complex tumor microenvironment in HCC is particularly important for stratifying patients and improving treatment response. In this study, we performed proteomic analysis on clinical samples of steatotic HCC and identified human-specific gene alcohol dehydrogenase 1C (ADH1C) as a key factor. ADH1C is a favorable prognostic factor in both steatotic and non-steatotic HCC. ADH1C promotes fatty acid degradation through a novel non-enzymatic function, inhibiting the development of hepatocellular carcinoma. Specifically, in vitro experiments revealed that ADH1C interacts with splicing factor retinitis pigmentosa 9 (RP9) to enhance the splicing of key transcription factor peroxisome proliferator activated receptor alpha (PPARa) pre-mRNA, which is crucial for fatty acid degradation. The regulation of the ADH1C/RP9/PPARa axis was supported by in vivo experiments and clinical relevance. This leads to a reduction in the critical metabolite palmitic acid, subsequently decreasing the palmitoylation levels of oncogenic protein TEA domain transcription factor 1 (TEAD1), thereby regulating the hippo pathway and subsequent cell proliferation inhibition. Additionally, we found that ADH1C and PPARa can serve as combined biomarkers to distinguish between patients with steatotic and non-steatotic HCC. Combination therapy targeting ADH1C and anti-programmed cell death protein 1 (PD1) enhances the response of steatotic HCC to anti- PD1 immunotherapy. Our study revealed a central role of ADH1C/PPARa in lipid metabolism and HCC suppression. Targeting lipid metabolism via ADH1C/PPARa may provide new therapeutic strategies for the treatment of liver cancer.
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Affiliation(s)
- Kequan Xu
- Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China; Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Hubei, PR China.
| | - Tiangen Wu
- Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China; Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Hubei, PR China.
| | - Xiaomian Li
- Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China; Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Hubei, PR China.
| | - Xiao Zhang
- Department of Liver Surgery, West China Hospital of Sichuan University, No. 37, Guoxue Lane, Chengdu, Sichuan Province, PR China.
| | - Xinyu Liu
- Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China; Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Hubei, PR China.
| | - Shuxian Ma
- Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China; Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Hubei, PR China.
| | - Wenlong Dong
- University of Chinese Academy of Sciences, Beijing 100049, PR China.
| | - Jialing Yang
- School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu Province, PR China.
| | - Yingyi Liu
- Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China; Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Hubei, PR China.
| | - Weixian Fang
- Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China; Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Hubei, PR China.
| | - Yi Ju
- Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China; Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Hubei, PR China.
| | - Yiran Chen
- Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, 180 Fenglin Road, Shanghai 200032, PR China.
| | - Caixia Dai
- Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China; Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Hubei, PR China.
| | - Zheng Gong
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
| | - Wenzhi He
- College of Life Sciences, Hubei Key Laboratory of Cell Homeostasis, Wuhan University, Wuhan 430072, PR China.
| | - Zan Huang
- College of Life Sciences, Hubei Key Laboratory of Cell Homeostasis, Wuhan University, Wuhan 430072, PR China.
| | - Lei Chang
- Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China; Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Hubei, PR China.
| | - Weijie Ma
- Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China; Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Hubei, PR China.
| | - Peng Xia
- Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China; Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Hubei, PR China; Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
| | - Xi Chen
- Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China; Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Hubei, PR China.
| | - Yufeng Yuan
- Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China; Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Hubei, PR China; TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan 430071, PR China.
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Zhang W, Fu H, Liu ZR, Xu L, Che X, Ning YT, Zhan ZY, Zhou GC. Transarterial chemoembolization combined with lenvatinib vs transarterial chemoembolization combined with sorafenib for unresectable hepatocellular carcinoma: A systematic review and meta-analysis. World J Gastrointest Oncol 2025; 17:105887. [DOI: 10.4251/wjgo.v17.i6.105887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2025] [Revised: 03/25/2025] [Accepted: 04/23/2025] [Indexed: 06/13/2025] Open
Abstract
BACKGROUND Lenvatinib and sorafenib are tyrosine kinase inhibitors that are effective in the treatment of unresectable hepatocellular carcinoma (uHCC). The efficacy of which of them is better suited to combine transarterial chemoembolization (TACE) for the treatment of uHCC is ripe.
AIM To compare the effectiveness of TACE combined with lenvatinib (TACE-lenvatinib) and TACE combined with sorafenib (TACE-sorafenib) in the treatment of uHCC, this study was carried out.
METHODS Publicly available studies comparing the efficacy of TACE-lenvatinib and TACE-sorafenib in the treatment of uHCC were collected from PubMed, Embase and Cochrane Library, with a cut-off date of December 2024. Stata SE 15 software was used for statistical analysis.
RESULTS A total of six studies involving 547 patients were included, 248 in the TACE-lenvatinib group and 299 in the TACE-sorafenib group. Meta-analysis results showed that TACE-lenvatinib was more effective than TACE-sorafenib in complete response [relative risk (RR) = 1.81, 95% confidence interval (CI): 1.11-2.96, P = 0.02], partial response (RR = 1.38, 95%CI: 1.12-1.70, P = 0.002), objective response rate (RR = 1.47, 95%CI: 1.24-1.74, P < 0.0001) and disease control rate (RR = 1.22, 95%CI: 1.00-1.49, P = 0.05). TACE-lenvatinib was significantly lower than TACE-sorafenib in progressive disease rate (RR = 0.54, 95%CI: 0.39-0.74, P = 0.002). No significant difference was found in stable disease rate (RR = 0.89, 95%CI: 0.60-1.33, P = 0.58) between the two groups. TACE-lenvatinib was significantly more effective than TACE-sorafenib in overall survival (hazard ratio = 2.00, 95%CI: 1.59-2.50, P < 0.05) and progression free survival (hazard ratio = 2.04, 95%CI: 1.49-2.86, P < 0.05). As regards adverse events, TACE-lenvatinib was better in reducing the incidence of hypertension than TACE-sorafenib, while no significant difference was found in overall adverse events, abdominal pain, fever, fatigue, nausea and vomiting, decreased appetite, liver dysfunction, hand-foot skin reaction, diarrhea, thrombocytopenia, and rash between the two groups.
CONCLUSION In patients with uHCC, TACE-lenvatinib induced a better tumor response rate and survival outcome than TACE-sorafenib, while TACE-lenvatinib resulted in a higher incidence of hypertension than TACE-sorafenib. However, these conclusions are derived from currently available medical evidence, and further confirmation by more rigorously designed randomized controlled studies is still needed.
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Affiliation(s)
- Wei Zhang
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, China
| | - Hua Fu
- Department of Hepatobiliary Surgery, People’s Hospital of Xiangxi Autonomous Prefecture, Jishou 416000, Hunan Province, China
| | - Zi-Rong Liu
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, China
| | - Lin Xu
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, China
| | - Xu Che
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, China
| | - Yan-Ting Ning
- Department of Nursing, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, China
| | - Zheng-Yin Zhan
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, China
| | - Guo-Chao Zhou
- Department of Hepatobiliary Surgery, People’s Hospital of Xiangxi Autonomous Prefecture, Jishou 416000, Hunan Province, China
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Li YH, Qian GX, Yao L, Lei XD, Zhu Y, Tang L, Xu ZL, Bu XY, Wei MT, Lu JL, Jia WD. Preoperative model for predicting early recurrence in hepatocellular carcinoma patients using radiomics and deep learning: A multicenter study. World J Gastrointest Oncol 2025; 17:106608. [DOI: 10.4251/wjgo.v17.i6.106608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2025] [Revised: 04/19/2025] [Accepted: 05/06/2025] [Indexed: 06/13/2025] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Ablation therapy is one of the first-line treatments for early HCC. Accurately predicting early recurrence (ER) is crucial for making precise treatment plans and improving patient prognosis.
AIM To establish an intratumoral and peritumoral model for predicting ER in HCC patients following curative ablation.
METHODS This study included a total of 288 patients from three Centers. The patients were divided into a primary cohort (n = 222) and an external cohort (n = 66). Radiomics and deep learning methods were combined for feature extraction, and models were constructed following a three-step feature selection process. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), while calibration curves and decision curve analysis (DCA) were used to assess calibration and clinical utility. Finally, Kaplan-Meier (K-M) analysis was used to stratify patients according to progression-free survival (PFS) and overall survival (OS).
RESULTS The combined model, which utilizes the light gradient boosting machine learning algorithm and incorporates both intratumoral and peritumoral regions (5 mm and 10 mm), demonstrated the best predictive performance for ER following HCC ablation, achieving AUCs of 0.924 in the training set, 0.899 in the internal validation set, and 0.839 in the external validation set. Calibration and DCA curves confirmed strong calibration and clinical utility, whereas K-M curves provided risk stratification for PFS and OS in HCC patients.
CONCLUSION The most efficient model integrated the tumor region with the peritumoral 5 mm and 10 mm regions. This model provides a noninvasive, effective, and reliable method for predicting ER after curative ablation of HCC.
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Affiliation(s)
- Yong-Hai Li
- Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
- The First Affiliated Hospital of University of Science and Technology of China, University of Science and Technology of China, Hefei 230001, Anhui Province, China
- The First People's Hospital of Hefei, The Third Affiliated Hospital of Anhui Medical University, Hefei 230001, Anhui Province, China
| | - Gui-Xiang Qian
- The First People's Hospital of Hefei, The Third Affiliated Hospital of Anhui Medical University, Hefei 230001, Anhui Province, China
| | - Ling Yao
- Department of Anorectal, Chinese Academy of Traditional Chinese Medicine, Xiyuan Hospital, Beijing 100091, China
| | - Xue-Di Lei
- Department of Colorectal Surgery, Bengbu Medical University, Bengbu 233000, Anhui Province, China
| | - Yu Zhu
- Department of Hepatopancreatobiliary Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou 318000, Zhejiang Province, China
| | - Lei Tang
- Department of Infectious Disease, The Second Hospital of Anhui Medical Univercity, Hefei 230001, Anhui Province, China
| | - Zi-Ling Xu
- Department of Hepatic Surgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Anhui Province, China
| | - Xiang-Yi Bu
- Division of Life Science and Medicine, Department of Hepatic Surgery, Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Ming-Tong Wei
- Department of Hepatic Surgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Anhui Province, China
| | - Jian-Lin Lu
- Department of Hepatic Surgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Anhui Province, China
| | - Wei-Dong Jia
- Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
- The First Affiliated Hospital of University of Science and Technology of China, University of Science and Technology of China, Hefei 230001, Anhui Province, China
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15
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Akkari I, Akkari H, Harbi R. Artificial intelligence to predict hepatocellular carcinoma risk in cirrhosis. World J Gastrointest Oncol 2025; 17:107414. [DOI: 10.4251/wjgo.v17.i6.107414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2025] [Revised: 04/14/2025] [Accepted: 05/20/2025] [Indexed: 06/13/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. The primary risk factor for HCC is cirrhosis. Identifying individuals who are at high risk of developing HCC will have numerous benefits for patient outcomes, patient quality of life, and the global healthcare system. Artificial intelligence (AI) has the capability to develop systems that emulate human intelligence. Recent studies have highlighted the potential of AI in the management of HCC, and the application of AI appears promising for identifying high-risk groups among patients with cirrhosis who require closer monitoring. Ultimately, the aim of AI in the field of HCC clinical care is to enable earlier diagnosis and consequently improve prognosis.
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Affiliation(s)
- Imen Akkari
- Department of Gastroenterology, University Hospital of Hached, University of Sousse, Faculty of Medicine of Sousse, Sousse 4000, Tunisia
| | - Hanen Akkari
- LATIS-Laboratory of Advanced Technology and Intelligent Systems, University of Sousse, National School of Engineering of Sousse, Sousse 4023, Tunisia
| | - Raida Harbi
- Department of Gastroenterology, University Hospital of Sahloul, University of Sousse, Faculty of Medicine of Sousse, Sousse 4054, Tunisia
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16
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Tamai H, Okamura J. Microwave Thermosphere Ablation Versus Radiofrequency Ablation in Hepatocellular Carcinoma: Optimizing Treatment Strategies for Tumor Size and Malignancy Grade. Hepatol Res 2025. [PMID: 40515741 DOI: 10.1111/hepr.14221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2025] [Revised: 05/11/2025] [Accepted: 05/28/2025] [Indexed: 06/16/2025]
Abstract
AIM The next-generation microwave thermosphere ablation (MTA) system was developed to overcome the limitations of conventional microwave ablation. However, the comparative oncologic efficacy of MTA versus radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) remains uncertain. This study aimed to evaluate the oncologic benefits of MTA. METHODS A retrospective analysis was conducted on 310 patients with primary HCC meeting the Milan criteria, treated with either RFA (n = 71) or MTA (n = 239). Metastatic recurrence was defined as ≥ 4 intrahepatic recurrences suggestive of intrahepatic metastases, extrahepatic metastases, or dissemination. High-grade malignant HCC was classified as non-single nodular type or alpha-fetoprotein lens culinaris-agglutinin reactive fraction (AFP-L3) positive (> 10%). RESULTS MTA was associated with significantly lower metastatic recurrence and HCC-specific mortality rates compared to RFA. Multivariate analysis identified the ablation method as an independent factor contributing to metastatic recurrence and HCC mortality. Among patients with HCC ≤ 2 cm, metastatic recurrence rates did not differ significantly between groups. However, for HCC > 2 cm, MTA showed significantly lower metastatic recurrence rates than RFA. In non-single nodular or AFP-L3-positive HCC, metastatic recurrence rates were similar between groups, whereas in single nodular or AFP-L3-negative HCC, MTA significantly reduced metastatic recurrence. CONCLUSIONS MTA provides superior oncologic outcomes compared to RFA, particularly in reducing HCC-specific mortality and metastatic recurrence rates. MTA should be considered the preferred ablative therapy for select HCC patients, in particular those with tumors > 2 cm or those without high-grade malignancy.
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Affiliation(s)
- Hideyuki Tamai
- Department of Hepatology, Wakayama Rosai Hospital, Wakayama, Japan
| | - Jumpei Okamura
- Department of Hepatology, Wakayama Rosai Hospital, Wakayama, Japan
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17
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Xu K, Gu T, Su K, Liu X, He B, He J, Chi H, Zhou X, Liu H, Xiao R, Tang X, Ye Q, Zhou X, Liu Y, Xiong J, Wang P, Li H, He K, Guo L, Han Y. Stereotactic body radiation therapy (SBRT) increases anti-PD-1 antitumor activity by enhancing the tumor immune microenvironment in mice with metastatic hepatocellular carcinoma. Discov Oncol 2025; 16:1081. [PMID: 40512454 DOI: 10.1007/s12672-025-02914-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Accepted: 06/04/2025] [Indexed: 06/16/2025] Open
Abstract
BACKGROUND To explore the effect of radiotherapy on anti-pd-1 anti-tumor activity in metastatic hepatocellular carcinoma. METHODS Patients with metastatic HCC treated with intensity-modulated radiation therapy (IMRT) in combination with immunotherapy (n = 13) were retrospectively analyzed by comparing its efficacy with that of immunotherapy alone (n = 12) as well as untreated (n = 20) patients with metastatic hepatocellular carcinoma. Animal experiment used mouse hepatocellular carcinoma H22 cell metastatic tumor model and were also divided into a control group, a PD-1 antibody group, an SBRT group, and an SBRT combined with a PD-1 antibody group. SBRT treatment is 8 Gy×3 F. The growth curves of body weight, irradiated tumor (the primary tumor), and non-irradiated tumor (secondary tumor) were plotted for each group of tumor-bearing mice. For this study, we used flow cytometry to examine effector CD8 + T cells expression in both irradiated and non-irradiated tumors, the CD4 + T and CD4+/CD8 + T cells ratio in the spleen, and used enzyme-linked immunosorbent assays (ELISA) to analyze the concentrations of IFN-γ and IL-10 in serum. Tumors were additionally stained with immunohistochemistry Ki-67 and TdT-mediated dUTP nick end labeling (TUNEL). We used hematoxylin-eosin (HE) staining of liver, spleen, lungs, kidneys, and heart to assess the anti-tumor activity of each group of tumor-bearing mice and their tolerance to determine the safety of the approach. RESULTS Clinical results: The median survival of IMRT + PD-1 group, PD-1 group, and control group were 17.5 months (95Confidence Interval (CI) 13.2-21.8), 12.5 months (95CI 9.0-16.0), and 5.2 months (95CI 5.5-12.9), respectively (P < 0.001). SBRT combined with PD-1 antibody improved tumor control in both radiated and non-radiated tumors, resulting in a complete cure of the half of mice in animal studies. This was linked to an increased in CD8 + effector T cells infiltration triggered by radiotherapy. HE staining of mice in the SBRT combined with the PD-1 treatment group suggested no damage to the liver, spleen, lungs, kidneys, and heart. CONCLUSIONS This study showed that SBRT, while being well-tolerated, significantly increased anti-PD-1 antitumor activity by enhancing the tumor immune microenvironment in mice with metastatic hepatocellular carcinoma without significant toxic side effects. DISCLAIMER This manuscript was previously submitted as a preprint only in Experimental Hematology & Oncology and has no conflict of interest with this submission.
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Affiliation(s)
- Ke Xu
- Department of Oncology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
- Department of Oncology, Chongqing General Hospital, Chongqing, 401147, China
| | - Tao Gu
- Department of Oncology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
| | - Ke Su
- Department of Oncology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
- Department of Radiation Oncology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100000, China
| | - Xin Liu
- Department of Oncology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
| | - Bingsheng He
- Department of Oncology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
| | - Jie He
- Department of Oncology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
| | - Hao Chi
- Clinical Medical College, Southwest Medical University, Luzhou, 646000, China
| | - Xuancheng Zhou
- Clinical Medical College, Southwest Medical University, Luzhou, 646000, China
| | - Hanlin Liu
- Clinical Medical College, Southwest Medical University, Luzhou, 646000, China
| | - Rui Xiao
- Clinical Medical College, Southwest Medical University, Luzhou, 646000, China
| | - Xue Tang
- Clinical Medical College, Southwest Medical University, Luzhou, 646000, China
| | - Qinni Ye
- Clinical Medical College, Southwest Medical University, Luzhou, 646000, China
| | - Xue Zhou
- Department of Oncology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
| | - Yingpeng Liu
- Department of Oncology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
| | - Jie Xiong
- Department of Public Health, Southwest Medical University, Luzhou, 646000, China
| | - Pan Wang
- Clinical Skills Center, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
| | - Han Li
- Department of Oncology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
| | - Kun He
- Clinical Research Institute, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
- The Affiliated Hospital of Southwest Medical University, 25 Taiping Street, Luzhou, Sichuan, China.
| | - Lu Guo
- Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
| | - Yunwei Han
- Department of Oncology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China.
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, 646000, China.
- Academician (Expert) Workstation of Sichuan Province, Luzhou, 646000, China.
- The Affiliated Hospital of Southwest Medical University, 25 Taiping Street, Luzhou, Sichuan, China.
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18
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Qin L, Qiu ZC, Zhang Y, Xie F, Yu Y, Leng SS, Dai JL, Wen TF, Li C. Intraoperative Blood Transfusion has a Distinct Impact on the Long-Term Prognosis of Hepatocellular Carcinoma Patients With Different Alpha-Fetoprotein-Tumor Burden Scores After Liver Resection: A Large-Scale Multicenter Study. World J Surg 2025. [PMID: 40490899 DOI: 10.1002/wjs.12658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Revised: 04/15/2025] [Accepted: 05/31/2025] [Indexed: 06/11/2025]
Abstract
BACKGROUND To identify the influence of intraoperative blood transfusion (IBT) on the long-term prognosis of patients with hepatocellular carcinoma (HCC) in patients with low/medium alpha-fetoprotein-tumor burden scores (ATSs) and high ATSs. METHODS Data from HCC patients (n = 3374) who underwent liver resection between 2014 and 2022 from a multicenter database were reviewed. The impact of IBT on overall survival (OS) and recurrence-free survival (RFS) in the whole cohort, low/medium ATS group, and high ATS group was evaluated via multivariate analyses, respectively. RESULTS Before propensity score matching (PSM), patients who underwent IBT had poorer RFS (5-year RFS: 37.7% vs. 49.6%, p < 0.001) and OS (5-year OS: 52.8% vs. 68.2%, p < 0.001) than those who did not undergo IBT. After PSM, both RFS (5-year RFS: 37.9%, vs. 45.8%, p = 0.207) and OS (5-year OS: 52.5% vs. 59.5%, p = 0.125) were similar between patients who did and did not receive IBT. Multivariate analysis revealed that the IBT was not associated with RFS or OS in the whole cohort or in patients with high ATSs. However, the IBT was independently related to both RFS (HR = 1.407, 95% CI = 1.089-1.818; p = 0.009) and OS (HR = 1.522, 95% CI = 1.114-2.080, p = 0.008) in patients with low/moderate ATSs. CONCLUSION Our study confirmed that the IBT had different effects on the prognosis of HCC patients with different ATSs after liver resection. The IBT negatively impacts on the prognosis of patients with low/medium ATSs patients, but not those with high ATSs.
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Affiliation(s)
- Li Qin
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Zhan-Cheng Qiu
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yu Zhang
- Department of HPB Surgery, Sichuan Province People's Hospital, Chengdu, China
| | - Fei Xie
- Department of HPB Surgery, The First People's Hospital of Neijiang, Neijiang, China
| | - Yu Yu
- Department of HPB Surgery, The Second People's Hospital of Yibin, Yibin, China
| | - Shu-Sheng Leng
- Department of HPB Surgery, The Affiliated Hospital of Chengdu University, Chengdu, China
| | - Jun-Long Dai
- Medical Data Analytics Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Tian-Fu Wen
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Chuan Li
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China
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19
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Akabane M, Kawashima J, Altaf A, Woldesenbet S, Cauchy F, Aucejo F, Popescu I, Kitago M, Martel G, Ratti F, Aldrighetti L, Poultsides GA, Imaoka Y, Ruzzenente A, Endo I, Gleisner A, Marques HP, Lam V, Hugh T, Bhimani N, Shen F, Pawlik TM. Impact of disparity between imaging and pathological tumor size on cancer-specific prognosis among patients with hepatocellular carcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109683. [PMID: 40009916 DOI: 10.1016/j.ejso.2025.109683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 01/28/2025] [Accepted: 02/08/2025] [Indexed: 02/28/2025]
Abstract
BACKGROUND The association between preoperative imaging and postoperative pathological tumor size disparity, and cancer-specific survival (CSS) among patients undergoing hepatectomy for hepatocellular carcinoma (HCC) remains unclear. We sought to evaluate this association and identify predictors of size disparity. METHOD Patients undergoing curative-intent hepatectomy for HCC (2000-2023) were identified from an international, multi-institutional database. Size ratio was defined as the ratio of pathological to imaging tumor size. Patients with a size ratio of 0.5-1.5 were classified as "without size disparity," while patients outside this range were considered "with size disparity." Multivariable Cox regression was used to identify predictors of CSS, while logistic regression was utilized to determine factors associated with size disparity. For variables identified as significant in multivariable analyses, further evaluation including cutoff determination, were performed using receiver operating characteristic (ROC) analysis. RESULTS Among 833 patients, median size ratio was 1.02, with a strong correlation between imaging and pathological tumor sizes (r = 0.87). Size disparity was present in 106 patients (12.7 %); in general, patients had smaller median imaging sizes (2.85 vs. 4.80 cm; p < 0.001) while size on pathology was noted to be larger(both 4.50 cm; p = 0.370). Patients with size disparity had worse 5-year CSS (60.1% vs. 79.0 %; p < 0.001). Multivariable Cox regression identified higher ALBI score (HR:2.56 [1.50-4.37]; p < 0.001), larger pathological tumor size (HR:1.09 [1.03-1.15]; p = 0.001), and size disparity (HR:2.53 [1.37-4.66]; p = 0.002) as independent predictors of CSS. Logistic regression demonstrated that cirrhosis (OR: 2.68 [1.43-5.02]; p = 0.002) and log alpha-fetoprotein (AFP) (OR:1.11 [1.01-1.22]; p = 0.030) were associated with an increased likelihood of size disparity. Cirrhosis and log AFP could be used to stratify patients relative to probability of a size disparity (low-risk:9.9 %, medium-risk:12.2 %, high-risk:17.7 %). The optimal AFP cutoff value was 3928 ng/mL for non-cirrhotic (AUC:0.90) versus 28.9 ng/mL for cirrhotic (AUC:0.74) patients. CONCLUSION Tumor size disparity was associated with worse CSS among patients with HCC undergoing hepatectomy. Size disparity could be predicted preoperatively using cirrhosis status and AFP level, which may help identify high-risk patients who may benefit from more detailed imaging assessments.
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Affiliation(s)
- Miho Akabane
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Jun Kawashima
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Abdullah Altaf
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Selamawit Woldesenbet
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - François Cauchy
- Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France
| | - Federico Aucejo
- Department of General Surgery, Cleveland Clinic Foundation, OH, USA
| | - Irinel Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | - Minoru Kitago
- Department of Surgery, Keio University, Tokyo, Japan
| | - Guillaume Martel
- Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada
| | | | | | | | - Yuki Imaoka
- Department of Surgery, Stanford University, Stanford, CA, USA
| | | | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Ana Gleisner
- Department of Surgery, University of Colorado, Denver, CO, USA
| | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - Vincent Lam
- Department of Surgery, Westmead Hospital, Sydney, NSW, Australia
| | - Tom Hugh
- Department of Surgery, School of Medicine, The University of Sydney, Sydney, NSW, Australia
| | - Nazim Bhimani
- Department of Surgery, School of Medicine, The University of Sydney, Sydney, NSW, Australia
| | - Feng Shen
- The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
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20
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Yang Q, Zhou J, Luo B, Zheng R, Liao J, Tang L, Cheng W, Jing X, Cai W, Cheng Z, Liu F, Han Z, Yu X, Yu J, Liang P. Non-radiomics imaging (US-CEUS) features and clinical text features: correlation with microvascular invasion and tumor grading in hepatocellular carcinoma. Abdom Radiol (NY) 2025; 50:2476-2493. [PMID: 39607454 DOI: 10.1007/s00261-024-04659-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 10/25/2024] [Accepted: 10/26/2024] [Indexed: 11/29/2024]
Abstract
OBJECTIVES To predict microvascular invasion (MVI) status and tumor grading of hepatocellular carcinoma (HCC) by evaluating preoperative non-radiomics ultrasound and contrast-enhanced ultrasound (US-CEUS) features and determine the influences of MVI/tumor grading on the category of CEUS LI-RADS for HCC. METHODS A total of 506 HCC patients who underwent preoperative US-CEUS examinations from 8 hospitals between July 2020 and June 2023 were enrolled. According to the MVI status, all the patients were classified, and HCC differentiation was assessed by using Edmondson-Steiner (ES) grading: MVI-negative (M0) and low-grade ES (GI/II) (MN-L, n = 297) and MVI-positive (M1/M2) and/or high-grade ES (GIII/IV) (MP-H, n = 209). Stratified analysis was performed based on fibrosis stage and tumor size. RESULTS The results proved that MN-L HCC was more frequently classified into the LR-5 category (p = 0.034), while MP-H HCC was more frequently classified into the LR-TIV (p = 0.010). The heterogeneously arterial phase hyperenhancement (APHE) is significantly correlated with MVI(+)/high grade-ES (p = 0.003). Compared with MN-L HCC, the onset of washout was earlier, washout rate was higher, and tumor-invasion border was larger (all p < 0.01) in MP-H HCC. In addition, fibrosis stage and tumor size significantly influenced the onset of washout and washout rate of HCC (all p < 0.01). The tumor-invasion border was only positively correlated with tumor size (p < 0.001) rather than fibrosis stage (p > 0.05). CONCLUSIONS MVI status and tumor grading influence the classification of LR-5 and LR-TIV. Heterogeneous APHE, higher washout rate, earlier onset of washout (≤65 s), larger tumor-invasion border (≥3 mm) and higher alpha fetoprotein level indicate the presence of MVI and/or high-grade ES.
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Affiliation(s)
- Qi Yang
- Chinese PLA General Hospital, Beijing, China
- Peking University Shenzhen Hospital, Shenzhen, China
| | - Jianhua Zhou
- Sun Yat-sen University Cancer Center, Guangzhou, China
- Sun Yat-sen Memorial Hospital, Guangzhou, China
| | - Baoming Luo
- Sun Yat-sen Memorial Hospital, Guangzhou, China
| | - Rongqin Zheng
- Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | | | - Lina Tang
- Fujian Provincial Cancer Hospital, Fuzhou, China
| | - Wen Cheng
- Harbin Medical University Cancer Hospital, Harbin, China
| | - Xiang Jing
- Tianjin Third Central Hospital, Tianjin, China
| | - Wenjia Cai
- Chinese PLA General Hospital, Beijing, China
| | | | - Fangyi Liu
- Chinese PLA General Hospital, Beijing, China
| | - Zhiyu Han
- Chinese PLA General Hospital, Beijing, China
| | - Xiaoling Yu
- Chinese PLA General Hospital, Beijing, China
| | - Jie Yu
- Chinese PLA General Hospital, Beijing, China
| | - Ping Liang
- Chinese PLA General Hospital, Beijing, China.
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21
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Shin H, Hur MH, Song BG, Park SY, Kim GA, Choi G, Nam JY, Kim MA, Park Y, Ko Y, Park J, Lee HA, Chung SW, Choi NR, Park MK, Lee YB, Sinn DH, Kim SU, Kim HY, Kim JM, Park SJ, Lee HC, Lee DH, Chung JW, Kim YJ, Yoon JH, Lee JH. AI model using CT-based imaging biomarkers to predict hepatocellular carcinoma in patients with chronic hepatitis B. J Hepatol 2025; 82:1080-1088. [PMID: 39710148 DOI: 10.1016/j.jhep.2024.12.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 11/12/2024] [Accepted: 12/07/2024] [Indexed: 12/24/2024]
Abstract
BACKGROUND & AIMS Various hepatocellular carcinoma (HCC) prediction models have been proposed for patients with chronic hepatitis B (CHB) using clinical variables. We aimed to develop an artificial intelligence (AI)-based HCC prediction model by incorporating imaging biomarkers derived from abdominal computed tomography (CT) images along with clinical variables. METHODS An AI prediction model employing a gradient-boosting machine algorithm was developed utilizing imaging biomarkers extracted by DeepFore, a deep learning-based CT auto-segmentation software. The derivation cohort (n = 5,585) was randomly divided into the training and internal validation sets at a 3:1 ratio. The external validation cohort included 2,883 patients. Six imaging biomarkers (i.e. abdominal visceral fat-total fat volume ratio, total fat-trunk volume ratio, spleen volume, liver volume, liver-spleen Hounsfield unit ratio, and muscle Hounsfield unit) and eight clinical variables were selected as the main variables of our model, PLAN-B-DF. RESULTS In the internal validation set (median follow-up duration = 7.4 years), PLAN-B-DF demonstrated an excellent predictive performance with a c-index of 0.91 and good calibration function (p = 0.78 by the Hosmer-Lemeshow test). In the external validation cohort (median follow-up duration = 4.6 years), PLAN-B-DF showed a significantly better discrimination function compared to previous models, including PLAN-B, PAGE-B, modified PAGE-B, and CU-HCC (c-index, 0.89 vs. 0.65-0.78; all p <0.001), and maintained a good calibration function (p = 0.42 by the Hosmer-Lemeshow test). When patients were classified into four groups according to the risk probability calculated by PLAN-B-DF, the 10-year cumulative HCC incidence was 0.0%, 0.4%, 16.0%, and 46.2% in the minimal-, low-, intermediate-, and high-risk groups, respectively. CONCLUSION This AI prediction model, integrating deep learning-based auto-segmentation of CT images, offers improved performance in predicting HCC risk among patients with CHB compared to previous models. IMPACT AND IMPLICATIONS The novel predictive model PLAN-B-DF, employing an automated computed tomography segmentation algorithm, significantly improves predictive accuracy and risk stratification for hepatocellular carcinoma in patients with chronic hepatitis B (CHB). Using a gradient-boosting algorithm and computed tomography metrics, such as visceral fat volume and myosteatosis, PLAN-B-DF outperforms previous models based solely on clinical and demographic data. This model not only shows a higher c-index compared to previous models, but also effectively classifies patients with CHB into different risk groups. This model uses machine learning to analyze the complex relationships among various risk factors contributing to hepatocellular carcinoma occurrence, thereby enabling more personalized surveillance for patients with CHB.
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Affiliation(s)
- Hyunjae Shin
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Gyeonggi-do, Korea
| | - Moon Haeng Hur
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Byeong Geun Song
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Gi-Ae Kim
- Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, Kyung Hee University Hospital, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Gwanghyeon Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Gyeonggi-do, Korea
| | | | - Minseok Albert Kim
- Department of Internal Medicine, ABC Hospital, Hwaseong, Gyeonggi-do, Korea
| | - Youngsu Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Yunmi Ko
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jeayeon Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea
| | - Sung Won Chung
- Division of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Na Ryung Choi
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | - Min Kyung Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Gyeonggi-do, Korea
| | - Yun Bin Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hwi Young Kim
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | | | - Sang Joon Park
- AI Center, MedicalIP. Co. Ltd., Seoul, Korea; Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Hyung-Chul Lee
- Department of Anesthesiology, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Ho Lee
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Jin Wook Chung
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea; Inocras Inc., San Diego, CA, USA.
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22
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Ben Khaled N, Zarka V, Hobeika B, Schneider J, Rau M, Weich A, Leicht HB, Ye L, Piseddu I, Dill MT, Kandulski A, Pinter M, Ehmer U, Schirmacher P, Marquardt JU, Mayerle J, De Toni EN, Geier A, Reiter FP. Therapeutic Sequences of Systemic Therapy After Atezolizumab Plus Bevacizumab for Hepatocellular Carcinoma: Real-World Analysis of the IMMUreal Cohort. Aliment Pharmacol Ther 2025; 61:1755-1766. [PMID: 40181694 PMCID: PMC12074566 DOI: 10.1111/apt.70090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 11/25/2024] [Accepted: 03/09/2025] [Indexed: 04/05/2025]
Abstract
BACKGROUND The introduction of several new systemic therapies in recent years has significantly altered the treatment landscape for advanced hepatocellular carcinoma. However, while the approval of the combination of atezolizumab and bevacizumab as the preferred first-line therapy over sorafenib represents progress, it has also raised uncertainties regarding optimal treatment sequencing for advanced disease. AIMS This study evaluates the sequential treatment of hepatocellular carcinoma following therapy with atezolizumab and bevacizumab, providing evidence from a prospective real-world cohort. METHODS Data were derived from the ongoing IMMUreal cohort, which investigates immunotherapy in hepatocellular carcinoma across two tertiary centres in Bavaria. A total of 124 patients treated with atezolizumab and bevacizumab as first-line therapy between June 2020 and December 2023 were analysed. Feasibility, treatment patterns, and outcomes of sequential therapy were assessed, with a focus on defined prognostic subgroups. RESULTS The median overall survival under real-world conditions was 19.8 months. Less than half of the patients (41.2%) proceeded to second-line therapy, and only 19.2% were eligible for third-line treatment. This decline in treatment eligibility corresponded to a marked reduction in therapy duration and progressive deterioration in liver function, as indicated by Albumin-Bilirubin and Child-Pugh scores. While patients with worse baseline liver function, such as patients with Child-Pugh B or ALBI > 1, had a significantly lower probability of transitioning to 2nd line therapy, no significant association was found between the number of treatment lines and factors such as liver cirrhosis, poor physical condition, extrahepatic disease, or macrovascular invasion. CONCLUSIONS Sequential therapy following atezolizumab and bevacizumab is feasible only for selected patients. However, preserving liver function seems crucial to optimising multi-line therapy and improving outcomes in advanced hepatocellular carcinoma.
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Affiliation(s)
- Najib Ben Khaled
- Department of Medicine IIUniversity Hospital, LMU MunichMunichGermany
| | - Valentina Zarka
- Division of Hepatology, Department of Medicine IIUniversity Hospital WürzburgWürzburgGermany
| | - Bernard Hobeika
- Department of Medicine IIUniversity Hospital, LMU MunichMunichGermany
| | - Julia Schneider
- Department of Medicine IIUniversity Hospital, LMU MunichMunichGermany
| | - Monika Rau
- Division of Hepatology, Department of Medicine IIUniversity Hospital WürzburgWürzburgGermany
| | - Alexander Weich
- Division of Gastroenterology, Department of Medicine IIUniversity Hospital WürzburgWürzburgGermany
| | - Hans Benno Leicht
- Division of Hepatology, Department of Medicine IIUniversity Hospital WürzburgWürzburgGermany
| | - Liangtao Ye
- Department of Medicine IIUniversity Hospital, LMU MunichMunichGermany
- Digestive Diseases CenterThe Seventh Affiliated Hospital, Sun Yat‐Sen UniversityShenzhenChina
| | - Ignazio Piseddu
- Department of Medicine IIUniversity Hospital, LMU MunichMunichGermany
| | - Michael T. Dill
- Department of Gastroenterology, Infectious Diseases and IntoxicationHeidelberg University HospitalHeidelbergGermany
- National Center for Tumor Diseases (NCT)NCT Heidelberg, a Partnership Between DKFZ and Heidelberg University HospitalHeidelbergGermany
- German Cancer Research Center (DKFZ) HeidelbergResearch Group Experimental Hepatology, Inflammation and CancerHeidelbergGermany
| | - Arne Kandulski
- Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, Department of Internal Medicine IUniversity Hospital RegensburgRegensburgGermany
| | - Matthias Pinter
- Division of Gastroenterology and Hepatology, Department of Medicine IIIMedical University of ViennaViennaAustria
| | - Ursula Ehmer
- Clinical Department for Internal Medicine II, Department of Clinical Medicine, TUM School of Medicine and Health, University Medical Center, Technical University of MunichMunichGermany
| | | | | | - Julia Mayerle
- Department of Medicine IIUniversity Hospital, LMU MunichMunichGermany
| | - Enrico N. De Toni
- Department of Medicine IIUniversity Hospital, LMU MunichMunichGermany
| | - Andreas Geier
- Division of Hepatology, Department of Medicine IIUniversity Hospital WürzburgWürzburgGermany
| | - Florian P. Reiter
- Division of Hepatology, Department of Medicine IIUniversity Hospital WürzburgWürzburgGermany
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23
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Zhang W, Li N, Li J, Zhao Y, Long Y, He C, Zhang C, Li B, Zhao Y, Lai S, Ding W, Gao M, Tan L, Wei X, Yang R, Jiang X. Noninvasive identification of proliferative hepatocellular carcinoma on multiphase dynamic CT: quantitative and LI-RADS lexicon-based evaluation. Eur Radiol 2025; 35:3460-3475. [PMID: 39665988 DOI: 10.1007/s00330-024-11247-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 10/20/2024] [Accepted: 11/24/2024] [Indexed: 12/13/2024]
Abstract
OBJECTIVE To identify proliferative hepatocellular carcinoma (HCC) preoperatively using quantitative measurements combined with the updated standard 2021 LI-RADS universal lexicon-based qualitative features on multiphase dynamic CT (MDCT). METHODS We retrospectively analyzed 273 patients (102 proliferative HCCs) who underwent preoperative MDCT with surgically confirmed HCC in two medical centers. Imaging features were evaluated according to the updated 2021 LI-RADS universal lexicon, and quantitative measurements were analyzed. All MDCT findings and clinical factors were compared. Four predictive models (clinical, CT quantitative-clinical, CT qualitative-clinical, and combinational models) were developed and validated in an external cohort for identifying proliferative HCC. ROC analysis was used to assess model performances. All models were tested in a subgroup of patients with a single lesion ≤ 5 cm (n = 124). RESULTS Both the CT quantitative-clinical and CT qualitative-clinical models effectively identified proliferative HCC in the training and external validation cohorts (all AUCs > 0.79). The combinational model, integrating one clinical (AFP ≥ 200 ng/mL), three qualitative (rim arterial phase hyperenhancement (APHE), non-smooth tumor margin, and incomplete or absent capsule), and one quantitative feature (standardized tumor-to-aorta density ratio in portal venous phase ≤ (- 0.13), showed significant improvement in the training cohort (AUC 0.871) and comparable performance in the validation cohort (AUC 0.870). Additionally, AFP ≥ 200 ng/mL and Rim APHE were significantly associated with HCC recurrence (p < 0.05). CONCLUSIONS The combinational model, integrating clinical, CT quantitative, and qualitative features, shows potential for the noninvasively preoperative prediction of proliferative HCC. Further validation is needed to establish its broader clinical utility. KEY POINTS Question Preoperative identification of proliferative HCC could influence patient treatment and prognosis, yet there is no CT-based universally applicable model to identify this subtype. Findings The updated standard 2021 LI-RADS universal lexicon-based features, in combination with quantitative MDCT measurements, could aid in the noninvasive detection of proliferative HCC. Clinical relevance The updated standard 2021 LI-RADS universal lexicon-based CT qualitative features and quantitative measurements may aid in identifying proliferative HCC and tumor recurrence, offering potential guidance for personalized treatment. Further studies are required to assess their generalizability to different clinical scenarios.
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Affiliation(s)
- Wanli Zhang
- Department of Radiology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- School of Medicine, South China University of Technology, Guangzhou, China
| | - Nan Li
- Department of Radiology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Jiamin Li
- Department of Radiology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- School of Medicine, South China University of Technology, Guangzhou, China
| | - Yue Zhao
- Department of Radiology, Central People's Hospital of Zhanjiang, Zhanjiang, China
| | - Yi Long
- Department of Radiology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- School of Medicine, South China University of Technology, Guangzhou, China
| | - Chutong He
- Medical Imaging Center, Jinan University First Affiliated Hospital, Guangzhou, China
| | - Chuanxian Zhang
- Department of Radiology, The Zhaoqing Hospital of the Third Affiliated Hospital, Sun Yat-sen University, Zhaoqing, China
| | - Bo Li
- Department of Radiology, The First People's Hospital of Foshan, Foshan, China
| | - Yandong Zhao
- Department of Radiology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- School of Medicine, South China University of Technology, Guangzhou, China
| | - Shengsheng Lai
- School of Medical Equipment, Guangdong Food and Drug Vocational College, Guangzhou, China
| | - Wenshuang Ding
- Department of Pathology, Guangzhou First People's Hospital, Guangzhou, China
| | - Mingyong Gao
- Department of Radiology, The First People's Hospital of Foshan, Foshan, China
| | - Lilian Tan
- Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Xinhua Wei
- Department of Radiology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- School of Medicine, South China University of Technology, Guangzhou, China
| | - Ruimeng Yang
- Department of Radiology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
- School of Medicine, South China University of Technology, Guangzhou, China.
| | - Xinqing Jiang
- Department of Radiology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
- School of Medicine, South China University of Technology, Guangzhou, China.
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24
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Wang Q, Sun L, Zhang G, Chen Z, Li G, Jin R. A novel nomogram based on machine learning predicting overall survival for hepatocellular carcinoma patients with dynamic α‑fetoprotein level changes after local resection. Oncol Lett 2025; 29:310. [PMID: 40342725 PMCID: PMC12059617 DOI: 10.3892/ol.2025.15056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Accepted: 03/20/2025] [Indexed: 05/11/2025] Open
Abstract
The principal aim of the present study was to develop and validate a nomogram predicting overall survival (OS) in patients with α-fetoprotein (AFP)-negative hepatocellular carcinoma (AFP-NHCC) who experience dynamic changes in AFP level after hepatectomy. A cohort of 870 patients were enrolled and randomly assigned into a training cohort (n=600) and a validation cohort (n=270) at a 7:3 ratio. The key variables contributing to the nomogram were determined through random survival forest analysis and multivariate Cox regression. The discriminative ability of the nomogram was evaluated using time-dependent receiver operating characteristic curves and the area under the curves. Furthermore, the nomogram was comprehensively assessed using the concordance index (C-index), calibration curves and clinical decision curve analysis (DCA). Kaplan-Meier (KM) curves analysis was employed to discern survival rates across diverse risk strata of patients. Ultimately, the nomogram incorporated critical factors including sex, tumor size, globulin levels, gamma-glutamyl transferase and fibrinogen levels. In the training and validation cohorts, the C-indexes were 0.72 [95% confidence interval (CI): 0.685-0.755) and 0.664 (95% CI: 0.611-0.717], respectively, attesting to its predictive validity. The nomogram demonstrated excellent calibration and DCA further confirmed its clinical usefulness. Additionally, KM curve analysis unveiled statistically significant differences in OS among three distinct risk groups. In conclusion, the present study successfully formulated a nomogram predicting 3-, 5- and 8-year OS in patients with AFP-NHCC with dynamic changes in AFP level post-local resection. This model serves as a valuable tool for clinicians to promptly identify high-risk patients, thereby facilitating timely interventions and potentially enhancing patient survival outcomes.
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Affiliation(s)
- Qi Wang
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China
- Beijing Institute of Hepatology, Beijing You'an Hospital, Capital Medical University, Beijing 100069, P.R. China
| | - Lina Sun
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China
- Beijing Institute of Hepatology, Beijing You'an Hospital, Capital Medical University, Beijing 100069, P.R. China
| | - Gongming Zhang
- Department of General Surgery, Beijing You'an Hospital, Capital Medical University, Beijing 100069, P.R. China
| | - Zhuangzhuang Chen
- Department of General Surgery, Beijing You'an Hospital, Capital Medical University, Beijing 100069, P.R. China
| | - Guangming Li
- Department of General Surgery, Beijing You'an Hospital, Capital Medical University, Beijing 100069, P.R. China
| | - Ronghua Jin
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China
- Beijing Institute of Hepatology, Beijing You'an Hospital, Capital Medical University, Beijing 100069, P.R. China
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25
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Luo Y, Yang Q, Hu J, Qin X, Jiang S, Liu Y. Preliminary study on detection and diagnosis of focal liver lesions based on a deep learning model using multimodal PET/CT images. Eur J Radiol Open 2025; 14:100624. [PMID: 39803389 PMCID: PMC11720101 DOI: 10.1016/j.ejro.2024.100624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 10/23/2024] [Accepted: 12/11/2024] [Indexed: 01/16/2025] Open
Abstract
Objectives To develop and validate a deep learning model using multimodal PET/CT imaging for detecting and classifying focal liver lesions (FLL). Methods This study included 185 patients who underwent 18F-FDG PET/CT imaging at our institution from March 2022 to February 2023. We analyzed serological data and imaging. Liver lesions were segmented on PET and CT, serving as the "reference standard". Deep learning models were trained using PET and CT images to generate predicted segmentations and classify lesion nature. Model performance was evaluated by comparing the predicted segmentations with the reference segmentations, using metrics such as Dice, Precision, Recall, F1-score, ROC, and AUC, and compared it with physician diagnoses. Results This study finally included 150 patients, comprising 46 patients with benign liver nodules, 51 patients with malignant liver nodules, and 53 patients with no FLLs. Significant differences were observed among groups for age, AST, ALP, GGT, AFP, CA19-9and CEA. On the validation set, the Dice coefficient of the model was 0.740. For the normal group, the recall was 0.918, precision was 0.904, F1-score was 0.909, and AUC was 0.976. For the benign group, the recall was 0.869, precision was 0.862, F1-score was 0.863, and AUC was 0.928. For the malignant group, the recall was 0.858, precision was 0.914, F1-score was 0.883, and AUC was 0.979. The model's overall diagnostic performance was between that of junior and senior physician. Conclusion This deep learning model demonstrated high sensitivity in detecting FLLs and effectively differentiated between benign and malignant lesions.
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Affiliation(s)
- Yingqi Luo
- Department of Nuclear medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Qingqi Yang
- Department of Vascular Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Jinglang Hu
- School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Xiaowen Qin
- Department of Nuclear medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Shengnan Jiang
- Department of Nuclear medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Ying Liu
- Department of Nuclear medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
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Sternby Eilard M, Helmersson M, Rizell M, Vaz J, Åberg F, Taflin H. Non-liver comorbidity in patients with hepatocellular carcinoma and curative treatments - a Swedish national registry study. Scand J Gastroenterol 2025; 60:572-580. [PMID: 40251969 DOI: 10.1080/00365521.2025.2487539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 02/26/2025] [Accepted: 03/10/2025] [Indexed: 04/21/2025]
Abstract
OBJECTIVES Treatment decisions for hepatocellular carcinoma (HCC) involve considering tumour stage, liver function and performance status, including comorbidities, although rarely analysed specifically. This study examines the patterns and prognostic impact of comorbidities in HCC patients. METHODS We included patients diagnosed with HCC before undergoing transplantation, resection or ablation, registered in the Swedish Registry for Cancers in the Liver and Bile ducts (SweLiv) 2008-2016. Data were cross-linked with the Swedish National Patient Registry (NPR) to capture International Classification of Diseases (ICD) codes reflecting comorbidities within 10 years before the HCC treatment decision. The Charlson Comorbidity Index (CCI), excluding the liver disease category (CCI-P), was used to estimate accumulated comorbidity. RESULTS We identified 980 HCC patients with transplantation (225), resection (425) or ablation (330). The comorbidity burden, assessed using the CCI-P, was highest in ablation patients and lowest in the transplanted group (p < 0.001). The CCI-P category distribution varied across treatment groups. After adjusting for age and tumour burden, several CCI-P categories were associated with 5-year mortality, including heart failure, cerebrovascular disease, pulmonary disease, ulcers, and renal disease. ICD diagnoses not included in the CCI, such as trauma, infection, psychiatric disease, anaemia, and obesity, were also linked to 5-year mortality. CONCLUSIONS Comorbidity burden and patterns differed between HCC treatment groups, with CCI-P significantly associated with mortality. Preoperative attention to cardiovascular disease is important, but other comorbid conditions may require vigilance. Given the higher prevalence of comorbidities in ablation and resection patients, efforts to optimize comorbidity in these groups may be warranted.
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Affiliation(s)
- Malin Sternby Eilard
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Transplantation, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Madeleine Helmersson
- Regional Cancer Centre West, Western Sweden Health Care Region, Gothenburg, Sweden
| | - Magnus Rizell
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Transplantation, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Juan Vaz
- School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden
- Department of Medicine, Huddinge, Karolinska Institute, Stockholm, Sweden
| | - Fredrik Åberg
- Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Finland
| | - Helena Taflin
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Transplantation, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
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27
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Collins AL, Kirkness K, Ramon-Gil E, Tzortzopoulou E, Geh D, Dishington J, Graham E, Muir R, Cameron R, Luli S, Khurram E, Storey D, Paish HL, Nelson G, McDonald D, Filby A, Borthwick LA, Oakley F, Mann DA, Leslie J. Precision-cut tumor slices for modeling hepatocellular carcinoma enable at-scale drug screening. Hepatol Commun 2025; 9:e0706. [PMID: 40377490 PMCID: PMC12088631 DOI: 10.1097/hc9.0000000000000706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 02/11/2025] [Indexed: 05/18/2025] Open
Abstract
BACKGROUND Disease modeling is vital for our understanding of disease mechanisms and for developing new therapeutic strategies. Accurately modeling the intact tumor microenvironment (TME) is increasingly recognized as essential for gaining insights into cancer biology and therapeutic response. Preclinical mouse models have provided utility for studying the evolving TME, but these models are costly and can lead to animal suffering and the discontinuation of drug investigations. To address these limitations, particularly in hepatocellular carcinoma (HCC), we have developed an ex vivo model using tumor precision-cut slices (TPCS) derived from orthotopic liver tumors. METHODS Murine HCC tumors were generated via intrahepatic injection of Hep-53.4 cells, providing a source of tumor tissue for TPCS generation. Subsequent scaling to a 96-well format and modification to include a secreted luciferase enabled longitudinal ex vivo screening of 26 drugs applied at 2 doses over an 8-day period, using just 5 tumors. One drug identified in the screen, salinomycin, was then validated in vivo via intraperitoneal injection of mice with orthotopic liver tumors. RESULTS Histological characterization determined that TPCS maintain the architecture, cellular complexity, and drug responsiveness of the original HCC-TME under simplified culture conditions that preserve viability and metabolic activity. In addition to typical HCC therapies, sorafenib and anti-PD1 immunotherapy, the screen identified 2 drugs as potent anticancer agents capable of impacting the viability of TPCS: salinomycin and rottlerin. Salinomycin was further validated in vivo, significantly reducing tumor burden without evidence of toxicity. CONCLUSIONS We present a 3Rs (Reduction, Refinement, Replacement) approach for studying HCC biology and performing 96-well-scale drug screening within an intact, metabolically active TME, offering a more ethical and effective platform for drug discovery.
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Affiliation(s)
- Amy L Collins
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- The Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK
| | - Keara Kirkness
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- The Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK
| | - Erik Ramon-Gil
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- The Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK
| | - Eleni Tzortzopoulou
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Daniel Geh
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- The Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK
| | - Jack Dishington
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- The Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK
| | - Eleanor Graham
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- The Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK
| | - Rhys Muir
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Rainie Cameron
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Saimir Luli
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Eman Khurram
- Newcastle University Medicine Malaysia, Iskandar Puteri, Malaysia
| | - Daniel Storey
- FibroFind Ltd, William Leech Building, Medical School, Newcastle University, Newcastle upon Tyne, UK
| | - Hannah L. Paish
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- FibroFind Ltd, William Leech Building, Medical School, Newcastle University, Newcastle upon Tyne, UK
| | - Glyn Nelson
- Bioimaging Unit, Newcastle University, Newcastle upon Tyne, UK
| | - David McDonald
- Flow Cytometry Core Facility, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Andrew Filby
- Flow Cytometry Core Facility, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Lee A. Borthwick
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- FibroFind Ltd, William Leech Building, Medical School, Newcastle University, Newcastle upon Tyne, UK
| | - Fiona Oakley
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- The Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK
- FibroFind Ltd, William Leech Building, Medical School, Newcastle University, Newcastle upon Tyne, UK
| | - Derek A. Mann
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- The Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK
- FibroFind Ltd, William Leech Building, Medical School, Newcastle University, Newcastle upon Tyne, UK
- Department of Gastroenterology and Hepatology, School of Medicine, Koç University, Istanbul, Turkey
| | - Jack Leslie
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- The Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK
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Feng H, Jin Y, Wu B. Strategies for neoantigen screening and immunogenicity validation in cancer immunotherapy (Review). Int J Oncol 2025; 66:43. [PMID: 40342048 PMCID: PMC12101193 DOI: 10.3892/ijo.2025.5749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2025] [Accepted: 04/11/2025] [Indexed: 05/11/2025] Open
Abstract
Cancer immunotherapy stimulates and enhances antitumor immune responses to eliminate cancer cells. Neoantigens, which originate from specific mutations within tumor cells, are key targets in cancer immunotherapy. Neoantigens manifest as abnormal peptide fragments or protein segments that are uniquely expressed in tumor cells, making them highly immunogenic. As a result, they activate the immune system, particularly T cell‑mediated immune responses, effectively identifying and eliminating tumor cells. Certain tumor‑associated antigens that are abnormally expressed in normal host proteins in cancer cells are promising targets for immunotherapy. Neoantigens derived from mutated proteins in cancer cells offer true cancer specificity and are often highly immunogenic. Furthermore, most neoantigens are unique to each patient, highlighting the need for personalized treatment strategies. The precise identification and screening of neoantigens are key for improving treatment efficacy and developing individualized therapeutic plans. The neoantigen prediction process involves somatic mutation identification, human leukocyte antigen (HLA) typing, peptide processing and peptide‑HLA binding prediction. The present review summarizes the major current methods used for neoantigen screening, available computational tools and the advantages and limitations of various techniques. Additionally, the present review aimed to summarize experimental strategies for validating the immunogenicity of the predicted neoantigens, which will determine whether these neoantigens can effectively trigger immune responses, as well as challenges encountered during neoantigen screening, providing relevant recommendations for the optimization of neoantigen‑based immunotherapy.
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Affiliation(s)
- Hua Feng
- College of Life Sciences, China Jiliang University, Hangzhou, Zhejiang 310018, P.R. China
| | - Yuanting Jin
- College of Life Sciences, China Jiliang University, Hangzhou, Zhejiang 310018, P.R. China
| | - Bin Wu
- Department of Neurosurgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, P.R. China
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29
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Le HDM, Vo DT, Do HT, Le HNG, Phan CC, Nguyen DT, Le QND. Hepatectomy in a young patient with advanced hepatocellular carcinoma and poor prognostic imaging features: A case of recurrence-free survival. Radiol Case Rep 2025; 20:2704-2709. [PMID: 40151292 PMCID: PMC11937630 DOI: 10.1016/j.radcr.2025.02.085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 02/18/2025] [Accepted: 02/19/2025] [Indexed: 03/29/2025] Open
Abstract
A 45-year-old male with chronic hepatitis B presented with an advanced hepatocellular carcinoma (HCC) occupying the entire left liver and invading the left portal vein. Despite multiple poor prognostic imaging features, including vascular invasion, corona enhancement, an incomplete capsule, intratumoral necrosis, intratumoral arteries, and irregular tumor borders, the patient elected to undergo a left hepatectomy. Although Barcelona Clinic Liver Cancer (BCLC) staging classified the case as stage C, a resection was successfully performed. Remarkably, 6 years postsurgery, the patient remains recurrence-free. This report highlights a rare, fortunate outcome in a high-risk HCC case and underscores the potential of surgical intervention even in advanced HCC.
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Affiliation(s)
- Huyen Duy Mai Le
- Department of Diagnostic Imaging, University Medical Center, Ho Chi Minh City, Vietnam
| | - Duc Tan Vo
- Department of Diagnostic Imaging, University Medical Center, Ho Chi Minh City, Vietnam
- Department of Diagnostic Imaging, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam
| | - Hai Trong Do
- Department of General Surgery, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam
| | - Hy Nguyen Gia Le
- Department of Diagnostic Imaging, University Medical Center, Ho Chi Minh City, Vietnam
| | - Chien Cong Phan
- Department of Diagnostic Imaging, University Medical Center, Ho Chi Minh City, Vietnam
| | - Duy Thanh Nguyen
- Department of Diagnostic Imaging, University Medical Center, Ho Chi Minh City, Vietnam
| | - Quynh Nguyen Diem Le
- Department of Diagnostic Imaging, University Medical Center, Ho Chi Minh City, Vietnam
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Oura K, Morishita A, Yano R, Manabe T, Takuma K, Nakahara M, Tadokoro T, Fujita K, Mimura S, Tani J, Tatsuta M, Himoto T, Masaki T, Kobara H. Circulating miR-485-3p as a biomarker for VEGF-associated therapeutic response to atezolizumab plus bevacizumab in hepatocellular carcinoma. J Gastroenterol 2025; 60:770-782. [PMID: 40180668 DOI: 10.1007/s00535-025-02239-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Accepted: 02/25/2025] [Indexed: 04/05/2025]
Abstract
BACKGROUND In atezolizumab/bevacizumab (atezo/bev) therapy for unresectable hepatocellular carcinoma (HCC), the tumor immune environment is regulated through vascular endothelial growth factor A (VEGFA) inhibition to maximize immune checkpoint blockade; however, evidence for VEGFA as a biomarker is limited. This study aimed to investigate serum VEGFA and associated microRNAs (miRNAs) as rapid biomarkers and their regulatory mechanisms in the microenvironment of HCC. METHODS Fifty-four patients with unresectable HCC who were treated with atezo/bev therapy were enrolled and assigned into objective response (OR) and non-OR groups according to the best therapeutic response in 12 weeks using the modified response evaluation criteria in solid tumors. Serum VEGFA levels and associated miRNA expression were compared. Furthermore, the effect of cell transfection with specific miRNA was investigated. RESULT There was no significant difference in the pre-treatment serum VEGFA levels between the groups; however, the 3-week/pre-treatment ratio of serum VEGFA levels was significantly lower in the OR group than in the non-OR group. The pre-treatment serum levels of 10 miRNAs, especially miR-485-3p involved in VEGFA expression, were higher in the OR group than in the non-OR group and were further elevated after 1-7 days and 3 weeks. MiR-485-3p suppressed HuH-7 migration, enhanced the expression of protein inhibitor of activated (PIA) signal transducer and activator of transcription 3 (STAT3) (PIAS3), and suppressed the expression of phosphorylated STAT3/VEGFA. CONCLUSION Circulating miR-485-3p is a more sensitive biomarker than VEGFA for the early prediction of therapeutic response in atezo/bev therapy for HCC.
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Affiliation(s)
- Kyoko Oura
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Asahiro Morishita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan.
| | - Rie Yano
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Takushi Manabe
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
- Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Kagawa, Japan
| | - Kei Takuma
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Mai Nakahara
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Tomoko Tadokoro
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Koji Fujita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Shima Mimura
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Joji Tani
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Miwa Tatsuta
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
- Department of Gastroenterology, KKR Takamatsu Hospital, Takamatsu, Kagawa, Japan
| | - Takashi Himoto
- Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Takamatsu, Japan
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
- Department of Gastroenterology, Kagawa Saiseikai Hospital, Takamatsu, Japan
| | - Hideki Kobara
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
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Artusa F, Lamatsch S, Phan MD, Özdirik B, Berger H, Egerer M, Knorr‐Klocke J, Fischer J, Veelken R, van Bömmel F, Berg T, Kappert K, Tauber R, Puengel T, Engelmann C, Demir M, Tacke F, Mohr R. Soluble Urokinase Plasminogen Activator Receptor Predicts Survival and Hepatic Decompensation in Advanced Hepatocellular Carcinoma. Liver Int 2025; 45:e70121. [PMID: 40317602 PMCID: PMC12046945 DOI: 10.1111/liv.70121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Revised: 04/01/2025] [Accepted: 04/22/2025] [Indexed: 05/07/2025]
Abstract
BACKGROUND AND AIMS The introduction of immune checkpoint inhibitor (ICI) based therapies has significantly improved the prognosis of patients with unresectable hepatocellular carcinoma (HCC). However, the variable treatment response and the uncertain benefit in patients with advanced liver cirrhosis emphasise the urgent need for prognostic and predictive biomarkers guiding patient selection. The soluble urokinase plasminogen activator receptor (suPAR) is strongly associated with inflammation, liver cirrhosis and various types of cancer. In this study, we investigated suPAR as a potential novel biomarker in patients with unresectable HCC. METHODS This multicenter retrospective study, conducted at three German tertiary care centers, included 90 patients with unresectable HCC and suPAR measurements prior to and during atezolizumab/bevacizumab therapy. Patients with liver cirrhosis without HCC (n = 235) and non-cirrhotic patients with other gastrointestinal tumours (n = 155) were selected as control cohorts. RESULTS Median suPAR levels were significantly higher in patients with liver cirrhosis compared to non-cirrhotic cancer patients. A strong association with parameters of liver function, but not with HCC characteristics, was observed. In patients with HCC receiving atezolizumab/bevacizumab, suPAR was the most accurate independent predictor of hepatic decompensation and overall survival (OS). In addition, suPAR was able to stratify the risk of hepatic decompensation within the different Child-Pugh classes. CONCLUSIONS SuPAR represents a promising novel biomarker in patients with HCC treated with ICI-based therapies and bears the potential to guide the selection of antitumoral systemic therapies in patients with advanced liver cirrhosis.
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Affiliation(s)
- Fabian Artusa
- Department of Hepatology and GastroenterologyCharité ‐ Universitätsmedizin Berlin, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM)BerlinGermany
| | - Sven Lamatsch
- Department of Hepatology and GastroenterologyCharité ‐ Universitätsmedizin Berlin, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM)BerlinGermany
| | - Minh Duc Phan
- Department of Hepatology and GastroenterologyCharité ‐ Universitätsmedizin Berlin, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM)BerlinGermany
| | - Burcin Özdirik
- Department of Hepatology and GastroenterologyCharité ‐ Universitätsmedizin Berlin, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM)BerlinGermany
| | - Hilmar Berger
- Department of Hepatology and GastroenterologyCharité ‐ Universitätsmedizin Berlin, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM)BerlinGermany
| | - Mara Egerer
- Department of Hepatology and GastroenterologyCharité ‐ Universitätsmedizin Berlin, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM)BerlinGermany
| | - Jana Knorr‐Klocke
- Department of Hepatology and GastroenterologyCharité ‐ Universitätsmedizin Berlin, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM)BerlinGermany
| | - Janett Fischer
- Division of Hepatology, Department of Medicine IILeipzig University Medical CenterLeipzigGermany
| | - Rhea Veelken
- Division of Hepatology, Department of Medicine IILeipzig University Medical CenterLeipzigGermany
| | - Florian van Bömmel
- Division of Hepatology, Department of Medicine IILeipzig University Medical CenterLeipzigGermany
| | - Thomas Berg
- Division of Hepatology, Department of Medicine IILeipzig University Medical CenterLeipzigGermany
| | - Kai Kappert
- Institute of Diagnostic Laboratory Medicine, Clinical Chemistry and PathobiochemistryCharité ‐ Universitätsmedizin BerlinBerlinGermany
- Labor Berlin – Charité Vivantes GmbHBerlinGermany
| | - Rudolf Tauber
- Institute of Diagnostic Laboratory Medicine, Clinical Chemistry and PathobiochemistryCharité ‐ Universitätsmedizin BerlinBerlinGermany
- Labor Berlin – Charité Vivantes GmbHBerlinGermany
| | - Tobias Puengel
- Department of Hepatology and GastroenterologyCharité ‐ Universitätsmedizin Berlin, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM)BerlinGermany
| | - Cornelius Engelmann
- Department of Hepatology and GastroenterologyCharité ‐ Universitätsmedizin Berlin, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM)BerlinGermany
- Institute for Liver and Digestive HealthUniversity College LondonLondonUK
| | - Münevver Demir
- Department of Hepatology and GastroenterologyCharité ‐ Universitätsmedizin Berlin, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM)BerlinGermany
| | - Frank Tacke
- Department of Hepatology and GastroenterologyCharité ‐ Universitätsmedizin Berlin, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM)BerlinGermany
| | - Raphael Mohr
- Department of Hepatology and GastroenterologyCharité ‐ Universitätsmedizin Berlin, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM)BerlinGermany
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Tasneem M, Gupta SD, Ahmed Jony MJ, Minkara M, Dey RK, Ferdoush J. Identification of key biomarker genes in liver hepatocellular carcinoma and kidney renal clear cell carcinoma progression: A shared high-throughput screening and molecular docking method with potentials for targeted therapeutic interventions. J Genet Eng Biotechnol 2025; 23:100497. [PMID: 40390492 PMCID: PMC12049835 DOI: 10.1016/j.jgeb.2025.100497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 04/14/2025] [Indexed: 05/21/2025]
Abstract
BACKGROUND AND OBJECTIVES Liver Hepatocellular Carcinoma (LIHC) and Kidney Renal Clear Cell Carcinoma (KIRC) are leading causes of cancer death worldwide, but their early detections remain hindered by a lack of genetic markers. Our study aims to find prospective biomarkers that could serve as prognostic indicators for efficient drug candidates for KIRC and LIHC treatment. METHODS To detect differentially expressed genes (DEGs), four datasets were used: GSE66271 and GSE213324 for KIRC, and GSE135631 and GSE202853 for LIHC. Visualization of DEGs was done using heatmaps, volcano plots, and Venn diagrams. Hub genes were identified via PPI analysis and the cytoHubba plugin in Cytoscape. Their expression was evaluated using box plots, stage plots, and survival plots for prognostic assessment via GEPIA2. Molecular docking with PyRx's AutoDock Vina identified optimal binding interactions between compounds and proteins. Pharmacokinetic and toxicity analyses reinforced the drug-likeness and safety of these compounds. RESULTS In this study, 47 DEGs were identified, with the top 10 hub genes being TOP2A, BUB1, PTTG1, CCNB2, NUSAP1, KIF20A, BIRC5, RRM2, NDC80 and CDC45, chosen for their high MCC scores. Data mining revealed a correlation between TOP2A expression and clinical survival outcomes in KIRC and LIHC patients. Docking studies of the TOP2A structure identified a promising compound from Andrographis paniculata with high binding energy and interactions with TOP2A. Pharmacokinetic and toxicity assessments support its potential as a drug candidate. CONCLUSION Our study emphasizes TOP2A's prognostic significance in KIRC and LIHC and recognizes Andrographis paniculata compound as potential therapeutics, offering prospective for enhanced treatment and patient outcomes in these cancers.
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Affiliation(s)
- Maisha Tasneem
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali 3814, Bangladesh
| | - Shipan Das Gupta
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali 3814, Bangladesh
| | - Md Jubair Ahmed Jony
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali 3814, Bangladesh
| | - Maya Minkara
- Department of Biology, Geology, and Environmental Science, University of Tennessee at Chattanooga, 615 McCallie Ave, Chattanooga, TN 37403, USA
| | | | - Jannatul Ferdoush
- Department of Biology, Geology, and Environmental Science, University of Tennessee at Chattanooga, 615 McCallie Ave, Chattanooga, TN 37403, USA.
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Jiang H, Li B, Zheng T, Qin Y, Wu Y, Wu Z, Ronot M, Chernyak V, Fowler KJ, Bashir MR, Chen W, Wang YC, Ju S, Song B. MRI-based prediction of microvascular invasion/high tumor grade and adjuvant therapy benefit for solitary HCC ≤ 5 cm: a multicenter cohort study. Eur Radiol 2025; 35:3223-3237. [PMID: 39702639 PMCID: PMC12081510 DOI: 10.1007/s00330-024-11295-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 10/25/2024] [Accepted: 11/16/2024] [Indexed: 12/21/2024]
Abstract
OBJECTIVES To develop and externally validate an MRI-based diagnostic model for microvascular invasion (MVI) or Edmondson-Steiner G3/4 (i.e., high-risk histopathology) in solitary BCLC 0/A hepatocellular carcinoma (HCC) ≤ 5 cm and to assess its performance in predicting adjuvant therapy benefits. MATERIALS AND METHODS This multicenter retrospective cohort study included 577 consecutive adult patients who underwent contrast-enhanced MRI and subsequent curative resection or ablation for solitary BCLC 0/A HCC ≤ 5 cm (December 2011 to January 2024) from four hospitals. For resection-treated patients, a diagnostic model integrating clinical and 50 semantic MRI features was developed against pathology with logistic regression analyses on the training set (center 1) and externally validated on the testing dataset (centers 2-4), with its utilities in predicting posttreatment recurrence-free survival (RFS) and adjuvant therapy benefit evaluated by Cox regression analyses. RESULTS Serum α-fetoprotein > 100 ng/mL (odds ratio (OR), 1.94; p = 0.006), non-simple nodular growth subtype (OR, 1.69; p = 0.03), and the VICT2 trait (OR, 4.49; p < 0.001) were included in the MVI or high-grade (MHG) trait, with testing set AUC, sensitivity, and specificity of 0.832, 74.0%, and 82.5%, respectively. In the multivariable Cox analysis, the MHG-positive status was associated with worse RFS (resection testing set HR, 3.55, p = 0.02; ablation HR, 3.45, p < 0.001), and adjuvant therapy was associated with improved RFS only for the MHG-positive patients (resection HR, 0.39, p < 0.001; ablation HR, 0.30, p = 0.005). CONCLUSION The MHG trait effectively predicted high-risk histopathology, RFS and adjuvant therapy benefit among patients receiving curative resection or ablation for solitary BCLC 0/A HCC ≤ 5 cm. KEY POINTS Question Despite being associated with increased recurrence and potential benefit from adjuvancy in HCC, microvascular invasion or Edmondson-Steiner grade 3/4 are hardly assessable noninvasively. Findings We developed and externally validated an MRI-based model for predicting high-risk histopathology, post-resection/ablation recurrence-free survival, and adjuvant therapy benefit in solitary HCC ≤ 5 cm. Clinical relevance Among patients receiving curative-intent resection or ablation for solitary HCC ≤ 5 cm, noninvasive identification of high-risk histopathology (MVI or high-grade) using our proposed MRI model may help improve individualized prognostication and patient selection for adjuvant therapies.
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Affiliation(s)
- Hanyu Jiang
- Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Binrong Li
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China
| | - Tianying Zheng
- Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yun Qin
- Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yuanan Wu
- Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Zhenru Wu
- Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Maxime Ronot
- Université Paris Cité, UMR 1149, CRI, Paris & Service de Radiologie, Hôpital Beaujon, APHP.Nord, Clichy, France
| | - Victoria Chernyak
- Department of Radiology, Memorial Sloan Kettering Cancer Center, NYC, New York, NY, USA
| | - Kathryn J Fowler
- Department of Radiology, University of California San Diego, San Diego, CA, USA
| | - Mustafa R Bashir
- Department of Radiology, Center for Advanced Magnetic Resonance in Medicine, and Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC, USA
| | - Weixia Chen
- Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yuan-Cheng Wang
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
| | - Shenghong Ju
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
| | - Bin Song
- Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
- Department of Radiology, Sanya People's Hospital, Sanya, Hainan, China.
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Degasperi E, Anolli MP, Jachs M, Reiberger T, De Ledinghen V, Metivier S, D'Offizi G, di Maria F, Schramm C, Schmidt H, Zöllner C, Tacke F, Dietz-Fricke C, Wedemeyer H, Papatheodoridi M, Papatheodoridis G, Carey I, Agarwal K, Van Bömmel F, Brunetto MR, Cardoso M, Verucchi G, Ciancio A, Zoulim F, Aleman S, Semmo N, Mangia A, Hilleret MN, Merle U, Santantonio TA, Coppola N, Pellicelli A, Roche B, Causse X, D'Alteroche L, Dumortier J, Ganne N, Heluwaert F, Ollivier I, Roulot D, Viganò M, Loglio A, Federico A, Pileri F, Maracci M, Tonnini M, Arpurt JP, Barange K, Billaud E, Pol S, Gervais A, Minello A, Rosa I, Puoti M, Lampertico P. Real-world effectiveness and safety of bulevirtide monotherapy for up to 96 weeks in patients with HDV-related cirrhosis. J Hepatol 2025; 82:1012-1022. [PMID: 39793613 DOI: 10.1016/j.jhep.2024.12.044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Revised: 12/04/2024] [Accepted: 12/17/2024] [Indexed: 01/13/2025]
Abstract
BACKGROUND & AIMS Bulevirtide (BLV) 2 mg/day is EMA approved for the treatment of compensated chronic HDV infection; however, real-world data in large cohorts of patients with cirrhosis are lacking. METHODS Consecutive HDV-infected patients with cirrhosis starting BLV 2 mg/day from September 2019 were included in a European retrospective multicenter real-world study (SAVE-D). Patient characteristics before and during BLV treatment were collected. Virological, biochemical, combined responses, adverse events and liver-related events (hepatocellular carcinoma [HCC], decompensation, liver transplant) were assessed. RESULTS A total of 244 patients with HDV-related cirrhosis receiving BLV monotherapy for a median of 92 (IQR 71-96) weeks were included: at BLV start, median (IQR) age was 49 (40-58) years and 61% were men; median ALT, LSM and platelet count were 80 (55-130) U/L, 18.3 (13.0-26.3) kPa, and 94 (67-145) x103/mm3, respectively; 54% had esophageal varices, 95% Child-Pugh A cirrhosis, and 10% HIV coinfection; 92% were on nucleos(t)ide analogues; median HDV RNA and HBsAg were 5.4 (4.1-6.5) log10 IU/ml and 3.8 (3.4-4.1) log10 IU/ml, respectively. At weeks 48 and 96, virological, biochemical and combined responses were observed in 65% and 79%, 61% and 64%, 44% and 54% of patients, respectively. AST, GGT, albumin, IgG and LSM values significantly improved throughout treatment. Serum bile acid levels increased in most patients, but only 10% reported mild and transient pruritus, which was independent of bile acid levels. The week 96 cumulative risks of de novo HCC and decompensation were 3.0% (95% CI 2-6%) and 2.8% (95% CI 1-5%), respectively. Thirteen (5%) patients underwent liver transplantation (n = 11 for HCC, n = 2 for decompensation). CONCLUSION BLV 2 mg/day monotherapy for up to 96 weeks was safe and effective in patients with HDV-related cirrhosis. Virological and clinical responses increased over time, while the incidence of liver-related complications was low. IMPACT AND IMPLICATIONS Bulevirtide 2 mg/day is EMA approved for the treatment of compensated chronic hepatitis delta; however, real-world data in large cohorts of patients with cirrhosis are lacking. Bulevirtide 2 mg/day monotherapy for up to 96 weeks was safe and effective (week 96: 79% virological, 64% biochemical and 54% combined response) in a large real-world cohort of patients with HDV-related cirrhosis, including patients with clinically significant portal hypertension. Liver function tests and liver stiffness improved, suggesting a potential clinical benefit in patients with advanced liver disease, while the incidence of de novo liver-related events (hepatocellular carcinoma and decompensation) was low during the 96-week study period.
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Affiliation(s)
- Elisabetta Degasperi
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Maria Paola Anolli
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Mathias Jachs
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | | | | | - Gianpiero D'Offizi
- Division of Infectious Diseases - Hepatology, Department of Transplantation and General Surgery, Istituto Nazionale per le Malattie Infettive "L. Spallanzani" IRCCS, Rome Italy
| | - Francesco di Maria
- Division of Infectious Diseases - Hepatology, Department of Transplantation and General Surgery, Istituto Nazionale per le Malattie Infettive "L. Spallanzani" IRCCS, Rome Italy
| | - Christoph Schramm
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Essen, Germany
| | - Hartmut Schmidt
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Essen, Germany
| | - Caroline Zöllner
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Christopher Dietz-Fricke
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Margarita Papatheodoridi
- Department of Gastroenterology, General Hospital of Athens "Laiko", Medical School of National & Kapodistrian University of Athens, Greece
| | - George Papatheodoridis
- Department of Gastroenterology, General Hospital of Athens "Laiko", Medical School of National & Kapodistrian University of Athens, Greece
| | - Ivana Carey
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Kosh Agarwal
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Florian Van Bömmel
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Laboratory for Clinical and Experimental Hepatology, Leipzig, Germany
| | - Maurizia R Brunetto
- Department of Clinical and Experimental Medicine, University of Pisa and Hepatology Unit, University Hospital of Pisa, Pisa, Italy
| | - Mariana Cardoso
- Gastroenterology Department, Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal
| | - Gabriella Verucchi
- Department of Medical and Surgical Sciences, Unit of Infectious Diseases, "Alma Mater Studiorum" University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Alessia Ciancio
- Department of Medical Sciences, University of Turin, Gastroenterology Division of Città della Salute e della Scienza of Turin, University Hospital, Turin, Italy
| | - Fabien Zoulim
- Lyon Hepatology Institute, Université Claude Bernard Lyon 1, Hospices Civils de Lyon, INSERM Unit 1052 - CRCL, Lyon, France
| | - Soo Aleman
- Department of Infectious Diseases, Karolinska University Hospital, and Karolinska Institutet, Stockholm, Sweden
| | - Nasser Semmo
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Alessandra Mangia
- Liver Unit, Fondazione IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy
| | | | - Uta Merle
- Department of Internal Medicine IV, Gastroenterology & Hepatology, Medical University of Heidelberg, Heidelberg, Germany
| | - Teresa A Santantonio
- Department of Medical and Surgical Sciences, Infectious Diseases Unit, University of Foggia, Foggia, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine - Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Adriano Pellicelli
- Liver Unit, San Camillo Hospital, Department of Transplantation and General Surgery, Rome, Italy
| | - Bruno Roche
- Hepato-Biliary Center, AP-HP Hôpital Universitaire Paul Brousse, Paris-Saclay University, Research INSERM-Paris Saclay Unit 1193, Villejuif, France
| | | | | | - Jérome Dumortier
- Department of Digestive Diseases, Hospices Civils de Lyon, Edouard Herriot hospital, France; Claude Bernard Lyon 1 University, France
| | - Nathalie Ganne
- AP-HP, Avicenne Hospital, Hepatology Department, F-93000 Bobigny, France
| | | | - Isabelle Ollivier
- Department of Hepatogastroenterology, CHU de Caen Normandie, Caen, France
| | - Dominique Roulot
- AP-HP, Avicenne hospital, Liver Unit, Sorbonne Paris Nord University, Bobigny, France
| | - Mauro Viganò
- Division of Hepatology, Ospedale San Giuseppe, Italy
| | - Alessandro Loglio
- Gastroenterology, Hepatology and Transplantation Division, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Alessandro Federico
- Division of Hepatogastroenterology, Department of Precision Medicine, Università della Campania "Luigi Vanvitelli", Naples, Italy
| | - Francesca Pileri
- Division of Internal Medicine and Center for Hemochromatosis, University of Modena and Reggio Emilia, Modena, Italy
| | - Monia Maracci
- Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy
| | - Matteo Tonnini
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | | | - Karl Barange
- Department of Gastroenterology, Toulouse University Hospital, Toulouse, France
| | - Eric Billaud
- Université de Nantes, INSERM UIC 1413, Department of Infectious Diseases, CHU Hôtel Dieu, Nantes, France
| | - Stanislas Pol
- Université Paris Cité, Assistance Publique des Hôpitaux de Paris, Hôpital Cochin, Hepatology/Addictology department, Paris, France
| | - Anne Gervais
- Assistance Publique des Hôpitaux de Paris, Hôpital Bichat Claude Bernard, Service des Maladies Infectieuses et Tropicales, Paris, France
| | - Anne Minello
- CHU Dijon, Service d'Hépato-gastroentérologie et oncologie digestive, INSERM EPICAD LNC-UMR1231, Université de Bourgogne-Franche Comté, Dijon, France
| | - Isabelle Rosa
- Service d'hépatogastroentérologie, Centre Hospitalier Intercommunal, Créteil, France
| | - Massimo Puoti
- School of Medicine and Surgery University of Milano Bicocca, Italy
| | - Pietro Lampertico
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; D-SOLVE consortium, Germany(†).
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Akabane M, Kawashima J, Altaf A, Woldesenbet S, Cauchy F, Aucejo F, Popescu I, Kitago M, Martel G, Ratti F, Aldrighetti L, Poultsides GA, Imaoka Y, Ruzzenente A, Endo I, Gleisner A, Marques HP, Lam V, Hugh T, Bhimani N, Shen F, Pawlik TM. Dynamic ALBI score and FIB-4 index trends to predict complications after resection of hepatocellular carcinoma: A K-means clustering approach. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109723. [PMID: 40023021 DOI: 10.1016/j.ejso.2025.109723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 02/22/2025] [Indexed: 03/04/2025]
Abstract
BACKGROUND Severe postoperative complications still occur following hepatectomy among patients with hepatocellular carcinoma (HCC). There is a need to identify high-risk patients for severe complications to enhance patient safety. We sought to evaluate the combined impact of pre- and postoperative albumin-bilirubin (ALBI) score and Fibrosis-4 (FIB-4) index trends to predict severe complications after HCC resection. METHOD Patients with HCC undergoing curative-intent hepatectomy (2000-2023) were identified from an international, multi-institutional database. The cohort was divided into training (n = 439) and testing (n = 651) sets. ALBI score and FIB-4 index trends from preoperative to postoperative days 1, 3, and 5 were used for K-means clustering (K = 3). A logistic regression model was developed using the training set, and its performance was evaluated using the area under the receiver operating characteristic curve (AUC) in both cohorts. RESULTS Severe complications (Clavien-Dindo Grade ≥ IIIa) occurred in 118 patients (10.8 %); 43 (9.8 %) in training and 75 (11.5 %) in testing set (p = 0.42). K-means clustering identified three groups: Cluster1 (low), Cluster2 (intermediate), and Cluster3 (high), which was associated with a progressively increasing risk of complications (p < 0.01). On multivariable logistic regression, patients in ALBI Cluster1 had 76 % decreased odds (odds ratio[OR] 0.24, 95 % CI 0.07-0.83, p = 0.02) of postoperative complications relative to Cluster3 patients. Individuals categorized into FIB-4 Cluster1 had 85 % decreased odds (OR 0.15, 95 % CI 0.02-1.24, p = 0.07) versus patients in FIB-4 Cluster3. A new prediction model incorporating ALBI and FIB-4 index clusters achieved an AUC of 0.71, outperforming models based on preoperative data. A tool was made available at https://nm49jf-miho-akabane.shinyapps.io/HCC_ALBI/. CONCLUSION A dynamic ALBI score and FIB-4 index trend tool improved risk stratification of patients undergoing resection of HCC relative to severe complications.
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Affiliation(s)
- Miho Akabane
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Jun Kawashima
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Abdullah Altaf
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Selamawit Woldesenbet
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - François Cauchy
- Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France
| | - Federico Aucejo
- Department of General Surgery, Cleveland Clinic Foundation, OH, USA
| | - Irinel Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | - Minoru Kitago
- Department of Surgery, Keio University, Tokyo, Japan
| | - Guillaume Martel
- Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada
| | | | | | | | - Yuki Imaoka
- Department of Surgery, Stanford University, Stanford, CA, USA
| | | | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Ana Gleisner
- Department of Surgery, University of Colorado, Denver, CO, USA
| | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - Vincent Lam
- Department of Surgery, Westmead Hospital, Sydney, NSW, Australia
| | - Tom Hugh
- Department of Surgery, School of Medicine, The University of Sydney, Sydney, NSW, Australia
| | - Nazim Bhimani
- Department of Surgery, School of Medicine, The University of Sydney, Sydney, NSW, Australia
| | - Feng Shen
- The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
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Hu Z, Deng M, Fu Y, Zhou Z, Chen H, Chen M, Zhang Y. Neoadjuvant hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin for resectable single large hepatocellular carcinoma. Int J Surg 2025; 111:3850-3858. [PMID: 40358645 PMCID: PMC12165535 DOI: 10.1097/js9.0000000000002437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Accepted: 04/13/2025] [Indexed: 05/15/2025]
Abstract
BACKGROUND AND AIMS Patients diagnosed with single large hepatocellular carcinoma (HCC) often face a daunting prognosis and pose a treatment challenge. In this study, we aimed to evaluate the effectiveness of neoadjuvant hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, fluorouracil, and leucovorin (FOLFOX) in patients with single large HCC. METHODS 397 patients with resectable single, ≥7 cm HCC from three centers in China between January 2016 and December 2021 were included, 268 patients underwent hepatectomy alone and 129 patients underwent neoadjuvant HAIC. The log-rank test was used to compare the overall survival (OS) and disease-free survival (DFS) by intension-to-treat analysis between the two groups. RESULTS The 1-, 3-, and 5-year OS rates were 83.3%, 62.9%, and 53.8% in the surgery alone group, and 97.5%, 80.7%, and 64.7% in the neoadjuvant HAIC group. The 1-, 3-, and 5-year DFS rates were 48.8%, 32.5%, and 26.2% in the surgery alone group, and 71.5%, 61.7%, and 59.5% in the neoadjuvant HAIC group. The neoadjuvant HAIC group showed significantly longer OS (hazard ratio [HR], 0.506; 95% confidence interval [CI], 0.347-0.734; P < 0.001) and DFS (HR, 0.466; 95% CI, 0.357-0.609; P < 0.001) than the surgery alone group. There was no HAIC-related death in the neoadjuvant HAIC group. CONCLUSIONS Neoadjuvant FOLFOX-HAIC significantly improved the OS and DFS with acceptable toxicities in HCC patients with resectable single, ≥7 cm tumor.
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Affiliation(s)
- Zili Hu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China
- Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China
| | - Min Deng
- Department of General Surgery, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, People’s Republic of China
| | - Yizhen Fu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China
- Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China
| | - Zhongguo Zhou
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China
- Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China
| | - Huanwei Chen
- Department of Hepatic Surgery, The Affiliated Foshan Hospital of Sun Yat-Sen University, Foshan, People’s Republic of China
| | - Minshan Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China
- Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China
| | - Yaojun Zhang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China
- Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China
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Zhang J, Zhou S, Jiang Y, Zhao W, Xu W, Zhang J, An T, Yan J, Duan C, Wang X, Yang S, Wang T, Dong D, Chen Y, Zou F, Yu X, Huang M, Fu S. 3D assessment of skeletal muscle and adipose tissue for prognosis of hepatocellular carcinoma: A multicenter cohort study. Clin Nutr ESPEN 2025; 67:626-634. [PMID: 40187734 DOI: 10.1016/j.clnesp.2025.03.168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 12/21/2024] [Accepted: 03/26/2025] [Indexed: 04/07/2025]
Abstract
BACKGROUND Changes in protein and lipid metabolism could provide additional prognostic information for hepatocellular carcinoma (HCC).This study aimed to explore whether 3D automatic assessment of skeletal muscle and adipose tissue can contribute to the precise prognosis for HCC. METHODS The data of 458 HCC patients from 6 hospitals were divided into training and external validation datasets. Preoperative CT Images were used for this study. First, we tested the stability of the 2D factors. Second, we tested whether standardization for volume assessment was necessary. Third, we compared the clinical (ModelC), skeletal muscle and adipose tissue (ModelNSA), and combined (ModelC-NSA) models by discrimination and calibration to identify the optimal model. Subgroup analysis was performed for the optimal model. RESULTS For the 16 2D factors, 13 factors were statistically different among the three 2D slices. Standardization of the volume factors was necessary. Among the three models, ModelC-NSA had a higher area under the curve [AUC] than ModelC and ModelNSA, both in the training dataset (0.809 vs. 0.649 vs. 0.797) and the validation dataset (0.770 vs. 0.718 vs. 0.719). For calibration, the performance of ModelC-NSA was similar to those of ModelC and ModelNSA. The performance of ModelC-NSA was not influenced by age (P = 0.753), sex (P = 0.781), treatments (P = 0.504), Barcelona Clinic Liver Cancer stage (P = 0.913), or Child-Pugh class (P = 0.580). CONCLUSIONS Compared to 2D evaluation, 3D assessment is more stable. 3D automatic assessment of skeletal muscle and adipose tissue can accurately predict progression in patients with HCC.
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Affiliation(s)
- Jinxiong Zhang
- Zhuhai Interventional Medical Center, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital), Zhuhai, China; Department of Interventional Radiology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China; Zhuhai Engineering Technology Research Center of Intelligent Medical Imaging, Zhuhai People's Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University), Zhuhai, China
| | - Shuoling Zhou
- School of Biomedical Engineering, Southern Medical University, Guangzhou, China
| | - Yurong Jiang
- Zhuhai Interventional Medical Center, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital), Zhuhai, China; Zhuhai Engineering Technology Research Center of Intelligent Medical Imaging, Zhuhai People's Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University), Zhuhai, China
| | - Wei Zhao
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Zhuhai, China; Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Guangzhou First People's Hospital, Guangzhou, China; Department of Management, School of Business, Macau University of Science and Technology, Macau, China
| | - Weiguo Xu
- Zhuhai Interventional Medical Center, Zhuhai Clinical Medical College of Jinan University (Zhuhai People's Hospital), Zhuhai, China
| | - Jiawei Zhang
- Zhuhai Engineering Technology Research Center of Intelligent Medical Imaging, Zhuhai People's Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University), Zhuhai, China; Department of Radiology, Zhuhai People's Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University), Zhuhai, China
| | - Taixue An
- Department of Clinical Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jianfeng Yan
- Department of Radiology, Zhuhai People's Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University), Zhuhai, China
| | - Chongyang Duan
- Department of Biostatistics, School of Public Health, Southern Medical University, Guangzhou, China
| | - Xiaojun Wang
- School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - Sihui Yang
- School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - Tao Wang
- School of Biomedical Engineering, Southern Medical University, Guangzhou, China
| | - Dandan Dong
- Department of Radiology, Zhuhai People's Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University), Zhuhai, China
| | - Yuan Chen
- Department of Interventional Treatment, Zhongshan City People's Hospital, Zhongshan, China
| | - Feixiang Zou
- Department of Radiology, People's Hospital of Wuchuan Gelao and Miao Autonomous County, Guizhou, China
| | - Xiangrong Yu
- Zhuhai Engineering Technology Research Center of Intelligent Medical Imaging, Zhuhai People's Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University), Zhuhai, China; Department of Radiology, Zhuhai People's Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University), Zhuhai, China.
| | - Meiyan Huang
- School of Biomedical Engineering, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Medical Image Processing, Southern Medical University, Guangzhou, China; Guangdong Province Engineering Laboratory for Medical Imaging and Diagnostic Technology, Southern Medical University, Guangzhou, China.
| | - Sirui Fu
- Zhuhai Engineering Technology Research Center of Intelligent Medical Imaging, Zhuhai People's Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University), Zhuhai, China; Department of Radiology, Zhuhai People's Hospital (The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University), Zhuhai, China; Guangdong Provincial Key Laboratory of Medical Image Processing, Southern Medical University, Guangzhou, China.
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Rodgers SK, Fetzer DT, Seow JH, McGillen K, Burrowes DP, Fung C, Udare AS, Wilson SR, Kamaya A. Optimizing US for HCC surveillance. Abdom Radiol (NY) 2025; 50:2453-2463. [PMID: 39585379 PMCID: PMC12069441 DOI: 10.1007/s00261-024-04631-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 10/02/2024] [Accepted: 10/04/2024] [Indexed: 11/26/2024]
Abstract
Ultrasound is the primary imaging modality used for surveillance of patients at risk for HCC. In 2017, the American College of Radiology Liver Imaging Reporting and Data Systems (ACR LI-RADS) introduced US LI-RADS to standardize the performance, interpretation, and reporting of US for HCC surveillance, with the algorithm recently updated as LI-RADS US Surveillance v2024. The American Association for the Study of Liver Diseases (AASLD) recommends reporting both the examination-level LI-RADS US Category as well as the US Visualization Score. The US Category conveys the overall findings of the exam and primarily determines follow up recommendations. The US Visualization Score conveys the expected sensitivity of the test and stratifies patients into appropriate surveillance pathways. One of the goals of routine surveillance is the detection of HCC at an early, potentially curable stage. Therefore, optimizing US technique is of critical importance. Increasing North American and worldwide utilization of LI-RADS US Surveillance, which includes technical recommendations, through education and outreach will undoubtedly benefit patients undergoing US HCC surveillance.
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Affiliation(s)
| | - David T Fetzer
- The University of Texas Southwestern Medical Center, Dallas, USA
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Badar W, Cooper EG, Florido CR, Rabaza M, Sheikh U, Guzman G, Gaba RC. Comparative Radiologic Response Assessment after Transarterial Chemoembolization, Percutaneous Ablation, and Multimodal Treatment: Radiologic-Pathologic Correlation in 81 Tumors. J Vasc Interv Radiol 2025; 36:961-970. [PMID: 39986373 DOI: 10.1016/j.jvir.2025.02.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 01/09/2025] [Accepted: 02/12/2025] [Indexed: 02/24/2025] Open
Abstract
PURPOSE To compare concordance of radiologic and pathologic response of hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE), percutaneous ablation, and multimodal treatment using radiologic-pathologic correlation. MATERIALS AND METHODS This single-center retrospective study analyzed 56 treatment-naive patients (male, 75%; Barcelona Clinic Liver Cancer Stage A, 63%) with 81 HCC tumors (mean diameter, 2.1 cm [SD ± 0.9]) who underwent locoregional therapy (LRT) (TACE, n = 44; ablation, n = 10; TACE + ablation, n = 27) prior to liver transplantation (LT) between 2010 and 2019. Immediate pre-LT cross-sectional imaging was used to assess modified Response Evaluation Criteria in Solid Tumours (mRECIST) response. Explant liver pathology was reviewed for percent pathologic necrosis (PN). Associations between imaging and pathologic observations were statistically characterized using the chi-square and Kruskal-Wallis tests. RESULTS Median time from imaging to LT was 37 days (range, 2-191 days). Across all LRT types, 68% (55/81), 19% (15/81), and 13% (11/83) of tumors displayed mRECIST complete response (CR), partial response (PR), and stable disease. The mean percent PN (%PN) in CR tumors (89% [SD ± 21]) was significantly higher than those in PR (68% [SD ± 34], P = .005) and stable disease (67% [SD ± 36], P = .009) tumors. Sixty percent (33/55) of CR tumors showed 100% complete PN (CPN), whereas only 20% (3/15) of PR tumors and 18% (2/11) of stable disease tumors showed CPN (P = .002). There was no association between %PN and CPN across different LRT modalities and radiologic response categories, indicating consistent performance between treatments. Sensitivity and specificity for radiologic CR to predict 100% PN were 87% and 49%, respectively. CONCLUSIONS Herein, radiologic-pathologic outcomes suggest that radiologic response criteria are associated with PN, with no differences across treatment modalities. However, the imperfect predictive capacity of imaging for PN supports surveillance of treated tumors before LT.
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Affiliation(s)
- Wali Badar
- Department of Radiology, University of Illinois at Chicago, Chicago, Illinois
| | - Eric G Cooper
- Department of Radiology, Northwestern University, Chicago, Illinois
| | - Christopher R Florido
- Department of Radiology, CHRISTUS Spohn Hospital Corpus Christi, Corpus Christi, Texas
| | - Michael Rabaza
- Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Ujalla Sheikh
- Department of Pathology, Ascension Resurrection, Chicago, Illinois
| | - Grace Guzman
- Department of Pathology, University of Illinois at Chicago, Chicago. Illinois
| | - Ron C Gaba
- Department of Radiology, University of Illinois at Chicago, Chicago, Illinois.
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Wang HY, Zhang GX, Fan WZ, Li JW, Hao SF, Ouyang YS, Li JP, Liu WD. Simultaneous versus sequential transcatheter arterial chemoembolization combined with microwave ablation for hepatocellular carcinoma: A retrospective propensity score-matched analysis. Hepatobiliary Pancreat Dis Int 2025; 24:286-293. [PMID: 40000294 DOI: 10.1016/j.hbpd.2025.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 02/05/2025] [Indexed: 02/27/2025]
Abstract
BACKGROUND Transcatheter arterial chemoembolization (TACE) combined with ablation has better clinical outcomes than monotherapy in patients with hepatocellular carcinoma (HCC). However, prolonged time intervals can lead to recanalization and neoangiogenesis, which may interfere with the synergistic effects of combination therapy. This study aimed to investigate whether TACE simultaneously combined with microwave ablation (MWA) is more effective than sequential therapy in patients with HCC. METHODS A total of 129 HCC patients who underwent TACE combined with MWA were included in this study. Based on the time interval between the first combination therapy of TACE and MWA, patients were divided into the simultaneous and sequential groups. Propensity score matching (PSM) was performed to reduce bias between the groups. Overall survival (OS), time-to-progression (TTP), tumor response, and liver function were compared. RESULTS Before PSM, the simultaneous group had a higher tumor load. Following PSM, 36 and 40 patients remained in the simultaneous and sequential groups, respectively. The median TTP and OS were 12.9 vs. 10.6 months (P = 0.262) and 44.0 vs. 26.5 months (P = 0.313) for the simultaneous and sequential groups, respectively. After 4-8 weeks, there were 16 complete responders and 17 partial responders in the simultaneous group and 15 and 22 patients in the sequential group, respectively (P = 0.504). The median complete response duration was 11.3 and 9.2 months for the simultaneous and sequential groups, respectively (P = 0.882). These results did not differ in BCLC stratified subgroups. Patients with small tumor sizes (≤ 5 cm), tumor nodules ≤ 3, well-defined boundaries, and early-stage tumors were more likely to achieve complete response (all P < 0.05). After 4-8 weeks, the liver function was significantly improved compared to that before or one day after treatment. CONCLUSIONS TACE simultaneously combined with MWA is safe and effective but not superior to sequential therapy.
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Affiliation(s)
- Hong-Yu Wang
- Department of Interventional Therapy, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Department of Interventional Oncology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Gui-Xiong Zhang
- Department of Interventional Oncology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Wen-Zhe Fan
- Department of Interventional Oncology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Jin-Wei Li
- Department of Interventional Therapy, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Shu-Fang Hao
- Department of Interventional Therapy, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Yu-Shu Ouyang
- Department of Interventional Therapy, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - Jia-Ping Li
- Department of Interventional Oncology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Wen-Dao Liu
- Department of Interventional Therapy, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.
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Ceriani R, Colapietro F, Gabbiadini R, Buono AD, Pugliese N, Masetti C, Brandaleone L, Ierace T, Solbiati L. Ultrasound-guided percutaneous biopsy for challenging perihilar focal liver lesions: diagnostic accuracy and safety assessment. J Ultrasound 2025; 28:537-540. [PMID: 39487923 PMCID: PMC12145379 DOI: 10.1007/s40477-024-00949-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 07/24/2024] [Indexed: 11/04/2024] Open
Abstract
PURPOSE In cases of perihilar focal liver lesions, distinguishing between benign strictures and malignancies is critical to prevent unnecessary surgery. Although the use of contrast-enhanced CT or MRI in combination with clinical and laboratory findings can aid in diagnosis, histologic examination is often necessary. Histologic specimens can be obtained through various techniques, including ERCP-guided brush cytology or intraductal biopsy, cholangioscopy-directed biopsy or endoscopic ultrasound (EUS). However, these methods have been associated with suboptimal sensitivity and specificity, sometimes leading to inconclusive results. Therefore, ultrasound-guided percutaneous biopsy (US-guided PB) may play a crucial role, but data is lacking for perihilar lesions. The objective of our study was to assess the technical feasibility and safety of US-guided PB for perihilar lesions. METHODS We included 20 consecutive patients who underwent US-guided PB of perihilar liver lesions that were not suitable for surgery between June 2018 and October 2023. RESULTS All samples were obtained using a Menghini needle 20G and were adequate for histological examination, with a mean diameter of 12.3 mm (range 3-40 mm). Out of the 20 patients, 11 were diagnosed with malignancy while the remaining 9 had inflammatory or fibrotic tissue samples. No adverse events related to the procedure were reported. CONCLUSION US-guided PB of perihilar liver lesions is a valuable and safe diagnostic approach to consider for patients who are not suitable for surgery.
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Affiliation(s)
- Roberto Ceriani
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy.
| | - Francesca Colapietro
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Roberto Gabbiadini
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Arianna Dal Buono
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Nicola Pugliese
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Chiara Masetti
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Luca Brandaleone
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Tiziana Ierace
- Department of Radiology, Humanitas Research Hospital IRCCS, Via Manzoni 56, 20089, Rozzano, Milano, Italy
| | - Luigi Solbiati
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Department of Radiology, Humanitas Research Hospital IRCCS, Via Manzoni 56, 20089, Rozzano, Milano, Italy
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Rhee H, Kim MJ, Kim DY, An C, Kang W, Han K, Roh YH, Han KH, Ahn SH, Choi JY, Park JY, Chung YE, Kim SU, Kim BK, Lee S, Lee HW, Lee JS. Noncontrast Magnetic Resonance Imaging vs Ultrasonography for Hepatocellular Carcinoma Surveillance: A Randomized, Single-Center Trial. Gastroenterology 2025; 168:1170-1177.e12. [PMID: 39855314 DOI: 10.1053/j.gastro.2024.12.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 12/19/2024] [Accepted: 12/26/2024] [Indexed: 01/27/2025]
Abstract
BACKGROUND & AIMS This study aimed to compare ultrasonography (US) and noncontrast magnetic resonance imaging (MRI) in the surveillance of hepatic malignancy. METHODS We conducted a randomized, nonblinded trial at a single center in South Korea. Eligible individuals were aged 20 to 70 years with liver cirrhosis, Child-Pugh class A, and no history of liver cancer or other recent malignancy. Participants were randomized 1:1 to receive up to 10 semiannual surveillance using US or noncontrast MRI with serum alpha-fetoprotein testing. The primary endpoints were the detection rates of Barcelona Clinic Liver Cancer (BCLC) stage 0 or A tumors, stage distribution at initial diagnosis, and false-positive referral rates. RESULTS From June 2015 to November 2017, 416 patients were screened, and 414 were enrolled and assigned to the US (n = 207) or MRI (n = 207) group. In total, 23 participants in the US group and 25 in the MRI group were diagnosed with liver cancer by November 2022. The detection rates of BCLC stage 0 or A tumors were not different between the US and MRI groups (7% [95% confidence interval (CI), 4%-11%] vs 12% [8%-17%]). BCLC stage 0 tumors were more frequently detected in the MRI group than in the US group (8% vs 2%). The MRI group had earlier BCLC stage (P = .014) and lower false-positive referral rate (0.7% [95% CI, 0.4%-1.2%] vs 3.1% [2.3%-4.1%], P < .001) compared with the US group. CONCLUSIONS Noncontrast MRI is a better alternative to US for the surveillance of cirrhotic patients offering earlier stage at initial diagnosis and lower false-positive referral rate. (ClincalTrials.gov, Number: NCT02514434.).
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Affiliation(s)
- Hyungjin Rhee
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Myeong-Jin Kim
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
| | - Do Young Kim
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
| | - Chansik An
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Wonseok Kang
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Kyunghwa Han
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Yun Ho Roh
- Biostatistics Collaboration Unit, Medical Research Center, Yonsei University College of Medicine, Seoul, South Korea
| | - Kwang-Hyub Han
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Jin-Young Choi
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Jun Yong Park
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Yong Eun Chung
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Seung Up Kim
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Sunyoung Lee
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Hye Won Lee
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Jae Seung Lee
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
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Yan F, Wang W, Yang Z, Huang Y, Rao Y, Qu G, Peng H, Shi M, Zeng W, Chen D, Xing W. Intra-arterial lidocaine improves long-term survival in patients with hepatocellular carcinoma undergoing transcatheter arterial chemoembolisation: a retrospective propensity score-matched study. Br J Anaesth 2025; 134:1628-1637. [PMID: 40118673 PMCID: PMC12106866 DOI: 10.1016/j.bja.2025.01.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 12/14/2024] [Accepted: 01/07/2025] [Indexed: 03/23/2025] Open
Abstract
BACKGROUND Lidocaine, the most widely used local anaesthetic, has anticancer effects in both laboratory findings and retrospective clinical studies. We explored the potential benefits of intra-arterial lidocaine on long-term survival in patients with hepatocellular carcinoma (HCC) undergoing transcatheter arterial chemoembolisation (TACE). METHODS This retrospective cohort study included patients with HCC who received TACE as initial treatment from August 2011 to October 2016. Eligible patients were categorised into no lidocaine and lidocaine groups. Propensity score matching was undertaken. Progression-free survival (PFS) and overall survival were compared between the two groups. Subgroup analysis was performed to explore the survival benefit of combining intra-arterial lidocaine with platinum-based chemotherapy during TACE. RESULTS Of 374 eligible patients, 96 were in the lidocaine group and 278 were in the no lidocaine group. Survival analysis showed that intra-arterial lidocaine was associated with longer PFS (P=0.004) and overall survival (P<0.001). After propensity score matching, PFS (P<0.001) and overall survival (P=0.001) benefits of lidocaine remained. Multivariate analysis showed that intra-arterial lidocaine was an independent prognostic factor for PFS (P=0.011) and overall survival (P=0.044). The impact of intra-arterial lidocaine was similar in patients receiving the TACE regimen with platinum (PFS: P=0.014; overall survival: P=0.023). CONCLUSIONS Intra-arterial lidocaine might improve long-term survival in patients with HCC undergoing TACE and in the subgroup of patients receiving platinum. The study highlights the potential antitumour benefits of combining lidocaine and chemotherapeutics in patients with cancer.
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Affiliation(s)
- Fang Yan
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Wanyu Wang
- Department of Anesthesiology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, PR China
| | - Zhiwen Yang
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Yang Huang
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Yan Rao
- Department of Anesthesiology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province, PR China
| | - Ge Qu
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Hui Peng
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Ming Shi
- Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Weian Zeng
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Dongtai Chen
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
| | - Wei Xing
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
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Dupuis M, Dupont A, Pizza S, Vilgrain V, Bando Delaunay A, Lebtahi R, Bouattour M, Ronot M, Grégory J. Prognostic value of early response in predicting survival in hepatocellular carcinoma patients treated with selective internal radiation therapy. Eur Radiol 2025; 35:3181-3191. [PMID: 39702632 DOI: 10.1007/s00330-024-11253-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 11/04/2024] [Accepted: 11/19/2024] [Indexed: 12/21/2024]
Abstract
OBJECTIVES This study evaluates the prognostic value of tumor response on CT at 3 months, assessed by Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), and Liver Imaging Reporting and Data System Treatment Response Algorithm (LR-TRA) in patients with hepatocellular carcinoma (HCC) treated with selective internal radiation therapy (SIRT). MATERIALS AND METHODS A retrospective analysis was conducted on 102 HCC patients treated with SIRT between 2018 and 2020. RECIST, mRECIST, and LR-TRA were assessed at 3 months post-SIRT. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier analysis and Cox proportional-hazards models. RESULTS The median age was 71 years, and most patients (90%) had advanced-stage tumors (Barcelona Clinic Liver Cancer-C). After a median follow-up of 32.0 months (95% CI: 16.8-60.9), 60/102 patients died (59%), and 90/102 patients showed tumor progression (88%). Median OS was 20.4 months (95% CI: 15.4-33.0), and median PFS was 14.5 months (95% CI: 6.5-24.5); 1-year OS and PFS rates were 65.6% and 50.7%. Multivariable analysis revealed that early response according to RECIST 1.1 (HR 1.66, p = 0.30), mRECIST (HR 1.40, p = 0.215), and LR-TRA (HR 0.67, p = 0.30) were not predictors of OS. Disease progression evaluated by RECIST (HR 2.55, p < 0.001) and mRECIST (HR 2.53, p < 0.001), bilirubin levels (HR 1.03, p < 0.001), and prothrombin time (HR 0.98, p = 0.005) were predictors of OS. For PFS, neither RECIST nor mRECIST response, disease progression, nor LR-TRA viability were predictors. CONCLUSION In this advanced-stage HCC population, early response assessed by RECIST, mRECIST, and LR-TRA criteria did not predict OS or PFS after SIRT. However, early disease progression and liver function indicators were prognostic factors for OS. KEY POINTS QuestionHow well does early tumor response, assessed at 3 months post-selective internal radiation therapy (SIRT), predict survival in advanced hepatocellular carcinoma (HCC) patients? Findings Early response, assessed by RECIST, mRECIST, and LR-TRA, did not predict overall or progression-free survival; disease progression and liver function indicators were significant predictors. Clinical relevance This study highlights the limitations of early imaging criteria in predicting survival outcomes in advanced HCC post-SIRT, suggesting the need for alternative or complementary prognostic indicators to guide treatment decisions.
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Affiliation(s)
- Michel Dupuis
- Department of Radiology, Beaujon Hospital, AP-HP.Nord, Clichy, France
| | - Axelle Dupont
- Clinical Research, Biostatistics and Epidemiology Department, AP-HP Nord-Université Paris Cité, HUPNVS, Paris, France
| | - Silvia Pizza
- Department of Radiology, Beaujon Hospital, AP-HP.Nord, Clichy, France
| | - Valérie Vilgrain
- Department of Radiology, Beaujon Hospital, AP-HP.Nord, Clichy, France
- Université Paris Cité, FHU MOSAIC, INSERM U1149 "Centre de Recherche sur l'Inflammation", CRI, Paris, France
| | - Aurélie Bando Delaunay
- Department of Nuclear Medicine, Beaujon Hospital, AP-HP.Nord, Clichy, France
- Université Paris Cité, INSERM U1149 "Centre de Recherche sur l'Inflammation", CRI, Paris, France
| | - Rachida Lebtahi
- Department of Nuclear Medicine, Beaujon Hospital, AP-HP.Nord, Clichy, France
- Université Paris Cité, INSERM U1149 "Centre de Recherche sur l'Inflammation", CRI, Paris, France
| | | | - Maxime Ronot
- Department of Radiology, Beaujon Hospital, AP-HP.Nord, Clichy, France
- Université Paris Cité, FHU MOSAIC, INSERM U1149 "Centre de Recherche sur l'Inflammation", CRI, Paris, France
| | - Jules Grégory
- Department of Radiology, Beaujon Hospital, AP-HP.Nord, Clichy, France.
- Université Paris Cité, FHU MOSAIC, INSERM U1149 "Centre de Recherche sur l'Inflammation", CRI, Paris, France.
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Kan XF, Liang B, Zhang XL, Yu L, Luo YC, Zhou S, Liu RB, Xu GH, Li HL, Liao ZY, Xiang H, Lu W, Xu LF, Ma YL, Xia XW, Qian K, Dong XJ, Xiong F, Song SL, Zhao C, Huang M, Zheng CS. Transarterial chemoembolization plus apatinib for unresectable hepatocellular carcinoma: a multicenter, randomized, open-label, phase III trial. BMC Med 2025; 23:313. [PMID: 40437469 PMCID: PMC12121135 DOI: 10.1186/s12916-025-04159-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Accepted: 05/21/2025] [Indexed: 06/01/2025] Open
Abstract
BACKGROUND This study aimed to assess the efficacy and safety of transarterial chemoembolization (TACE) in combination with apatinib (TACE-apatinib) for patients with unresectable hepatocellular carcinoma (HCC). METHODS This study was a multicenter, randomized, open-label, prospective, phase III trial. Patients with unresectable HCC were randomly assigned in a 1:1 ratio to receive either TACE-apatinib or TACE-alone treatment. Patients in the TACE-apatinib group began with a dosage of 500 mg/day of oral apatinib administered 4 days after the first TACE. The primary endpoint of this study was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), time to untreatable (unTACEable) progression (TTUP), and safety assessment. RESULTS From November 1, 2018 to November 18, 2021, a total of 196 patients were randomly assigned to either the TACE-apatinib (n = 86) or TACE-alone (n = 92) group. The median PFS in the TACE-apatinib group was significantly longer than that of in the TACE-alone group (6.1 months vs. 3.4 months, p < 0.0001). The median OS was significantly prolonged in the TACE-apatinib group compared to the TACE-alone group (28.9 months vs. 24.0 months, p = 0.0005). The median TTUP in the TACE-apatinib group was 26.8 months, which was significantly longer than that of 20.1 months in the TACE-alone group (p = 0.0003). A significantly higher ORR and DCR were observed in the TACE-apatinib group compared to the TACE-alone group (ORR: 58.1% vs. 31.5%, p < 0.001; DCR: 87.2% vs. 69.6%, p = 0.004). Most of the treatment-related adverse events were grades 1-2, and no treatment-related deaths were observed. CONCLUSIONS Apatinib significantly improved the treatment effects of TACE for patients with unresectable HCC. TACE-apatinib could serve as a promising treatment option for this patient population, offering notable survival benefits while maintaining an acceptable safety profile. TRIAL REGISTRATION Chinese Clinical Trial Register, No. ChiCTR1800018621.
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Affiliation(s)
- Xue-Feng Kan
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Bin Liang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xiao-Lin Zhang
- Department of Interventional Radiology, The First College of Clinical Medical Science, Yichang Central People's Hospital, China Three Gorges University, Yichang, Hubei, China
| | - Lei Yu
- Department of Interventional Radiology, Guangxi Zhuang Autonomous Region People's Hospital, Nanning, China
| | - Yao-Chang Luo
- Department of Catheter Intervention, First Affiliated Hospital of Guangxi, University of Traditional Chinese Medicine, Nanning, China
| | - Shi Zhou
- Department of Interventional Radiology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, China
- Department of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Rui-Bao Liu
- Department of Interventional Radiology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Guo-Hui Xu
- Department of Interventional Radiology, School of Medicine, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China
| | - Hai-Liang Li
- Department of Radiology and Intervention, The Affiliated Tumor Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
| | - Zheng-Yin Liao
- Department of Abdominal Oncology, West China Medical School, West China Hospital, Sichuan University, Chengdu, China
| | - Hua Xiang
- Department of Interventional Radiology and Vascular Surgery, Hunan Provincial People's Hospital, Changsha, China
| | - Wei Lu
- Department of Interventional Medicine, The Sixth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Lin-Feng Xu
- Department of Interventional Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yi-Long Ma
- Department of Interventional Radiology, Guangxi Medical University Cancer Hospital, Guangxi Medical University, Nanning, China
| | - Xiang-Wen Xia
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Kun Qian
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xiang-Jun Dong
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Fu Xiong
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Song-Lin Song
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Chang Zhao
- Department of Interventional Radiology, Guangxi Medical University Cancer Hospital, Guangxi Medical University, Nanning, China.
| | - Ming Huang
- Department of Minimally Invasive International Therapy, The Third Affiliated Hospital of Kunming University, Tumor Hospital of Yunnan Province, Kunming, Yunnan Province, 650000, China.
| | - Chuan-Sheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Sacco R, Giannini EG, Tortora R, Di Costanzo GG, Mega A, Marzi L, Pieri G, Pasta A, Daniele B, Federico P, Cabibbo G, Russello M, Cocuzza C, Giacomelli L, Silletta M, Gallo P, Gentilucci UV, Casadei-Gardini A, Claar E, Pellicelli A, Bellini M, Morisco F, Tatali C, Pace Palitti V, Izzi A, Di Stefano M, Rinaldi L, Facciorusso A. Lenvatinib Is Highly Effective in Patients with Hepatocellular Carcinoma Related to Both Metabolic Dysfunction-Associated Steatohepatitis and Alcoholic Etiology: A Propensity Score Analysis. Cancers (Basel) 2025; 17:1808. [PMID: 40507289 PMCID: PMC12153599 DOI: 10.3390/cancers17111808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2025] [Revised: 04/30/2025] [Accepted: 05/19/2025] [Indexed: 06/16/2025] Open
Abstract
Background and aims: Metabolic dysfunction-associated steatotic liver disease (MASLD)-related hepatocellular carcinoma (HCC) may have distinct biological characteristics influencing systemic treatment response. However, the prognostic impact of MASLD vs. alcohol-related HCC in patients receiving lenvatinib remains unclear. This study aimed to assess lenvatinib's effectiveness and safety in these populations. Methods: A multicenter cohort of 378 HCC patients treated with lenvatinib (2019-2024) was analyzed. Propensity score matching was performed based on age, sex, tumoral stage, alpha-fetoprotein levels and Child-Pugh class. Survival was estimated using Kaplan-Meier analysis and compared with the log-rank test. Results were expressed as HR and 95% CI. Results: After matching, 115 patients per group were compared. Median OS was 21 months (95% CI: 20-23) in the group with metabolic dysfunction-associated steatohepatitis (MASH) and 19 months (95% CI: 18-21) in the group with alcohol etiology (p = 0.18). In multivariate analysis, only Child-Pugh class (HR 2.67, 95% CI: 1.84-5.41) and tumor stage (HR 2.18, 95% CI: 1.57-6.93) resulted as significant predictors of OS. Median PFS was 9 months (95% CI: 8-9) in patients with MASH and 9 months (95% CI: 7-10) in patients with alcohol etiology (p = 0.33). Only the Child-Pugh class was a significant predictor of PFS in univariate analysis (HR 1.56, 95% CI: 1.15-3.41; p = 0.03). No difference in terms of adverse event rate was observed between the two groups. Conclusions: Lenvatinib is effective in patients with both MASH- and alcohol-related HCC, with no difference in oncological outcomes between the two groups.
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Affiliation(s)
- Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Department of Surgical and Medical Sciences, University of Foggia, Viale Pinto 1, 71122 Foggia, Italy;
| | - Edoardo G. Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genova, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Policlinico San Martino, 16126 Genova, Italy; (E.G.G.); (G.P.); (A.P.)
| | - Raffaella Tortora
- Liver Unit, Department of Transplantation, Cardarelli Hospital, 80131 Naples, Italy; (R.T.); (G.G.D.C.)
| | | | - Andrea Mega
- Gastroenterology Unit, Bolzano Regional Hospital, 39100 Bolzano, Italy; (A.M.); (L.M.)
| | - Luca Marzi
- Gastroenterology Unit, Bolzano Regional Hospital, 39100 Bolzano, Italy; (A.M.); (L.M.)
| | - Giulia Pieri
- Gastroenterology Unit, Department of Internal Medicine, University of Genova, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Policlinico San Martino, 16126 Genova, Italy; (E.G.G.); (G.P.); (A.P.)
| | - Andrea Pasta
- Gastroenterology Unit, Department of Internal Medicine, University of Genova, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Policlinico San Martino, 16126 Genova, Italy; (E.G.G.); (G.P.); (A.P.)
| | - Bruno Daniele
- Medical Oncology Unit, Ospedale del Mare, 80147 Naples, Italy; (B.D.); (P.F.)
| | - Piera Federico
- Medical Oncology Unit, Ospedale del Mare, 80147 Naples, Italy; (B.D.); (P.F.)
| | - Giuseppe Cabibbo
- Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy;
| | - Maurizio Russello
- Liver Unit, ARNAS Garibaldi-Nesima, 95122 Catania, Italy; (M.R.); (C.C.)
| | - Caterina Cocuzza
- Liver Unit, ARNAS Garibaldi-Nesima, 95122 Catania, Italy; (M.R.); (C.C.)
| | | | - Marianna Silletta
- Division of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy;
| | - Paolo Gallo
- Clinical Medicine and Hepatology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy; (P.G.); (U.V.G.)
| | - Umberto Vespasiani Gentilucci
- Clinical Medicine and Hepatology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy; (P.G.); (U.V.G.)
| | - Andrea Casadei-Gardini
- Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, 20132 Milan, Italy;
| | - Ernesto Claar
- Department of Medicine, Ospedale Evangelico Villa Betania, 80147 Naples, Italy;
| | - Adriano Pellicelli
- Liver Unit, Department of Liver Transplant, A.O. San Camillo Forlanini, 00152 Rome, Italy;
| | - Massimo Bellini
- Gastroenterology Unit, University of Pisa, 56124 Pisa, Italy;
| | - Filomena Morisco
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy;
| | - Concetta Tatali
- Gastroenterology and Digestive Endoscopy Unit, Department of Surgical and Medical Sciences, University of Foggia, Viale Pinto 1, 71122 Foggia, Italy;
| | | | - Antonio Izzi
- Emergency and Highly Contagious Infectious Diseases, A.O. dei Colli, P.O.D. Cotugno, 80131 Naples, Italy;
| | | | - Luca Rinaldi
- Department of Medicine and Health Sciences, University of Molise, 86100 Campobasso, Italy;
| | - Antonio Facciorusso
- Gastroenterology Unit, Department of Experimental Medicine, Università del Salento, 73100 Lecce, Italy;
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Duong H, Ngo M, Dao T, Hoang T, Nguyen U, Ho T. Sensitive Detection of Plasma Fibrinogen Chain A mRNA in Hepatocellular Carcinoma Using Semi-Nested RT-PCR. Diagnostics (Basel) 2025; 15:1364. [PMID: 40506936 PMCID: PMC12155491 DOI: 10.3390/diagnostics15111364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2025] [Revised: 05/20/2025] [Accepted: 05/27/2025] [Indexed: 06/16/2025] Open
Abstract
Background/Objectives: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality, with diagnostic limitations of existing biomarkers such as alpha-fetoprotein (AFP). This study evaluates plasma Fibrinogen chain A mRNA (FGA mRNA), alone and combined with AFP, for improving HCC diagnosis. Methods: A semi-nested RT-PCR assay was developed to quantify plasma FGA mRNA in 80 HCC patients and 74 controls (57 chronic liver disease [CLD] and 17 healthy donors [HDs]). Receiver operating characteristic (ROC) analysis was used to assess diagnostic performance, and logistic regression evaluated the combined biomarker model. Results: Plasma FGA mRNA levels were significantly higher in HCC patients than in CLD and HD controls (p < 0.0001). The area under the curve (AUC) for HCC vs. the combined control group (CLD + HD) was 0.721 (95% CI: 0.643-0.790), improving to 0.866 (95% CI: 0.782-0.927) when comparing HCC to HDs alone but declining for HCC vs. CLD (AUC = 0.678, 95% CI: 0.592-0.755). Combining FGA mRNA with AFP significantly enhanced diagnostic accuracy for HCC vs. CLD (AUC = 0.859, 95% CI: 0.790-0.913), with a sensitivity of 87.50% and specificity of 71.93%. In patients with low AFP levels (<20 ng/mL), the combined model identified 68.75% of HCC cases, outperforming AFP alone. Conclusions: FGA mRNA alone provides moderate diagnostic utility but substantially improves accuracy when combined with AFP, especially in low-AFP cases. This multi-biomarker approach holds promise for improving HCC detection and warrants further validation in larger cohorts.
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Affiliation(s)
- Huy Duong
- Department of Gastroenterology and Hepatology, 103 Military Hospital, Vietnam Military Medical University, Hanoi 100000, Vietnam; (H.D.)
| | - Minh Ngo
- Department of Gastroenterology and Hepatology, 103 Military Hospital, Vietnam Military Medical University, Hanoi 100000, Vietnam; (H.D.)
- Radiology Center, 103 Military Hospital, Vietnam Military Medical University, Hanoi 100000, Vietnam
| | - Trang Dao
- Department of Genomics and Cytogenetics, Institute of Biomedicine and Pharmacy (IBP), Vietnam Military Medical University, No. 222, Phung Hung, Ha Dong, Hanoi 100000, Vietnam
| | - Trang Hoang
- Department of Genomics and Cytogenetics, Institute of Biomedicine and Pharmacy (IBP), Vietnam Military Medical University, No. 222, Phung Hung, Ha Dong, Hanoi 100000, Vietnam
| | - Ung Nguyen
- Department of Translational Clinical Research, Institute of Biomedicine and Pharmacy (IBP), Vietnam Military Medical University, Hanoi 100000, Vietnam
| | - Tho Ho
- Department of Genomics and Cytogenetics, Institute of Biomedicine and Pharmacy (IBP), Vietnam Military Medical University, No. 222, Phung Hung, Ha Dong, Hanoi 100000, Vietnam
- Department of Microbiology, 103 Military Hospital, Vietnam Military Medical University, Hanoi 100000, Vietnam
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48
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Kawai-Kitahata F, Asahina Y, Kakinuma S, Inada K, Mochida T, Watakabe K, Nobusawa T, Shimizu T, Tsuchiya J, Miyoshi M, Kaneko S, Murakawa M, Nitta S, Nakagawa M, Kinowaki Y, Ban D, Tanaka S, Anzai T, Takano S, Maekawa S, Enomoto N, Okamoto R. Genetic alterations in hepatocellular carcinoma after sustained virological response in relation to the molecular characterization of metabolic diseases. Hepatol Res 2025. [PMID: 40423574 DOI: 10.1111/hepr.14214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2025] [Revised: 05/09/2025] [Accepted: 05/19/2025] [Indexed: 05/28/2025]
Abstract
AIM The mechanism of hepatocarcinogenesis after sustained virological response (SVR) in hepatitis C virus (HCV) patients is unclear. We compared gene profiles of hepatocellular carcinoma (HCC) between HCV-SVR, steatotic liver disease (SLD), and HCV-non-SVR patients. METHODS This study analyzed 126 resected HCCs from patients with HCV and SLD, classifying them as HCV-SVR (n = 22), HCV-non-SVR (n = 56), and SLD (n = 48). Deep sequencing of 2910 hotspots in 55 cancer-related genes was conducted to examine mutations and copy number variations in both cancerous and background liver tissues. RESULTS The HCV-SVR group comprised more patients who consumed alcohol (45.5% vs. 15.7%, p = 0.008), were obese (54.5% vs. 17.9%, p = 0.002), and had dyslipidemia (18.2% vs. 3.6%, p = 0.029) and hyperuricemia (18.2% vs. 3.6%, p = 0.029) than the HCV-non-SVR group. Mutational profiling of the HCV-SVR HCC showed significantly lower alteration rates of AXIN1 (13.6% vs. 42.9%, p = 0.016), ARID2 (9.1% vs. 39.3%, p = 0.013), and TP53 (9.1% vs. 32.1%, p = 0.030) than HCV-non-SVR patients. Compared with HCV-non-SVR-HCC, SLD-HCCs showed significantly lower rates of TERT promoter mutations (62.5% vs. 85.7%, p = 0.004), ARID2 alterations (12.5% vs. 39.3%, p = 0.003), and AXIN1 alterations (12.5% vs. 42.9%, p = 0.002). HCV-SVR/MASH/MASLD/ALD-HCC had significantly lower alteration rates of the Wnt/β-catenin (41.4% vs. 60.7%, p = 0.048) and chromatin remodeling pathways (27.1% vs. 48.2%, p = 0.026) than HCV-non-SVR-HCC. CONCLUSIONS HCV-SVR HCC is linked to alcohol use and metabolic diseases, showing a mutational profile similar to SLD-HCC.
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Affiliation(s)
- Fukiko Kawai-Kitahata
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
| | - Yasuhiro Asahina
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
| | - Sei Kakinuma
- Department of Clinical and Diagnostic Laboratory Science, Institute of Science Tokyo, Tokyo, Japan
| | - Kento Inada
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
| | - Tomohiro Mochida
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
| | - Keiya Watakabe
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
| | - Tsubasa Nobusawa
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
| | - Taro Shimizu
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
| | - Jun Tsuchiya
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
| | - Masato Miyoshi
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
| | - Shun Kaneko
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
| | - Miyako Murakawa
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
| | - Sayuri Nitta
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
| | - Mina Nakagawa
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
| | - Yuko Kinowaki
- Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Advanced Therapeutic Sciences, Institute of Science Tokyo, Tokyo, Japan
| | - Daisuke Ban
- Department of Hepato-Biliary-Pancreatic Surgery, Institute of Science Tokyo, Tokyo, Japan
| | - Shinji Tanaka
- Department of Molecular Oncology, Institute of Science Tokyo, Tokyo, Japan
| | - Tatsuhiko Anzai
- Department of Biostatistics, M&D Data Science Center, Institute of Integrated Research, Institute of Science Tokyo, Tokyo, Japan
| | - Shinichi Takano
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
| | - Shinya Maekawa
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
| | - Nobuyuki Enomoto
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
| | - Ryuichi Okamoto
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
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49
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Cicerone O, Mantovani S, Oliviero B, Basilico G, Corallo S, Quaretti P, Maestri M. Navigating the evidence for hepatocellular carcinoma treatment: Surgery vs radiofrequency ablation through sentiment and meta-analysis. World J Clin Oncol 2025; 16:105881. [DOI: 10.5306/wjco.v16.i5.105881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2025] [Revised: 03/13/2025] [Accepted: 04/08/2025] [Indexed: 05/19/2025] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is among the most aggressive primary liver cancers, leading to significant global mortality. While early diagnosis improves prognosis, treatment decisions, particularly between surgical resection and radiofrequency ablation (RFA), remain controversial.
AIM To clarify this issue using sentiment analysis of medical literature alongside a meta-analysis of overall survival (OS).
METHODS We included studies comparing liver resection and RFA, excluding case reports, editorials, and studies without relevant outcomes. A systematic search in PubMed and Web of Science identified 197 studies. Abstracts underwent sentiment analysis using Python’s Natural Language Toolkit library, categorizing them as favoring resection, ablation, or neutral. We also performed a meta-analysis using a random-effects model on 11 studies reporting hazard ratios (HRs) for OS.
RESULTS Sentiment analysis revealed that 75.1% of abstracts were neutral, 14.2% favored resection, and 10.7% favored RFA. The meta-analysis showed a significant survival advantage for liver resection, with a pooled HR of 0.5924 (95% confidence interval: 0.540-0.649). Heterogeneity was moderate (I² = 39.98%). Despite the meta-analysis demonstrating clear survival benefits of liver resection, most abstracts maintained a neutral stance. This discrepancy highlights potential biases or hesitancy in drawing definitive conclusions.
CONCLUSION The study emphasizes the need for clinicians to prioritize robust statistical evidence over narrative impressions. Liver resection remains the preferred treatment for HCC in eligible patients.
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Affiliation(s)
- Ottavia Cicerone
- Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia 27100, Italy
| | - Stefania Mantovani
- Department of Infectious Diseases-Clinical Immunology, Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy
| | - Barbara Oliviero
- Department of Infectious Diseases-Clinical Immunology, Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy
| | - Giorgia Basilico
- Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia 27100, Italy
| | - Salvatore Corallo
- Department of Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy
| | - Pietro Quaretti
- Department of Diagnostic Imaging-Interventional Radiology, Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy
| | - Marcello Maestri
- Department of General Surgery I-Liver Service, Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy
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50
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Oura K, Morishita A, Manabe T, Takuma K, Nakahara M, Tadokoro T, Fujita K, Mimura S, Tani J, Ono M, Sanomura T, Nishiyama Y, Himoto T, Kobara H. Efficacy of olanzapine as an antiemetic drug for transcatheter arterial chemoembolization for hepatocellular carcinoma. Sci Rep 2025; 15:18095. [PMID: 40413249 PMCID: PMC12103546 DOI: 10.1038/s41598-025-01632-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 05/07/2025] [Indexed: 05/27/2025] Open
Abstract
Although the addition of olanzapine to conventional antiemetic therapy has been reported to be useful for systemic chemotherapy with highly emetogenic agents such as cisplatin, no studies have evaluated its efficacy in transcatheter arterial chemoembolization (TACE) for patients with hepatocellular carcinoma (HCC). We evaluated the antiemetic efficacy of olanzapine in patients with HCC undergoing cisplatin-based TACE. This prospective study included 68 patients with HCC scheduled for cisplatin-based TACE between 2021 and 2022. Patients were divided into two groups: an olanzapine group receiving olanzapine 5 mg plus the conventional triple antiemetic combination and a control group receiving only the conventional triple combination therapy. The incidence of digestive symptoms and adverse events (AEs) in both groups were compared. For TACE-induced nausea and vomiting, the olanzapine group had similar antiemetic complete response (aCR) and complete control (CC) rates at 12 h post-TACE as the control group but significantly higher aCR and CC rates during the delayed-phase after 24 h and better patient satisfaction scores. No significant differences were noted in the occurrence of severe AEs in the two groups. The use of olanzapine, in addition to conventional antiemetics, may be a new standard for patients undergoing cisplatin-based TACE.
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Affiliation(s)
- Kyoko Oura
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Asahiro Morishita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan.
| | - Takushi Manabe
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
- Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Kagawa, Japan
| | - Kei Takuma
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Mai Nakahara
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Tomoko Tadokoro
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Koji Fujita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Shima Mimura
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Joji Tani
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Masafumi Ono
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
| | - Takayuki Sanomura
- Department of Radiology, Faculty of Medicine, Kagawa University, Kita, Kagawa, Japan
| | - Yoshihiro Nishiyama
- Department of Radiology, Faculty of Medicine, Kagawa University, Kita, Kagawa, Japan
| | - Takashi Himoto
- Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Takamatsu, Japan
| | - Hideki Kobara
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan
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