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1
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Yeo YH, Lee YT, Tseng HR, Zhu Y, You S, Agopian VG, Yang JD. Alpha-fetoprotein: Past, present, and future. Hepatol Commun 2024; 8:e0422. [PMID: 38619448 PMCID: PMC11019827 DOI: 10.1097/hc9.0000000000000422] [Citation(s) in RCA: 24] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Accepted: 01/29/2024] [Indexed: 04/16/2024] Open
Abstract
Alpha-fetoprotein (AFP) is a glycoprotein that plays an important role in immune regulation with critical involvement in early human development and maintaining the immune balance during pregnancy. Postfetal development, the regulatory mechanisms controlling AFP undergo a shift and AFP gene transcription is suppressed. Instead, these enhancers refocus their activity to maintain albumin gene transcription throughout adulthood. During the postnatal period, AFP expression can increase in the setting of hepatocyte injury, regeneration, and malignant transformation. It is the first oncoprotein discovered and is routinely used as part of a screening strategy for HCC. AFP has been shown to be a powerful prognostic biomarker, and multiple HCC prognosis models confirmed the independent prognostic utility of AFP. AFP is also a useful predictive biomarker for monitoring the treatment response of HCC. In addition to its role as a biomarker, AFP plays important roles in immune modulation to promote tumorigenesis and thus has been investigated as a therapeutic target in HCC. In this review article, we aim to provide an overview of AFP, encompassing the discovery, biological role, and utility as an HCC biomarker in combination with other biomarkers and how it impacts clinical practice and future direction.
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Affiliation(s)
- Yee Hui Yeo
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Yi-Te Lee
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Hsian-Rong Tseng
- Department of Molecular and Medical Pharmacology, California NanoSystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles, California, USA
- Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California, USA
| | - Yazhen Zhu
- Department of Molecular and Medical Pharmacology, California NanoSystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles, California, USA
- Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California, USA
- Department of Pathology and Laboratory Medicine, Ronald Reagan Medical Center, David Geffen School of Medicine, University of California, Los Angeles, California, USA
| | - Sungyong You
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Department of Surgery, Division of Cancer Biology and Therapeutics, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Vatche G. Agopian
- Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, California, USA
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA
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2
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Zhong BY, Jiang JQ, Sun JH, Huang JT, Wang WD, Wang Q, Ding WB, Zhu XL, Ni CF. Prognostic Performance of the China Liver Cancer Staging System in Hepatocellular Carcinoma Following Transarterial Chemoembolization. J Clin Transl Hepatol 2023; 11:1321-1328. [PMID: 37719966 PMCID: PMC10500297 DOI: 10.14218/jcth.2023.00099] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 05/22/2023] [Accepted: 06/02/2023] [Indexed: 09/19/2023] Open
Abstract
Background and Aims To validate prognostic performance of the China liver cancer (CNLC) staging system as well as to compare these parameters with those of the Barcelona Clinic Liver Cancer (BCLC) staging system for Chinese hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). Methods This multicenter retrospective study included 1,124 patients with HCC between January 2012 and December 2020 from six Chinese hospitals. Based on overall survival (OS), the prognostic performance outcomes for the CNLC and BCLC staging systems were compared by model discrimination [C statistic and Akaike information criterion (AIC)], monotonicity of the gradient (linear trend chi-square test), homogeneity (likelihood ratio chi-square test), and calibration (calibration plots). A prospective cohort of 44 patients receiving TACE-based therapy included between January 2021 and December 2022 was used to prospectively validate the outcomes. Results Median OS was 19.1 (18.2-20.0) months, with significant differences in OS between stages defined by the CNLC and BCLC observed (p<0.001). The CNLC performed better than the BCLC regarding model discrimination (C-index: 0.661 vs. 0.644; AIC: 10,583.28 vs. 10,583.72), model monotonicity of the gradient (linear trend chi-square test: 66.107 vs. 57.418; p<0.001), model homogeneity (159.2 vs. 158.7; p<0.001). Both staging systems had good model calibration. Similar results were observed in the prospective cohort. Conclusions Combining model discrimination, gradient monotonicity, homogeneity, and calibration, the CNLC performed better than the BCLC for Chinese HCC patients receiving TACE.
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Affiliation(s)
- Bin-Yan Zhong
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Jian-Qiang Jiang
- Department of Interventional Therapy, Nantong Tumor Hospital, Nantong, Jiangsu, China
| | - Jun-Hui Sun
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jin-Tao Huang
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Wei-Dong Wang
- Department of Interventional Radiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, Jiangsu, China
| | - Qi Wang
- Department of Interventional Radiology, Third Affiliated Hospital of Soochow University, Changzhou First Hospital, Changzhou, Jiangsu, China
| | - Wen-Bin Ding
- Department of Interventional Radiology, Nantong First People’s Hospital, Nantong, Jiangsu, China
| | - Xiao-Li Zhu
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Cai-Fang Ni
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
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3
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Saeki I, Suehiro Y, Yamauchi Y, Hoshida T, Tanabe N, Oono T, Kawamoto D, Nishimura T, Matsumoto T, Ishikawa T, Shimokawa M, Tamori A, Kawada N, Tamai Y, Iwasa M, Nakagawa H, Nagano H, Takami T, Yamasaki T. Methylated SEPT9 assay-based liquid biopsy as a biomarker in molecular targeted agent-treated hepatocellular carcinoma. Hepatol Int 2023; 17:1289-1299. [PMID: 37186217 DOI: 10.1007/s12072-023-10488-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 01/16/2023] [Indexed: 05/17/2023]
Abstract
BACKGROUND The development of molecular targeted agents (MTAs) has changed the treatment strategy for hepatocellular carcinoma (HCC). However, currently, there are no established predictive biomarkers for the treatment efficacy of MTAs. Previously, we developed a novel liquid biopsy test for HCC screening using sensitive methylated DNA testing of septin 9 gene (SEPT9). Here, we hypothesized that SEPT9 could be used as a biomarker for MTA treatment efficacy. METHODS We enrolled 157 patients receiving sorafenib or lenvatinib as a first-line therapy and allocated 85 and 72 patients to the training and validation cohorts, respectively. For the methylation assay, DNA was treated with methylation-sensitive restriction enzymes, followed by multiplex droplet digital PCR. Various clinical parameters were compared with clinical outcomes. RESULTS The multivariate analysis revealed Eastern Cooperative Oncology Group performance status (≥ 1; p = 0.048), alpha-fetoprotein (AFP) (≥ 400 ng/mL; p < 0.001), and methylated-septin-9 (m-SEPT9) (≥ 205 copies/mL; p = 0.018) as significant predictors of poor overall survival (OS) in the training cohort. m-SEPT9 was identified as a predictor of poor OS in the validation cohort. We developed a predictive score, called the MTA score, consisting of these three significant OS parameters (two points were added for AFP and one point for each of the other predictors). Patients with MTA scores ≥ 2 showed a significantly poor prognosis compared to those with MTA scores ≤ 1 in both the training and validation cohorts. CONCLUSIONS m-SEPT9 could be a potential predictive biomarker for survival in patients with HCC treated with MTAs.
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Affiliation(s)
- Issei Saeki
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan
| | - Yutaka Suehiro
- Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan
| | - Yurika Yamauchi
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan
| | - Tomomi Hoshida
- Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan
| | - Norikazu Tanabe
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan
- Division of Laboratory, Yamaguchi University Hospital, Ube, Yamaguchi, 755-8505, Japan
| | - Takashi Oono
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan
| | - Daiki Kawamoto
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan
| | - Tatsuro Nishimura
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan
| | - Toshihiko Matsumoto
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan
| | - Tsuyoshi Ishikawa
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan
| | - Mototsugu Shimokawa
- Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan
| | - Akihiro Tamori
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Abeno-ku, Osaka, 545-8585, Japan
| | - Norifumi Kawada
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Abeno-ku, Osaka, 545-8585, Japan
| | - Yasuyuki Tamai
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Mie University, Tsu, Mie, 514-8507, Japan
| | - Motoh Iwasa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Mie University, Tsu, Mie, 514-8507, Japan
| | - Hayato Nakagawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Mie University, Tsu, Mie, 514-8507, Japan
| | - Hiroaki Nagano
- Department of Gastroenterological, Breast, and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan
| | - Taro Takami
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan
| | - Takahiro Yamasaki
- Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan.
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4
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Huo TI, Liao JI, Ho SY. Developing real-world prognostic models for patients with advanced hepatocellular carcinoma: CRAFITY, mALF and beyond. Hepatol Int 2023; 17:512-513. [PMID: 36565397 DOI: 10.1007/s12072-022-10467-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 12/03/2022] [Indexed: 12/25/2022]
Affiliation(s)
- Teh-Ia Huo
- Department of Medical Research, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Taipei, 11217, Taiwan.
- Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Jia-I Liao
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Shu-Yein Ho
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Min-Sheng General Hospital, Taoyuan, Taiwan
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5
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Lima HA, Endo Y, Moazzam Z, Alaimo L, Shaikh C, Munir MM, Resende V, Guglielmi A, Marques HP, Cauchy F, Lam V, Poultsides GA, Popescu I, Alexandrescu S, Martel G, Endo I, Kitago M, Shen F, Pawlik TM. TAC score better predicts survival than the BCLC following resection of hepatocellular carcinoma. J Surg Oncol 2023; 127:374-384. [PMID: 36194039 PMCID: PMC10091702 DOI: 10.1002/jso.27116] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 09/24/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND Heterogeneity in hepatocellular carcinoma (HCC) still exists within the Barcelona clinic liver cancer (BCLC) subcategories. We developed a simple model to better discriminate and predict prognosis following resection. METHODS Patients who underwent curative-intent resection for HCC were identified from a multi-institutional database. Predictive factors of survival were identified to develop TAC (tumor burden score [TBS], alpha-fetoprotein [AFP], Child-Pugh CP]) score. RESULTS Among 1435 patients, median TBS was 5.1 (interquartile range [IQR]: 3.2-8.1), median AFP was 18.3 ng/ml (IQR 4.0-362.5), and 1391 (96.9%) patients were classified as CP-A. Factors associated with overall survival (OS) included TBS (low: referent; medium: HR 2.26, 95% CI: 1.73-2.96; high: HR = 3.35, 95% CI: 2.22-5.07), AFP (<400 ng/ml: referent; >400 ng/ml: HR = 1.56, 95% CI: 1.27-1.92), and CP (A: referent; B: HR = 1.81, 95% CI: 1.12-2.92) (all p < 0.05). A simplified risk score demonstrated superior concordance index, Akaike information criteria, homogeneity, and area under the curve versus BCLC (0.620 vs. 0.541; 5484.655 vs. 5536.454; 60.099 vs. 16.194; 0.62 vs. 0.55, respectively), and further stratified patients within BCLC groups relative to OS (BCLC 0, very low: 86.8%, low: 47.8%) (BCLC A, very low: 79.7%, low: 68.1%, medium: 52.5%, high: 35.6%) (BCLC B, low: 59.8%, medium: 43.7%, high: N/A). CONCLUSION TAC is a simple, holistic score that consistently outperformed BCLC relative to discrimination power and prognostication following resection of HCC.
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Affiliation(s)
- Henrique A Lima
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA.,School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Yutaka Endo
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Zorays Moazzam
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Laura Alaimo
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Chanza Shaikh
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Muhammad M Munir
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Vivian Resende
- School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | | | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - François Cauchy
- Department of Hepatibiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France
| | - Vincent Lam
- Department of Surgery, Westmead Hospital, Sydney, New South Wales, Australia
| | | | - Irinel Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | | | - Guillaume Martel
- Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada
| | - Itaru Endo
- School of Medicine, Yokohama City University, Yokohama, Japan
| | - Minoru Kitago
- Department of Surgery, Keio University, Tokyo, Japan
| | - Feng Shen
- Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
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6
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Hepatocellular Carcinoma: Current Therapeutic Algorithm for Localized and Advanced Disease. JOURNAL OF ONCOLOGY 2022; 2022:3817724. [PMID: 36624801 PMCID: PMC9825221 DOI: 10.1155/2022/3817724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 12/16/2022] [Accepted: 12/19/2022] [Indexed: 01/02/2023]
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer in patients with liver cirrhosis of various etiologies. In recent years, there has been an advance in the knowledge of molecular mechanisms and a better staging definition of patients which has allowed the development of new therapies that have entered the therapeutic workup of these patients. Deep information on molecular drivers of HCC contributed to the development of targeted therapies with remarkable benefits. The novel strategies of targeting immune evasion using immune checkpoint inhibitors and CAR-T and TCR-T therapeutics have also shown promising results. For advanced diseases, the therapeutic algorithm has been recently updated, thanks to the efficacy of combining immunotherapy and antiangiogenic therapy in the first-line setting, and new drugs, both as single-agents or combinations, are currently under investigation.
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7
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Huo TI, Liao JI, Ho SY. Prognostic prediction for patients with hepatocellular carcinoma receiving immunotherapy: Are we there yet? J Hepatol 2022; 76:987-988. [PMID: 34780876 DOI: 10.1016/j.jhep.2021.11.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 11/06/2021] [Indexed: 02/06/2023]
Affiliation(s)
- Teh-Ia Huo
- Division of Basic Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Jia-I Liao
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Shu-Yein Ho
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Min-Sheng General Hospital, Taoyuan, Taiwan
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8
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Demirtas CO, Ricco G, Ozdogan OC, Baltacioglu F, Ones T, Yumuk PF, Dulundu E, Uzun S, Colombatto P, Oliveri F, Brunetto MR, Gunduz F. Proposal and Validation of a Novel Scoring System for Hepatocellular Carcinomas Beyond Curability Borders. Hepatol Commun 2022; 6:633-645. [PMID: 34751001 PMCID: PMC8870011 DOI: 10.1002/hep4.1836] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 08/12/2021] [Accepted: 08/30/2021] [Indexed: 01/21/2023] Open
Abstract
Optimal scoring system for clinical prognostic factors in patients with unresectable hepatocellular carcinoma (HCC) is currently uncertain. We aimed to develop and externally validate an easy to use tool, particularly for this population, and named it the "unresectable hepatocellular carcinoma prognostic index" (UHPI). We evaluated the data of patients with treatment-naive unresectable HCC who were diagnosed in the training center from 2010 to 2019 (n = 209). A simple prognostic model was developed by assigning points for each covariate in proportion to the beta coefficients in the Cox multivariable model. Predictive performance and distinction ability of the UHPI were further evaluated in an independent European validation cohort (n = 147) and compared with 11 other available models. A simple scoring system was derived, assigning 0.5/1/2 scores for six independent covariates including, the Child-Pugh score, Eastern Cooperative Oncology Group performance status, maximum tumor size, vascular invasion or extrahepatic metastasis, lymph node involvement, and alpha-fetoprotein. The UHPI score, ranging from 0 to 6, showed superior performance in prognosis prediction and outperformed 11 other staging or prognostic models, giving the highest homogeneity (c-index, 6-month and 1-year area under the receiver operator characteristic curves), lowest Akaike information criterion, and -2 log-likelihood ratio values. The UHPI score allocated well the risk of patients with unresectable HCC for mortality within the first year, using two cut-off values (low-risk, <0.5; intermediate-risk, 0.5-2; high-risk, >2). Conclusion: The UHPI score can predict prognosis better than other systems in subjects with unresectable HCC and can be used in clinical practice or trials to estimate the 6-month and 1-year survival probabilities for this group.
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Affiliation(s)
- Coskun Ozer Demirtas
- Division of Gastroenterology and HepatologyMarmara University School of MedicineIstanbulTurkey
| | - Gabrielle Ricco
- Hepatology UnitPisa University HospitalPisaItaly.,Biostructure and Bio-imaging Institute of National Research Council of ItalyNaplesItaly
| | - Osman Cavit Ozdogan
- Division of Gastroenterology and HepatologyMarmara University School of MedicineIstanbulTurkey
| | - Feyyaz Baltacioglu
- Department of RadiologyMarmara University School of MedicineIstanbulTurkey
| | - Tunc Ones
- Department of Nuclear MedicineMarmara University School of MedicineIstanbulTurkey
| | - Perran Fulden Yumuk
- Division of Medical OncologyMarmara University School of MedicineIstanbulTurkey
| | - Ender Dulundu
- Department of General SurgeryMarmara University School of MedicineIstanbulTurkey
| | - Sinan Uzun
- Department of Medical BiostatisticsMarmara University School of MedicineIstanbulTurkey
| | | | | | - Maurizia Rosanna Brunetto
- Hepatology UnitPisa University HospitalPisaItaly.,Biostructure and Bio-imaging Institute of National Research Council of ItalyNaplesItaly.,Department of Clinical and Experimental MedicinePisa UniversityPisaItaly
| | - Feyza Gunduz
- Division of Gastroenterology and HepatologyMarmara University School of MedicineIstanbulTurkey
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9
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Huo TI, Ho SY, Liao JI. Improving the accuracy of outcome prediction for hepatocellular carcinoma: Asia strategies. Liver Int 2022; 42:714-715. [PMID: 35065002 DOI: 10.1111/liv.15167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 01/17/2022] [Indexed: 02/13/2023]
Affiliation(s)
- Teh-Ia Huo
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Shu-Yein Ho
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Min-Sheng General Hospital, Taoyuan, Taiwan
| | - Jia-I Liao
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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10
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Papaconstantinou D, Hewitt DB, Brown ZJ, Schizas D, Tsilimigras DI, Pawlik TM. Patient stratification in hepatocellular carcinoma: impact on choice of therapy. Expert Rev Anticancer Ther 2022; 22:297-306. [PMID: 35157530 DOI: 10.1080/14737140.2022.2041415] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
INTRODUCTION HCC comprises around 60 to 80% of all primary liver cancers and exhibits wide geographical variability. Appropriate treatment allocation needs to include both patient and tumor characteristics. AREAS COVERED Current HCC classification systems to guide therapy are either liver function-centric and evaluate physiologic liver function to guide therapy or prognostic stratification classification systems broadly based on tumor morphologic parameters, patient performance status, and liver reserve assessment. This review focuses on different classification systems for HCC, their strengths, and weaknesses as well as the use of artificial intelligence in improving prognostication in HCC. EXPERT OPINION Future HCC classification systems will need to incorporate clinic-pathologic data from a multitude of sources and emerging therapies to develop patient-specific treatment plans targeting a patient's unique tumor profile.
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Affiliation(s)
- Dimitrios Papaconstantinou
- Third Department of Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, Medical School, Greece
| | - D Brock Hewitt
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
| | - Zachary J Brown
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
| | - Dimitrios Schizas
- First Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, Medical School, Greece
| | - Diamantis I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
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11
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Swersky A, Kulik L, Kalyan A, Grace K, Caicedo JC, Lewandowski RJ, Salem R. Contemporary Algorithm for the Management of Hepatocellular Carcinoma in 2021: The Northwestern Approach. Semin Intervent Radiol 2021; 38:432-437. [PMID: 34629710 DOI: 10.1055/s-0041-1735528] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a major cause of cancer-related morbidity and mortality around the world. Frequently, concurrent liver dysfunction and variations in tumor burden make it difficult to design effective and standardized treatment pathways. Contemporary treatment guidelines designed for an era of personalized medicine should consider these features in a more clinically meaningful way to improve outcomes for patients across the HCC spectrum. Given the heterogeneity of HCC, we propose a detailed clinical algorithm for selecting optimal treatment using an evidence-based and practical approach, incorporating liver function, tumor burden, the extent of disease, and ultimate treatment intent, with the goal of individualizing clinical decision making.
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Affiliation(s)
- Adam Swersky
- Section of Interventional Radiology, Department of Radiology, Northwestern Feinberg School of Medicine, Chicago, Illinois
| | - Laura Kulik
- Division of Hepatology, Department of Medicine, Northwestern Feinberg School of Medicine, Chicago, Illinois
| | - Aparna Kalyan
- Division of Medical Oncology, Department of Medicine, Northwestern Feinberg School of Medicine, Chicago, Illinois
| | - Karen Grace
- Section of Interventional Radiology, Department of Radiology, Northwestern Feinberg School of Medicine, Chicago, Illinois
| | - Juan Carlos Caicedo
- Division of Transplantation, Department of Surgery, Northwestern Feinberg School of Medicine, Chicago, Illinois
| | - Robert J Lewandowski
- Section of Interventional Radiology, Department of Radiology, Northwestern Feinberg School of Medicine, Chicago, Illinois
| | - Riad Salem
- Section of Interventional Radiology, Department of Radiology, Northwestern Feinberg School of Medicine, Chicago, Illinois
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12
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Huo TI, Ho SY, Liu PH. Selecting an optimal prognostic model for advanced hepatocellular carcinoma: Any new ideas? Dig Liver Dis 2021; 53:1208-1209. [PMID: 34011481 DOI: 10.1016/j.dld.2021.04.025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 04/19/2021] [Indexed: 12/11/2022]
Affiliation(s)
- Teh-Ia Huo
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Shu-Yein Ho
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Min-Sheng General Hospital, Taoyuan, Taiwan
| | - Po-Hong Liu
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States
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13
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Marasco G, Trevisani F. Time to move beyond the classical prognostic systems for patients with advanced hepatocellular carcinoma undergoing Sorafenib. Dig Liver Dis 2021; 53:1210-1211. [PMID: 34052178 DOI: 10.1016/j.dld.2021.04.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 04/28/2021] [Indexed: 12/11/2022]
Affiliation(s)
- Giovanni Marasco
- Internal Medicine and Digestive Physiopathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Science, Gastroenterology Unit, University of Bologna, Bologna, Italy.
| | - Franco Trevisani
- Division of Semeiotics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Science, Gastroenterology Unit, University of Bologna, Bologna, Italy
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14
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Huo TI, Liu PH, Hsu CY. Letter to the Editor: Using Circulating Biomarkers to Stage HCC: Pitfalls and Limitations. Hepatology 2021; 73:2611. [PMID: 33170973 DOI: 10.1002/hep.31618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Affiliation(s)
- Teh-Ia Huo
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Po-Hong Liu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX
| | - Chia-Yang Hsu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
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15
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Vitale A, Farinati F, Finotti M, Di Renzo C, Brancaccio G, Piscaglia F, Cabibbo G, Caturelli E, Missale G, Marra F, Sacco R, Giannini EG, Trevisani F, Cillo U, Associazione Italiana per lo Studio del Fegato (AISF) HCC Special Interest Group, Italian Liver Cancer (ITA.LI.CA) Study Group. Overview of Prognostic Systems for Hepatocellular Carcinoma and ITA.LI.CA External Validation of MESH and CNLC Classifications. Cancers (Basel) 2021; 13:1673. [PMID: 33918125 PMCID: PMC8037197 DOI: 10.3390/cancers13071673] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 03/23/2021] [Accepted: 03/25/2021] [Indexed: 02/07/2023] Open
Abstract
Prognostic assessment in patients with HCC remains an extremely difficult clinical task due to the complexity of this cancer where tumour characteristics interact with degree of liver dysfunction, patient general health status, and a large span of available treatment options. Several prognostic systems have been proposed in the last three decades, both from the Asian and European/North American countries. Prognostic scores, such as the CLIP score and the recent MESH score, have been generated on a solid statistical basis from real life population data, while staging systems, such as the BCLC scheme and the recent CNLC classification, have been created by experts according to recent HCC prognostic evidences from the literature. A third category includes combined prognostic systems that can be used both as prognostic scores and staging systems. A recent example is the ITA.LI.CA prognostic system including either a prognostic score and a simplified staging system. This review focuses first on an overview of the main prognostic systems for HCC classified according to the above three categories, and, second, on a comprehensive description of the methodology required for a correct comparison between different systems in terms of prognostic performance. In this second section the main studies in the literature comparing different prognostic systems are described in detail. Lastly, a formal comparison between the last prognostic systems proposed for each of the above three categories is performed using a large Italian database including 6882 HCC patients in order to concretely apply the comparison rules previously described.
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Affiliation(s)
- Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy; (A.V.); (F.F.); (C.D.R.); (U.C.)
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy; (A.V.); (F.F.); (C.D.R.); (U.C.)
| | - Michele Finotti
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy; (A.V.); (F.F.); (C.D.R.); (U.C.)
| | - Chiara Di Renzo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy; (A.V.); (F.F.); (C.D.R.); (U.C.)
| | - Giuseppina Brancaccio
- Infectious Diseases Unit, Department of Internal Medicine, Padua University Hospital, 35123 Padua, Italy;
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy;
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
| | - Giuseppe Cabibbo
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, 90127 Palermo, Italy;
| | | | - Gabriele Missale
- Infectious Diseases and Hepatology Unit, Azienda Ospedaliero-Universitaria of Parma, 43126 Parma, Italy;
| | - Fabio Marra
- Internal Medicine and Hepatology Unit, Department of Experimental and Clinical Medicine, University of Firenze, 50139 Firenze, Italy;
| | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, 71122 Foggia, Italy;
| | - Edoardo G. Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy;
| | - Franco Trevisani
- Division of Semeiotics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy; (A.V.); (F.F.); (C.D.R.); (U.C.)
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16
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Campani C, Vitale A, Dragoni G, Arena U, Laffi G, Cillo U, Giannini EG, Tovoli F, Rapaccini GL, Di Marco M, Caturelli E, Zoli M, Sacco R, Cabibbo G, Mega A, Guarino M, Gasbarrini A, Svegliati-Baroni G, Foschi FG, Biasini E, Masotto A, Nardone G, Raimondo G, Azzaroli F, Vidili G, Brunetto MR, Farinati F, Trevisani F, Marra F. Time-Varying mHAP-III Is the Most Accurate Predictor of Survival in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization. Liver Cancer 2021; 10:126-136. [PMID: 33977089 PMCID: PMC8077424 DOI: 10.1159/000513404] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 10/31/2020] [Indexed: 02/05/2023] Open
Abstract
INTRODUCTION The prognosis of patients undergoing transarterial chemoembolization (TACE) is extremely variable, and a confounding factor is that TACE is often repeated several times. We retrospectively evaluated the accuracy of different prognostic scores and staging systems in estimating overall survival (OS) in patients with hepatocellular carcinoma (HCC). METHODS An analysis considering prognostic models as time-varying variables was performed, calculating OS from the time of TACE to the time of the subsequent treatment. Total follow-up time for each patient was therefore split into several observation times accounting for each TACE procedure. Values of the likelihood ratio test (LRT) and Akaike information criterion (AIC) were used to compare different systems. Univariable and multivariable analyses were conducted to identify additional factors predictive of OS. We analyzed 1,610 TACE performed in 1,058 patients recorded in the Italian Liver Cancer database from 2008 through 2016. RESULTS The median OS of the enrolled patients was 41 months. According to LRT χ2 and AIC values based on the time-varying analysis, mHAP-III achieved the best values (41.72 and 4,625.49, respectively, p < 0.0001), indicating the highest predictive performance compared with all other scores (HAP, mHAP-II, ALBI, and pALBI) and staging systems (MELD, ITALICA, CLIP, MESH, MESIAH, JIS, HKLC, and BCLC). In the multivariable Cox proportional hazards model, mHAP-III maintained an independent effect on OS (hazard ratio 1.31, 95% CI: 1.10-1.55, p < 0.0001). Time-varying age, alcoholic etiology, radiologic response to TACE, and performing ablation or surgery after TACE were additional significant variables resulting from the multivariable model. CONCLUSION An innovative time-varying analysis revealed that mHAP-III was the most accurate model in predicting OS in patients with HCC undergoing TACE. Other clinical pre- and post-TACE variables were also found to be relevant for this prediction.
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Affiliation(s)
- Claudia Campani
- Internal Medicine and Hepatology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Gabriele Dragoni
- Internal Medicine and Hepatology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Umberto Arena
- Internal Medicine and Hepatology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Giacomo Laffi
- Internal Medicine and Hepatology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Edoardo G. Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Policlinico San Martino, Genoa, Italy
| | - Francesco Tovoli
- Internal Medicine-Piscaglia Unit, Azienda Ospedaliero-Universitaria S. Orsola-Malpighi, University of Bologna, Bologna, Italy
| | | | | | | | - Marco Zoli
- Internal Medicine-Zoli Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Italy
| | - Giuseppe Cabibbo
- Gastroenterology & Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Andrea Mega
- Gastroenterology Unit, Bolzano Regional Hospital, Bolzano, Italy
| | - Maria Guarino
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, University of Naples “Federico II”, Naples, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology Unit, Policlinico Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gianluca Svegliati-Baroni
- Liver Injury and Transplant Unit, and Obesity Center, Polytechnic University of Marche, Ancona, Italy
| | | | - Elisabetta Biasini
- Infectious Diseases and Hepatology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Alberto Masotto
- Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Gerardo Nardone
- Hepato-Gastroenterology Unit, Department of Clinical Medicine and Surgery, University of Naples “Federico II”, Naples, Italy
| | - Giovanni Raimondo
- Clinical and Molecular Hepatology Unit, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Francesco Azzaroli
- Gastroenterology Unit, Department of Surgical and Medical Sciences, Alma Mater Studiorum − Università of Bologna, Bologna, Italy
| | - Gianpaolo Vidili
- Department of Medical, Surgical and Experimental Sciences, Sassari, Italy
- Clinica Medica Unit, University of Sassari, Azienda Ospedaliero-Universitaria di Sassari, Sassari, Italy
| | - Maurizia Rossana Brunetto
- Hepatology and Liver Physiopathology Laboratory and Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Franco Trevisani
- Department of Medical and Surgical Sciences, Semeiotics Unit, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Fabio Marra
- Internal Medicine and Hepatology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
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Key Enzymes in Pyrimidine Synthesis, CAD and CPS1, Predict Prognosis in Hepatocellular Carcinoma. Cancers (Basel) 2021; 13:cancers13040744. [PMID: 33670206 PMCID: PMC7916936 DOI: 10.3390/cancers13040744] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 02/05/2021] [Indexed: 02/06/2023] Open
Abstract
Patients with hepatocellular carcinoma (HCC) have a highly variable clinical course. Therefore, there is an urgent need to identify new prognostic markers to determine prognosis and select specific therapies. Recently, it has been demonstrated that dysregulation of the urea cycle (UC) is a common phenomenon in multiple types of cancer. Upon UC dysregulation, nitrogen is diverted toward the multifunctional enzyme carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase (CAD), and increases pyrimidine synthesis. In this study, we investigated the role of CAD and carbamoyl-phosphate synthetase 1 (CPS1), a rate-limiting enzyme of the UC highly expressed in hepatocytes, in HCC. We created a tissue microarray to analyze expression of both enzymes by immunohistochemistry in a large and well-characterized overall cohort of 871 HCCs of 561 patients that underwent surgery. CAD was induced in recurrent HCCs, and high expression predicted shorter overall survival. CPS1 was downregulated in HCC and further reduced in recurrent tumors and distant metastases. Additionally, low CPS1 was associated with short overall survival. A combined score of both enzymes was an independent prognostic marker in a multivariate Cox regression model (HR = 1.37, 95% confidence interval 1.06-1.75, p = 0.014). Inhibition of pyrimidine synthesis may represent a novel therapeutic strategy for HCC.
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Zhang X, El-Serag HB, Thrift AP. Predictors of five-year survival among patients with hepatocellular carcinoma in the United States: an analysis of SEER-Medicare. Cancer Causes Control 2021; 32:317-325. [PMID: 33394207 DOI: 10.1007/s10552-020-01386-x] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 12/17/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND Most patients with hepatocellular carcinoma (HCC) are ≥ 65 years old at diagnosis and ~ 20% present with disease amenable to curative intent surgical therapy. The aim of this study was to examine whether treatment, the demographic variables, and clinical factors could predict 5-year survival among HCC patients. METHODS We included patients, 66 years or older, diagnosed with a first primary HCC from 1994 through 2007 in the SEER-Medicare database, and followed up until death or 31 December 2012. Curative intent treatment was defined as liver transplantation, surgery resection, or ablation. We estimated odds ratios (OR) and 95% confidence intervals (CI) for associations with 5-year survival using logistic regression. RESULTS We identified 10,826 patients with HCC with mean age 75.3 (standard deviation, 6.4) years. Most were male (62.2%) and non-Hispanic white (59.7%). Overall, only 8.1% of patients were alive 5 years post-HCC diagnosis date. Among all patients that survived ≥ 5 years, 69.8% received potentially curative treatment. Conversely, patients who received potentially curative treatment represented only 15.7% of patients who survived < 5 years. Curative intent treatment was the strongest predictor for surviving ≥ 5 years (vs. none/palliative treatment; adjusted OR 8.12, 95% CI 6.90-9.64). While stage at diagnosis and comorbidities were also independently associated with ≥ 5-year survival in HCC patients, these factors did not improve discrimination between short- and long-term survivors. CONCLUSIONS Curative intent treatment was the strongest predictor for survival ≥ 5 years among HCC patients. Given the limited availability of liver transplant and limited eligibility for surgical resection, finding curative intent HCC therapies remain critically important.
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Affiliation(s)
- Xiaotao Zhang
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX, USA. .,Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA. .,Baylor College of Medicine, One Baylor Plaza, MS: BCM307, Room 613D, Houston, TX, 77030-3498, USA.
| | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.,Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - Aaron P Thrift
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.,Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA
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Campigotto M, Giuffrè M, Colombo A, Visintin A, Aversano A, Budel M, Masutti F, Abazia C, Crocé LS. Comparison between hepatocellular carcinoma prognostic scores: A 10-year single-center experience and brief review of the current literature. World J Hepatol 2020; 12:1239-1257. [PMID: 33442451 PMCID: PMC7772726 DOI: 10.4254/wjh.v12.i12.1239] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 08/14/2020] [Accepted: 10/09/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) represents the most common primitive liver malignancy. A relevant concern involves the lack of agreement on staging systems, prognostic scores, and treatment allocation algorithms. AIM To compare the survival rates among already developed prognostic scores. METHODS We retrospectively evaluated 140 patients with HCC diagnosed between February 2006 and November 2017. Patients were categorized according to 15 prognostic scoring systems and estimated median survivals were compared with those available from the current medical literature. RESULTS The median overall survival of the cohort of patients was 35 (17; 67) mo, and it was statistically different in relation to treatment choice, ultrasound surveillance, and serum alpha-fetoprotein. The Italian Liver Cancer (ITA.LI.CA) tumor staging system performed best in predicting survival according to stage allocation among all 15 evaluated prognostic scores. Using the ITA.LI.CA prognostic system, 28.6%, 40.7%, 22.1%, and 8.6% of patients fell within stages 0-1, 2-3, 4-5 and > 5 respectively. The median survival was 57.9 mo for stages 0-1, 43 mo for stages 2-3, 21.7 mo for stages 4-5, and 10.4 mo for stage > 5. The 1-, 3-, and 5-year survival rates were respectively 95%, 65%, and 20%, for stages 0-1; 94.7%, 43.9% and 26.3% for stages 2-3; 71%, 25.8% and 16.1% for stages 4-5; and 50%, 16.7% and 8.3% for stage > 5. At the same time, although statistically significant in prognostic stratification, the most commonly used Barcelona Clinic Liver Cancer system showed one of the most relevant differences in median survival, especially for stages A and C, when compared to the medical literature. In fact, 10.7%, 59.3%, 27.1%, 1.4%, and 0% of patients were stratified into stages 0, A, B, C, and D respectively. The median survival was > 81.1 mo for stage 0, 44.9 mo for stage A, 21.3 mo for stage B, and 3.1 mo for stage C. The 1-, 3-, and 5-year survival rates were respectively 86.7%, 60%, and 46.7% for stage 0; 91.6%, 50.6%, and 20.5% for stage A; 73.7%, 23.7% and 13.2% for stage B; and 2%, 0% and 0% for stage C. CONCLUSION Survival analysis shows excellent prognostic ability of the ITA.LI.CA scoring system compared to other staging systems.
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Affiliation(s)
- Michele Campigotto
- Dipartimento Universitario Clinico di Scienze Mediche, Chirurgiche e Della Salute, Università degli Studi di Trieste, Trieste 34149, Italy
| | - Mauro Giuffrè
- Dipartimento Universitario Clinico di Scienze Mediche, Chirurgiche e Della Salute, Università degli Studi di Trieste, Trieste 34149, Italy.
| | - Anna Colombo
- Dipartimento Universitario Clinico di Scienze Mediche, Chirurgiche e Della Salute, Università degli Studi di Trieste, Trieste 34149, Italy
| | - Alessia Visintin
- Dipartimento Universitario Clinico di Scienze Mediche, Chirurgiche e Della Salute, Università degli Studi di Trieste, Trieste 34149, Italy
| | - Alessandro Aversano
- Dipartimento Universitario Clinico di Scienze Mediche, Chirurgiche e Della Salute, Università degli Studi di Trieste, Trieste 34149, Italy
| | - Martina Budel
- Dipartimento Universitario Clinico di Scienze Mediche, Chirurgiche e Della Salute, Università degli Studi di Trieste, Trieste 34149, Italy
| | - Flora Masutti
- Clinica Patologie del Fegato, Azienda Sanitaria Universitaria Giuliano Isontina, Trieste 34149, Italy
| | - Cristiana Abazia
- Clinica Patologie del Fegato, Azienda Sanitaria Universitaria Giuliano Isontina, Trieste 34149, Italy
| | - Lory Saveria Crocé
- Dipartimento Universitario Clinico di Scienze Mediche, Chirurgiche e Della Salute, Università degli Studi di Trieste, Trieste 34149, Italy
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Zhang R, Chen J, Jiang Y, Wang J, Chen S. Prognostic nomogram for hepatocellular carcinoma with fibrosis of varying degrees: a retrospective cohort study. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1429. [PMID: 33313174 PMCID: PMC7723572 DOI: 10.21037/atm-20-3267] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Background Hepatocellular carcinoma (HCC) is a common and biologically aggressive malignancy linked to cirrhotic and pre-cirrhotic changes in the liver. We analyzed degrees of fibrosis in affected patients as indices of survival, to establish an effective prognostic nomogram. Methods Eligible patients with HCC and hepatic fibrosis, of varying degrees, were selected from the Surveillance, Epidemiology, and End Results (SEER) database for propensity score matching (PSM). The prognostic value of data was determined using Kaplan-Meier and Cox proportional hazards model. A nomogram based on variables derived from multivariate analyses was established and subjected to internal validation. Its predictive accuracy was tested by concordance index (C-index) and calibration plots. Results In this propensity score-matched cohort, advanced fibrosis/cirrhosis (vs. none-to-moderate fibrosis) correlated with poorer survival [hazard ratio (HR): 1.131, 95% confidence interval (CI): 1.032-1.240; P=0.009]. Multivariate analysis identified the following as independent risk factors for HCC: age >63 years, higher fibrosis score, American Joint Cancer Committee (AJCC) stages T3-4, distant metastasis (M1), tumor size >1 cm, major vascular invasion, and elevated alpha-fetoprotein (AFP) level. A nomogram that integrated these factors offered a superior prognostic prediction for HCC patients (C-index: 0.749, 95% CI: 0.7485-0.7495) relative to conventional tumor staging the AJCC tumor-node-metastasis (TNM) staging system (0.730). In calibration plots, optimal agreement between nomogram-predicted and observed survival was evident. Conclusions Increased fibrosis was an independent risk factor for survival of HCC patients. A prognostic nomogram integrating fibrosis score and other independent risk factors offered more accurate depictions in this regard.
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Affiliation(s)
- Rui Zhang
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.,Center of Evidence-Based Medicine, Fudan University, Shanghai, China.,Shanghai Institute of Liver Disease, Shanghai, China
| | - Jie Chen
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.,Center of Evidence-Based Medicine, Fudan University, Shanghai, China.,Shanghai Institute of Liver Disease, Shanghai, China
| | - Yingyi Jiang
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.,Center of Evidence-Based Medicine, Fudan University, Shanghai, China.,Shanghai Institute of Liver Disease, Shanghai, China
| | - Jian Wang
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.,Shanghai Institute of Liver Disease, Shanghai, China
| | - Shiyao Chen
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.,Center of Evidence-Based Medicine, Fudan University, Shanghai, China.,Shanghai Institute of Liver Disease, Shanghai, China.,Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
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21
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Bednarsch J, Czigany Z, Heise D, Joechle K, Luedde T, Heij L, Bruners P, Ulmer TF, Neumann UP, Lang SA. Prognostic evaluation of HCC patients undergoing surgical resection: an analysis of 8 different staging systems. Langenbecks Arch Surg 2020; 406:75-86. [PMID: 33294952 PMCID: PMC7870608 DOI: 10.1007/s00423-020-02052-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 12/02/2020] [Indexed: 02/06/2023]
Abstract
Purpose No consensus exists regarding the most appropriate staging system to predict overall survival (OS) for hepatocellular carcinoma (HCC) in surgical candidates. Thus, we aimed to determine the prognostic ability of eight different staging systems in a European cohort of patients undergoing liver resection for HCC. Methods Patients resected for HCC between 2010 and 2019 at our institution were analyzed with Kaplan-Meier and Cox regression analyses. Likelihood ratio (LR) χ2 (homogeneity), linear trend (LT) χ2 (discriminatory ability), and Akaike Information Criterion (AIC, explanatory ability) were used to determine the staging system with the best overall prognostic performance. Results Liver resection for HCC was performed in 160 patients. Median OS was 39 months (95% confidence interval (CI): 32–46 months) and median RFS was 26 months (95% CI: 16–34 months). All staging systems (BCLC, HKLC, Okuda, CLIP, ITA.LI.CA staging and score, MESH, and GRETCH) showed significant discriminatory ability regarding OS, with ITA.LI.CA score (LR χ2 30.08, LT χ2 13.90, AIC 455.27) and CLIP (LR χ2 28.65, LT χ2 18.95, AIC 460.07) being the best performing staging systems. Conclusions ITA.LI.CA and CLIP are the most suitable staging system to predict OS in European HCC patients scheduled for curative-intent surgery.
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Affiliation(s)
- Jan Bednarsch
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany
| | - Zoltan Czigany
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany
| | - Daniel Heise
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany
| | - Katharina Joechle
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany
| | - Tom Luedde
- Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Lara Heij
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany
- Institute of Pathology, University Hospital RWTH Aachen, Aachen, Germany
| | - Philipp Bruners
- Department of Radiology, University Hospital RWTH Aachen, Aachen, Germany
| | - Tom Florian Ulmer
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany
| | - Ulf Peter Neumann
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany
- Department of Surgery, Maastricht University Medical Centre (MUMC), Maastricht, Netherlands
| | - Sven Arke Lang
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
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22
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Adhoute X, Pénaranda G, Raoul JL, Bronowicki JP, Anty R, Bourlière M. “Six-and-twelve” score for outcome prediction of hepatocellular carcinoma following transarterial chemoembolization. In-depth analysis from a multicenter French cohort. World J Hepatol 2020; 12:525-532. [PMID: 32952879 PMCID: PMC7475776 DOI: 10.4254/wjh.v12.i8.525] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 07/05/2020] [Accepted: 07/19/2020] [Indexed: 02/06/2023] Open
Abstract
The “six-and-twelve” (6&12) score is a new hepatocellular carcinoma (HCC) prognostic index designed for recommended transarterial chemoembolization (TACE) candidates. Quick and easy to use by the sum of tumor size (cm) and number, this model identifies three groups with different survival time (the sum is ≤ 6; or > 6 but ≤ 12; or > 12); a survival benefit with TACE can be expected for HCC patients with a score not exceeding twelve. Recently, Wang ZW et al showed that the “6&12” model was the best system correlated with radiological response after the first TACE. Thus, we wanted to assess its survival prediction ability as well as its prognostic value and compared it to other systems (Barcelona Clinic Liver Cancer, Hong Kong Liver Cancer (HKLC) staging, Albumin-Bilirubin grade, tumor nodularity, infiltrative nature of the tumor, alpha-fetoprotein, Child-Pugh class, and Performance Status score, Cancer of the Liver Italian Program, Model to Estimate Survival for HCC scores, up-to-seven criteria) different from Wang ZW et al study in a multicenter French cohort of HCC including only recommended TACE candidates retrospectively enrolled. As previously demonstrated, we show that the "6&12” score can classify survival within this French cohort, with a prognostic value comparable to that of other systems, except HKLC staging. More importantly, the “6&12” score simplicity and ability in patients’ stratification outperform other systems for a routine clinical practice.
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Affiliation(s)
- Xavier Adhoute
- Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille 13008, France
| | | | - Jean-Luc Raoul
- Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Nantes 44805, France
| | - Jean-Pierre Bronowicki
- Department of Gastroenterology and Hepatology, Centre Hospitalo-Universitaire de, Nancy 54511, France
| | - Rodolphe Anty
- Department of Gastroenterology and Hepatology, Hôpital Universitaire de l’Archet, Nice 06200, France
| | - Marc Bourlière
- Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille 13008, France
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23
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Ho SY, Liu PH, Hsu CY, Hsia CY, Su CW, Huang YH, Lei HJ, He YJ, Hou MC, Huo TI. An Albumin-Bilirubin (ALBI) Grade-based Prognostic Model For Patients With Hepatocellular Carcinoma Within Milan Criteria. Am J Clin Oncol 2020; 42:698-704. [PMID: 31335351 DOI: 10.1097/coc.0000000000000581] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE The Milan criteria are recommended as the major reference for liver transplantation in patients with small hepatocellular carcinoma (HCC). However, alternative anticancer treatments are often utilized due to severe donor organ shortage. This study aimed to develop and validate an albumin-bilirubin (ALBI) grade-based prognostic model to stratify survival in patients within Milan criteria undergoing nontransplant therapy. PATIENTS AND METHODS A total of 1655 patients were assigned into the derivation and validation cohort according to treatment modalities. Multivariate analysis was used to identify independent predictors of survival in the derivation cohort. An ALBI-based model was evaluated in the validation cohort. RESULTS In the Cox multivariate model, age 65 years or older (hazard ratio [HR]=1.576, P<0.001), serum α-fetoprotein (AFP) level >100 ng/mL (HR=1.671, P<0.001), ascites (HR=1.808, P<0.001), performance status 1 to 4 (HR=1.738, P<0.001), ALBI grade 2 (HR=1.827, P<0.001), and ALBI grade 3 (HR=3.589, P<0.001) were independent predictors of poor survival in the derivation cohort. An ALBI-based prognostic model with a total of 0 to 6 points was derived with the sum of 5 variables: 1 point each for age 65 years or older, AFP >100 ng/mL, presence of ascites, performance status 1 to 4, and ALBI grade 2, and 2 points for ALBI grade 3. This model can accurately predict long-term outcome in the validation cohort (P<0.001) and discriminate survival in patients stratified by curative and noncurative treatments (both P<0.001). CONCLUSION The proposed ALBI grade-based model is feasible in predicting survival in HCC patients within the Milan criteria, and helps identify high-risk patients who need timely liver transplantation.
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Affiliation(s)
- Shu-Yein Ho
- Departments of Medicine.,Faculty of Medicine
| | - Po-Hong Liu
- Faculty of Medicine.,Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX
| | - Chia-Yang Hsu
- Faculty of Medicine.,Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
| | | | | | - Yi-Hsiang Huang
- Departments of Medicine.,Faculty of Medicine.,Institute of Clinical Medicine
| | | | | | | | - Teh-Ia Huo
- Faculty of Medicine.,Medical Research, Taipei Veterans General Hospital.,Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan
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24
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Heinrich S, Sprinzl M, Schmidtmann I, Heil E, Koch S, Czauderna C, Heinrich B, Philippe P Diggs L, Wörns MA, Kloeckner R, Galle PR, Marquardt JU, Weinmann A. Validation of prognostic accuracy of MESH, HKLC, and BCLC classifications in a large German cohort of hepatocellular carcinoma patients. United European Gastroenterol J 2020; 8:444-452. [PMID: 32213028 DOI: 10.1177/2050640620904524] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND AND AIM The Barcelona Clinic Liver Cancer (BCLC) staging system is commonly used to classify hepatocellular carcinoma (HCC) patients. However, other staging classification schemes have been proposed. We aimed to compare the prognostic accuracy of the Hong Kong Liver Cancer Staging (HKLC), the Model to Estimate Survival for HCC (MESH), and the BCLC staging systems using a Western cohort of HCC patients. METHODS We retrospectively analyzed 918 patients diagnosed with HCC treated at the University Medical Center of Mainz between 2005 and 2014. We compared the predictive power of survival time of the BCLC, HKLC, and MESH. Predictive ability was tested using the integrated Brier score (IBS) and Harrell's C index. RESULTS Kaplan-Meier analyses showed significant differences in survival between stages defined by the BCLC, HKLC, and MESH. The HKLC classification demonstrated a more robust classification concordance and lower prediction error compared to the BCLC and MESH. In addition, we found that the BCLC offers superior predictive ability to the MESH in the first four years, whereas the MESH is superior for long-term predictions. CONCLUSION Our analyses confirm the prognostic value of three different HCC scoring systems. When compared, the HKLC provides superior prognostication ability.
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Affiliation(s)
- Sophia Heinrich
- Department of Medicine I, University Medical Center, Mainz, Germany
| | - Martin Sprinzl
- Department of Medicine I, University Medical Center, Mainz, Germany
| | | | - Elena Heil
- Department of Medicine I, University Medical Center, Mainz, Germany
| | - Sandra Koch
- Department of Medicine I, University Medical Center, Mainz, Germany
| | | | - Bernd Heinrich
- Department of Medicine I, University Medical Center, Mainz, Germany
| | - Laurence Philippe P Diggs
- Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, USA
| | | | - Roman Kloeckner
- Department of Diagnostic and Interventional Radiology, University Medical Center, Mainz, Germany
| | - Peter R Galle
- Department of Medicine I, University Medical Center, Mainz, Germany
| | - Jens U Marquardt
- Department of Medicine I, University Medical Center, Mainz, Germany
| | - Arndt Weinmann
- Department of Medicine I, University Medical Center, Mainz, Germany
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25
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Zhang XP, Gao YZ, Jiang YB, Wang K, Chen ZH, Guo WX, Shi J, Zhang YJ, Chen MS, Lau WY, Cheng SQ. A serological scoring system to predict lymph node metastasis in patients with hepatocellular carcinoma. HPB (Oxford) 2019; 21:335-344. [PMID: 30104175 DOI: 10.1016/j.hpb.2018.07.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Revised: 06/25/2018] [Accepted: 07/09/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Lymph node metastasis (LNM)has widely been recognized as a poor prognostic indicator for hepatocellular carcinoma (HCC) patients. Preoperative prediction of LNM is important for clinicians to decide on treatment. This study was designed to develop a simple and convenient system to predict LNM. METHODS Consecutive HCC patients who were suspected to have LNM were divided into a training, an internal validation and an external validation cohort. The receiver operating characteristic (ROC) analysis was used to determine the threshold value of the preoperative serological variables. A nomogram visualization system model was then established. RESULT Of the 287 patients, there were 31 patients who had LNM (10.8%), and 21 of 203 patients (10.3%) were in the training cohort and 10 of 84 patients (11.9%) in the internal validation cohort. Sixteen of 176 patients (9.1%) in the external validation cohort had LNM. The serological indices including neutrophil/lymphocyte rate, age, platelet, prothrombin time, and total protein, were included in the nomogram. The areas of the ROC curve were 0.846, 0.679 and 0.738 in predicting LNM in the training cohort, the internal validation cohort and the external validation cohort, respectively. CONCLUSION The scoring system constructed using the preoperative serological variables predicted LNM in HCC patients.
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Affiliation(s)
- Xiu-Ping Zhang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Yu-Zhen Gao
- Department of Molecular Diagnosis, Clinical Medical College, Yangzhou University, China
| | - Ya-Bo Jiang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Kang Wang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Zhen-Hua Chen
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wei-Xing Guo
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jie Shi
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Yao-Jun Zhang
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Min-Shan Chen
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wan Y Lau
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China; Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
| | - Shu-Qun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
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26
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Chen PC, Chiu NC, Su CW, Huang YH, Hou MC, Lin HC, Wu JC. Albumin-bilirubin grade may determine the outcomes of patients with very early stage hepatocellular carcinoma after radiofrequency ablation therapy. J Chin Med Assoc 2019; 82:2-10. [PMID: 30839396 DOI: 10.1097/jcma.0000000000000001] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND To assess long-term prognoses of patients with solitary hepatocellular carcinoma (HCC) < 2 cm (the Barcelona Clinic Liver Cancer, BCLC stage 0) after radiofrequency ablation (RFA). METHODS We retrospectively enrolled 271 patients with BCLC stage 0 HCC who had undergone RFA at Taipei Veterans General Hospital from 2002 to 2016. Factors determining poor overall survival (OS) and recurrence after RFA were analyzed by Cox proportional hazards model. RESULTS After a median follow-up duration of 43.4 months, 76 patients had died. The cumulative 5- and 10-year OS rates were 67.1% and 56.4%, respectively. Multivariate analysis disclosed age > 65 years (hazard ratio [HR] 1.608, 95% confidence interval, [CI] 1.015-2.545; p = 0.043), platelet count < 100,000/mm (HR 1.704, 95% CI 1.027-2.828; p = 0.039), and albumin-bilirubin (ALBI) grade 2 or 3 (HR 2.191, 95% CI 1.261-3.805; p = 0.005) were the independent risk factors predicting worse OS. One-hundred twelve patients had tumor recurrence after undergoing RFA. Multivariate analysis showed that ALBI grade 2 or 3 (HR 1.825, 95% CI 1.288-2.585; p = 0.001) was the only one independent risk factor associated with poor recurrence-free survival (RFS) after RFA. Most of the subgroup analyses also demonstrated that patients with ALBI grade 2 or 3 had poorer OS and RFS than those with ALBI grade 1. CONCLUSION For patients with BCLC stage 0 HCC, RFA could provide a long-term outcome with a 10-year overall survival rate of 56.4%. Moreover, the ALBI grade can discriminate prognosis in such patients.
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Affiliation(s)
- Po-Chun Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Nai-Chi Chiu
- Division of Gastrointestinal Radiology, Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Jaw-Ching Wu
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
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27
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Huo TI, Liu PH, Hsu CY. Staging and Restaging for Hepatocellular Carcinoma: Solution of Confusion? Hepatology 2019; 69:464-465. [PMID: 30353930 DOI: 10.1002/hep.30324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Affiliation(s)
- Teh-Ia Huo
- Department of Medicine, National Yang-Ming University School of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Po-Hong Liu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX
| | - Chia-Yang Hsu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
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28
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Shen J, He L, Li C, Wen T, Chen W, Lu C, Yan L, Li B, Yang J. Prognostic nomograms for patients with resectable hepatocelluar carcinoma incorporating systemic inflammation and tumor characteristics. Oncotarget 2018; 7:80783-80793. [PMID: 27811374 PMCID: PMC5348354 DOI: 10.18632/oncotarget.13038] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Accepted: 10/28/2016] [Indexed: 02/05/2023] Open
Abstract
Background The model to predict the prognosis of resectable hepatocelluar carcinoma (HCC) has not been determined. Methods Predictors were selected using Cox model. Nomograms were generated in the training set and validated in the validation set. The predictive ability of the nomogram was determined by concordance index and calibration curve. Results Independent factors for overall survival including alpha-fetoprotein level (hazard ratio (HR):1.292), tumor size (HR:1.092), tumor number (HR:1.472), microvascular invasion (HR:1.660), neutrophil to lymphocyte count ratio (NLR) (HR:1.428), major vascular invasion (HR:2.485) and satellite lesions(HR:1.392) were selected into the nomogram for survival. The c-index in the training set and validation set were 0.767 and 0.719, respectively, which were statistically higher than those of the four conventional staging systems.(Barcelona Clinic Liver Cancer: 0.644 and 0.609; the seventh American Joint Committee on Cancer: 0.678 and 0.674; Cancer of the Liver Italian Program: 0.692 and 0.648; Hong Kong Liver Cancer: 0.689 and 0.639, p < 0.001 for all). A nomogram for predicting 3- and 5-year recurrence free survival was generated with the c-index of 0.746 for the training set and 0.718 for the validation set, respectively. Conclusions We have generated nomograms predicting prognosis for HCC treated by hepatectomy with a higher predictive power.
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Affiliation(s)
- Junyi Shen
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Linye He
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Chuan Li
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Tianfu Wen
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Weixia Chen
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Changli Lu
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Lvnan Yan
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Bo Li
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Jiayin Yang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
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29
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Adhoute X, Penaranda G, Raoul JL, Bourlière M. Prediction of benefit after transarterial chemoembolization (TACE): Subclassifications or scoring systems? Liver Int 2018; 38:184. [PMID: 28695577 DOI: 10.1111/liv.13516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Affiliation(s)
- Xavier Adhoute
- Department of Hepato-Gastroenterology, Hôpital Saint-Joseph, Marseille, France
| | | | - Jean-Luc Raoul
- Department of Hepato-Gastroenterology and Digestive Oncology, Institut Paoli-Calmette, Marseille, France
| | - Marc Bourlière
- Department of Hepato-Gastroenterology, Hôpital Saint-Joseph, Marseille, France
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30
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Chen ZH, Hong YF, Chen X, Chen J, Lin Q, Lin J, Li X, Wen JY, Ruan DY, Dong M, Wei L, Wang TT, Lin ZX, Ma XK, Wu DH, Wu XY, Xu R. Comparison of five staging systems in predicting the survival rate of patients with hepatocellular carcinoma undergoing trans-arterial chemoembolization therapy. Oncol Lett 2018; 15:855-862. [PMID: 29403561 PMCID: PMC5780749 DOI: 10.3892/ol.2017.7419] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2017] [Accepted: 10/13/2017] [Indexed: 12/14/2022] Open
Abstract
The majority of patients with unresectable hepatocellular carcinoma (HCC) undergo trans-arterial chemoembolization (TACE). However, the prognosis of HCC remains poor. In the present study, five staging systems were compared to predict the survival rate of patients with HCC undergoing TACE treatment. A total of 220 patients with HCC were examined according to the model to estimate survival for hepatocellular carcinoma (MESH), hepatoma arterial embolization prognostic score (HAP), modified HAP (mHAP), performance status combined Japan Integrated Staging system (PSJIS) and tumor-node-metastasis (TNM) staging systems. The endpoints of the study were 3-month survival, 6-month survival, 1-year survival and overall survival (OS) rates. Receiver operating characteristic curve analysis indicated that the area under the curve of MESH, HAP, mHAP, PSJIS and TNM was 0.858, 0.728, 0.690, 0.688 and 0.699, respectively, in predicting 3-month survival rates; 0.822, 0.747, 0.720, 0.722 and 0.715, respectively, in predicting 6-month survival rates and 0.725, 0.664, 0.672, 0.645 and 0.654, respectively, in predicting 1-year survival rates. Discriminatory ability, homogeneity, monotonicity and prognostic stratification ability was evaluated using a likelihood ratio test and Akaike information criterion values among the five staging systems, and revealed that the MESH system was the optimal prognostic staging system for HCC. In conclusion, the results of the present study suggest that the MESH system is the most accurate prognostic staging system of 3-month survival, 6-month survival, 1-year survival and OS rates among the five systems analyzed in patients with HCC who have received TACE treatment.
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Affiliation(s)
- Zhan-Hong Chen
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
- Department of Medical Oncology of Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China
| | - Ying-Fen Hong
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Xiangwei Chen
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Jie Chen
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Qu Lin
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Jinxiang Lin
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Xing Li
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Jing-Yun Wen
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Dan-Yun Ruan
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Min Dong
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Li Wei
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Tian-Tian Wang
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Ze-Xiao Lin
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Xiao-Kun Ma
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Dong-Hao Wu
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Xiang-Yuan Wu
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Ruihua Xu
- Department of Medical Oncology of Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China
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31
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Elevation of MAP17 enhances the malignant behavior of cells via the Akt/mTOR pathway in hepatocellular carcinoma. Oncotarget 2017; 8:92589-92603. [PMID: 29190940 PMCID: PMC5696206 DOI: 10.18632/oncotarget.21506] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2016] [Accepted: 08/28/2017] [Indexed: 02/06/2023] Open
Abstract
MAP17, a small non-glycosylated membrane protein, was significantly up-regulated in hepatocellular carcinoma (HCC) tissues in our previous genome-wide microarray analysis. In this study, quantitative real-time RT-PCR and immunohistochemistry were applied to examine MAP17 mRNA and protein expression in primary HCC and matched peritumoral tissues. The disease-free survival (DFS) and overall survival (OS) was estimated using the Kaplan-Meier analysis. The expression of MAP17 was significantly higher in HCC tissues compared to the paired peritumoral tissues at both mRNA and protein levels. High MAP17 expression was positively correlated with gender, distant metastasis, early recurrence (≤ 2 year), and serum alpha-fetoprotein (all p < 0.05). Kaplan-Meier analysis showed that the DFS (p = 0.004) and OS (p = 0.013) in HCC patients with elevated expression of MAP17 were much worse than that in the low expression subgroup. High level of MAP17 was also significantly associated with a high probability of HCC early recurrence after surgical resection (p = 0.005). Cox regression analysis indicated MAP17 was an independent prognostic factor for DFS (HR, 1.710; 95% CI, 1.156-2.449, p = 0.012) and OS (HR, 1.743; 95% CI, 1.152-2.639, p = 0.009) in HCC. Silencing MAP17 significantly inhibited the proliferation, invasion and migration of HCC cells in vitro, and decreased the expression levels of Akt, p-Akt (Ser473), mTOR, p-mTOR (Ser2448) and MMP-9. Suggesting MAP17 was a novel diagnostic and prognostic biomarker for HCC patients and promoted HCC cell proliferation, invasion and migration via the Akt/mTOR pathway.
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Hsu CY, Liu PH, Hsia CY, Lee YH, Nagaria TS, Lee RC, Ho SY, Hou MC, Huo TI. A New Treatment-integrated Prognostic Nomogram of the Barcelona Clinic Liver Cancer System for Hepatocellular Carcinoma. Sci Rep 2017; 7:7914. [PMID: 28801646 PMCID: PMC5554253 DOI: 10.1038/s41598-017-08382-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Accepted: 07/10/2017] [Indexed: 12/18/2022] Open
Abstract
The nomogram of the Barcelona Clinic Liver Cancer (BCLC) has accurate outcome prediction. This study aims to propose a treatment-integrated nomogram derived from BCLC for patients with hepatocellular carcinoma (HCC). A total of 3,371 patients were randomly grouped into derivation (n = 2,247) and validation (n = 1,124) sets. Multivariate Cox proportional hazards model was used to generate the nomogram from tumor burden, cirrhosis, performance status (PS) and primary anti-cancer treatments. Concordance indices and calibration plots were used to evaluate the performance of nomogram. The derivation and validation sets had the same concordance index of 0.774 (95% confidence intervals: 0.717-0.826 and 0.656-0.874, respectively). In calibration plots, survival distributions predicted by the nomogram and observed by the Kaplan-Meier method were similar at 3- and 5-year for patients from derivation and validation sets. Validation group patients divided into 10 subgroups by the original and new treatment-integrated BCLC nomogram were used to evaluate the prognostic performance of integrating primary anti-cancer treatments. Compared to the nomogram of original BCLC system, the treatment-integrated nomogram of BCLC system had larger linear trend and likelihood ratio X2. In conclusion, based on the results of concordance index tests, integrating primary anti-cancer treatments into the BCLC system provides similar discriminatory ability.
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Affiliation(s)
- Chia-Yang Hsu
- Department of Medicine, Taipei Veterans General Hospital, Taipei: No 201, Sec. 2, Shipai Rd, Taipei, 112, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei: No 155, Sec. 2, Linong St, Taipei, 112, Taiwan.,Department of Internal Medicine, University of Nevada School of Medicine Reno, 1155 Mill Street, Reno, NV, 89502, USA
| | - Po-Hong Liu
- Department of Medicine, Taipei Veterans General Hospital, Taipei: No 201, Sec. 2, Shipai Rd, Taipei, 112, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei: No 155, Sec. 2, Linong St, Taipei, 112, Taiwan.,Harvard T.H. Chan School of Public Health, Boston: 677 Huntington Ave, Boston, MA, 02115, USA
| | - Cheng-Yuan Hsia
- Department of Surgery, Taipei Veterans General Hospital, Taipei: No 201, Sec. 2, Shipai Rd, Taipei, 112, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei: No 155, Sec. 2, Linong St, Taipei, 112, Taiwan
| | - Yun-Hsuan Lee
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei: No 155, Sec. 2, Linong St, Taipei, 112, Taiwan
| | - Teddy S Nagaria
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Building, 6th Floor, 1 King's College Cir, Toronto, Canada
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei: No 201, Sec. 2, Shipai Rd, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei: No 155, Sec. 2, Linong St, Taipei, 112, Taiwan
| | - Shu-Yein Ho
- Department of Medicine, Taipei Veterans General Hospital, Taipei: No 201, Sec. 2, Shipai Rd, Taipei, 112, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei: No 155, Sec. 2, Linong St, Taipei, 112, Taiwan
| | - Ming-Chih Hou
- Department of Medicine, Taipei Veterans General Hospital, Taipei: No 201, Sec. 2, Shipai Rd, Taipei, 112, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei: No 155, Sec. 2, Linong St, Taipei, 112, Taiwan
| | - Teh-Ia Huo
- Department of Medicine, Taipei Veterans General Hospital, Taipei: No 201, Sec. 2, Shipai Rd, Taipei, 112, Taiwan. .,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei: No 155, Sec. 2, Linong St, Taipei, 112, Taiwan. .,Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei: No 155, Sec. 2, Linong St, Taipei, 112, Taiwan.
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Ho SY, Liu PH, Hsu CY, Hsia CY, Lee YH, Lee RC, Huang YH, Lee FY, Hou MC, Tsai YJ, Huo TI. Prognostic role of noninvasive liver reserve markers in patients with hepatocellular carcinoma undergoing transarterial chemoembolization. PLoS One 2017; 12:e0180408. [PMID: 28672011 PMCID: PMC5495392 DOI: 10.1371/journal.pone.0180408] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2017] [Accepted: 06/15/2017] [Indexed: 02/08/2023] Open
Abstract
Background Various noninvasive liver reserve markers were proposed to indicate the severity of liver damage. However, the role and feasibility of these markers to predict the prognosis of patients with hepatocellular carcinoma (HCC) are unknown. We aimed to identify the prognostic role of the 8 currently used hepatic reserve markers in patients with HCC undergoing transarterial chemoembolization (TACE). Methods Between 2002 and 2013, a total of 881 patients with HCC undergoing TACE were prospectively identified and retrospectively analyzed. The baseline characteristics, tumor status and noninvasive markers were collected. Homogeneity and corrected Akaike information criteria (AICc) were compared between these markers. The Cox proportional hazards model was used to identify independent predictors of survival. Results Significant differences in survival distribution were found for albumin-bilirubin (ALBI) grade, Child-Turcotte-Pugh (CTP) class, Lok index, fibrosis index based on 4 factors (FIB-4), Göteborg University cirrhosis index (GUCI), cirrhosis discriminant index (CDI) and model for end-stage liver disease (MELD) score (all p values <0.05). Among these markers, the ALBI grade showed the highest homogeneity and lowest AICc value, indicating a better prognostic performance. Cox multivariate analysis confirmed that ALBI grade 2, ascites, serum alkaline phosphatase and α-fetoprotein level, tumor diameter, vascular invasion and performance status were significant independent prognostic predictors. The distribution of the ALBI score well correlated with baseline CTP and MLED scores. Conclusions Our data suggest that among the currently used liver reserve markers, ALBI grade may serve as an objective and feasible surrogate to predict the prognosis of HCC patients undergoing TACE.
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Affiliation(s)
- Shu-Yein Ho
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Po-Hong Liu
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America
| | - Chia-Yang Hsu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Internal Medicine, University of Nevada School of Medicine, Reno, Nevada, United States of America
| | - Cheng-Yuan Hsia
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yun-Hsuan Lee
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Rheun-Chuan Lee
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Fa-Yauh Lee
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Ming-Chih Hou
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Ya-Ju Tsai
- Renown Regional Medical Center, Reno, Nevada, United States of America
| | - Teh-Ia Huo
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan
- * E-mail:
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Lin Z, Cai YJ, Chen RC, Chen BC, Zhao L, Xu SH, Wang XD, Song M, Wu JM, Wang YQ, Zhou MT, Shi KQ. A microRNA expression profile for vascular invasion can predict overall survival in hepatocellular carcinoma. Clin Chim Acta 2017; 469:171-179. [DOI: 10.1016/j.cca.2017.03.026] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Revised: 03/21/2017] [Accepted: 03/28/2017] [Indexed: 12/11/2022]
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Adhoute X, Pénaranda G, Raoul JL, Edeline J, Blanc JF, Pol B, Campanile M, Perrier H, Bayle O, Monnet O, Beaurain P, Muller C, Castellani P, Le Treut YP, Bronowicki JP, Bourlière M. Barcelona clinic liver cancer nomogram and others staging/scoring systems in a French hepatocellular carcinoma cohort. World J Gastroenterol 2017; 23:2545-2555. [PMID: 28465639 PMCID: PMC5394518 DOI: 10.3748/wjg.v23.i14.2545] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2016] [Revised: 02/27/2017] [Accepted: 03/21/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To compare the performances of the Barcelona clinic liver cancer (BCLC) nomogram and others systems (BCLC, HKLC, CLIP, NIACE) for survival prediction in a large hepatocellular carcinoma (HCC) French cohort.
METHODS Data were collected retrospectively from 01/2007 to 12/2013 in five French centers. Newly diagnosed HCC patients were analyzed. The discriminatory ability, homogeneity ability, prognostic stratification ability Akaike information criterion (AIC) and C-index were compared among scoring systems.
RESULTS The cohort included 1102 patients, mostly men, median age 68 [60-74] years with cirrhosis (81%), child-Pugh A (73%), alcohol-related (41%), HCV-related (27%). HCC were multinodular (59%) and vascular invasion was present in 41% of cases. At time of HCC diagnosis BCLC stages were A (17%), B (16%), C (60%) and D (7%). First line HCC treatment was curative in 23.5%, palliative in 59.5%, BSC in 17% of our population. Median OS was 10.8 mo [4.9-28.0]. Each system distinguished different survival prognosis groups (P < 0.0001). The nomogram had the highest discriminatory ability, the highest C-index value. NIACE score had the lowest AIC value. The nomogram distinguished sixteen different prognosis groups. By classifying unifocal large HCC into tumor burden 1, the nomogram was less powerful.
CONCLUSION In this French cohort, the BCLC nomogram and the NIACE score provided the best prognostic information, but the NIACE could even help treatment strategies.
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Zhong JH, Peng NF, You XM, Ma L, Xiang X, Wang YY, Gong WF, Wu FX, Xiang BD, Li LQ. Tumor stage and primary treatment of hepatocellular carcinoma at a large tertiary hospital in China: A real-world study. Oncotarget 2017; 8:18296-18302. [PMID: 28407686 PMCID: PMC5392328 DOI: 10.18632/oncotarget.15433] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Accepted: 01/18/2017] [Indexed: 02/06/2023] Open
Abstract
The current clinical reality of tumor stages and primary treatments of hepatocellular carcinoma (HCC) is poorly understood. This study reviewed the distribution of tumor stages and primary treatment modalities among a large population of patients with primary HCC. Medical records of patients treated between January 2003 and October 2013 for primary HCC at our tertiary hospital in China were retrospectively reviewed. A total of 6241 patients were analyzed. The distribution of Barcelona Clinic Liver Cancer (BCLC) stages was as follows: stage 0/A, 28.9%; stage B, 16.2%; stage C, 53.6%; stage D, 1.3%. The distribution of Hong Kong Liver Cancer (HKLC) stages was as follows: stage I, 8.4%; stage IIa, 1.5%; stage IIb, 29.0%; stage IIIa, 10.0%; stage IIIb, 33.6%; stage IVa, 3.4%; stage IVb, 2.5%; stage Va, 0.2%; stage Vb, 11.4%. The most frequent therapy was hepatic resection for patients with BCLC-0/A/B disease, and transarterial chemoembolization for patients with BCLC-C disease. Both these treatments were the most frequent for patients with HKLC I to IIIb disease, while systemic chemotherapy was the most frequent first-line therapy for patients with HKLC IVa or IVb disease. The most frequent treatment for patients with HKLC Va/Vb disease was traditional Chinese medicine. In conclusion, Prevalences of BCLC-B and -C disease, and of HKLC I to IIIb disease, were relatively high in our patient population. Hepatic resection and transarterial chemoembolization were frequent first-line therapies.
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Affiliation(s)
- Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, China
| | - Ning-Fu Peng
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, China
| | - Xue-Mei You
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, China
| | - Liang Ma
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, China
| | - Xiao Xiang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China
| | - Yan-Yan Wang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China
| | - Wen-Feng Gong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, China
| | - Fei-Xiang Wu
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, China
| | - Bang-De Xiang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, China
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, China
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Zhong JH, Torzilli G, Xing H, Li C, Han J, Liang L, Zhang H, Dai SY, Li LQ, Shen F, Yang T. Controversies and evidence of hepatic resection for hepatocellular carcinoma. BBA CLINICAL 2016; 6:125-130. [PMID: 27761414 PMCID: PMC5067978 DOI: 10.1016/j.bbacli.2016.10.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/13/2016] [Revised: 10/06/2016] [Accepted: 10/10/2016] [Indexed: 02/07/2023]
Abstract
Symptoms of early hepatocellular carcinoma (HCC) often go unnoticed, so more than half of patients with primary HCC are diagnosed after their disease has already reached an intermediate or advanced stage, or after portal hypertension has appeared. While hepatic resection is widely recognized as a first-line therapy to treat very early or early HCC, its use in treating intermediate or advanced HCC or HCC involving portal hypertension remains controversial. Here we review PubMed-indexed literature covering the use of hepatic resection for such patients. The available evidence strongly suggests that, as a result of improvements in surgical techniques and perioperative care, hepatic resection can benefit many patients with intermediate or advanced HCC or with HCC associated with portal hypertension.
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Affiliation(s)
- Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Guido Torzilli
- Department of Surgery, Division of Hepatobiliary and General Surgery, Humanitas University, Humanitas Research Hospital-IRCCS, Rozzano, Milan, Italy
| | - Hao Xing
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jun Han
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Lei Liang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Han Zhang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Shu-Yang Dai
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
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Sang W, Chan SL, Chan AWH. Comments on "Proposal and validation of a new model to estimate survival for hepatocellular carcinoma patients". Eur J Cancer 2016; 68:203-205. [PMID: 27720569 DOI: 10.1016/j.ejca.2016.08.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Accepted: 08/25/2016] [Indexed: 11/18/2022]
Affiliation(s)
- Wei Sang
- Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People's Republic of China
| | - Stephen L Chan
- Department of Clinical Oncology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong; Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Anthony W H Chan
- Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.
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Carr BI, Guerra V, Giannini EG, Farinati F, Ciccarese F, Rapaccini GL, Di Marco M, Benvegnù L, Zoli M, Borzio F, Caturelli E, Masotto A, Trevisani F. A Liver Index and its Relationship to Indices of HCC Aggressiveness. JOURNAL OF INTEGRATIVE ONCOLOGY 2016; 5:178. [PMID: 28580457 PMCID: PMC5450974 DOI: 10.4172/2329-6771.1000178] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
A Hepatocellular (HCC) Aggressiveness Index was recently constructed, consisting of the sum of the scores for the 4 clinical parameters of maximum tumor size, multifocality, presence of portal vein thrombus and blood alphafetoprotein levels. It was observed that there was an association with several liver function tests. We have now formed a Liver Index from the 4 liver parameters with the highest hazard ratios with respect to HCC aggressiveness, namely: blood total bilirubin, gamma glutamyl transpeptidase (GGTP), albumin and platelet levels (cirrhosis surrogate). We found that the scores for the Liver Index related significantly to survival, but also to the Aggressiveness Index and to its individual HCC components as well as showing significant trends with the components. These results support the hypothesis that liver function is not only an important prognostic factor in HCC patients, but may also be involved in HCC biology and aggressiveness. Blood albumin, GGTP, albumin and platelet levels were used to create a Liver Index that related significantly to parameters of HCC aggressiveness.
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Affiliation(s)
- Brian I Carr
- Izmir Biomedicine and Genome Center, Dokuz Eylul University, Turkey and Lusaka Apex Medical University, Zambia
| | - Vito Guerra
- Department of Clinical Trials and Epidemiology, IRCCS de Bellis, Castellana Grotte, Italy
| | - Edoardo G Giannini
- Department of Internal Medicine, Gastroenterology Unit, University of Genoa, Italy
| | - Fabio Farinati
- Department of Surgical Science and Gastroenterology, Gastroenterology Unit, University of Padua, Italy
| | | | | | - Maria Di Marco
- Division of Medicine, Azienda Ospedaliera Bolognini, Seriate, Italy
| | - Luisa Benvegnù
- Department of Clinical and Experimental Medicine, Medical Unit, University of Padua, Italy
| | - Marco Zoli
- Department of Medical and Surgical Science, Internal Medicine Unit, Alma Mater Studiorum, University of Bologna, Italy
| | - Franco Borzio
- Department of Medicine, Internal Medicine and Hepatology Unit, Ospedale Fatebenefratelli, Milan, Italy
| | | | - Alberto Masotto
- Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Franco Trevisani
- Department of Medical Surgical Sciences, Medical Semiotics Unit, Alma Mater Studiorum, University of Bologna, Italy
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Utility of prognostic scoring systems in management of hepatocellular carcinoma. Eur J Cancer 2016; 68:206-207. [PMID: 27697407 DOI: 10.1016/j.ejca.2016.08.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Accepted: 08/25/2016] [Indexed: 01/31/2023]
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