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Sala M, Pascual S, Rota Roca MR, Matilla AM, Campos M, Delgado M, Ferrer MT, Montero JL, González-Santiago JM, Guerrero A, Aracil C, Rodríguez-Lope C, Romero-Gutiérrez M, Sogbe M, Vázquez-Rodríguez S, Olmo JF, Mínguez B, Cortés-García L, Vallejo-Senra N, Unceta PR, Clos A, Díaz-Bethencourt D, Sánchez AG, Castro RQ, Bustamante J, Perelló C, Urquijo Ponce JJ, Serra HA, Llamoza-Torres CJ, Montoliu S, Fernández-Marcos C, Guiberteau A, Hernández-Guerra M, Vergara M, Fernández-López AM, Valer López-Fando MP, Gutiérrez-García ML, Hernáez-Alsina T, Coll S, Cuyás B, Morillas MJ, Olmedo SR, Fernández-Bermejo M, Roget M, Ramos IC, Pacheco del Río G, Rifà R, Gacho PC, Barrio ML, Gómez-Rubio M, Peñas I, Serra I, Cachero A, Reig M, Giraldez Á, Guerrero M, Segarra JX, Lledó JL, Díaz-González Á, Delgado C, Iñarrairaegui M, Rodríguez-González MM, Lázaro M, Bermúdez-Ramos M, Lué A, Molina E, Macías-Rodríguez MA, Rodríguez M, Chiminazzo V, Varela M. Evolving epidemiology of HCC in Spain. JHEP Rep 2025; 7:101336. [PMID: 40248605 PMCID: PMC12005282 DOI: 10.1016/j.jhepr.2025.101336] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 01/20/2025] [Accepted: 01/22/2025] [Indexed: 04/19/2025] Open
Abstract
Background & Aims The epidemiological landscape of hepatocellular carcinoma (HCC) in Europe is evolving. This study aims to provide an updated description of the current epidemiology of liver cancer in Spain. Methods This multicenter prospective study collected demographic and clinical data on primary liver cancer between October 2022 and January 2023. We conducted descriptive and comparative analyses with data collected in 2008 and 2014. Results Of the 767 cases of primary liver cancer collected from 52 centers, 91% were diagnosed as HCC. The majority of patients were male (83.3%), average age 68 years, 80.7% had cirrhosis. The primary causes were alcohol (29.9% alone, 55% combined with other etiologies), liver disease related to metabolic syndrome (LDrMS, 23%) and hepatitis C (17.3%). Treatments included ablation (15.7%), systemic therapy (14.7%), and chemoembolization (14.6%). Data from 29 centers (n = 1,351) across three registries revealed a significant increase in LDrMS (from 4.9% to 24%) and HCC in non-cirrhotic livers (from 4.2% to 7.9%). Meanwhile, hepatitis C decreased sharply (from 43% to 17.5%). Alcohol-related cases remained stable. There was a slight increase in male patients and hypertension, diabetes, and obesity. Patients with cirrhosis diagnosed outside of screening programs presented with larger tumors and more advanced disease. This led to fewer evaluations for curative treatments. Conclusions Alcohol accounts for 30% of HCC cases and is the main etiology. The registry shows a decrease in hepatitis C-related HCC, an increase in LDrMS and HCC in non-cirrhotic livers. Surveillance was implemented in ∼80% of the recommended population. There is a need for improved screening and prevention strategies, particularly for alcohol abuse and LDrMS, to enhance HCC management. Impact and implications Our study showcases the involvement of numerous reference centers across Spain and examines over 1,300 patients to track the changing epidemiology of hepatocellular carcinoma (HCC) over 14 years. In patients with known liver cirrhosis, more than 80% of HCC diagnoses were made through screening leading to early-stage identification and curative treatment opportunities. Notably, there has been a shift in HCC etiology within the registries from hepatitis C to liver disease related to metabolic syndrome, with an increase in cases without cirrhosis. Findings indicate a need for the prevention and early detection of HCC, particularly focusing on alcohol and liver disease related to metabolic syndrome, along with greater involvement of health authorities, to improve the participation of at-risk patients in screening programs.
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Affiliation(s)
- Margarita Sala
- Unidad Hepatología, Servicio Digestivo, Hospital Universitari Doctor Josep Trueta, IDIBGI (Institut d’Investigació Biomédica de Girona), Girona, Spain
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Sonia Pascual
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Unidad Hepática, Servicio Digestivo, Hospital General Universitario Doctor Balmis, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABAL), Alicante, Spain
| | - Maria Rosa Rota Roca
- Servicio Aparato Digestivo, Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain
| | - Ana María Matilla
- Servicio Digestivo, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Marta Campos
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Grupo BCLC, Unidad de Oncología Hepática, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain
| | - Manuel Delgado
- Servicio de Aparato Digestivo, Hospital Universitario La Coruña, A Coruña, Spain
| | | | - José Luís Montero
- Unidad de Hepatología, Hospital Universitario Reina Sofía, Córdoba, Spain
| | - Jesús Manuel González-Santiago
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Servicio de Aparato Digestivo, Complejo Asistencial Universitario de Salamanca, Laboratorio de Hepatología Experimental y Vectorización de Fármacos (HEVEPHARM), IBSAL (Instituto de Investigación Biomédica de Salamanca), Salamanca, Spain
| | - Antonio Guerrero
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
| | - Carles Aracil
- Servicio Aparato Digestivo (Hepatología), Hospital Universitari Arnau de Vilanova, IRBLleida, Lleida, Spain
| | - Carlos Rodríguez-Lope
- Servicio de Gastroenterología y Hepatología, Grupo de Investigación Clínica y Traslacional en Enfermedades Digestivas, Instituto de Investigación Valdecilla (IDIVAL), Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Marta Romero-Gutiérrez
- Servicio de Aparato Digestivo (Sección Hepatología), Hospital Universitario de Toledo, Toledo, Spain
| | - Miguel Sogbe
- Liver Unit and HPB Oncology Area, Clínica Universidad de Navarra, Pamplona, Spain
| | - Sergio Vázquez-Rodríguez
- Department of Gastroenterology, Xerencia Xestion Integrada de Vigo, Research Group in Digestive Diseases, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain
| | - Javier Fuentes Olmo
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, Zaragoza, Spain
| | - Beatriz Mínguez
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Servicio de Hepatología, Hospital Universitario Vall d’Hebron, Vall d’Hebron Institute of Research (VHIR), Universitat Autónoma de Barcelona, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Luís Cortés-García
- Servicio de Aparato Digestivo, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Instituto de Investigación Sanitaria de Aragón (ISS Aragón), Spain
| | - Nicolau Vallejo-Senra
- Servicio Aparato Digestivo, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
| | | | - Ariadna Clos
- Servicio Aparato Digestivo, Sección Hepatología, Hospital Universitario Germans Trias i Pujol, Badalona, Spain
| | - Dácil Díaz-Bethencourt
- Servicio de Digestivo, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Santa Cruz de Tenerife, Spain
| | | | | | - Javier Bustamante
- Servicio de Gastroenterología y Hepatología, Osakidetza Basque Health Service, Ezkerraldea-Enkarterri-Cruces IHO, Cruces University Hospital, Barakaldo, Spain
| | - Christie Perelló
- Servicio de Aparato Digestivo, Hospital Universitario Puerta de Hierro, Madrid, Spain
| | | | | | - Camilo Julio Llamoza-Torres
- Sección de Hepatología, Servicio de Aparato Digestivo, Hospital Clínico Universitario Virgen de la Arrixaca, Laboratorio de Obesidad y Metabolismo, Instituto Murciano de Investigación Biosanitaria (IMIB), Murcia, Spain
| | - Silvia Montoliu
- Servicio de Aparato Digestivo, Hospital Universitari Joan XXIII, Institut d’Investigació Sanitaria Pere Virgili (IISPV), Tarragona, Spain
| | | | - Ana Guiberteau
- Servicio Aparato Digestivo, Unidad de Hepatología y Trasplante Hepático, Hospital Universitario de Badajoz, Badajoz, Spain
| | | | - Mercedes Vergara
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Unidad de Hepatología, Servicio de Digestivo, Parc Taulí Sabadell Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autónoma de Barcelona, Barcelona, Spain
| | | | | | | | | | - Susana Coll
- Servei Digestiu, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
| | - Berta Cuyás
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Servicio de Patología Digestiva, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain
| | | | | | | | - Mercè Roget
- Unidad de Hepatología, Servicio de Digestivo, Consorci Sanitari de Terrassa, Barcelona, Spain
| | - Irina Calvo Ramos
- Servicio de Aparato Digestivo, Hospital Universitario Doce de Octubre, Madrid, Spain
| | - Gemma Pacheco del Río
- Servicio de Medicina Digestiva, Hospital Universitario de La Ribera, Alzira, Valencia, Spain
| | - Raimon Rifà
- Servicio de Digestivo, Hospital Universitari Mútua de Terrassa, Terrassa, Barcelona, Spain
| | | | | | | | - Irene Peñas
- Servicio de Aparato Digestivo, Unidad de Hepatología, Hospital Universitario Río Hortega, Valladolid, Spain
| | - Isabel Serra
- Unidad Hepatología, Servicio Digestivo, Hospital Universitari Doctor Josep Trueta, IDIBGI (Institut d’Investigació Biomédica de Girona), Girona, Spain
| | - Alba Cachero
- Servicio Aparato Digestivo, Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain
| | - María Reig
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Grupo BCLC, Unidad de Oncología Hepática, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain
| | - Álvaro Giraldez
- Servicio de Digestivo, Hospital Virgen del Rocío, Sevilla, Spain
| | - Marta Guerrero
- Unidad de Hepatología, Hospital Universitario Reina Sofía, Córdoba, Spain
| | - José Xavier Segarra
- Servicio de Aparato Digestivo, Complejo Asistencial Universitario de Salamanca, Laboratorio de Hepatología Experimental y Vectorización de Fármacos (HEVEPHARM), IBSAL (Instituto de Investigación Biomédica de Salamanca), Salamanca, Spain
| | - José Luis Lledó
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
| | - Álvaro Díaz-González
- Servicio de Gastroenterología y Hepatología, Grupo de Investigación Clínica y Traslacional en Enfermedades Digestivas, Instituto de Investigación Valdecilla (IDIVAL), Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Carolina Delgado
- Servicio de Aparato Digestivo (Sección Hepatología), Hospital Universitario de Toledo, Toledo, Spain
| | - Mercedes Iñarrairaegui
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Liver Unit and HPB Oncology Area, Clínica Universidad de Navarra, Pamplona, Spain
| | - María Milagros Rodríguez-González
- Department of Gastroenterology, Xerencia Xestion Integrada de Vigo, Research Group in Digestive Diseases, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain
| | - María Lázaro
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, Zaragoza, Spain
| | - María Bermúdez-Ramos
- Servicio de Hepatología, Hospital Universitario Vall d’Hebron, Vall d’Hebron Institute of Research (VHIR), Universitat Autónoma de Barcelona, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Alberto Lué
- Servicio de Aparato Digestivo, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Instituto de Investigación Sanitaria de Aragón (ISS Aragón), Spain
| | - Esther Molina
- Servicio Aparato Digestivo, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
| | | | - Manuel Rodríguez
- Servicio de Aparato Digestivo, Sección de Hepatología, Hospital Universitario Central de Asturias, IUOPA (Instituto Universitario de Oncología de Principado de Asturias), ISPA (Instituto de Investigación Sanitaria del Principado de Asturias), FINBA (Fundación para la Investigación y la Innovación Biosanitaria del Principado de Asturias), Universidad de Oviedo, Oviedo, Spain
| | - Valentina Chiminazzo
- Plataforma de Bioestadística y Epidemiología, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
| | - María Varela
- Servicio de Aparato Digestivo, Sección de Hepatología, Hospital Universitario Central de Asturias, IUOPA (Instituto Universitario de Oncología de Principado de Asturias), ISPA (Instituto de Investigación Sanitaria del Principado de Asturias), FINBA (Fundación para la Investigación y la Innovación Biosanitaria del Principado de Asturias), Universidad de Oviedo, Oviedo, Spain
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Sharafeldin MA, Suef RA, Mousa AA, Ziada DH, Farag MMS. Serum miRNA-101 expression signature as non-invasive diagnostic biomarker for Hepatitis C virus-associated hepatocellular carcinoma in Egyptian patients. Sci Rep 2025; 15:645. [PMID: 39753619 PMCID: PMC11698908 DOI: 10.1038/s41598-024-81207-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Accepted: 11/25/2024] [Indexed: 01/06/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally due to HCC late diagnosis and limited treatment options. MiRNAs (miRNAs) emerged as potential biomarkers for various diseases, including HCC. However, the value of miRNA-101 as a serum biomarker for HCV-induced HCC has not been fully investigated. Our study aims to investigate the miRNA-101 differential expression in Egyptian HCV-induced HCC patients' serum versus HCV liver cirrhosis (LC) as prospective diagnostic biomarkers compared to alpha-fetoprotein (AFP). Blood samples were collected for clinical chemistry profile, liver function, and serum AFP investigations. The serum miR-101 expression levels were evaluated using real-time quantitative PCR (RT-qPCR) in 100 Egyptian subjects: 40 HCV-induced HCC, 40 HCV-induced cirrhosis, and 20 healthy controls. HCC patients showed significantly higher TB, DB, and AFP levels than those cirrhosis and control groups, whereas ALB and Total Protein exhibited significantly reduced levels. AFP sensitivity and specificity in differentiating HCC reported 60 and 67%, respectively, at the cut-off values of 7ng/dl. miR-101 shows fold change upregulation in HCC patients (P < 0.0001) compared to LC and control groups. ROC curve demonstrated miR-101 (AUC) of 0.9556, sensitivity 92.5%, and specificity 97.5%, highlighting the miR-101 diagnostic potential as a biomarker for HCC detection. Elevated miR-101 levels in HCC are significantly correlated with a higher number and larger size of focal lesions, advanced BCLC staging, and Child-Pugh score. These findings highlight the utility of miR-101 as a predictive and diagnostic non-invasive biomarker for HCV-related HCC from cirrhotic populations. More research is warranted to validate the clinical validity of miR-101 and explore underlying mechanisms in HCV-HCC progression.
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Affiliation(s)
- Mostafa A Sharafeldin
- Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Cairo, 11884, Egypt
| | - Reda A Suef
- Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Cairo, 11884, Egypt.
| | - Adel A Mousa
- Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Cairo, 11884, Egypt
| | - Dina H Ziada
- Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Mohamed M S Farag
- Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Cairo, 11884, Egypt.
- Biomedical Research Department, Armed Forces College of Medicine (AFCM), Cairo, Egypt.
- The Regional Centre for Mycology and Biotechnology, Al-Azhar University, Cairo, Egypt.
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Wong K, Davis S, Partridge G, McWhinney B, Mott N, Klages P, Bain R, Cheung N. Stability of doxorubicin in radiocontrast medium for use in conventional transarterial chemo-embolisation procedures. J Med Imaging Radiat Oncol 2024; 68:434-439. [PMID: 38437190 DOI: 10.1111/1754-9485.13628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 02/21/2024] [Indexed: 03/06/2024]
Affiliation(s)
- Kennedy Wong
- Department of Medical Imaging, Royal Brisbane Women's Hospital, Brisbane, Queensland, Australia
| | - Samuel Davis
- Department of Medical Imaging, Royal Brisbane Women's Hospital, Brisbane, Queensland, Australia
| | - Grant Partridge
- Cancer Care Services, Royal Brisbane Women's Hospital, Brisbane, Queensland, Australia
| | - Brett McWhinney
- Department of Chemical Pathology, Pathology Queensland, Royal Brisbane Women's Hospital, Brisbane, Queensland, Australia
| | - Nigel Mott
- Department of Medical Imaging, Royal Brisbane Women's Hospital, Brisbane, Queensland, Australia
| | - Paul Klages
- Cancer Care Services, Royal Brisbane Women's Hospital, Brisbane, Queensland, Australia
| | - Roger Bain
- Department of Medical Imaging, Royal Brisbane Women's Hospital, Brisbane, Queensland, Australia
| | - Nicholas Cheung
- Department of Medical Imaging, Launceston General Hospital, Launceston, Tasmania, Australia
- University of Tasmania, College of Health and Medicine, Hobart, Tasmania, Australia
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Renzulli M, Peta G, Vasuri F, Marasco G, Caretti D, Bartalena L, Spinelli D, Giampalma E, D'Errico A, Golfieri R. Standardization of conventional chemoembolization for hepatocellular carcinoma. Ann Hepatol 2021; 22:100278. [PMID: 33129978 DOI: 10.1016/j.aohep.2020.10.006] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 10/19/2020] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Conventional transarterial chemoembolization (cTACE) has several limitations due to the lack of standardization. The aim of this study was to evaluate the chemical and physical characteristics and behaviors over time of emulsions for cTACE and to assess intra- and inter-operator variabilities in the preparation processes. MATERIALS AND METHODS This in vitro study involved evaluation of emulsions for cTACE prepared using two methods: water-in-oil (WiO) and chemotherapeutic-in-oil (CiO). Three emulsions were prepared with each method and obtained after 20, 50, and 100 pumping exchanges. A drop from each final mixture was analyzed via light microscopy (time 1) and after 5, 10, 15, and 20min since the end of preparation. After 20min, all preparations were re-mixed and new drops were re-evaluated. The intra- and inter-operator variabilities were analyzed. RESULTS The mean droplet diameter decreased non-significantly when the number of pumping exchanges increased and increased significantly over time for both WiO and CiO. The droplets returned to their initial diameters after re-mixing. There were no significant differences in the intra- and inter-operator variabilities (P>0.01). CONCLUSIONS Any interventional radiologist, regardless of their experience, may prepare these emulsions. These data may represent a set of instructions to standardize cTACE.
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Affiliation(s)
- Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy.
| | - Giuliano Peta
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | - Francesco Vasuri
- Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | - Giovanni Marasco
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | - Daniele Caretti
- "Toso Montanari" Industrial Chemistry Department, University of Bologna, Bologna, Italy
| | - Laura Bartalena
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | - Daniele Spinelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | | | - Antonietta D'Errico
- Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | - Rita Golfieri
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
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Granito A, Facciorusso A, Sacco R, Bartalena L, Mosconi C, Cea UV, Cappelli A, Antonino M, Modestino F, Brandi N, Tovoli F, Piscaglia F, Golfieri R, Renzulli M. TRANS-TACE: Prognostic Role of the Transient Hypertransaminasemia after Conventional Chemoembolization for Hepatocellular Carcinoma. J Pers Med 2021; 11:1041. [PMID: 34683182 PMCID: PMC8539564 DOI: 10.3390/jpm11101041] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 10/12/2021] [Accepted: 10/13/2021] [Indexed: 02/07/2023] Open
Abstract
The aim of the present study was to correlate laboratory data and postprocedural parameters after conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC) with the radiological response. The study consisted of a retrospective analysis of prospectively collected data from 70 consecutive patients who underwent cTACE. Laboratory parameters were assessed daily after cTACE and compared to pretreatment values. Post-treatment radiological response was assessed using mRECIST at one month from cTACE, and factors associated with treatment response (complete and objective response) were assessed by logistic regression analysis. The optimal cutoff points in predicting the complete response of target lesions were a 52% ALT and a 46% AST increase after cTACE compared to the pre-treatment values. Using multivariate analyses, >46% AST and >52% ALT increases with respect to the pre-treatment value were significantly correlated with the objective response (p = 0.03 and p = 0.04, respectively) and the complete response (p = 0.02 and p = 0.02, respectively). No patients experienced liver function deterioration after cTACE, and no specific treatment was required. This study showed that post-treatment transient transaminase elevation was predictive of objective response to superselective cTACE in clinical practice, representing a simple tool to guide treatment strategy of HCC patients in a tailored approach.
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Affiliation(s)
- Alessandro Granito
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40137 Bologna, Italy; (A.G.); (F.T.); (F.P.)
| | - Antonio Facciorusso
- Gastroenterology and Digestive Endoscopy, Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy; (A.F.); (R.S.); (U.V.C.); (M.A.)
| | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy, Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy; (A.F.); (R.S.); (U.V.C.); (M.A.)
| | - Laura Bartalena
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40137 Bologna, Italy; (L.B.); (C.M.); (A.C.); (F.M.); (N.B.); (R.G.)
| | - Cristina Mosconi
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40137 Bologna, Italy; (L.B.); (C.M.); (A.C.); (F.M.); (N.B.); (R.G.)
| | - Ugo Vittorio Cea
- Gastroenterology and Digestive Endoscopy, Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy; (A.F.); (R.S.); (U.V.C.); (M.A.)
| | - Alberta Cappelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40137 Bologna, Italy; (L.B.); (C.M.); (A.C.); (F.M.); (N.B.); (R.G.)
| | - Matteo Antonino
- Gastroenterology and Digestive Endoscopy, Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy; (A.F.); (R.S.); (U.V.C.); (M.A.)
| | - Francesco Modestino
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40137 Bologna, Italy; (L.B.); (C.M.); (A.C.); (F.M.); (N.B.); (R.G.)
| | - Nicolò Brandi
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40137 Bologna, Italy; (L.B.); (C.M.); (A.C.); (F.M.); (N.B.); (R.G.)
| | - Francesco Tovoli
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40137 Bologna, Italy; (A.G.); (F.T.); (F.P.)
| | - Fabio Piscaglia
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40137 Bologna, Italy; (A.G.); (F.T.); (F.P.)
| | - Rita Golfieri
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40137 Bologna, Italy; (L.B.); (C.M.); (A.C.); (F.M.); (N.B.); (R.G.)
| | - Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40137 Bologna, Italy; (L.B.); (C.M.); (A.C.); (F.M.); (N.B.); (R.G.)
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Reig M, Forner A, Ávila MA, Ayuso C, Mínguez B, Varela M, Bilbao I, Bilbao JI, Burrel M, Bustamante J, Ferrer J, Gómez MÁ, Llovet JM, De la Mata M, Matilla A, Pardo F, Pastrana MA, Rodríguez-Perálvarez M, Tabernero J, Urbano J, Vera R, Sangro B, Bruix J. Diagnosis and treatment of hepatocellular carcinoma. Update of the consensus document of the AEEH, AEC, SEOM, SERAM, SERVEI, and SETH. Med Clin (Barc) 2021; 156:463.e1-463.e30. [PMID: 33461840 DOI: 10.1016/j.medcli.2020.09.022] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 09/12/2020] [Accepted: 09/15/2020] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver neoplasm and one of the most common causes of death in patients with cirrhosis of the liver. In parallel, with recognition of the clinical relevance of this cancer, major new developments have recently appeared in its diagnosis, prognostic assessment and in particular, in its treatment. Therefore, the Spanish Association for the Study of the Liver (AEEH) has driven the need to update the clinical practice guidelines, once again inviting all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document: Spanish Society for Liver Transplantation (SETH), Spanish Society of Diagnostic Radiology (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Association of Surgeons (AEC) and Spanish Society of Medical Oncology (SEOM). The clinical practice guidelines published in 2016 and accepted as National Health System Clinical Practice Guidelines were taken as the reference documents, incorporating the most important recent advances. The scientific evidence and the strength of the recommendation is based on the GRADE system.
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Affiliation(s)
- María Reig
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España
| | - Alejandro Forner
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España
| | - Matías A Ávila
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Programa de Hepatología, Centro de Investigación Médica Aplicada, Universidad de Navarra-IDISNA, Pamplona, España
| | - Carmen Ayuso
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Servicio de Radiodiagnóstico, Hospital Clínic Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Beatriz Mínguez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Servicio de Hepatología, Hospital Universitario Vall d́Hebron, Grupo de Investigación en Enfermedades Hepáticas (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universidad Autónoma de Barcelona. Barcelona, España
| | - María Varela
- Sección de Hepatología, Servicio de Aparato Digestivo, Hospital Universitario Central de Asturias. Oviedo, España
| | - Itxarone Bilbao
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Servicio de Cirugía Hepatobiliopancreática y Trasplantes Digestivos, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona. Barcelona, España
| | - José Ignacio Bilbao
- Unidad de Radiología Vascular e Intervencionista, Departamento de Radiodiagnóstico, Clínica Universidad de Navarra, Pamplona, España
| | - Marta Burrel
- Servicio de Radiodiagnóstico, Hospital Clínic Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Javier Bustamante
- Servicio de Gastroenterología y Hepatología, Sección de Hepatología y Trasplante, Hospital Universitario de Cruces, Baracaldo, España
| | - Joana Ferrer
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Cirugía Hepatobiliopancreática, Hospital Clínic, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Miguel Ángel Gómez
- Unidad de Cirugía Hepatobiliopancreática y Trasplantes, Hospital Universitario Virgen del Rocío, Sevilla, España
| | - Josep María Llovet
- Grupo de Investigación Traslacional en Oncología Hepática, Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Manuel De la Mata
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Unidad Clínica de Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, España
| | - Ana Matilla
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Sección de Hepatología, Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Madrid, España
| | - Fernando Pardo
- Servicio de Cirugía Hepatobiliopancreática y Trasplante, Clínica Universidad de Navarra, Pamplona, España
| | - Miguel A Pastrana
- Servicio de Radiodiagnóstico, Hospital Universitario Puerta de Hierro, Universidad Autónoma de Madrid, Madrid, España
| | - Manuel Rodríguez-Perálvarez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Unidad Clínica de Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, España
| | - Josep Tabernero
- Servicio de Oncología Médica, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona, Barcelona, España
| | - José Urbano
- Unidad de Radiología Vascular e Intervencionista, Servicio de Radiodiagnóstico, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, España
| | - Ruth Vera
- Servicio de Oncología Médica, Complejo hospitalario de Navarra, Navarrabiomed-IDISNA, Pamplona, España
| | - Bruno Sangro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Unidad de Hepatología y Área de Oncología HBP, Clínica Universidad de Navarra-IDISNA, Pamplona, España.
| | - Jordi Bruix
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
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Yen YH, Cheng YF, Wang JH, Lin CC, Chen CH, Wang CC. Adherence to the modified Barcelona Clinic Liver Cancer guidelines: Results from a high-volume liver surgery center in East Asias. PLoS One 2021; 16:e0249194. [PMID: 33765059 PMCID: PMC7993871 DOI: 10.1371/journal.pone.0249194] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 03/15/2021] [Indexed: 02/07/2023] Open
Abstract
Background and aims The Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely applied staging system for hepatocellular carcinoma (HCC) and is recommended for treatment allocation and prognostic prediction. The BCLC guidelines were modified in 2018 to indicate that Child-Pugh A without any ascites is essential for all stages except stage D. This study sought to provide a description of patients with HCC treated at a high-volume liver surgery center in Taiwan where referral is not needed and all treatment modalities are available and reimbursed by the National Health Insurance program. As such, certain variables that could modulate treatment decisions in clinical practice, including financial constraints, the availability of treatment procedures, and the expertise of the hospital, could be excluded. The study further sought to evaluate the adherence to the modified BCLC guidelines. Methods This was a retrospective study with prospectively collected data. 1801 consecutive patients with de novo HCC were enrolled through our institution from 2011–2017. Results There were 302 patients with stage 0, 783 with stage A, 242 with stage B, 358 with stage C, and 116 with stage D HCC. Treatment adhering to the modified BCLC guidelines recommendations was provided to 259 (85.8%) stage 0 patients, 606 (77.4%) stage A patients, 120 (49.6%) stage B patients, 93 (26.0%) stage C patients, and 83 (71.6%) stage D patients. Conclusions We reported treatment adhering to the modified BCLC guidelines at a high-volume liver surgery center in Taiwan. We found that non-adherence to the modified BCLC staging system was common in treating stage B and C patients.
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Affiliation(s)
- Yi-Hao Yen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
- * E-mail:
| | - Yu-Fan Cheng
- Department of Diagnostic Radiology, Liver Transplantation Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chih-Che Lin
- Department of Surgery, Liver Transplantation Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chih-Chi Wang
- Department of Surgery, Liver Transplantation Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
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Zeng Z, Cao Z, Tang Y. Identification of diagnostic and prognostic biomarkers, and candidate targeted agents for hepatitis B virus-associated early stage hepatocellular carcinoma based on RNA-sequencing data. Oncol Lett 2020; 20:231. [PMID: 32968453 PMCID: PMC7499982 DOI: 10.3892/ol.2020.12094] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 07/15/2020] [Indexed: 02/07/2023] Open
Abstract
Primary liver cancer is a rapidly progressing neoplasm with high morbidity and mortality rates. The present study aimed to identify potential diagnostic and prognostic biomarkers, and candidate targeted agents for hepatitis B virus (HBV)-associated early stage hepatocellular carcinoma (HCC). The gene expression profiles were extracted from the Gene Expression Omnibus database. Differentially expressed genes (DEGs), hub genes and the enrichment of signaling pathways were filtered out via a high-throughput sequencing method. The association between hub genes and the effects of the abnormal expression of hub genes on the rate of genetic variation, overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS) and disease-free survival (DSS) of patients with HCC, as well as pathological stage and grade, were analyzed using different databases. A total of 1,582 DEGs were identified. Gene Ontology analysis revealed that the DEGs were mainly involved in the ‘oxidation-reduction process’, ‘steroid metabolic process’, ‘metabolic process’ and ‘fatty acid beta-oxidation’. Enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways revealed that the DEGs were mainly associated with ‘metabolic pathways’, ‘PPAR signaling pathway’, ‘fatty acid degradation’ and the ‘cell cycle’. A total of 8 hub genes were extracted. Additionally, the abnormal expression levels of hub genes were closely associated with the OS, RFS, PFS and DSS of patients, the pathological stage and the grade. Furthermore, abnormal expression levels of the 8 hub genes were found in >30% of all samples. Several small molecular compounds that may reverse the altered DEGs were identified based on Connectivity Map analysis, including phenoxybenzamine, GW-8510, resveratrol, 0175029-0000 and daunorubicin. In conclusion, the dysfunction of fat metabolic pathways, the cell cycle, oxidation-reduction processes and viral carcinogenesis may serve critical roles in the occurrence of HBV-associated early stage HCC. The identified 8 hub genes may act as robust biomarkers for diagnosis and prognosis. Some small molecular compounds may be promising targeted agents against HBV-associated early stage HCC.
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Affiliation(s)
- Zhili Zeng
- Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Zebiao Cao
- Department of Endocrinology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Ying Tang
- Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China.,Department of Oncology, Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
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Calandri M, Gazzera C, Giurazza F, Yevich S, Strazzarino GA, Brino J, Marra P, Contegiacomo A, Bargellini I, Cariati M, Fonio P, Veltri A. Oligometastatic Colorectal Cancer Management: A Survey of the Italian College of Interventional Radiology. Cardiovasc Intervent Radiol 2020; 43:1474-1483. [PMID: 32449016 DOI: 10.1007/s00270-020-02516-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2019] [Accepted: 05/02/2020] [Indexed: 12/17/2022]
Abstract
AIM European Society for Medical Oncology (ESMO) and National Comprehensive Cancer Network guidelines (NCCN) have recently included interventional procedures among the standard treatments for the management of colorectal cancer (CRC) oligometastatic disease (OMD). This study overviews the practice of Interventional Radiology (IR) in Italian centers. METHODS A practice focused questionnaire on locoregional treatments of CRC-OMD was submitted to all Italian IR centers to assess practice patterns. RESULTS Thirty-three IR centers completed the questionnaire. The majority reported practice was established within a tumor board (97%), which included input from hepatobiliary surgery (94%). When considering the number of percutaneous ablation and liver-directed trans-arterial therapies performed for all tumor types, 33.5% and 13.4% were performed to specifically treat CRC-OMD. Lung ablations for CRC OMD were performed in 45.5% of centers. Regarding liver ablation, The most common technology was the microwave ablation (68.1%), which was typically performed under US guidance (78%) with conscious sedation used as the most common anaesthesia method (81%). While indication for percutaneous IR treatments was heterogeneous, 51% were performed in combination with chemotherapy in unresectable OMD. Despite new ESMO and NCCN guidelines, 59% of centers did not subjectively appreciate any change in the perception of IR treatments by other specialists; however, 63%of respondents believe that IR will have a more relevant role in the CRC-OMD management in the future. CONCLUSION CRC-OMD treatment represents a relevant part of the everyday clinical practice of the IR Italian centers with promising future prospects. Heterogeneity persists in clinical indications, requiring more robust evidence to set indications and to diffuse clinical applications.
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Affiliation(s)
- Marco Calandri
- Department of Oncology, University of Torino, Regione Gonzole 10, Orbassano, TO, Italy.
- Radiology Unit, A.O.U. San Luigi Gonzaga Di Orbassano, Regione Gonzole 10, Orbassano, TO, Italy.
| | - Carlo Gazzera
- Radiology Unit, A.O.U. Città Della Salute E Della Scienza, Presidio Molinette, Via Genova 3, Torino, TO, Italy
| | - Francesco Giurazza
- Vascular and Interventional Radiology Department, Cardarelli Hospital, Via Cardarelli 9, Napoli, Italy
| | - Steven Yevich
- Division of Diagnostic Imaging, Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Giulio Antonino Strazzarino
- Radiology Unit, A.O.U. Città Della Salute E Della Scienza, Presidio Molinette, Via Genova 3, Torino, TO, Italy
| | - Jacopo Brino
- Radiology Unit, A.O.U. San Luigi Gonzaga Di Orbassano, Regione Gonzole 10, Orbassano, TO, Italy
| | - Paolo Marra
- Radiology Department, IRCCS Ospedale San Raffaele E Università Vita-Salute, Via Olgettina 60, Milan, Italy
| | - Andrea Contegiacomo
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00136, Rome, Italy
| | - Irene Bargellini
- Department of Interventional Radiology, Pisa University Hospital, Pisa, Italy
| | - Maurizio Cariati
- Diagnostic-Therapeutic Advanced Technology Department, ASST Santi Paolo E Carlo, Via Pio II 3, 20153, Milan, Italy
| | - Paolo Fonio
- Radiology Unit, A.O.U. Città Della Salute E Della Scienza, Presidio Molinette, Via Genova 3, Torino, TO, Italy
- Department of Surgical Sciences, University of Torino, Via Genova 3, Torino, Italy
| | - Andrea Veltri
- Department of Oncology, University of Torino, Regione Gonzole 10, Orbassano, TO, Italy
- Radiology Unit, A.O.U. San Luigi Gonzaga Di Orbassano, Regione Gonzole 10, Orbassano, TO, Italy
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Only one-third of hepatocellular carcinoma cases are diagnosed via screening or surveillance: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2020; 32:406-419. [PMID: 31490419 DOI: 10.1097/meg.0000000000001523] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND/OBJECTS Early hepatocellular carcinoma diagnosis is associated with better long-term survival. Studies of at-risk patients who are monitored in routine practice have reported an overall adherence rate to hepatocellular carcinoma screening/surveillance of approximately 60% and suboptimal diagnostic efficacy of the current screening/surveillance tools. However, it is unclear how many hepatocellular carcinoma patients were actually diagnosed via screening/surveillance given these obstacles. Therefore, via a systematic review of PubMed and Scopus databases from 2000 to 2019, we aimed to identify the proportion of patients with hepatocellular carcinoma diagnosed via screening/surveillance in routine practice. METHODS We included original research articles of studies of patients already diagnosed with hepatocellular carcinoma that reported the proportion of hepatocellular carcinoma diagnosed via screening/surveillance. RESULTS The study included 60 studies and 50 554 hepatocellular carcinoma cases. The pooled proportion of hepatocellular carcinoma diagnosed by screening/surveillance was 37% (95% confidence interval: 31%-44%) and differed by geographic region (North America/Asia/Europe/Oceania/Africa/South America, 31%/42%/41%/30%/29%/47%, P = 0.017, respectively) and by surveillance interval (<12 months 39% vs. 12 months 19%, P < 0.01) but not by disease etiology, cirrhosis status, clinical setting, practice setting, hepatocellular carcinoma diagnosis period, or surveillance method. CONCLUSION Globally, hepatocellular carcinoma was diagnosed via screening/surveillance in less than half of the patients (37%) regardless of healthcare setting or liver disease etiology and without improvement over time despite several recent guideline updates. Research is needed to understand the barriers to screening/surveillance to include medical as well as social and cultural influences.
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Crespo J, Andrade RJ. Shadows in the current management of hepatocellular carcinoma in Spain - An embarrassing truth. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2019; 111:727-730. [PMID: 31566408 DOI: 10.17235/reed.2019.6594/2019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deaths worldwide. Up to 80% of patients with HCC have concomitant cirrhosis as a result of hepatitis B or C virus, alcohol abuse, or non-alcoholic steatohepatitis.
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Affiliation(s)
- Javier Crespo
- Servicio Aparato Digestivo, Hospital Universitario Marqués de Valdecilla, 39002
| | - Raúl J Andrade
- Servicio de Aparato Digestivo, Hospital Universitario Virgen de la Victoria.
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Sangiovanni A, Triolo M, Iavarone M, Forzenigo LV, Nicolini A, Rossi G, La Mura V, Colombo M, Lampertico P. Multimodality treatment of hepatocellular carcinoma: How field practice complies with international recommendations. Liver Int 2018; 38:1624-1634. [PMID: 29791968 DOI: 10.1111/liv.13888] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Accepted: 05/12/2018] [Indexed: 02/13/2023]
Abstract
BACKGROUND Management of hepatocellular carcinoma (HCC) is framed within standardized protocols released by Scientific Societies, whose applicability and efficacy in field practice need refining. AIM We evaluated the applicability and effectiveness of guidelines for the treatment of HCC of the American Association for the Study of the Liver (AASLD). METHODS 370 consecutive cirrhotic patients with de novo HCC in different stages, 253 BCLC A, 66 BCLC B, 51 BCLC C received treatment through a multidisciplinary team (MDT) decision and were followed until death or end of follow-up. RESULTS Treatment was adherent to AASLD recommendations in 205 (81%) BCLC A patients, 36 (54%) BCLC B, and 27 (53%) BCLC C. Radiological complete response was achieved in 165 (45%) patients after the first-line treatment, in 22 (19%) after a second-line and in 9 (23%) after a third-line treatment. Adherence to AASLD recommendation allowed a lower yearly mean mortality rate in BCLC A patients compared with other treatment (5.0% vs 10.4% P = .004), whereas upward treatment stage migration compared with the standard of care was associated with reduced yearly mortality in BCLC B (8.6% vs 20.7%, P = .029) and BCLC C (42.6% vs 59.0%, P = .04) patients. CONCLUSIONS HCC multimodality treatment including other than first-line therapy is common in clinical practice and impact on the achievement of complete response. Personalized treatment was able to provide survival benefits to patients whose profile is not accounted for by international recommendations, which need to be amended.
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Affiliation(s)
- Angelo Sangiovanni
- Division of Gastroenterology and Hepatology, CRC "A.M. and A. Migliavacca" Center for the study of Liver Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Michela Triolo
- Division of Internal Medicine, Policlinico S. Donato, University of Milan, San Donato Milanese, Italy
| | - Massimo Iavarone
- Division of Gastroenterology and Hepatology, CRC "A.M. and A. Migliavacca" Center for the study of Liver Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Laura V Forzenigo
- Division of Radiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Antonio Nicolini
- Division of Interventional Radiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Giorgio Rossi
- Division of Surgery and Liver Transplant, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Vincenzo La Mura
- Internal Medicine Hemostasis and Thrombosis Division, Biomedical Sciences for Health Department, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Massimo Colombo
- Department of Medicine and Hepatology, Humanitas Clinical and Research Center, Rozzano, Italy
| | - Pietro Lampertico
- Division of Gastroenterology and Hepatology, CRC "A.M. and A. Migliavacca" Center for the study of Liver Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
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Mancebo A, Varela M, González-Diéguez ML, Navascués CA, Cadahía V, Mesa-Álvarez A, Rodrigo L, Rodríguez M. Incidence and risk factors associated with hepatocellular carcinoma surveillance failure. J Gastroenterol Hepatol 2018; 33:1524-1529. [PMID: 29384236 DOI: 10.1111/jgh.14108] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2017] [Revised: 12/21/2017] [Accepted: 01/18/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM Surveillance for hepatocellular carcinoma (HCC) intends to detect tumors at an early stage to improve survival. The study aims were to assess the frequency and risk factors associated with HCC surveillance failure. METHODS The study analyzed data from 188 consecutive patients diagnosed with HCC within a surveillance program conducted among 1,242 cirrhotic patients and based on ultrasonography and alpha-fetoprotein (AFP) testing every 3 or 6 months. Program failure was defined as the detection of HCC exceeding the Milan criteria. Variables recorded at entry into the program, during follow-up and at HCC diagnosis, were analyzed. RESULTS At diagnosis, 50 (26.6%) HCC tumors were beyond the Milan criteria. In univariate analysis, Child-Pugh B at entry (P = 0.03), development of complications of portal hypertension before tumor diagnosis (P = 0.03), and failure to complete the prior screening round (P = 0.02), Child-Pugh B/C (P = 0.001) and AFP ≥ 100 ng/mL (P = 0.03) at diagnosis, were associated with failure. In multivariate analysis, only Child-Pugh B/C (hazard ratio, 3.18; 95% confidence interval, 1.66-6.10, P < 0.001) and AFP ≥ 100 ng/mL, both at diagnosis (hazard ratio, 2.80; 95% confidence interval, 1.37-5.71, P = 0.005), were independently associated with failure. Survival was higher among patients with tumors within the Milan criteria than those with program failure (33.9 vs 7.6 months, P < 0.001). CONCLUSIONS Approximately 25% of HCC cases diagnosed among patients included in a surveillance program were beyond the Milan criteria. Child-Pugh B/C and AFP ≥ 100 ng/mL at diagnosis were associated with program failure. However, Child-Pugh B at entry and development of liver-related complications during follow-up can be early predictors of failure.
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Affiliation(s)
- Alejo Mancebo
- Liver Unit, Department of Gastroenterology and Hepatology, Hospital Universitario Central de Asturias, University of Oviedo, Oviedo, Spain
| | - María Varela
- Liver Unit, Department of Gastroenterology and Hepatology, Hospital Universitario Central de Asturias, University of Oviedo, Oviedo, Spain
| | - María Luisa González-Diéguez
- Liver Unit, Department of Gastroenterology and Hepatology, Hospital Universitario Central de Asturias, University of Oviedo, Oviedo, Spain
| | - Carmen A Navascués
- Liver Unit, Department of Gastroenterology and Hepatology, Hospital Universitario Central de Asturias, University of Oviedo, Oviedo, Spain
| | - Valle Cadahía
- Liver Unit, Department of Gastroenterology and Hepatology, Hospital Universitario Central de Asturias, University of Oviedo, Oviedo, Spain
| | - Alicia Mesa-Álvarez
- Department of Radiology, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Luis Rodrigo
- Liver Unit, Department of Gastroenterology and Hepatology, Hospital Universitario Central de Asturias, University of Oviedo, Oviedo, Spain
| | - Manuel Rodríguez
- Liver Unit, Department of Gastroenterology and Hepatology, Hospital Universitario Central de Asturias, University of Oviedo, Oviedo, Spain
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Díaz-González Á, Forner A, Rodríguez de Lope C, Varela M. New challenges in clinical research on hepatocellular carcinoma. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2017; 108:485-93. [PMID: 26653993 DOI: 10.17235/reed.2015.4012/2015] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
This is an updated review of screening, early diagnosis and treatment of hepatocellular carcinoma, focusing on the advancements occurred in the last years and highlighting the challenges in clinical research. Hepatocellular carcinoma (HCC) is nowadays the sixth most frequent cancer worldwide with up to 740,000 new cases diagnosed each year, and it is the third most prevalent cause of cancer-related-death worldwide (1). This neoplasm usually appears linked to an underlying liver disease, being one of the most relevant causes of death in patients diagnosed of liver cirrhosis (2,3). In the last years, important advancements in terms of diagnosis, staging and treatment of HCC, improving the management and outcome of the disease, have been made (4-7). Despite the fact that these improvements have absolutely changed natural history of HCC, there are several areas that still need further advancements. The aim of this document is to discuss some controversial aspects, which in our opinion constitute real challenges in clinical research of HCC.
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Affiliation(s)
- Álvaro Díaz-González
- Servicio de Hepatología. Hospital Clínic Barcelona, Unidad de Oncología Hepática (BCLC)
| | - Alejandro Forner
- Hospital Clínic Barcelona. Ciberehd, Unidad de Oncología Hepática (BCLC)
| | | | - María Varela
- Digestivo. Sección de Hepatología, Hospital Universitario Central de Asturias, España
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Sapir E, Tao Y, Schipper MJ, Bazzi L, Novelli PM, Devlin P, Owen D, Cuneo KC, Lawrence TS, Parikh ND, Feng M. Stereotactic Body Radiation Therapy as an Alternative to Transarterial Chemoembolization for Hepatocellular Carcinoma. Int J Radiat Oncol Biol Phys 2017; 100:122-130. [PMID: 29066120 DOI: 10.1016/j.ijrobp.2017.09.001] [Citation(s) in RCA: 128] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Revised: 08/16/2017] [Accepted: 09/01/2017] [Indexed: 12/13/2022]
Abstract
PURPOSE To conduct a large single-institution comparison of transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT) outcomes in similar groups of patients with hepatocellular carcinoma (HCC). METHODS AND MATERIALS From 2006 to 2014, 209 patients with 1 to 2 tumors underwent TACE (n=84) to 114 tumors or image guided SBRT (n=125) to 173 tumors. Propensity score analysis with inverse probability of treatment weighting was used to compare outcomes between treatments while adjusting for imbalances in treatment assignment. Local control (LC), toxicity, and overall survival (OS) were retrospectively analyzed. RESULTS The TACE and SBRT groups were similar with respect to the number of tumors treated per patient, underlying liver disease, and baseline liver function. Patients treated with SBRT were older (65 vs 61 years, P=.01), had smaller tumors (2.3 vs 2.9 cm, P<.001), and less frequently underwent liver transplantation (8% vs 18%, P=.01). The 1- and 2-year LC favored SBRT: 97% and 91%, respectively, for SBRT and 47% and 23% for TACE (hazard ratio 66.5, P<.001). For patients treated with TACE, higher alpha-fetoprotein (hazard ratio 1.11 per doubling, P=.008) and segmental portal vein thrombosis (hazard ratio 9.9, P<.001) were associated with worse LC. Predictors associated with LC after SBRT were not identified. Grade 3+ toxicity occurred after 13% and 8% of TACE and SBRT treatments, respectively (P=.05). There was no difference in OS between patients treated with TACE or SBRT. CONCLUSIONS Stereotactic body radiation therapy is a safe alternative to TACE for 1 to 2 tumors and provides better LC, with no observed difference in OS. Prospective comparative trials of TACE and SBRT are warranted.
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Affiliation(s)
- Eli Sapir
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Department of Radiation Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Yebin Tao
- Department of Biostatistics, University of Michigan, Ann Arbor, Michigan
| | - Matthew J Schipper
- Department of Biostatistics, University of Michigan, Ann Arbor, Michigan
| | - Latifa Bazzi
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Paula M Novelli
- Vascular/Interventional Radiology Division, University of Michigan, Ann Arbor, Michigan
| | - Pauline Devlin
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | - Dawn Owen
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Kyle C Cuneo
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Theodore S Lawrence
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Neehar D Parikh
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | - Mary Feng
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Department of Radiation Oncology, University of California, San Francisco, San Francisco, California.
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Adherence to a Semiannual Surveillance Program for Hepatocellular Carcinoma in Patients With Liver Cirrhosis. J Clin Gastroenterol 2017; 51:557-563. [PMID: 27775957 DOI: 10.1097/mcg.0000000000000734] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Patient adherence to screening for hepatocellular carcinoma (HCC) is not well known. Our aims were to analyze the adherence to a surveillance program in a prospective cohort of cirrhotic patients and to examine its association with HCC stage at diagnosis. MATERIALS AND METHODS A total of 770 patients with cirrhosis were examined semiannually by ultrasound and alpha-fetoprotein at a tertiary center. We collected data on 17 variables at baseline. Suboptimal adherence was defined as failure to complete 2 consecutive screening rounds. RESULTS Over a median follow-up period of 42.0 months (interquartile range: 60.0), 125 patients (16.2%) had suboptimal adherence. Active or previous intravenous drug use [hazard ratio (HR), 5.33; 95% confidence interval (CI), 3.07-9.23], active alcohol consumption (HR, 3.03; 95% CI, 2.03-4.51), absence of liver decompensation before the inclusion in the program (HR, 1.65; 95% CI, 1.07-2.55) and aspartate transaminase/alanine transaminase ratio ≥1.6 (HR, 1.82; 95% CI, 1.23-2.70) were independent predictors of suboptimal adherence. Compared with those with optimal adherence, patients with suboptimal adherence had a more advanced HCC stage at diagnosis (P=0.015), they were less frequently treated with curative intention (P=0.078) and survived less (median: 14.2 mo; IQR: 36.0 vs. 22.7 mo; IQR: 47.4; P=0.160), although these differences were not significant. CONCLUSIONS The adherence to the process of HCC surveillance can be considered as adequate among cirrhotic patients. Active alcohol consumption and a history of intravenous drug use are the strongest predictors of suboptimal adherence. These patients have a more advanced HCC stage at diagnosis and tend to be less frequently treated with curative intention.
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Rodríguez de Lope C, Reig M, Matilla A, Ferrer MT, Dueñas E, Mínguez B, F Castroagudín J, Ortiz I, Pascual S, Lledó JL, Gallego A, Arenas JI, Aracil C, Forne M, Muñoz C, Pons F, Sala M, Iñarrairaegui M, Martin-Llahi M, Andreu V, Garre C, Rendón P, Fuentes J, Crespo J, Rodríguez M, Bruix J, Varela M. Clinical characteristics of hepatocellular carcinoma in Spain. Comparison with the 2008-2009 period and analysis of the causes of diagnosis out of screening programs. Analysis of 686 cases in 73 centers. Med Clin (Barc) 2017; 149:61-71. [PMID: 28279536 DOI: 10.1016/j.medcli.2016.12.048] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Revised: 12/23/2016] [Accepted: 12/29/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND OBJECTIVE In 2010 we published that 53% of cases of hepatocellular carcinoma (HCC) detected in Spain were diagnosed outside the context of standard screening programs, which consequently leads to lower survival rates. The aim of this study was to analyze the current situation and the causes of diagnosis out of screening programs. MATERIAL AND METHODS Prospective registry of 73 second- and third-level Spanish healthcare centers carried out between October 1, 2014 and January 31, 2015. The baseline characteristics of the disease and the first treatment administered for the incidental primary liver tumors during such period were recorded. RESULTS A total of 720 patients were included in the study: HCC (n=686), intrahepatic cholangiocarcinoma (n=29), hepatic cholangiocarcinoma (n=2), other (n=3). HCC characteristics: male 82%; mean age 67 years; cirrhosis 87%; main etiologies: alcohol 35%, HCV 30%, alcohol and HCV 15%, non-alcoholic fatty liver disease 6%; tumor stage: BCLC-0 11%, A 43%, B 19%, C 16% and D 11%; first treatment: transarterial chemoembolization (23%), percutaneous ablation (22%), symptomatic treatment (20%), resection (11%), sorafenib (11%). Three hundred and fifty-six patients (53%) were diagnosed outside of screening programs, mainly owing to the fact that they suffered from an undiagnosed liver disease (76%) and to the poor adherence to the screening program (18%). These patients were mainly male (P<.001), with an alcoholic etiology (P<.001) and active alcohol consumption (P<.001). Moreover, the disease was predominantly diagnosed at more advanced stages (P<.001) and was addressed with less radical treatments (P<.001). CONCLUSIONS In Spain, the main cause of diagnosis of a HCC outside the context of a screening program is the absence of a prior diagnosis of a liver disease, particularly in alcohol-consuming men. Detecting a liver disease in asymptomatic populations and improving adherence to screening programs are the main areas that must be subject to improvement in order to improve the early detection of HCC.
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Affiliation(s)
- Carlos Rodríguez de Lope
- Servicio de Digestivo, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla (IDIVAL), Santander, España
| | - María Reig
- Servicio de Hepatología, Hospital Clínic, Barcelona Clinic Liver Cancer (BCLC), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, España
| | - Ana Matilla
- Servicio de Digestivo, Hospital General Universitario Gregorio Marañón, Madrid, España
| | - María Teresa Ferrer
- Unidad de Gestión Clínica de Enfermedades Digestivas, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, España
| | - Eva Dueñas
- Servicio de Digestivo, Sección de Hepatología, Hospital de Bellvitge, Universitat Autónoma de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, España
| | - Beatriz Mínguez
- Servicio de Medicina Interna-Hepatología, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Universitat Autónoma de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, España
| | - Javier F Castroagudín
- Servicio de Digestivo, Complexo Hospitalario Universitario de Santiago, Santiago de Compostela, La Coruña, España
| | | | - Sonia Pascual
- Unidad Hepática, Servicio de Digestivo, Hospital General Universitario de Alicante, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Alicante, España
| | - José Luis Lledó
- Sección de Hepatología, Servicio de Digestivo, Hospital Universitario Ramón y Cajal, Madrid, España
| | - Adolfo Gallego
- Servicio de Digestivo, Hospital de la Santa Creu i Sant Pau, Barcelona, España
| | - Juan I Arenas
- Servicio de Digestivo, Hospital General Universitario de Donosti, San Sebastián, Guipúzcoa, España
| | - Carles Aracil
- Servicio de Digestivo, Hospital Universitario Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida (IRBLleida), Lleida, España
| | - Montserrat Forne
- Servicio de Digestivo, Mútua de Terrassa, Terrassa, Barcelona, España
| | - Carolina Muñoz
- Sección de Hepatología, Servicio de Digestivo, Hospital 12 de Octubre, Madrid, España
| | - Fernando Pons
- Sección de Hepatología, Servicio de Digestivo, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, España
| | - Margarita Sala
- Servicio de Digestivo, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, España
| | - Mercedes Iñarrairaegui
- Sección de Hepatología, Servicio de Medicina Interna, Clínica Universitaria de Navarra, Pamplona, Navarra, España
| | - Marta Martin-Llahi
- Servicio de Aparato Digestivo, Hospital Moisés Broggi, Sant Joan Despí, Barcelona, España
| | - Victoria Andreu
- Servicio de Digestivo, Hospital de Viladecans, Viladecans, Barcelona, España
| | - Carmen Garre
- Servicio de Aparato Digestivo, Hospital Virgen de la Arrixaca, Murcia, España
| | - Paloma Rendón
- Servicio de Digestivo, Hospital Universitario Puerta del Mar, Cádiz, España
| | - Javier Fuentes
- Servicio de Digestivo, Hospital Universitario Miguel Servet, Zaragoza, España
| | - Javier Crespo
- Servicio de Digestivo, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla (IDIVAL), Santander, España
| | - Manuel Rodríguez
- Sección de Hepatología, Servicio de Aparato Digestivo, Hospital Universitario Central de Asturias, Universidad de Oviedo, Oviedo, Asturias, España
| | - Jordi Bruix
- Servicio de Hepatología, Hospital Clínic, Barcelona Clinic Liver Cancer (BCLC), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, España
| | - María Varela
- Sección de Hepatología, Servicio de Aparato Digestivo, Hospital Universitario Central de Asturias, Universidad de Oviedo, Oviedo, Asturias, España.
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Díaz-González Á, Forner A. Surveillance for hepatocellular carcinoma. Best Pract Res Clin Gastroenterol 2016; 30:1001-1010. [PMID: 27938779 DOI: 10.1016/j.bpg.2016.10.006] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2016] [Accepted: 10/13/2016] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) appears mainly in patients with underlying liver disease and it is recognized as one of the most important causes of death in this population. Early detection by surveillance has been suggested as an effective tool for reducing cancer-specific mortality and the most accepted strategy is semiannual abdominal ultrasound in those patients at risk of HCC development. The benefit of HCC surveillance is proven by a randomized-controlled study, several prospective or retrospective analyses, and multiple modeling studies and according to the current scientific evidence, surveillance of HCC should be recommended and widely implemented. Major efforts should be done for improving the diagnostic accuracy of the screening tools and for better identifying those patients at risk of HCC development in whom a surveillance program would be cost-effective.
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Affiliation(s)
- Álvaro Díaz-González
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain; Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Spain
| | - Alejandro Forner
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain; Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Spain.
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Peres NP, Galbiatti-Dias ALS, Castanhole-Nunes MMU, da Silva RF, Pavarino ÉC, Goloni-Bertollo EM, Ruiz-Cintra MT. Polymorphisms of folate metabolism genes in patients with cirrhosis and hepatocellular carcinoma. World J Hepatol 2016; 8:1234-1243. [PMID: 27803768 PMCID: PMC5067443 DOI: 10.4254/wjh.v8.i29.1234] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2016] [Revised: 06/22/2016] [Accepted: 08/16/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluated the association of the risk factors and polymorphisms in MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G genes.
METHODS Patients with cirrhosis (n = 116), hepatocellular carcinoma (HCC) (n = 71) and controls (n = 356) were included. Polymerase chain reaction followed by enzymatic digestion and allelic discrimination technique real-time PCR techniques were used for analysis. MINITAB-14.0 and SNPstats were utilized for statistical analysis.
RESULTS Showed that age ≥ 46 years (OR = 10.31; 95%CI: 5.66-18.76; P < 0.001) and smoking (OR = 0.47; 95%CI: 0.28-0.78; P = 0.003) were associated with cirrhosis. Age ≥ 46 years (OR = 16.36; 95%CI: 6.68-40.05; P < 0.001) and alcohol habit (OR = 2.01; 95%CI: 1.03-3.89; P = 0.039) were associated with HCC. MTHFR A1298C in codominant model (OR = 3.37; 95%CI: 1.52-7.50; P = 0.014), recessive model (OR = 3.04; 95%CI: 1.43-6.47; P = 0.0051) and additive model (OR = 1.71; 95%CI: 1.16-2.52; P = 0.0072) was associated with HCC, as well as MTR A2756G in the additive model (OR = 1.68; 95%CI: 1.01-2.77; P = 0.047), and MTRR A66G in the codominant model (OR = 3.26; 95%CI: 1.54-6.87; P < 0.001), dominant model (OR = 2.55; 95%CI: 1.24-5.25; P = 0.007) and overdominant model (OR = 3.05; 95%CI: 1.66-5.62; P < 0.001). MTR A2756G in the additive model (OR = 1.54; 95%CI: 1.02-2.33; P = 0.042) and smokers who presented at least one polymorphic allele for MTRR A66G (OR = 1.71; 95%CI: 0.77-3.82; P = 0.0051) showed increased risk for cirrhosis. There was no association between clinical parameters and polymorphisms.
CONCLUSION Age ≥ 46 years, alcohol habit and MTR A2756G, MTHFR A1298C and MTRR A66G polymorphisms are associated with an increased risk of HCC development; age ≥ 46 years, tobacco habit and the MTR A2756G polymorphism are associated with cirrhosis.
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Forner A, Reig M, Varela M, Burrel M, Feliu J, Briceño J, Sastre J, Martí-Bonmati L, Llovet JM, Bilbao JI, Sangro B, Pardo F, Ayuso C, Bru C, Tabernero J, Bruix J. [Diagnosis and treatment of hepatocellular carcinoma. Update consensus document from the AEEH, SEOM, SERAM, SERVEI and SETH]. Med Clin (Barc) 2016; 146:511.e1-511.e22. [PMID: 26971984 DOI: 10.1016/j.medcli.2016.01.028] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2015] [Revised: 01/22/2016] [Accepted: 01/28/2016] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma is the most common primary malignancy of the liver and one of the most frequent causes of death in patients with liver cirrhosis. Simultaneously with the recognition of the clinical relevance of this neoplasm, in recent years there have been important developments in the diagnosis, staging and treatment of HCC. Consequently, the Asociación Española para el Estudio del Hígado has driven the need to update clinical practice guidelines, continuing to invite all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document (Sociedad Española de Trasplante Hepático, Sociedad Española de Radiología Médica, Sociedad Española de Radiología Vascular e Intervencionista y Sociedad Española de Oncología Médica). The clinical practice guidelines published in 2009 accepted as Clinical Practice Guidelines of the National Health System has been taken as reference document, incorporating the most important advances that have been made in recent years. The scientific evidence for the treatment of HCC has been evaluated according to the recommendations of the National Cancer Institute (www.cancer.gov) and the strength of recommendation is based on the GRADE system.
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Affiliation(s)
- Alejandro Forner
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España
| | - María Reig
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España
| | - María Varela
- Sección de Hepatología, Servicio de Aparato Digestivo, Hospital Universitario Central de Asturias (HUCA), Universidad de Oviedo, Oviedo, España
| | - Marta Burrel
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Radiodiagnóstico, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Jaime Feliu
- Servicio de Oncología Médica, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Sociedad Española de Oncología Médica, Madrid, España
| | - Javier Briceño
- Unidad de Trasplante Hepático, Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, España
| | - Javier Sastre
- Servicio de Oncología Médica, Hospital Clínico San Carlos, Madrid, España
| | - Luis Martí-Bonmati
- Departamento de Radiología, Hospital Universitario y Politécnico La Fe, Valencia, España
| | - Josep María Llovet
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Mount Sinai Liver Cancer Program, Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, Estados Unidos
| | - José Ignacio Bilbao
- Unidad de Radiología Vascular e Intervencionista, Departamento de Radiodiagnóstico, Clínica Universidad de Navarra, Pamplona, España
| | - Bruno Sangro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Unidad de Hepatología, Departamento de Medicina Interna, Clínica Universidad de Navarra, Pamplona, España
| | - Fernando Pardo
- Servicio de Cirugía Hepatobliopancreática y Trasplante, Clínica Universidad de Navarra, Pamplona, España
| | - Carmen Ayuso
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Radiodiagnóstico, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Concepció Bru
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Radiodiagnóstico, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Josep Tabernero
- Servicio de Oncología Médica, Hospital Universitario Vall d'Hebrón, Barcelona, Universidad Autónoma de Barcelona, Barcelona, España
| | - Jordi Bruix
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España.
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Manini MA, Sangiovanni A, Martinetti L, Viganò D, La Mura V, Aghemo A, Iavarone M, Crespi S, Nicolini A, Colombo M. Transarterial chemoembolization with drug-eluting beads is effective for the maintenance of the Milan-in status in patients with a small hepatocellular carcinoma. Liver Transpl 2015; 21:1259-1269. [PMID: 26074360 DOI: 10.1002/lt.24196] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2015] [Revised: 04/30/2015] [Accepted: 05/31/2015] [Indexed: 12/13/2022]
Abstract
Transarterial chemoembolization (TACE) is the standard of care for the treatment of patients with an intermediate (Barcelona Clinic Liver Cancer [BCLC] B) hepatocellular carcinoma and to bridge patients with an early cancer to liver transplantation (LT). We explored the efficacy of TACE with drug-eluting beads (DEB) in BCLC A patients. Included are all BCLC A patients unsuitable for resection or locoregional ablation who underwent a DEB TACE between 2006 and 2012. Treatment was carried out "a la demande" until complete tumor devascularization or progression beyond Milan criteria. In patients with a complete response (CR), a contrast computed tomography (CT) scan was repeated at 3-month intervals during the first 2 years and then every 6 months alternating with abdominal ultrasound in the subsequent 3 years. Fifty-five patients had 79 tumor nodules ranging 7 to 50 mm; 32 (58%) achieved a CR that was maintained up to 4 and 7 months in 21 (38%) and 17 (31%) patients, respectively. The 24- and 36-month tumor-free survivals were 21% and 9%, respectively. The overall cumulative progression beyond Milan criteria at 3, 6, 12, and 24 months was 2%, 5%, 30%, and 54%. LT eligibility was maintained for a median of 19 months (range, 2-63 months). CR to first TACE was the strongest independent predictor of Milan-in maintenance. In conclusion, DEB TACE may effectively bridge patients with an early cancer to LT, and a CR to the first procedure may guide patient prioritization during the waiting list.
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Affiliation(s)
| | - Angelo Sangiovanni
- Divisions of Gastroenterology and Hepatology, University of Milan, Milan, Italy
| | - Laura Martinetti
- Radiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Davide Viganò
- Divisions of Gastroenterology and Hepatology, University of Milan, Milan, Italy
| | - Vincenzo La Mura
- Divisions of Gastroenterology and Hepatology, University of Milan, Milan, Italy
| | - Alessio Aghemo
- Divisions of Gastroenterology and Hepatology, University of Milan, Milan, Italy
| | - Massimo Iavarone
- Divisions of Gastroenterology and Hepatology, University of Milan, Milan, Italy
| | - Silvia Crespi
- Radiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Antonio Nicolini
- Radiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Massimo Colombo
- Divisions of Gastroenterology and Hepatology, University of Milan, Milan, Italy
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[Therapeutic decisions in the treatment of hepatocellular carcinoma and patterns of sorafenib use. Results of the international observational GIDEON trial in Spain]. GASTROENTEROLOGIA Y HEPATOLOGIA 2015; 38:263-73. [PMID: 25583146 DOI: 10.1016/j.gastrohep.2014.11.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2014] [Revised: 10/27/2014] [Accepted: 11/03/2014] [Indexed: 12/19/2022]
Abstract
INTRODUCTION GIDEON is a non-interventional, prospective, international study that evaluated the safety of sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in daily clinical practice, including Child-Pugh B patients. OBJECTIVES To analyze data collected in Spain on the safety and efficacy of sorafenib and treatment patterns. METHODS Data were collected during follow-up on demographic and disease characteristics, the initial dose used, treatment-emergent adverse events (AEs) and dose modifications. Overall survival was evaluated, as well as time to disease progression. Efficacy and safety were analyzed according to the Child-Pugh classification and the initial dose. RESULTS We included 143 patients from 19 Spanish hospitals. A total of 24.5% of the patients were Child-Pugh B. An initial dose of 400 mg/12 h was used in 90.9% of patients. In Child-Pugh A patients, dose modifications occurred more frequently and the treatment duration was longer. The incidence of AEs and drug-related AEs were similar in Child-Pugh A and B patients, although serious AEs were more frequent in Child-Pugh B patients. The most common AEs were diarrhea, fatigue and hand-foot skin reactions. The median overall survival was 384 days and was higher in Child-Pugh A patients (593 vs. 211 days in Child-Pugh B). The median time to disease progression was 177 days, similar in both subgroups. CONCLUSION The safety profile of sorafenib in Spanish patients with unresectable HCC is independent of liver function. Child-Pugh status does not seem to influence the approach to sorafenib dosage or time to progression but does seem to be a strong prognostic factor for survival.
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Romero Gutiérrez M, Ruano Díaz L, Muñoz López D, Artaza Varasa T, González de Frutos C, Sánchez Ruano JJ, de la Cruz Pérez G, Gómez Rodríguez R. [Percutaneous ablation of hepatocellular carcinoma in older patients in clinical practice]. GASTROENTEROLOGIA Y HEPATOLOGIA 2014; 38:54-61. [PMID: 25499846 DOI: 10.1016/j.gastrohep.2014.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2014] [Revised: 10/05/2014] [Accepted: 11/03/2014] [Indexed: 11/17/2022]
Abstract
INTRODUCTION A high percentage of older patients with early-stage hepatocellular carcinoma (HCC) are potential candidates for percutaneous ablation. MATERIAL AND METHODS We prospectively assessed data from patients older than 70 years with HCC. We determined their demographic and clinical characteristics, the treatment provided and the response, complications and survival among those treated with radiofrequency ablation (RFA) and/or percutaneous ethanol injection (PEI). RESULTS Of 194 patients with HCC, 84 were older than 70 years (43.3%). The mean age was 76.8 ± 4.5 years. Seventy-five percent were male and 91.7% had cirrhosis. Cancer was initially identified by a surveillance program in 61.9%. According to the Barcelona Clinic Liver Cancer staging system, 60.7% were classified as having early stage cancer (0-A), 19% as stage B, 12% as stage C, and 8.3% as stage D. Potentially curative initial treatment was provided in 38.2% (surgical resection in 4.8%, PEI in 22.6%, RFA in 4.8%, PEI+RFA in 6%), transarterial chemoembolization in 20.2%, and sorafenib in 3.6%. Twenty-five percent of patients were not treatment candidates and 13% refused the recommended treatment. The median follow-up after percutaneous ablation was 23 months (IQR 14.2-40.6). The mean number of sessions was 3.5 ± 2.2 for PEI and 1.8 ± 1.6 for RFA. The complications rate per session was 4%. Remission was achieved in 35.7%. The overall median survival was 45.7 months (95% CI 20.8-70.6). CONCLUSIONS Almost half of the patients with HCC in our sample were elderly and more than half were diagnosed at an early stage. Percutaneous ablation was performed in one-third of the sample, achieving remission in 37.5%. There were few complications. Therefore, these patients should be assessed for percutaneous ablation.
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Affiliation(s)
- Marta Romero Gutiérrez
- Servicio de Aparato Digestivo, Hospital Virgen de la Salud, Complejo Hospitalario de Toledo, Toledo, España.
| | - Lucía Ruano Díaz
- Servicio de Aparato Digestivo, Hospital Virgen de la Salud, Complejo Hospitalario de Toledo, Toledo, España
| | - Diego Muñoz López
- Servicio de Aparato Digestivo, Hospital Virgen de la Salud, Complejo Hospitalario de Toledo, Toledo, España
| | - Tomás Artaza Varasa
- Servicio de Aparato Digestivo, Hospital Virgen de la Salud, Complejo Hospitalario de Toledo, Toledo, España
| | | | - Juan José Sánchez Ruano
- Servicio de Aparato Digestivo, Hospital Virgen de la Salud, Complejo Hospitalario de Toledo, Toledo, España
| | - Gema de la Cruz Pérez
- Servicio de Aparato Digestivo, Hospital Virgen de la Salud, Complejo Hospitalario de Toledo, Toledo, España
| | - Rafael Gómez Rodríguez
- Servicio de Aparato Digestivo, Hospital Virgen de la Salud, Complejo Hospitalario de Toledo, Toledo, España
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Golfieri R, Giampalma E, Renzulli M, Cioni R, Bargellini I, Bartolozzi C, Breatta AD, Gandini G, Nani R, Gasparini D, Cucchetti A, Bolondi L, Trevisani F. Randomised controlled trial of doxorubicin-eluting beads vs conventional chemoembolisation for hepatocellular carcinoma. Br J Cancer 2014; 111:255-64. [PMID: 24937669 PMCID: PMC4102934 DOI: 10.1038/bjc.2014.199] [Citation(s) in RCA: 469] [Impact Index Per Article: 42.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2013] [Revised: 03/09/2014] [Accepted: 03/20/2014] [Indexed: 11/08/2022] Open
Abstract
BACKGROUND Transcatheter arterial chemoembolisation (TACE) is the treatment of choice for intermediate stage hepatocellular carcinoma (HCC). Doxorubicin-loaded drug-eluting beads (DEB)-TACE is expected to improve the performance of conventional TACE (cTACE). The aim of this study was to compare DEB-TACE with cTACE in terms of time-to-tumour progression (TTP), adverse events (AEs), and 2-year survival. METHODS Patients were randomised one-to-one to undergo cTACE or DEB-TACE and followed-up for at least 2 years or until death. Transcatheter arterial chemoembolisation was repeated 'on-demand'. RESULTS We enrolled 177 patients: 89 underwent DEB-TACE and 88 cTACE. The median number of procedures was 2 in each arm, and the in-hospital stay was 3 and 4 days, respectively (P=0.323). No differences were found in local and overall tumour response. The median TTP was 9 months in both arms. The AE incidence and severity did not differ between the arms, except for post-procedural pain, more frequent and severe after cTACE (P<0.001). The 1- and 2-year survival rates were 86.2% and 56.8% after DEB-TACE and 83.5% and 55.4% after cTACE (P=0.949). Eastern Cooperative Oncology Group (ECOG), serum albumin, and tumour number independently predicted survival (P<0.05). CONCLUSIONS The DEB-TACE and the cTACE are equally effective and safe, with the only advantage of DEB-TACE being less post-procedural abdominal pain.
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Affiliation(s)
- R Golfieri
- Radiology Unit, Department of Digestive Disease and Internal Medicine, S. Orsola-Malpighi Hospital, Bologna University, Albertoni Street 15, 40138 Bologna, Italy
| | - E Giampalma
- Radiology Unit, Department of Digestive Disease and Internal Medicine, S. Orsola-Malpighi Hospital, Bologna University, Albertoni Street 15, 40138 Bologna, Italy
| | - M Renzulli
- Radiology Unit, Department of Digestive Disease and Internal Medicine, S. Orsola-Malpighi Hospital, Bologna University, Albertoni Street 15, 40138 Bologna, Italy
| | - R Cioni
- Diagnostic and Interventional Radiology, Department of Oncology, Transplants and Advanced Technologies in Medicine, University of Pisa, Pisa, Italy
| | - I Bargellini
- Diagnostic and Interventional Radiology, Department of Oncology, Transplants and Advanced Technologies in Medicine, University of Pisa, Pisa, Italy
| | - C Bartolozzi
- Diagnostic and Interventional Radiology, Department of Oncology, Transplants and Advanced Technologies in Medicine, University of Pisa, Pisa, Italy
| | - A D Breatta
- Diagnostic Imaging Division, Department of Medical and Surgical Disciplines University of Turin, AOU S. Giovanni Battista, Turin, Italy
| | - G Gandini
- Diagnostic Imaging Division, Department of Medical and Surgical Disciplines University of Turin, AOU S. Giovanni Battista, Turin, Italy
| | - R Nani
- CeLiveR, Ospedali Riuniti di Bergamo, Bergamo, Italy
| | - D Gasparini
- Department of Radiologic Sciences, University Hospital, S. Maria della Misericordia, Udine, Italy
| | - A Cucchetti
- Department of Medical and Surgical Sciences, Alma Mater Studiorum – University of Bologna, Bologna, Italy
| | - L Bolondi
- Department of Medical and Surgical Sciences, Alma Mater Studiorum – University of Bologna, Bologna, Italy
| | - F Trevisani
- Department of Medical and Surgical Sciences, Alma Mater Studiorum – University of Bologna, Bologna, Italy
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Abstract
Hepatocellular carcinoma (HCC) is a highly prevalent and lethal neoplasia. Several studies have shown that HCC is the main cause of death in patients with cirrhosis. A better knowledge of the natural history of the tumor and the development of staging systems has allowed to refine the prognosis of the patients. The Barcelona Clinic Liver Cancer system (BCLC) has become the preferred staging system since it takes into account the tumor characteristics, the degree of liver impairment and the physical performance. It has been endorsed by several scientific associations and research consortia as it does not just define prognosis, but, more interestingly, it links staging with prognosis assessment and treatment recommendation. Curative therapies such as resection, transplantation and ablation can improve survival in patients diagnosed at an early HCC stage and may offer a long-term cure with overall survival that may exceed 70% at 5 years. Patients with intermediate stage HCC benefit from chemoembolization and proper selection of candidates permits a 50% survival at 3-4 years. Finally, patients diagnosed at an advanced stage benefit from sorafenib, an oral available, multikinase inhibitor with antiangiogenic and antiproliferative effects. Current research efforts are aimed at further refining prognosis prediction through molecular profiling and enhanced clinical characterization. At the same time, better knowledge of the molecular mechanisms of cancer should result in a further improvement of the current life expectancy of patients.
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Affiliation(s)
- Alexandre Liccioni
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
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Lee MH, Lu SN, Yuan Y, Yang HI, Jen CL, You SL, Wang LY, L'Italien G, Chen CJ. Development and validation of a clinical scoring system for predicting risk of HCC in asymptomatic individuals seropositive for anti-HCV antibodies. PLoS One 2014; 9:e94760. [PMID: 24801353 PMCID: PMC4011690 DOI: 10.1371/journal.pone.0094760] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Accepted: 03/19/2014] [Indexed: 02/07/2023] Open
Abstract
Background The development of a risk assessment tool for long-term hepatocellular carcinoma risk would be helpful in identifying high-risk patients and providing information of clinical consultation. Methods The model derivation and validation cohorts consisted of 975 and 572 anti-HCV seropositives, respectively. The model included age, alanine aminotransferase (ALT), the ratio of aspirate aminotransferase to ALT, serum HCV RNA levels and cirrhosis status and HCV genotype. Two risk prediction models were developed: one was for all-anti-HCV seropositives, and the other was for anti-HCV seropositives with detectable HCV RNA. The Cox's proportional hazards models were utilized to estimate regression coefficients of HCC risk predictors to derive risk scores. The cumulative HCC risks in the validation cohort were estimated by Kaplan-Meier methods. The area under receiver operating curve (AUROC) was used to evaluate the performance of the risk models. Results All predictors were significantly associated with HCC. The summary risk scores of two models derived from the derivation cohort had predictability of HCC risk in the validation cohort. The summary risk score of the two risk prediction models clearly divided the validation cohort into three groups (p<0.001). The AUROC for predicting 5-year HCC risk in the validation cohort was satisfactory for the two models, with 0.73 and 0.70, respectively. Conclusion Scoring systems for predicting HCC risk of HCV-infected patients had good validity and discrimination capability, which may triage patients for alternative management strategies.
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Affiliation(s)
- Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
- * E-mail: (MHL); (SNL); (CJC)
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung, Taiwan
- * E-mail: (MHL); (SNL); (CJC)
| | - Yong Yuan
- Global Health Economics and Outcomes Research, Bristol Myers-Squibb, Princeton, New Jersey, United States of America
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
- Molecular and Genomic Epidemiology Center, China Medical University Hospital, Taichung, Taiwan
- Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
| | - Chin-Lan Jen
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - San-Lin You
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Li-Yu Wang
- Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
| | - Gilbert L'Italien
- Global Health Economics and Outcomes Research, Bristol Myers-Squibb, Princeton, New Jersey, United States of America
- Yale University School of Medicine, New Haven, Connecticut, United States of America
| | - Chien-Jen Chen
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
- * E-mail: (MHL); (SNL); (CJC)
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Lee MH, Lu SN, Yuan Y, Yang HI, Jen CL, You SL, Wang LY, L'Italien G, Chen CJ. Development and validation of a clinical scoring system for predicting risk of HCC in asymptomatic individuals seropositive for anti-HCV antibodies. PLoS One 2014. [PMID: 24801353 DOI: 10.1371/journal.pone.0094760;] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND The development of a risk assessment tool for long-term hepatocellular carcinoma risk would be helpful in identifying high-risk patients and providing information of clinical consultation. METHODS The model derivation and validation cohorts consisted of 975 and 572 anti-HCV seropositives, respectively. The model included age, alanine aminotransferase (ALT), the ratio of aspirate aminotransferase to ALT, serum HCV RNA levels and cirrhosis status and HCV genotype. Two risk prediction models were developed: one was for all-anti-HCV seropositives, and the other was for anti-HCV seropositives with detectable HCV RNA. The Cox's proportional hazards models were utilized to estimate regression coefficients of HCC risk predictors to derive risk scores. The cumulative HCC risks in the validation cohort were estimated by Kaplan-Meier methods. The area under receiver operating curve (AUROC) was used to evaluate the performance of the risk models. RESULTS All predictors were significantly associated with HCC. The summary risk scores of two models derived from the derivation cohort had predictability of HCC risk in the validation cohort. The summary risk score of the two risk prediction models clearly divided the validation cohort into three groups (p<0.001). The AUROC for predicting 5-year HCC risk in the validation cohort was satisfactory for the two models, with 0.73 and 0.70, respectively. CONCLUSION Scoring systems for predicting HCC risk of HCV-infected patients had good validity and discrimination capability, which may triage patients for alternative management strategies.
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Affiliation(s)
- Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung, Taiwan
| | - Yong Yuan
- Global Health Economics and Outcomes Research, Bristol Myers-Squibb, Princeton, New Jersey, United States of America
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan; Molecular and Genomic Epidemiology Center, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
| | - Chin-Lan Jen
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - San-Lin You
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Li-Yu Wang
- Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
| | - Gilbert L'Italien
- Global Health Economics and Outcomes Research, Bristol Myers-Squibb, Princeton, New Jersey, United States of America; Yale University School of Medicine, New Haven, Connecticut, United States of America
| | - Chien-Jen Chen
- Genomics Research Center, Academia Sinica, Taipei, Taiwan; Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
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Grado de homogeneidad de los grupos españoles de trasplante hepático en el tratamiento del hepatocarcinoma. Med Clin (Barc) 2013; 141:406-10. [DOI: 10.1016/j.medcli.2013.03.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2013] [Revised: 03/18/2013] [Accepted: 03/21/2013] [Indexed: 12/12/2022]
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Bargellini I, Florio F, Golfieri R, Grosso M, Lauretti DL, Cioni R. Trends in utilization of transarterial treatments for hepatocellular carcinoma: results of a survey by the Italian Society of Interventional Radiology. Cardiovasc Intervent Radiol 2013; 37:438-44. [PMID: 23719667 DOI: 10.1007/s00270-013-0656-5] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2013] [Accepted: 04/30/2013] [Indexed: 02/06/2023]
Abstract
PURPOSE This study was designed to provide an overview of the practice of locoregional treatments for HCC by the Italian centers of Interventional Radiology (IR) with particular reference to transarterial modalities. METHODS A questionnaire of 11 questions on locoregional treatment of HCC was e-mailed to 134 Italian IR centers. RESULTS The response rate was 64.9% (87/135 centers). Of 8,959 procedures in 2011, 67% were transarterial treatments, 31% percutaneous ablations, and 2% Y90-radioembolizations. Regarding (chemo)embolization, approximately 59% of procedures were performed in the intermediate stage, 28% in the early stage, and 12.8% in the advanced stage. TACE techniques varied greatly; approximately 52% of procedures were performed with drug-eluting particles and 32% with lipiodol, drug, and reabsorbable particles. In selected cases, 53 of 78 (68%) centers combine chemoembolization and ablation, whereas 28 centers (35.9%) combine Sorafenib and chemoembolization. In 2011, 13 of 78 (16.7%) responding centers performed Y90-radioembolization, with approximately 52% of procedures performed in the advanced stage and 46% in the intermediate stage. Approximately 62% of Y90-radioembolizations were performed using resin spheres and 38% using glass spheres. CONCLUSIONS With almost 9,000 procedures performed each year, locoregional treatments of HCC, most of all transarterial (chemo)embolizations, represent a major part of daily clinical practice in many Italian IR centers. The high variability in responses regarding transarterial treatments for HCC patients highlights the need for solid scientific evidence allowing better definition of clinical indications and standardization of technical approaches.
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Affiliation(s)
- Irene Bargellini
- Diagnostic and Interventional Radiology, Pisa University Hospital, Via Paradisa 2, 56100, Pisa, Italy,
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Deuffic-Burban S, Deltenre P, Buti M, Stroffolini T, Parkes J, Mühlberger N, Siebert U, Moreno C, Hatzakis A, Rosenberg W, Zeuzem S, Mathurin P. Predicted effects of treatment for HCV infection vary among European countries. Gastroenterology 2012; 143:974-85.e14. [PMID: 22863764 DOI: 10.1053/j.gastro.2012.05.054] [Citation(s) in RCA: 99] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2011] [Revised: 05/25/2012] [Accepted: 05/30/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS The dynamics of hepatitis C virus (HCV) infection, as well as screening practices and access to therapy, vary among European countries. It is important to determine the magnitude of the effects of such differences on incidence and mortality of infection. We compared the dynamics of infection and screening and treatment practices among Belgium, France, Germany, Italy, Spain, and the United Kingdom. We also assessed the effects of treatment with pegylated interferon and additional effects of triple therapy with protease inhibitors. METHODS We created a country-specific Markov model of HCV progression based on published epidemiologic data (on HCV prevalence, screening, genotype, alcohol consumption among patients, and treatments) and reports of competitive and hepatocellular carcinoma mortality for the 6 countries. The model was used to predict the incidence of HCV-related cirrhosis and its mortality until 2021 for each country. RESULTS From 2002 to 2011, antiviral therapy reduced the cumulative incidence of cirrhosis by 7.1% and deaths by 3.4% overall. Reductions in incidence and mortality values ranged from 4.0% and 1.9%, respectively, in Italy to 16.3% and 9.0%, respectively, in France. From 2012 to 2021, antiviral treatment of patients with HCV genotype 1 infection that includes protease inhibitor-based triple therapy will reduce the cumulative incidence of cirrhosis by 17.7% and mortality by 9.7% overall. The smallest reduction is predicted for Italy (incidence reduced by 10.1% and mortality by 5.4%) and the highest is for France (reductions of 34.3% and 20.7%, respectively). CONCLUSIONS Although HCV infection is treated with the same therapies in different countries, the effects of the therapies on morbidity and mortality vary significantly. In addition to common guidelines that are based on virologic response-guided therapy, there is a need for public health policies based on population-guided therapy.
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Iñarrairaegui M, Pardo F, Bilbao J, Rotellar F, Benito A, D'Avola D, Herrero J, Rodriguez M, Martí P, Zozaya G, Dominguez I, Quiroga J, Sangro B. Response to radioembolization with yttrium-90 resin microspheres may allow surgical treatment with curative intent and prolonged survival in previously unresectable hepatocellular carcinoma. Eur J Surg Oncol 2012; 38:594-601. [DOI: 10.1016/j.ejso.2012.02.189] [Citation(s) in RCA: 84] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2011] [Revised: 01/18/2012] [Accepted: 02/27/2012] [Indexed: 12/13/2022] Open
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Deuffic-Burban S, Yazdanpanah Y. It is time to change the paradigm for hepatitis C virus testing. Clin Infect Dis 2012; 54:1272-4. [PMID: 22419684 DOI: 10.1093/cid/cis047] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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Gómez Rodríguez R, Romero Gutiérrez M, González de Frutos C, de Artaza Varasa T, de la Cruz Perez G, Ciampi Dopazo JJ, Lanciego Pérez C, Gómez Moreno AZ. [Clinical characteristics, staging and treatment of patients with hepatocellular carcinoma in clinical practice. Prospective study of 136 patients]. GASTROENTEROLOGIA Y HEPATOLOGIA 2011; 34:524-31. [PMID: 21940068 DOI: 10.1016/j.gastrohep.2011.06.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2011] [Revised: 06/05/2011] [Accepted: 06/07/2011] [Indexed: 12/12/2022]
Abstract
UNLABELLED Hepatocellular carcinoma (HCC) is the most frequent cause of mortality in patients with liver cirrhosis. There are no prospective series from a single tertiary hospital in Spain. MATERIAL AND METHODS We performed a prospective study of patients with HCC in our center. Clinical and epidemiological characteristics, diagnostic method, staging according to the Barcelona Clinic Liver Cancer (BCLC) system and treatment were analyzed. RESULTS A total of 136 patients were included (80.9% men). The mean age was 66.62 ± 11.68 years and 91.2% were cirrhotic. Hepatitis C virus (HCV) was the leading cause of liver disease (38.97%). The suspected diagnosis was established by a surveillance program in 63.2%. Noninvasive American Association criteria for the Study of Liver Diseases (AASLD) were the main diagnostic method (73.5%). According to the BCLC, 58.1% were in the early stage (0-A), 21.3% in stage B, 12.5% in stage C and 8.1% in stage D. Early stage patients had followed a surveillance program more frequently than those with non-early stages (79.75% versus 44.35%, p <0.001). Potentially curative initial treatment was used in 45.58%, the most common treatment being percutaneous ethanol injection (23.13%). CONCLUSIONS Most patients with HCC in our hospital have cirrhosis, the most frequent cause being HCV. HCC surveillance in at-risk patients could increase diagnosis of HCC at an early stage. We achieved an early diagnosis in more than half of cases. The most common initial treatment was percutaneous therapy.
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Estudio descriptivo de la experiencia sobre carcinoma hepatocelular en hígado no cirrótico. GASTROENTEROLOGIA Y HEPATOLOGIA 2011; 34:322-8. [DOI: 10.1016/j.gastrohep.2011.02.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/28/2010] [Revised: 02/05/2011] [Accepted: 02/08/2011] [Indexed: 11/19/2022]
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Bargellini I, Sacco R, Bozzi E, Bertini M, Ginanni B, Romano A, Cicorelli A, Tumino E, Federici G, Cioni R, Metrangolo S, Bertoni M, Bresci G, Parisi G, Altomare E, Capria A, Bartolozzi C. Transarterial chemoembolization in very early and early-stage hepatocellular carcinoma patients excluded from curative treatment: a prospective cohort study. Eur J Radiol 2011; 81:1173-8. [PMID: 21466931 DOI: 10.1016/j.ejrad.2011.03.046] [Citation(s) in RCA: 91] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2011] [Revised: 03/09/2011] [Accepted: 03/11/2011] [Indexed: 12/16/2022]
Abstract
AIM To assess clinical outcome of transarterial chemoembolization (TACE) in a series of patients with early-stage hepatocellular carcinoma (HCC), within Milan criteria, but clinically unfit for liver transplantation (OLT). METHODS From January 2006 to May 2009, 67 patients (43 males, mean age 70 ± 7.6 years) with very early or early-stage unresectable HCC, within Milan selection criteria but clinically unfit for OLT, underwent TACE. The primary endpoint of the study was overall survival. Secondary endpoints were: safety, liver toxicity, 1-month tumour response according to the amended RECIST criteria, time to local and distant intrahepatic tumour recurrence and time to radiological progression. RESULTS Two major periprocedural complications occurred (3%), consisting of liver failure. Periprocedural mortality rate was 1.5% (1 patient). A significant increase in ALT and bilirubin levels 24h after treatment was reported, with progressive decrease at discharge. At 1-month follow-up, complete and partial tumour response rates were 67.2% and 29.8%, respectively, with two cases of progressive disease. Mean follow-up was 37.3 ± 15 months. The 1-, 2-, and 3-year overall survival rates were 90.9%, 86.1%, and 80.5%, respectively. Median expected time to local tumour recurrence and intrahepatic tumour recurrence were 7.9 and 13.8 months, respectively. Radiological disease progression was observed in 12 patients (17.9%) with a mean expected time of 26.5 months. CONCLUSION In patients with early-stage HCC, clinically excluded from OLT and unfit for surgery or percutaneous ablation, TACE is a safe and effective option, with favourable long-term survival.
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Affiliation(s)
- Irene Bargellini
- Diagnostic and Interventional Radiology, Pisa University Hospital, Via Paradisa 2, 56124 Pisa, Italy.
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Mota A, Areias J, Cardoso MF. Chronic liver disease and cirrhosis among patients with hepatitis B virus infection in northern Portugal with reference to the viral genotypes. J Med Virol 2011; 83:71-7. [PMID: 21108341 DOI: 10.1002/jmv.21939] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The prevalence of infection with hepatitis B virus in Portugal is around 1% of the population; 20-30% of those infected typically develop cirrhosis. The study focuses on the epidemiological profile of patients with hepatitis B infection and liver damage, in particular, cirrhosis. Of the 358 individuals that comprised the study, a liver biopsy was performed in 249 to identify the presence of cirrhosis. Cirrhosis was observed in 59 patients (23.7%) The Child-Pugh classification was used to assess the prognosis of cirrhosis: 3 out of the 59 patients were classified as Child-Pugh grade C, the most severe, 17 (28.8%) as grade B, and 39 (66.2%) as grade A. Patients classified as grade B were older, drank more, and showed higher levels of AST and alkaline phosphatase when compared with individuals classified as grade A. Genotypes A and D were predominant, and no significant differences with respect to genotype distribution were observed. Analysis of the hematological parameters showed that patients classified as Child's grade B had lower levels of platelets and higher levels of prothrombin time than those classified as Child's grade A. The profile of the patients with cirrhosis, including an extended number of individual characteristics, provides useful information, however, only a prospective study could evaluate definitively if liver disease is influenced by these factors. Future studies would benefit from the analysis of the impact of genotypes on liver disease, particularly genotypes A and D, the most predominant genotypes in northern Portugal.
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Affiliation(s)
- Ana Mota
- ICBAS Abel Salazar Biomedical Institute, University of Porto, Porto, Portugal
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