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Cillo U, Gringeri E, D'Amico FE, Lanari J, Furlanetto A, Vitale A. Hepatocellular carcinoma: Revising the surgical approach in light of the concept of multiparametric therapeutic hierarchy. Dig Liver Dis 2025; 57:809-818. [PMID: 39828438 DOI: 10.1016/j.dld.2024.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 11/20/2024] [Accepted: 12/02/2024] [Indexed: 01/22/2025]
Abstract
The clinical management of hepatocellular carcinoma (HCC) is strongly influenced by several prognostic factors, mainly tumor stage, patient's health, liver function and specific characteristics of each intervention. The interplay between these factors should be carefully evaluated by a multidisciplinary tumor board. To support this, the novel "multiparametric therapeutic hierarchy" (MTH) concept has been recently proposed. This review will present the main features of available surgical treatments for HCC (liver transplantation, liver resection, ablation). Strengths and weaknesses are reported in the light of clinical decision making and of treatment allocation, with a special focus on the collocation of each treatment in the MTH framework and on how MTH may be useful in supporting clinical decision. Sequential treatments and their role to allow further surgical treatments will also be analyzed.
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Affiliation(s)
- Umberto Cillo
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy.
| | - Enrico Gringeri
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy
| | - Francesco Enrico D'Amico
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy
| | - Jacopo Lanari
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy
| | - Alessandro Furlanetto
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy
| | - Alessandro Vitale
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy
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Giannini EG, Pieri G, Plaz Torres MC. Towards an integrated management model for hepatocellular carcinoma. Dig Liver Dis 2024; 56:2022-2024. [PMID: 38862369 DOI: 10.1016/j.dld.2024.05.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 05/28/2024] [Indexed: 06/13/2024]
Affiliation(s)
- Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy; Liver Center, Digestive Diseases Section, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA; Gastroenterology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
| | - Giulia Pieri
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy; Gastroenterology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Maria Corina Plaz Torres
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy; Gastroenterology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
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Kusuhara T, Gon H, Terashima K, Komatsu S, Matsuo Y, Tokumaru S, Toyama H, Kido M, Okimoto T, Fukumoto T. Comparison of Prognostic Outcomes Between Repeat Liver Resection and Particle Therapy for Patients with Recurrent Hepatocellular Carcinoma. Ann Surg Oncol 2024:10.1245/s10434-024-16363-w. [PMID: 39453585 DOI: 10.1245/s10434-024-16363-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 09/30/2024] [Indexed: 10/26/2024]
Abstract
BACKGROUND Particle therapy (PT) as an initial hepatocellular carcinoma (HCC) treatment has been reported to be effective; however, its efficacy for the treatment of recurrent HCC remains unclear. OBJECTIVE This study aimed to evaluate the efficacy of PT compared with repeat liver resection for treating recurrent HCC after initial LR, with a focus on prognostic outcomes. METHODS Between 2005 and 2019, 89 and 49 patients underwent repeat LR and PT for recurrent HCC after initial LR, respectively. The 5-year overall survival (OS) and recurrence-free survival (RFS) were evaluated using propensity score matching. Treatment-related complications were scored using the National Institute Common Terminology Criteria for Adverse Events (CTCAE) and were compared between the repeat LR and PT groups. RESULTS In the entire cohort, the 5-year OS was significantly better in the repeat LR group than in the PT group (75% vs. 48%; p = 0.0003), and the 5-year RFS was comparable in both groups (22% vs. 13%; p = 0.088). Propensity score matching created 34 pairs of patients; no significant differences in the 5-year OS (65% vs. 48%; p = 0.310) and RFS (21% vs. 8%; p = 0.271) were observed between the repeat LR and PT groups. The proportion of CTCAE grade ≥3 complications was 8.8% and 5.9% in the repeat LR and PT groups, respectively (p = 0.641). CONCLUSIONS After initial LR, the prognosis and treatment-related complications in patients with recurrent HCC were comparable between the repeat LR and PT groups in the matched cohort; therefore, PT may remain one of the multidisciplinary treatment options for recurrent HCC.
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Affiliation(s)
- Tatsuki Kusuhara
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Hidetoshi Gon
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
| | - Kazuki Terashima
- Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo, Japan
| | - Shohei Komatsu
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Yoshiro Matsuo
- Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo, Japan
| | - Sunao Tokumaru
- Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo, Japan
| | - Hirochika Toyama
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Masahiro Kido
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Tomoaki Okimoto
- Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo, Japan
| | - Takumi Fukumoto
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
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Vitale A, Romano P, Cillo U. Liver Resection vs Nonsurgical Treatments for Patients With Early Multinodular Hepatocellular Carcinoma. JAMA Surg 2024; 159:881-889. [PMID: 38771633 PMCID: PMC11097094 DOI: 10.1001/jamasurg.2024.1184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Accepted: 03/01/2024] [Indexed: 05/22/2024]
Abstract
Importance The 2022 Barcelona Clinic Liver Cancer algorithm currently discourages liver resection (LR) for patients with multinodular hepatocellular carcinoma (HCC) presenting with 2 or 3 nodules that are each 3 cm or smaller. Objective To compare the efficacy of liver resection (LR), percutaneous radiofrequency ablation (PRFA), and transarterial chemoembolization (TACE) in patients with multinodular HCC. Design, Setting, and Participants This cohort study is a retrospective analysis conducted using data from the HE.RC.O.LE.S register (n = 5331) for LR patients and the ITA.LI.CA database (n = 7056) for PRFA and TACE patients. A matching-adjusted indirect comparison (MAIC) method was applied to balance data and potential confounding factors between the 3 groups. Included were patients from multiple centers from 2008 to 2020; data were analyzed from January to December 2023. Interventions LR, PRFA, or TACE. Main Outcomes and Measures Survival rates at 1, 3, and 5 years were calculated. Cox MAIC-weighted multivariable analysis and competing risk analysis were used to assess outcomes. Results A total of 720 patients with early multinodular HCC were included, 543 males (75.4%), 177 females (24.6%), and 350 individuals older than 70 years (48.6%). There were 296 patients in the LR group, 240 who underwent PRFA, and 184 who underwent TACE. After MAIC, LR exhibited 1-, 3-, and 5-year survival rates of 89.11%, 70.98%, and 56.44%, respectively. PRFA showed rates of 94.01%, 65.20%, and 39.93%, while TACE displayed rates of 90.88%, 48.95%, and 29.24%. Multivariable Cox survival analysis in the weighted population showed a survival benefit over alternative treatments (PRFA vs LR: hazard ratio [HR], 1.41; 95% CI, 1.07-1.86; P = .01; TACE vs LR: HR, 1.86; 95% CI, 1.29-2.68; P = .001). Competing risk analysis confirmed a lower risk of cancer-related death in LR compared with PRFA and TACE. Conclusions and Relevance For patients with early multinodular HCC who are ineligible for transplant, LR should be prioritized as the primary therapeutic option, followed by PRFA and TACE when LR is not feasible. These findings provide valuable insights for clinical decision-making in this patient population.
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Affiliation(s)
- Alessandro Vitale
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova, Second General Surgical Unit, Padova Teaching Hospital, Padua, Italy
| | - Pierluigi Romano
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova, Second General Surgical Unit, Padova Teaching Hospital, Padua, Italy
| | - Umberto Cillo
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova, Second General Surgical Unit, Padova Teaching Hospital, Padua, Italy
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Trevisani F, Vitale A, Kudo M, Kulik L, Park JW, Pinato DJ, Cillo U. Merits and boundaries of the BCLC staging and treatment algorithm: Learning from the past to improve the future with a novel proposal. J Hepatol 2024; 80:661-669. [PMID: 38266658 DOI: 10.1016/j.jhep.2024.01.010] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 12/03/2023] [Accepted: 01/04/2024] [Indexed: 01/26/2024]
Abstract
In this Expert Opinion, we thoroughly analyse the Barcelona Clinic Liver Cancer (BCLC) staging and treatment algorithm for hepatocellular carcinoma (HCC) that, since 1999, has standardised HCC management, offering a structured approach for the prognostic evaluation and treatment of patients with HCC. The first part of the article presents the strengths and evolutionary improvements of the BCLC staging system. Nevertheless, both patient characteristics and available treatments have changed in the last two decades, limiting the role of the BCLC criteria for treatment allocation in a growing number of patients. As therapeutic options expand and become more effective, the stage-linked treatment decision-making algorithm may lead to undertreatment and suboptimal outcomes for patients with disease beyond early-stage HCC. Consequently, strict adherence to BCLC criteria is limited in expert centres, particularly for patients diagnosed beyond early-stage HCC. Although the BCLC system remains the benchmark against which other therapeutic frameworks must be judged, the era of precision medicine calls for patient-tailored therapeutic decision-making (by a multidisciplinary tumour board) rather than stage-dictated treatment allocation. Acknowledging this conceptual difference in clinical management, the second part of the article describes a novel "multiparametric therapeutic hierarchy", which integrates a comprehensive assessment of clinical factors, biomarkers, technical feasibility, and resource availability. Lastly, considering the increasing efficacy of locoregional and systemic treatments, the concept of "converse therapeutic hierarchy" is introduced. These treatments can increase the feasibility (conversion approach) and effectiveness (adjuvant approach of systemic therapy) of potentially curative approaches to greatly improve clinical outcomes.
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Affiliation(s)
- Franco Trevisani
- Unit of Semetiotics, Liver and Alcohol-related Disease, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Units of Semetiotics, Liver and Alcohol-related disease, Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Alessandro Vitale
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy.
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | | | - Joon-Won Park
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - David J Pinato
- Department of Surgery & Cancer, Imperial College London, London, UK; Division of Oncology, Department of Translational Medicine (DIMET), The University of Piemonte Orientale "A. Avogadro", Novara, Italy
| | - Umberto Cillo
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy
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Biselli M, Reggidori N, Iavarone M, Renzulli M, Lani L, Granito A, Piscaglia F, Lorenzini S, Alimenti E, Vara G, Caraceni P, Sangiovanni A, Marignani M, Gigante E, Brandi N, Gramenzi A, Trevisani F. Impact of Sarcopenia on the Survival of Patients with Hepatocellular Carcinoma Treated with Sorafenib. Cancers (Basel) 2024; 16:1080. [PMID: 38539416 PMCID: PMC10968777 DOI: 10.3390/cancers16061080] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 02/29/2024] [Accepted: 03/05/2024] [Indexed: 01/04/2025] Open
Abstract
BACKGROUND AND AIMS Sarcopenia has been associated with poor outcomes in patients with cirrhosis and hepatocellular carcinoma. We investigated the impact of sarcopenia on survival in patients with advanced hepatocellular carcinoma treated with Sorafenib. METHODS A total of 328 patients were retrospectively analyzed. All patients had an abdominal CT scan within 8 weeks prior to the start of treatment. Two cohorts of patients were analyzed: the "Training Group" (215 patients) and the "Validation Group" (113 patients). Sarcopenia was defined by reduced skeletal muscle index, calculated from an L3 section CT image. RESULTS Sarcopenia was present in 48% of the training group and 50% of the validation group. At multivariate analysis, sarcopenia (HR: 1.47, p = 0.026 in training; HR 1.99, p = 0.033 in validation) and MELD > 9 (HR: 1.37, p = 0.037 in training; HR 1.78, p = 0.035 in validation) emerged as independent prognostic factors in both groups. We assembled a prognostic indicator named "SARCO-MELD" based on the two independent prognostic factors, creating three groups: group 1 (0 prognostic factors), group 2 (1 factor) and group 3 (2 factors), the latter with significantly worse survival and shorter time receiving treatment.
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Affiliation(s)
- Maurizio Biselli
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40124 Bologna, Italy; (M.B.); (L.L.); (S.L.); (P.C.); (A.G.); (F.T.)
- Department of Medical and Surgical Sciences, University of Bologna, 40124 Bologna, Italy; (A.G.); (F.P.)
| | - Nicola Reggidori
- Department of Internal Medicine, Ospedale per gli Infermi di Faenza, 48018 Faenza, Italy
| | - Massimo Iavarone
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (M.I.); (E.A.); (A.S.)
| | - Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (M.R.); (G.V.); (N.B.)
| | - Lorenzo Lani
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40124 Bologna, Italy; (M.B.); (L.L.); (S.L.); (P.C.); (A.G.); (F.T.)
- Department of Medical and Surgical Sciences, University of Bologna, 40124 Bologna, Italy; (A.G.); (F.P.)
| | - Alessandro Granito
- Department of Medical and Surgical Sciences, University of Bologna, 40124 Bologna, Italy; (A.G.); (F.P.)
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Fabio Piscaglia
- Department of Medical and Surgical Sciences, University of Bologna, 40124 Bologna, Italy; (A.G.); (F.P.)
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Stefania Lorenzini
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40124 Bologna, Italy; (M.B.); (L.L.); (S.L.); (P.C.); (A.G.); (F.T.)
| | - Eleonora Alimenti
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (M.I.); (E.A.); (A.S.)
| | - Giulio Vara
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (M.R.); (G.V.); (N.B.)
| | - Paolo Caraceni
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40124 Bologna, Italy; (M.B.); (L.L.); (S.L.); (P.C.); (A.G.); (F.T.)
- Department of Medical and Surgical Sciences, University of Bologna, 40124 Bologna, Italy; (A.G.); (F.P.)
| | - Angelo Sangiovanni
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (M.I.); (E.A.); (A.S.)
| | - Massimo Marignani
- Division of Gastroenterology and Hepatology, Ospedale Regina Apostolorum, 00041 Albano Laziale, Italy;
| | - Elia Gigante
- Service d’Hépato-Gastroentérologie et de Cancérologie Digestive, Hôpital Robert Debré, Université Reims-Champagne-Ardenne, 51092 Reims, France;
| | - Nicolò Brandi
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (M.R.); (G.V.); (N.B.)
| | - Annagiulia Gramenzi
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40124 Bologna, Italy; (M.B.); (L.L.); (S.L.); (P.C.); (A.G.); (F.T.)
- Department of Medical and Surgical Sciences, University of Bologna, 40124 Bologna, Italy; (A.G.); (F.P.)
| | - Franco Trevisani
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40124 Bologna, Italy; (M.B.); (L.L.); (S.L.); (P.C.); (A.G.); (F.T.)
- Department of Medical and Surgical Sciences, University of Bologna, 40124 Bologna, Italy; (A.G.); (F.P.)
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Yang H, Cong T, Luo Y, Yang C, Ren J, Li X. Prognostic Effect of Sarcopenia in Hepatocellular Carcinoma Patients Targeted with Interventional Therapy Combined with Immunotherapy and Targeted Therapy. J Hepatocell Carcinoma 2024; 11:175-189. [PMID: 38283695 PMCID: PMC10822115 DOI: 10.2147/jhc.s444530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 01/11/2024] [Indexed: 01/30/2024] Open
Abstract
Objective To investigated the association between sarcopenia and the prognosis and adverse events of hepatocellular carcinoma (HCC) patients undergoing interventional therapy combined with immunotherapy and targeted therapy. Methods Between January 2019 and December 2022, patients with unresectable HCC who received interventional therapy combined with immunotherapy and targeted therapy were included in this study. Total skeletal muscle area at the L3 level was normalized for height in m2 as the skeletal muscle index (SMI). All patients were divided into low and high SMI group according to the median SMI. Results Ninety-six consecutive patients were included eventually, with 49 patients in the high-SMI group and 47 patients in the low-SMI group. In the low-SMI group, the median overall survival (OS) was 459.00 days (95% CI, 334.76-583.24 days), and the 3-, 6-, and 12-month OS rates were 100%, 89.4% and 68.1%, respectively. In the high-SMI group, the median OS was not reached, and the 3-, 6-, and 12-month OS rates were 100%, 98% and 79.5%, respectively (p<0.05). SMI and Barcelona Clinic Liver Cancer (BCLC) C stage were independent prognostic factors for OS (p<0.05). In the low-SMI group, 26 patients had treatment-related adverse events (TRAEs), resulting in dose adjustment or treatment suspension for 10 patients. In the high-SMI group, 33 patients had TRAEs, and 18 patients received dose adjustment or treatment suspension; the between-group difference was nonsignificant (p>0.05). Conclusion SMI is associated with the prognosis of HCC patients receiving interventional therapy combined with immunotherapy and targeted therapy, and sarcopenia is an independent risk factor for OS. However, sarcopenia does not seem to predict the occurrence of adverse events.
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Affiliation(s)
- Hongcai Yang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China
| | - Tianhao Cong
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China
| | - Yingen Luo
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China
| | - Chao Yang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China
| | - Jinrui Ren
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China
| | - Xiao Li
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China
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Romano P, Busti M, Billato I, D’Amico F, Marchegiani G, Pelizzaro F, Vitale A, Cillo U. Liver resection versus radiofrequency ablation or trans-arterial chemoembolization for early-stage (BCLC A) oligo-nodular hepatocellular carcinoma: meta-analysis. BJS Open 2024; 8:zrad158. [PMID: 38323881 PMCID: PMC10848305 DOI: 10.1093/bjsopen/zrad158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 10/25/2023] [Accepted: 11/26/2023] [Indexed: 02/08/2024] Open
Abstract
BACKGROUND The 2022 Barcelona Clinic Liver Cancer (BCLC) algorithm does not recommend liver resection (LR) in BCLC A patients with oligo-nodular (two or three nodules ≤3 cm) hepatocellular carcinoma (HCC). This sharply contrasts with the therapeutic hierarchy concept, implying a precise treatment order exists within each BCLC stage. This study aimed to compare the outcomes of LR versus radiofrequency ablation (RFA) or trans-arterial chemoembolization (TACE) in BCLC A patients. METHODS A meta-analysis adhering to PRISMA guidelines and the Cochrane Handbook was performed. All RCT, cohort and case-control studies that compared LR versus RFA or TACE in oligo-nodular BCLC A HCC published between January 2000 and October 2023 were comprehensively searched on PubMed, Embase, the Cochrane Library and China Biology Medicine databases. Primary outcomes were overall survival (OS) and disease-free survival (DFS) at 3 and 5 years. Risk ratio (RR) was computed as a measure of treatment effect (OS and DFS benefit) to calculate common and random effects estimates for meta-analyses with binary outcome data. RESULTS 2601 patients from 14 included studies were analysed (LR = 1227, RFA = 686, TACE = 688). There was a significant 3- and 5-year OS benefit of LR over TACE (RR = 0.55, 95% c.i. 0.44 to 0.69, P < 0.001 and RR 0.57, 95% c.i. 0.36 to 0.90, P = 0.030, respectively), while there was no significant 3- and 5-year OS benefit of LR over RFA (RR = 0.78, 95% c.i. 0.37 to 1.62, P = 0.452 and RR 0.74, 95% c.i. 0.50 to 1.09, P = 0.103, respectively). However, a significant 3- and 5-year DFS benefit of LR over RFA was found (RR = 0.70, 95% c.i. 0.54 to 0.93, P = 0.020 and RR 0.82, 95% c.i. 0.72 to 0.95, P = 0.015, respectively). A single study comparing LR and TACE regarding DFS showed a significant superiority of LR. The Newcastle-Ottawa Scale quality of studies was high in eight (57%) and moderate in six (43%). CONCLUSIONS In BCLC A oligo-nodular HCC patients, LR should be preferred to RFA or TACE (therapeutic hierarchy concept). Additional comparative cohort studies are urgently needed to increase the certainty of this evidence.
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Affiliation(s)
- Pierluigi Romano
- Department of Surgical Oncological and Gastroenterological Sciences, Padua University Hospital, Padua, Italy
| | - Marco Busti
- Department of Surgical Oncological and Gastroenterological Sciences, Padua University Hospital, Padua, Italy
| | - Ilaria Billato
- Department of Surgical Oncological and Gastroenterological Sciences, Padua University Hospital, Padua, Italy
- Department of Biology, University of Padua, Padua, Italy
| | - Francesco D’Amico
- Bari University Hospital, Policlinico di Bari Ospedale Giovanni XXIII, U.O.S.D. Hepatobiliary Surgery, Bari, Italy
| | - Giovanni Marchegiani
- Department of Surgical Oncological and Gastroenterological Sciences, Padua University Hospital, Padua, Italy
| | - Filippo Pelizzaro
- Department of Surgical Oncological and Gastroenterological Sciences, Padua University Hospital, Padua, Italy
| | - Alessandro Vitale
- Department of Surgical Oncological and Gastroenterological Sciences, Padua University Hospital, Padua, Italy
| | - Umberto Cillo
- Department of Surgical Oncological and Gastroenterological Sciences, Padua University Hospital, Padua, Italy
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Vitale A, Cabibbo G, Iavarone M, Viganò L, Pinato DJ, Ponziani FR, Lai Q, Casadei-Gardini A, Celsa C, Galati G, Gambato M, Crocetti L, Renzulli M, Giannini EG, Farinati F, Trevisani F, Cillo U. Personalised management of patients with hepatocellular carcinoma: a multiparametric therapeutic hierarchy concept. Lancet Oncol 2023; 24:e312-e322. [PMID: 37414020 DOI: 10.1016/s1470-2045(23)00186-9] [Citation(s) in RCA: 95] [Impact Index Per Article: 47.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 04/07/2023] [Accepted: 04/20/2023] [Indexed: 07/08/2023]
Abstract
Advances in the surgical and systemic therapeutic landscape of hepatocellular carcinoma have increased the complexity of patient management. A dynamic adaptation of the available staging-based algorithms is required to allow flexible therapeutic allocation. In particular, real-world hepatocellular carcinoma management increasingly relies on factors independent of oncological staging, including patients' frailty, comorbid burden, critical tumour location, multiple liver functional parameters, and specific technical contraindications impacting the delivery of treatment and resource availability. In this Policy Review we critically appraise how treatment allocation strictly based on pretreatment staging features has shifted towards a more personalised treatment approach, in which expert tumour boards assume a central role. We propose an evidence-based framework for hepatocellular carcinoma treatment based on the novel concept of multiparametric therapeutic hierarchy, in which different therapeutic options are ordered according to their survival benefit (ie, from surgery to systemic therapy). Moreover, we introduce the concept of converse therapeutic hierarchy, in which therapies are ordered according to their conversion abilities or adjuvant abilities (ie, from systemic therapy to surgery).
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Affiliation(s)
- Alessandro Vitale
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy.
| | - Giuseppe Cabibbo
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy.
| | - Massimo Iavarone
- Division of Gastroenterology and Hepatology, Foundation Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Luca Viganò
- Hepatobiliary Unit, Department of Minimally Invasive General & Oncologic Surgery, Humanitas Gavazzeni University Hospital, Bergamo, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - David J Pinato
- Department of Surgery & Cancer, Imperial College London, London, UK; Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
| | - Francesca Romana Ponziani
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, Azienda Ospedaliero-Universitaria Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Andrea Casadei-Gardini
- Department of Oncology, Istituto di Ricovero Cura a Carattere Scientifico San Raffaele Scientific Institute Hospital, Vita-Salute San Raffaele University, Milan, Italy
| | - Ciro Celsa
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy; Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy
| | - Giovanni Galati
- Unit of Clinical Medicine and Hepatology, University Campus Bio-Medico, Rome, Italy
| | - Martina Gambato
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy
| | - Laura Crocetti
- Department of Radiology and Interventional Radiology, University of Pisa, Pisa, Italy
| | - Matteo Renzulli
- Department of Radiology, Istituto di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genova, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Policlinico San Martino, Genova, Italy
| | - Fabio Farinati
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy
| | - Franco Trevisani
- Unit of Semeiotics, Liver and Alcohol-related diseases, Istituto di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Umberto Cillo
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy
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10
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Wong JK, Lim HJ, Tam VC, Burak KW, Dawson LA, Chaudhury P, Abraham RJ, Meyers BM, Sapisochin G, Valenti D, Samimi S, Ramjeesingh R, Mujoomdar A, Martins I, Dixon E, Segedi M, Liu DM. Clinical consensus statement: Establishing the roles of locoregional and systemic therapies for the treatment of intermediate-stage hepatocellular carcinoma in Canada. Cancer Treat Rev 2023; 115:102526. [PMID: 36924644 DOI: 10.1016/j.ctrv.2023.102526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 02/12/2023] [Accepted: 02/14/2023] [Indexed: 03/06/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) a leading cause of cancer mortality worldwide and approximately one-third of patients present with intermediate-stage disease. The treatment landscape of intermediate-stage HCC is rapidly evolving due to developments in local, locoregional and systemic therapies. Treatment recommendations focused on this heterogenous disease stage and that take into account the Canadian reality are lacking. To address this gap, a pan-Canadian group of experts in hepatology, transplant, surgery, radiation therapy, nuclear medicine, interventional radiology, and medical oncology came together to develop consensus recommendations on management of intermediate-stage HCC relevant to the Canadian context. METHODS A modified Delphi framework was used to develop consensus statements with strengths of recommendation and supporting levels of evidence graded using the AHA/ACC classification system. Tentative consensus statements were drafted based on a systematic search and expert input in a series of iterative feedback cycles and were then circulated via online survey to assess the level of agreement. RESULTS & CONCLUSION The pre-defined ratification threshold of 80 % agreement was reached for all statements in the areas of multidisciplinary treatment (n = 4), intra-arterial therapy (n = 14), biologics (n = 5), radiation therapy (n = 3), surgical resection and transplantation (n = 7), and percutaneous ablative therapy (n = 4). These generally reflected an expansion in treatment options due to developments in previously established or emergent techniques, introduction of new and more active therapies and increased therapeutic flexibility. These developments have allowed for greater treatment tailoring and personalization as well as a paradigm shift toward strategies with curative intent in a wider range of disease settings.
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Affiliation(s)
- Jason K Wong
- University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.
| | - Howard J Lim
- BC Cancer Agency, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada.
| | - Vincent C Tam
- Tom Baker Cancer Centre, University of Calgary, 1331 29 St NW, Calgary, AB T2N 4N2, Canada.
| | - Kelly W Burak
- University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.
| | - Laura A Dawson
- Princess Margaret Cancer Centre, University of Toronto, 610 University Ave, Toronto, ON M5G 2C1, Canada.
| | | | - Robert J Abraham
- Department of Diagnostic Radiology, Dalhousie University, 6299 South St, Halifax, NS B3H 4R2, Canada.
| | - Brandon M Meyers
- Juravinski Cancer Centre, 699 Concession St, Hamilton, ON L8V 5C2, Canada.
| | | | - David Valenti
- McGill University, 845 Rue Sherbrooke O, Montréal, QC H3A 0G4, Canada.
| | - Setareh Samimi
- Hopital Sacre-Coeur de Montreal, University of Montreal, 5400 Boul Gouin O, Montréal, QC H4J 1C5, Canada.
| | - Ravi Ramjeesingh
- Department of Medicine, Dalhousie University, 6299 South St, Halifax, NS B3H 4R2, Canada.
| | - Amol Mujoomdar
- Western University, 1151 Richmond Street, London, ON N6A 5B9, Canada.
| | - Ilidio Martins
- Kaleidoscope Strategic, Inc. 1 King Street W, Suite 4800 - 117, Toronto, ON M5H 1A1, Canada.
| | - Elijah Dixon
- University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.
| | - Maja Segedi
- Department of Surgery, Vancouver General Hospital, Jim Pattison Pavilion, 899 W 12th Ave, Vancouver, BC V5Z 1M9, Canada.
| | - David M Liu
- School of Biomedical Engineering, University of British Columbia, 2329 West Mall Vancouver, BC V6T 1Z4, Canada.
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11
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Milana F, Polidoro MA, Famularo S, Lleo A, Boldorini R, Donadon M, Torzilli G. Surgical Strategies for Recurrent Hepatocellular Carcinoma after Resection: A Review of Current Evidence. Cancers (Basel) 2023; 15:508. [PMID: 36672457 PMCID: PMC9856445 DOI: 10.3390/cancers15020508] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 01/07/2023] [Accepted: 01/10/2023] [Indexed: 01/17/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and both liver resection and liver transplantation are considered potentially curative options. However, high recurrence rates affect the prognosis depending both on the primary HCC pathology characteristics or on the type and time of the relapse. While great attention has been usually posted on treatment algorithms for the first HCC, treatment algorithms for recurrent HCC (rHCC) are lacking. In these cases, surgery still represents a curative option with both redo hepatectomy and/or salvage liver transplantation, which are considered valid treatments in selected patients. In the current era of personalised medicine with promises of new systemic-targeted immuno-chemotherapies, we wished to perform a narrative review of the literature on the role of surgical strategies for rHCC.
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Affiliation(s)
- Flavio Milana
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy
- Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy
| | - Michela Anna Polidoro
- Hepatobiliary Immunopathology Laboratory, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy
| | - Simone Famularo
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy
- Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy
| | - Ana Lleo
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy
- Department of Internal Medicine, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy
| | - Renzo Boldorini
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, NO, Italy
- Department of Pathology, University Maggiore Hospital, 28100 Novara, NO, Italy
| | - Matteo Donadon
- Hepatobiliary Immunopathology Laboratory, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, NO, Italy
- Department of General Surgery, University Maggiore Hospital, 28100 Novara, NO, Italy
| | - Guido Torzilli
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy
- Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy
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12
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Vitale A, Svegliati-Baroni G, Ortolani A, Cucco M, Dalla Riva GV, Giannini EG, Piscaglia F, Rapaccini G, Di Marco M, Caturelli E, Zoli M, Sacco R, Cabibbo G, Marra F, Mega A, Morisco F, Gasbarrini A, Foschi FG, Missale G, Masotto A, Nardone G, Raimondo G, Azzaroli F, Vidili G, Oliveri F, Pelizzaro F, Ramirez Morales R, Cillo U, Trevisani F, Miele L, Marchesini G, Farinati F. Epidemiological trends and trajectories of MAFLD-associated hepatocellular carcinoma 2002-2033: the ITA.LI.CA database. Gut 2023; 72:141-152. [PMID: 34933916 DOI: 10.1136/gutjnl-2021-324915] [Citation(s) in RCA: 89] [Impact Index Per Article: 44.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Accepted: 11/29/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a new inclusive definition of the whole spectrum of liver diseases associated to metabolic disorders. The main objective of this study was to compare patients with MAFLD and non-MAFLD with hepatocellular carcinoma (HCC) included in a nationally representative cohort. METHODS We analysed 6882 consecutive patients with HCC enrolled from 2002 to 2019 by 23 Italian Liver Cancer centres to compare epidemiological and future trends in three subgroups: pure, single aetiology MAFLD (S-MAFLD); mixed aetiology MAFLD (metabolic and others, M-MAFLD); and non-MAFLD HCC. RESULTS MAFLD was diagnosed in the majority of patients with HCC (68.4%). The proportion of both total MAFLD and S-MAFLD HCC significantly increased over time (from 50.4% and 3.6% in 2002-2003, to 77.3% and 28.9% in 2018-2019, respectively, p<0.001). In Italy S-MAFLD HCC is expected to overcome M-MAFLD HCC in about 6 years. Patients with S-MAFLD HCC were older, more frequently men and less frequently cirrhotic with clinically relevant portal hypertension and a surveillance-related diagnosis. They had more frequently large tumours and extrahepatic metastases. After weighting, and compared with patients with non-MAFLD, S-MAFLD and M-MAFLD HCC showed a significantly lower overall (p=0.026, p=0.004) and HCC-related (p<0.001, for both) risk of death. Patients with S-MAFLD HCC showed a significantly higher risk of non-HCC-related death (p=0.006). CONCLUSIONS The prevalence of MAFLD HCC in Italy is rapidly increasing to cover the majority of patients with HCC. Despite a less favourable cancer stage at diagnosis, patients with MAFLD HCC have a lower risk of HCC-related death, suggesting reduced cancer aggressiveness.
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Affiliation(s)
- Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
| | - Gianluca Svegliati-Baroni
- Liver Disease and Transplant Unit, Polytechnic University of Marche, Ancona, Italy
- Obesity Center, Polytechnic University of Marche, Ancona, Italy
| | - Alessio Ortolani
- Department of Gastroenterology, Azienda Ospedaliera Marche Nord Pesaro, Pesaro, Italy
| | - Monica Cucco
- Liver Disease and Transplant Unit, Polytechnic University of Marche, Ancona, Italy
- Department of Gastroenterology, Polytechnic University of Marche, Ancona, Italy
| | - Giulio V Dalla Riva
- School of Mathematics and Statistics University of Canterbury, Statistics University of Canterbury, Canterbury, New Zealand
| | - Edoardo G Giannini
- Department of Internal Medicine, Gastroenterology Unit, University of Genova, IRCCS Policlinico San Martino, Genoa, Italy
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gianludovico Rapaccini
- Gastroenterology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
| | | | | | - Marco Zoli
- Department of Medical and Surgical Sciences, Internal Medicine-Zoli Unit, Alma Mater Studiorum - Università di Bologna, Padova, Italy
| | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Puglia, Italy
| | - Giuseppe Cabibbo
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Florence, Florence, Italy
| | - Andrea Mega
- Gastroenterology Unit, Ospedale Generale Regionale di Bolzano, Bolzano, Italy
| | - Filomena Morisco
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples Federico II, Portici, Italy
| | - Antonio Gasbarrini
- Internal Medicine, Gastroenterology, and Liver Unit, University Hospital Agostino Gemelli, Roma, Lazio, Italy
| | | | - Gabriele Missale
- Infectious Diseases and Hepatology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Emilia-Romagna, Italy
| | - Alberto Masotto
- Gastroenterology Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Veneto, Italy
| | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, Federico II University Hospital, Napoli, Italy
| | - Giovanni Raimondo
- Clinical and Experimental Medicine, University Hospital of Messina, Messina, Italy
| | - Francesco Azzaroli
- Division of Gastroenterology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gianpaolo Vidili
- Department of Clinical and Experimental Medicine, Universita degli Studi di Sassari, Sassari, Italy
| | - Filippo Oliveri
- Department of Clinical and Experimental Medicine, Hepatology and Liver Physiopathology Laboratory and Internal Medicine, University of Pisa, Pisa, Italy
| | - Filippo Pelizzaro
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
| | - Rafael Ramirez Morales
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
| | - Franco Trevisani
- Division of Medical Semeiotics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Luca Miele
- Internal Medicine and Gastroenterology, Fondazione Policlinico Gemelli, Rome, Italy
- Internal Medicine, Universita Cattolica del Sacro Cuore, Roma, Italy
| | - Giulio Marchesini
- Department of Medical & Surgical Sciences, University of Bologna Hospital of Bologna Sant'Orsola-Malpighi Polyclinic, Bologna, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
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13
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Finotti M, Romano M, Brizzolari M, Scopelliti M, Zanus G. Comment on: " A review on radiofrequency, microwave and high-intensity focused ultrasound ablations for hepatocellular carcinoma with cirrhosis". Hepatobiliary Surg Nutr 2022; 11:640-642. [PMID: 36016748 PMCID: PMC9396087 DOI: 10.21037/hbsn-22-202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 06/14/2022] [Indexed: 11/30/2022]
Affiliation(s)
- Michele Finotti
- 4th Surgery Unit, Regional Hospital Treviso, University of Padua, Dipartimento di Scienze Chirurgiche Oncologiche e Gastroenterologiche (DISCOG), Padua, Italy
- Baylor Scott & White Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical, Dallas, TX, USA
| | - Maurizio Romano
- 4th Surgery Unit, Regional Hospital Treviso, University of Padua, Dipartimento di Scienze Chirurgiche Oncologiche e Gastroenterologiche (DISCOG), Padua, Italy
| | - Marco Brizzolari
- 4th Surgery Unit, Regional Hospital Treviso, University of Padua, Dipartimento di Scienze Chirurgiche Oncologiche e Gastroenterologiche (DISCOG), Padua, Italy
| | - Michele Scopelliti
- 4th Surgery Unit, Regional Hospital Treviso, University of Padua, Dipartimento di Scienze Chirurgiche Oncologiche e Gastroenterologiche (DISCOG), Padua, Italy
| | - Giacomo Zanus
- 4th Surgery Unit, Regional Hospital Treviso, University of Padua, Dipartimento di Scienze Chirurgiche Oncologiche e Gastroenterologiche (DISCOG), Padua, Italy
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14
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Pelizzaro F, Haxhi S, Penzo B, Vitale A, Giannini EG, Sansone V, Rapaccini GL, Di Marco M, Caturelli E, Magalotti D, Sacco R, Celsa C, Campani C, Mega A, Guarino M, Gasbarrini A, Svegliati-Baroni G, Foschi FG, Olivani A, Masotto A, Nardone G, Raimondo G, Azzaroli F, Vidili G, Brunetto MR, Trevisani F, Farinati F. Transarterial Chemoembolization for Hepatocellular Carcinoma in Clinical Practice: Temporal Trends and Survival Outcomes of an Iterative Treatment. Front Oncol 2022; 12:822507. [PMID: 35174092 PMCID: PMC8841805 DOI: 10.3389/fonc.2022.822507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 01/07/2022] [Indexed: 12/04/2022] Open
Abstract
Background Transarterial chemoembolization (TACE) is one of the most frequently applied treatments for hepatocellular carcinoma (HCC) worldwide. In this study, we aimed at evaluating whether and how TACE application and repetition, as well as the related outcome, have changed over the last three decades in Italy. Methods Data of 7,184 patients with HCC were retrieved from the Italian Liver Cancer (ITA.LI.CA) database. Patients were divided according to the period of diagnosis in six cohorts: P1 (1988–1993), P2 (1994–1998), P3 (1999–2004), P4 (2005–2009), P5 (2010–2014), and P6 (2015–2019). All the analyses were repeated in the overall patient population and in Barcelona Clinic Liver Cancer (BCLC) B patients, who are the subgroup of HCC patients originally supposed to receive TACE according to guidelines. TACE was defined as either the first or the main (more effective) treatment. Results The proportion of patients receiving TACE as first or main therapy declined over time, and less than 50% of BCLC B patients were treated with chemoembolization from P3 onward. Conversely, TACE was widely used even outside the intermediate stage. Survival of TACE-treated patients progressively increased from P1 to P6. Although TACE was performed only once in the majority of patients, there was an increasing proportion of those receiving 2 or ≥3 treatments sessions over time. The overall survival (OS) of patients undergoing repeated treatments was significantly higher compared to those managed with a single TACE (median OS 40.0 vs. 65.0 vs. 71.8 months in 1, 2, and ≥3 TACE groups, respectively; p < 0.0001). However, after a first-line TACE, the adoption of curative therapies provided longer survival than repeating TACE (83.0 vs. 42.0 months; p < 0.0001), which in turn was associated with better outcomes compared to systemic therapies or best supportive care (BSC). Conclusions Despite a decline in the percentage of treated patients over time, TACE has still an important role in the management of HCC patients. The survival of TACE-treated patients gradually improved over time, probably due to a better patient selection. Iterative TACE is effective, but an upward shift to curative therapies provides better outcomes while transition to systemic therapies and BSC leads to a worse prognosis.
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Affiliation(s)
- Filippo Pelizzaro
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padova, Padova, Italy
| | - Selion Haxhi
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padova, Padova, Italy
| | - Barbara Penzo
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padova, Padova, Italy
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, University of Padova, Padova, Italy
| | - Edoardo G. Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genova, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Policlinico San Martino, Genova, Italy
| | - Vito Sansone
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gian Ludovico Rapaccini
- Gastroenterology Unit, Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Roma, Italy
| | | | | | - Donatella Magalotti
- Internal Medicine Unit, Department of Medical and Surgical Sciences, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Italy
| | - Ciro Celsa
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties (PROMISE), Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy
- Department of Surgical, Oncological and Oral Sciences (Di.Chir.On.S.), University of Palermo, Palermo, Italy
| | - Claudia Campani
- Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Firenze, Firenze, Italy
| | - Andrea Mega
- Gastroenterology Unit, Bolzano Regional Hospital, Bolzano, Italy
| | - Maria Guarino
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Napoli “Federico II”, Napoli, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Università Cattolica del Sacro Cuore, Roma, Italy
| | | | | | - Andrea Olivani
- Infectious Diseases and Hepatology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Alberto Masotto
- Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, University of Napoli “Federico II”, Napoli, Italy
| | - Giovanni Raimondo
- Department of Clinical and Experimental Medicine, Clinical and Molecular Hepatology Unit, University of Messina, Messina, Italy
| | - Francesco Azzaroli
- Gastroenterology Unit, Department of Surgical and Medical Sciences, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gianpaolo Vidili
- Department of Medical, Surgical and Experimental Sciences, Clinica Medica Unit, University of Sassari, Azienda Ospedaliero-Universitaria di Sassari, Sassari, Italy
| | - Maurizia Rossana Brunetto
- Department of Clinical and Experimental Medicine, Hepatology and Liver Physiopathology Laboratory and Internal Medicine Unit, University of Pisa, Pisa, Italy
| | - Franco Trevisani
- Medical Semeiotics Unit, Department of Medical and Surgical Sciences, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padova, Padova, Italy
- *Correspondence: Fabio Farinati,
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15
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Perisetti A, Goyal H, Yendala R, Chandan S, Tharian B, Thandassery RB. Sarcopenia in hepatocellular carcinoma: Current knowledge and future directions. World J Gastroenterol 2022; 28:432-448. [PMID: 35125828 PMCID: PMC8790553 DOI: 10.3748/wjg.v28.i4.432] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 06/29/2021] [Accepted: 01/11/2022] [Indexed: 02/06/2023] Open
Abstract
Liver cancer is the second most occurring cancer worldwide and is one of the leading causes of cancer-related deaths. Hepatocellular carcinoma (HCC) is the most common (80%-90%) type among malignant liver cancers. Sarcopenia occurs very early in HCC and can predict and provide an opportunity to improve muscle health before engaging in the treatment options such as loco-regional, systemic, and transplant management. Multiple prognostic stating systems have been developed in HCC, such as Barcelona Clinic Liver Cancer, Child-Pugh score and Albumin-Bilirubin grade. However, the evaluation of patients' performance status is a major limitation of these scoring systems. In this review, we aim to summarize the current knowledge and recent advances about the role of sarcopenia in cirrhosis in general, while focusing specifically on HCC. Additionally, the role of sarcopenia in predicting clinical outcomes and prognostication in HCC patients undergoing loco-regional therapies, liver resection, liver transplantation and systematic therapy has been discussed. A literature review was performed using databases PubMed/MEDLINE, EMBASE, Cochrane, Web of Science, and CINAHL on April 1, 2021, to identify published reports on sarcopenia in HCC. Sarcopenia can independently predict HCC-related mortality especially in patients undergoing treatments such as loco-regional, surgical liver transplantation and systemic therapies. Basic research is focused on evaluating a balance of anabolic and catabolic pathways responsible for muscle health. Early clinical studies have shown promising results in methods to improve sarcopenia in HCC which can potentially increase prognosis in these patients. As sarcopenia occurs very early in HCC, it can predict and provide an opportunity to improve muscle health before engaging in the treatment options such as loco-regional, systemic, and transplant management. Further, sarcopenia measurement can obviate the confounding caused by the abdominal ascites in these patients. The use of sarcopenia can add to the existing scoring systems to better prognosticate the HCC.
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Affiliation(s)
- Abhilash Perisetti
- Department of Internal Medicine, Gastroenterology and Hepatology Division, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States
- Department of Interventional Oncology and Surgical Endoscopy, Parkview Health, Fort Wayne, IN 46825, United States
| | - Hemant Goyal
- Department of Internal Medicine, The Wright Center for Graduate Medical Education, The Wright Center for Graduate Medical Education, Scranton, PA 18501, United States
| | - Rachana Yendala
- Department of Hematology and Oncology, Conway Regional Medical Center, Conway, AR 72034, United States
| | - Saurabh Chandan
- Department of Internal Medicine, Gastroenterology and Hepatology Division, CHI Creighton University Medical Center, Omaha, NE 68107, United States
| | - Benjamin Tharian
- Department of Internal Medicine, Gastroenterology and Hepatology Division, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States
| | - Ragesh Babu Thandassery
- Department of Medicine, Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, United States
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Trevisani F, Giannini EG. The ITA.LI.CA Consortium: How multicentre collaboration helped shape the management of patients with hepatocellular carcinoma on the basis of real-world evidence. Ann Hepatol 2022; 27 Suppl 1:100564. [PMID: 34688886 DOI: 10.1016/j.aohep.2021.100564] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 08/19/2021] [Indexed: 02/04/2023]
Abstract
The growing diffusion of digitalisation and informatics has promoted the creation and analysis of large databases able to provide solid information. Analyses of "big data" generated by real-world practice are particularly useful for knowing incidence and mortality, disparities, temporal trends of diseases, identifying risk factors, predicting future scenarios, obtaining inputs for cost-effectiveness and treatment benefit modelling, designing new studies, and monitoring rare diseases. Although randomised controlled trials (RCTs) represent the gold-standard for generating evidence about new diagnostic, preventive or therapeutic procedures, their results should be integrated with real-world data to personalise patient management. Indeed, a substantial proportion of patients observed in field-practice have characteristics that prevent the access to RCTs or, when included, form sub-groups too small to provide robust post-hoc analyses. Furthermore, as RCTs are resource-consuming and designed to maximize the probability of success, they are generally performed in expert centres of high-income areas, excluding economically-deprived regions which could complementarily contribute to the medical progress as huge sources of real-world data. These considerations fuelled the creation in 1998 of the Italian Liver Cancer (ITA.LI.CA) consortium, with the aim to merge data of patients with hepatocellular carcinoma (HCC) managed in several centres. This cooperation permitted to analyse a multicentre, large cohort of HCC patients. Since then, the ITA.LI.CA group has progressively expanded to currently include 24 centres, and its database counts more than 9,000 patients. This article describes the history of the ITA.LI.CA consortium and presents its scientific production whose results greatly contributed to the incessant improvement of HCC management.
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Affiliation(s)
- Franco Trevisani
- Medical Semeiotics Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Italy; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
| | - Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy
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Hu S, Gan W, Qiao L, Ye C, Wu D, Liao B, Yang X, Jiang X. A New Prognostic Algorithm Predicting HCC Recurrence in Patients With Barcelona Clinic Liver Cancer Stage B Who Received PA-TACE. Front Oncol 2021; 11:742630. [PMID: 34745962 PMCID: PMC8566809 DOI: 10.3389/fonc.2021.742630] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 09/27/2021] [Indexed: 01/05/2023] Open
Abstract
Background Postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) is effective in preventing the recurrence of hepatocellular carcinoma (HCC) in patients treated with surgery. However, there is a lack of reports studying the risk factors associated with recurrence in HCC patients who received PA-TACE. In this study, we identified the independent risk factors for recurrence of HCC patients who received PA-TACE. We also developed a novel, effective, and valid nomogram to predict the individual probability of recurrence, 1, 3, and 5 years after PA-TACE. Methods A retrospective study was performed to identify the independent risk factors for recurrence of HCC in a group of 502 patients diagnosed in stage B based on the Barcelona Clinic Liver Cancer (BCLC) evaluation system for HCC that underwent curative resections. Then, subgroup analysis was performed for 184 patients who received PA-TACE, who were included in the training cohort. The other 147 HCC patients were included in a validation cohort. A recurrence-free survival (RFS)-predicting nomogram was constructed, and results were assessed using calibration and decision curves and a time-dependent AUC diagram. Results PA-TACE was shown to be a significant independent prognostic value for patients with BCLC stage B [p < 0.001, hazard ratio (HR) = 0.508, 95% CI = 0.375–0.689 for OS, p = 0.002; HR = 0.670, 95%CI = 0.517–0.868 for RFS]. Alpha fetoprotein (AFP), tumor number, tumor size, microvascular invasion (MVI), and differentiation were considered as independent risk factors for RFS in the training cohort, and these were further confirmed in the validation cohort. Next, a nomogram was constructed to predict RFS. The C-index for RFS in the nomogram was 0.721 (95% CI = 0.718–0.724), which was higher than SNACOR, HAP, and CHIP scores (0.587, 0.573, and 0.607, respectively). Calibration and decision curve analyses and a time-dependent AUC diagram were used. Our nomogram showed stronger performance than these other nomograms in both the training and validation cohorts. Conclusions HCC patients diagnosed as stage B according to BCLC may benefit from PA-TACE after surgery. The RFS nomogram presented here provides an accurate and reliable prognostic model to monitor recurrence. Patients with a high recurrence score based on the nomogram should receive additional high-end imaging exams and shorter timeframes in between follow-up visits.
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Affiliation(s)
- Shuyang Hu
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Wei Gan
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis & Cancer Invasion, The Chinese Ministry of Education, Shanghai, China
| | - Liang Qiao
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Cheng Ye
- Medical Center of Fudan University, Shanghai, China
| | - Demin Wu
- Department of Health Physical Examination, Shanghai Electric Power Hospital, Shanghai, China
| | - Boyi Liao
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Xiaoyu Yang
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Xiaoqing Jiang
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
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Li Q, Zhang L, Hou ZH, Zhao DX, Li JB, Zhang S, Yin Y, Ni CF, Chen T. High Visceral Adipose Tissue Density Correlates With Unfavorable Outcomes in Patients With Intermediate-Stage Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization. Front Cell Dev Biol 2021; 9:710104. [PMID: 34568324 PMCID: PMC8455878 DOI: 10.3389/fcell.2021.710104] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Accepted: 08/11/2021] [Indexed: 12/14/2022] Open
Abstract
Objectives: This study aimed to evaluate the association between different body composition features with prognostic outcomes of intermediate stage hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE). Methods: The areas and density of skeletal muscle area (SM) and adipose tissue [subcutaneous (SAT); visceral (VAT)] were calculated on the pre-TACE CT scans. Overall survival (OS) and progression-free survival (PFS) curves were calculated using the Kaplan-Meier method and compared with log-rank test. The discrimination and performance of body composition features were measured by area under time-dependent receiver operating characteristic (ROC) curve. Univariate and multivariate Cox proportional hazard analyses were applied to identify the association between body composition parameters and outcomes. Results: A significant prolonged OS and PFS was displayed by Kaplan-Meier curve analysis for HCC patients with VAT HU below -89.1 (25.1 months, 95% CI: 18.1-32.1 vs. 17.6 months, 95% CI: 16.3-18.8, p < 0.0001, 15.4 months, 95% CI: 10.6-20.2 vs. 6.6 months, 95% CI: 4.9-8.3, p < 0.0001, respectively). The 1-, 2-, 3-, and 5-year OS area under the curve (AUC) values of the VAT HU were higher than the other body composition parameters. Meanwhile, it is also found that 3-, 6-, 9-, and 12-month PFS AUC values of VAT HU were the highest among all the parameters. Univariate and multivariate Cox-regression analysis suggested a significant association between VAT density and outcomes (OS, HR: 1.015, 95% CI: 1.004-1.025, p = 0.005, PFS, HR: 1.026, 95% CI: 1.016-1.036, p < 0.0001, respectively). Conclusion: The VAT density could provide prognostic prediction value and may be helpful to stratify the intermediate stage HCC patients.
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Affiliation(s)
- Qiang Li
- Department of Radiology, The Affiliated People's Hospital of Ningbo University, Ningbo, China
| | - Lei Zhang
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Zhong-Heng Hou
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Dong-Xu Zhao
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jian-Bin Li
- Department of Radiology, The Affiliated People's Hospital of Ningbo University, Ningbo, China
| | - Shuai Zhang
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yu Yin
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Cai-Fang Ni
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Tao Chen
- Department of General Surgery, Jiangsu Province Hospital, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
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Famularo S, Donadon M, Cipriani F, Bernasconi DP, LaBarba G, Dominioni T, Iaria M, Molfino S, Conci S, Ferrari C, Garatti M, Delvecchio A, Troci A, Patauner S, Frassani S, Cosimelli M, Zanus G, Giuliante F, Jovine E, Valsecchi MG, Grazi G, Antonucci A, Frena A, Crespi M, Memeo R, Zimmitti G, Griseri G, Ruzzenente A, Baiocchi G, DallaValle R, Maestri M, Ercolani G, Aldrighetti L, Torzilli G, Romano F. Curative versus palliative treatments for recurrent hepatocellular carcinoma: a multicentric weighted comparison. HPB (Oxford) 2021; 23:889-898. [PMID: 33144053 DOI: 10.1016/j.hpb.2020.10.007] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 09/17/2020] [Accepted: 10/05/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Management of recurrence after surgery for hepatocellular carcinoma (rHCC) is still a debate. The aim was to compare the Survival after Recurrence (SAR) of curative (surgery or thermoablation) versus palliative (TACE or Sorafenib) treatments for patients with rHCC. METHODS This is a multicentric Italian study, which collected data between 2007 and 2018 from 16 centers. Selected patients were then divided according to treatment allocation in Curative (CUR) or Palliative (PAL) Group. Inverse Probability Weighting (IPW) was used to weight the groups. RESULTS 1,560 patients were evaluated, of which 421 experienced recurrence and were then eligible: 156 in CUR group and 256 in PAL group. Tumor burden and liver function were weighted by IPW, and two pseudo-population were obtained (CUR = 397.5 and PAL = 415.38). SAR rates at 1, 3 and 5 years were respectively 98.3%, 76.7%, 63.8% for CUR and 91.7%, 64.2% and 48.9% for PAL (p = 0.007). Median DFS was 43 months (95%CI = 32-74) for CUR group, while it was 23 months (95%CI = 18-27) for PAL (p = 0.017). Being treated by palliative approach (HR = 1.75; 95%CI = 1.14-2.67; p = 0.01) and having a median size of the recurrent nodule>5 cm (HR = 1.875; 95%CI = 1.22-2.86; p = 0.004) were the only predictors of mortality after recurrence, while time to recurrence was the only protective factor (HR = 0.616; 95%CI = 0.54-0.69; p<0.001). CONCLUSION Curative approaches may guarantee long-term survival in case of recurrence.
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Affiliation(s)
- Simone Famularo
- School of Medicine and Surgery, University of Milano-Bicocca, Department of Surgery, San Gerardo Hospital, Monza, Italy; Department of Hepatobiliary and General Surgery, Humanitas University, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
| | - Matteo Donadon
- Department of Hepatobiliary and General Surgery, Humanitas University, Humanitas Clinical and Research Center, Rozzano, Milan, Italy
| | - Federica Cipriani
- Hepatobiliary Surgery Division, Ospedale San Raffaele, Milano, Italy
| | - Davide P Bernasconi
- Center of Biostatistics for Clinical Epidemiology, School of Medicine and Surgery, University of Milano - Bicocca, Monza, Italy
| | - Giuliano LaBarba
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Tommaso Dominioni
- Unit of General Surgery 1, University of Pavia and Foundation IRCCS Policlinico San Matteo, Pavia, Italy
| | - Maurizio Iaria
- Department of Surgery, University of Parma, Parma, Italy
| | - Sarah Molfino
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Simone Conci
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
| | | | - Marco Garatti
- Department of General Surgery, Poliambulanza Foundation Hospital, Brescia, Italy
| | | | - Albert Troci
- Department of Surgery, L. Sacco Hospital, Milan, Italy
| | - Stefan Patauner
- Department of Surgery, Bolzano Central Hospital, Bolzano, Italy
| | | | - Maurizio Cosimelli
- Division of Hepatobiliarypancreatic Surgery, IRCCS - Regina Elena National Cancer Institute, Rome, Italy
| | - Giacomo Zanus
- Department of Surgical, Oncological and Gastroenterological Science (DISCOG), University of Padua, Hepatobiliary and Pancreatic Surgery Unit - Treviso Hospital, Italy
| | - Felice Giuliante
- Hepatobiliary Surgery Unit, Fondazione "Policlinico Universitario A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | - Elio Jovine
- AOU Sant'Orsola Malpighi, IRCCS, Bologna, Italy
| | - Maria G Valsecchi
- Center of Biostatistics for Clinical Epidemiology, School of Medicine and Surgery, University of Milano - Bicocca, Monza, Italy
| | - GianLuca Grazi
- Division of Hepatobiliarypancreatic Surgery, IRCCS - Regina Elena National Cancer Institute, Rome, Italy
| | | | - Antonio Frena
- Department of Surgery, Bolzano Central Hospital, Bolzano, Italy
| | | | - Riccardo Memeo
- Department of Hepato-Pancreatic-Biliary Surgery, Miulli Hospital, Bari, Italy
| | - Giuseppe Zimmitti
- Department of General Surgery, Poliambulanza Foundation Hospital, Brescia, Italy
| | - Guido Griseri
- HPB Surgical Unit, San Paolo Hospital, Savona, Italy
| | - Andrea Ruzzenente
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
| | - Gianluca Baiocchi
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | | | - Marcello Maestri
- Unit of General Surgery 1, University of Pavia and Foundation IRCCS Policlinico San Matteo, Pavia, Italy
| | - Giorgio Ercolani
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Luca Aldrighetti
- Hepatobiliary Surgery Division, Ospedale San Raffaele, Milano, Italy
| | - Guido Torzilli
- Department of Hepatobiliary and General Surgery, Humanitas University, Humanitas Clinical and Research Center, Rozzano, Milan, Italy
| | - Fabrizio Romano
- School of Medicine and Surgery, University of Milano-Bicocca, Department of Surgery, San Gerardo Hospital, Monza, Italy
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20
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Vitale A, Farinati F, Finotti M, Di Renzo C, Brancaccio G, Piscaglia F, Cabibbo G, Caturelli E, Missale G, Marra F, Sacco R, Giannini EG, Trevisani F, Cillo U. Overview of Prognostic Systems for Hepatocellular Carcinoma and ITA.LI.CA External Validation of MESH and CNLC Classifications. Cancers (Basel) 2021; 13:1673. [PMID: 33918125 PMCID: PMC8037197 DOI: 10.3390/cancers13071673] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 03/23/2021] [Accepted: 03/25/2021] [Indexed: 02/07/2023] Open
Abstract
Prognostic assessment in patients with HCC remains an extremely difficult clinical task due to the complexity of this cancer where tumour characteristics interact with degree of liver dysfunction, patient general health status, and a large span of available treatment options. Several prognostic systems have been proposed in the last three decades, both from the Asian and European/North American countries. Prognostic scores, such as the CLIP score and the recent MESH score, have been generated on a solid statistical basis from real life population data, while staging systems, such as the BCLC scheme and the recent CNLC classification, have been created by experts according to recent HCC prognostic evidences from the literature. A third category includes combined prognostic systems that can be used both as prognostic scores and staging systems. A recent example is the ITA.LI.CA prognostic system including either a prognostic score and a simplified staging system. This review focuses first on an overview of the main prognostic systems for HCC classified according to the above three categories, and, second, on a comprehensive description of the methodology required for a correct comparison between different systems in terms of prognostic performance. In this second section the main studies in the literature comparing different prognostic systems are described in detail. Lastly, a formal comparison between the last prognostic systems proposed for each of the above three categories is performed using a large Italian database including 6882 HCC patients in order to concretely apply the comparison rules previously described.
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Affiliation(s)
- Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy; (A.V.); (F.F.); (C.D.R.); (U.C.)
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy; (A.V.); (F.F.); (C.D.R.); (U.C.)
| | - Michele Finotti
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy; (A.V.); (F.F.); (C.D.R.); (U.C.)
| | - Chiara Di Renzo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy; (A.V.); (F.F.); (C.D.R.); (U.C.)
| | - Giuseppina Brancaccio
- Infectious Diseases Unit, Department of Internal Medicine, Padua University Hospital, 35123 Padua, Italy;
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy;
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
| | - Giuseppe Cabibbo
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, 90127 Palermo, Italy;
| | | | - Gabriele Missale
- Infectious Diseases and Hepatology Unit, Azienda Ospedaliero-Universitaria of Parma, 43126 Parma, Italy;
| | - Fabio Marra
- Internal Medicine and Hepatology Unit, Department of Experimental and Clinical Medicine, University of Firenze, 50139 Firenze, Italy;
| | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, 71122 Foggia, Italy;
| | - Edoardo G. Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy;
| | - Franco Trevisani
- Division of Semeiotics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy; (A.V.); (F.F.); (C.D.R.); (U.C.)
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21
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Lai Q, Vitale A. BCLC staging system and liver transplantation: From a stage to a therapeutic hierarchy. Hepatobiliary Pancreat Dis Int 2021; 20:4-5. [PMID: 33358081 DOI: 10.1016/j.hbpd.2020.12.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 12/09/2020] [Indexed: 02/05/2023]
Affiliation(s)
- Quirino Lai
- Hepato-biliary and Organ Transplant Unit, Department of Surgery, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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22
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Vitale A, Trevisani F, Farinati F, Cillo U. Treatment of Hepatocellular Carcinoma in the Precision Medicine Era: From Treatment Stage Migration to Therapeutic Hierarchy. Hepatology 2020; 72:2206-2218. [PMID: 32064645 DOI: 10.1002/hep.31187] [Citation(s) in RCA: 122] [Impact Index Per Article: 24.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Accepted: 01/28/2020] [Indexed: 01/27/2023]
Abstract
Treatment allocation is extremely complex in patients with hepatocellular carcinoma (HCC) because this neoplasm arises, in most cases, in patients with cirrhosis and additional comorbidities. The "stage hierarchy" approach, which involves linking each stage (or substage) of the disease to a specific treatment, has become the main proposed treatment strategy for the clinical management of HCC, particularly in the West. The Barcelona Clinic Liver Cancer (BCLC) scheme serves as the main example of the application of this strategy. In an attempt to increase the plasticity of the "stage hierarchy" approach as well as its adaptability to the requirements of real-world clinical practice, the latest versions of European and American guidelines have introduced certain relevant elements of flexibility, which were not intrinsic to the original BCLC scheme. These elements are as follows: the "treatment stage migration" strategy, which allows moving to another treatment (generally the one that is associated with the subsequent stage) if the approach linked with the current stage proves to be unfeasible, and the "treatment stage alternative" approach, which proposes further therapeutic options for each BCLC-defined stage. In regard to most of the solid cancers, another potential strategy is to consider the treatment decision to be hierarchically dictated by the efficacy of each therapy with complete or partial independence from the tumor stage. This concept of "therapeutic hierarchy" has been historically endorsed by the Asia-Pacific treatment algorithm as well as by the recent Italian multisociety guidelines. The present review provides a critical analysis of the different conceptual approaches to HCC management, highlighting their advantages and disadvantages and focusing on the remarkable differences between the stage-guided and the hierarchical strategies.
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Affiliation(s)
- Alessandro Vitale
- Department of Surgical, Oncological, and Gastroenterological Sciences, Hepatobiliary Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Franco Trevisani
- Department of Medical and Surgical Sciences, Semeiotics Unit, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Fabio Farinati
- Department of Surgical, Oncological, and Gastroenterological Sciences, Gastroenterology Division, Padua University Hospital, Padua, Italy
| | - Umberto Cillo
- Department of Surgical, Oncological, and Gastroenterological Sciences, Hepatobiliary Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
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Marasco G, Serenari M, Renzulli M, Alemanni LV, Rossini B, Pettinari I, Dajti E, Ravaioli F, Golfieri R, Cescon M, Festi D, Colecchia A. Clinical impact of sarcopenia assessment in patients with hepatocellular carcinoma undergoing treatments. J Gastroenterol 2020; 55:927-943. [PMID: 32748172 PMCID: PMC7519899 DOI: 10.1007/s00535-020-01711-w] [Citation(s) in RCA: 74] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Accepted: 07/15/2020] [Indexed: 02/04/2023]
Abstract
Changes in body composition are associated with poor outcomes in cancer patients including hepatocellular carcinoma (HCC). Sarcopenia, defined as the loss of skeletal muscle mass, quality and function, has been associated with a higher rate of complications and recurrences in patients with cirrhosis and HCC. The assessment of patient general status before HCC treatment, including the presence of sarcopenia, is a key-point for achieving therapy tolerability and to avoid short- and long-term complications leading to poor patients' survival. Thus, we aimed to review the current literature evaluating the role of sarcopenia assessment related to HCC treatments and to critically provide the clinicians with the most recent and valuable evidence. As a result, sarcopenia can be predictive of poor outcomes in patients undergoing liver resection, transplantation and systemic therapies, offering the chance to clinicians to improve the muscular status of these patients, especially those with high-grade sarcopenia at high risk of mortality. Further studies are needed to clarify the predictive value of sarcopenia in other HCC treatment settings and to evaluate its role as an additional staging tool for identifying the most appropriate treatment. Besides, interventional studies aiming at increasing the skeletal muscle mass for reducing complications and increasing the survival in patients with HCC are needed.
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Affiliation(s)
- Giovanni Marasco
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40126, Bologna, Italy.
| | - Matteo Serenari
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40126, Bologna, Italy
| | - Matteo Renzulli
- Radiology Unit, Sant'Orsola Malpighi Hospital, Via Albertoni 4, 40138, Bologna, Italy
| | - Luigina Vanessa Alemanni
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40126, Bologna, Italy
| | - Benedetta Rossini
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40126, Bologna, Italy
| | - Irene Pettinari
- Radiology Unit, Sant'Orsola Malpighi Hospital, Via Albertoni 4, 40138, Bologna, Italy
| | - Elton Dajti
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40126, Bologna, Italy
| | - Federico Ravaioli
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40126, Bologna, Italy
| | - Rita Golfieri
- Radiology Unit, Sant'Orsola Malpighi Hospital, Via Albertoni 4, 40138, Bologna, Italy
| | - Matteo Cescon
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40126, Bologna, Italy
| | - Davide Festi
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40126, Bologna, Italy
| | - Antonio Colecchia
- Gastroenterology Unit, University Hospital Borgo Trento, Verona, Italy
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Yu JI, Lee SJ, Lee J, Lim HY, Paik SW, Yoo GS, Choi C, Park HC. Clinical significance of radiotherapy before and/or during nivolumab treatment in hepatocellular carcinoma. Cancer Med 2019; 8:6986-6994. [PMID: 31588679 PMCID: PMC6853810 DOI: 10.1002/cam4.2570] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Revised: 09/10/2019] [Accepted: 09/10/2019] [Indexed: 12/11/2022] Open
Abstract
Background This study aimed to investigate the clinical significance of previous and/or concurrent application of radiotherapy (RT) in the course of nivolumab treatment for advanced hepatocellular carcinoma (HCC). Methods Patients with advanced HCC who received nivolumab treatment between March 2017 and May 2018. were included. Nivolumab treatment was indicated in patients who did not respond to conventional therapy including locoregional therapy and/or sorafenib. RT was performed when necessary for curative/palliative purpose. Results Among the 76 HCC patients who received nivolumab, 54 (71.1%) had received RT for HCC before and/or during the treatment. The period from initial HCC diagnosis to nivolumab treatment was significantly longer (P = .007) and the rate of undergoing transarterial chemoembolization (TACE; P = .006) and sorafenib treatment (P = .007) was significantly higher in patients who received previous/concurrent RT than in those who did not. Nivolumab‐related toxicities were generally tolerable regardless of the history of RT. During the follow‐up, 39 (51.3%) patients died and 54 (71.1%) patients experienced disease progression according to the RECIST v1.1. Patients who had received previous/concurrent RT had a significantly longer progression‐free survival (PFS; P = .008) and overall survival (OS; P = .007) than those who did not receive RT; however, this trend was not observed in patients with a history of radiofrequency ablation or TACE (all P > .05). Conclusion Previous and/or concurrent application of RT in the course of nivolumab treatment was related with longer PFS and OS in advanced HCC patients. Nonetheless, further clinical studies are warranted to confirm our findings.
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Affiliation(s)
- Jeong Il Yu
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Su Jin Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.,Division of Hematology-Oncology, Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Jeeyun Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ho Yeong Lim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seung Woon Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Gyu Sang Yoo
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Changhoon Choi
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hee Chul Park
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.,Department of Medical Device Management and Research, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea
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25
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Giannini EG, Trevisani F. Ramucirumab as a second-line treatment for hepatocellular carcinoma: reaching out further to patients with elevated alpha-fetoprotein. Hepatobiliary Surg Nutr 2019; 8:515-518. [PMID: 31673543 DOI: 10.21037/hbsn.2019.04.19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, Ospedale Policlinico San Martino IRCCS per l'Oncologia, University of Genoa, Genoa, Italy
| | - Franco Trevisani
- Medical Semeiotics Unit, Sant'Orsola Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy
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26
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Vitale A, Farinati F, Pawlik TM, Frigo AC, Giannini EG, Napoli L, Ciccarese F, Rapaccini GL, Di Marco M, Caturelli E, Zoli M, Borzio F, Sacco R, Cabibbo G, Virdone R, Marra F, Felder M, Morisco F, Benvegnù L, Gasbarrini A, Svegliati-Baroni G, Foschi FG, Missale G, Masotto A, Nardone G, Colecchia A, Bernardi M, Trevisani F, Cillo U. The concept of therapeutic hierarchy for patients with hepatocellular carcinoma: A multicenter cohort study. Liver Int 2019; 39:1478-1489. [PMID: 31131974 DOI: 10.1111/liv.14154] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Revised: 03/26/2019] [Accepted: 04/16/2019] [Indexed: 01/27/2023]
Abstract
BACKGROUND The Italian Liver Cancer (ITA.LI.CA) prognostic system for patients with hepatocellular carcinoma (HCC) has recently been proposed and validated. We sought to explore the relationship among the ITA.LI.CA prognostic variables (ie tumour stage, functional score based on performance status and Child-Pugh score, and alpha-fetoprotein), treatment selection and survival outcome in HCC patients. PATIENTS AND METHODS We analysed 4,867 consecutive HCC patients undergoing six main treatment strategies (liver transplantation, LT; liver resection, LR; ablation, ABL; intra-arterial therapy, IAT; Sorafenib, SOR; and best supportive care, BSC) and enrolled during 2002-2015 in a multicenter Italian database. In order to control pretreatment imbalances in observed variables, a machine learning methodology was used and inverse probability of treatment weights (IPTW) was calculated. An IPTW-adjusted multivariate survival model that included ITA.LI.CA prognostic variables, treatment period and treatment strategy was then developed. The survival benefit of HCC treatments was described as a hazard ratio (95% confidence interval), using BSC as a reference value and as predicted median survival. RESULTS After the IPTW, the six treatment groups became well balanced for most baseline characteristics. In the IPTW-adjusted multivariate survival model, treatment strategy was found to be the strongest survival predictor, irrespective of ITA.LI.CA prognostic variables and treatment period. The survival benefit of different therapies over BSC was: LT = 0.19 (0.18-0.20); RES = 0.40 (0.37-0.42); ABL 0.42 (0.40-0.44); IAT = 0.58 (0.55-0.61); SOR = 0.92 (0.87-0.97). This multivariate model was then used to predict median survival for each therapy within each ITA.LI.CA stage. CONCLUSION The concept of therapeutic hierarchy was established within each ITA.LI.CA stage.
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Affiliation(s)
- Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Timothy M Pawlik
- Department of Surgery, Wexner Medical Center at The Ohio State University, Columbus, Ohio
| | | | - Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, IRCCS-Azienda Ospedaliera Universitaria San Martino-IST, University of Genoa, Genoa, Italy
| | - Lucia Napoli
- Division of Internal Medicine, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | | | - Gian Ludovico Rapaccini
- Division of Internal Medicine and Gastroenterology, Complesso Integrato Columbus, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Maria Di Marco
- Division of Medicine, Bolognini Hospital, Seriate, Italy
| | | | - Marco Zoli
- Division of Internal Medicine, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Franco Borzio
- Division of Radiology, Department of Medicine, Fatebenefratelli Hospital, Milan, Italy
| | - Rodolfo Sacco
- Division of Gastroenterology and Metabolic Diseases, University Hospital of Pisa, Pisa, Italy
| | - Giuseppe Cabibbo
- Division of Gastroenterology, Biomedical Department of Internal and Specialistic Medicine, University of Palermo, Palermo, Italy
| | - Roberto Virdone
- Division of Internal Medicine 2, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
| | - Fabio Marra
- Internal Medicine and Hepatology, Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy
| | - Martina Felder
- Division of Gastroenterology, Bolzano Regional Hospital, Bolzano, Italy
| | - Filomena Morisco
- Division of Gastroenterology, Department of Medicine and Surgery, University of Naples, "Federico II", Naples, Italy
| | - Luisa Benvegnù
- Department of Molecular Medicine, University of Padova, Padova, Italy
| | - Antonio Gasbarrini
- Division of Internal Medicine and Gastroenterology, Policlinico Gemelli, Università Cattolica del Sacro Cuore, Roma, Italy
| | | | | | - Gabriele Missale
- Division of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Alberto Masotto
- Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Gerardo Nardone
- Hepato-Gastroenterology Unit, Department of Clinical Medicine and Surgery, University of Naples "Federico II", Napoli, Italy
| | - Antonio Colecchia
- Gastroenterology Unit, Department of Surgical and Medical sciences, Alma Mater Studiorum-Università of Bologna, Bologna, Italy
| | - Mauro Bernardi
- Division of Semeiotics, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Franco Trevisani
- Division of Semeiotics, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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27
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Yan WT, Quan B, Yu JJ, Yang T. Should we invariably follow the current guidelines to treat our HCC patients? Hepatobiliary Pancreat Dis Int 2019; 18:301-302. [PMID: 30686653 DOI: 10.1016/j.hbpd.2019.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Accepted: 01/04/2019] [Indexed: 02/05/2023]
Affiliation(s)
- Wen-Tao Yan
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China; Department of Clinical Medicine, Second Military Medical University, Shanghai 200433, China
| | - Bing Quan
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China; Department of Clinical Medicine, Second Military Medical University, Shanghai 200433, China
| | - Jiong-Jie Yu
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China; Department of Clinical Medicine, Second Military Medical University, Shanghai 200433, China
| | - Tian Yang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
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28
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Vitale A, Farinati F, Borzio M, Trevisani F, Cllo U. Reply. Hepatology 2019; 69:465-466. [PMID: 30376183 DOI: 10.1002/hep.30322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Affiliation(s)
- Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Mauro Borzio
- U.O.C. Gastroenterologia, ASST Melegnano-Martesana, Melegnano, Italy
| | - Franco Trevisani
- Department of Medical and Surgical Sciences, Division of Semeiotics, Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Umberto Cllo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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29
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Huo TI, Liu PH, Hsu CY. Staging and Restaging for Hepatocellular Carcinoma: Solution of Confusion? Hepatology 2019; 69:464-465. [PMID: 30353930 DOI: 10.1002/hep.30324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Affiliation(s)
- Teh-Ia Huo
- Department of Medicine, National Yang-Ming University School of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Po-Hong Liu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX
| | - Chia-Yang Hsu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
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