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2. Presence of Hepatocellular Carcinoma Does Not Affect Course and Response to Anticoagulation of Bland Portal Vein Thrombosis in Cirrhotic Patients

Author

Benevento F, Pecorelli A, Stefanescu H, Sparchez Z, Vukotic R, Pettinari I, Grigoras CA, Tovoli F, Ravaioli F, Stefanini B, Andreone P, and Piscaglia F

Subjects
lc: liver cirrhosis, hcc: hepatocellular carcinoma, pvt: portal vein thrombosis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Francesca Benevento,1 Anna Pecorelli,2 Horia Stefanescu,3 Zeno Sparchez,3 Ranka Vukotic,1,4 Irene Pettinari,2 Crina-Anca Grigoras,3 Francesco Tovoli,1,5 Federico Ravaioli,1 Bernardo Stefanini,1 Pietro Andreone,6 Fabio Piscaglia1,5 1Department of Medicine and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy; 2Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 3Gastroenterology Department, Liver Unit & Ultrasound Laboratory, Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania; 4Medicina Interna 4, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; 5Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 6Divisione di Medicina Interna a Indirizzo Metabolico-Nutrizionale, Azienda Ospedaliero-Universitaria di Modena, Modena, ItalyCorrespondence: Fabio Piscaglia, Email Fabio.piscaglia@unibo.itBackground: Malignancies are generally considered a risk factor for deep vein thrombosis and may hamper the recanalisation of thrombosed veins.Aim: We investigate whether the natural course and response to anticoagulant treatment of bland portal vein thrombosis (PVT) in patients with cirrhosis complicated by hepatocellular carcinoma (HCC) differ from those without HCC.Methods: Retrospective study in two hepatology referral centres, in Italy and Romania where patients with a diagnosis of PVT on cirrhosis and follow-up of at least 3 months with repeated imaging were included.Results: A total of 162 patients with PVT and matching inclusion and exclusion criteria were identified: 30 with HCC were compared to 132 without HCC. Etiologies, Child-Pugh Score (7 vs 7) and MELD scores (11 vs 12, p=0.3679) did not differ. Anticoagulation was administered to 43% HCC vs 42% nonHCC. The extension of PVT in the main portal trunk was similar: partial/total involvement was 73.3/6.7% in HCC vs 67.4/6.1% in nonHCC, p=0.760. The remainder had intrahepatic PVT. The recanalization rate was 61.5% and 60.7% in HCC/nonHCC in anticoagulated patients (p=1). Overall PVT recanalisation, including treated and untreated patients, was observed in 30% of HCC vs 37.9% of nonHCC, p=0.530. Major bleeding incidence was almost identical (3.3% vs 3.8%, p=1). Progression of PVT after stopping anticoagulation did not differ (10% vs 15.9%, respectively, HCC/nHCC, p=0.109).Conclusion: The course of bland non-malignant PVT in cirrhosis is not affected by the presence of active HCC. Treatment with anticoagulation in patients with active HCC is safe and as effective as in nonHCC patients, this can potentially allow us to use otherwise contraindicated therapies (ie TACE) if a complete recanalization is achieved with anticoagulation.Keywords: LC, liver cirrhosis, HCC, hepatocellular carcinoma, PVT, portal vein thrombosis

Published
2023

6. Animal Models of Hepatocellular Carcinoma: Current Applications in Clinical Research

Author

Fornari F, Giovannini C, Piscaglia F, and Gramantieri L

Subjects
hcc, nash, animal models, treatments, immunotherapy, tkis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Francesca Fornari,1,2 Catia Giovannini,1,3 Fabio Piscaglia,4,5 Laura Gramantieri4 1Centre for Applied Biomedical Research - CRBA, University of Bologna, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy; 2Department for Life Quality Studies, University of Bologna, Rimini, Italy; 3Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; 4Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy; 5Department of Medical and Surgical Sciences, University of Bologna, Bologna, ItalyCorrespondence: Laura Gramantieri; Francesca Fornari, Via Massarenti, 9, Bologna, 40138, Italy, Tel/Fax +390512143902, Email laura.gramantieri@aosp.bo.it; francesca.fornari2@unibo.itAbstract: In the last decade, relevant advances have occurred in the treatment of hepatocellular carcinoma (HCC), with novel drugs entering the clinical practice, among which tyrosine kinase inhibitors (TKIs) such as lenvatinib, cabozantinib and regorafenib, and immune checkpoint inhibitors (ICPIs) either alone or in combination with VEGF inhibitors. Clinical trials have driven the introduction of such novel molecules into the clinics but, at present, no biomarker drives the choice of first-line options, which relies only upon clinical and imaging assessment. Remarkably, clinical and imaging-based evaluations do not consider the huge heterogeneity of HCC and do not allow to realize the potential of personalized treatments. Preclinical research still does not inform the design of clinical trials, even though many animal models mimicking specific subgroups of HCC are available and might provide relevant information. Although animal models directly informing the clinical practice, such as patients-derived xenografts, are not used to help the choice of treatment in advanced HCC, however, the preclinical research can count on a wide range of valuable models. Here we will review some HCC models which might turn informative for specific questions in defined patient subgroups, and we will describe recent preclinical studies for the mechanistic evaluation of immunotherapy-based treatment approaches. To this aim, we will mainly focus on two issues: (i) HCC models informative on NAFLD-NASH HCC and (ii) HCC models helping to elucidate mechanisms underneath immunotherapy. We have chosen these two settings since they represent, respectively, the most rapidly arising cause of chronic liver disease (CLD) and HCC in western countries and the most promising therapeutic option for advanced HCC.Keywords: HCC, NASH, animal models, treatments, immunotherapy, TKIs

Published
2022

7. Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis

Author

Rimini, M., Rimassa, L., Ueshima, K., Burgio, V., Shigeo, S., Tada, T., Suda, G., Yoo, C., Cheon, J., Pinato, D.J., Lonardi, S., Scartozzi, M., Iavarone, M., Di Costanzo, G.G., Marra, F., Soldà, C., Tamburini, E., Piscaglia, F., Masi, G., Cabibbo, G., Foschi, F.G., Silletta, M., Pressiani, T., Nishida, N., Iwamoto, H., Sakamoto, N., Ryoo, B.-Y., Chon, H.J., Claudia, F., Niizeki, T., Sho, T., Kang, B., D’Alessio, A., Kumada, T., Hiraoka, A., Hirooka, M., Kariyama, K., Tani, J., Atsukawa, M., Takaguchi, K., Itobayashi, E., Fukunishi, S., Tsuji, K., Ishikawa, T., Tajiri, K., Ochi, H., Yasuda, S., Toyoda, H., Ogawa, C., Nishimur, T., Hatanaka, T., Kakizaki, S., Shimada, N., Kawata, K., Tanaka, T., Ohama, H., Nouso, K., Morishita, A., Tsutsui, A., Nagano, T., Itokawa, N., Okubo, T., Arai, T., Imai, M., Naganuma, A., Koizumi, Y., Nakamura, S., Joko, K., Iijima, H., Hiasa, Y., Pedica, F., De Cobelli, F., Ratti, F., Aldrighetti, L., Kudo, M., Cascinu, S., and Casadei-Gardini, A.

Published
2022
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8. Real-Life Clinical Data of Lenvatinib versus Sorafenib for Unresectable Hepatocellular Carcinoma in Italy

Author

Burgio V, Iavarone M, Di Costanzo GG, Marra F, Lonardi S, Tamburini E, Piscaglia F, Masi G, Celsa C, Foschi FG, Silletta M, Amoruso DC, Rimini M, Bruccoleri M, Tortora R, Campani C, Soldà C, Viola MG, Forgione A, Conti F, Salani F, Catanese S, Giacchetto CM, Fulgenzi C, Coppola C, Lampertico P, Pellino A, Rancatore G, Cabibbo G, Ratti F, Pedica F, Della Corte A, Colombo M, De Cobelli F, Aldrighetti L, Cascinu S, and Casadei-Gardini A

Subjects
hepatocarcinoma, sorafenib, lenvatinib, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Valentina Burgio,1 Massimo Iavarone,2 Giovanni Giuseppe Di Costanzo,3 Fabio Marra,4 Sara Lonardi,5,6 Emiliano Tamburini,7 Fabio Piscaglia,8 Gianluca Masi,9,10 Ciro Celsa,11 Francesco Giuseppe Foschi,12 Marianna Silletta,13 Daniela Caterina Amoruso,14 Margherita Rimini,15 Mariangela Bruccoleri,2 Raffaella Tortora,3 Claudia Campani,4 Caterina Soldà,6 Massimo Giuseppe Viola,16 Antonella Forgione,8 Fabio Conti,12 Francesca Salani,9,10 Silvia Catanese,9,10 Carmelo Marco Giacchetto,17 Claudia Fulgenzi,13 Carmine Coppola,14 Pietro Lampertico,18 Antonio Pellino,6,19 Gabriele Rancatore,17 Giuseppe Cabibbo,17 Francesca Ratti,20 Federica Pedica,21 Angelo Della Corte,22 Massimo Colombo,18 Francesco De Cobelli,23 Luca Aldrighetti,20 Stefano Cascinu,1,23 Andrea Casadei-Gardini1,23 1Department of Medical Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy; 2Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy; 3Department of Hepatology, Naples, 80131, Italy; 4Dipartimento di Medicina Sperimentale e Clinica, Università di Firenze, Firenze, Italy; 5Early Phase Clinical Trial Unit, Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy; 6Medical Oncology Unit 1, Department of Oncology, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy; 7Department of Oncology and Palliative Care, Cardinale Hospital, Naples, Italy; 8Division of Internal Medicine, Hepatobiliary and Immunoallergic Disease, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 9Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy; 10Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; 11Department of Surgical, Oncological and Oral Sciences (Di.Chir.On.S.), University of Palermo, Palermo, 90127, Italy; 12Internal Medicine, Infermi Hospital, Faenza (AUSL ROMAGNA), Ravenna, Italy; 13Department of Oncology, Campus Bio Medico, Roma, Italy; 14Hepatology Unit, Internal Medicine, Area Stabiese Hospital, Naples, Italy; 15Department of Oncology and Hematology, Division of Oncology, University of Modena and Reggio Emilia, Modena, 4121, Italy; 16Department of General Surgery and Emergency Surgery, Cardinale Hospital, Tricase, Italy; 17Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, 90127, Italy; 18Liver Center, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy; 19Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; 20Hepatobiliary Surgery Division, Liver Center, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy; 21Department of Experimental Oncology, Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy; 22Department of Radiology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy; 23School of Medicine, Vita-Salute San Raffaele University, Milan, 20132, ItalyCorrespondence: Andrea Casadei-GardiniDepartment of Medical Oncology, IRCCS San Raffaele Hospital, Via Olgettina n. 60, Milan, ItalyEmail casadeigardini@gmail.comBackground: Lenvatinib has been approved in Italy since October 2019 as a first-line therapy for advanced hepatocellular carcinoma (HCC) and to date data on effectiveness and safety of lenvatinib are not available in our region. To fill this gap, we performed a multicentric analysis of the real-world treatment outcomes with the propensity score matching in a cohort of Italian patients with unresectable HCC who were treated with either sorafenib or lenvatinib.Aims and Methods: To evaluate the effectiveness of sorafenib and lenvatinib as primary treatment of advanced HCC in clinical practice we performed a multicentric analysis of the treatment outcomes of 288 such patients recruited in 11 centers in Italy. A propensity score was used to mitigate confounding due to referral biases in the assessment of mortality and progression-free survival.Results: Over a follow-up period of 11 months the Cox regression model showed 48% reduction of death risk for patients treated with lenvatinib (95% CI: 0.34– 0.81; p = 0.0034), compared with those treated with sorafenib. The median PFS was 9.0 and 4.9 months for lenvatinib and sorafenib arm, respectively. Patients treated with lenvatinib showed a higher percentage of response rate (29.4% vs 2.8%; p < 0.00001) compared with patients treated with sorafenib. Sorafenib was shown to be correlated with more HFSR, diarrhea and fatigue, while lenvatinib with more hypertension and fatigue.Conclusion: Our study highlighted for the first time the efficacy and safety of lenvatinib in an Italian cohort of patients.Keywords: hepatocarcinoma, sorafenib, lenvatinib

Published
2021

9. Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib

Author

Rimini, M., Kudo, M., Tada, T., Shigeo, S., Kang, W., Suda, G., Jefremow, A., Burgio, V., Iavarone, M., Tortora, R., Marra, F., Lonardi, S., Tamburini, E., Piscaglia, F., Masi, G., Cabibbo, G., Foschi, F.G., Silletta, M., Kumada, T., Iwamoto, H., Aoki, T., Goh, M.J., Sakamoto, N., Siebler, J., Hiraoka, A., Niizeki, T., Ueshima, K., Sho, T., Atsukawa, M., Hirooka, M., Tsuji, K., Ishikawa, T., Takaguchi, K., Kariyama, K., Itobayashi, E., Tajiri, K., Shimada, N., Shibata, H., Ochi, H., Yasuda, S., Toyoda, H., Fukunishi, S., Ohama, H., Kawata, K., Tani, J., Nakamura, S., Nouso, K., Tsutsui, A., Nagano, T., Takaaki, T., Itokawa, N., Okubo, T., Arai, T., Imai, M., Joko, K., Koizumi, Y., Hiasa, Y., Cucchetti, A., Ratti, F., Aldrighetti, L., Cascinu, S., and Casadei-Gardini, A.

Published
2021
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10. Identification of lenvatinib prognostic index via recursive partitioning analysis in advanced hepatocellular carcinoma

Author

Rapposelli, I.G., Shimose, S., Kumada, T., Okamura, S., Hiraoka, A., Di Costanzo, G.G., Marra, F., Tamburini, E., Forgione, A., Foschi, F.G., Silletta, M., Lonardi, S., Masi, G., Scartozzi, M., Nakano, M., Shibata, H., Kawata, K., Pellino, A., Vivaldi, C., Lai, E., Takata, A., Tajiri, K., Toyoda, H., Tortora, R., Campani, C., Viola, M.G., Piscaglia, F., Conti, F., Fulgenzi, C.A.M., Frassineti, G.L., Rizzato, M.D., Salani, F., Astara, G., Torimura, T., Atsukawa, M., Tada, T., Burgio, V., Rimini, M., Cascinu, S., and Casadei-Gardini, A.

Published
2021
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11. Elucidating the Molecular Basis of Sorafenib Resistance in HCC: Current Findings and Future Directions

Author

Fornari F, Giovannini C, Piscaglia F, and Gramantieri L

Subjects
hcc, sorafenib, microrna, autophagy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Francesca Fornari,1,2 Catia Giovannini,1,3 Fabio Piscaglia,4,5 Laura Gramantieri4 1Centre for Applied Biomedical Research - CRBA, University of Bologna, St. Orsola Hospital, Bologna, Italy; 2Department for Life Quality Studies, University of Bologna, Rimini, Italy; 3Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, 40138, Italy; 4Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 5Department of Medical and Surgical Sciences, University of Bologna, Bologna, ItalyCorrespondence: Francesca Fornari; Laura Gramantieri Tel/Fax +390512143902+390512142579Email francesca.fornari2@unibo.it; laura.gramantieri@aosp.bo.itAbstract: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. Sorafenib is the first multi-tyrosine kinase inhibitor approved for HCC and it has represented the standard of care for advanced HCC for almost 10 years, offering a survival benefit when compared to placebo. However, this benefit is limited, showing rare objective responses and a disease control rate approaching 50– 60%, with most patients experiencing disease progression at 6 months. These scant results dictate the urgent need for strategies to overcome both primary and acquired resistance. Herein we report several mechanisms supporting resistance to sorafenib in HCC patients, including activation of oncogenic pathways. Among these, the AKT/mTOR pathway plays a crucial role being at the crossroad of multiple driving events. Autophagy, multidrug-resistant phenotype, hypoxia-related mechanisms and endoplasmic reticulum stress are gaining more and more relevance as crucial events driving the response to anticancer drugs, including sorafenib. Several HCC-specific miRNAs take part to the regulation of these cellular processes. Remarkably, molecularly targeted strategies able to overcome resistance in these settings have also been reported. So far, the vast majority of data has been derived from laboratory studies, which means the need for an extensive validation. Indeed, most of the possible drug associations displaying promising effects in improving sorafenib efficacy herein described derive from preclinical explorations. Notably, data obtained in animal models can be inconsistent with regard to the human disease for efficacy, safety, side effects, best formulation and pharmacokinetics. However, they represent the necessary preliminary step to improve the management of advanced HCC.Keywords: HCC, sorafenib, microRNA, autophagy

Published
2021

13. MicroRNAs as Modulators of Tumor Metabolism, Microenvironment, and Immune Response in Hepatocellular Carcinoma

Author

Gramantieri L, Giovannini C, Piscaglia F, and Fornari F

Subjects
hcc, microrna, biomarkers, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Laura Gramantieri,1 Catia Giovannini,2,3 Fabio Piscaglia,1,4 Francesca Fornari3,5 1Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 2Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy; 3Centre for Applied Biomedical Research - CRBA, University of Bologna, St. Orsola Hospital, Bologna, Italy; 4Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; 5Department for Life Quality Studies (QuVi), University of Bologna, Rimini, ItalyCorrespondence: Laura Gramantieri; Francesca FornariUniversity of Bologna, Via Massarenti, 9, Bologna, 40138, ItalyTel/Fax +390512143902Email laura.gramantieri@aosp.bo.it; francesca.fornari2@unibo.itAbstract: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality. Molecular heterogeneity and absence of biomarkers helping patient allocation to the best therapeutic option contribute to poor prognosis in advanced stages. MicroRNAs’ (miRNAs) deregulated expression contributes to tumor development and progression and influences drug resistance in HCC. Accordingly, miRNAs have been extensively investigated as both biomarkers and therapeutic targets. The diagnostic and prognostic roles of circulating miRNAs have been ascertained, though with some inconsistencies across studies. From a therapeutic perspective, miRNA-based approaches demonstrated safety profiles and antitumor efficacy in HCC animal models. Nevertheless, caution should be used when transferring preclinical findings to the clinic, due to possible molecular inconsistency between animal models and the heterogeneous patterns of human diseases. A wealth of information is offered by preclinical studies exploring the mechanisms driving miRNAs’ aberrant expression, the molecular cascades triggered by miRNAs and the corresponding phenotypic changes. Ex-vivo analyses confirmed these results, further shedding light on the intricacy of the human disease often overcoming pre-clinical models. This complexity seems to be ascribed to the intrinsic heterogeneity of HCC, to different risk factors driving its development, as well as to changes across stages and previous treatments. Preliminary findings suggest that miRNAs associated with specific risk factors might be more informative in defined patients’ subgroups. The first issue to be considered when trying to envisage a possible translational perspective is the molecular context that often drives different miRNA functions, as clearly evidenced by “dual” miRNAs. Concerning the possible roles of miRNAs as biomarkers and therapeutic targets, we will focus on miRNAs’ involvement in metabolic pathways and in the modulation of tumor microenvironment, to support their exploitation in defined contexts.Keywords: HCC, microRNA, biomarkers

Published
2021

16. 88P Adverse events (AEs) as potential predictive factors of activity in patients with advanced hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (AB)

Author

Persano, M., primary, Rimini, M., additional, Tada, T., additional, Suda, G., additional, Shimose, S., additional, Kudo, M., additional, Yoo, C., additional, Cheon, J., additional, Finkelmeier, F., additional, Lim, H.Y., additional, Presa, J., additional, Masi, G., additional, Bergamo, F., additional, Iavarone, M.A., additional, Cabibbo, G., additional, Foschi, F.G., additional, Piscaglia, F., additional, Cascinu, S., additional, Scartozzi, M., additional, and Gardini, A. Casadei, additional

Published
2023
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17. Personalised management of patients with hepatocellular carcinoma: a multiparametric therapeutic hierarchy concept

Author

Vitale, A, Cabibbo, G, Iavarone, M, Vigano, L, Pinato, D, Ponziani, F, Lai, Q, Casadei-Gardini, A, Celsa, C, Galati, G, Gambato, M, Crocetti, L, Renzulli, M, Giannini, E, Farinati, F, Trevisani, F, Cillo, U, Baccarani, U, Brancaccio, G, Cozzolongo, R, Cucchetti, A, De Matthaeis, N, Di Sandro, S, Famularo, S, Finotti, M, Foschi, F, Ghinolfi, D, Guarracino, M, Gruttadauria, S, Guarino, M, Kostandini, A, Lenci, I, Levi Sandri, G, Manzia, T, Marasco, G, Masarone, M, Mazzarelli, C, Melandro, F, Miele, L, Morisco, F, Nicolini, D, Pagano, D, Pelizzaro, F, Pieri, G, Piscaglia, F, Plaz Torres, M, Pravisani, R, Rendina, M, Romano, F, Russo, F, Sacco, R, Sangiovanni, A, Sposito, C, Tortora, R, Tovoli, F, Vigano, M, Violi, P, Vitale A., Cabibbo G., Iavarone M., Vigano L., Pinato D. J., Ponziani F. R., Lai Q., Casadei-Gardini A., Celsa C., Galati G., Gambato M., Crocetti L., Renzulli M., Giannini E. G., Farinati F., Trevisani F., Cillo U., Baccarani U., Brancaccio G., Cozzolongo R., Cucchetti A., De Matthaeis N., Di Sandro S., Famularo S., Finotti M., Foschi F. G., Ghinolfi D., Guarracino M., Gruttadauria S., Guarino M., Kostandini A., Lenci I., Levi Sandri G. B., Manzia T. M., Marasco G., Masarone M., Mazzarelli C., Melandro F., Miele L., Morisco F., Nicolini D., Pagano D., Pelizzaro F., Pieri G., Piscaglia F., Plaz Torres M. C., Pravisani R., Rendina M., Romano F., Russo F. P., Sacco R., Sangiovanni A., Sposito C., Tortora R., Tovoli F., Vigano M., Violi P., Vitale, A, Cabibbo, G, Iavarone, M, Vigano, L, Pinato, D, Ponziani, F, Lai, Q, Casadei-Gardini, A, Celsa, C, Galati, G, Gambato, M, Crocetti, L, Renzulli, M, Giannini, E, Farinati, F, Trevisani, F, Cillo, U, Baccarani, U, Brancaccio, G, Cozzolongo, R, Cucchetti, A, De Matthaeis, N, Di Sandro, S, Famularo, S, Finotti, M, Foschi, F, Ghinolfi, D, Guarracino, M, Gruttadauria, S, Guarino, M, Kostandini, A, Lenci, I, Levi Sandri, G, Manzia, T, Marasco, G, Masarone, M, Mazzarelli, C, Melandro, F, Miele, L, Morisco, F, Nicolini, D, Pagano, D, Pelizzaro, F, Pieri, G, Piscaglia, F, Plaz Torres, M, Pravisani, R, Rendina, M, Romano, F, Russo, F, Sacco, R, Sangiovanni, A, Sposito, C, Tortora, R, Tovoli, F, Vigano, M, Violi, P, Vitale A., Cabibbo G., Iavarone M., Vigano L., Pinato D. J., Ponziani F. R., Lai Q., Casadei-Gardini A., Celsa C., Galati G., Gambato M., Crocetti L., Renzulli M., Giannini E. G., Farinati F., Trevisani F., Cillo U., Baccarani U., Brancaccio G., Cozzolongo R., Cucchetti A., De Matthaeis N., Di Sandro S., Famularo S., Finotti M., Foschi F. G., Ghinolfi D., Guarracino M., Gruttadauria S., Guarino M., Kostandini A., Lenci I., Levi Sandri G. B., Manzia T. M., Marasco G., Masarone M., Mazzarelli C., Melandro F., Miele L., Morisco F., Nicolini D., Pagano D., Pelizzaro F., Pieri G., Piscaglia F., Plaz Torres M. C., Pravisani R., Rendina M., Romano F., Russo F. P., Sacco R., Sangiovanni A., Sposito C., Tortora R., Tovoli F., Vigano M., and Violi P.

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).

Published
2023

18. Artificial Intelligence and liver: Opportunities and barriers

Author

Balsano, C, Burra, P, Duvoux, C, Alisi, A, Piscaglia, F, Gerussi, A, Brunetto, M, Bonino, F, Montalti, R, Campanile, S, Persico, M, Alvaro, D, Santini, S, Invernizzi, P, Carbone, M, Masarone, M, Eccher, A, Siciliano, B, Vento, M, Ficuciello, F, Cabitza, F, Penasa, S, Donatelli, P, Balsano C., Burra P., Duvoux C., Alisi A., Piscaglia F., Gerussi A., Brunetto M. R., Bonino F., Montalti R., Campanile S., Persico M., Alvaro D., Santini S., Invernizzi P., Carbone M., Masarone M., Eccher A., Siciliano B., Vento M., Ficuciello F., Cabitza F., Penasa S., Donatelli P., Balsano, C, Burra, P, Duvoux, C, Alisi, A, Piscaglia, F, Gerussi, A, Brunetto, M, Bonino, F, Montalti, R, Campanile, S, Persico, M, Alvaro, D, Santini, S, Invernizzi, P, Carbone, M, Masarone, M, Eccher, A, Siciliano, B, Vento, M, Ficuciello, F, Cabitza, F, Penasa, S, Donatelli, P, Balsano C., Burra P., Duvoux C., Alisi A., Piscaglia F., Gerussi A., Brunetto M. R., Bonino F., Montalti R., Campanile S., Persico M., Alvaro D., Santini S., Invernizzi P., Carbone M., Masarone M., Eccher A., Siciliano B., Vento M., Ficuciello F., Cabitza F., Penasa S., and Donatelli P.

Abstract

Artificial Intelligence (AI) has recently been shown as an excellent tool for the study of the liver; however, many obstacles still have to be overcome for the digitalization of real-world hepatology. The authors present an overview of the current state of the art on the use of innovative technologies in different areas (big data, translational hepatology, imaging, and transplant setting). In clinical practice, physicians must integrate a vast array of data modalities (medical history, clinical data, laboratory tests, imaging, and pathology slides) to achieve a diagnostic or therapeutic decision. Unfortunately, machine learning and deep learning are still far from really supporting clinicians in real life. In fact, the accuracy of any technological support has no value in medicine without the support of clinicians. To make better use of new technologies, it is essential to improve clinicians’ knowledge about them. To this end, the authors propose that collaborative networks for multidisciplinary approaches will improve the rapid implementation of AI systems for developing disease-customized AI-powered clinical decision support tools. The authors also discuss ethical, educational, and legal challenges that must be overcome to build robust bridges and deploy potentially effective AI in real-world clinical settings.

Published
2023

19. Trends in chronic hepatitis B virus infection in Italy over a 10-year period: Clues from the nationwide PITER and MASTER cohorts toward elimination

Author

Brancaccio, G, Coco, B, Nardi, A, Quaranta, M, Tosti, M, Ferrigno, L, Cacciola, I, Messina, V, Chessa, L, Morisco, F, Milella, M, Barbaro, F, Ciancio, A, Russo, F, Coppola, N, Blanc, P, Claar, E, Verucchi, G, Puoti, M, Zignego, A, Chemello, L, Madonia, S, Fagiuoli, S, Marzano, A, Ferrari, C, Lampertico, P, Di Marco, V, Craxì, A, Santantonio, T, Raimondo, G, Brunetto, M, Gaeta, G, Kondili, L, Pasulo, L, Coppola, C, Pisano, F, Romano, M, Porcu, C, Bottalico, I, Cossiga, V, Tata, X, Sagnelli, C, Pierotti, P, Degasperi, E, Rosato, V, Badia, L, Ieluzzi, D, Monti, M, Bavetta, M, Cavalletto, L, Toniutto, P, Fornasiere, E, Colecchia, A, Ferrarese, A, Nardone, G, Rocco, A, Viganò, M, Foschi, F, Conti, F, Morsica, G, Salpietro, S, Torti, C, Costa, C, Federico, A, Dallio, M, Giorgini, A, Anselmo, M, De Leo, P, Zaltron, S, Cambianica, A, Piscaglia, F, Serio, I, Schivazappa, S, Mastroianni, A, Chidichimo, L, Massari, M, Mazzaro, C, Marrone, A, D'Amore, F, D'Offizi, G, Licata, A, Niro, G, Pollicino, T, Aghemo, A, Brancaccio G., Coco B., Nardi A., Quaranta M. G., Tosti M. E., Ferrigno L., Cacciola I., Messina V., Chessa L., Morisco F., Milella M., Barbaro F., Ciancio A., Russo F. P., Coppola N., Blanc P., Claar E., Verucchi G., Puoti M., Zignego A. L., Chemello L., Madonia S., Fagiuoli S., Marzano A., Ferrari C., Lampertico P., Di Marco V., Craxì A., Santantonio T. A., Raimondo G., Brunetto M. R., Gaeta G. B., Kondili L. A., Pasulo L., Coppola C., Pisano F., Romano M., Porcu C., Bottalico I. F., Cossiga V., Tata X., Sagnelli C., Pierotti P., Degasperi E., Rosato V., Badia L., Ieluzzi D., Monti M., Bavetta M. G., Cavalletto L., Toniutto P., Fornasiere E., Colecchia A., Ferrarese A., Nardone G., Rocco A., Viganò M., Foschi F. G., Conti F., Morsica G., Salpietro S., Torti C., Costa C., Federico A., Dallio M., Giorgini A., Anselmo M., De Leo P., Zaltron S., Cambianica A., Piscaglia F., Serio I., Schivazappa S., Mastroianni A., Chidichimo L., Massari M., Mazzaro C., Marrone A., D'Amore F. M., D'Offizi G., Licata A., Niro G. A., Pollicino T., Aghemo A., Brancaccio, G, Coco, B, Nardi, A, Quaranta, M, Tosti, M, Ferrigno, L, Cacciola, I, Messina, V, Chessa, L, Morisco, F, Milella, M, Barbaro, F, Ciancio, A, Russo, F, Coppola, N, Blanc, P, Claar, E, Verucchi, G, Puoti, M, Zignego, A, Chemello, L, Madonia, S, Fagiuoli, S, Marzano, A, Ferrari, C, Lampertico, P, Di Marco, V, Craxì, A, Santantonio, T, Raimondo, G, Brunetto, M, Gaeta, G, Kondili, L, Pasulo, L, Coppola, C, Pisano, F, Romano, M, Porcu, C, Bottalico, I, Cossiga, V, Tata, X, Sagnelli, C, Pierotti, P, Degasperi, E, Rosato, V, Badia, L, Ieluzzi, D, Monti, M, Bavetta, M, Cavalletto, L, Toniutto, P, Fornasiere, E, Colecchia, A, Ferrarese, A, Nardone, G, Rocco, A, Viganò, M, Foschi, F, Conti, F, Morsica, G, Salpietro, S, Torti, C, Costa, C, Federico, A, Dallio, M, Giorgini, A, Anselmo, M, De Leo, P, Zaltron, S, Cambianica, A, Piscaglia, F, Serio, I, Schivazappa, S, Mastroianni, A, Chidichimo, L, Massari, M, Mazzaro, C, Marrone, A, D'Amore, F, D'Offizi, G, Licata, A, Niro, G, Pollicino, T, Aghemo, A, Brancaccio G., Coco B., Nardi A., Quaranta M. G., Tosti M. E., Ferrigno L., Cacciola I., Messina V., Chessa L., Morisco F., Milella M., Barbaro F., Ciancio A., Russo F. P., Coppola N., Blanc P., Claar E., Verucchi G., Puoti M., Zignego A. L., Chemello L., Madonia S., Fagiuoli S., Marzano A., Ferrari C., Lampertico P., Di Marco V., Craxì A., Santantonio T. A., Raimondo G., Brunetto M. R., Gaeta G. B., Kondili L. A., Pasulo L., Coppola C., Pisano F., Romano M., Porcu C., Bottalico I. F., Cossiga V., Tata X., Sagnelli C., Pierotti P., Degasperi E., Rosato V., Badia L., Ieluzzi D., Monti M., Bavetta M. G., Cavalletto L., Toniutto P., Fornasiere E., Colecchia A., Ferrarese A., Nardone G., Rocco A., Viganò M., Foschi F. G., Conti F., Morsica G., Salpietro S., Torti C., Costa C., Federico A., Dallio M., Giorgini A., Anselmo M., De Leo P., Zaltron S., Cambianica A., Piscaglia F., Serio I., Schivazappa S., Mastroianni A., Chidichimo L., Massari M., Mazzaro C., Marrone A., D'Amore F. M., D'Offizi G., Licata A., Niro G. A., Pollicino T., and Aghemo A.

Abstract

Objectives: The study measures trends in the profile of patients with chronic hepatitis B virus linked to care in Italy. Methods: A cross-sectional, multicenter, observational cohort (PITER cohort) of consecutive patients with hepatitis B surface antigen (HBsAg) over the period 2019-2021 from 46 centers was evaluated. The reference was the MASTER cohort collected over the years 2012-2015. Standard statistical methods were used. Results: The PITER cohort enrolled 4583 patients, of whom 21.8% were non-Italian natives. Compared with those in MASTER, the patients were older and more often female. The prevalence of hepatitis B e antigen (HBeAg) declined (7.2% vs 12.3; P <0.0001) and that of anti-hepatitis D virus (HDV) remained stable (9.3% vs 8.3%). In both cohorts, about 25% of the patients had cirrhosis, and those in the PITER cohort were older. HBeAg-positive was 5.0% vs 12.6% (P <0.0001) and anti-HDV positive 24.8% vs 17.5% (P <0.0017). In the logistic model, the variables associated with cirrhosis were anti-HDV-positive (odds ratio = 10.08; confidence interval 7.63-13.43), age, sex, and body mass index; the likelihood of cirrhosis was reduced by 40% in the PITER cohort. Among non-Italians, 12.3% were HBeAg-positive (vs 23.4% in the MASTER cohort; P <0.0001), and 12.3% were anti-HDV-positive (vs 11.1%). Overall, the adherence to the European Association for the Study of the Liver recommendations for antiviral treatment increased over time. Conclusion: Chronic hepatitis B virus infection appears to be in the process of becoming under control in Italy; however, HDV infection is still a health concern in patients with cirrhosis and in migrants.

Published
2023

21. Clinical impact of relative dose intensity of cabozantinib during the first 8 weeks and of subsequent dose reductions in patients with unresectable hepatocellular carcinoma

Author

Tovoli, F., primary, Dadduzio, V., additional, De Lorenzo, S., additional, Rimassa, L., additional, Masi, G., additional, Iavarone, M., additional, Marra, F., additional, Garajova, I., additional, Brizzi, M.P., additional, Daniele, B., additional, Trevisani, F., additional, Messina, C., additional, Clemente, F. Di, additional, Pini, S., additional, Cabibbo, G., additional, Granito, A., additional, Rizzato, M.D., additional, Zagonel, V., additional, Brandi, G., additional, Pressiani, T., additional, Federico, P., additional, Vivaldi, C., additional, Bergna, I., additional, Campani, C., additional, and Piscaglia, F., additional

Published
2023
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23. Predictors of extrahepatic progression in patients with hepatocellular carcinoma receiving transarterial chemoembolization

Author

Pinto, E., primary, Pelizzaro, F., additional, Vitale, A., additional, Sangiovanni, A., additional, Cabibbo, G., additional, Caturelli, E., additional, Svegliati-Baroni, G., additional, Masotto, A., additional, Trevisani, F., additional, Foschi, F.G., additional, Piscaglia, F., additional, Raimondo, G., additional, Giannini, E.G., additional, Azzaroli, F., additional, Marra, F., additional, Mega, A., additional, Vidili, G., additional, Brunetto, M.R., additional, Missale, G., additional, Gasbarrini, A., additional, Rapaccini, G.L., additional, Guarino, M., additional, Magalotti, D., additional, Sacco, R., additional, Nardone, G., additional, Marco, M. Di, additional, and Farinati, F., additional

Published
2023
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26. The application of artificial intelligence in hepatology: A systematic review

Author

Balsano, C, Alisi, A, Brunetto, M, Invernizzi, P, Burra, P, Piscaglia, F, Alvaro, D, Bonino, F, Carbone, M, Faita, F, Gerussi, A, Persico, M, Santini, S, Zanetto, A, Balsano C., Alisi A., Brunetto M. R., Invernizzi P., Burra P., Piscaglia F., Alvaro D., Bonino F., Carbone M., Faita F., Gerussi A., Persico M., Santini S. J., Zanetto A., Balsano, C, Alisi, A, Brunetto, M, Invernizzi, P, Burra, P, Piscaglia, F, Alvaro, D, Bonino, F, Carbone, M, Faita, F, Gerussi, A, Persico, M, Santini, S, Zanetto, A, Balsano C., Alisi A., Brunetto M. R., Invernizzi P., Burra P., Piscaglia F., Alvaro D., Bonino F., Carbone M., Faita F., Gerussi A., Persico M., Santini S. J., and Zanetto A.

Abstract

The integration of human and artificial intelligence (AI) in medicine has only recently begun but it has already become obvious that intelligent systems can dramatically improve the management of liver diseases. Big data made it possible to envisage transformative developments of the use of AI for diagnosing, predicting prognosis and treating liver diseases, but there is still a lot of work to do. If we want to achieve the 21st century digital revolution, there is an urgent need for specific national and international rules, and to adhere to bioethical parameters when collecting data. Avoiding misleading results is essential for the effective use of AI. A crucial question is whether it is possible to sustain, technically and morally, the process of integration between man and machine. We present a systematic review on the applications of AI to hepatology, highlighting the current challenges and crucial issues related to the use of such technologies.

Published
2022

28. Preoperative predictors of recurrence beyond Milan criteria in hepatocellular carcinoma patients treated with frontline liver resection

Author

Pelizzaro, F., primary, Trevisani, F., additional, Vitale, A., additional, Cillo, U., additional, Piscaglia, F., additional, Missale, G., additional, Sangiovanni, A., additional, Foschi, F.G., additional, Cabibbo, G., additional, Caturelli, E., additional, Di Marco, M., additional, Azzaroli, F., additional, Brunetto, M.R., additional, Raimondo, G., additional, Vidili, G., additional, Guarino, M., additional, Gasbarrini, A., additional, Campani, C., additional, Svegliati-Baroni, G., additional, Giannini, E.G., additional, Mega, A., additional, Masotto, A., additional, Rapaccini, G.L., additional, Magalotti, D., additional, Sacco, R., additional, Nardone, G., additional, and Farinati, F., additional

Published
2023
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29. Incidence and risk factors of esophagogastric varices bleeding in cirrhotic patients with advanced hepatocellular carcinoma treated with lenvatinib

Author

Iavarone, M., primary, Alimenti, E., additional, Tada, T., additional, Shimose, S., additional, Suda, G., additional, Yoo, C., additional, Soldà, C., additional, Piscaglia, F., additional, Casadei-Gardini, A., additional, Marra, F., additional, Vivaldi, C., additional, Conti, F., additional, Schirripa, M., additional, Iwamoto, H., additional, Sho, T., additional, Lee, So Heun, additional, Rizzato, M.D., additional, Tonnini, M., additional, Rimini, M., additional, Campani, C., additional, Masi, G., additional, Foschi, F., additional, Bruccoleri, M., additional, Kawaguchi, T., additional, Kumada, T., additional, Hiraoka, A., additional, Atsukawa, M., additional, Fukunishi, S., additional, Ishikawa, T., additional, Tajiri, K., additional, Ochi, H., additional, Yasuda, S., additional, Toyoda, H., additional, Hatanaka, T., additional, Kakizaki, S., additional, Kawata, K., additional, Tada, F., additional, Ohama, H., additional, Itokawa, N., additional, Okubo, T., additional, Arai, T., additional, Imai, M., additional, Naganuma, A., additional, Tosetti, G., additional, and Lampertico, P., additional

Published
2023
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31. Extension of Bulevirtide monotherapy to 72 weeks in HDV patients with compensated cirrhosis: Efficacy and safety from the italian multicenter study (HEP4Di)

Author

Anolli, M.P., primary, Degasperi, E., additional, D'Offizi, G., additional, Brunetto, M.R., additional, Verucchi, G., additional, Federico, A., additional, Ciancio, A., additional, Mangia, A., additional, Santantonio, T.A., additional, Coppola, N., additional, Pellicelli, A., additional, Loglio, A., additional, Viganò, M., additional, Pileri, F., additional, Maracci, Monia, additional, Puoti, M., additional, Piscaglia, F., additional, and Lampertico, P., additional

Published
2023
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32. MiR-494 induces metabolic reprogramming through G6pc targeting and modulates sorafenib response in hepatocellular carcinoma

Author

Galvani, G., primary, Leoni, I., additional, Bergamini, C., additional, Rizzardi, N., additional, Melli, M., additional, Coada, C.A., additional, Monti, E., additional, Giovannini, C., additional, Liparulo, I., additional, Ferracin, M., additional, Ravaioli, M., additional, Cescon, M., additional, Vasuri, F., additional, Piscaglia, F., additional, Negrini, M., additional, Stefanelli, C., additional, Fato, R., additional, Gramantieri, L., additional, and Fornari, F., additional

Published
2023
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35. Machine Learning Predictive Model to Guide Treatment Allocation for Recurrent Hepatocellular Carcinoma After Surgery

Author

Famularo, S., Donadon, M., Cipriani, F., Fazio, F., Ardito, Francesco, Iaria, M., Perri, P., Conci, S., Dominioni, T., Lai, Q., La Barba, G., Patauner, S., Molfino, S., Germani, P., Zimmitti, G., Pinotti, E., Zanello, M., Fumagalli, L., Ferrari, C., Romano, M., Delvecchio, A., Valsecchi, M. G., Antonucci, A., Piscaglia, F., Farinati, F., Kawaguchi, Y., Hasegawa, K., Memeo, R., Zanus, G., Griseri, G., Chiarelli, M., Jovine, E., Zago, M., Abu Hilal, M., Tarchi, P., Baiocchi, G. L., Frena, A., Ercolani, G., Rossi, M., Maestri, M., Ruzzenente, A., Grazi, G. L., Dalla Valle, R., Romano, F., Giuliante, Felice, Ferrero, A., Aldrighetti, L., Bernasconi, D. P., Torzilli, G., Ardito F. (ORCID:0000-0003-1596-2862), Giuliante F. (ORCID:0000-0001-9517-8220), Famularo, S., Donadon, M., Cipriani, F., Fazio, F., Ardito, Francesco, Iaria, M., Perri, P., Conci, S., Dominioni, T., Lai, Q., La Barba, G., Patauner, S., Molfino, S., Germani, P., Zimmitti, G., Pinotti, E., Zanello, M., Fumagalli, L., Ferrari, C., Romano, M., Delvecchio, A., Valsecchi, M. G., Antonucci, A., Piscaglia, F., Farinati, F., Kawaguchi, Y., Hasegawa, K., Memeo, R., Zanus, G., Griseri, G., Chiarelli, M., Jovine, E., Zago, M., Abu Hilal, M., Tarchi, P., Baiocchi, G. L., Frena, A., Ercolani, G., Rossi, M., Maestri, M., Ruzzenente, A., Grazi, G. L., Dalla Valle, R., Romano, F., Giuliante, Felice, Ferrero, A., Aldrighetti, L., Bernasconi, D. P., Torzilli, G., Ardito F. (ORCID:0000-0003-1596-2862), and Giuliante F. (ORCID:0000-0001-9517-8220)

Abstract

Importance: Clear indications on how to select retreatments for recurrent hepatocellular carcinoma (HCC) are still lacking. Objective: To create a machine learning predictive model of survival after HCC recurrence to allocate patients to their best potential treatment. Design, Setting, and Participants: Real-life data were obtained from an Italian registry of hepatocellular carcinoma between January 2008 and December 2019 after a median (IQR) follow-up of 27 (12-51) months. External validation was made on data derived by another Italian cohort and a Japanese cohort. Patients who experienced a recurrent HCC after a first surgical approach were included. Patients were profiled, and factors predicting survival after recurrence under different treatments that acted also as treatment effect modifiers were assessed. The model was then fitted individually to identify the best potential treatment. Analysis took place between January and April 2021. Exposures: Patients were enrolled if treated by reoperative hepatectomy or thermoablation, chemoembolization, or sorafenib. Main Outcomes and Measures: Survival after recurrence was the end point. Results: A total of 701 patients with recurrent HCC were enrolled (mean [SD] age, 71 [9] years; 151 [21.5%] female). Of those, 293 patients (41.8%) received reoperative hepatectomy or thermoablation, 188 (26.8%) received sorafenib, and 220 (31.4%) received chemoembolization. Treatment, age, cirrhosis, number, size, and lobar localization of the recurrent nodules, extrahepatic spread, and time to recurrence were all treatment effect modifiers and survival after recurrence predictors. The area under the receiver operating characteristic curve of the predictive model was 78.5% (95% CI, 71.7%-85.3%) at 5 years after recurrence. According to the model, 611 patients (87.2%) would have benefited from reoperative hepatectomy or thermoablation, 37 (5.2%) from sorafenib, and 53 (7.6%) from chemoembolization in terms of potential survival after re

Published
2023

37. 67P Real-world data for atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma

Author

Persano, M., primary, Rimini, M., additional, Tada, T., additional, Suda, G., additional, Shimose, S., additional, Kudo, M., additional, Cheon, J., additional, Finkelmeier, F., additional, Rimassa, L., additional, Presa, J., additional, Masi, G., additional, Yoo, C., additional, Lonardi, S., additional, Piscaglia, F., additional, Burgio, V., additional, Scartozzi, M., additional, Cascinu, S., additional, and Casadei Gardini, A., additional

Published
2022
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38. 65P Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: A large real life worldwide population

Author

Rimini, M., primary, Casadei Gardini, A., additional, Persano, M., additional, Suda, G., additional, Tada, T., additional, Shimose, S., additional, Kudo, M., additional, Cheon, J., additional, Finkelmeier, F., additional, Rimassa, L., additional, Presa, J., additional, Masi, G., additional, Yoo, C., additional, Lonardi, S., additional, Tovoli, F., additional, Piscaglia, F., additional, Iavarone, M.A., additional, Scartozzi, M., additional, Burgio, V., additional, Cascinu, S., additional, and Cucchetti, A., additional

Published
2022
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42. Overview of prognostic systems for hepatocellular carcinoma and ITA.LI.CA external validation of MESH and CNLC classifications

Author

Vitale, A, Farinati, F, Finotti, M, Di Renzo, C, Brancaccio, G, Piscaglia, F, Cabibbo, G, Caturelli, E, Missale, G, Marra, F, Sacco, R, Giannini, E, Trevisani, F, Cillo, U, Bhoori, S, Borzio, M, Burra, P, Casadei Gardini, A, Carrai, P, Conti, F, Cozzolongo, R, Cucchetti, A, D'Ambrosio, R, Dell'Unto, C, De Matthaeis, N, Di Costanzo, G, Di Sandro, S, Famularo, S, Foschi, F, Fucilli, F, Galati, G, Gambato, M, Gasbarrini, A, Giuliante, F, Ghinolfi, D, Grieco, A, Gruttadauria, S, Guarino, M, Iavarone, M, Kostandini, A, Lai, Q, Lenci, I, Levi Sandri, G, Losito, F, Lupo, L, Marasco, G, Manzia, T, Mazzocato, S, Masarone, M, Melandro, F, Mescoli, C, Miele, L, Morisco, F, Muley, M, Nicolini, D, Pagano, D, Persico, M, Pompili, M, Ponziani, F, Pravisani, R, Rapaccini, G, Rendina, M, Renzulli, M, Romano, F, Rossi, M, Rreka, E, Russo, F, Sangiovanni, A, Sessa, A, Simonetti, N, Sposito, C, Tortora, R, Vigano, L, Vigano, M, Villa, E, Vincenzi, V, Violi, P, Azzaroli, F, Brunetto, M, Di Marco, A, Masotto, A, Mega, A, Nardone, G, Oliveri, F, Raimondo, G, Svegliati Baroni, G, Vidili, G, Zoli, M, Vitale A., Farinati F., Finotti M., Di Renzo C., Brancaccio G., Piscaglia F., Cabibbo G., Caturelli E., Missale G., Marra F., Sacco R., Giannini E. G., Trevisani F., Cillo U., Bhoori S., Borzio M., Burra P., Casadei Gardini A., Carrai P., Conti F., Cozzolongo R., Cucchetti A., D'ambrosio R., Dell'unto C., De Matthaeis N., Di Costanzo G. G., Di Sandro S., Famularo S., Foschi F. G., Fucilli F., Galati G., Gambato M., Gasbarrini A., Giuliante F., Ghinolfi D., Grieco A., Gruttadauria S., Guarino M., Iavarone M., Kostandini A., Lai Q., Lenci I., Levi Sandri G. V., Losito F., Lupo L. G., Marasco G., Manzia T. M., Mazzocato S., Masarone M., Melandro F., Mescoli C., Miele L., Morisco F., Muley M., Nicolini D., Pagano D., Persico M., Pompili M., Ponziani F. R., Pravisani R., Rapaccini G. L., Rendina M., Renzulli M., Romano F., Rossi M., Rreka E., Russo F. P., Sangiovanni A., Sessa A., Simonetti N., Sposito C., Tortora R., Vigano L., Vigano M., Villa E., Vincenzi V., Violi P., Azzaroli F., Brunetto M. R., Di Marco A., Masotto A., Mega A., Nardone G., Oliveri F., Raimondo G., Svegliati Baroni G., Vidili G., Zoli M., Vitale, A, Farinati, F, Finotti, M, Di Renzo, C, Brancaccio, G, Piscaglia, F, Cabibbo, G, Caturelli, E, Missale, G, Marra, F, Sacco, R, Giannini, E, Trevisani, F, Cillo, U, Bhoori, S, Borzio, M, Burra, P, Casadei Gardini, A, Carrai, P, Conti, F, Cozzolongo, R, Cucchetti, A, D'Ambrosio, R, Dell'Unto, C, De Matthaeis, N, Di Costanzo, G, Di Sandro, S, Famularo, S, Foschi, F, Fucilli, F, Galati, G, Gambato, M, Gasbarrini, A, Giuliante, F, Ghinolfi, D, Grieco, A, Gruttadauria, S, Guarino, M, Iavarone, M, Kostandini, A, Lai, Q, Lenci, I, Levi Sandri, G, Losito, F, Lupo, L, Marasco, G, Manzia, T, Mazzocato, S, Masarone, M, Melandro, F, Mescoli, C, Miele, L, Morisco, F, Muley, M, Nicolini, D, Pagano, D, Persico, M, Pompili, M, Ponziani, F, Pravisani, R, Rapaccini, G, Rendina, M, Renzulli, M, Romano, F, Rossi, M, Rreka, E, Russo, F, Sangiovanni, A, Sessa, A, Simonetti, N, Sposito, C, Tortora, R, Vigano, L, Vigano, M, Villa, E, Vincenzi, V, Violi, P, Azzaroli, F, Brunetto, M, Di Marco, A, Masotto, A, Mega, A, Nardone, G, Oliveri, F, Raimondo, G, Svegliati Baroni, G, Vidili, G, Zoli, M, Vitale A., Farinati F., Finotti M., Di Renzo C., Brancaccio G., Piscaglia F., Cabibbo G., Caturelli E., Missale G., Marra F., Sacco R., Giannini E. G., Trevisani F., Cillo U., Bhoori S., Borzio M., Burra P., Casadei Gardini A., Carrai P., Conti F., Cozzolongo R., Cucchetti A., D'ambrosio R., Dell'unto C., De Matthaeis N., Di Costanzo G. G., Di Sandro S., Famularo S., Foschi F. G., Fucilli F., Galati G., Gambato M., Gasbarrini A., Giuliante F., Ghinolfi D., Grieco A., Gruttadauria S., Guarino M., Iavarone M., Kostandini A., Lai Q., Lenci I., Levi Sandri G. V., Losito F., Lupo L. G., Marasco G., Manzia T. M., Mazzocato S., Masarone M., Melandro F., Mescoli C., Miele L., Morisco F., Muley M., Nicolini D., Pagano D., Persico M., Pompili M., Ponziani F. R., Pravisani R., Rapaccini G. L., Rendina M., Renzulli M., Romano F., Rossi M., Rreka E., Russo F. P., Sangiovanni A., Sessa A., Simonetti N., Sposito C., Tortora R., Vigano L., Vigano M., Villa E., Vincenzi V., Violi P., Azzaroli F., Brunetto M. R., Di Marco A., Masotto A., Mega A., Nardone G., Oliveri F., Raimondo G., Svegliati Baroni G., Vidili G., and Zoli M.

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.

Published
2021

43. Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort

Author

Quaranta, M, Ferrigno, L, Tata, X, D'Angelo, F, Massari, M, Coppola, C, Biliotti, E, Giorgini, A, Laccabue, D, Ciancio, A, Blanc, P, Margotti, M, Ieluzzi, D, Brunetto, M, Barbaro, F, Russo, F, Beretta, I, Morsica, G, Verucchi, G, Saracino, A, Galli, M, Kondili, L, Mazzaro, C, Bertola, M, Benedetti, A, Schiada, L, Cucco, M, Giacometti, A, Brescini, L, Castelletti, S, Fiorentini, A, Angarano, G, Milella, M, Leo, A, Rendina, M, Salvatore D'ABRAMO, F, Lillo, C, Iannone, A, Piazzolla, M, Badia, L, Piscaglia, F, Benevento, F, Serio, I, Castelli, F, Zaltron, S, Spinetti, A, Odolini, S, Bruno, R, Mondelli, M, Chessa, L, Loi, M, Torti, C, Costa, C, Mazzitelli, M, Pisani, V, Scaglione, V, Trecarichi, E, Zignego, A, Monti, M, Madia, F, Attala, L, Pierotti, P, Salomoni, E, Mariabelli, E, Santantonio, T, Bruno, S, Cela, E, Bassetti, M, Mazzarello, G, Alessandrini, A, Biagio, A, Nicolini, L, Raimondo, G, Filomia, R, Aghemo, A, Meli, R, Lazzarin, A, Salpietro, S, Fracanzani, A, Fatta, E, Lombardi, R, Lampertico, P, Borghi, M, D'Ambrosio, R, Degasperi, E, Puoti, M, Baiguera, C, D'Amico, F, Vinci, M, Rumi, M, Zuin, M, Zermiani, P, Andreone, P, Caraceni, P, Guarneri, V, Villa, E, Bernabucci, V, Bristot, L, Paradiso, M, Migliorino, G, Gambaro, A, Lapadula, G, Spolti, A, Soria, A, Invernizzi, P, Ciaccio, A, Luca, M, Malinverno, F, Ratti, L, Amoruso, D, Pisano, F, Scarano, F, Staiano, L, Morisco, F, Cossiga, V, Gentile, I, Buonomo, A, Foggia, M, Zappulo, E, Federico, A, Dallio, M, Coppola, N, Sagnelli, C, Martini, S, Monari, C, Nardone, G, Sgamato, C, Chemello, L, Cavalletto, L, Sterrantino, D, Zanetto, A, Zanaga, P, Brancaccio, G, Craxi, A, Petta, S, Calvaruso, V, Crapanzano, L, Madonia, S, Cannizzaro, M, Bruno, E, Licata, A, Amodeo, S, Capitano, A, Ferrari, C, Negri, E, Orlandini, A, Pesci, M, Gulminetti, R, Pagnucco, L, Parruti, G, Stefano, P, Coco, B, Corsini, R, Garlassi, E, Andreoni, M, Teti, E, Cerva, C, Baiocchi, L, Grassi, G, Gasbarrini, A, Pompili, M, Siena, M, Taliani, G, Spaziante, M, Persico, M, Masarone, M, Aglitti, A, Calvanese, G, Anselmo, M, Leo, P, Marturano, M, Saracco, G, Quaranta M. G., Ferrigno L., Tata X., D'Angelo F., Massari M., Coppola C., Biliotti E., Giorgini A., Laccabue D., Ciancio A., Blanc P. L., Margotti M., Ieluzzi D., Brunetto M. R., Barbaro F., Russo F. P., Beretta I., Morsica G., Verucchi G., Saracino A., Galli M., Kondili L. A., Mazzaro C., Bertola M., Benedetti A., Schiada L., Cucco M., Giacometti A., Brescini L., Castelletti S., Fiorentini A., Angarano G., Milella M., Leo A. D., Rendina M., Salvatore D'ABRAMO F., Lillo C., Iannone A., Piazzolla M., Badia L., Piscaglia F., Benevento F., Serio I., Castelli F., Zaltron S., Spinetti A., Odolini S., Bruno R., Mondelli M., Chessa L., Loi M., Torti C., Costa C., Mazzitelli M., Pisani V., Scaglione V., Trecarichi E. M., Zignego A. L., Monti M., Madia F., Attala L., Pierotti P., Salomoni E., Mariabelli E., Santantonio T. A., Bruno S. R., Cela E. M., Bassetti M., Mazzarello G., Alessandrini A. I., Biagio A. D., Nicolini L. A., Raimondo G., Filomia R., Aghemo A., Meli R., Lazzarin A., Salpietro S., Fracanzani A. L., Fatta E., Lombardi R., Lampertico P., Borghi M., D'ambrosio R., Degasperi E., Puoti M., Baiguera C., D'AMICO F., Vinci M., Rumi M. G., Zuin M., Zermiani P., Andreone P., Caraceni P., Guarneri V., Villa E., Bernabucci V., Bristot L., Paradiso M. L., Migliorino G., Gambaro A., Lapadula G., Spolti A., Soria A., Invernizzi P., Ciaccio A., LucA M., Malinverno F., Ratti L., Amoruso D. C., Pisano F., Scarano F., Staiano L., Morisco F., Cossiga V., Gentile I., Buonomo A. R., Foggia M., Zappulo E., Federico A., Dallio M., Coppola N., Sagnelli C., Martini S., Monari C., Nardone G., Sgamato C., Chemello L., Cavalletto L., Sterrantino D., Zanetto A., Zanaga P., Brancaccio G., Craxi A., Petta S., Calvaruso V., Crapanzano L., Madonia S., Cannizzaro M., Bruno E. M., Licata A., Amodeo S., Capitano A. R., Ferrari C., Negri E., Orlandini A., Pesci M., Gulminetti R., Pagnucco L., Parruti G., Stefano P. D., Coco B., Corsini R., Garlassi E., Andreoni M., Teti E., Cerva C., Baiocchi L., Grassi G., Gasbarrini A., Pompili M., Siena M. D., Taliani G., Spaziante M., Persico M., Masarone M., Aglitti A., Calvanese G., Anselmo M., Leo P. D., Marturano M., Saracco G. M., Quaranta, M, Ferrigno, L, Tata, X, D'Angelo, F, Massari, M, Coppola, C, Biliotti, E, Giorgini, A, Laccabue, D, Ciancio, A, Blanc, P, Margotti, M, Ieluzzi, D, Brunetto, M, Barbaro, F, Russo, F, Beretta, I, Morsica, G, Verucchi, G, Saracino, A, Galli, M, Kondili, L, Mazzaro, C, Bertola, M, Benedetti, A, Schiada, L, Cucco, M, Giacometti, A, Brescini, L, Castelletti, S, Fiorentini, A, Angarano, G, Milella, M, Leo, A, Rendina, M, Salvatore D'ABRAMO, F, Lillo, C, Iannone, A, Piazzolla, M, Badia, L, Piscaglia, F, Benevento, F, Serio, I, Castelli, F, Zaltron, S, Spinetti, A, Odolini, S, Bruno, R, Mondelli, M, Chessa, L, Loi, M, Torti, C, Costa, C, Mazzitelli, M, Pisani, V, Scaglione, V, Trecarichi, E, Zignego, A, Monti, M, Madia, F, Attala, L, Pierotti, P, Salomoni, E, Mariabelli, E, Santantonio, T, Bruno, S, Cela, E, Bassetti, M, Mazzarello, G, Alessandrini, A, Biagio, A, Nicolini, L, Raimondo, G, Filomia, R, Aghemo, A, Meli, R, Lazzarin, A, Salpietro, S, Fracanzani, A, Fatta, E, Lombardi, R, Lampertico, P, Borghi, M, D'Ambrosio, R, Degasperi, E, Puoti, M, Baiguera, C, D'Amico, F, Vinci, M, Rumi, M, Zuin, M, Zermiani, P, Andreone, P, Caraceni, P, Guarneri, V, Villa, E, Bernabucci, V, Bristot, L, Paradiso, M, Migliorino, G, Gambaro, A, Lapadula, G, Spolti, A, Soria, A, Invernizzi, P, Ciaccio, A, Luca, M, Malinverno, F, Ratti, L, Amoruso, D, Pisano, F, Scarano, F, Staiano, L, Morisco, F, Cossiga, V, Gentile, I, Buonomo, A, Foggia, M, Zappulo, E, Federico, A, Dallio, M, Coppola, N, Sagnelli, C, Martini, S, Monari, C, Nardone, G, Sgamato, C, Chemello, L, Cavalletto, L, Sterrantino, D, Zanetto, A, Zanaga, P, Brancaccio, G, Craxi, A, Petta, S, Calvaruso, V, Crapanzano, L, Madonia, S, Cannizzaro, M, Bruno, E, Licata, A, Amodeo, S, Capitano, A, Ferrari, C, Negri, E, Orlandini, A, Pesci, M, Gulminetti, R, Pagnucco, L, Parruti, G, Stefano, P, Coco, B, Corsini, R, Garlassi, E, Andreoni, M, Teti, E, Cerva, C, Baiocchi, L, Grassi, G, Gasbarrini, A, Pompili, M, Siena, M, Taliani, G, Spaziante, M, Persico, M, Masarone, M, Aglitti, A, Calvanese, G, Anselmo, M, Leo, P, Marturano, M, Saracco, G, Quaranta M. G., Ferrigno L., Tata X., D'Angelo F., Massari M., Coppola C., Biliotti E., Giorgini A., Laccabue D., Ciancio A., Blanc P. L., Margotti M., Ieluzzi D., Brunetto M. R., Barbaro F., Russo F. P., Beretta I., Morsica G., Verucchi G., Saracino A., Galli M., Kondili L. A., Mazzaro C., Bertola M., Benedetti A., Schiada L., Cucco M., Giacometti A., Brescini L., Castelletti S., Fiorentini A., Angarano G., Milella M., Leo A. D., Rendina M., Salvatore D'ABRAMO F., Lillo C., Iannone A., Piazzolla M., Badia L., Piscaglia F., Benevento F., Serio I., Castelli F., Zaltron S., Spinetti A., Odolini S., Bruno R., Mondelli M., Chessa L., Loi M., Torti C., Costa C., Mazzitelli M., Pisani V., Scaglione V., Trecarichi E. M., Zignego A. L., Monti M., Madia F., Attala L., Pierotti P., Salomoni E., Mariabelli E., Santantonio T. A., Bruno S. R., Cela E. M., Bassetti M., Mazzarello G., Alessandrini A. I., Biagio A. D., Nicolini L. A., Raimondo G., Filomia R., Aghemo A., Meli R., Lazzarin A., Salpietro S., Fracanzani A. L., Fatta E., Lombardi R., Lampertico P., Borghi M., D'ambrosio R., Degasperi E., Puoti M., Baiguera C., D'AMICO F., Vinci M., Rumi M. G., Zuin M., Zermiani P., Andreone P., Caraceni P., Guarneri V., Villa E., Bernabucci V., Bristot L., Paradiso M. L., Migliorino G., Gambaro A., Lapadula G., Spolti A., Soria A., Invernizzi P., Ciaccio A., LucA M., Malinverno F., Ratti L., Amoruso D. C., Pisano F., Scarano F., Staiano L., Morisco F., Cossiga V., Gentile I., Buonomo A. R., Foggia M., Zappulo E., Federico A., Dallio M., Coppola N., Sagnelli C., Martini S., Monari C., Nardone G., Sgamato C., Chemello L., Cavalletto L., Sterrantino D., Zanetto A., Zanaga P., Brancaccio G., Craxi A., Petta S., Calvaruso V., Crapanzano L., Madonia S., Cannizzaro M., Bruno E. M., Licata A., Amodeo S., Capitano A. R., Ferrari C., Negri E., Orlandini A., Pesci M., Gulminetti R., Pagnucco L., Parruti G., Stefano P. D., Coco B., Corsini R., Garlassi E., Andreoni M., Teti E., Cerva C., Baiocchi L., Grassi G., Gasbarrini A., Pompili M., Siena M. D., Taliani G., Spaziante M., Persico M., Masarone M., Aglitti A., Calvanese G., Anselmo M., Leo P. D., Marturano M., and Saracco G. M.

Abstract

Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively. Conclusion: Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted.

Published
2021

44. Pattern of macrovascular invasion in hepatocellular carcinoma

Author

Guarino, M., Cucchetti, A., Pontillo, G., Farinati, F., Benevento, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Rodolfo, S., Cabibbo, G., Marra, F., Mega, A., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F. G., Missale, G., Masotto, A., Nardone, G., Raimondo, G., Azzaroli, F., Vidili, G., Oliveri, F., Trevisani, F., Giannini, E. G., Morisco, F., Biselli, M., Caraceni, P., Garuti, F., Gramenzi, A., Neri, A., Rampoldi, D., Santi, V., Forgione, A., Granito, A., Muratori, L., Piscaglia, F., Sansone, V., Tovoli, F., Dajti, E., Marasco, G., Ravaioli, F., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Cela, E. M., Facciorusso, A., Pelizzaro, F., Imondi, A., Sartori, A., Penzo, B., Cacciato, V., Casagrande, E., Moscatelli, A., Pellegatta, G., Pieri, G., de Matthaeis, N., Allegrini, G., Lauria, V., Ghittoni, G., Pelecca, G., Chegai, F., Coratella, F., Ortenzi, M., Olivari, A., Inno, A., Marchetti, F., Busacca, A., Camma, C., Di Martino, V., Rizzo, G. E. M., Franze, M. S., Saitta, C., Sauchella, A., Bevilacqua, V., Borghi, A., Gardini, A. C., Conti, F., Berardinelli, D., Ercolani, G., Napoli, L., Campani, C., Di Bonaventura, C., Gitto, S., Coccoli, P., Malerba, A., Capasso, M., Fiorentino, A., Pignata, L., Cossiga, V., Romagnoli, V., Guarino M., Cucchetti A., Pontillo G., Farinati F., Benevento F., Rapaccini G.L., Di Marco M., Caturelli E., Zoli M., Rodolfo S., Cabibbo G., Marra F., Mega A., Gasbarrini A., Svegliati-Baroni G., Foschi F.G., Missale G., Masotto A., Nardone G., Raimondo G., Azzaroli F., Vidili G., Oliveri F., Trevisani F., Giannini E.G., Morisco F., Biselli M., Caraceni P., Garuti F., Gramenzi A., Neri A., Rampoldi D., Santi V., Forgione A., Granito A., Muratori L., Piscaglia F., Sansone V., Tovoli F., Dajti E., Marasco G., Ravaioli F., Cappelli A., Golfieri R., Mosconi C., Renzulli M., Cela E.M., Facciorusso A., Pelizzaro F., Imondi A., Sartori A., Penzo B., Cacciato V., Casagrande E., Moscatelli A., Pellegatta G., Pieri G., de Matthaeis N., Allegrini G., Lauria V., Ghittoni G., Pelecca G., Chegai F., Coratella F., Ortenzi M., Olivari A., Inno A., Marchetti F., Busacca A., Camma C., Di Martino V., Rizzo G.E.M., Franze M.S., Saitta C., Sauchella A., Bevilacqua V., Borghi A., Gardini A.C., Conti F., Berardinelli D., Ercolani G., Napoli L., Campani C., Di Bonaventura C., Gitto S., Coccoli P., Malerba A., Capasso M., Fiorentino A., Pignata L., Cossiga V., Romagnoli V., Guarino, M., Cucchetti, A., Pontillo, G., Farinati, F., Benevento, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Rodolfo, S., Cabibbo, G., Marra, F., Mega, A., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F. G., Missale, G., Masotto, A., Nardone, G., Raimondo, G., Azzaroli, F., Vidili, G., Oliveri, F., Trevisani, F., Giannini, E. G., Morisco, F., Biselli, M., Caraceni, P., Garuti, F., Gramenzi, A., Neri, A., Rampoldi, D., Santi, V., Forgione, A., Granito, A., Muratori, L., Piscaglia, F., Sansone, V., Tovoli, F., Dajti, E., Marasco, G., Ravaioli, F., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Cela, E. M., Facciorusso, A., Pelizzaro, F., Imondi, A., Sartori, A., Penzo, B., Cacciato, V., Casagrande, E., Moscatelli, A., Pellegatta, G., Pieri, G., de Matthaeis, N., Allegrini, G., Lauria, V., Ghittoni, G., Pelecca, G., Chegai, F., Coratella, F., Ortenzi, M., Olivari, A., Inno, A., Marchetti, F., Busacca, A., Camma, C., Di Martino, V., Rizzo, G. E. M., Franze, M. S., Saitta, C., Sauchella, A., Bevilacqua, V., Borghi, A., Gardini, A. C., Conti, F., Berardinelli, D., Ercolani, G., Napoli, L., Campani, C., Di Bonaventura, C., Gitto, S., Coccoli, P., Malerba, A., Capasso, M., Fiorentino, A., Pignata, L., Cossiga, V., and Romagnoli, V.

Subjects
Ablation Techniques, Male, Registrie, Cirrhosis, Clinical Biochemistry, Mesenteric Vein, loco-regional treatment, 030204 cardiovascular system & hematology, Biochemistry, Gastroenterology, surgery, Antineoplastic Agent, Liver disease, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, cirrhosis, hepatocellular carcinoma, portal vein thrombosis, transplantation, Ascites, Ablation Technique, Registries, 030212 general & internal medicine, Chronic, Settore MED/12 - Gastroenterologia, Portal Vein, Liver Diseases, Liver Neoplasms, General Medicine, Middle Aged, Sorafenib, Prognosis, Hepatitis B, Alcoholic, Hepatitis C, Tumor Burden, Survival Rate, Italy, Liver Neoplasm, Hepatocellular carcinoma, Ascite, Female, medicine.symptom, Liver cancer, Human, medicine.medical_specialty, Carcinoma, Hepatocellular, Prognosi, Antineoplastic Agents, End Stage Liver Disease, 03 medical and health sciences, Mesenteric Veins, Hepatitis B, Chronic, Internal medicine, medicine, Humans, Hepatectomy, Neoplasm Invasiveness, portal vein thrombosi, Liver Diseases, Alcoholic, Aged, Neoplasm Invasivene, Performance status, business.industry, Carcinoma, Settore MED/09 - MEDICINA INTERNA, Patient Acuity, Hepatocellular, Hepatitis C, Chronic, medicine.disease, Liver Transplantation, Transplantation, Liver function, business, cirrhosi
Abstract

Background and aims: In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MaVI) limits treatment options and decreases survival. Detailed data on the relationship between MaVI extension and patients' characteristics, and its impact on patients' outcome are limited. We evaluated the prevalence and extension of MaVI in a large cohort of consecutive HCC patients, analysing its association with liver disease and tumour characteristics, as well as with treatments performed and patients' survival. Methods: We analysed data of 4774 patients diagnosed with HCC recorded in the Italian Liver Cancer (ITA.LI.CA) database (2008-2018). Recursive partition analysis (RPA) was performed to evaluate interactions between MaVI, clinical variables and treatment, exploring the inter-relationship determining overall survival. Results: MaVI prevalence was 11.1%, and median survival of these patients was 6.0months (95% CI, 5.1-7.1). MaVI was associated with younger age at diagnosis, presence of symptoms, worse Performance Status (PS) and liver function, high alphafetoprotein levels and large HCCs. MaVI extension was associated with worse PS, ascites and greater impairment in liver function. RPA identified patients' categories with different treatment indications and survival, ranging from 2.4months in those with PS>1 and ascites, regardless of MaVI extension (receiving best supportive care in 90.3% of cases), to 14.1months in patients with PS 0-1, no ascites and Vp1-Vp2 MaVI (treated with surgery in 19.1% of cases). Conclusions: MaVI presence and extension, together with PS and ascites, significantly affect patients' survival and treatment selection. The decision tree based on these parameters may help assess patients' prognosis and inform therapeutic decisions.

Published
2021

45. Clinical factors associated with death in 3044 COVID-19 patients managed in internal medicine wards in Italy: results from the SIMI-COVID-19 study of the Italian Society of Internal Medicine (SIMI)

Author

Corradini E., Ventura P., Ageno W., Cogliati C. B., Muiesan M. L., Girelli D., Pirisi M., Gasbarrini A., Angeli P., Querini P. R., Bosi E., Tresoldi M., Vettor R., Cattaneo M., Piscaglia F., Brucato A. L., Perlini S., Martelletti P., Pontremoli R., Porta M., Minuz P., Olivieri O., Sesti G., Biolo G., Rizzoni D., Serviddio G., Cipollone F., Grassi D., Manfredini R., Moreo G. L., Pietrangelo A., Teatini T., Salvetti M., Crisafulli E., Sainaghi P. P., Zileri Dal Verme L., Piano S., De Lorenzo R., Arcidiacono G., Podda M., Muratori L., Gabiati C., Salinaro F., Luciani M., Barnini C., Morra di Cella S., Dalbeni A., Friso S., Mearelli F., Malerba P., Cavallone F., D'Ardes D., Notargiacomo S., De Giorgi A., Mansi M., Buzzetti E., Ricci A., Martelli F., Corradini E., Ventura P., Ageno W., Cogliati C.B., Muiesan M.L., Girelli D., Pirisi M., Gasbarrini A., Angeli P., Querini P.R., Bosi E., Tresoldi M., Vettor R., Cattaneo M., Piscaglia F., Brucato A.L., Perlini S., Martelletti P., Pontremoli R., Porta M., Minuz P., Olivieri O., Sesti G., Biolo G., Rizzoni D., Serviddio G., Cipollone F., Grassi D., Manfredini R., Moreo G.L., Pietrangelo A., Teatini T., Salvetti M., Crisafulli E., Sainaghi P.P., Zileri Dal Verme L., Piano S., De Lorenzo R., Arcidiacono G., Podda M., Muratori L., Gabiati C., Salinaro F., Luciani M., Barnini C., Morra di Cella S., Dalbeni A., Friso S., Mearelli F., Malerba P., Cavallone F., D'Ardes D., Notargiacomo S., De Giorgi A., Mansi M., Buzzetti E., Ricci A., Martelli F., Corradini, E., Ventura, P., Ageno, W., Cogliati, C. B., Muiesan, M. L., Girelli, D., Pirisi, M., Gasbarrini, A., Angeli, P., Rovere-Querini, P., Bosi, E., Tresoldi, M., Vettor, R., Cattaneo, M., Piscaglia, F., Brucato, A. L., Perlini, S., Martelletti, P., Pontremoli, R., Porta, M., Minuz, P., Olivieri, O., Sesti, G., Biolo, G., Rizzoni, D., Serviddio, G., Cipollone, F., Grassi, D., Manfredini, R., Moreo, G. L., Pietrangelo, A., Teatini, T., Salvetti, M., Crisafulli, E., Sainaghi, P. P., Zileri Dal Verme, L., Piano, S., De Lorenzo, R., Arcidiacono, G., Podda, M., Muratori, L., Gabiati, C., Salinaro, F., Luciani, M., Barnini, C., Morra di Cella, S., Dalbeni, A., Friso, S., Mearelli, F., Malerba, P., Cavallone, F., D'Ardes, D., Notargiacomo, S., De Giorgi, A., Mansi, M., Buzzetti, E., Ricci, A., and Martelli, F.

Subjects
Mortality from COVID-19, Comorbidity, 030204 cardiovascular system & hematology, Cohort Studies, 0302 clinical medicine, 80 and over, Medicine, 030212 general & internal medicine, Hospital Mortality, Internal medicine, Comorbidity, Internal medicine, Mortality from COVID-19, Polypharmacy, SARS-CoV-2, Aged, 80 and over, LS7_9, Mortality rate, Respiration, Middle Aged, Hospitals, Survival Rate, Hospitalization, Italy, Polypharmacy, SARS-CoV-2, Cohort, Artificial, Emergency Medicine, Adult, Aged, COVID-19, Critical Care, Humans, Respiration, Artificial, Internal Medicine, medicine.symptom, Cohort study, medicine.medical_specialty, Settore MED/12 - GASTROENTEROLOGIA, Socio-culturale, 03 medical and health sciences, Intensive care, Survival rate, business.industry, Organ dysfunction, Settore MED/09 - MEDICINA INTERNA, medicine.disease, Im - Original, business
Abstract

During the COVID-19 2020 outbreak, a large body of data has been provided on general management and outcomes of hospitalized COVID-19 patients. Yet, relatively little is known on characteristics and outcome of patients managedin Internal Medicine Units (IMU). To address this gap, the Italian Society of Internal Medicine has conducted a nationwide cohort multicentre study on death outcome in adult COVID-19 patients admitted and managed in IMU. This study assessed 3044 COVID-19 patients at 41 referral hospitals across Italy from February 3rd to May 8th 2020. Demographics, comorbidities, organ dysfunction, treatment, and outcomes including death were assessed. During the study period, 697 patients (22.9%) were transferred to intensive care units, and 351 died in IMU (death rate 14.9%). At admission, factors independently associated with in-hospital mortality were age (OR 2.46, p = 0.000), productive cough (OR 2.04, p = 0.000), pre-existing chronic heart failure (OR 1.58, p = 0.017) and chronic obstructive pulmonary disease (OR 1.17, p = 0.048), the number of comorbidities (OR 1.34, p = 0.000) and polypharmacy (OR 1.20, p = 0.000). Of note, up to 40% of elderly patients did not report fever at admission. Decreasing PaO2/FiO2 ratio at admission was strongly inversely associated with survival. The use of conventional oxygen supplementation increased with the number of pre-existing comorbidities, but it did not associate with better survival in patients with PaO2/FiO2 ratio

Published
2021

49. The role of PNI to predict survival in advanced hepatocellular carcinoma treated with Sorafenib

Author

Caputo F., Dadduzio V., Tovoli F., Bertolini G., Cabibbo G., Cerma K., Vivaldi C., Faloppi L., Rizzato M. D., Piscaglia F., Celsa C., Fornaro L., Marisi G., Conti F., Silvestris N., Silletta M., Lonardi S., Granito A., Stornello C., Massa V., Astara G., Delcuratolo S., Cascinu S., Scartozzi M., Casadei-Gardini A., Francesco Caputo,Vincenzo Dadduzio,Francesco Tovoli,Giulia Bertolini,Giuseppe Cabibbo,Krisida Cerma,Caterina Vivaldi,Luca Faloppi,Mario Domenico Rizzato,Fabio Piscaglia,Ciro Celsa,Lorenzo Fornaro,Giorgia Marisi,Fabio Conti,Nicola Silvestris,Marianna Silletta,Sara Lonardi,Alessandro Granito,Caterina Stornello,Valentina Massa,Giorgio Astara,Sabina Delcuratolo,Stefano Cascinu,Mario Scartozzi,Andrea Casadei-Gardini, Caputo, F., Dadduzio, V., Tovoli, F., Bertolini, G., Cabibbo, G., Cerma, K., Vivaldi, C., Faloppi, L., Rizzato, M. D., Piscaglia, F., Celsa, C., Fornaro, L., Marisi, G., Conti, F., Silvestris, N., Silletta, M., Lonardi, S., Granito, A., Stornello, C., Massa, V., Astara, G., Delcuratolo, S., Cascinu, S., Scartozzi, M., Casadei Gardini, A., Caputo F., Dadduzio V., Tovoli F., Bertolini G., Cabibbo G., Cerma K., Vivaldi C., Faloppi L., Rizzato M.D., Piscaglia F., Celsa C., Fornaro L., Marisi G., Conti F., Silvestris N., Silletta M., Lonardi S., Granito A., Stornello C., Massa V., Astara G., Delcuratolo S., Cascinu S., Scartozzi M., and Casadei-Gardini A.

Subjects
RNA viruses, Male, Etiology, Cancer Treatment, Hepacivirus, Kaplan-Meier Estimate, Biochemistry, Cohort Studies, White Blood Cells, Mathematical and Statistical Techniques, Retrospective Studie, Animal Cells, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Carcinoma, Hepatocellular, Female, Humans, Italy, Liver Neoplasms, Lymphocyte Count, Middle Aged, Prognosis, Retrospective Studies, Serum Albumin, Sorafenib, Nutrition Assessment, Medicine and Health Sciences, 80 and over, Lymphocytes, Pathology and laboratory medicine, Hepatitis C virus, Liver Diseases, Statistics, Medical microbiology, Oncology, Liver Neoplasm, Physical Sciences, Viruses, Medicine, Pathogens, Cellular Types, Human, Research Article, Hepatitis B virus, Immune Cells, Science, Immunology, Gastroenterology and Hepatology, Research and Analysis Methods, Carcinomas, Microbiology, Albumins, Gastrointestinal Tumors, Statistical Methods, Blood Cells, Adult, Aged, 80 and over, Antineoplastic Agents, Carcinoma, Hepatocellular, Cohort Studies, Female, Humans, Italy, Kaplan-Meier Estimate, Liver Neoplasms, Lymphocyte Count, Male, Middle Aged, Prognosis, Retrospective Studies, Serum Albumin, Sorafenib, Nutrition Assessment, Biology and life sciences, Flaviviruses, Carcinoma, Viral pathogens, Organisms, Cancers and Neoplasms, Proteins, Hepatocellular, Hepatocellular Carcinoma, Cell Biology, prognostic nutritional index (PNI), hepatocellular carcinoma (HCC), sorafenib., survival, mRECIST, Hepatitis viruses, Microbial pathogens, Multivariate Analysis, Cohort Studie, Mathematics
Abstract

Background and aims The present study aims to investigate the role of the prognostic nutritional index (PNI) on survival in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. Methods This multicentric study included a training cohort of 194 HCC patients and three external validation cohorts of 129, 76 and 265 HCC patients treated with Sorafenib, respectively. The PNI was calculated as follows: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). Univariate and multivariate analyses were performed to investigate the association between the covariates and the overall survival (OS). Results A PNI cut-off value of 31.3 was established using the ROC analysis. In the training cohort, the median OS was 14.8 months (95% CI 12–76.3) and 6.8 months (95% CI 2.7–24.6) for patients with a high (>31.3) and low ( 70 years (p< 0.0038) were independent prognostic factors for OS. By performing the same multivariate analysis of the training cohort, the PNI 31.3 was found to be an independent prognostic factor for predicting OS in all the three validation cohorts. Conclusions PNI represents a prognostic tool in advanced HCC treated with first-line Sorafenib. It is readily available and low-cost, and it could be implemented in clinical practice in patients with HCC.

Published
2020

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