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19 results on '"Svegliati Baroni, Gianluca"'

1. Recalibrating survival prediction among patients receiving trans‐arterial chemoembolization for hepatocellular carcinoma

Author

Cucchetti, Alessandro, Giannini, Edoardo G., Mosconi, Cristina, Plaz Torres, Maria Corina, Pieri, Giulia, Farinati, Fabio, Rapaccini, Gian Ludovico, Di Marco, Maria, Caturelli, Eugenio, Sacco, Rodolfo, Cabibbo, Giuseppe, Campani, Claudia, Mega, Andrea, Guarino, Maria, Gasbarrini, Antonio, Svegliati‐Baroni, Gianluca, Foschi, Francesco Giuseppe, Missale, Gabriele, Masotto, Alberto, Nardone, Gerardo, Raimondo, Giovanni, Vidili, Gianpaolo, Brunetto, Maurizia Rossana, Sansone, Vito, Zoli, Marco, Azzaroli, Francesco, Trevisani, Franco, Biselli, Maurizio, Caraceni, Paolo, Gramenzi, Annagiulia, Rampoldi, Davide, Reggidori, Nicola, Santi, Valentina, Stefanini, Benedetta, Granito, Alessandro, Muratori, Luca, Piscaglia, Fabio, Tovoli, Francesco, Magalotti, Donatella, Dajti, Elton, Marasco, Giovanni, Ravaioli, Federico, Cappelli, Alberta, Golfieri, Rita, Renzulli, Matteo, Pelizzaro, Filippo, Penzo, Barbara, Marina Cela, Ester, Facciorusso, Antonio, Cacciato, Valentina, Casagrande, Edoardo, de Matthaeis, Nicoletta, Allegrini, Gloria, Lauria, Valentina, Ghittoni, Giorgia, Pelecca, Giorgio, Chegai, Fabrizio, Coratella, Fabio, Ortenzi, Mariano, Dell'Isola, Serena, Biasini, Elisabetta, Olivani, Andrea, Inno, Alessandro, Marchetti, Fabiana, Celsa, Ciro, Grova, Mauro, Stornello, Caterina, Busacca, Anita, Cammà, Calogero, Maria Rizzo, Giacomo Emanuele, Franzè, Maria Stella, Saitta, Carlo, Sauchella, Assunta, Napoli, Lucia, Bevilacqua, Vittoria, Berardinelli, Dante, Borghi, Alberto, Gardini, Andrea Casadei, Conti, Fabio, Dall'Aglio, Anna Chiara, Ercolani, Giorgio, Marra, Fabio, Di Bonaventura, Chiara, Gitto, Stefano, Adotti, Valentina, Coccoli, Pietro, Malerba, Antonio, Capasso, Mario, Morisco, Filomena, Oliveri, Filippo, Romagnoli, Veronica, Cucchetti, Alessandro, Giannini, Edoardo G., Mosconi, Cristina, Plaz Torres, Maria Corina, Pieri, Giulia, Farinati, Fabio, Rapaccini, Gian Ludovico, Di Marco, Maria, Caturelli, Eugenio, Sacco, Rodolfo, Cabibbo, Giuseppe, Campani, Claudia, Mega, Andrea, Guarino, Maria, Gasbarrini, Antonio, Svegliati‐Baroni, Gianluca, Foschi, Francesco Giuseppe, Missale, Gabriele, Masotto, Alberto, Nardone, Gerardo, Raimondo, Giovanni, Vidili, Gianpaolo, Brunetto, Maurizia Rossana, Sansone, Vito, Zoli, Marco, Azzaroli, Francesco, Trevisani, Franco, Biselli, Maurizio, Caraceni, Paolo, Gramenzi, Annagiulia, Rampoldi, Davide, Reggidori, Nicola, Santi, Valentina, Stefanini, Benedetta, Granito, Alessandro, Muratori, Luca, Piscaglia, Fabio, Tovoli, Francesco, Magalotti, Donatella, Dajti, Elton, Marasco, Giovanni, Ravaioli, Federico, Cappelli, Alberta, Golfieri, Rita, Renzulli, Matteo, Pelizzaro, Filippo, Penzo, Barbara, Marina Cela, Ester, Facciorusso, Antonio, Cacciato, Valentina, Casagrande, Edoardo, de Matthaeis, Nicoletta, Allegrini, Gloria, Lauria, Valentina, Ghittoni, Giorgia, Pelecca, Giorgio, Chegai, Fabrizio, Coratella, Fabio, Ortenzi, Mariano, Dell'Isola, Serena, Biasini, Elisabetta, Olivani, Andrea, Inno, Alessandro, Marchetti, Fabiana, Celsa, Ciro, Grova, Mauro, Stornello, Caterina, Busacca, Anita, Cammà, Calogero, Maria Rizzo, Giacomo Emanuele, Franzè, Maria Stella, Saitta, Carlo, Sauchella, Assunta, Napoli, Lucia, Bevilacqua, Vittoria, Berardinelli, Dante, Borghi, Alberto, Gardini, Andrea Casadei, Conti, Fabio, Dall'Aglio, Anna Chiara, Ercolani, Giorgio, Marra, Fabio, Di Bonaventura, Chiara, Gitto, Stefano, Adotti, Valentina, Coccoli, Pietro, Malerba, Antonio, Capasso, Mario, Morisco, Filomena, Oliveri, Filippo, and Romagnoli, Veronica

Subjects
Liver Cancer, Pre-TACE-Predict model, medicine.medical_specialty, business.industry, Trans-arterial chemoembolization, Pharmaceutical Science, hepatocellular carcinoma, medicine.disease, Gastroenterology, Complementary and alternative medicine, Internal medicine, Hepatocellular carcinoma, medicine, Pharmacology (medical), Trans arterial chemoembolization, business
Abstract

Background & Aims The Pre-TACE-Predict model was devised to assess prognosis of patients treated with trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). However, before entering clinical practice, a model should demonstrate that it performs a useful role. Methods We performed an independent external validation of the Pre-TACE model in a cohort that differs in setting and time period from the one that generated the original model. Data from 826 patients treated with TACE for naïve HCC (2008-2018) were used to assess calibration and discrimination of the Pre-TACE-Predict model. Results The four risk-categories identified by the Pre-TACE-Predict model had gradient monotonicity, with median survivals of 52.0, 36.2, 29.9, and 14.1 months respectively. However, predicted survivals systematically underestimated observed survivals (R2: 0.667). A recalibration was adopted maintaining fixed the prognostic index and modifying the baseline survival function. This resulted in an almost perfect calibration (R2: 0.995) in all the four risk categories. Cox regressions showed that aetiology and macrovascular invasion, included in the Pre-TACE-Predict model, had no prognostic impact in the present study population, and that coefficients for tumour size and multiplicity were overestimated. The c-index was similar to that of the m-HAP-III, but higher than those of HAP, m-HAP-II and the six-and-twelve models. Conclusions The recalibration of Pre-TACE-Predict model improved the estimation of survival probabilities of HCC patients treated with TACE. The highest discriminatory ability of the Pre-TACE-model in comparison to other available models, together with risk stratification and recalibration, makes it the best prognostic tool currently available for these patients.

Published
2021
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2. Predictors of non‐transplantable recurrence in hepatocellular carcinoma patients treated with frontline liver resection.

Author

Pelizzaro, Filippo, Trevisani, Franco, Simeon, Vittorio, Vitale, Alessandro, Cillo, Umberto, Piscaglia, Fabio, Missale, Gabriele, Sangiovanni, Angelo, Foschi, Francesco G., Cabibbo, Giuseppe, Caturelli, Eugenio, Di Marco, Maria, Azzaroli, Francesco, Brunetto, Maurizia R., Raimondo, Giovanni, Vidili, Gianpaolo, Guarino, Maria, Gasbarrini, Antonio, Campani, Claudia, and Svegliati‐Baroni, Gianluca

Subjects
LIVER cancer, LIVER, OVERALL survival, DISEASE relapse, DATABASES
Abstract

Background and Aims: Hepatocellular carcinoma (HCC) recurrence is common in patients treated with liver resection (LR). In this study, we aimed to evaluate the incidence and preoperative predictors of non‐transplantable recurrence in patients with single HCC ≤5 cm treated with frontline LR. Methods: From the Italian Liver Cancer (ITA.LI.CA) database, 512 patients receiving frontline LR for single HCC ≤5 cm were retrieved. Incidence and predictors of recurrence beyond Milan criteria (MC) and up‐to‐seven criteria were compared between patients with HCC <4 and ≥4 cm. Results: During a median follow‐up of 4.2 years, the overall recurrence rate was 55.9%. In the ≥4 cm group, a significantly higher proportion of patients recurred beyond MC at first recurrence (28.9% vs. 14.1%; p < 0.001) and overall (44.4% vs. 25.2%; p < 0.001). Similar results were found considering recurrence beyond up‐to‐seven criteria. Compared to those with larger tumours, patients with HCC <4 cm had a longer recurrence‐free survival and overall survival. HCC size ≥4 cm and high alpha‐fetoprotein (AFP) level at the time of LR were independent predictors of recurrence beyond MC (and up‐to‐seven criteria). In the subgroup of patients with available histologic information (n = 354), microvascular invasion and microsatellite lesions were identified as additional independent risk factors for non‐transplantable recurrence. Conclusions: Despite the high recurrence rate, LR for single HCC ≤5 cm offers excellent long‐term survival. Non‐transplantable recurrence is predicted by HCC size and AFP levels, among pre‐operatively available variables. High‐risk patients could be considered for frontline LT or listed for transplantation even before recurrence. [ABSTRACT FROM AUTHOR]

Published
2023
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3. Perspective on the Role of Gut Microbiome in the Treatment of Hepatocellular Carcinoma with Immune Checkpoint Inhibitors.

Author

Abenavoli, Ludovico, Montori, Michele, Svegliati Baroni, Gianluca, Argenziano, Maria Eva, Giorgi, Francesca, Scarlata, Giuseppe Guido Maria, Ponziani, Francesca, and Scarpellini, Emidio

Subjects
IMMUNE checkpoint inhibitors, GUT microbiome, FECAL microbiota transplantation, SORAFENIB, LIVER cancer, LIVER transplantation, IPILIMUMAB
Abstract

Background and Objectives: Hepatocellular carcinoma (HCC) is the leading cause of liver cancer worldwide and has a high mortality rate. Its incidence has increased due to metabolic-associated liver disease (MAFLD) epidemics. Liver transplantation and surgery remain the most resolute measures. Despite the optimistic use of multi-kinase inhibitors, namely sorafenib, the co-existence of chronic liver disease made the response rate low in these patients. Immune checkpoint inhibitors (ICIs) have become a promising hope for certain advanced solid tumors and, also, for advanced HCC. Unfortunately, a large cohort of patients with HCC fail to respond to immunotherapy. Materials and Methods: We conducted a narrative search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials, and case series using the following keywords and acronyms and their associations: hepatocellular carcinoma, immunotherapy, checkpoint inhibitors, gut microbiota, and fecal microbiota transplantation. Results: ICIs are a promising and sufficiently safe treatment option for HCC. In detail, they have significantly improved survival and prognosis in these patients vs. sorafenib. Although there are several highlighted mechanisms of resistance, the gut microbiota signature can be used both as a response biomarker and as an effect enhancer. Practically, probiotic dose-finding and fecal microbiota transplantation are the weapons that can be used to increase ICI's treatment-response-reducing resistance mechanisms. Conclusion: Immunotherapy has been a significant step-up in HCC treatment, and gut microbiota modulation is an effective liaison to increase its efficacy. [ABSTRACT FROM AUTHOR]

Published
2023
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4. Monofocal hepatocellular carcinoma: How much does size matter?

Author

Pelizzaro, Filippo, Penzo, Barbara, Peserico, Giulia, Imondi, Angela, Sartori, Anna, Vitale, Alessandro, Cillo, Umberto, Giannini, Edoardo G., Forgione, Antonella, Ludovico Rapaccini, Gian, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Sacco, Rodolfo, Cabibbo, Giuseppe, Marra, Fabio, Mega, Andrea, Morisco, Filomena, Gasbarrini, Antonio, Svegliati‐Baroni, Gianluca, Giuseppe Foschi, Francesco, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Raimondo, Giovanni, Azzaroli, Francesco, Vidili, Gianpaolo, Oliveri, Filippo, Trevisani, Franco, Farinati, Fabio, Biselli, Maurizio, Caraceni, Paolo, Garuti, Francesca, Gramenzi, Annagiulia, Neri, Andrea, Santi, Valentina, Granito, Alessandro, Muratori, Luca, Piscaglia, Fabio, Sansone, Vito, Tovoli, Francesco, Dajti, Elton, Marasco, Giovanni, Ravaioli, Federico, Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Sammarco, Ambra, Cela, Ester Marina, Facciorusso, Antonio, Cacciato, Valentina, Casagrande, Edoardo, Moscatelli, Alessandro, Pellegatta, Gaia, de Matthaeis, Nicoletta, Allegrini, Gloria, Lauria, Valentina, Ghittoni, Giorgia, Pelecca, Giorgio, Chegai, Fabrizio, Coratella, Fabio, Ortenzi, Mariano, Missale, Gabriele, Inno, Alessandro, Marchetti, Fabiana, Busacca, Anita, Cammà, Calogero, Martino, Vincenzo Di, Emanuele Maria Rizzo, Giacomo, Franzè, Maria Stella, Saitta, Carlo, Sauchella, Assunta, Bevilacqua, Vittoria, Borghi, Alberto, Casadei Gardini, Andrea, Conti, Fabio, Dall'Aglio, Anna Chiara, Ercolani, Giorgio, Mirici, Federica, Campani, Claudia, Bonaventura, Chiara Di, Gitto, Stefano, Coccoli, Pietro, Malerba, Antonio, Guarino, Maria, Brunetto, Maurizia, Romagnoli, Veronica, Pelizzaro, Filippo, Penzo, Barbara, Peserico, Giulia, Imondi, Angela, Sartori, Anna, Vitale, Alessandro, Cillo, Umberto, Giannini, Edoardo G., Forgione, Antonella, Ludovico Rapaccini, Gian, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Sacco, Rodolfo, Cabibbo, Giuseppe, Marra, Fabio, Mega, Andrea, Morisco, Filomena, Gasbarrini, Antonio, Svegliati‐Baroni, Gianluca, Giuseppe Foschi, Francesco, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Raimondo, Giovanni, Azzaroli, Francesco, Vidili, Gianpaolo, Oliveri, Filippo, Trevisani, Franco, Farinati, Fabio, Biselli, Maurizio, Caraceni, Paolo, Garuti, Francesca, Gramenzi, Annagiulia, Neri, Andrea, Santi, Valentina, Granito, Alessandro, Muratori, Luca, Piscaglia, Fabio, Sansone, Vito, Tovoli, Francesco, Dajti, Elton, Marasco, Giovanni, Ravaioli, Federico, Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Sammarco, Ambra, Cela, Ester Marina, Facciorusso, Antonio, Cacciato, Valentina, Casagrande, Edoardo, Moscatelli, Alessandro, Pellegatta, Gaia, de Matthaeis, Nicoletta, Allegrini, Gloria, Lauria, Valentina, Ghittoni, Giorgia, Pelecca, Giorgio, Chegai, Fabrizio, Coratella, Fabio, Ortenzi, Mariano, Missale, Gabriele, Inno, Alessandro, Marchetti, Fabiana, Busacca, Anita, Cammà, Calogero, Martino, Vincenzo Di, Emanuele Maria Rizzo, Giacomo, Franzè, Maria Stella, Saitta, Carlo, Sauchella, Assunta, Bevilacqua, Vittoria, Borghi, Alberto, Casadei Gardini, Andrea, Conti, Fabio, Dall'Aglio, Anna Chiara, Ercolani, Giorgio, Mirici, Federica, Campani, Claudia, Bonaventura, Chiara Di, Gitto, Stefano, Coccoli, Pietro, Malerba, Antonio, Guarino, Maria, Brunetto, Maurizia, Romagnoli, Veronica, Giannini, Edoardo G, Svegliati-Baroni, Gianluca, for the Italica, Group, Pelizzaro F., Penzo B., Peserico G., Imondi A., Sartori A., Vitale A., Cillo U., Giannini E.G., Forgione A., Ludovico Rapaccini G., Di Marco M., Caturelli E., Zoli M., Sacco R., Cabibbo G., Marra F., Mega A., Morisco F., Gasbarrini A., Svegliati-Baroni G., Giuseppe Foschi F., Olivani A., Masotto A., Nardone G., Raimondo G., Azzaroli F., Vidili G., Oliveri F., Trevisani F., Farinati F., Biselli M., Caraceni P., Garuti F., Gramenzi A., Neri A., Santi V., Granito A., Muratori L., Piscaglia F., Sansone V., Tovoli F., Dajti E., Marasco G., Ravaioli F., Cappelli A., Golfieri R., Mosconi C., Renzulli M., Sammarco A., Cela E.M., Facciorusso A., Cacciato V., Casagrande E., Moscatelli A., Pellegatta G., de Matthaeis N., Allegrini G., Lauria V., Ghittoni G., Pelecca G., Chegai F., Coratella F., Ortenzi M., Missale G., Inno A., Marchetti F., Busacca A., Qabibboz G., Camma C., Martino V.D., Emanuele Maria Rizzo G., Franze M.S., Saitta C., Sauchella A., Bevilacqua V., Borghi A., Casadei Gardini A., Conti F., Dall'Aglio A.C., Ercolani G., Mirici F., Campani C., Bonaventura C.D., Gitto S., Coccoli P., Malerba A., Guarino M., Brunetto M., Romagnoli V., Rapaccini, Gian Ludovico, and Foschi, Francesco Giuseppe

Subjects
medicine.medical_specialty, Multivariate analysis, Carcinoma, Hepatocellular, Independent predictor, Gastroenterology, Resection, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Overall survival, Hepatectomy, Humans, Staging system, Neoplasm Staging, Retrospective Studies, Settore MED/12 - Gastroenterologia, Hepatology, treatment, business.industry, Settore MED/09 - MEDICINA INTERNA, Liver Neoplasms, bclc staging system, monofocal hepatocellular carcinoma, medicine.disease, digestive system diseases, Survival benefit, Italy, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, liver resection, prognosis, 030211 gastroenterology & hepatology, business, Liver cancer, prognosi
Abstract

Background & Aims: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, monofocal hepatocellular carcinoma (HCC) is classified as early (BCLC A) irrespective of its size, even though controversies still exist regarding staging and treatment of large tumours. We aimed at evaluating the appropriate staging and treatment for large (>5cm) monofocal (HCC). Methods: From the Italian Liver Cancer database, we selected 924 patients with small early monofocal HCC (2-5cm; SEM-HCC), 163 patients with larger tumours (>5cm; LEM-HCC) and 1048 intermediate stage patients (BCLC B). Results: LEM-HCC patients had a worse overall survival (OS) than SEM-HCC (31.0 vs 49.0months; P&nbsp

Published
2021

5. Transarterial Chemoembolization for Hepatocellular Carcinoma in Clinical Practice: Temporal Trends and Survival Outcomes of an Iterative Treatment.

Author

Pelizzaro, Filippo, Haxhi, Selion, Penzo, Barbara, Vitale, Alessandro, Giannini, Edoardo G., Sansone, Vito, Rapaccini, Gian Ludovico, Di Marco, Maria, Caturelli, Eugenio, Magalotti, Donatella, Sacco, Rodolfo, Celsa, Ciro, Campani, Claudia, Mega, Andrea, Guarino, Maria, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Olivani, Andrea, and Masotto, Alberto

Subjects
HEPATOCELLULAR carcinoma, CHEMOEMBOLIZATION, SURVIVAL rate, TREATMENT effectiveness, PATIENT selection, LIVER cancer
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. [ABSTRACT FROM AUTHOR]

Published
2022
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6. The evolutionary scenario of hepatocellular carcinoma in Italy: an update

Author

Bucci, Laura, Garuti, Francesca, Lenzi, Barbara, Pecorelli, Anna, Farinati, Fabio, Giannini, Edoardo G., Granito, Alessandro, Ciccarese, Francesca, Rapaccini, Gian Lodovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cammà, Calogero, Virdone, Roberto, Marra, Fabio, Felder, Martina, Morisco, Filomena, Benvegnù, Luisa, Gasbarrini, Antonio, Svegliati Baroni, Gianluca, Foschi, Francesco Giuseppe, Missale, Gabriele, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Bernardi, Mauro, Trevisani, Franco, Biselli, Maurizio, Caraceni, Paolo, Cucchetti, Alessandro, Domenicali, Marco, Gramenzi, Annagiulia, Magalotti, Donatella, Napoli, Lucia, Negrini, Giulia, Piscaglia, Fabio, Serra, Carla, Tovoli, Francesco, Marafatto, Filippo, Murer, Francesca, Peserico, Giulia, Pozzan, Caterina, Vanin, Veronica, Moscatelli, Alessandro, Pellegatta, Gaia, Picciotto, Antonino, Savarino, Vincenzo, Poggio, Paolo Del, Olmi, Stefano, De Matthaeis, Nicoletta, Balsamo, Claudia, Vavassori, Elena, Roselli, Paola, Dell’Isola, Serena, Ialungo, Anna Maria, Rastrelli, Elena, Barcellona, Maria Rosa, Cabibbo, Giuseppe, Costantino, Andrea, Maida, Marcello, Affronti, Andrea, Mega, Andrea, Rinninella, Emanuele, Mismas, Valeria, Dall’Aglio, Anna Chiara, Feletti, Valentina, Lanzi, Arianna, Cappa, Federica Mirici, Neri, Elga, Stefanini, Giuseppe Francesco, Tamberi, Stefano, Biasini, Elisabetta, Porro, Emanuela, Guarino, Maria, Gemini, Stefano, Schiadà, Laura, Chiaramonte, Maria, Marchetti, Fabiana, Valerio, Matteo, Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Coccoli, Piero, Zamparelli, Marco Sanduzzi, Aburas, Sami, Inghilesi, Andrea Lorenzo, Bucci, Laura, Garuti, Francesca, Lenzi, Barbara, Pecorelli, Anna, Farinati, Fabio, Giannini, Edoardo G, Granito, Alessandro, Ciccarese, Francesca, Rapaccini, Gian Lodovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cammà, Calogero, Virdone, Roberto, Marra, Fabio, Felder, Martina, Morisco, Filomena, Benvegnù, Luisa, Gasbarrini, Antonio, Svegliati Baroni, Gianluca, Foschi, Francesco Giuseppe, Missale, Gabriele, Masotto, Alberto, Nardone, GERARDO ANTONIO PIO, Colecchia, Antonio, Bernardi, Mauro, Trevisani, Franco, Bucci, L, Garuti, F, Lenzi, B, Granito, A, Zoli, M, Colecchia, A, Bernardi, M, Trevisani, F, Biselli, M, Caraceni, P, Cucchetti, A, Gramenzi, A, Piscaglia, F., Bucci, L., Garuti, F., Lenzi, B., Pecorelli, A., Farinati, F., Giannini, E., Granito, A., Ciccarese, F., Rapaccini, G., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Cammà, C., Virdone, R., Marra, F., Felder, M., Morisco, F., Benvegnù, L., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F., Missale, G., Masotto, A., Nardone, G., Colecchia, A., Bernardi, M., and Trevisani, F.

Subjects
Oncology, Male, Etiology, Databases, Factual, Radiofrequency ablation, medicine.medical_treatment, law.invention, 0302 clinical medicine, law, Epidemiology, epidemiology, hepatocellular carcinoma, survival, treatment, Hepatology, Aged, 80 and over, Surveillance, Liver Neoplasms, Middle Aged, Prognosis, Italy, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Catheter Ablation, 030211 gastroenterology & hepatology, Female, alpha-Fetoproteins, Liver cancer, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, 03 medical and health sciences, Young Adult, Age Distribution, Internal medicine, medicine, Humans, Sex Distribution, Aged, Neoplasm Staging, Retrospective Studies, Cirrhosi, business.industry, Cancer stage, Settore MED/09 - MEDICINA INTERNA, Cancer, medicine.disease, Surgery, Percutaneous ethanol injection, business
Abstract

Background and aims Epidemiology of hepatocellular carcinoma is changing worldwide. This study aimed at evaluating the changing scenario of etiology, presentation, management and prognosis of hepatocellular carcinoma in Italy during the last 15 years. Methods Retrospective analysis of the ITA.LI.CA (Italian Liver Cancer) database including 5192 hepatocellular carcinoma patients managed in 24 centers from 2000 to 2014. Patients were divided into three groups according to the date of cancer diagnosis (2000-2004, 2005-2009 and 2010-2014). Results The main results were: 1) progressive patient aging; 2) progressive expansion of non-viral cases and, namely, of “metabolic” hepatocellular carcinomas; 3) increasing proportion of hepatocellular carcinoma diagnosed during a correct (semiannual) surveillance program; 4) favourable cancer stage migration; 4) increased use of radiofrequency ablation to the detriment of percutaneous ethanol injection; 5) improved outcomes of ablative and transarterial treatments; 6) improved overall survival (adjusted for the lead time in surveyed patients), particularly after 2009, of both viral and non-viral patients presenting with an early or intermediate stage hepatocellular carcinoma. Conclusions During the last 15 years several etiological and clinical features of hepatocellular carcinoma patients have changed, as their management. The observed improvement of overall survival was due both to the wider use of semiannual surveillance, expanding the proportion of tumors that qualified for curative treatments, and to the improved outcome of locoregional treatments. This article is protected by copyright. All rights reserved.

Published
2017

7. Hepatic decompensation is the major driver of death in HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma

Author

Cabibbo, Giuseppe, Petta, Salvatore, Barbara, Marco, Attardo, Simona, Bucci, Laura, Farinati, Fabio, Giannini, Edoardo G., Negrini, Giulia, Ciccarese, Francesca, Rapaccini, Gian Ludovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Virdone, Roberto, Marra, Fabio, Mega, Andrea, Morisco, Filomena, Benvegnã¹, Luisa, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Persico, Marcello, Craxã¬, Antonio, Trevisani, Franco, Cammã&nbsp, Calogero, Cabibbo, G., Petta, S., Barbara, M., Attardo, S., Bucci, L., Farinati, F., Giannini, E., Negrini, G., Ciccarese, F., Rapaccini, G., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Virdone, R., Marra, F., Mega, A., Morisco, F., Benvegnã¹, L., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F., Olivani, A., Masotto, A., Nardone, G., Colecchia, A., Persico, M., Craxi, A., Trevisani, F., Camma', C., G. Cabibbo, S. Petta, M. Barbara, S. Attardo, L. Bucci, F. Farinati, E. G. Giannini, G. Negrini, F. Ciccarese, G. L. Rapaccini, M. Di Marco, E. Caturelli, M. Zoli, F. Borzio, R. Sacco, R. Virdone, F. Marra, A. Mega, F. Morisco, L. Benvegnù, A. Gasbarrini, G. Svegliati-Baroni, F. G. Foschi, A. Olivani, A. Masotto, G. Nardone, A. Colecchia, M. Persico, A. Craxì, F. Trevisani, C. Cammà, Cabibbo, Giuseppe, Petta, Salvatore, Barbara, Marco, Attardo, Simona, Bucci, Laura, Farinati, Fabio, Giannini, Edoardo G, Negrini, Giulia, Ciccarese, Francesca, Lodovico Rapaccini, Gian, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Virdone, Roberto, Marra Mega, Fabio Andrea, Morisco, Filomena, Benvegnù, Luisa, Gasbarrini, Antonio, Svegliati Baroni, Gianluca, Giuseppe Foschi, Francesco, Olivani, Andrea, Masotto, Alberto, Nardone, GERARDO ANTONIO PIO, Colecchia, Antonio, Persico, Marcello, Craxì, Antonio, Trevisani, Franco, and Cammà, Calogero

Subjects
Liver Cirrhosis, Male, Hepatocellular Carcinoma, Liver Cirrhosis, hepatitis C virus, Survival, direct-acting antiviral agents, Survival rate, Cirrhosis, Antiviral agent, Gastroenterology, Liver cirrhosi, 0302 clinical medicine, Recurrence, Hepatic decompensation, Hepatitis C Virus (HCV), Hepatocellular carcinoma (HCC), Prognosis, Recurrences, Sustained virological response (SVR), overall survival (OS), Overall survival, Liver Neoplasms, Hepatitis C, Middle Aged, Sustained virological response, Local, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Female, Antiviral agents, Carcinoma, hepatocellular, Liver cirrhosis, Aged, Carcinoma, Hepatocellular, Humans, Neoplasm Recurrence, Local, Proportional Hazards Models, Liver cancer, medicine.medical_specialty, Prognosi, Settore MED/12 - GASTROENTEROLOGIA, 03 medical and health sciences, hepatocellular, Internal medicine, medicine, Early Hepatocellular Carcinoma, Hepatology, business.industry, Carcinoma, Hepatocellular, medicine.disease, digestive system diseases, Neoplasm Recurrence, Liver function, business
Abstract

Background & Aims Assessment of long-term outcome is required in hepatitis C virus (HCV)-infected patients with cirrhosis, who have been successfully treated for Barcelona Clinic Liver Cancer (BCLC) stage A hepatocellular carcinoma (HCC). However, problems arise due to the lack of models accounting for early changes during follow-up. The aim of this study was to estimate the impact of early events (HCC recurrence or hepatic decompensation within 12Âmonths of complete radiological response) on 5-year overall survival (OS) in a large cohort of patients with HCV and cirrhosis, successfully treated HCC. Methods A total of 328 consecutive Caucasian patients with HCV-related cirrhosis and BCLC stage 0/A HCC who had complete radiological response after curative resection or thermal ablation were prospectively recruited to this study. Primary endpoint of the study was 5-year OS. Independent baseline and time-dependent predictors of 5-year OS were identified by Cox model. Results The observed 5-year survival rate was 44%. The observed HCC early recurrence and early hepatic decompensation rate were 21% and 10%, respectively. Early hepatic decompensation (Hazard Ratio [HR] 7.52; 95% confidence intervals (CI): 1.23–13.48) and HCC early recurrence as time-dependent covariates (HR 2.50; 95%CI: 1.23–5.05), presence of esophageal varices at baseline (HR 1.66; 95% CI: 1.02–2.70) and age (HR 1.04; 95% CI: 1.02–1.07) were significantly associated with the 5-year OS. Conclusion Survival in HCV-infected patients with cirrhosis and successfully treated HCC is influenced by early hepatic decompensation. Our study indirectly suggests that direct-acting antiviral agents could improve OS of HCC patients through long-term preservation of liver function, resulting in a lower cirrhosis-related mortality and a greater change of receiving curative treatments. Lay summary Survival in hepatitis C virus (HCV) infected patients with cirrhosis and successfully treated hepatocellular carcinoma (HCC), is mainly influenced by early hepatic decompensation. HCV eradication after treatment with new direct-acting antiviral agents could improve overall survival of HCC patients through long-term preservation of liver function.

Published
2017

8. Pattern of macrovascular invasion in hepatocellular carcinoma.

Author

Guarino, Maria, Cucchetti, Alessandro, Pontillo, Giuseppina, Farinati, Fabio, Benevento, Francesca, Rapaccini, Gian Ludovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Rodolfo, Sacco, Cabibbo, Giuseppe, Marra, Fabio, Mega, Andrea, Gasbarrini, Antonio, Svegliati‐Baroni, Gianluca, Foschi, Francesco Giuseppe, Missale, Gabriele, Masotto, Alberto, Nardone, Gerardo, and Raimondo, Giovanni

Subjects
OVERALL survival, SURVIVAL rate, HEPATOCELLULAR carcinoma, RECURSIVE partitioning, LIVER cancer, DECISION trees
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 6.0 months (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 2.4 months in those with PS > 1 and ascites, regardless of MaVI extension (receiving best supportive care in 90.3% of cases), to 14.1 months 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. [ABSTRACT FROM AUTHOR]

Published
2021
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9. Time-Varying mHAP-III Is the Most Accurate Predictor of Survival in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

Author

Campani, Claudia, Vitale, Alessandro, Dragoni, Gabriele, Arena, Umberto, Laffi, Giacomo, Cillo, Umberto, Giannini, Edoardo G., Tovoli, Francesco, Rapaccini, Gian Ludovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Sacco, Rodolfo, Cabibbo, Giuseppe, Mega, Andrea, Guarino, Maria, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, and Biasini, Elisabetta

Subjects
CHEMOEMBOLIZATION, LIVER cancer, LIKELIHOOD ratio tests, AKAIKE information criterion, ABLATION techniques
Abstract

Introduction: The prognosis of patients undergoing transarterial chemoembolization (TACE) is extremely variable, and a confounding factor is that TACE is often repeated several times. We retrospectively evaluated the accuracy of different prognostic scores and staging systems in estimating overall survival (OS) in patients with hepatocellular carcinoma (HCC). Methods: An analysis considering prognostic models as time-varying variables was performed, calculating OS from the time of TACE to the time of the subsequent treatment. Total follow-up time for each patient was therefore split into several observation times accounting for each TACE procedure. Values of the likelihood ratio test (LRT) and Akaike information criterion (AIC) were used to compare different systems. Univariable and multivariable analyses were conducted to identify additional factors predictive of OS. We analyzed 1,610 TACE performed in 1,058 patients recorded in the Italian Liver Cancer database from 2008 through 2016. Results: The median OS of the enrolled patients was 41 months. According to LRT χ2 and AIC values based on the time-varying analysis, mHAP-III achieved the best values (41.72 and 4,625.49, respectively, p < 0.0001), indicating the highest predictive performance compared with all other scores (HAP, mHAP-II, ALBI, and pALBI) and staging systems (MELD, ITALICA, CLIP, MESH, MESIAH, JIS, HKLC, and BCLC). In the multivariable Cox proportional hazards model, mHAPIII maintained an independent effect on OS (hazard ratio 1.31, 95% CI: 1.10--1.55, p < 0.0001). Time-varying age, alcoholic etiology, radiologic response to TACE, and performing ablation or surgery after TACE were additional significant variables resulting from the multivariable model. Conclusion: An innovative time-varying analysis revealed that mHAP-III was the most accurate model in predicting OS in patients with HCC undergoing TACE. Other clinical pre- and post-TACE variables were also found to be relevant for this prediction. [ABSTRACT FROM AUTHOR]

Published
2021
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10. The changing scenario of hepatocellular carcinoma in Italy: an update.

Author

Garuti, Francesca, Neri, Andrea, Avanzato, Francesca, Gramenzi, Annagiulia, Rampoldi, Davide, Rucci, Paola, Farinati, Fabio, Giannini, Edoardo G., Piscaglia, Fabio, Rapaccini, Gian Ludovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Sacco, Rodolfo, Cabibbo, Giuseppe, Marra, Fabio, Mega, Andrea, Morisco, Filomena, Gasbarrini, Antonio, and Svegliati‐Baroni, Gianluca

Subjects
LIVER cancer, LIVER analysis, CATHETER ablation, LIVER transplantation
Abstract

Background and aims: Epidemiology of hepatocellular carcinoma (HCC) is changing in most areas of the world. This study aimed at updating the changing scenario of aetiology, clinical presentation, management and prognosis of HCC in Italy during the last 15 years. Methods: Retrospective analysis of the Italian Liver Cancer (ITA.LI.CA) database included 6034 HCC patients managed in 23 centres from 2004 to 2018. Patients were divided into three groups according to the date of cancer diagnosis (2004‐2008, 2009‐2013 and 2014‐2018). Results: The main results were: (i) a progressive patient ageing; (ii) a progressive increase of non‐viral cases and, particularly, of 'metabolic' and 'metabolic + alcohol' HCCs; (iii) a slightly decline of cases diagnosed under surveillance, but with an incremental use of the semiannual schedule; (iv) a favourable cancer stage migration; (v) an increased use of radiofrequency ablation to the detriment of percutaneous ethanol injection; (vi) improved outcomes of ablative and transarterial treatments; (vii) an improved overall survival (adjusted for the lead time in surveyed patients) in the last calendar period, particularly in viral patients; (viii) a large gap between the number of potential candidates (according to oncologic criteria and age) to liver transplant and that of transplanted patients. Conclusions: During the last 15 years several aspects of HCC scenario have changed, as well as its management. The improvement in patient survival observed in the last period was likely because of a larger use of thermal ablation with respect to the less effective alcohol injection and to an improved management of intermediate stage patients. [ABSTRACT FROM AUTHOR]

Published
2021
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11. Hepatocellular carcinoma recurrence in patients with curative resection or ablation: impact of HCV eradication does not depend on the use of interferon

Author

Petta, S., Cabibbo, G., Barbara, M., Attardo, S., Bucci, L., Farinati, F., Giannini, E. G., Tovoli, F., Ciccarese, F., Rapaccini, Gian Ludovico, Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Virdone, R., Marra, F., Felder, M., Morisco, F., Benvegnù, L., Gasbarrini, Antonio, Svegliati-Baroni, G., Foschi, F. G., Olivani, A., Masotto, A., Nardone, G., Colecchia, A., Persico, M., Boccaccio, V., Craxì, A., Bruno, S., Trevisani, F., Cammà, C, Biselli, Maurizio, Caraceni, Paolo, Cucchetti, Alessandro, Domenicali, Marco, Piscaglia, Fabio, Gramenzi, Annagiulia, Granito, Alessandro, Magalotti, Donatella, Serra, Carla, Negrini, Giulia, Napoli, L., Napoli, Lucia, Salvatore, Veronica, Benevento, Francesca, Gazzola, Alessia, Murer, Francesca, Pozzan, Caterina, Vanin, Veronica, Moscatelli, Alessandro, Pellegatta, Gaia, Picciotto, Antonino, Savarino, Vincenzo, Delpoggio, Paolo, Olmi, Stefano, De Matthaeis, Nicoletta, Balsamo, Claudia, Vavassori, Elena, Roselli, Paola, Dell’Isola, Serena, Ialungo, Anna Maria, Rastrelli, Elena, Rini, Francesca, Costantino, Andrea, Affronti, Andrea, Affronti, Marco, Mascari, Marta, Mega, Andrea, Pompili, Maurizio, Rinninella, Emanuele, Mismas, Valeria, Dall’Aglio, Anna Chiara, Feletti, Valentina, Lanzi, Arianna, Cappa, Federica Mirici, Neri, Elga, Stefanini, Giuseppe Francesco, Tamberi, Stefano, Biasini, Elisabetta, Missale, Gabriele, Guarino, Maria, Ortolani, Alessio, Chiaramonte, Maria, Marchetti, Fabiana, Valerio, Matteo, Aburas, Sami, Inghilesi, Andrea L., Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Coccoli, Piero, Zamparelli, Marco Sanduzzi, Petta, Salvatore, Cabibbo, Giuseppe, Barbara, Marco, Attardo, Simona, Bucci, Laura, Farinati, Fabio, Giannini, Edoardo G., Tovoli, Francesco, Ciccarese, Francesca, Rapaccini, Gian Lodovico, Dimarco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Virdone, Roberto, Marra, Fabio, Felder, Martina, Morisco, Filomena, Benvegnù, Luisa, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Persico, Marcello, Boccaccio, Vincenzo, Craxì, Antonio, Bruno, Savino, Trevisani, Franco, Cammà, Calogero, Petta, S, Cabibbo, G, Barbara, M, Attardo, S, Bucci, L, Farinati, F, Giannini, E. G, Tovoli, F, Ciccarese, F, Rapaccini, G. L, Di Marco, M, Caturelli, E, Zoli, M, Borzio, F, Sacco, R, Virdone, R, Marra, F, Felder, M, Morisco, Filomena, Benvegnù, L, Gasbarrini, A, Svegliati Baroni, G, Foschi, F. G, Olivani, A, Masotto, A, Nardone, GERARDO ANTONIO PIO, Colecchia, A, Persico, M, Boccaccio, V, Craxì, A, Bruno, S, Trevisani, F, Cammà, C., DIPARTIMENTO DI MEDICINA SPECIALISTICA, DIAGNOSTICA E SPERIMENTALE, DIPARTIMENTO DI SCIENZE MEDICHE E CHIRURGICHE, Facolta' di MEDICINA e CHIRURGIA, Da definire, AREA MIN. 06 - Scienze mediche, Petta, S., Cabibbo, G., Barbara, M., Attardo, S., Bucci, L., Farinati, F., Giannini, E., Tovoli, F., Ciccarese, F., Rapaccini, G., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Virdone, R., Marra, F., Felder, M., Morisco, F., Benvegnã¹, L., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F., Olivani, A., Masotto, A., Nardone, G., Colecchia, A., Persico, M., Boccaccio, V., Craxi, A., Bruno, S., Trevisani, F., Camma', C., Biselli, M., Caraceni, P., Cucchetti, A., Domenicali, M., Piscaglia, F., Gramenzi, A., Granito, A., Magalotti, D., Serra, C., Negrini, G., Napoli, L., Salvatore, V., Benevento, F., Gazzola, A., Murer, F., Pozzan, C., Vanin, V., Moscatelli, A., Pellegatta, G., Picciotto, A., Savarino, V., Delpoggio, P., Olmi, S., Dematthaeis, N., Balsamo, C., Vavassori, E., Roselli, P., Dell’Isola, S., Ialungo, A., Rastrelli, E., Rini, F., Costantino, A., Affronti, A., Affronti, M., Mascari, M., Mega, A., Pompili, M., Rinninella, E., Mismas, V., Dall’Aglio, A., Feletti, V., Lanzi, A., Cappa, F., Neri, E., Stefanini, G., Tamberi, S., Biasini, E., Missale, G., Guarino, M., Ortolani, A., Chiaramonte, M., Marchetti, F., Valerio, M., Aburas, S., Inghilesi, A., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Coccoli, P., Zamparelli, M., Giannini, E.G., Rapaccini, G.L., Benvegnù, L., Foschi, F.G., Craxì, A., Cammà, C, the Italian Liver Cancer (ITALICA) Group [, Maurizio Biselli, Paolo Caraceni, Alessandro Cucchetti, Marco Domenicali, Fabio Piscaglia, Annagiulia Gramenzi, Alessandro Granito, Donatella Magalotti, Carla Serra, Giulia Negrini, Lucia Napoli, Veronica Salvatore, Francesca Benevento, ], Giannini, E. G., Rapaccini, G. L., Benvegnu, L., Foschi, F. G., Camma, C., Dell'Isola, S., Ialungo, A. M., Dall'Aglio, A. C., Cappa, F. M., Stefanini, G. F., Inghilesi, A. L., and Zamparelli, M. S.

Subjects
Liver Cirrhosis, Male, Cirrhosis, Databases, Factual, Gastroenterology, HCV-infected cirrhotic patients, hepatocellular carcinoma, HCC, sustained viral eradication, SVR, interferon, 0302 clinical medicine, Retrospective Studie, Pharmacology (medical), Prospective Studies, Prospective cohort study, Aged, 80 and over, Liver Neoplasms, virus diseases, Hepatitis C, Middle Aged, Liver Neoplasm, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Catheter Ablation, Interferon, 030211 gastroenterology & hepatology, Female, Liver cancer, Human, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Liver Cirrhosi, Antiviral Agents, Follow-Up Studie, 03 medical and health sciences, Internal medicine, medicine, Carcinoma, Early Hepatocellular Carcinoma, Humans, Aged, Retrospective Studies, Antiviral Agent, Hepatology, business.industry, Settore MED/09 - MEDICINA INTERNA, Retrospective cohort study, medicine.disease, digestive system diseases, Surgery, Prospective Studie, Interferons, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract

none 48 no Background: In HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma (HCC), the time to HCC recurrence and the effects of sustained viral eradication (SVR) by interferon (IFN)-based or IFN-free regimens on HCC recurrence remain unclear. Aim: To perform an indirect comparison of time to recurrence (TTR) in patients with successfully treated early HCC and active HCV infection with those of patients with SVR by IFN-based and by IFN-free regimens. Methods: We evaluated 443 patients with HCV-related cirrhosis and Barcelona Clinic Liver Cancer Stage A/0 HCC who had a complete radiological response after curative resection or ablation. Active HCV infection was present in 328, selected from the Italian Liver Cancer group cohort; 58 patients had SVR achieved by IFN-free regimens after HCC cure, and 57 patients had SVR achieved by IFN-based regimens after HCC cure. Individual data of patients in the last two groups were extracted from available publications. Results: TTR by Kaplan–Meier curve was significantly lower in patients with active HCV infection compared with those with SVR both by IFN-free (P = 0.02) and by IFN-based (P < 0.001) treatments. TTR was similar in patients with SVR by IFN-free or by IFN-based (P = 0.49) strategies. Conclusion: In HCV-infected, successfully treated patients with early HCC, SVR obtained by IFN-based or IFN-free regimens significantly reduce tumour recurrence without differences related to the anti-viral strategy used. Petta, S.; Cabibbo, G.; Barbara, M.; Attardo, S.; Bucci, L.; Farinati, F.; Giannini, E.G.; Tovoli, F.; Ciccarese, F.; Rapaccini, G.L.; Di Marco, M.; Caturelli, E.; Zoli, M.; Borzio, F.; Sacco, R.; Virdone, R.; Marra, F.; Felder, M.; Morisco, F.; Benvegnù, L.; Gasbarrini, A.; Svegliati-Baroni, G.; Foschi, F.G.; Olivani, A.; Masotto, A.; Nardone, G.; Colecchia, A.; Persico, M.; Boccaccio, V.; Craxì, A.; Bruno, S.; Trevisani, F.; Cammà, C; the Italian Liver Cancer (ITALICA) Group [ ; Maurizio Biselli; Paolo Caraceni; Alessandro Cucchetti; Marco Domenicali; Fabio Piscaglia; Annagiulia Gramenzi; Alessandro Granito; Donatella Magalotti; Carla Serra; Giulia Negrini; Lucia Napoli; Veronica Salvatore; Francesca Benevento;] Petta, S.; Cabibbo, G.; Barbara, M.; Attardo, S.; Bucci, L.; Farinati, F.; Giannini, E.G.; Tovoli, F.; Ciccarese, F.; Rapaccini, G.L.; Di Marco, M.; Caturelli, E.; Zoli, M.; Borzio, F.; Sacco, R.; Virdone, R.; Marra, F.; Felder, M.; Morisco, F.; Benvegnù, L.; Gasbarrini, A.; Svegliati-Baroni, G.; Foschi, F.G.; Olivani, A.; Masotto, A.; Nardone, G.; Colecchia, A.; Persico, M.; Boccaccio, V.; Craxì, A.; Bruno, S.; Trevisani, F.; Cammà, C; the Italian Liver Cancer (ITALICA) Group [ ; Maurizio Biselli; Paolo Caraceni; Alessandro Cucchetti; Marco Domenicali; Fabio Piscaglia; Annagiulia Gramenzi; Alessandro Granito; Donatella Magalotti; Carla Serra; Giulia Negrini; Lucia Napoli; Veronica Salvatore; Francesca Benevento;]

Published
2017

12. Determinants of alpha-fetoprotein levels in patients with hepatocellular carcinoma: Implications for its clinical use.

Author

Giannini, Edoardo G., Sammito, Giorgio, Farinati, Fabio, Ciccarese, Francesca, Pecorelli, Anna, Rapaccini, Gian Lodovico, Di Marco, Mariella, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Cabibbo, Giuseppe, Felder, Martina, Gasbarrini, Antonio, Sacco, Rodolfo, Foschi, Francesco Giuseppe, Missale, Gabriele, Morisco, Filomena, Svegliati Baroni, Gianluca, Virdone, Roberto, and Trevisani, Franco

Subjects
ALPHA fetoproteins, LIVER cancer, BIOMARKERS, BLOOD serum analysis, CIRRHOSIS of the liver, ALANINE aminotransferase
Abstract

BACKGROUND α-Fetoprotein (AFP) is a biomarker commonly used in the management of patients with hepatocellular carcinoma (HCC), although the possible determinants of its serum levels in these patients have not been adequately explored. For this study, the authors evaluated the relevance of demographic, clinical, and oncologic factors to the presence of elevated AFP levels in large cohort of patients with HCC. METHODS In 4123 patients with HCC who were managed by the Italian Liver Cancer Group, AFP levels were assessed along with their association with demographic, biochemical, clinical, and oncologic characteristics. Patients were subdivided according to the presence of elevated AFP (ie, >10 ng/mL). RESULTS AFP levels were elevated in 62.4% of patients with HCC. Multivariate logistic regression analysis indicated that being a woman (odds ratio [OR], 1.497; 95% confidence interval [95%CI], 1.250-1.793; P < .0001), the presence of cirrhosis (OR, 1.538; 95% CI, 1.050-2.254; P = .027), liver disease with viral etiology (OR, 1.900; 95% CI, 1.589-2.272; P < .0001), an elevated alanine aminotransferase level (OR, 1.878; 95% CI, 1.602-2.202; P < .0001), a low albumin level (OR, 1.301; 95% CI, 1.110-1.525; P = .012), an HCC tumor size >2 cm (OR, 1.346; 95% CI, 1.135-2.596; P = .001), multinodular HCC (OR, 1.641; 95% CI, 1.403-1.920; P < .0001), and the presence of vascular invasion (OR, 1.774; 95% CI, 1.361-2.311; P < .0001) were associated independently with elevated levels of AFP. Both the median AFP level and the proportion of patients who had elevated levels increased with decreasing degrees of HCC differentiation ( P < .0001). CONCLUSIONS Sex and features of chronic liver disease were identified as nontumor characteristics that influence serum AFP levels in patients with HCC. These findings should be taken into account as limitations in interpreting the oncologic meaning of this biomarker in clinical practice. Cancer 2014;120:2150-2157. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Published
2014
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13. HCC Development Is Associated to Peripheral Insulin Resistance in a Mouse Model of NASH.

Author

De Minicis, Samuele, Agostinelli, Laura, Rychlicki, Chiara, Sorice, Gian Pio, Saccomanno, Stefania, Candelaresi, Cinzia, Giaccari, Andrea, Trozzi, Luciano, Pierantonelli, Irene, Mingarelli, Eleonora, Marzioni, Marco, Muscogiuri, Giovanna, Gaggini, Melania, Benedetti, Antonio, Gastaldelli, Amalia, Guido, Maria, and Svegliati-Baroni, Gianluca

Subjects
LIVER cancer, TUMOR growth, INSULIN resistance, AMINO acid content of food, DRUG dosage, INSULIN-like growth factor receptors, CARCINOGENESIS, LABORATORY mice
Abstract

NAFLD is the most common liver disease worldwide but it is the potential evolution to NASH and eventually to hepatocellular carcinoma (HCC), even in the absence of cirrhosis, that makes NAFLD of such clinical importance. Aim: we aimed to create a mouse model reproducing the pathological spectrum of NAFLD and to investigate the role of possible co-factors in promoting HCC. Methods: mice were treated with a choline-deficient L-amino-acid-defined-diet (CDAA) or its control (CSAA diet) and subjected to a low-dose i.p. injection of CCl4 or vehicle. Insulin resistance was measured by the euglycemic-hyperinsulinemic clamp method. Steatosis, fibrosis and HCC were evaluated by histological and molecular analysis. Results: CDAA-treated mice showed peripheral insulin resistance at 1 month. At 1–3 months, extensive steatosis and fibrosis were observed in CDAA and CDAA+CCl4 groups. At 6 months, equal increase in steatosis and fibrosis was observed between the two groups, together with the appearance of tumor. At 9 months of treatment, the 100% of CDAA+CCl4 treated mice revealed tumor versus 40% of CDAA mice. Insulin-like Growth Factor-2 (IGF-2) and Osteopontin (SPP-1) were increased in CDAA mice versus CSAA. Furthermore, Immunostaining for p-AKT, p-c-Myc and Glypican-3 revealed increased positivity in the tumors. Conclusions: the CDAA model promotes the development of HCC from NAFLD-NASH in the presence of insulin resistance but in the absence of cirrhosis. Since this condition is increasingly recognized in humans, our study provides a model that may help understanding mechanisms of carcinogenesis in NAFLD. [ABSTRACT FROM AUTHOR]

Published
2014
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14. Subcellular distribution and Nrf2/Keap1-interacting properties of Glutathione S-transferase P in hepatocellular carcinoma.

Author

Bartolini, Desirée, Stabile, Anna Maria, Migni, Anna, Gurrado, Fabio, Lioci, Gessica, De Franco, Francesca, Mandarano, Martina, Svegliati-Baroni, Gianluca, Di Cristina, Manlio, Bellezza, Guido, Rende, Mario, and Galli, Francesco

Subjects
*GLUTATHIONE transferase, *NUCLEAR factor E2 related factor, *TRANSCRIPTION factors, *HEPATOCELLULAR carcinoma, *KEAP1 (Protein), *IMMUNOPRECIPITATION, *ERYTHROCYTE membranes, *GLUTATHIONE
Abstract

The oncogene and drug metabolism enzyme glutathione S-transferase P (GSTP) is also a GSH-dependent chaperone of signal transduction and transcriptional proteins with key role in liver carcinogenesis. In this study, we explored this role of GSTP in hepatocellular carcinoma (HCC) investigating the possible interaction of this protein with one of its transcription factor and metronome of the cancer cell redox, namely the nuclear factor erythroid 2–related factor 2 (Nrf2). Expression, cellular distribution, and function as glutathionylation factor of GSTP1-1 isoform were investigated in the mouse model of N-nitrosodiethylamine (DEN)-induced HCC and in vitro in human HCC cell lines. The physical and functional interaction of GSTP protein with Nrf2 and Keap1 were investigated by immunoprecipitation and gene manipulation experiments. GSTP protein increased its liver expression, enzymatic activity and nuclear levels during DEN-induced tumor development in mice; protein glutathionylation (PSSG) was increased in the tumor masses. Higher levels and a preferential nuclear localization of GSTP protein were also observed in HepG2 and Huh-7 hepatocarcinoma cells compared to HepaRG non-cancerous cells, along with increased basal and Ebselen-stimulated levels of free GSH and PSSG. GSTP activity inhibition with the GSH analogue EZT induced apoptotic cell death in HCC cells. Hepatic Nrf2 and c-Jun, two transcription factors involved in GSTP expression and GSH biosynthesis, were induced in DEN-HCC compared to control animals; the Nrf2 inhibitory proteins Keap1 and β−TrCP also increased and oligomeric forms of GSTP co-immunoprecipitated with both Nrf2 and Keap1. Nrf2 nuclear translocation and β−TrCP expression also increased in HCC cells, and GSTP transfection in HepaRG cells induced Nrf2 activation. In conclusion, GSTP expression and subcellular distribution are modified in HCC cells and apparently contribute to the GSH-dependent reprogramming of the cellular redox in this type of cancer directly influencing the transcriptional system Nrf2/Keap1. [Display omitted] • GSTP overexpression and nuclear translocation characterize DEN-induced HCC development. • These changes of GSTP protein are also observed in human HCC cell lines. • Gene transfection-induced GSTP overexpression activates Nrf2 in human liver cells. • GSTP coimmunoprecipitates with Nrf2 and Keap1 in the mouse liver. • Specific multimeric forms of GSTP coimmunoprecipitate with Nrf2. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Molecular basis and mechanisms of progression of non-alcoholic steatohepatitis

Author

Marra, Fabio, Gastaldelli, Amalia, Svegliati Baroni, Gianluca, Tell, Gianluca, and Tiribelli, Claudio

Subjects
*HEPATITIS, *CIRRHOSIS of the liver, *LIVER cancer, *INFLAMMATION, *APOPTOSIS
Abstract

Non-alcoholic steatohepatitis (NASH), a cause of cirrhosis and hepatocellular carcinoma, is characterized by fatty infiltration of the liver, inflammation, hepatocellular damage and fibrosis. Progress has been made in understanding the molecular and cellular mechanisms implicated in the pathogenesis of this condition, therefore, we here review recent developments regarding the basic mechanisms of NASH development. Accumulation of triglycerides in the hepatocytes is the result of increased inflow of free fatty acids and de novo lipogenesis. Steatosis leads to lipotoxicity, which causes apoptosis, necrosis, generation of oxidative stress and inflammation. The resulting chronic injury activates a fibrogenic response that leads eventually to end-stage liver disease. A better understanding of these mechanisms is crucial for the design of novel diagnostic and therapeutic strategies. [Copyright &y& Elsevier]

Published
2008
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16. Surveillance for hepatocellular carcinoma with a 3-months interval in 'extremely high-risk' patients does not further improve survival

Author

Filippo Pelizzaro, Giulia Peserico, Marco D'Elia, Nora Cazzagon, Francesco Paolo Russo, Alessandro Vitale, Edoardo G. Giannini, Manuela Piccinnu, Gian Ludovico Rapaccini, Maria Di Marco, Eugenio Caturelli, Marco Zoli, Rodolfo Sacco, Giuseppe Cabibbo, Fabio Marra, Andrea Mega, Filomena Morisco, Antonio Gasbarrini, Gianluca Svegliati-Baroni, Francesco Giuseppe Foschi, Andrea Olivani, Alberto Masotto, Gerardo Nardone, Giovanni Raimondo, Francesco Azzaroli, Gianpaolo Vidili, Filippo Oliveri, Franco Trevisani, Fabio Farinati, Maurizio Biselli, Paolo Caraceni, Francesca Garuti, Annagiulia Gramenzi, Andrea Neri, Valentina Santi, Fabio Piscaglia, Francesco Tovoli, Alessandro Granito, Luca Muratori, Francesca Benevento, Elton Dajti, Giovanni Marasco, Federico Ravaioli, Alberta Cappelli, Rita Golfieri, Cristina Mosconi, Matteo Renzulli, Angela Imondi, Anna Sartori, Barbara Penzo, Elisa Pinto, Ester Marina Cela, Antonio Facciorusso, Valentina Cacciato, Edoardo Casagrande, Alessandro Moscatelli, Gaia Pellegatta, Nicoletta De Matthaeis, Gloria Allegrini, Valentina Lauria, Giorgia Ghittoni, Giorgio Pelecca, Fabrizio Chegai, Fabio Coratella, Mariano Ortenzi, Gabriele Missale, Alessandro Inno, Fabiana Marchetti, Anita Busacca, Calogero Cammà, Vincenzo Di Martino, Giacomo Emanuele Maria Rizzo, Maria Stella Franzè, Carlo Saitta, Assunta Sauchella, Vittoria Bevilacqua, Alberto Borghi, Andrea Casadei Gardini, Fabio Conti, Anna Chiara Dall'aglio, Giorgio Ercolani, Federica Mirici, Claudia Campani, Chiara Di Bonaventura, Stefano Gitto, Pietro Coccoli, Antonio Malerba, Maria Guarino, Maurizia Brunetto, Veronica Romagnoli, Pelizzaro, F., Peserico, G., D'Elia, M., Cazzagon, N., Russo, F. P., Vitale, A., Giannini, E. G., Piccinnu, M., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Sacco, R., Cabibbo, G., Marra, F., Mega, A., Morisco, F., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F. G., Olivani, A., Masotto, A., Nardone, G., Raimondo, G., Azzaroli, F., Vidili, G., Oliveri, F., Trevisani, F., Farinati, F., Biselli, M., Caraceni, P., Garuti, F., Gramenzi, A., Neri, A., Santi, V., Piscaglia, F., Tovoli, F., Granito, A., Muratori, L., Benevento, F., Dajti, E., Marasco, G., Ravaioli, F., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Imondi, A., Sartori, A., Penzo, B., Pinto, E., Cela, E. M., Facciorusso, A., Cacciato, V., Casagrande, E., Moscatelli, A., Pellegatta, G., De Matthaeis, N., Allegrini, G., Lauria, V., Ghittoni, G., Pelecca, G., Chegai, F., Coratella, F., Ortenzi, M., Missale, G., 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., Casadei Gardini, A., Conti, F., Dall'Aglio, A. C., Ercolani, G., Mirici, F., Campani, C., Di Bonaventura, C., Gitto, S., Coccoli, P., Malerba, A., Guarino, M., Brunetto, M., Romagnoli, V., Pelizzaro, Filippo, Peserico, Giulia, D'Elia, Marco, Cazzagon, Nora, Russo, Francesco Paolo, Vitale, Alessandro, Giannini, Edoardo G., Piccinnu, Manuela, Rapaccini, Gian Ludovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Sacco, Rodolfo, Cabibbo, Giuseppe, Marra, Fabio, Mega, Andrea, Morisco, Filomena, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Raimondo, Giovanni, Azzaroli, Francesco, Vidili, Gianpaolo, Oliveri, Filippo, Trevisani, Franco, Farinati, Fabio, Biselli, Maurizio, Caraceni, Paolo, Garuti, Francesca, Gramenzi, Annagiulia, Neri, Andrea, Santi, Valentina, Piscaglia, Fabio, Tovoli, Francesco, Granito, Alessandro, Muratori, Luca, Benevento, Francesca, Dajti, Elton, Marasco, Giovanni, Ravaioli, Federico, Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Imondi, Angela, Sartori, Anna, Penzo, Barbara, Pinto, Elisa, Cela, Ester Marina, Facciorusso, Antonio, Cacciato, Valentina, Casagrande, Edoardo, Moscatelli, Alessandro, Pellegatta, Gaia, De Matthaeis, Nicoletta, Allegrini, Gloria, Lauria, Valentina, Ghittoni, Giorgia, Pelecca, Giorgio, Chegai, Fabrizio, Coratella, Fabio, Ortenzi, Mariano, Missale, Gabriele, Inno, Alessandro, Marchetti, Fabiana, Busacca, Anita, Cammà, Calogero, Di Martino, Vincenzo, Rizzo, Giacomo Emanuele Maria, Franzè, Maria Stella, Saitta, Carlo, Sauchella, Assunta, Bevilacqua, Vittoria, Borghi, Alberto, Casadei Gardini, Andrea, Conti, Fabio, Dall'aglio, Anna Chiara, Ercolani, Giorgio, Mirici, Federica, Campani, Claudia, Di Bonaventura, Chiara, Gitto, Stefano, Coccoli, Pietro, Malerba, Antonio, Guarino, Maria, Brunetto, Maurizia, and Romagnoli, Veronica

Subjects
medicine.medical_specialty, Carcinoma, Hepatocellular, Survival, Hepatocellular carcinoma, Cancer stage, Surveillance interval, Internal medicine, medicine, Humans, Propensity Score, Survival analysis, High risk patients, Hepatology, business.industry, Liver Neoplasms, Settore MED/09 - MEDICINA INTERNA, Gastroenterology, Patient survival, medicine.disease, Survival Analysis, Propensity score matching, Survival Analysi, Liver cancer, business, Median survival, Human
Abstract

Background An enhanced surveillance schedule has been proposed for cirrhotics with viral etiology, who are considered at extremely high-risk of hepatocellular carcinoma (HCC). Aims We compared the 3- and 6-months surveillance interval, evaluating cancer stage at diagnosis and patient survival. Methods Data of 777 HBV and HCV cirrhotic patients with HCC diagnosed under a 3-months (n = 109, 3MS group) or a 6-months (n = 668, 6MS group) surveillance were retrieved from the Italian Liver Cancer database. Survival in the 3MS group was considered as observed and adjusted for lead-time bias, and survival analysis was repeated after a propensity score matching. Results The 3-months surveillance interval neither reduced the share of patients diagnosed outside the Milano criteria, nor increased their probability to receive curative treatments. The median survival of 6MS patients (55.0 months [45.9–64.0]) was not significantly different from the observed (47.0 months [35.0–58.9]; p = 0.43) and adjusted (44.9 months [33.4–56.4]; p = 0.30) survival of 3MS patients. A propensity score analysis confirmed the absence of a survival advantage for 3MS patients. Conclusions A tightening of surveillance schedule does not increase the diagnosis of early-stage tumors, the feasibility of curative treatments and the survival. Therefore, we should maintain the 6-months interval in the surveillance of viral cirrhotics.

Published
2022

17. Restaging Patients With Hepatocellular Carcinoma Before Additional Treatment Decisions: A Multicenter Cohort Study

Author

Vitale, A, Farinati, F, Noaro, G, Burra, P, Pawlik, Tm, Bucci, L, Giannini, Eg, Faggiano, C, 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, Olivani, A, Masotto, A, Nardone, G, Colecchia, A, Fornari, F, Marignani, M, Vicari, S, Bortolini, E, Cozzolongo, R, Grasso, A, Aliberti, C, Bernardi, M, Frigo, Ac, Borzio, M, Trevisani, F, Cillo, U, CA) group, Italian Liver Cancer (ITA. LI., Vitale, Alessandro, Farinati, Fabio, Noaro, Giulia, Burra, Patrizia, Pawlik, Timothy M., Bucci, Laura, Giannini, Edoardo G., Faggiano, Chiara, Ciccarese, Francesca, Rapaccini, Gian Lodovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cabibbo, Giuseppe, Virdone, Roberto, Marra, Fabio, Felder, Martina, Morisco, Filomena, Benvegnù, Luisa, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Fornari, Fabio, Marignani, Massimo, Vicari, Susanna, Bortolini, Emanuela, Cozzolongo, Raffaele, Grasso, Alessandro, Aliberti, Camillo, Bernardi, Mauro, Frigo, Anna Chiara, Borzio, Mauro, Trevisani, Franco, and Cillo, Umberto

Subjects
Male, Oncology, Databases, Factual, Liver cancer, non surgical therapy, prognostic system, surgical therapy, survival, hepatocellular carcinoma, stage, treatment, Kaplan-Meier Estimate, Cohort Studies, Liver disease, 0302 clinical medicine, Middle Aged, Sorafenib, Prognosis, Italy, 030220 oncology & carcinogenesis, Catheter Ablation, Disease Progression, Female, 030211 gastroenterology & hepatology, medicine.drug, Cohort study, medicine.medical_specialty, Carcinoma, Hepatocellular, Settore MED/12 - GASTROENTEROLOGIA, Clinical Decision-Making, Risk Assessment, Disease-Free Survival, Statistics, Nonparametric, 03 medical and health sciences, Internal medicine, medicine, Hepatectomy, Humans, Infusions, Intra-Arterial, Neoplasm Invasiveness, Survival analysis, Aged, Neoplasm Staging, Retrospective Studies, Analysis of Variance, Hepatology, business.industry, Reproducibility of Results, Cancer, Retrospective cohort study, medicine.disease, Survival Analysis, business, Progressive disease
Abstract

Prognostic assessment of patients with hepatocellular carcinoma (HCC) at the time of diagnosis remains controversial and becomes even more complex at the time of restaging when new variables need to be considered. The aim of the current study was to evaluate the prognostic utility of restaging patients before proceeding with additional therapies for HCC. Two independent Italian prospective databases were used to identify 1,196 (training cohort) and 648 (validation cohort) consecutive patients with HCC treated over the same study period (2008-2015) who had complete restaging before decisions about additional therapies. The performance of the Italian Liver Cancer (ITA.LI.CA) prognostic score at restaging was compared with that of the Barcelona Clinic Liver Cancer, Hong Kong Liver Cancer, and Cancer of the Liver Italian Program systems. A multivariable Cox survival analysis was performed to identify baseline, restaging, or dynamic variables that were able to improve the predictive performance of the prognostic systems. At restaging, 35.3% of patients maintained stable disease; most patients were either down-staged by treatment (27.2%) or had disease progression (37.5%). The ITA.LI.CA scoring system at restaging demonstrated the best prognostic performance in both the training and validation cohorts (c-index 0.707 and 0.722, respectively) among all systems examined. On multivariable analysis, several variables improved the prognostic ability of the ITA.LI.CA score at restaging, including progressive disease after the first treatment, Model for End-Stage Liver Disease at restaging, and choice of nonsurgical treatment as additional therapy. A new ITA.LI.CA restaging model was created that demonstrated high discriminative power in both the training and validation cohorts (c-index 0.753 and 0.745, respectively). Conclusion: Although the ITA.LI.CA score demonstrated the best prognostic performance at restaging, other variables should be considered to improve the prognostic assessment of patients at the time of deciding additional therapies for HCC.

Published
2018

18. Survival benefit of liver resection for patients with hepatocellular carcinoma across different Barcelona Clinic Liver Cancer stages: a multicentre study

Author

Vitale A, Burra P, Frigo AC, Farinati F, Spolverato G, Volk M, Giannini EG, Ciccarese F, Rapaccini GL, Di Marco M, Caturelli E, Borzio F, Cabibbo G, Felder M, Gasbarrini A, Sacco R, Foschi FG, Missale G, Morisco F, Svegliati Baroni G, Virdone R, Cillo U, Italian Liver Cancer group, TREVISANI, FRANCO, PISCAGLIA, FABIO, ZOLI, MARCO, BERNARDI, MAURO, BOLONDI, LUIGI, BISELLI, MAURIZIO, CARACENI, PAOLO, CUCCHETTI, ALESSANDRO, DOMENICALI, MARCO, GRAMENZI, ANNAGIULIA, Vitale, A., Burra, P., Frigo, A. C., Trevisani, F., Farinati, F., Spolverato, G., Volk, M., Giannini, E. G., Ciccarese, F., Piscaglia, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Cabibbo, G., Felder, M., Gasbarrini, A., Sacco, R., Foschi, F. G., Missale, G., Morisco, F., Svegliati Baroni, G., Virdone, R., Cillo, U, Olmi, S, on behalf of Italian Liver Cancer, (ITA. LI. CA) group., Vitale, Alessandro, Burra, Patrizia, Frigo, Anna Chiara, Trevisani, Franco, Farinati, Fabio, Spolverato, Gaya, Volk, Michael, Giannini, Edoardo G, Ciccarese, Francesca, Piscaglia, Fabio, Rapaccini, Gian Lodovico, Di Marco, Mariella, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Cabibbo, Giuseppe, Felder, Martina, Gasbarrini, Antonio, Sacco, Rodolfo, Foschi, Francesco Giuseppe, Missale, Gabriele, Morisco, Filomena, Svegliati Baroni, Gianluca, Virdone, Roberto, Cillo, Umberto, Guarino, Maria, Vitale A, Burra P, Frigo AC, Trevisani F, Farinati F, Spolverato G, Volk M, Giannini EG, Ciccarese F, Piscaglia F, Rapaccini GL, Di Marco M, Caturelli E, Zoli M, Borzio F, Cabibbo G, Felder M, Gasbarrini A, Sacco R, Foschi FG, Missale G, Morisco F, Svegliati Baroni G, Virdone R, Cillo U, Italian Liver Cancer (ITA.LI.CA) group, Bernardi M, Bolondi L, Biselli M, Caraceni P, Cucchetti A, Domenicali M, and Gramenzi A

Subjects
Male, medicine.medical_specialty, Cirrhosis, Carcinoma, Hepatocellular, Loco-regional therapie, Hepatocellular carcinoma, Settore MED/12 - GASTROENTEROLOGIA, Hepatitis C virus, Kaplan-Meier Estimate, medicine.disease_cause, Gastroenterology, Cohort Studies, Liver disease, Interquartile range, Internal medicine, medicine, Humans, Best supportive care, Liver resection, Loco-regional therapies, Survival benefit, Aged, Female, Italy, Liver Neoplasms, Middle Aged, Multivariate Analysis, Neoplasm Staging, Prognosis, Treatment Outcome, Medicine (all), Hepatology, BEST SUPPORTING CARE, Cirrhosi, Performance status, business.industry, CIRRHOISIS, Carcinoma, Hepatocellular, medicine.disease, BCLC Stage, Liver cancer, business
Abstract

Background & Aims The role of hepatic resection for hepatocellular carcinoma (HCC) in different Barcelona Clinic Liver Cancer (BCLC) stages is controversial. We aimed at measuring the survival benefit of resection vs. non-surgical-therapies in each BCLC stage. Methods Using the ITA.LI.CA database, we identified 2090 BCLC A, B, and C HCC patients observed between 2000 and 2012: 550 underwent resection, 1046 loco-regional therapy (LRT), and 494 best supportive care (BSC). A multivariate log-logistic model was chosen to predict median survival (MS) after resection vs. MS after LRT or BSC. The results were expressed as net survival benefit of resection: (MS resection - MS LRT)/MS BSC. Results After stratifying for BCLC stage, the median net survival benefit of resection over LRT was: BCLC 0 = 62% (40%, 82%), A = 45% (13%, 65%), B = 46% (9%, 76%), C = -16% (-55%, 33%). Model for end-stage liver disease (MELD) score >9, Child B class, and performance status (PST) = 2 were the main risk factors for liver resection. 1181 Child A patients (57%) with MELD ≤9 and PST 9 or PST = 2 or Child B class), resection did not prove any survival benefit over LRT. Conclusions Resection could result in survival benefit over LRT for HCC patients regardless of their BCLC stage, provided that liver dysfunction (Child B or MELD >9) and PST >1 are absent.

Published
2014

19. PP68 - Cytochrome P450 metabolism of vitamin E in models of non-alcoholic fatty liver disease and steatohepatitis.

Author

Bartolini, Desirée, Faccani, Veronica, Russo, Angelo, Pieri, Vanessa, Torquato, Pierangelo, Agostinelli, Laura, Rychlicki, Chiara, Svegliati-Baroni, Gianluca, and Galli, Francesco

Subjects
*CYTOCHROME P-450, *FATTY liver, *VITAMIN E, *INFLAMMATION, *LIVER cancer, *ANTIOXIDANTS
Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease worldwide in association with oxidative stress and insulin resistance. Steatosis can evolve to steatohepatitis (NASH) by lipotoxicity, inflammation, fibrosis and cell death leading to cirrhosis and hepatocellular carcinoma. No valid therapy has been developed so far to control inflammatory and fibrogenic pathways of NAFLD/NASH. α-Tocopherol (α-TOH) is an antioxidant that partially reverts the histopatological spectrum of NASH. However, the biological mechanism that may support a preventive or therapeutic role of vitamin E in NASH and chronic liver diseases remain elusive. In this study we explored in vitro and in vivo the metabolism of vitamin E in liver cells and in the whole liver exposed to some pathogenic stimuli associated with the progression of NAFLD/NASH. Protein levels of CYP4F2, the cytochrome P450 isoenzyme involved in the metabolism of vitamin E increased in HepG2 cells incubated with α-TOH. This effect increased with a synergic action by the treatment with the fatty acids oleic acid or palmitic acid, or with fructose, which are well-known NASH stimuli. In mice fed control or NAFLD/NASH diets, e.g. high-fat (HFD) or HFD plus fructose diet, the abnormal lipid metabolism of liver tissue was associated with a lowered expression of CYP4F2 protein. The same finding was observed in animals treated with CCl4, a free radical-generating hepatotoxic xenobiotic leading to hepatic fibrosis, in the presence of lowered levels of liver α-TOH. In conclusion, either acute or chronic challenges with NAFLD/NASH stimuli influence the liver expression of CYP4F2. The observed acute transcriptional upregulation and the in vivo downregulation of this protein, point to a role for CYP4F2 in the inflammatory and lipotoxicity signaling of NASH. Transcriptional effects of vitamin E on this gene may help to explain earlier and positive clinical findings, which are worth of further investigation. [ABSTRACT FROM AUTHOR]

Published
2015
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