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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

2. Targeting Stress Sensor Kinases in Hepatocellular Carcinoma-Infiltrating Human NK Cells as a Novel Immunotherapeutic Strategy for Liver Cancer.

Author

Zecca, Alessandra, Barili, Valeria, Olivani, Andrea, Biasini, Elisabetta, Boni, Carolina, Fisicaro, Paola, Montali, Ilaria, Tiezzi, Camilla, Dalla Valle, Raffaele, Ferrari, Carlo, Cariani, Elisabetta, and Missale, Gabriele

Subjects
KILLER cells, MITOGEN-activated protein kinases, LIVER cancer, METABOLIC regulation, KINASES, GENE expression profiling
Abstract

Natural killer (NK) cells may become functionally exhausted entering hepatocellular carcinoma (HCC), and this has been associated with tumor progression and poor clinical outcome. Hypoxia, low nutrients, immunosuppressive cells, and soluble mediators characterize the intratumor microenvironment responsible for the metabolic deregulation of infiltrating immune cells such as NK cells. HCC-infiltrating NK cells from patients undergoing liver resection for HCC were sorted, and genome-wide transcriptome profiling was performed. We have identified a marked general upregulation of gene expression profile along with metabolic impairment of glycolysis, OXPHOS, and autophagy as well as functional defects of NK cells. Targeting p38 kinase, a stress-responsive mitogen-activated protein kinase, we could positively modify the metabolic profile of NK cells with functional restoration in terms of TNF-α production and cytotoxicity. We found a metabolic and functional derangement of HCC-infiltrating NK cells that is part of the immune defects associated with tumor progression and recurrence. NK cell exhaustion due to the hostile tumor microenvironment may be restored with p38 inhibitors with a selective mechanism that is specific for tumor-infiltrating—not affecting liver-infiltrating—NK cells. These results may represent the basis for the development of a new immunotherapeutic strategy to integrate and improve the available treatments for HCC. [ABSTRACT FROM AUTHOR]

Published
2022
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3. 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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4. 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

5. 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

6. ATL>Diagnosis of liver nodules observed in chronic liver disease patients during ultrasound screening for early detection of hepatocellular carcinoma.

Author

Caturelli, Eugenio, Bartolucci, Francesca, Biasini, Elisabetta, Vigliotti, Maria Luigia, Andriulli, Angelo, Siena, Domenico Angelo, Attino, Vito, and Bisceglia, Michele

Subjects
LIVER cancer, INTRAVASCULAR ultrasonography
Abstract

OBJECTIVES:The aim of our study was to evaluate the nature of focal liver lesions detected during the ultrasound follow-up of a population (prevalently anti-hepatitis C virus [anti-HCV] positive) with chronic liver disease.METHODS:The study population consisted of 1827 consecutive newly diagnosed chronic liver disease cases without liver nodules at enrollment. Patients were screened at 4-month intervals by ultrasound and serum α-fetoprotein assessment. All lesions detected on imaging studies (except those accompanied by diagnostic α-fetoprotein levels) were subjected to biopsy (histology and cytology).RESULTS:During the 7-yr follow-up period (mean = 43.1 months), one or more solid focal lesions were found in 287 patients. α-Fetoprotein was diagnostic for hepatocellular carcinoma in 51 patients. Ultrasound-guided fine-needle biopsy was performed in the remaining 236 patients, yielding a diagnosis in 214: 198 hepatocellular carcinomas, 11 dysplastic nodules, and five B-cell non-Hodgkin’s lymphomas (all confined to the liver and all in patients with chronic HCV infection). Twenty-two patients with nondiagnostic biopsies received diagnoses of hepatocellular carcinoma (20) or dysplastic nodules (two) based on arteriography or surgical biopsy.CONCLUSIONS:Focal lesions arising in patients with HCV-related chronic liver disease can be other than hepatocellular carcinoma, and ultrasound-guided fine-needle biopsy plays an important role in their diagnosis. The prevalence of non-Hodgkin’s lymphoma in this selected population was 0.31%. The fact that all five lymphoma patients had cirrhosis related to hepatitis C strengthens the hypothesis of an etiological correlation between the latter infection and B-cell lymphoproliferative disorders. [Copyright &y& Elsevier]

Published
2002
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7. Treatment of Hepatocellular Carcinoma with Immune Checkpoint Inhibitors and Applicability of First-Line Atezolizumab/Bevacizumab in a Real-Life Setting.

Author

Plaz Torres, Maria Corina, Lai, Quirino, Piscaglia, Fabio, Caturelli, Eugenio, Cabibbo, Giuseppe, Biasini, Elisabetta, Pelizzaro, Filippo, Marra, Fabio, Trevisani, Franco, and Giannini, Edoardo G.

Subjects
IMMUNE checkpoint inhibitors, SORAFENIB, ATEZOLIZUMAB, HEPATOCELLULAR carcinoma, BEVACIZUMAB, ENDOTHELIAL growth factors
Abstract

Immune checkpoint inhibitors (ICIs) are the new frontier for the treatment of advanced hepatocellular carcinoma (HCC). Since the first trial with tremelimumab, a cytotoxic T-lymphocyte-associated protein 4 inhibitor, increasing evidence has confirmed that these drugs can significantly extend the survival of patients with advanced hepatocellular carcinoma (HCC). As a matter of fact, the overall survival and objective response rates reported in patients with advanced HCC treated with ICIs are the highest ever reported in the second-line setting and, most recently, the combination of the anti-programmed death ligand protein-1 atezolizumab with bevacizumab—an anti-vascular endothelial growth factor monoclonal antibody—demonstrated superiority to sorafenib in a Phase III randomized clinical trial. Therefore, this regimen has been approved in several countries as first-line treatment for advanced HCC and is soon expected to be widely used in clinical practice. However, despite the promising results of trials exploring ICIs alone or in combination with other agents, there are still some critical issues to deal with to optimize the prognosis of advanced HCC patients. For instance, the actual proportion of patients who are deemed eligible for ICIs in the real-life ranges from 10% to 20% in the first-line setting, and is even lower in the second-line scenario. Moreover, long-term data regarding the safety of ICIs in the population of patients with cirrhosis and impaired liver function are lacking. Lastly, no biomarkers have been identified to predict response, and thus to help clinicians to individually tailor treatment. This review aimed to summarize the state of the art immunotherapy in HCC and, by analyzing a large, multicenter cohort of Italian patients with HCC, to assess the potential applicability of the combination of atezolizumab/bevacizumab in the real-life setting. [ABSTRACT FROM AUTHOR]

Published
2021
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8. Curative therapies are superior to standard of care (transarterial chemoembolization) for intermediate stage hepatocellular carcinoma

Author

Pecorelli A, Lenzi B, Gramenzi A, Garuti F, Farinati F, Giannini EG, Ciccarese F, Piscaglia F, Rapaccini GL, Di Marco M, Caturelli E, Zoli M, Borzio F, Sacco R, Cabibbo G, Felder M, Morisco F, Gasbarrini A, Baroni GS, Foschi FG, Biasini E, Masotto A, Virdone R, Bernardi M, Trevisani F, Bolondi L, Biselli M, Bucci L, Caraceni P, Cucchetti A, Domenicali M, Venerandi L, Giacomin A, Maddalo G, Pozzan C, Vani V, Poggio PD, Olmi S, Balsamo C, Vavassori E, Benvegnù L, Cappelli A, Golfieri R, Mosconi C, Renzulli M, Bosco G, Roselli P, Dell'Isola S, Ialungo AM, Bruzzone L, Picciotto A, Marenco S, Risso D, Sammito G, Savarino V, Cammà C, Maida M, Costantino A, Barcellona MR, Affronti A, Mega A, Rinninella E, Mismas V, Cappa FM, Dall'Aglio AC, Feletti V, Lanzi A, Neri E, Stefanini GF, Tamberi S, Missale G, Porro E, Guarino M, Gemini S, Schiadà L, for the Italian LiverCancer (ITA. LI. CA) group, Donatella Magalotti, Carla Serra, Pecorelli A, Lenzi B, Gramenzi A, Garuti F, Farinati F, Giannini EG, Ciccarese F, Piscaglia F, Rapaccini GL, Di Marco M, Caturelli E, Zoli M, Borzio F, Sacco R, Cabibbo G, Felder M, Morisco F, Gasbarrini A, Baroni GS, Foschi FG, Biasini E, Masotto A, Virdone R, Bernardi M, Trevisani F, Bolondi L, Biselli M, Bucci L, Caraceni P, Cucchetti A, Domenicali M, Magalotti D, Serra C, Venerandi L, Giacomin A, Maddalo G, Pozzan C, Vani V, Poggio PD, Olmi S, Balsamo C, Vavassori E, Benvegnù L, Cappelli A, Golfieri R, Mosconi C, Renzulli M, Bosco G, Roselli P, Dell'Isola S, Ialungo AM, Bruzzone L, Picciotto A, Marenco S, Risso D, Sammito G, Savarino V, Cammà C, Maida M, Costantino A, Barcellona MR, Affronti A, Mega A, Rinninella E, Mismas V, Cappa FM, Dall'Aglio AC, Feletti V, Lanzi A, Neri E, Stefanini GF, Tamberi S, Missale G, Porro E, Guarino M, Gemini S, Schiadà L, Pecorelli, A., Lenzi, B., Gramenzi, A., Garuti, F., Farinati, F., Giannini, E. G., Ciccarese, F., Piscaglia, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Cabibbo, G., Felder, M., Morisco, F., Gasbarrini, A., Baroni, G. S., Foschi, F. G., Biasini, E., Masotto, A., Virdone, R., Bernardi, M., Trevisani, F., Bolondi, L., Biselli, M., Bucci, L., Caraceni, P., Cucchetti, A., Domenicali, M., Magalotti, D., Serra, C., Venerandi, L., Giacomin, A., Maddalo, G., Pozzan, C., Vani, V., Poggio, P. D., Olmi, S., Balsamo, C., Vavassori, E., Benvegnu, L., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Bosco, G., Roselli, P., Dell'Isola, S., Ialungo, A. M., Bruzzone, L., Picciotto, A., Marenco, S., Risso, D., Sammito, G., Savarino, V., Camma, C., Maida, M., Costantino, A., Barcellona, M. R., Affronti, A., Mega, A., Rinninella, E., Mismas, V., Cappa, F. M., Dall'Aglio, A. C., Feletti, V., Lanzi, A., Neri, E., Stefanini, G. F., Tamberi, S., Missale, G., Porro, E., Guarino, M., Gemini, S., Schiada, L., Pecorelli, Anna, Lenzi, Barbara, Gramenzi, Annagiulia, Garuti, Francesca, Farinati, Fabio, Giannini, Edoardo G, Ciccarese, Francesca, Piscaglia, Fabio, Rapaccini, Gian Lodovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cabibbo, Giuseppe, Felder, Martina, Morisco, Filomena, Gasbarrini, Antonio, Baroni, Gianluca Svegliati, Foschi, Francesco G, Biasini, Elisabetta, Masotto, Alberto, Virdone, Roberto, Bernardi, Mauro, and Trevisani, Franco

Subjects
Sorafenib, Male, Niacinamide, medicine.medical_specialty, Standard of care, Carcinoma, Hepatocellular, Antineoplastic Agents, Gastroenterology, Intermediate stage, 03 medical and health sciences, 0302 clinical medicine, HCC, BCLC-B, Treatment, Hepatology, Internal medicine, medicine, Humans, Chemoembolization, Therapeutic, Propensity Score, Aged, Neoplasm Staging, Retrospective Studies, intermediate stage, treatment, business.industry, Patient Selection, Phenylurea Compounds, Liver Neoplasms, Settore MED/09 - MEDICINA INTERNA, Standard of Care, Middle Aged, medicine.disease, Survival Analysis, Treatment Outcome, Italy, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Propensity score matching, Multivariate Analysis, 030211 gastroenterology & hepatology, Female, Liver function, Liver cancer, business, medicine.drug
Abstract

Background and aims the Barcelona Clinic Liver Cancer intermediate stage (BCLC-B) of hepatocellular carcinoma (HCC) includes extremely heterogeneous patients in terms of tumor burden and liver function. Transarterial-chemoembolization (TACE) is the first-line treatment for these patients although it may be risky/useless for someone, while others could undergo curative treatments. This study assesses the treatment type performed in a large cohort of BCLC-B patients and its outcome. Methods retrospective analysis of 485 consecutive BCLC-B patients from the ITA.LI.CA database diagnosed with naive HCC after 1999. Patients were stratified by treatment. Results 29 patients (6%) were lost to follow-up before receiving treatment. Treatment distribution was: TACE (233, 51.1%), curative treatments (145 patients, 31.8%), sorafenib (18, 3.9%), other (39, 8.5%), best supportive care (BSC) (21, 4.6%). Median survival (95% CI) was 45 months (37.4-52.7) for curative treatments, 30 (24.7-35.3) for TACE, 14 (10.5-17.5) for sorafenib, 14 (5.2-22.7) for other treatments and 10 (6.0-14.2) for BSC (p

Published
2017

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