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1. Pattern of macrovascular invasion in hepatocellular carcinoma

Author

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

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

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

Published
2021

3. The perioperative period of liver transplantation from unconventional extended criteria donors: data from two high-volume centres

Author

Pescarissi, C, Penzo, B, Ghinolfi, D, Lai, Q, Bindi, L, De Carlis, R, Melandro, F, Balzano, E, Desimone, P, De Carlis, L, Degasperi, A, Biancofiore, G, Pescarissi, Claudia, Penzo, Beatrice, Ghinolfi, Davide, Lai, Quirino, Bindi, Lucia, De Carlis, Riccardo, Melandro, Fabio, Balzano, Emanuele, DeSimone, Paolo, De Carlis, Luciano, DeGasperi, Andrea, Biancofiore, Giandomenico L, Pescarissi, C, Penzo, B, Ghinolfi, D, Lai, Q, Bindi, L, De Carlis, R, Melandro, F, Balzano, E, Desimone, P, De Carlis, L, Degasperi, A, Biancofiore, G, Pescarissi, Claudia, Penzo, Beatrice, Ghinolfi, Davide, Lai, Quirino, Bindi, Lucia, De Carlis, Riccardo, Melandro, Fabio, Balzano, Emanuele, DeSimone, Paolo, De Carlis, Luciano, DeGasperi, Andrea, and Biancofiore, Giandomenico L

Abstract

Background: As literature largely focuses on long-term outcomes, this study aimed at elucidating the perioperative outcomes of liver transplant patients receiving a graft from two groups of unconventional expanded criteria donors: brain dead aged > 80 years and cardiac dead. Methods: Data of 247 cirrhotic patients transplanted at two high volume liver transplant centers were analysed. Confounders were balanced using a stabilized inverse probability therapy weighting and a propensity score for each patient on the original population was generated. The score was created using a multivariate logistic regression model considering a Comprehensive Complication Index ≥ 42 (no versus yes) as the dependent variable and 11 possible clinically relevant confounders as covariate. Results: Forty-four patients received the graft from a cardiac-dead donor and 203 from a brain-dead donor aged > 80 years. Intraoperatively, cardiac-dead donors liver transplant cases required more fresh frozen plasma units (P < 0.0001) with similar reduced need of fibrinogen to old brain-dead donors cases. The incidence of reperfusion syndrome was similar (P = 0.80). In the Intensive Care Unit, both the groups presented a comparable low need for blood transfusions, renal replacement therapy and inotropes. Cardiac-dead donors liver transplantations required more time to tracheal extubation (P < 0.0001) and scored higher Comprehensive Complication Index (P < 0.0001) however the incidence of a severe complication status (Comprehensive Complication Index ≥ 42) was similar (P = 0.52). ICU stay (P = 0.97), total hospital stay (P = 0.57), in hospital (P = 1.00) and 6 months (P = 1.00) death were similar. Conclusion: Selected octogenarian and cardiac-dead donors can be used safely for liver transplantation.

Published
2022

9. Pattern of macrovascular invasion in hepatocellular carcinoma

Author

Guarino, Mariateresa, Cucchetti, A., Pontillo, G., Farinati, F., Benevento, F., Rapaccini, Gian Ludovico, Di Marco, Maria Teresa, Caturelli, E., Zoli, M., Rodolfo, S., Cabibbo, G., Marra, F., Mega, A., Gasbarrini, Antonio, Svegliati-Baroni, G., Foschi, F. G., Missale, G., Masotto, A., Nardone, G., Raimondo, G., Azzaroli, F., Vidili, G., Oliveri, F., Trevisani, F., Giannini, E. G., Morisco, F., Biselli, M., Caraceni, P., Garuti, F., Gramenzi, A., Neri, A., Rampoldi, D., Santi, V., Forgione, Alessandra, Granito, A., Muratori, L., Piscaglia, F., Sansone, V., Tovoli, F., Dajti, E., Marasco, G., Ravaioli, F., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Cela, E. M., Facciorusso, A., Pelizzaro, F., Imondi, A., Sartori, A., Penzo, B., Cacciato, V., Casagrande, E., Moscatelli, A., Pellegatta, G., Pieri, G., De Matthaeis, Nicoletta, Allegrini, G., Lauria, V., Ghittoni, G., Pelecca, G., Chegai, F., Coratella, F., Ortenzi, M., Olivari, Elena Armida, Inno, A., Marchetti, F., Busacca, A., Camma, C., Di Martino, V., Rizzo, G. E. M., Franze, M. S., Saitta, C., Sauchella, A., Bevilacqua, V., Borghi, A., Gardini, A. C., Conti, Francesco, Berardinelli, D., Ercolani, G., Napoli, L., Campani, C., Di Bonaventura, C., Gitto, S., Coccoli, P., Malerba, A., Capasso, Monica, Fiorentino, Alice, Pignata, L., Cossiga, V., Romagnoli, V., Guarino M., Rapaccini G. L. (ORCID:0000-0002-6467-857X), Di Marco M., Gasbarrini A. (ORCID:0000-0002-7278-4823), Forgione A., de Matthaeis N., Olivari A., Conti F., Capasso M., Fiorentino A., Guarino, Mariateresa, Cucchetti, A., Pontillo, G., Farinati, F., Benevento, F., Rapaccini, Gian Ludovico, Di Marco, Maria Teresa, Caturelli, E., Zoli, M., Rodolfo, S., Cabibbo, G., Marra, F., Mega, A., Gasbarrini, Antonio, Svegliati-Baroni, G., Foschi, F. G., Missale, G., Masotto, A., Nardone, G., Raimondo, G., Azzaroli, F., Vidili, G., Oliveri, F., Trevisani, F., Giannini, E. G., Morisco, F., Biselli, M., Caraceni, P., Garuti, F., Gramenzi, A., Neri, A., Rampoldi, D., Santi, V., Forgione, Alessandra, Granito, A., Muratori, L., Piscaglia, F., Sansone, V., Tovoli, F., Dajti, E., Marasco, G., Ravaioli, F., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Cela, E. M., Facciorusso, A., Pelizzaro, F., Imondi, A., Sartori, A., Penzo, B., Cacciato, V., Casagrande, E., Moscatelli, A., Pellegatta, G., Pieri, G., De Matthaeis, Nicoletta, Allegrini, G., Lauria, V., Ghittoni, G., Pelecca, G., Chegai, F., Coratella, F., Ortenzi, M., Olivari, Elena Armida, Inno, A., Marchetti, F., Busacca, A., Camma, C., Di Martino, V., Rizzo, G. E. M., Franze, M. S., Saitta, C., Sauchella, A., Bevilacqua, V., Borghi, A., Gardini, A. C., Conti, Francesco, Berardinelli, D., Ercolani, G., Napoli, L., Campani, C., Di Bonaventura, C., Gitto, S., Coccoli, P., Malerba, A., Capasso, Monica, Fiorentino, Alice, Pignata, L., Cossiga, V., Romagnoli, V., Guarino M., Rapaccini G. L. (ORCID:0000-0002-6467-857X), Di Marco M., Gasbarrini A. (ORCID:0000-0002-7278-4823), Forgione A., de Matthaeis N., Olivari A., Conti F., Capasso M., and Fiorentino A.

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.

Published
2021

10. Monofocal hepatocellular carcinoma: How much does size matter?

Author

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., Vitale A., Forgione A., Di Marco M., Gasbarrini A. (ORCID:0000-0002-7278-4823), 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., Vitale A., Forgione A., Di Marco M., and Gasbarrini A. (ORCID:0000-0002-7278-4823)

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 (>5 cm) monofocal (HCC). METHODS: From the Italian Liver Cancer database, we selected 924 patients with small early monofocal HCC (2-5 cm; SEM-HCC), 163 patients with larger tumours (>5 cm; 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 49.0 months; P < .0001), and this was confirmed at multivariate analysis (HR 1.63, 95% CI 1.29-2.05; P < .0001). The small difference in OS between LEM-HCC and BCLC B patients (31.0 vs 27.0 months; P = .03) disappeared in the multivariate model (HR 0.98, 95% CI 0.77-1.25; P = .89). In all monofocal tumours, treatment was the strongest independent predictor of survival, with a progressively decreasing survival benefit moving from "curative" to "palliative" therapies. The survival of resected patients with LEM-HCC was significantly shorter than that of SEM-HCC (44.0 vs 78.0 months; P = .002), but liver resection provided the highest survival benefit in both groups compared to other treatments. CONCLUSIONS: Monofocal HCC larger than 5 cm should not be staged as BCLC A and either a different staging system or a different subgrouping of patients (e.g. BCLC AB) should be used. Liver resection, if feasible, remains the recommended treatment for all these patients.

Published
2021

11. Surveillance as determinant of long-term survival in non-transplanted hepatocellular carcinoma patients

Author

Pelizzaro, F., Vitale, Antonio, Sartori, A., Vieno, A., Penzo, B., Russo, F. P., Frigo, A. C., Giannini, E. G., Piccinnu, M., Rapaccini, Gian Ludovico, Di Marco, Maria Teresa, Caturelli, E., Zoli, M., Sacco, R., Celsa, C., Marra, F., Mega, A., Guarino, Mariateresa, Gasbarrini, Antonio, Svegliati-Baroni, G., Foschi, F. G., Olivani, A., Masotto, A., Coccoli, P., Raimondo, G., Azzaroli, F., Vidili, G., Brunetto, M. R., Trevisani, F., Farinati, F., Vitale A., Rapaccini G. L. (ORCID:0000-0002-6467-857X), Di Marco M., Guarino M., Gasbarrini A. (ORCID:0000-0002-7278-4823), Pelizzaro, F., Vitale, Antonio, Sartori, A., Vieno, A., Penzo, B., Russo, F. P., Frigo, A. C., Giannini, E. G., Piccinnu, M., Rapaccini, Gian Ludovico, Di Marco, Maria Teresa, Caturelli, E., Zoli, M., Sacco, R., Celsa, C., Marra, F., Mega, A., Guarino, Mariateresa, Gasbarrini, Antonio, Svegliati-Baroni, G., Foschi, F. G., Olivani, A., Masotto, A., Coccoli, P., Raimondo, G., Azzaroli, F., Vidili, G., Brunetto, M. R., Trevisani, F., Farinati, F., Vitale A., Rapaccini G. L. (ORCID:0000-0002-6467-857X), Di Marco M., Guarino M., and Gasbarrini A. (ORCID:0000-0002-7278-4823)

Abstract

Purpose: We aimed at assessing the impact of surveillance on long-term survival in HCC patients. Methods: From the ITA.LI.CA database, we selected 1028 cases with long (≥5 years, LS group) and 2721 controls with short-term survival (<5 years, SS group). The association between surveillance and LS was adjusted for confounders by multivariable logistic regression analysis. Survival of surveilled patients was presented both as observed and corrected for the lead-time bias, and the comparison of survival between surveillance and no surveillance groups was also performed after balancing the baseline characteristics with inverse probability weights (IPW). Results: LS patients were more frequently diagnosed under surveillance (p < 0.0001), and had more favorable baseline characteristics. Surveillance was an independent predictor of LS (OR = 1.413, 95% CI 1.195– 1.671; p < 0.0001). The observed and the lead-time corrected survival of surveilled patients were significantly longer compared to the survival of not surveilled patients (p < 0.0001 and p = 0.0008, respectively). In IPW adjusted populations, no survival differences were demonstrated between the two groups (p = 0.30). Conclusions: Surveillance, increasing early-stage diagnosis and applicability of curative treatments, is a fundamental determinant of long-term survival in HCC patients. A wide implementation of surveillance programs should be pursued in order to improve HCC patients’ prognosis.

Published
2021

16. OC.05.1 MICRORNA-21 AND MICRORNA-122: PROGNOSIS PREDICTION AND CORRELATION WITH HIF-1ALPHA IN HEPATOCELLULAR CARCINOMA PATIENTS TREATED WITH TRANSARTERIAL CHEMOEMBOLIZATION

Author

Pelizzaro, F., primary, Cardin, R., additional, Minotto, M., additional, Carlotto, C., additional, Imondi, A., additional, Sartori, A., additional, Penzo, B., additional, Sammarco, A., additional, Peserico, G., additional, Aliberti, C., additional, Vitale, A., additional, Cillo, U., additional, and Farinati, F., additional

Published
2020
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25. Transarterial Chemoembolization for Hepatocellular Carcinoma in Clinical Practice: Temporal Trends and Survival Outcomes of an Iterative Treatment

Author

Filippo Pelizzaro, Selion Haxhi, Barbara Penzo, Alessandro Vitale, Edoardo G. Giannini, Vito Sansone, Gian Ludovico Rapaccini, Maria Di Marco, Eugenio Caturelli, Donatella Magalotti, Rodolfo Sacco, Ciro Celsa, Claudia Campani, Andrea Mega, Maria Guarino, Antonio Gasbarrini, Gianluca Svegliati-Baroni, Francesco Giuseppe Foschi, Andrea Olivani, Alberto Masotto, Gerardo Nardone, Giovanni Raimondo, Francesco Azzaroli, Gianpaolo Vidili, Maurizia Rossana Brunetto, Franco Trevisani, Fabio Farinati, Pelizzaro F., Haxhi S., Penzo B., Vitale A., Giannini E.G., Sansone V., Rapaccini G.L., Di Marco M., Caturelli E., Magalotti D., Sacco R., Celsa C., Campani C., Mega A., Guarino M., Gasbarrini A., Svegliati-Baroni G., Foschi F.G., Olivani A., Masotto A., Nardone G., Raimondo G., Azzaroli F., Vidili G., Brunetto M.R., Trevisani F., Farinati F., Pelizzaro, F., Haxhi, S., Penzo, B., Vitale, A., Giannini, E. G., Sansone, V., Rapaccini, G. L., Di Marco, M., Caturelli, E., Magalotti, D., Sacco, R., Celsa, C., Campani, C., Mega, A., Guarino, M., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F. G., Olivani, A., Masotto, A., Nardone, G., Raimondo, G., Azzaroli, F., Vidili, G., Brunetto, M. R., Trevisani, F., Farinati, F., 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, Masotto, Alberto, Nardone, Gerardo, Raimondo, Giovanni, Azzaroli, Francesco, Vidili, Gianpaolo, Brunetto, Maurizia Rossana, Trevisani, Franco, and Farinati, Fabio

Subjects
Cancer Research, Oncology, Settore MED/09 - MEDICINA INTERNA, iterative treatment, hepatocellular carcinoma, survival, therapeutic hierarchy, transarterial chemoembolization, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

BackgroundTransarterial 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.MethodsData 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.ResultsThe 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).ConclusionsDespite 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.

Published
2022

26. The perioperative period of liver transplantation from unconventional extended criteria donors: data from two high-volume centres

Author

Pescarissi, Claudia, Penzo, Beatrice, Ghinolfi, Davide, Lai, Quirino, Bindi, Lucia, De Carlis, Riccardo, Melandro, Fabio, Balzano, Emanuele, DeSimone, Paolo, De Carlis, Luciano, DeGasperi, Andrea, Biancofiore, Giandomenico L, Pescarissi, C, Penzo, B, Ghinolfi, D, Lai, Q, Bindi, L, De Carlis, R, Melandro, F, Balzano, E, Desimone, P, De Carlis, L, Degasperi, A, and Biancofiore, G

Subjects
Aged, 80 and over, Brain Death, Liver transplantation, complications, Tissue Donors, Organ donation, Anesthesiology and Pain Medicine, intensive care unit, liver transplantation, organ donation, perioperative care, Humans, Intensive care unit, Perioperative Period, Complication, Retrospective Studies, Perioperative care
Abstract

BackgroundAs literature largely focuses on long-term outcomes, this study aimed at elucidating the perioperative outcomes of liver transplant patients receiving a graft from two groups of unconventional expanded criteria donors: brain dead aged > 80 years and cardiac dead.MethodsData of 247 cirrhotic patients transplanted at two high volume liver transplant centers were analysed. Confounders were balanced using a stabilized inverse probability therapy weighting and a propensity score for each patient on the original population was generated. The score was created using a multivariate logistic regression model considering a Comprehensive Complication Index ≥ 42 (no versus yes) as the dependent variable and 11 possible clinically relevant confounders as covariate.ResultsForty-four patients received the graft from a cardiac-dead donor and 203 from a brain-dead donor aged > 80 years. Intraoperatively, cardiac-dead donors liver transplant cases required more fresh frozen plasma units (P P = 0.80). In the Intensive Care Unit, both the groups presented a comparable low need for blood transfusions, renal replacement therapy and inotropes. Cardiac-dead donors liver transplantations required more time to tracheal extubation (P P P = 0.52). ICU stay (P = 0.97), total hospital stay (P = 0.57), in hospital (P = 1.00) and 6 months (P = 1.00) death were similar.ConclusionSelected octogenarian and cardiac-dead donors can be used safely for liver transplantation.

Published
2022

27. Characteristics and survival of patients with primary biliary cholangitis and hepatocellular carcinoma

Author

Edoardo G. Giannini, Giulia Pieri, Sara Labanca, Maria Corina Plaz Torres, Antonio Gasbarrini, Elisabetta Biasini, Claudia Campani, Nora Cazzagon, Francesco Giuseppe Foschi, Andrea Mega, Alberto Masotto, Giovanni Raimondo, Gian Ludovico Rapaccini, Rodolfo Sacco, Eugenio Caturelli, Maria Guarino, Francesco Tovoli, Gianpaolo Vidili, Maurizia Rossana Brunetto, Gerardo Nardone, Gianluca Svegliati-Baroni, Donatella Magalotti, Francesco Azzaroli, Giuseppe Cabibbo, Maria Di Marco, Angelo Sangiovanni, Franco Trevisani, Maurizio Biselli, Paolo Caraceni, Annagiulia Gramenzi, Francesca Benevento, Alessandro Granito, Luca Muratori, Fabio Piscaglia, Federica Bertellini, Fabio Farinati, Giorgio Palano, Filippo Pelizzaro, Barbara Penzo, Elisa Pinto, Gloria Allegrini, Calogero Cammà, Ciro Celsa, Paolo Giuffrida, Caterina Stornello, Mauro Grova, Carmelo Marco Giacchetto, Gabriele Rancatore, Maria Vittoria Grassini, Valentina Adotti, Stefano Gitto, Fabio Marra, Martina Rosi, Vittoria Bevilacqua, Alberto Borghi, Andrea Casadei Gardini, Fabio Conti, Lucia Napoli, Marco Domenicali, Maria Teresa Migliano, Nicoletta de Matthaeis, Francesca Romana Ponziani, Andrea Olivani, Gabriele Missale, Valentina Cossiga, Mario Capasso, Filomena Morisco, Ester Marina Cela, Antonio Facciorusso, Valentina Lauria, Giorgia Ghittoni, Giorgio Pelecca, Fabrizio Chegai, Fabio Coratella, Mariano Ortenzi, Serena Dell'Isola, Maria Stella Franzè, Carlo Saitta, Assunta Sauchella, Elton Dajti, Federico Ravaioli, Filippo Oliveri, Gabriele Ricco, Veronica Romagnoli, Alessandro Inno, Fabiana Marchetti, Pietro Coccoli, Antonio Malerba, Alberta Cappelli, Rita Golfieri, Cristina Mosconi, Matteo Renzulli, Giannini, Edoardo G, Pieri, Giulia, Labanca, Sara, Plaz Torres, Maria Corina, Gasbarrini, Antonio, Biasini, Elisabetta, Campani, Claudia, Cazzagon, Nora, Foschi, Francesco Giuseppe, Mega, Andrea, Masotto, Alberto, Raimondo, Giovanni, Rapaccini, Gian Ludovico, Sacco, Rodolfo, Caturelli, Eugenio, Guarino, Maria, Tovoli, Francesco, Vidili, Gianpaolo, Brunetto, Maurizia Rossana, Nardone, Gerardo, Svegliati-Baroni, Gianluca, Magalotti, Donatella, Azzaroli, Francesco, Cabibbo, Giuseppe, Di Marco, Maria, Sangiovanni, Angelo, Trevisani, Franco, Giannini, E. G., Pieri, G., Labanca, S., Plaz Torres, M. C., Gasbarrini, A., Biasini, E., Campani, C., Cazzagon, N., Foschi, F. G., Mega, A., Masotto, A., Raimondo, G., Rapaccini, G. L., Sacco, R., Caturelli, E., Guarino, M., Tovoli, F., Vidili, G., Brunetto, M. R., Nardone, G., Svegliati-Baroni, G., Magalotti, D., Azzaroli, F., Cabibbo, G., Di Marco, M., Sangiovanni, A., Trevisani, F., Biselli, M., Caraceni, P., Gramenzi, A., Benevento, F., Granito, A., Muratori, L., Piscaglia, F., Bertellini, F., Farinati, F., Palano, G., Pelizzaro, F., Penzo, B., Pinto, E., Allegrini, G., Camma, C., Celsa, C., Giuffrida, P., Stornello, C., Grova, M., Giacchetto, C. M., Rancatore, G., Grassini, M. V., Adotti, V., Gitto, S., Marra, F., Rosi, M., Bevilacqua, V., Borghi, A., Gardini, A. C., Conti, F., Napoli, L., Domenicali, M., Migliano, M. T., de Matthaeis, N., Ponziani, F. R., Olivani, A., Missale, G., Cossiga, V., Capasso, M., Morisco, F., Cela, E. M., Facciorusso, A., Lauria, V., Ghittoni, G., Pelecca, G., Chegai, F., Coratella, F., Ortenzi, M., Dell'Isola, S., Franze, M. S., Saitta, C., Sauchella, A., Dajti, E., Ravaioli, F., Oliveri, F., Ricco, G., Romagnoli, V., Inno, A., Marchetti, F., Coccoli, P., Malerba, A., Cappelli, A., Golfieri, R., Mosconi, C., and Renzulli, M.

Subjects
Male, Carcinoma, Hepatocellular, Cholestatic liver disease, Outcome, Surveillance, Survival, Treatment, Hepatology, Prognosi, Liver Cirrhosis, Biliary, Risk Factor, Settore MED/12 - GASTROENTEROLOGIA, Liver Neoplasms, Gastroenterology, Prognosis, Risk Factors, Humans, Female, Human, Aged
Abstract

Background: Comprehensive and contemporary data pertaining large populations of patients with Primary Biliary Cholangitis (PBC) and hepatocellular carcinoma (HCC) are missing. Aim: To describe main characteristics and outcome of PBC patients with HCC diagnosed in the new millennium. Methods: Analysing the Italian Liver Cancer registry we identified 80 PBC patients with HCC diagnosed after the year 2000, and described their clinical characteristics, access to treatment and survival. Results: Median age of patients was 71 years and 50.0% were males. Cirrhosis was present in 86.3% of patients, being well-compensated in 58.0%. Median HCC diameter was smaller in patients under surveillance (2.6vs 4.0cm, P=0.007). Curative treatment, feasible in 50.0% of patients, was associated with improved survival compared to palliative and supportive care (42vs 33vs 6 months, P

Published
2022

28. 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

29. Surveillance as determinant of long-term survival in non-transplanted hepatocellular carcinoma patients

Author

Pelizzaro, Filippo, Vitale, Alessandro, Sartori, Anna, Vieno, Andrea, Penzo, Barbara, Russo, Francesco, Frigo, Anna, Giannini, Edoardo, Piccinnu, Manuela, Rapaccini, Gian, Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Sacco, Rodolfo, Celsa, Ciro, Marra, Fabio, Mega, Andrea, Guarino, Maria, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco, Olivani, Andrea, Masotto, Alberto, Coccoli, Pietro, Raimondo, Giovanni, Azzaroli, Francesco, Vidili, Gianpaolo, Brunetto, Maurizia, Trevisani, Franco, Farinati, Fabio, Group, on behalf of ITA.LI.CA study, Pelizzaro F., Vitale A., Sartori A., Vieno A., Penzo B., Russo F.P., Frigo A.C., Giannini E.G., Piccinnu M., Rapaccini G.L., Di Marco M., Caturelli E., Zoli M., Sacco R., Celsa C., Marra F., Mega A., Guarino M., Gasbarrini A., Svegliati-Baroni G., Foschi F.G., Olivani A., Masotto A., Coccoli P., Raimondo G., Azzaroli F., Vidili G., Brunetto M.R., Trevisani F., and Farinati F.

Subjects
Cancer Research, medicine.medical_specialty, Hepatocellular carcinoma, Settore MED/12 - GASTROENTEROLOGIA, Cancer stage, Independent predictor, Logistic regression, lcsh:RC254-282, Article, 03 medical and health sciences, Long-term survival, 0302 clinical medicine, Internal medicine, Long term survival, medicine, Treatment, Surveillance, business.industry, Settore MED/09 - MEDICINA INTERNA, Confounding, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Oncology, 030220 oncology & carcinogenesis, Baseline characteristics, 030211 gastroenterology & hepatology, business
Abstract

Purpose: We aimed at assessing the impact of surveillance on long-term survival in HCC patients. Methods: From the ITA.LI.CA database, we selected 1028 cases with long (≥5 years, LS group) and 2721 controls with short-term survival (&lt, 5 years, SS group). The association between surveillance and LS was adjusted for confounders by multivariable logistic regression analysis. Survival of surveilled patients was presented both as observed and corrected for the lead-time bias, and the comparison of survival between surveillance and no surveillance groups was also performed after balancing the baseline characteristics with inverse probability weights (IPW). Results: LS patients were more frequently diagnosed under surveillance (p &lt, 0.0001), and had more favorable baseline characteristics. Surveillance was an independent predictor of LS (OR = 1.413, 95% CI 1.195–1.671, p &lt, 0.0001). The observed and the lead-time corrected survival of surveilled patients were significantly longer compared to the survival of not surveilled patients (p &lt, 0.0001 and p = 0.0008, respectively). In IPW adjusted populations, no survival differences were demonstrated between the two groups (p = 0.30). Conclusions: Surveillance, increasing early-stage diagnosis and applicability of curative treatments, is a fundamental determinant of long-term survival in HCC patients. A wide implementation of surveillance programs should be pursued in order to improve HCC patients’ prognosis.

Published
2021

30. 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

31. Major liver resections, perioperative issues and posthepatectomy liver failure: A comprehensive update for the anesthesiologist.

Author

De Gasperi A, Petrò L, Amici O, Scaffidi I, Molinari P, Barbaglio C, Cibelli E, Penzo B, Roselli E, Brunetti A, Neganov M, Giacomoni A, Aseni P, and Guffanti E

Abstract

Significant advances in surgical techniques and relevant medium- and long-term outcomes over the past two decades have led to a substantial expansion in the indications for major liver resections. To support these outstanding results and to reduce perioperative complications, anesthesiologists must address and master key perioperative issues (preoperative assessment, proactive intraoperative anesthesia strategies, and implementation of the Enhanced Recovery After Surgery approach). Intensive care unit monitoring immediately following liver surgery remains a subject of active and often unresolved debate. Among postoperative complications, posthepatectomy liver failure (PHLF) occurs in different grades of severity (A-C) and frequency (9%-30%), and it is the main cause of 90-d postoperative mortality. PHLF, recently redefined with pragmatic clinical criteria and perioperative scores, can be predicted, prevented, or anticipated. This review highlights: (1) The systemic consequences of surgical manipulations anesthesiologists must respond to or prevent, to positively impact PHLF (a proactive approach); and (2) the maximal intensive treatment of PHLF, including artificial options, mainly based, so far, on Acute Liver Failure treatment(s), to buy time waiting for the recovery of the native liver or, when appropriate and in very selected cases, toward liver transplant. Such a clinical context requires a strong commitment to surgeons, anesthesiologists, and intensivists to work together, for a fruitful collaboration in a mandatory clinical continuum., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Published
2024
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32. The perioperative period of liver transplantation from unconventional extended criteria donors: data from two high-volume centres.

Author

Pescarissi C, Penzo B, Ghinolfi D, Lai Q, Bindi L, DeCarlis R, Melandro F, Balzano E, DeSimone P, DeCarlis L, DeGasperi A, and Biancofiore GL

Subjects
Aged, 80 and over, Humans, Retrospective Studies, Tissue Donors, Brain Death, Perioperative Period, Liver Transplantation adverse effects
Abstract

Background: As literature largely focuses on long-term outcomes, this study aimed at elucidating the perioperative outcomes of liver transplant patients receiving a graft from two groups of unconventional expanded criteria donors: brain dead aged > 80 years and cardiac dead., Methods: Data of 247 cirrhotic patients transplanted at two high volume liver transplant centers were analysed. Confounders were balanced using a stabilized inverse probability therapy weighting and a propensity score for each patient on the original population was generated. The score was created using a multivariate logistic regression model considering a Comprehensive Complication Index ≥ 42 (no versus yes) as the dependent variable and 11 possible clinically relevant confounders as covariate., Results: Forty-four patients received the graft from a cardiac-dead donor and 203 from a brain-dead donor aged > 80 years. Intraoperatively, cardiac-dead donors liver transplant cases required more fresh frozen plasma units (P < 0.0001) with similar reduced need of fibrinogen to old brain-dead donors cases. The incidence of reperfusion syndrome was similar (P = 0.80). In the Intensive Care Unit, both the groups presented a comparable low need for blood transfusions, renal replacement therapy and inotropes. Cardiac-dead donors liver transplantations required more time to tracheal extubation (P < 0.0001) and scored higher Comprehensive Complication Index (P < 0.0001) however the incidence of a severe complication status (Comprehensive Complication Index  ≥ 42) was similar (P = 0.52). ICU stay (P = 0.97), total hospital stay (P = 0.57), in hospital (P = 1.00) and 6 months (P = 1.00) death were similar., Conclusion: Selected octogenarian and cardiac-dead donors can be used safely for liver transplantation., (© 2022. The Author(s).)

Published
2022
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33. Transarterial Chemoembolization for Hepatocellular Carcinoma in Clinical Practice: Temporal Trends and Survival Outcomes of an Iterative Treatment.

Author

Pelizzaro F, Haxhi S, Penzo B, Vitale A, Giannini EG, Sansone V, Rapaccini GL, Di Marco M, Caturelli E, Magalotti D, Sacco R, Celsa C, Campani C, Mega A, Guarino M, Gasbarrini A, Svegliati-Baroni G, Foschi FG, Olivani A, Masotto A, Nardone G, Raimondo G, Azzaroli F, Vidili G, Brunetto MR, Trevisani F, and Farinati F

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pelizzaro, Haxhi, Penzo, Vitale, Giannini, Sansone, Rapaccini, Di Marco, Caturelli, Magalotti, Sacco, Celsa, Campani, Mega, Guarino, Gasbarrini, Svegliati-Baroni, Foschi, Olivani, Masotto, Nardone, Raimondo, Azzaroli, Vidili, Brunetto, Trevisani and Farinati.)

Published
2022
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34. Hepatocellular Carcinoma in Chronic Viral Hepatitis: Where Do We Stand?

Author

Russo FP, Zanetto A, Pinto E, Battistella S, Penzo B, Burra P, and Farinati F

Subjects
Antiviral Agents therapeutic use, Carcinoma, Hepatocellular diagnostic imaging, Carcinoma, Hepatocellular etiology, Carcinoma, Hepatocellular prevention & control, Hepatitis B, Chronic drug therapy, Hepatitis C, Chronic drug therapy, Hepatitis D, Chronic, Humans, Carcinoma, Hepatocellular physiopathology, Hepatitis B, Chronic complications, Hepatitis C, Chronic complications
Abstract

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death. Although the burden of alcohol- and NASH-related HCC is growing, chronic viral hepatitis (HBV and HCV) remains a major cause of HCC development worldwide. The pathophysiology of viral-related HCC includes liver inflammation, oxidative stress, and deregulation of cell signaling pathways. HBV is particularly oncogenic because, contrary to HCV, integrates in the cell DNA and persists despite virological suppression by nucleotide analogues. Surveillance by six-month ultrasound is recommended in patients with cirrhosis and in "high-risk" patients with chronic HBV infection. Antiviral therapy reduces the risks of development and recurrence of HCC; however, patients with advanced chronic liver disease remain at risk of HCC despite virological suppression/cure and should therefore continue surveillance. Multiple scores have been developed in patients with chronic hepatitis B to predict the risk of HCC development and may be used to stratify individual patient's risk. In patients with HCV-related liver disease who achieve sustained virological response by direct acting antivirals, there is a strong need for markers/scores to predict long-term risk of HCC. In this review, we discuss the most recent advances regarding viral-related HCC.

Published
2022
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35. Circulating MicroRNA-21 and MicroRNA-122 as Prognostic Biomarkers in Hepatocellular Carcinoma Patients Treated with Transarterial Chemoembolization.

Author

Pelizzaro F, Cardin R, Sartori A, Imondi A, Penzo B, Aliberti C, Ponzoni A, Vitale A, Cillo U, and Farinati F

Abstract

Background: MicroRNAs (miRNAs) have been proposed as biomarkers in hepatocellular carcinoma (HCC). We aim at evaluating miR-21 and miR-122 in HCC patients treated with drug-eluting beads transarterial chemoembolization (DEB-TACE) as prognostic biomarkers and investigating their correlation with hypoxia inducible factor-1α (HIF-1α) serum levels., Methods: In this retrospective study, 12 healthy subjects, 28 cirrhotics, and 54 HCC patients (tested before and four weeks after DEB-TACE) were included. Whole blood miR-21 and miR-122 levels were measured by quantitative real time (qRT)-PCR, while serum HIF-1α was assessed by an enzyme-linked immunosorbent assay (ELISA) test., Results: The highest level of miR-21 was found in cirrhotics, while HCC patients had the highest level of miR-122 (which was even higher in "viral" HCC, p = 0.006). miR-21 ratio (after/before DEB-TACE) and miR-122 below their respective cut-offs identified patients with longer progression-free survival ( p = 0.0002 and p = 0.02, respectively). The combined assessment of alpha-fetoprotein and miR-21 ratio, both independent prognostic predictors, identified early progressors among patients with complete or partial radiological response. miR-21 levels positively correlated with HIF-1α before ( p = 0.045) and after DEB-TACE ( p = 0.035)., Conclusions: miR-21 ratio and miR-122 are useful prognostic markers after DEB-TACE. miR-21 correlates with HIF-1α and probably has a role in modulating angiogenesis in HCC.

Published
2021
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36. Liquid Biopsy in Hepatocellular Carcinoma: Where Are We Now?

Author

Pelizzaro F, Cardin R, Penzo B, Pinto E, Vitale A, Cillo U, Russo FP, and Farinati F

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related death worldwide. Diagnostic, prognostic, and predictive biomarkers are urgently needed in order to improve patient survival. Indeed, the most widely used biomarkers, such as alpha-fetoprotein (AFP), have limited accuracy as both diagnostic and prognostic tests. Liver biopsy provides an insight on the biology of the tumor, but it is an invasive procedure, not routinely used, and not representative of the whole neoplasia due to the demonstrated intra-tumoral heterogeneity. In recent years, liquid biopsy, defined as the molecular analysis of cancer by-products, released by the tumor in the bloodstream, emerged as an appealing source of new biomarkers. Several studies focused on evaluating extracellular vesicles, circulating tumor cells, cell-free DNA and non-coding RNA as novel reliable biomarkers. In this review, we aimed to provide a comprehensive overview on the most relevant available evidence on novel circulating biomarkers for early diagnosis, prognostic stratification, and therapeutic monitoring. Liquid biopsy seems to be a very promising instrument and, in the near future, some of these new non-invasive tools will probably change the clinical management of HCC patients.

Published
2021
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38. Surveillance as Determinant of Long-Term Survival in Non-Transplanted Hepatocellular Carcinoma Patients.

Author

Pelizzaro F, Vitale A, Sartori A, Vieno A, Penzo B, Russo FP, Frigo AC, Giannini EG, Piccinnu M, Rapaccini GL, Di Marco M, Caturelli E, Zoli M, Sacco R, Celsa C, Marra F, Mega A, Guarino M, Gasbarrini A, Svegliati-Baroni G, Foschi FG, Olivani A, Masotto A, Coccoli P, Raimondo G, Azzaroli F, Vidili G, Brunetto MR, Trevisani F, Farinati F, and On Behalf Of Ita Li Ca Study Group

Abstract

Purpose: We aimed at assessing the impact of surveillance on long-term survival in HCC patients., Methods: From the ITA.LI.CA database, we selected 1028 cases with long (≥5 years, LS group) and 2721 controls with short-term survival (<5 years, SS group). The association between surveillance and LS was adjusted for confounders by multivariable logistic regression analysis. Survival of surveilled patients was presented both as observed and corrected for the lead-time bias, and the comparison of survival between surveillance and no surveillance groups was also performed after balancing the baseline characteristics with inverse probability weights (IPW)., Results: LS patients were more frequently diagnosed under surveillance ( p < 0.0001), and had more favorable baseline characteristics. Surveillance was an independent predictor of LS (OR = 1.413, 95% CI 1.195-1.671; p < 0.0001). The observed and the lead-time corrected survival of surveilled patients were significantly longer compared to the survival of not surveilled patients ( p < 0.0001 and p = 0.0008, respectively). In IPW adjusted populations, no survival differences were demonstrated between the two groups ( p = 0.30)., Conclusions: Surveillance, increasing early-stage diagnosis and applicability of curative treatments, is a fundamental determinant of long-term survival in HCC patients. A wide implementation of surveillance programs should be pursued in order to improve HCC patients' prognosis.

Published
2021
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39. Monofocal hepatocellular carcinoma: How much does size matter?

Author

Pelizzaro F, Penzo B, Peserico G, Imondi A, Sartori A, Vitale A, Cillo U, Giannini EG, 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, and Farinati F

Subjects
Hepatectomy, Humans, Italy, Neoplasm Staging, Retrospective Studies, Carcinoma, Hepatocellular pathology, Liver Neoplasms pathology
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 (>5 cm) monofocal (HCC)., Methods: From the Italian Liver Cancer database, we selected 924 patients with small early monofocal HCC (2-5 cm; SEM-HCC), 163 patients with larger tumours (>5 cm; 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 49.0 months; P < .0001), and this was confirmed at multivariate analysis (HR 1.63, 95% CI 1.29-2.05; P < .0001). The small difference in OS between LEM-HCC and BCLC B patients (31.0 vs 27.0 months; P = .03) disappeared in the multivariate model (HR 0.98, 95% CI 0.77-1.25; P = .89). In all monofocal tumours, treatment was the strongest independent predictor of survival, with a progressively decreasing survival benefit moving from "curative" to "palliative" therapies. The survival of resected patients with LEM-HCC was significantly shorter than that of SEM-HCC (44.0 vs 78.0 months; P = .002), but liver resection provided the highest survival benefit in both groups compared to other treatments., Conclusions: Monofocal HCC larger than 5 cm should not be staged as BCLC A and either a different staging system or a different subgrouping of patients (e.g. BCLC AB) should be used. Liver resection, if feasible, remains the recommended treatment for all these patients., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Published
2021
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40. SCCA-IgM in hepatocellular carcinoma patients treated with transarterial chemoembolization: gender-related differences.

Author

Pelizzaro F, Soldà F, Cardin R, Imondi A, Sartori A, Penzo B, Sammarco A, Aliberti C, Vitale A, Cillo U, and Farinati F

Abstract

Aim: Squamous cell carcinoma antigen immune complexed with immunoglobulin M (SCCA-IgM) is a useful but not completely satisfactory biomarker of hepatocellular carcinoma (HCC). Considering its gender-specific behavior in preclinical models, we investigated gender-related differences of SCCA-IgM as a prognostic marker in HCC. Patients & methods: Two hundred and eight prospectively recruited patients treated with transarterial chemoembolization in a single tertiary care hospital were retrospectively evaluated. Correlations between SCCA-IgM levels, clinical characteristics and survival were assessed according to gender. Results: When the disease was advanced, SCCA-IgM was higher in males and lower in females. Levels below 130 AU/ml predicted a significantly longer survival in males (p = 0.007) and a shorter survival in females (p = 0.01). Conclusion: In predicting the prognosis of HCC patients, the interpretation of SCCA-IgM should consider gender as a relevant variable.

Published
2020
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