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2. Waiting list mortality and 5-year transplant survival benefit of patients with MASLD: An Italian liver transplant registry study

Author

Vitale, A, Trapani, S, Russo, F, Miele, L, Svegliati Baroni, G, Marchesini, G, Burra, P, Ottoveggio, M, Romagnoli, R, Martini, S, De Simone, P, Carrai, P, Cescon, M, Morelli, M, De Carlis, L, Belli, L, Gruttadauria, S, Volpes, R, Colledan, M, Fagiuoli, S, Di Benedetto, F, De Maria, N, Rossi, G, Caccamo, L, Donato, F, Vennarecci, G, Di Costanzo, G, Vivarelli, M, Carraro, A, Sacerdoti, D, Ettorre, G, Giannelli, V, Agnes, S, Gasbarrini, A, Rossi, M, Ginanni Corradini, S, Mazzaferro, V, Bhoori, S, Manzia, T, Lenci, I, Zamboni, F, Mameli, L, Baccarani, U, Toniutto, P, Lupo, L, Tandoi, F, Rendina, M, Andorno, E, Giannini, E, Spada, M, Billato, I, Marchini, A, Romano, P, Brancaccio, G, D'Amico, F, Ricci, A, Cardillo, M, Cillo, U, Vitale A., Trapani S., Russo F. P., Miele L., Svegliati Baroni G., Marchesini G., Burra P., Ottoveggio M. S., Romagnoli R., Martini S., De Simone P., Carrai P., Cescon M., Morelli M. C., De Carlis L., Belli L., Gruttadauria S., Volpes R., Colledan M., Fagiuoli S., Di Benedetto F., De Maria N., Rossi G., Caccamo L., Donato F., Vennarecci G., Di Costanzo G. G., Vivarelli M., Carraro A., Sacerdoti D., Ettorre G. M., Giannelli V., Agnes S., Gasbarrini A., Rossi M., Ginanni Corradini S., Mazzaferro V., Bhoori S., Manzia T. M., Lenci I., Zamboni F., Mameli L., Baccarani U., Toniutto P., Lupo L. G., Tandoi F., Rendina M., Andorno E., Giannini E. G., Spada M., Billato I., Marchini A., Romano P., Brancaccio G., D'Amico F., Ricci A., Cardillo M., Cillo U., Vitale, A, Trapani, S, Russo, F, Miele, L, Svegliati Baroni, G, Marchesini, G, Burra, P, Ottoveggio, M, Romagnoli, R, Martini, S, De Simone, P, Carrai, P, Cescon, M, Morelli, M, De Carlis, L, Belli, L, Gruttadauria, S, Volpes, R, Colledan, M, Fagiuoli, S, Di Benedetto, F, De Maria, N, Rossi, G, Caccamo, L, Donato, F, Vennarecci, G, Di Costanzo, G, Vivarelli, M, Carraro, A, Sacerdoti, D, Ettorre, G, Giannelli, V, Agnes, S, Gasbarrini, A, Rossi, M, Ginanni Corradini, S, Mazzaferro, V, Bhoori, S, Manzia, T, Lenci, I, Zamboni, F, Mameli, L, Baccarani, U, Toniutto, P, Lupo, L, Tandoi, F, Rendina, M, Andorno, E, Giannini, E, Spada, M, Billato, I, Marchini, A, Romano, P, Brancaccio, G, D'Amico, F, Ricci, A, Cardillo, M, Cillo, U, Vitale A., Trapani S., Russo F. P., Miele L., Svegliati Baroni G., Marchesini G., Burra P., Ottoveggio M. S., Romagnoli R., Martini S., De Simone P., Carrai P., Cescon M., Morelli M. C., De Carlis L., Belli L., Gruttadauria S., Volpes R., Colledan M., Fagiuoli S., Di Benedetto F., De Maria N., Rossi G., Caccamo L., Donato F., Vennarecci G., Di Costanzo G. G., Vivarelli M., Carraro A., Sacerdoti D., Ettorre G. M., Giannelli V., Agnes S., Gasbarrini A., Rossi M., Ginanni Corradini S., Mazzaferro V., Bhoori S., Manzia T. M., Lenci I., Zamboni F., Mameli L., Baccarani U., Toniutto P., Lupo L. G., Tandoi F., Rendina M., Andorno E., Giannini E. G., Spada M., Billato I., Marchini A., Romano P., Brancaccio G., D'Amico F., Ricci A., Cardillo M., and Cillo U.

Abstract

Background & Aims: International consensus has recently introduced a new definition of metabolic dysfunction-associated steatotic liver disease (MASLD). We sought to analyse epidemiological trends, prognostic features, and transplant survival benefits of patients with MASLD and without MASLD waiting for liver transplantation (LT) in Italy. Methods: Using the Italian Liver Transplant Registry database, we analysed data from adult patients listed for primary LT attributable to end-stage chronic liver disease between January 2012 and December 2022. Independent multivariable waiting lists and post-transplant survival models were developed for patients with and without hepatocellular carcinoma (HCC). A Monte Carlo simulation was used to create 5-year transplant benefit distributions based on the presence of MASLD, HCC, and model for end-stage liver disease (MELD)-sodium values. Results: A total sample of 1,941 patients with MASLD and 11,201 patients without MASLD was considered. A significant increase in the prevalence of MASLD as an indication for LT was observed from 2012 to 2022, for both cohorts with HCC (from 17.7 to 30%) and without HCC (from 9.5 to 11.8%) cohorts. Projections suggest that, as early as next year, MASLD will overcome HCV as the second most common indication for transplantation after alcoholic liver disease in Italy. According to univariate and multivariate analyses, MASLD was not an independent predictive factor for patient survival after transplantation. However, it increased the risk of death for patients on the waiting list without HCC (hazard ratio 1.62, p <0.001). At the same MELD-sodium, the 5-year transplant benefit was higher in patients with non-HCC MASLD, followed by patients with HCC, whereas it was lower in patients without HCC and without MASLD. Conclusions: Patients with non-HCC MASLD had an increased waitlist mortality and 5-year transplant survival benefit compared with other candidates. Impact and implications: The present re

Published
2024

3. Single large hepatocellular carcinoma > 5 cm with surgical indication: is it mandatory a major hepatectomy? a propensity-score weighted analysis

Author

Garancini, M, Serenari, M, Famularo, S, Cipriani, F, Ardito, F, Russolillo, N, Conci, S, Nicolini, D, Perri, P, Zanello, M, Iaria, M, Lai, Q, Romano, M, La Barba, G, Molfino, S, Germani, P, Dominioni, T, Zimmiti, G, Conticchio, M, Fumagalli, L, Zago, M, Troci, A, Sciannamea, I, Ferrari, C, Scotti, M, Griseri, G, Antonucci, A, Crespi, M, Pinotti, E, Chiarelli, M, Memeo, R, Hilal, M, Maestri, M, Tarchi, P, Baiocchi, G, Ercolani, G, Zanus, G, Rossi, M, Valle, R, Jovine, E, Frena, A, Patauner, S, Grazi, G, Vivarelli, M, Ruzzenente, A, Ferrero, A, Giuliante, F, Aldrighetti, L, Torzilli, G, Cescon, M, Bernasconi, D, Romano, F, Milana, F, Bertacco, A, Ratti, F, Razionale, F, Cicerone, O, Fazio, F, Ciulli, C, Carissimi, F, Laureiro, Z, Marinelli, L, De Peppo, V, Montuori, M, Marchitelli, I, Franceschi, A, Manzoni, A, Cosola, D, Corleone, P, Salvador, L, Cucchetti, A, Pennacchi, L, Giuffrida, M, Fugazzola, P, Casella, A, Calcagno, P, Garancini M., Serenari M., Famularo S., Cipriani F., Ardito F., Russolillo N., Conci S., Nicolini D., Perri P., Zanello M., Iaria M., Lai Q., Romano M., La Barba G., Molfino S., Germani P., Dominioni T., Zimmiti G., Conticchio M., Fumagalli L., Zago M., Troci A., Sciannamea I., Ferrari C., Scotti M. A., Griseri G., Antonucci A., Crespi M., Pinotti E., Chiarelli M., Memeo R., Hilal M. A., Maestri M., Tarchi P., Baiocchi G., Ercolani G., Zanus G., Rossi M., Valle R. D., Jovine E., Frena A., Patauner S., Grazi G. L., Vivarelli M., Ruzzenente A., Ferrero A., Giuliante F., Aldrighetti L., Torzilli G., Cescon M., Bernasconi D., Romano F., Milana F., Bertacco A., Ratti F., Razionale F., Cicerone O., Fazio F., Ciulli C., Carissimi F., Laureiro Z. L., Marinelli L., De Peppo V., Montuori M., Marchitelli I., Franceschi A., Manzoni A., Cosola D., Corleone P., Salvador L., Cucchetti A., Pennacchi L., Giuffrida M., Fugazzola P., Casella A., Calcagno P., Garancini, M, Serenari, M, Famularo, S, Cipriani, F, Ardito, F, Russolillo, N, Conci, S, Nicolini, D, Perri, P, Zanello, M, Iaria, M, Lai, Q, Romano, M, La Barba, G, Molfino, S, Germani, P, Dominioni, T, Zimmiti, G, Conticchio, M, Fumagalli, L, Zago, M, Troci, A, Sciannamea, I, Ferrari, C, Scotti, M, Griseri, G, Antonucci, A, Crespi, M, Pinotti, E, Chiarelli, M, Memeo, R, Hilal, M, Maestri, M, Tarchi, P, Baiocchi, G, Ercolani, G, Zanus, G, Rossi, M, Valle, R, Jovine, E, Frena, A, Patauner, S, Grazi, G, Vivarelli, M, Ruzzenente, A, Ferrero, A, Giuliante, F, Aldrighetti, L, Torzilli, G, Cescon, M, Bernasconi, D, Romano, F, Milana, F, Bertacco, A, Ratti, F, Razionale, F, Cicerone, O, Fazio, F, Ciulli, C, Carissimi, F, Laureiro, Z, Marinelli, L, De Peppo, V, Montuori, M, Marchitelli, I, Franceschi, A, Manzoni, A, Cosola, D, Corleone, P, Salvador, L, Cucchetti, A, Pennacchi, L, Giuffrida, M, Fugazzola, P, Casella, A, Calcagno, P, Garancini M., Serenari M., Famularo S., Cipriani F., Ardito F., Russolillo N., Conci S., Nicolini D., Perri P., Zanello M., Iaria M., Lai Q., Romano M., La Barba G., Molfino S., Germani P., Dominioni T., Zimmiti G., Conticchio M., Fumagalli L., Zago M., Troci A., Sciannamea I., Ferrari C., Scotti M. A., Griseri G., Antonucci A., Crespi M., Pinotti E., Chiarelli M., Memeo R., Hilal M. A., Maestri M., Tarchi P., Baiocchi G., Ercolani G., Zanus G., Rossi M., Valle R. D., Jovine E., Frena A., Patauner S., Grazi G. L., Vivarelli M., Ruzzenente A., Ferrero A., Giuliante F., Aldrighetti L., Torzilli G., Cescon M., Bernasconi D., Romano F., Milana F., Bertacco A., Ratti F., Razionale F., Cicerone O., Fazio F., Ciulli C., Carissimi F., Laureiro Z. L., Marinelli L., De Peppo V., Montuori M., Marchitelli I., Franceschi A., Manzoni A., Cosola D., Corleone P., Salvador L., Cucchetti A., Pennacchi L., Giuffrida M., Fugazzola P., Casella A., and Calcagno P.

Abstract

Purpose: Single large hepatocellular carcinoma >5cm (SLHCC) traditionally requires a major liver resection. Minor resections are often performed with the goal to reduce morbidity and mortality. Aim of the study was to establish if a major resection should be considered the best treatment for SLHCC or a more limited resection should be preferred. Methods: A multicenter retrospective analysis of the HE.RC.O.LE.S. Group register was performed. All collected patients with surgically treated SLHCC were divided in 5 groups of treatment (major hepatectomy, sectorectomy, left lateral sectionectomy, segmentectomy, non-anatomical resection) and compared for baseline characteristics, short and long-term results. A propensity-score weighted analysis was performed. Results: 535 patients were enrolled in the study. Major resection was associated with significantly increased major complications compared to left lateral sectionanectomy, segmentectomy and non-anatomical resection (all p<0.05) and borderline significant increased major complications compared to sectorectomy (p=0.08). Left lateral sectionectomy showed better overall survival compared to major resection (p=0.02), while other groups of treatment resulted similar to major hepatectomy group for the same item. Absence of oncological benefit after major resection and similar outcomes among the 5 groups of treatment was confirmed even in the sub-population excluding patients with macrovascular invasion. Conclusion: Major resection was associated to increased major post-operative morbidity without long-term survival benefit; when technically feasible and oncologically adequate, minor resections should be preferred for the surgical treatment of SLHCC.

Published
2024

5. Innovation and the labor market: theory, evidence, and challenges

Author

Corrocher, N, Moschella, D, Staccioli, Jacopo, Vivarelli, Marco, Staccioli, J (ORCID:0000-0002-9068-2927), Vivarelli, M (ORCID:0000-0002-8746-9324), Corrocher, N, Moschella, D, Staccioli, Jacopo, Vivarelli, Marco, Staccioli, J (ORCID:0000-0002-9068-2927), and Vivarelli, M (ORCID:0000-0002-8746-9324)

Abstract

This paper deals with the complex relationship between innovation and the labor market, analyzing the impact of new technological advancements on overall employment, skills, and wages. After a critical review of the extant literature and the available empirical studies, novel evidence is presented on the distribution of labor-saving automation [namely robotics and artificial intelligence (AI)], based on natural language processing of US patents. This mapping shows that both upstream high-tech providers and downstream users of new technologies-such as Boeing and Amazon-lead the underlying innovative effort.

Published
2024

6. Was Robert Gibrat right? A test based on the graphical model methodology

Author

Guerzoni, M, Riso, L, Vivarelli, M, Guerzoni, M, Riso, L, and Vivarelli, M

Abstract

Using both regression analysis and an unsupervised graphical model approach (never applied before to this issue), we confirm the rejection of Gibrat’s Law (stating that a firm’s growth is independent of that firm’s initial size) when our firm-level data are considered over the entire investigated period, while the opposite is true when we allow for market selection; indeed, the growth behavior of the surviving most efficient firms is in line with Gibrat’s Law. This evidence reconciles early and current literature and may have interesting implications in terms of both theoretical research and policy suggestions regarding subsidies to small firms, which do not necessarily grow faster than their larger counterparts.

Published
2024

7. Portal vein thrombosis and liver transplantation: management, matching, and outcomes: a retrospective multicenter cohort study

Author

Di Benedetto, F, Magistri, P, Di Sandro, S, Boetto, R, Tandoi, F, Camagni, S, Lauterio, A, Pagano, D, Nicolini, D, Violi, P, Dondossola, D, Guglielmo, N, Cherchi, V, Lai, Q, Toti, L, Bongini, M, Frassoni, S, Bagnardi, V, Mazzaferro, V, Tisone, G, Rossi, M, Baccarani, U, Ettorre, G, Caccamo, L, Carraro, A, Vivarelli, M, Gruttadauria, S, De Carlis, L, Colledan, M, Romagnoli, R, Cillo, U, Di Benedetto, Fabrizio, Magistri, Paolo, Di Sandro, Stefano, Boetto, Riccardo, Tandoi, Francesco, Camagni, Stefania, Lauterio, Andrea, Pagano, Duilio, Nicolini, Daniele, Violi, Paola, Dondossola, Daniele, Guglielmo, Nicola, Cherchi, Vittorio, Lai, Quirino, Toti, Luca, Bongini, Marco, Frassoni, Samuele, Bagnardi, Vincenzo, Mazzaferro, Vincenzo, Tisone, Giuseppe, Rossi, Massimo, Baccarani, Umberto, Ettorre, Giuseppe Maria, Caccamo, Lucio, Carraro, Amedeo, Vivarelli, Marco, Gruttadauria, Salvatore, De Carlis, Luciano, Colledan, Michele, Romagnoli, Renato, Cillo, Umberto, Di Benedetto, F, Magistri, P, Di Sandro, S, Boetto, R, Tandoi, F, Camagni, S, Lauterio, A, Pagano, D, Nicolini, D, Violi, P, Dondossola, D, Guglielmo, N, Cherchi, V, Lai, Q, Toti, L, Bongini, M, Frassoni, S, Bagnardi, V, Mazzaferro, V, Tisone, G, Rossi, M, Baccarani, U, Ettorre, G, Caccamo, L, Carraro, A, Vivarelli, M, Gruttadauria, S, De Carlis, L, Colledan, M, Romagnoli, R, Cillo, U, Di Benedetto, Fabrizio, Magistri, Paolo, Di Sandro, Stefano, Boetto, Riccardo, Tandoi, Francesco, Camagni, Stefania, Lauterio, Andrea, Pagano, Duilio, Nicolini, Daniele, Violi, Paola, Dondossola, Daniele, Guglielmo, Nicola, Cherchi, Vittorio, Lai, Quirino, Toti, Luca, Bongini, Marco, Frassoni, Samuele, Bagnardi, Vincenzo, Mazzaferro, Vincenzo, Tisone, Giuseppe, Rossi, Massimo, Baccarani, Umberto, Ettorre, Giuseppe Maria, Caccamo, Lucio, Carraro, Amedeo, Vivarelli, Marco, Gruttadauria, Salvatore, De Carlis, Luciano, Colledan, Michele, Romagnoli, Renato, and Cillo, Umberto

Abstract

BACKGROUND AND AIMS: Besides the increased risk of perioperative morbidity, graft failure, and mortality, the majority of PVT are diagnosed at liver transplantation (LT). Improving preoperative management and patient selection may lead to better short-term and long-term outcomes and reduce the risk of a futile LT. The authors aimed to identify predictors of adverse outcomes after LT in patients with nonmalignant portal vein thrombosis (PVT) and improve donor to recipient matching by analyzing the results of the Italian cohort of LT recipients. METHODS: Adult patients who underwent LT in Italy between January 2000 and February 2020 diagnosed with PVT pre-LT or at time of LT were considered eligible for inclusion. Based on a survey encompassing all 26 surgeons participating in the study, a binary composite outcome was defined. Patients were classified as having the composite event if at least one of these conditions occurred: operative time more than 600 min, estimated blood loss greater than 5000 ml, more than 20 ICU days, 90 days mortality, 90 days retransplant. RESULTS: Seven hundred fourteen patients were screened and 698 met the inclusion criteria. The analysis reports the results of 568 patients that fulfilled the criteria to enter the composite outcome analysis.Overall, 156 patients (27.5%) developed the composite outcome. PVT stage 3/4 at transplant and need for any surgical correction of PVT are independent predictors of the composite outcome occurrence. When stratified by PVT grade, overall survival at 1-year ranges from 89.0% with PVT grade 0/1 to 67.4% in patients with PVT grade 3/4 at LT ( P <0.001). Nevertheless, patients with severe PVT can improve their survival when identified risk factors are not present. CONCLUSIONS: Potential LT candidates affected by PVT have a benefit from LT that should be adequately balanced on liver function and type of inflow reconstruction needed to mitigate the incidence of adverse events. Nonetheless, the absence of spe

Published
2024

8. Was Robert Gibrat right? A test based on the graphical model methodology

Author

Guerzoni, M., Riso, Luigi, Vivarelli, Marco, Riso L. (ORCID:0000-0001-9858-7353), Vivarelli M. (ORCID:0000-0002-8746-9324), Guerzoni, M., Riso, Luigi, Vivarelli, Marco, Riso L. (ORCID:0000-0001-9858-7353), and Vivarelli M. (ORCID:0000-0002-8746-9324)

Abstract

Using both regression analysis and an unsupervised graphical model approach (never applied before to this issue), we confirm the rejection of Gibrat's Law (stating that a firm's growth is independent of that firm's initial size) when our firm-level data are considered over the entire investigated period, while the opposite is true when we allow for market selection; indeed, the growth behavior of the surviving most efficient firms is in line with Gibrat's Law. This evidence reconciles early and current literature and may have interesting implications in terms of both theoretical research and policy suggestions regarding subsidies to small firms, which do not necessarily grow faster than their larger counterparts.Challenging Gibrat's Law, this study reveals that small Italian firms initially outpace larger ones in growth, but selection evens the field over time; this evidence calls for smarter and targeted policies. Indeed, our analysis challenges the widely accepted result that small firms grow faster than their larger counterparts, thus rejecting Gibrat's Law stating that a firm's growth is independent of that firm's initial size. Using a unique combination of regression analysis and innovative graphical models, we tracked newly founded Italian manufacturing firms over 11 years. We discovered that initially, smaller firms grow faster, rejecting Gibrat's Law. However, over time, as less efficient firms exit the market, the surviving, more efficient firms display growth patterns consistent with Gibrat's Law. This finding bridges the gap between previous and recent studies on firm growth. The study's key implication is for policy makers: support for young and small firms is crucial, but policy focus should shift to ensuring markets function efficiently, and aiding the most promising businesses. This approach could foster a more dynamic and robust economic environment, benefiting society by promoting sustainable business growth and stability.

Published
2024

10. C5 Convertase Blockade in Membranoproliferative Glomerulonephritis: A Single-Arm Clinical Trial

Author

Remuzzi, G., Ruggenenti, P., Mondo, E., Rota, S., Carrara, C., Portalupi, V., Pasini, A., Monitini, G., Monti, E., Rigotti, A., De Giovanni, F., Giacon, B., Lerchner, R.M., Passler, W., Santoro, D., Visconti, L., Pisani, A., Riccio, E., Pasi, A., Dugo, M., Tuono, C., Emma, F., Vivarelli, M., Murer, L., Benetti, E., Coppo, R., Amore, A., Gambaro, G., Passalacqua, S., Ruggiero, B., Daina, E., Bresin, E., Gamba, S., Prandini, S., Lecchi, V., Cugini, D., Gherardi, G., Rubis, N., Diadei, O., Villa, A., Villa, D., Boccardo, P., Peracchi, S., Martinetti, D., Perna, A., Peraro, F., Giuliano, G.A., Gaspari, F., Carrara, F., Ferrari, S., Stucchi, N., Cannata, A., Noris, M., Bettoni, S., Alberti, M., Cuccarolo, P., Rizzo, P., Marchetti, G.F., Sonzogni, A., Ruggenenti, Piero, Daina, Erica, Gennarini, Alessia, Carrara, Camillo, Gamba, Sara, Noris, Marina, Rubis, Nadia, Peraro, Francesco, Gaspari, Flavio, Pasini, Andrea, Rigotti, Angelo, Lerchner, Renelda M., Santoro, Domenico, Pisani, Antonio, Pasi, Alessandra, and Remuzzi, Giuseppe

Published
2019
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11. Correction to: Improving clinical paediatric research and learning from COVID-19: recommendations by the Conect4Children expert advice group (Pediatric Research, (2022), 91, 5, (1069-1077), 10.1038/s41390-021-01587-3)

Author

Ramanan A. V., Ramanan, A, Modi, N, de Wildt, S, Aurich, B, Bakhtadze, S, Sirvent, F, Cabanas, F, Campbell, L, Casanova, M, Charlton, P, Crandall, W, Eichler, I, Fregonese, L, Hawcutt, D, Iveli, P, Jaki, T, Jocic-Jakubi, B, Johnson, M, Kaguelidou, F, Karadag, B, Kelly, L, Lim, M, Moreno, C, Neumann, E, Ollivier, C, Oualha, M, Raffaeli, G, Ribeiro, M, Roilides, E, de Rojas, T, Simon, A, Ruperto, N, Scarpa, M, Schwab, M, Siapkara, A, Singh, Y, Smits, A, Striano, P, Urru, S, Vivarelli, M, Zivkoviz, Z, Ramanan A. V., Modi N., de Wildt S. N., Aurich B., Bakhtadze S., Sirvent F. J. B., Cabanas F., Campbell L., Casanova M., Charlton P., Crandall W., Eichler I., Fregonese L., Hawcutt D. B., Iveli P., Jaki T., Jocic-Jakubi B., Johnson M., Kaguelidou F., Karadag B., Kelly L. E., Lim M., Moreno C., Neumann E., Ollivier C., Oualha M., Raffaeli G., Ribeiro M. A., Roilides E., de Rojas T., Simon A. R. S., Ruperto N., Scarpa M., Schwab M., Siapkara A., Singh Y., Smits A., Striano P., Urru S. A. M., Vivarelli M., Zivkoviz Z., Ramanan A. V., Ramanan, A, Modi, N, de Wildt, S, Aurich, B, Bakhtadze, S, Sirvent, F, Cabanas, F, Campbell, L, Casanova, M, Charlton, P, Crandall, W, Eichler, I, Fregonese, L, Hawcutt, D, Iveli, P, Jaki, T, Jocic-Jakubi, B, Johnson, M, Kaguelidou, F, Karadag, B, Kelly, L, Lim, M, Moreno, C, Neumann, E, Ollivier, C, Oualha, M, Raffaeli, G, Ribeiro, M, Roilides, E, de Rojas, T, Simon, A, Ruperto, N, Scarpa, M, Schwab, M, Siapkara, A, Singh, Y, Smits, A, Striano, P, Urru, S, Vivarelli, M, Zivkoviz, Z, Ramanan A. V., Modi N., de Wildt S. N., Aurich B., Bakhtadze S., Sirvent F. J. B., Cabanas F., Campbell L., Casanova M., Charlton P., Crandall W., Eichler I., Fregonese L., Hawcutt D. B., Iveli P., Jaki T., Jocic-Jakubi B., Johnson M., Kaguelidou F., Karadag B., Kelly L. E., Lim M., Moreno C., Neumann E., Ollivier C., Oualha M., Raffaeli G., Ribeiro M. A., Roilides E., de Rojas T., Simon A. R. S., Ruperto N., Scarpa M., Schwab M., Siapkara A., Singh Y., Smits A., Striano P., Urru S. A. M., Vivarelli M., and Zivkoviz Z.

Abstract

Correction to: Pediatric Research (2021) 91:1069–1077; The following publication disclaimer was added to the article: “The publication reflects the author’s view and neither IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information contained therein.” The original article has been corrected.

Published
2023

12. The Effect of a Liver Transplant Program on the Outcomes of Resectable Hepatocellular Carcinoma: A Nationwide Multicenter Analysis

Author

Serenari, M, Lenzi, J, Cucchetti, A, Cipriani, F, Donadon, M, Ardito, F, Fazio, F, Nicolini, D, Iaria, M, Famularo, S, Perri, P, Ansaloni, L, Zanello, M, Lai, Q, Conci, S, Molfino, S, Ferrari, C, Germani, P, Zago, M, Romano, M, Zimmitti, G, Antonucci, A, Fumagalli, L, Troci, A, Ferraro, V, Memeo, R, Crespi, M, Chiarelli, M, Ercolani, G, Hilal, M, Zanus, G, Pinotti, E, Tarchi, P, Griseri, G, Baiocchi, G, Ruzzenente, A, Rossi, M, Jovine, E, Maestri, M, Grazi, G, Romano, F, Dalla Valle, R, Ravaioli, M, Vivarelli, M, Ferrero, A, Giuliante, F, Torzilli, G, Aldrighetti, L, Cescon, M, Gorgone, M, Ratti, F, Costa, G, Razionale, F, Russolillo, N, Marinelli, L, Giuffrida, M, Scotti, M, Garancini, M, De Peppo, V, De Stefano, F, Laureiro, Z, Marchitelli, I, Franceschi, A, Cosola, D, Corleone, P, Montuori, M, Salvador, L, Manzoni, A, La Barba, G, Calcagno, P, Pennacchi, L, Conticchio, M, Serenari M., Lenzi J., Cucchetti A., Cipriani F., Donadon M., Ardito F., Fazio F., Nicolini D., Iaria M., Famularo S., Perri P., Ansaloni L., Zanello M., Lai Q., Conci S., Molfino S., Ferrari C., Germani P., Zago M., Romano M., Zimmitti G., Antonucci A., Fumagalli L., Troci A., Ferraro V., Memeo R., Crespi M., Chiarelli M., Ercolani G., Hilal M. A., Zanus G., Pinotti E., Tarchi P., Griseri G., Baiocchi G. L., Ruzzenente A., Rossi M., Jovine E., Maestri M., Grazi G. L., Romano F., Dalla Valle R., Ravaioli M., Vivarelli M., Ferrero A., Giuliante F., Torzilli G., Aldrighetti L., Cescon M., Gorgone M., Ratti F., Costa G., Razionale F., Russolillo N., Marinelli L., Giuffrida M., Scotti M., Garancini M., De Peppo V., De Stefano F., Laureiro Z. L., Marchitelli I., Franceschi A., Cosola D., Corleone P., Montuori M., Salvador L., Manzoni A., La Barba G., Calcagno P., Pennacchi L., Conticchio M., Serenari, M, Lenzi, J, Cucchetti, A, Cipriani, F, Donadon, M, Ardito, F, Fazio, F, Nicolini, D, Iaria, M, Famularo, S, Perri, P, Ansaloni, L, Zanello, M, Lai, Q, Conci, S, Molfino, S, Ferrari, C, Germani, P, Zago, M, Romano, M, Zimmitti, G, Antonucci, A, Fumagalli, L, Troci, A, Ferraro, V, Memeo, R, Crespi, M, Chiarelli, M, Ercolani, G, Hilal, M, Zanus, G, Pinotti, E, Tarchi, P, Griseri, G, Baiocchi, G, Ruzzenente, A, Rossi, M, Jovine, E, Maestri, M, Grazi, G, Romano, F, Dalla Valle, R, Ravaioli, M, Vivarelli, M, Ferrero, A, Giuliante, F, Torzilli, G, Aldrighetti, L, Cescon, M, Gorgone, M, Ratti, F, Costa, G, Razionale, F, Russolillo, N, Marinelli, L, Giuffrida, M, Scotti, M, Garancini, M, De Peppo, V, De Stefano, F, Laureiro, Z, Marchitelli, I, Franceschi, A, Cosola, D, Corleone, P, Montuori, M, Salvador, L, Manzoni, A, La Barba, G, Calcagno, P, Pennacchi, L, Conticchio, M, Serenari M., Lenzi J., Cucchetti A., Cipriani F., Donadon M., Ardito F., Fazio F., Nicolini D., Iaria M., Famularo S., Perri P., Ansaloni L., Zanello M., Lai Q., Conci S., Molfino S., Ferrari C., Germani P., Zago M., Romano M., Zimmitti G., Antonucci A., Fumagalli L., Troci A., Ferraro V., Memeo R., Crespi M., Chiarelli M., Ercolani G., Hilal M. A., Zanus G., Pinotti E., Tarchi P., Griseri G., Baiocchi G. L., Ruzzenente A., Rossi M., Jovine E., Maestri M., Grazi G. L., Romano F., Dalla Valle R., Ravaioli M., Vivarelli M., Ferrero A., Giuliante F., Torzilli G., Aldrighetti L., Cescon M., Gorgone M., Ratti F., Costa G., Razionale F., Russolillo N., Marinelli L., Giuffrida M., Scotti M., Garancini M., De Peppo V., De Stefano F., Laureiro Z. L., Marchitelli I., Franceschi A., Cosola D., Corleone P., Montuori M., Salvador L., Manzoni A., La Barba G., Calcagno P., Pennacchi L., and Conticchio M.

Abstract

Objective: To evaluate the effect of a liver transplantation (LT) program on the outcomes of resectable hepatocellular carcinoma (HCC). Background: Surgical treatment of HCC includes both hepatic resection (HR) and LT. However, the presence of cirrhosis and the possibility of recurrence make the management of this disease complex and probably different according to the presence of a LT program. Methods: Patients undergoing HR for HCC between January 2005 and December 2019 were identified from a national database of HCC. The main study outcomes were major surgical complications according to the Comprehensive Complication Index, posthepatectomy liver failure (PHLF), 90-day mortality, overall survival, and disease-free survival. Secondary outcomes were salvage liver transplantation (SLT) and postrecurrence survival. Results: A total of 3202 patients were included from 25 hospitals over the study period. Three of 25 (12%) had an LT program. The presence of an LT program within a center was associated with a reduced probability of PHLF (odds ratio=0.38) but not with overall survival and disease-free survival. There was an increased probability of SLT when HR was performed in a transplant hospital (odds ratio=12.05). Among transplant-eligible patients, those who underwent LT had a significantly longer postrecurrence survival. Conclusions: This study showed that the presence of a LT program was associated with decreased PHLF rates and an increased probability to receive SLT in case of recurrence.

Published
2023

13. Survival benefit of second line therapies for recurrent hepatocellular carcinoma: repeated hepatectomy, thermoablation and second-line transplant referral in a real life national scenario

Author

Famularo, S, Cillo, U, Lauterio, A, Donadon, M, Vitale, A, Serenari, M, Cipriani, F, Fazio, F, Giuffrida, M, Ardito, F, Dominioni, T, Garancini, M, Lai, Q, Nicolini, D, Molfino, S, Perri, P, Pinotti, E, Conci, S, Ferrari, C, Zanello, M, Patauner, S, Zimmitti, G, Germani, P, Chiarelli, M, Romano, M, De Angelis, M, La Barba, G, Troci, A, Ferraro, V, Izzo, F, Antonucci, A, Belli, A, Memeo, R, Crespi, M, Ercolani, G, Boccia, L, Zanus, G, Tarchi, P, Hilal, M, Frena, A, Jovine, E, Griseri, G, Ruzzenente, A, Zago, M, Grazi, G, Baiocchi, G, Vivarelli, M, Rossi, M, Romano, F, Maestri, M, Giuliante, F, Valle, R, Ferrero, A, Aldrighetti, L, De Carlis, L, Cescon, M, Torzilli, G, Milana, F, Bertacco, A, De Carlis, R, Ratti, F, Russolillo, N, Iaria, M, Razionale, F, Tartaglia, G, Ciulli, C, Carissimi, F, Laureiro, Z, Marinelli, L, Depeppo, V, Montuori, M, Marchitelli, I, Franceschi, A, Notte, F, Manzoni, A, Cosola, D, Corleone, P, Fumagalli, L, Salvador, L, Mantovani, G, Cucchetti, A, Cammarata, F, Conticchio, M, Patrone, R, Bernasconi, D, Famularo S., Cillo U., Lauterio A., Donadon M., Vitale A., Serenari M., Cipriani F., Fazio F., Giuffrida M., Ardito F., Dominioni T., Garancini M., Lai Q., Nicolini D., Molfino S., Perri P., Pinotti E., Conci S., Ferrari C., Zanello M., Patauner S., Zimmitti G., Germani P., Chiarelli M., Romano M., De Angelis M., La Barba G., Troci A., Ferraro V., Izzo F., Antonucci A., Belli A., Memeo R., Crespi M., Ercolani G., Boccia L., Zanus G., Tarchi P., Hilal M. A., Frena A., Jovine E., Griseri G., Ruzzenente A., Zago M., Grazi G., Baiocchi G. L., Vivarelli M., Rossi M., Romano F., Maestri M., Giuliante F., Valle R. D., Ferrero A., Aldrighetti L., De Carlis L., Cescon M., Torzilli G., Milana F., Bertacco A., De Carlis R., Ratti F., Russolillo N., Iaria M., Razionale F., Tartaglia G., Ciulli C., Carissimi F., Laureiro Z. L., Marinelli L., DePeppo V., Montuori M., Marchitelli I., Franceschi A., Notte F., Manzoni A., Cosola D., Corleone P., Fumagalli L., Salvador L., Mantovani G., Cucchetti A., Cammarata F., Conticchio M., Patrone R., Bernasconi D. P., Famularo, S, Cillo, U, Lauterio, A, Donadon, M, Vitale, A, Serenari, M, Cipriani, F, Fazio, F, Giuffrida, M, Ardito, F, Dominioni, T, Garancini, M, Lai, Q, Nicolini, D, Molfino, S, Perri, P, Pinotti, E, Conci, S, Ferrari, C, Zanello, M, Patauner, S, Zimmitti, G, Germani, P, Chiarelli, M, Romano, M, De Angelis, M, La Barba, G, Troci, A, Ferraro, V, Izzo, F, Antonucci, A, Belli, A, Memeo, R, Crespi, M, Ercolani, G, Boccia, L, Zanus, G, Tarchi, P, Hilal, M, Frena, A, Jovine, E, Griseri, G, Ruzzenente, A, Zago, M, Grazi, G, Baiocchi, G, Vivarelli, M, Rossi, M, Romano, F, Maestri, M, Giuliante, F, Valle, R, Ferrero, A, Aldrighetti, L, De Carlis, L, Cescon, M, Torzilli, G, Milana, F, Bertacco, A, De Carlis, R, Ratti, F, Russolillo, N, Iaria, M, Razionale, F, Tartaglia, G, Ciulli, C, Carissimi, F, Laureiro, Z, Marinelli, L, Depeppo, V, Montuori, M, Marchitelli, I, Franceschi, A, Notte, F, Manzoni, A, Cosola, D, Corleone, P, Fumagalli, L, Salvador, L, Mantovani, G, Cucchetti, A, Cammarata, F, Conticchio, M, Patrone, R, Bernasconi, D, Famularo S., Cillo U., Lauterio A., Donadon M., Vitale A., Serenari M., Cipriani F., Fazio F., Giuffrida M., Ardito F., Dominioni T., Garancini M., Lai Q., Nicolini D., Molfino S., Perri P., Pinotti E., Conci S., Ferrari C., Zanello M., Patauner S., Zimmitti G., Germani P., Chiarelli M., Romano M., De Angelis M., La Barba G., Troci A., Ferraro V., Izzo F., Antonucci A., Belli A., Memeo R., Crespi M., Ercolani G., Boccia L., Zanus G., Tarchi P., Hilal M. A., Frena A., Jovine E., Griseri G., Ruzzenente A., Zago M., Grazi G., Baiocchi G. L., Vivarelli M., Rossi M., Romano F., Maestri M., Giuliante F., Valle R. D., Ferrero A., Aldrighetti L., De Carlis L., Cescon M., Torzilli G., Milana F., Bertacco A., De Carlis R., Ratti F., Russolillo N., Iaria M., Razionale F., Tartaglia G., Ciulli C., Carissimi F., Laureiro Z. L., Marinelli L., DePeppo V., Montuori M., Marchitelli I., Franceschi A., Notte F., Manzoni A., Cosola D., Corleone P., Fumagalli L., Salvador L., Mantovani G., Cucchetti A., Cammarata F., Conticchio M., Patrone R., and Bernasconi D. P.

Abstract

Background: Despite second-line transplant(SLT) for recurrent hepatocellular carcinoma(rHCC) leads to the longest survival after recurrence(SAR), its real applicability has never been reported. The aim was to compare the SAR of SLT versus repeated hepatectomy and thermoablation(CUR group). Methods: Patients were enrolled from the Italian register HE.RC.O.LE.S. between 2008 and 2021. Two groups were created: CUR versus SLT. A propensity score matching (PSM) was run to balance the groups. Results: 743 patients were enrolled, CUR = 611 and SLT = 132. Median age at recurrence was 71(IQR 6575) years old and 60(IQR 53-64, p < 0.001) for CUR and SLT respectively. After PSM, median SAR for CUR was 43 months(95%CI = 37 – 93) and not reached for SLT(p < 0.001). SLT patients gained a survival benefit of 9.4 months if compared with CUR. MilanCriteria(MC)-In patients were 82.7% of the CUR group. SLT(HR 0.386, 95%CI = 0.23 – 0.63, p < 0.001) and the MELD score(HR 1.169, 95%CI = 1.07 – 1.27, p < 0.001) were the only predictors of mortality. In case of MC-Out, the only predictor of mortality was the number of nodules at recurrence(HR 1.45, 95%CI= 1.09 – 1.93, p = 0.011). Conclusion: It emerged an important transplant under referral in favour of repeated hepatectomy or thermoablation. In patients with MC-Out relapse, the benefit of SLT over CUR was not observed.

Published
2023

14. Improving outcomes of in situ split liver transplantation in Italy over the last 25 years

Author

Lauterio, A, Cillo, U, Spada, M, Trapani, S, De Carlis, R, Bottino, G, Bernasconi, D, Scalamogna, C, Pinelli, D, Cintorino, D, D'Amico, F, Spagnoletti, G, Miggino, M, Romagnoli, R, Centonze, L, Caccamo, L, Baccarani, U, Carraro, A, Cescon, M, Vivarelli, M, Mazaferro, V, Ettorre, G, Rossi, M, Vennarecci, G, De Simone, P, Angelico, R, Agnes, S, Di Benedetto, F, Lupo, L, Zamboni, F, Zefelippo, A, Patrono, D, Diviacco, P, Laureiro, Z, Gringeri, E, Di Francesco, F, Lucianetti, A, Valsecchi, M, Gruttadauria, S, De Feo, T, Cardillo, M, De Carlis, L, Colledan, M, Andorno, E, Lauterio A., Cillo U., Spada M., Trapani S., De Carlis R., Bottino G., Bernasconi D., Scalamogna C., Pinelli D., Cintorino D., D'Amico F. E., Spagnoletti G., Miggino M., Romagnoli R., Centonze L., Caccamo L., Baccarani U., Carraro A., Cescon M., Vivarelli M., Mazaferro V., Ettorre G. M., Rossi M., Vennarecci G., De Simone P., Angelico R., Agnes S., Di Benedetto F., Lupo L. G., Zamboni F., Zefelippo A., Patrono D., Diviacco P., Laureiro Z. L., Gringeri E., Di Francesco F., Lucianetti A., Valsecchi M. G., Gruttadauria S., De Feo T., Cardillo M., De Carlis L., Colledan M., Andorno E., Lauterio, A, Cillo, U, Spada, M, Trapani, S, De Carlis, R, Bottino, G, Bernasconi, D, Scalamogna, C, Pinelli, D, Cintorino, D, D'Amico, F, Spagnoletti, G, Miggino, M, Romagnoli, R, Centonze, L, Caccamo, L, Baccarani, U, Carraro, A, Cescon, M, Vivarelli, M, Mazaferro, V, Ettorre, G, Rossi, M, Vennarecci, G, De Simone, P, Angelico, R, Agnes, S, Di Benedetto, F, Lupo, L, Zamboni, F, Zefelippo, A, Patrono, D, Diviacco, P, Laureiro, Z, Gringeri, E, Di Francesco, F, Lucianetti, A, Valsecchi, M, Gruttadauria, S, De Feo, T, Cardillo, M, De Carlis, L, Colledan, M, Andorno, E, Lauterio A., Cillo U., Spada M., Trapani S., De Carlis R., Bottino G., Bernasconi D., Scalamogna C., Pinelli D., Cintorino D., D'Amico F. E., Spagnoletti G., Miggino M., Romagnoli R., Centonze L., Caccamo L., Baccarani U., Carraro A., Cescon M., Vivarelli M., Mazaferro V., Ettorre G. M., Rossi M., Vennarecci G., De Simone P., Angelico R., Agnes S., Di Benedetto F., Lupo L. G., Zamboni F., Zefelippo A., Patrono D., Diviacco P., Laureiro Z. L., Gringeri E., Di Francesco F., Lucianetti A., Valsecchi M. G., Gruttadauria S., De Feo T., Cardillo M., De Carlis L., Colledan M., and Andorno E.

Abstract

Background & Aims: Split liver transplant(ation) (SLT) is still considered a challenging procedure that is by no means widely accepted. We aimed to present data on 25-year trends in SLT in Italy, and to investigate if, and to what extent, outcomes have improved nationwide during this time. Methods: The study included all consecutive SLTs performed from May 1993 to December 2019, divided into three consecutive periods: 1993–2005, 2006–2014, and 2015–2019, which match changes in national allocation policies. Primary outcomes were patient and graft survival, and the relative impact of each study period. Results: SLT accounted for 8.9% of all liver transplants performed in Italy. A total of 1,715 in situ split liver grafts were included in the analysis: 868 left lateral segments (LLSs) and 847 extended right grafts (ERGs). A significant improvement in patient and graft survival (p <0.001) was observed with ERGs over the three periods. Predictors of graft survival were cold ischaemia time (CIT) <6 h (p = 0.009), UNOS status 2b (p <0.001), UNOS status 3 (p = 0.009), and transplant centre volumes: 25–50 cases vs. <25 cases (p = 0.003). Patient survival was significantly higher with LLS grafts in period 2 vs. period 1 (p = 0.008). No significant improvement in graft survival was seen over the three periods, where predictors of graft survival were CIT <6 h (p = 0.007), CIT <6 h vs. ≥10 h (p = 0.019), UNOS status 2b (p = 0.038), and UNOS status 3 (p = 0.009). Retransplantation was a risk factor in split liver graft recipients, with significantly worse graft and patient survival for both types of graft (p <0.001). Conclusions: Our analysis showed Italian SLT outcomes to have improved over the last 25 years. These results could help to dispel reservations regarding the use of this procedure. Impact and implications: Split liver transplant(ation) (SLT) is still considered a challenging procedure and is by no means widely accepted. This study included all

Published
2023

15. The Italian data on SARS-CoV-2 infection in transplanted patients support an organ specific immune response in liver recipients

Author

Rendina, M, Barone, M, Lillo, C, Trapani, S, Masiero, L, Trerotoli, P, Puoti, F, Lupo, L, Tandoi, F, Agnes, S, Grieco, A, Andorno, E, Marenco, S, Giannini, E, Baccarani, U, Toniutto, P, Carraro, A, Colecchia, A, Cescon, M, Morelli, M, Cillo, U, Burra, P, Angeli, P, Colledan, M, Fagiuoli, S, De Carlis, L, Belli, L, De Simone, P, Carrai, P, Di Benedetto, F, De Maria, N, Ettorre, G, Giannelli, V, Gruttadauria, S, Volpes, R, Corsale, S, Mazzaferro, V, Bhoori, S, Romagnoli, R, Martini, S, Rossi, G, Caccamo, L, Donato, M, Rossi, M, Ginanni Corradini, S, Spada, M, Maggiore, G, Tisone, G, Lenci, I, Vennarecci, G, Tortora, R, Vivarelli, M, Svegliati Baroni, G, Zamboni, F, Mameli, L, Tafuri, S, Simone, S, Gesualdo, L, Cardillo, M, Di Leo, A, Rendina M., Barone M., Lillo C., Trapani S., Masiero L., Trerotoli P., Puoti F., Lupo L. G., Tandoi F., Agnes S., Grieco A., Andorno E., Marenco S., Giannini E. G., Baccarani U., Toniutto P., Carraro A., Colecchia A., Cescon M., Morelli M. C., Cillo U., Burra P., Angeli P., Colledan M., Fagiuoli S., De Carlis L., Belli L., De Simone P., Carrai P., Di Benedetto F., De Maria N., Ettorre G. M., Giannelli V., Gruttadauria S., Volpes R., Corsale S., Mazzaferro V., Bhoori S., Romagnoli R., Martini S., Rossi G., Caccamo L., Donato M. F., Rossi M., Ginanni Corradini S., Spada M., Maggiore G., Tisone G., Lenci I., Vennarecci G., Tortora R., Vivarelli M., Svegliati Baroni G., Zamboni F., Mameli L., Tafuri S., Simone S., Gesualdo L., Cardillo M., Di Leo A., Rendina, M, Barone, M, Lillo, C, Trapani, S, Masiero, L, Trerotoli, P, Puoti, F, Lupo, L, Tandoi, F, Agnes, S, Grieco, A, Andorno, E, Marenco, S, Giannini, E, Baccarani, U, Toniutto, P, Carraro, A, Colecchia, A, Cescon, M, Morelli, M, Cillo, U, Burra, P, Angeli, P, Colledan, M, Fagiuoli, S, De Carlis, L, Belli, L, De Simone, P, Carrai, P, Di Benedetto, F, De Maria, N, Ettorre, G, Giannelli, V, Gruttadauria, S, Volpes, R, Corsale, S, Mazzaferro, V, Bhoori, S, Romagnoli, R, Martini, S, Rossi, G, Caccamo, L, Donato, M, Rossi, M, Ginanni Corradini, S, Spada, M, Maggiore, G, Tisone, G, Lenci, I, Vennarecci, G, Tortora, R, Vivarelli, M, Svegliati Baroni, G, Zamboni, F, Mameli, L, Tafuri, S, Simone, S, Gesualdo, L, Cardillo, M, Di Leo, A, Rendina M., Barone M., Lillo C., Trapani S., Masiero L., Trerotoli P., Puoti F., Lupo L. G., Tandoi F., Agnes S., Grieco A., Andorno E., Marenco S., Giannini E. G., Baccarani U., Toniutto P., Carraro A., Colecchia A., Cescon M., Morelli M. C., Cillo U., Burra P., Angeli P., Colledan M., Fagiuoli S., De Carlis L., Belli L., De Simone P., Carrai P., Di Benedetto F., De Maria N., Ettorre G. M., Giannelli V., Gruttadauria S., Volpes R., Corsale S., Mazzaferro V., Bhoori S., Romagnoli R., Martini S., Rossi G., Caccamo L., Donato M. F., Rossi M., Ginanni Corradini S., Spada M., Maggiore G., Tisone G., Lenci I., Vennarecci G., Tortora R., Vivarelli M., Svegliati Baroni G., Zamboni F., Mameli L., Tafuri S., Simone S., Gesualdo L., Cardillo M., and Di Leo A.

Abstract

Introduction: The study of immune response to SARSCoV-2 infection in different solid organ transplant settings represents an opportunity for clarifying the interplay between SARS-CoV-2 and the immune system. In our nationwide registry study from Italy, we specifically evaluated, during the first wave pandemic, i.e., in non-vaccinated patients, COVID-19 prevalence of infection, mortality, and lethality in liver transplant recipients (LTRs), using non-liver solid transplant recipients (NL-SOTRs) and the Italian general population (GP) as comparators. Methods: Case collection started from February 21 to June 22, 2020, using the data from the National Institute of Health and National Transplant Center, whereas the data analysis was performed on September 30, 2020.To compare the sex- and age-adjusted distribution of infection, mortality, and lethality in LTRs, NL-SOTRs, and Italian GP we applied an indirect standardization method to determine the standardized rate. Results: Among the 43,983 Italian SOTRs with a functioning graft, LTRs accounted for 14,168 patients, of whom 89 were SARS-CoV-2 infected. In the 29,815 NL-SOTRs, 361 cases of SARS-CoV-2 infection were observed. The geographical distribution of the disease was highly variable across the different Italian regions. The standardized rate of infection, mortality, and lethality rates in LTRs resulted lower compared to NL-SOTRs [1.02 (95%CI 0.81-1.23) vs. 2.01 (95%CI 1.8-2.2); 1.0 (95%CI 0.5-1.5) vs. 4.5 (95%CI 3.6-5.3); 1.6 (95%CI 0.7-2.4) vs. 2.8 (95%CI 2.2-3.3), respectively] and comparable to the Italian GP. Discussion: According to the most recent studies on SOTRs and SARS-CoV-2 infection, our data strongly suggest that, in contrast to what was observed in NL-SOTRs receiving a similar immunosuppressive therapy, LTRs have the same risk of SARS-CoV-2 infection, mortality, and lethality observed in the general population. These results suggest an immune response to SARS-CoV-2 infection in LTRS that is different fr

Published
2023

16. Evolution of minimally invasive techniques and surgical outcomes of ALPPS in Italy: a comprehensive trend analysis over 10 years from a national prospective registry

Author

Serenari, M, Ratti, F, Guglielmo, N, Zanello, M, Mocchegiani, F, Lenzi, J, Colledan, M, Mazzaferro, V, Cillo, U, Ferrero, A, Cescon, M, Di Benedetto, F, Massani, M, Grazi, G, Valle, R, Vivarelli, M, Ettorre, G, Aldrighetti, L, Jovine, E, Serenari M., Ratti F., Guglielmo N., Zanello M., Mocchegiani F., Lenzi J., Colledan M., Mazzaferro V., Cillo U., Ferrero A., Cescon M., Di Benedetto F., Massani M., Grazi G., Valle R. D., Vivarelli M., Ettorre G. M., Aldrighetti L., Jovine E., Serenari, M, Ratti, F, Guglielmo, N, Zanello, M, Mocchegiani, F, Lenzi, J, Colledan, M, Mazzaferro, V, Cillo, U, Ferrero, A, Cescon, M, Di Benedetto, F, Massani, M, Grazi, G, Valle, R, Vivarelli, M, Ettorre, G, Aldrighetti, L, Jovine, E, Serenari M., Ratti F., Guglielmo N., Zanello M., Mocchegiani F., Lenzi J., Colledan M., Mazzaferro V., Cillo U., Ferrero A., Cescon M., Di Benedetto F., Massani M., Grazi G., Valle R. D., Vivarelli M., Ettorre G. M., Aldrighetti L., and Jovine E.

Abstract

Background: Since 2012, Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) has encountered several modifications of its original technique. The primary endpoint of this study was to analyze the trend of ALPPS in Italy over a 10-year period. The secondary endpoint was to evaluate factors affecting the risk of morbidity/mortality/post-hepatectomy liver failure (PHLF). Methods: Data of patients submitted to ALPPS between 2012 and 2021 were identified from the ALPPS Italian Registry and evaluation of time trends was performed. Results: From 2012 to 2021, a total of 268 ALPPS were performed within 17 centers. The number of ALPPS divided by the total number of liver resections performed by each center slightly declined (APC = - 2.0%, p = 0.111). Minimally invasive (MI) approach significantly increased over the years (APC = + 49.5%, p = 0.002). According to multivariable analysis, MI completion of stage 1 was protective against 90-day mortality (OR = 0.05, p = 0.040) as well as enrollment within high-volume centers for liver surgery (OR = 0.32, p = 0.009). Use of interstage hepatobiliary scintigraphy (HBS) and biliary tumors were independent predictors of PHLF. Conclusions: This national study showed that use of ALPPS only slightly declined over the years with an increased use of MI techniques, leading to lower 90-day mortality. PHLF still remains an open issue.

Published
2023

17. Improving Outcome of Selected Patients With Non-Resectable Hepatic Metastases From Colorectal Cancer With Liver Transplantation: A Prospective Parallel Trial (COLT trial)

Author

Sposito, C, Pietrantonio, F, Maspero, M, Di Benedetto, F, Vivarelli, M, Tisone, G, De Carlis, L, Romagnoli, R, Gruttadauria, S, Colledan, M, Agnes, S, Ettorre, G, Baccarani, U, Torzilli, G, Di Sandro, S, Pinelli, D, Caccamo, L, Sartore Bianchi, A, Spreafico, C, Torri, V, Mazzaferro, V, Sposito C., Pietrantonio F., Maspero M., Di Benedetto F., Vivarelli M., Tisone G., De Carlis L., Romagnoli R., Gruttadauria S., Colledan M., Agnes S., Ettorre G., Baccarani U., Torzilli G., Di Sandro S., Pinelli D., Caccamo L., Sartore Bianchi A., Spreafico C., Torri V., Mazzaferro V., Sposito, C, Pietrantonio, F, Maspero, M, Di Benedetto, F, Vivarelli, M, Tisone, G, De Carlis, L, Romagnoli, R, Gruttadauria, S, Colledan, M, Agnes, S, Ettorre, G, Baccarani, U, Torzilli, G, Di Sandro, S, Pinelli, D, Caccamo, L, Sartore Bianchi, A, Spreafico, C, Torri, V, Mazzaferro, V, Sposito C., Pietrantonio F., Maspero M., Di Benedetto F., Vivarelli M., Tisone G., De Carlis L., Romagnoli R., Gruttadauria S., Colledan M., Agnes S., Ettorre G., Baccarani U., Torzilli G., Di Sandro S., Pinelli D., Caccamo L., Sartore Bianchi A., Spreafico C., Torri V., and Mazzaferro V.

Abstract

Background: Patients with unresectable Colorectal Liver Metastases (CLM) receiving palliative chemotherapy have a 5-year overall survival (OS) of less than 30%. Liver transplantation (LT) can improve OS up to 60%-83% (SECA-I and SECA-II trials). The aim of the study is to assess the efficacy of LT in liver-only metastatic CRC compared with a matched cohort of patients included in a phase III trial on triplet chemotherapy + antiEGFR. Patients and Methods: The COLT trial is an investigator-driven, multicenter, non-randomized, open-label, controlled, prospective, parallel trial (ClinicalTrials.gov NCT03803436). Hyperselected patients with liver-limited unresectable CLM, RAS and BRAF wild-type and curatively removed primary colon cancer are included. The observed post-transplant outcomes will be prospectively compared 1:5 with those obtained in a matched cohort from the TRIPLETE trial (NCT03231722). Results: Primary endpoint is to compare the 3 and 5-years OS of patients enrolled in the COLT trial with COLT-eligible population enrolled in the TRIPLETE trial. An expected gain in OS of 40% at 5-years is predicted for the COLT population (the expected OS at 5-years in COLT vs. TRIPLETE is 70% vs. 30%). Secondary endpoints are to compare the 5-years disease-free survival and to assess the safety of LT (Dindo-Clavien Classification and the Comprehensive Complication Index). Conclusion: LT offers the longest OS reported in selected patients with CLM. Improving the selection strategies can give patients a 5-year OS similar to other indications for LT and a better outcome than those undergoing chemotherapy alone.

Published
2023

20. Tailoring allocation policies and improving access to pediatric liver transplantation over a 16-year period

Author

Spada, Marco, primary, Angelico, Roberta, additional, Trapani, Silvia, additional, Masiero, Lucia, additional, Puoti, Francesca, additional, Colledan, Michele, additional, Cintorino, Davide, additional, Romagnoli, Renato, additional, Cillo, Umberto, additional, Cardillo, Massimo, additional, Agnes, S., additional, Andorno, E., additional, Baccarani, U., additional, Caccamo, L., additional, Rossi, G., additional, Carraro, A., additional, Cescon, M., additional, Simone, P.De, additional, Carlis, L.De, additional, Benedetto, F.Di, additional, Ettorre, G.M., additional, Gruttadauria, S., additional, Lupo, L.G., additional, Tandoi, F., additional, Mazzaferro, V., additional, Rossi, M., additional, Tisone, G., additional, Vennarecci, G., additional, Vivarelli, M., additional, and Zamboni, F., additional

Published
2023
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21. Liver transplantation for metastatic colorectal cancer after optimal systemic treatment (COLT trial): feasibility and safety data

Author

Mazzaferro, V., primary, Maspero, M., additional, Pietrantonio, F., additional, Benedetto, F. Di, additional, Vivarelli, M., additional, Tisone, G., additional, De Carlis, L., additional, Romagnoli, R., additional, Gruttadauria, S., additional, Colledan, M., additional, Baccarani, U., additional, Torzilli, G., additional, and Sposito, C., additional

Published
2023
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22. Evolution of minimally invasive techniques and surgical outcomes of ALPPS in Italy: a comprehensive trend analysis over 10 years from a national prospective registry

Author

Serenari M., Ratti F., Guglielmo N., Zanello M., Mocchegiani F., Lenzi J., Colledan M., Mazzaferro V., Cillo U., Ferrero A., Cescon M., Di Benedetto F., Massani M., Grazi G., Valle R. D., Vivarelli M., Ettorre G. M., Aldrighetti L., Jovine E., Serenari, M, Ratti, F, Guglielmo, N, Zanello, M, Mocchegiani, F, Lenzi, J, Colledan, M, Mazzaferro, V, Cillo, U, Ferrero, A, Cescon, M, Di Benedetto, F, Massani, M, Grazi, G, Valle, R, Vivarelli, M, Ettorre, G, Aldrighetti, L, and Jovine, E

Subjects
Hepatectomy, Laparoscopy, ALPPS, Minimally invasive, Outcome
Abstract

Background: Since 2012, Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) has encountered several modifications of its original technique. The primary endpoint of this study was to analyze the trend of ALPPS in Italy over a 10-year period. The secondary endpoint was to evaluate factors affecting the risk of morbidity/mortality/post-hepatectomy liver failure (PHLF). Methods: Data of patients submitted to ALPPS between 2012 and 2021 were identified from the ALPPS Italian Registry and evaluation of time trends was performed. Results: From 2012 to 2021, a total of 268 ALPPS were performed within 17 centers. The number of ALPPS divided by the total number of liver resections performed by each center slightly declined (APC = -2.0%, p = 0.111). Minimally invasive (MI) approach significantly increased over the years (APC = + 49.5%, p = 0.002). According to multivariable analysis, MI completion of stage 1 was protective against 90-day mortality (OR = 0.05, p = 0.040) as well as enrollment within high-volume centers for liver surgery (OR = 0.32, p = 0.009). Use of interstage hepatobiliary scintigraphy (HBS) and biliary tumors were independent predictors of PHLF. Conclusions: This national study showed that use of ALPPS only slightly declined over the years with an increased use of MI techniques, leading to lower 90-day mortality. PHLF still remains an open issue.

Published
2023

23. Improving clinical paediatric research and learning from COVID-19: recommendations by the Conect4Children expert advice group

Author

Ramanan, A, Modi, N, de Wildt, S, Aurich, B, Bakhtadze, S, Sirvent, F, Cabanas, F, Campbell, L, Casanova, M, Charlton, P, Crandall, W, Eichler, I, Fregonese, L, Hawcutt, D, Iveli, P, Jaki, T, Jocic-Jakubi, B, Johnson, M, Kaguelidou, F, Karadag, B, Kelly, L, Lim, M, Moreno, C, Neumann, E, Ollivier, C, Oualha, M, Raffaeli, G, Ribeiro, M, Roilides, E, de Rojas, T, Simon, A, Ruperto, N, Scarpa, M, Schwab, M, Siapkara, A, Singh, Y, Smits, A, Striano, P, Urru, S, Vivarelli, M, Zivkoviz, Z, Ramanan A. V., Modi N., de Wildt S. N., Aurich B., Bakhtadze S., Sirvent F. J. B., Cabanas F., Campbell L., Casanova M., Charlton P., Crandall W., Eichler I., Fregonese L., Hawcutt D. B., Iveli P., Jaki T., Jocic-Jakubi B., Johnson M., Kaguelidou F., Karadag B., Kelly L. E., Lim M., Moreno C., Neumann E., Ollivier C., Oualha M., Raffaeli G., Ribeiro M. A., Roilides E., de Rojas T., Simon A. R. S., Ruperto N., Scarpa M., Schwab M., Siapkara A., Singh Y., Smits A., Striano P., Urru S. A. M., Vivarelli M., de Wildt S., Zivkoviz Z., Ramanan, A, Modi, N, de Wildt, S, Aurich, B, Bakhtadze, S, Sirvent, F, Cabanas, F, Campbell, L, Casanova, M, Charlton, P, Crandall, W, Eichler, I, Fregonese, L, Hawcutt, D, Iveli, P, Jaki, T, Jocic-Jakubi, B, Johnson, M, Kaguelidou, F, Karadag, B, Kelly, L, Lim, M, Moreno, C, Neumann, E, Ollivier, C, Oualha, M, Raffaeli, G, Ribeiro, M, Roilides, E, de Rojas, T, Simon, A, Ruperto, N, Scarpa, M, Schwab, M, Siapkara, A, Singh, Y, Smits, A, Striano, P, Urru, S, Vivarelli, M, Zivkoviz, Z, Ramanan A. V., Modi N., de Wildt S. N., Aurich B., Bakhtadze S., Sirvent F. J. B., Cabanas F., Campbell L., Casanova M., Charlton P., Crandall W., Eichler I., Fregonese L., Hawcutt D. B., Iveli P., Jaki T., Jocic-Jakubi B., Johnson M., Kaguelidou F., Karadag B., Kelly L. E., Lim M., Moreno C., Neumann E., Ollivier C., Oualha M., Raffaeli G., Ribeiro M. A., Roilides E., de Rojas T., Simon A. R. S., Ruperto N., Scarpa M., Schwab M., Siapkara A., Singh Y., Smits A., Striano P., Urru S. A. M., Vivarelli M., de Wildt S., and Zivkoviz Z.

Abstract

Background: The COVID-19 pandemic has had a devastating impact on multiple aspects of healthcare, but has also triggered new ways of working, stimulated novel approaches in clinical research and reinforced the value of previous innovations. Conect4children (c4c, www.conect4children.org) is a large collaborative European network to facilitate the development of new medicines for paediatric populations, and is made up of 35 academic and 10 industry partners from 20 European countries, more than 50 third parties, and around 500 affiliated partners. Methods: We summarise aspects of clinical research in paediatrics stimulated and reinforced by COVID-19 that the Conect4children group recommends regulators, sponsors, and investigators retain for the future, to enhance the efficiency, reduce the cost and burden of medicines and non-interventional studies, and deliver research-equity. Findings: We summarise aspects of clinical research in paediatrics stimulated and reinforced by COVID-19 that the Conect4children group recommends regulators, sponsors, and investigators retain for the future, to enhance the efficiency, reduce the cost and burden of medicines and non-interventional studies, and deliver research-equityWe provide examples of research innovation, and follow this with recommendations to improve the efficiency of future trials, drawing on industry perspectives, regulatory considerations, infrastructure requirements and parent–patient–public involvement. We end with a comment on progress made towards greater international harmonisation of paediatric research and how lessons learned from COVID-19 studies might assist in further improvements in this important area.

Published
2022

24. Temporal trends of waitlistings for liver transplantation in Italy: The ECALITA (Evolution of IndiCAtion in LIver transplantation in ITAly) registry study

Author

Manzia, T, Trapani, S, Nardi, A, Ricci, A, Lenci, I, Milana, M, Angelico, R, De Feo, T, Agnes, S, Andorno, E, Baccarani, U, Carraro, A, Cescon, M, Cillo, U, Colledan, M, De Carlis, L, De Simone, P, Di Benedetto, F, Ettorre, G, Gruttadauria, S, Lupo, L, Mazzaferro, V, Romagnoli, R, Rossi, G, Rossi, M, Spada, M, Vennarecci, G, Vivarelli, M, Zamboni, F, Tisone, G, Cardillo, M, Angelico, M, Manzia T. M., Trapani S., Nardi A., Ricci A., Lenci I., Milana M., Angelico R., De Feo T. M., Agnes S., Andorno E., Baccarani U., Carraro A., Cescon M., Cillo U., Colledan M., De Carlis L., De Simone P., Di Benedetto F., Ettorre G. M., Gruttadauria S., Lupo L. G., Mazzaferro V., Romagnoli R., Rossi G., Rossi M., Spada M., Vennarecci G., Vivarelli M., Zamboni F., Tisone G., Cardillo M., Angelico M., Manzia, T, Trapani, S, Nardi, A, Ricci, A, Lenci, I, Milana, M, Angelico, R, De Feo, T, Agnes, S, Andorno, E, Baccarani, U, Carraro, A, Cescon, M, Cillo, U, Colledan, M, De Carlis, L, De Simone, P, Di Benedetto, F, Ettorre, G, Gruttadauria, S, Lupo, L, Mazzaferro, V, Romagnoli, R, Rossi, G, Rossi, M, Spada, M, Vennarecci, G, Vivarelli, M, Zamboni, F, Tisone, G, Cardillo, M, Angelico, M, Manzia T. M., Trapani S., Nardi A., Ricci A., Lenci I., Milana M., Angelico R., De Feo T. M., Agnes S., Andorno E., Baccarani U., Carraro A., Cescon M., Cillo U., Colledan M., De Carlis L., De Simone P., Di Benedetto F., Ettorre G. M., Gruttadauria S., Lupo L. G., Mazzaferro V., Romagnoli R., Rossi G., Rossi M., Spada M., Vennarecci G., Vivarelli M., Zamboni F., Tisone G., Cardillo M., and Angelico M.

Abstract

Background: Over the last decades relevant epidemiological changes of liver diseases have occurred, together with greatly improved treatment opportunities. Aim: To investigate how the indications for elective adult liver transplantation and the underlying disease etiologies have evolved in Italy. Methods: We recruited from the National Transplant Registry a cohort comprising 17,317 adults patients waitlisted for primary liver transplantation from January-2004 to December-2020. Patients were divided into three Eras:1(2004–2011),2(2012–2014) and 3(2015–2020). Results: Waitlistings for cirrhosis decreased from 65.9% in Era 1 to 46.1% in Era 3, while those for HCC increased from 28.7% to 48.7%. Comparing Eras 1 and 3, waitlistings for HCV-related cirrhosis decreased from 35.9% to 12.1%, yet those for HCV-related HCC increased from 8.5% to 26.7%. Waitlistings for HBV-related cirrhosis remained almost unchanged (13.2% and 12.4%), while those for HBV-related HCC increased from 4.0% to 11.6%. ALD-related cirrhosis decreased from 16.9% to 12.9% while ALD-related HCC increased from 1.9% to 3.9%. Conclusions: A sharp increase in liver transplant waitlisting for HCC and a concomitant decrease of waitlisting for cirrhosis have occurred In Italy. Despite HCV infection has noticeably decreased, still remains the primary etiology of waitlisting for HCC, while ALD and HBV represent the main causes for cirrhosis.

Published
2022

25. Migration rate using fully covered metal stent in anastomotic strictures after liver transplantation: Results from the BASALT study group

Author

Conigliaro, R, Pigo, F, Bertani, H, Greco, S, Burti, C, Indriolo, A, Di Sario, A, Ortolani, A, Maroni, L, Tringali, A, Barbaro, F, Costamagna, G, Magarotto, A, Masci, E, Mutignani, M, Forti, E, Parodi, M, Assandri, L, Marrone, C, Fantin, A, Penagini, R, Cantu, P, Di Benedetto, F, Ravelli, P, Vivarelli, M, Agnes, S, Mazzaferro, V, De Carlis, L, Andorno, E, Cillo, U, Rossi, G, Conigliaro R., Pigo F., Bertani H., Greco S., Burti C., Indriolo A., Di Sario A., Ortolani A., Maroni L., Tringali A., Barbaro F., Costamagna G., Magarotto A., Masci E., Mutignani M., Forti E., Parodi M. C., Assandri L., Marrone C., Fantin A., Penagini R., Cantu P., Di Benedetto F., Ravelli P., Vivarelli M., Agnes S., Mazzaferro V., De Carlis L., Andorno E., Cillo U., Rossi G., Conigliaro, R, Pigo, F, Bertani, H, Greco, S, Burti, C, Indriolo, A, Di Sario, A, Ortolani, A, Maroni, L, Tringali, A, Barbaro, F, Costamagna, G, Magarotto, A, Masci, E, Mutignani, M, Forti, E, Parodi, M, Assandri, L, Marrone, C, Fantin, A, Penagini, R, Cantu, P, Di Benedetto, F, Ravelli, P, Vivarelli, M, Agnes, S, Mazzaferro, V, De Carlis, L, Andorno, E, Cillo, U, Rossi, G, Conigliaro R., Pigo F., Bertani H., Greco S., Burti C., Indriolo A., Di Sario A., Ortolani A., Maroni L., Tringali A., Barbaro F., Costamagna G., Magarotto A., Masci E., Mutignani M., Forti E., Parodi M. C., Assandri L., Marrone C., Fantin A., Penagini R., Cantu P., Di Benedetto F., Ravelli P., Vivarelli M., Agnes S., Mazzaferro V., De Carlis L., Andorno E., Cillo U., and Rossi G.

Abstract

Background and Study Aim: The traditional endoscopic therapy of anastomotic strictures (AS) after orthotopic liver transplantation (OLT) is multiple ERCPs with the insertion of an increasing number of plastic stents side-by-side. Fully covered self-expanding metal stents (cSEMS) could be a valuable option to decrease the number of procedures needed or non-responders to plastic stents. This study aims to retrospectively analyse the results of AS endoscopic treatment by cSEMS and to identify any factors associated with its success. Patients and Methods: Ninety-one patients (mean age 55.9 ± 7.6 SD; 73 males) from nine Italian transplantation centres, had a cSEMS positioned for post-OLT-AS between 2007 and 2017. Forty-nine (54%) patients were treated with cSEMS as a second-line treatment. Results: All the procedures were successfully performed without immediate complications. After ERCP, adverse events occurred in 11% of cases (2 moderate pancreatitis and 8 cholangitis). In 49 patients (54%), cSEMSs migrated. After cSEMS removal, 46 patients (51%) needed further endoscopic (45 patients) or radiological (1 patient) treatments to solve the AS. Lastly, seven patients underwent surgery. Multivariable stepwise logistic regression showed that cSEMS migration was the only factor associated with further treatments (OR 2.6, 95% CI 1.0–6.6; p value 0.03); cSEMS implantation before 12 months from OLT was associated with stent migration (OR 5.2, 95% CI 1.7–16.0; p value 0.004). Conclusions: cSEMS appears to be a safe tool to treat AS. cSEMS migration is the main limitation to its routinary implantation and needs to be prevented, probably with the use of new generation anti-migration stents.

Published
2022

26. Current practice of normothermic regional perfusion and machine perfusion in donation after circulatory death liver transplants in Italy

Author

De Carlis, R, Lauterio, A, Centonze, L, Buscemi, V, Schlegel, A, Muiesan, P, De Carlis, L, Carraro, A, Ghinolfi, D, De Simone, P, Ravaioli, M, Cescon, M, Dondossola, D, Bongini, M, Mazzaferro, V, Pagano, D, Gruttadauria, S, Gringeri, E, Cillo, U, Patrono, D, Romagnoli, R, Camagni, S, Colledan, M, Olivieri, T, Di Benedetto, F, Vennarecci, G, Baccarani, U, Lai, Q, Rossi, M, Manzia, T, Tisone, G, Vivarelli, M, Scalera, I, Lupo, L, Andorno, E, Meniconi, R, Ettorre, G, Avolio, A, Agnes, S, Pellegrino, R, Zamboni, F, De Carlis R., Lauterio A., Centonze L., Buscemi V., Schlegel A., Muiesan P., De Carlis L., Carraro A., Ghinolfi D., De Simone P., Ravaioli M., Cescon M., Dondossola D., Bongini M., Mazzaferro V., Pagano D., Gruttadauria S., Gringeri E., Cillo U., Patrono D., Romagnoli R., Camagni S., Colledan M., Olivieri T., Di Benedetto F., Vennarecci G., Baccarani U., Lai Q., Rossi M., Manzia T. M., Tisone G., Vivarelli M., Scalera I., Lupo L. G., Andorno E., Meniconi R. L., Ettorre G. M., Avolio A. W., Agnes S., Pellegrino R. A., Zamboni F., De Carlis, R, Lauterio, A, Centonze, L, Buscemi, V, Schlegel, A, Muiesan, P, De Carlis, L, Carraro, A, Ghinolfi, D, De Simone, P, Ravaioli, M, Cescon, M, Dondossola, D, Bongini, M, Mazzaferro, V, Pagano, D, Gruttadauria, S, Gringeri, E, Cillo, U, Patrono, D, Romagnoli, R, Camagni, S, Colledan, M, Olivieri, T, Di Benedetto, F, Vennarecci, G, Baccarani, U, Lai, Q, Rossi, M, Manzia, T, Tisone, G, Vivarelli, M, Scalera, I, Lupo, L, Andorno, E, Meniconi, R, Ettorre, G, Avolio, A, Agnes, S, Pellegrino, R, Zamboni, F, De Carlis R., Lauterio A., Centonze L., Buscemi V., Schlegel A., Muiesan P., De Carlis L., Carraro A., Ghinolfi D., De Simone P., Ravaioli M., Cescon M., Dondossola D., Bongini M., Mazzaferro V., Pagano D., Gruttadauria S., Gringeri E., Cillo U., Patrono D., Romagnoli R., Camagni S., Colledan M., Olivieri T., Di Benedetto F., Vennarecci G., Baccarani U., Lai Q., Rossi M., Manzia T. M., Tisone G., Vivarelli M., Scalera I., Lupo L. G., Andorno E., Meniconi R. L., Ettorre G. M., Avolio A. W., Agnes S., Pellegrino R. A., and Zamboni F.

Abstract

Background: Normothermic regional perfusion (NRP) and machine perfusion (MP) are variously used in many European centers to improve the outcomes after liver transplantation from donation after circulatory death (DCD). In Italy, a combination of NRP and subsequent MP has been used since the start of the activity. While NRP is mandatory for every DCD recovery, the subsequent use of MP is left to each center. Methods: We have designed a national survey to investigate practices and policies of these techniques. The questionnaire included 46 questions and was distributed to all the 21 Italian centers using an online form between June and July 2021. Results: The overall response rate was 100%. A local NRP program for controlled Maastricht type 3 DCD was active in 11/21 (52.4%) centers. Organization and availability of personnel were perceived as the main difficulties in starting such a program. Between 2015 and 2020, 119 DCD livers were transplanted, with an overall utilization rate of 69.2%. Pump flow and gross aspect were considered the most reliable parameters in liver selection during NRP. Eight (72.7%) centers adopted subsequent hypothermic MP, 1 (9.1%) center normothermic MP, and the remaining 2 (18.2%) used both MP types. Conclusion: This first snapshot survey shows that NRP with subsequent MP is the most used protocol in Italy for DCD livers, although some heterogeneity exists in the type and purpose of MP between centers. Overall, this policy ensures a high utilization rate, considering the high risk of the DCD donor population in Italy. Graphical abstract: [Figure not available: see fulltext.]

Published
2022

27. A multicenter retrospective study of calcineurin inhibitors in nephrotic syndrome secondary to podocyte gene variants

Author

Malakasioti, G. Iancu, D. Milovanova, A. Tsygin, A. Horinouchi, T. Nagano, C. Nozu, K. Kamei, K. Fujinaga, S. Iijima, K. Sinha, R. Basu, B. Morello, W. Montini, G. Waters, A. Boyer, O. Yıldırım, Z.Y. Yel, S. Dursun, İ. McCarthy, H.J. Vivarelli, M. Prikhodina, L. Besouw, M.T.P. Chan, E.Y.-H. Huang, W. Kemper, M.J. Loos, S. Prestidge, C. Wong, W. Zlatanova, G. Ehren, R. Weber, L.T. Chehade, H. Hooman, N. Tkaczyk, M. Stańczyk, M. Miligkos, M. Tullus, K. CNI in Monogenic SRNS Study Investigators and Malakasioti, G. Iancu, D. Milovanova, A. Tsygin, A. Horinouchi, T. Nagano, C. Nozu, K. Kamei, K. Fujinaga, S. Iijima, K. Sinha, R. Basu, B. Morello, W. Montini, G. Waters, A. Boyer, O. Yıldırım, Z.Y. Yel, S. Dursun, İ. McCarthy, H.J. Vivarelli, M. Prikhodina, L. Besouw, M.T.P. Chan, E.Y.-H. Huang, W. Kemper, M.J. Loos, S. Prestidge, C. Wong, W. Zlatanova, G. Ehren, R. Weber, L.T. Chehade, H. Hooman, N. Tkaczyk, M. Stańczyk, M. Miligkos, M. Tullus, K. CNI in Monogenic SRNS Study Investigators

Abstract

While 44-83% of children with steroid-resistant nephrotic syndrome (SRNS) without a proven genetic cause respond to treatment with a calcineurin inhibitor (CNI), current guidelines recommend against the use of immunosuppression in monogenic SRNS. This is despite existing evidence suggesting that remission with CNI treatment is possible and can improve prognosis in some cases of monogenic SRNS. Herein, our retrospective study assessed response frequency, predictors of response and kidney function outcomes among children with monogenic SRNS treated with a CNI for at least three months. Data from 203 cases (age 0-18 years) were collected from 37 pediatric nephrology centers. Variant pathogenicity was reviewed by a geneticist, and 122 patients with a pathogenic and 19 with a possible pathogenic genotype were included in the analysis. After six months of treatment and at last visit, 27.6% and 22.5% of all patients respectively, demonstrated partial or full response. Achievement of at least partial response at six months of treatment conferred a significant reduction in kidney failure risk at last follow-up compared to no response (hazard ratio [95% confidence interval] 0.25, [0.10-0.62]). Moreover, risk of kidney failure was significantly lower when only those with a follow-up longer than two years were considered (hazard ratio 0.35, [0.14-0.91]). Higher serum albumin level at CNI initiation was the only factor related to increased likelihood of significant remission at six months (odds ratio [95% confidence interval] 1.16, [1.08-1.24]). Thus, our findings justify a treatment trial with a CNI also in children with monogenic SRNS. © 2023 International Society of Nephrology

Published
2023

28. IPNA clinical practice recommendations for the diagnosis and management of children with steroid-sensitive nephrotic syndrome.

Author

Trautmann, A., Boyer, O., Hodson, E., Bagga, A., Gipson, D.S., Samuel, S., Wetzels, J., Alhasan, K., Banerjee, S., Bhimma, R., Bonilla-Felix, M., Cano, F., Christian, M., Hahn, D., Kang, H.G., Nakanishi, K., Safouh, H., Trachtman, H., Xu, H., Cook, W., Vivarelli, M., Haffner, D., Trautmann, A., Boyer, O., Hodson, E., Bagga, A., Gipson, D.S., Samuel, S., Wetzels, J., Alhasan, K., Banerjee, S., Bhimma, R., Bonilla-Felix, M., Cano, F., Christian, M., Hahn, D., Kang, H.G., Nakanishi, K., Safouh, H., Trachtman, H., Xu, H., Cook, W., Vivarelli, M., and Haffner, D.

Abstract

Item does not contain fulltext, Idiopathic nephrotic syndrome is the most frequent pediatric glomerular disease, affecting from 1.15 to 16.9 per 100,000 children per year globally. It is characterized by massive proteinuria, hypoalbuminemia, and/or concomitant edema. Approximately 85-90% of patients attain complete remission of proteinuria within 4-6 weeks of treatment with glucocorticoids, and therefore, have steroid-sensitive nephrotic syndrome (SSNS). Among those patients who are steroid sensitive, 70-80% will have at least one relapse during follow-up, and up to 50% of these patients will experience frequent relapses or become dependent on glucocorticoids to maintain remission. The dose and duration of steroid treatment to prolong time between relapses remains a subject of much debate, and patients continue to experience a high prevalence of steroid-related morbidity. Various steroid-sparing immunosuppressive drugs have been used in clinical practice; however, there is marked practice variation in the selection of these drugs and timing of their introduction during the course of the disease. Therefore, international evidence-based clinical practice recommendations (CPRs) are needed to guide clinical practice and reduce practice variation. The International Pediatric Nephrology Association (IPNA) convened a team of experts including pediatric nephrologists, an adult nephrologist, and a patient representative to develop comprehensive CPRs on the diagnosis and management of SSNS in children. After performing a systematic literature review on 12 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, recommendations were formulated and formally graded at several virtual consensus meetings. New definitions for treatment outcomes to help guide change of therapy and recommendations for important research questions are given.

Published
2023

29. Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome.

Author

Barry, A., McNulty, M.T., Jia, X., Gupta, Y., Debiec, H., Luo, Y, Nagano, C., Horinouchi, T., Jung, S., Colucci, M., Ahram, D.F., Mitrotti, A., Sinha, A., Teeninga, N., Jin, G., Shril, S., Caridi, G., Bodria, M., Lim, T.Y., Westland, R., Zanoni, F., Marasa, M., Turudic, D., Giordano, M., Gesualdo, L., Magistroni, R., Pisani, I., Fiaccadori, E., Reiterova, J., Maringhini, S., Morello, W., Montini, G., Weng, P.L., Scolari, F., Saraga, M., Tasic, V., Santoro, D., Wijk, J.A. van, Milošević, D., Kawai, Y., Kiryluk, K., Pollak, M.R., Gharavi, A., Lin, F., Simœs E Silva, A.C., Loos, R.J., Kenny, E.E., Schreuder, M.F., Zurowska, A., Dossier, C., Ariceta, G., Drozynska-Duklas, M., Hogan, J., Jankauskiene, A., Hildebrandt, F., Prikhodina, L., Song, K., Bagga, A., Cheong H, 2.n.d., Ghiggeri, G.M., Vachvanichsanong, P., Nozu, K., Lee, D., Vivarelli, M., Raychaudhuri, S., Tokunaga, K., Sanna-Cherchi, S., Ronco, P., Iijima, K., Sampson, M.G., Barry, A., McNulty, M.T., Jia, X., Gupta, Y., Debiec, H., Luo, Y, Nagano, C., Horinouchi, T., Jung, S., Colucci, M., Ahram, D.F., Mitrotti, A., Sinha, A., Teeninga, N., Jin, G., Shril, S., Caridi, G., Bodria, M., Lim, T.Y., Westland, R., Zanoni, F., Marasa, M., Turudic, D., Giordano, M., Gesualdo, L., Magistroni, R., Pisani, I., Fiaccadori, E., Reiterova, J., Maringhini, S., Morello, W., Montini, G., Weng, P.L., Scolari, F., Saraga, M., Tasic, V., Santoro, D., Wijk, J.A. van, Milošević, D., Kawai, Y., Kiryluk, K., Pollak, M.R., Gharavi, A., Lin, F., Simœs E Silva, A.C., Loos, R.J., Kenny, E.E., Schreuder, M.F., Zurowska, A., Dossier, C., Ariceta, G., Drozynska-Duklas, M., Hogan, J., Jankauskiene, A., Hildebrandt, F., Prikhodina, L., Song, K., Bagga, A., Cheong H, 2.n.d., Ghiggeri, G.M., Vachvanichsanong, P., Nozu, K., Lee, D., Vivarelli, M., Raychaudhuri, S., Tokunaga, K., Sanna-Cherchi, S., Ronco, P., Iijima, K., and Sampson, M.G.

Abstract

Item does not contain fulltext, Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. Here, we conduct a multi-population GWAS meta-analysis in 38,463 participants (2440 cases). We then conduct conditional analyses and population specific GWAS. We discover twelve significant associations-eight from the multi-population meta-analysis (four novel), two from the multi-population conditional analysis (one novel), and two additional novel loci from the European meta-analysis. Fine-mapping implicates specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk locus. Non-HLA loci colocalize with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs is lacking but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associates with earlier disease onset. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cell-specific insights into its molecular drivers. Evaluating these associations in additional cohorts will refine our understanding of population specificity, heterogeneity, and clinical and molecular associations.

Published
2023

30. Prospective minimally invasive pancreatic resections from the IGOMIPS registry: a snapshot of daily practice in Italy on 1191 between 2019 and 2022

Author

Boggi, U., Donisi, G., Napoli, N., Partelli, S., Esposito, A., Ferrari, G., Butturini, G., Morelli, L., Abu Hilal, M., Viola, M., Di Benedetto, F., Troisi, R., Vivarelli, M., Jovine, E., Ferrero, A., Bracale, U., Alfieri, Sergio, Casadei, R., Ercolani, G., Moraldi, L., Molino, C., Dalla Valle, R., Ettorre, G., Memeo, R., Zanus, G., Belli, A., Gruttadauria, S., Brolese, A., Coratti, A., Garulli, G., Romagnoli, R., Massani, M., Borghi, F., Belli, G., Coppola, R., Falconi, M., Salvia, R., Zerbi, A., Kauffmann, E. F., Capretti, G., Genova, L., Matteo, P., Mazzola, M., Giardino, A., Palmieri, M., Manzoni, A., Barbieri, V., Ballarin, R., Rompianesi, G., Rossi, R., Mastrangelo, L., Langella, S., Ilardi, M., Menghi, Roberta, Ricci, C., Gardini, A., Campra, D., Crolla, E., Cecconi, S., Meniconi, R. L., Ferraro, V., Brizzolari, M., Izzo, F., Cintorino, D., Marcucci, S., Giuliani, G., Veneroni, L., Moro, F., Nistri, C., Caputo, D., Gianluca, B., Mazzaferro, V., Alfieri S. (ORCID:0000-0002-0404-724X), Menghi R., Boggi, U., Donisi, G., Napoli, N., Partelli, S., Esposito, A., Ferrari, G., Butturini, G., Morelli, L., Abu Hilal, M., Viola, M., Di Benedetto, F., Troisi, R., Vivarelli, M., Jovine, E., Ferrero, A., Bracale, U., Alfieri, Sergio, Casadei, R., Ercolani, G., Moraldi, L., Molino, C., Dalla Valle, R., Ettorre, G., Memeo, R., Zanus, G., Belli, A., Gruttadauria, S., Brolese, A., Coratti, A., Garulli, G., Romagnoli, R., Massani, M., Borghi, F., Belli, G., Coppola, R., Falconi, M., Salvia, R., Zerbi, A., Kauffmann, E. F., Capretti, G., Genova, L., Matteo, P., Mazzola, M., Giardino, A., Palmieri, M., Manzoni, A., Barbieri, V., Ballarin, R., Rompianesi, G., Rossi, R., Mastrangelo, L., Langella, S., Ilardi, M., Menghi, Roberta, Ricci, C., Gardini, A., Campra, D., Crolla, E., Cecconi, S., Meniconi, R. L., Ferraro, V., Brizzolari, M., Izzo, F., Cintorino, D., Marcucci, S., Giuliani, G., Veneroni, L., Moro, F., Nistri, C., Caputo, D., Gianluca, B., Mazzaferro, V., Alfieri S. (ORCID:0000-0002-0404-724X), and Menghi R.

Abstract

This retrospective analysis of the prospective IGOMIPS registry reports on 1191 minimally invasive pancreatic resections (MIPR) performed in Italy between 2019 and 2022, including 668 distal pancreatectomies (DP) (55.7%), 435 pancreatoduodenectomies (PD) (36.3%), 44 total pancreatectomies (3.7%), 36 tumor enucleations (3.0%), and 8 central pancreatectomies (0.7%). Spleen-preserving DP was performed in 109 patients (16.3%). Overall incidence of severe complications (Clavien-Dindo & GE; 3) was 17.6% with a 90-day mortality of 1.9%. This registry analysis provided some important information. First, robotic assistance was preferred for all MIPR but DP with splenectomy. Second, robotic assistance reduced conversion to open surgery and blood loss in comparison to laparoscopy. Robotic PD was also associated with lower incidence of severe postoperative complications and a trend toward lower mortality. Fourth, the annual cut-off of & GE; 20 MIPR and & GE; 20 MIPD improved selected outcome measures. Fifth, most MIPR were performed by a single surgeon. Sixth, only two-thirds of the centers performed spleen-preserving DP. Seventh, DP with splenectomy was associated with higher conversion rate when compared to spleen-preserving DP. Eighth, the use of pancreatojejunostomy was the prevalent reconstruction in PD. Ninth, final histology was similar for MIPR performed at high- and low-volume centers, but neoadjuvant chemotherapy was used more frequently at high-volume centers. Finally, this registry analysis raises important concerns about the reliability of R1 assessment underscoring the importance of standardized pathology of pancreatic specimens. In conclusion, MIPR can be safely implemented on a national scale. Further analyses are required to understand nuances of implementation of MIPR in Italy.

Published
2023

31. The Effect of a Liver Transplant Program on the Outcomes of Resectable Hepatocellular Carcinoma: A Nationwide Multicenter Analysis

Author

Serenari, M., Lenzi, J., Cucchetti, A., Cipriani, F., Donadon, M., Ardito, Francesco, Fazio, F., Nicolini, D., Iaria, M., Famularo, S., Perri, P., Ansaloni, L., Zanello, M., Lai, Q., Conci, S., Molfino, S., Ferrari, C., Germani, P., Zago, M., Romano, M., Zimmitti, G., Antonucci, A., Fumagalli, L., Troci, A., Ferraro, V., Memeo, R., Crespi, M., Chiarelli, M., Ercolani, G., Hilal, M. A., Zanus, G., Pinotti, E., Tarchi, P., Griseri, G., Baiocchi, G. L., Ruzzenente, A., Rossi, M., Jovine, E., Maestri, M., Grazi, G. L., Romano, F., Dalla Valle, R., Ravaioli, M., Vivarelli, M., Ferrero, A., Giuliante, Felice, Torzilli, G., Aldrighetti, L., Cescon, M., Gorgone, M., Ratti, F., Costa, G., Razionale, Francesco, Russolillo, N., Marinelli, Luca, Giuffrida, M., Scotti, M., Garancini, M., De Peppo, V., De Stefano, F., Laureiro, Z. L., Marchitelli, I., Franceschi, A., Cosola, D., Corleone, P., Montuori, M., Salvador, L., Manzoni, Annamaria, La Barba, G., Calcagno, P., Pennacchi, L., Conticchio, M., Ardito F. (ORCID:0000-0003-1596-2862), Giuliante F. (ORCID:0000-0001-9517-8220), Razionale F., Marinelli L., Manzoni A., Serenari, M., Lenzi, J., Cucchetti, A., Cipriani, F., Donadon, M., Ardito, Francesco, Fazio, F., Nicolini, D., Iaria, M., Famularo, S., Perri, P., Ansaloni, L., Zanello, M., Lai, Q., Conci, S., Molfino, S., Ferrari, C., Germani, P., Zago, M., Romano, M., Zimmitti, G., Antonucci, A., Fumagalli, L., Troci, A., Ferraro, V., Memeo, R., Crespi, M., Chiarelli, M., Ercolani, G., Hilal, M. A., Zanus, G., Pinotti, E., Tarchi, P., Griseri, G., Baiocchi, G. L., Ruzzenente, A., Rossi, M., Jovine, E., Maestri, M., Grazi, G. L., Romano, F., Dalla Valle, R., Ravaioli, M., Vivarelli, M., Ferrero, A., Giuliante, Felice, Torzilli, G., Aldrighetti, L., Cescon, M., Gorgone, M., Ratti, F., Costa, G., Razionale, Francesco, Russolillo, N., Marinelli, Luca, Giuffrida, M., Scotti, M., Garancini, M., De Peppo, V., De Stefano, F., Laureiro, Z. L., Marchitelli, I., Franceschi, A., Cosola, D., Corleone, P., Montuori, M., Salvador, L., Manzoni, Annamaria, La Barba, G., Calcagno, P., Pennacchi, L., Conticchio, M., Ardito F. (ORCID:0000-0003-1596-2862), Giuliante F. (ORCID:0000-0001-9517-8220), Razionale F., Marinelli L., and Manzoni A.

Abstract

Objective: To evaluate the effect of a liver transplantation (LT) program on the outcomes of resectable hepatocellular carcinoma (HCC). Background: Surgical treatment of HCC includes both hepatic resection (HR) and LT. However, the presence of cirrhosis and the possibility of recurrence make the management of this disease complex and probably different according to the presence of a LT program. Methods: Patients undergoing HR for HCC between January 2005 and December 2019 were identified from a national database of HCC. The main study outcomes were major surgical complications according to the Comprehensive Complication Index, posthepatectomy liver failure (PHLF), 90-day mortality, overall survival, and disease-free survival. Secondary outcomes were salvage liver transplantation (SLT) and postrecurrence survival. Results: A total of 3202 patients were included from 25 hospitals over the study period. Three of 25 (12%) had an LT program. The presence of an LT program within a center was associated with a reduced probability of PHLF (odds ratio=0.38) but not with overall survival and disease-free survival. There was an increased probability of SLT when HR was performed in a transplant hospital (odds ratio=12.05). Among transplant-eligible patients, those who underwent LT had a significantly longer postrecurrence survival. Conclusions: This study showed that the presence of a LT program was associated with decreased PHLF rates and an increased probability to receive SLT in case of recurrence.

Published
2023

32. Impact of neoadjuvant chemotherapy on the difficulty and outcomes of laparoscopic and robotic major liver resections for colorectal liver metastases: A propensity-score and coarsened exact-matched controlled study

Author

Ghotbi, J., Aghayan, D., Fretland, A., Edwin, B., Syn, N. L., Cipriani, F., Alzoubi, M., Lim, C., Scatton, O., Long, T. C. D., Herman, P., Coelho, F. F., Marino, M. V., Mazzaferro, V., Chiow, A. K. H., Sucandy, I., Ivanecz, A., Choi, S. -H., Lee, J. H., Prieto, M., Vivarelli, M., Giuliante, Felice, Ruzzenente, A., Yong, C. -C., Yin, M., Fondevila, C., Efanov, M., Morise, Z., Di Benedetto, F., Brustia, R., Dalla Valle, R., Boggi, U., Geller, D., Belli, A., Memeo, R., Mejia, A., Park, J. O., Rotellar, F., Choi, G. -H., Robles-Campos, R., Wang, X., Sutcliffe, R. P., Pratschke, J., Tang, C. -N., Chong, C. C. N., D'Hondt, M., Monden, K., Lopez-Ben, S., Kingham, T. P., Ferrero, A., Ettorre, G. M., Levi Sandri, G. B., Pascual, F., Cherqui, D., Liang, X., Mazzotta, A., Wakabayashi, G., Giglio, M., Troisi, R. I., Han, H. -S., Cheung, T. -T., Sugioka, A., Chen, K. -H., Liu, R., Soubrane, O., Fuks, D., Aldrighetti, L., Abu Hilal, M., Goh, B. K. P., Gastaca, M., Meurs, J., De Meyere, C., Lee, K. -F., Ng, K. K., Salimgereeva, D., Alikhanov, R., Lee, L. -S., Jang, J. Y., Kato, Y., Kojima, M., Pirola Kruger, J. A., Lopez-Lopez, V., Casellas I Robert, M., Montalti, R., Lee, B., D'Silva, M., Wang, H. -P., Saleh, M., Chen, Z., Yu, S., Vani, S., Ardito, Francesco, Giustizieri, U., Citterio, D., Mocchegiani, F., Colasanti, M., Guzman, Y., Labadie, K. P., Conticchio, M., Dogeas, E., Kauffmann, E. F., Giuffrida, M., Sommacale, D., Laurent, A., Magistri, P., Nghia, P. P., Mishima, K., Valle, B. D., Krenzien, F., Schmelzle, M., Kadam, P., Liu, Q., Lai, E. C. H., Zheng, J., Siow, T. F., Forchino, F., Giuliante F. (ORCID:0000-0001-9517-8220), Ardito F. (ORCID:0000-0003-1596-2862), Ghotbi, J., Aghayan, D., Fretland, A., Edwin, B., Syn, N. L., Cipriani, F., Alzoubi, M., Lim, C., Scatton, O., Long, T. C. D., Herman, P., Coelho, F. F., Marino, M. V., Mazzaferro, V., Chiow, A. K. H., Sucandy, I., Ivanecz, A., Choi, S. -H., Lee, J. H., Prieto, M., Vivarelli, M., Giuliante, Felice, Ruzzenente, A., Yong, C. -C., Yin, M., Fondevila, C., Efanov, M., Morise, Z., Di Benedetto, F., Brustia, R., Dalla Valle, R., Boggi, U., Geller, D., Belli, A., Memeo, R., Mejia, A., Park, J. O., Rotellar, F., Choi, G. -H., Robles-Campos, R., Wang, X., Sutcliffe, R. P., Pratschke, J., Tang, C. -N., Chong, C. C. N., D'Hondt, M., Monden, K., Lopez-Ben, S., Kingham, T. P., Ferrero, A., Ettorre, G. M., Levi Sandri, G. B., Pascual, F., Cherqui, D., Liang, X., Mazzotta, A., Wakabayashi, G., Giglio, M., Troisi, R. I., Han, H. -S., Cheung, T. -T., Sugioka, A., Chen, K. -H., Liu, R., Soubrane, O., Fuks, D., Aldrighetti, L., Abu Hilal, M., Goh, B. K. P., Gastaca, M., Meurs, J., De Meyere, C., Lee, K. -F., Ng, K. K., Salimgereeva, D., Alikhanov, R., Lee, L. -S., Jang, J. Y., Kato, Y., Kojima, M., Pirola Kruger, J. A., Lopez-Lopez, V., Casellas I Robert, M., Montalti, R., Lee, B., D'Silva, M., Wang, H. -P., Saleh, M., Chen, Z., Yu, S., Vani, S., Ardito, Francesco, Giustizieri, U., Citterio, D., Mocchegiani, F., Colasanti, M., Guzman, Y., Labadie, K. P., Conticchio, M., Dogeas, E., Kauffmann, E. F., Giuffrida, M., Sommacale, D., Laurent, A., Magistri, P., Nghia, P. P., Mishima, K., Valle, B. D., Krenzien, F., Schmelzle, M., Kadam, P., Liu, Q., Lai, E. C. H., Zheng, J., Siow, T. F., Forchino, F., Giuliante F. (ORCID:0000-0001-9517-8220), and Ardito F. (ORCID:0000-0003-1596-2862)

Abstract

Background: Minimal invasive liver resections are a safe alternative to open surgery. Different scoring systems considering different risks factors have been developed to predict the risks associated with these procedures, especially challenging major liver resections (MLR). However, the impact of neoadjuvant chemotherapy (NAT) on the difficulty of minimally invasive MLRs remains poorly investigated. Methods: Patients who underwent laparoscopic and robotic MLRs for colorectal liver metastases (CRLM) performed across 57 centers between January 2005 to December 2021 were included in this analysis. Patients who did or did not receive NAT were matched based on 1:1 coarsened exact and 1:2 propensity-score matching. Pre- and post-matching comparisons were performed. Results: In total, the data of 5189 patients were reviewed. Of these, 1411 procedures were performed for CRLM, and 1061 cases met the inclusion criteria. After excluding 27 cases with missing data on NAT, 1034 patients (NAT: n = 641; non-NAT: n = 393) were included. Before matching, baseline characteristics were vastly different. Before matching, the morbidity rate was significantly higher in the NAT-group (33.2% vs. 27.2%, p-value = 0.043). No significant differences were seen in perioperative outcomes after the coarsened exact matching. After the propensity-score matching, statistically significant higher blood loss (mean, 300 (SD 128–596) vs. 250 (SD 100–400) ml, p-value = 0.047) but shorter hospital stay (mean, 6 [4-8] vs. 6 [5-9] days, p-value = 0.043) were found in the NAT-group. Conclusion: The current study demonstrated that NAT had minimal impact on the difficulty and outcomes of minimally-invasive MLR for CRLM.

Published
2023

33. Defining Global Benchmarks for Laparoscopic Liver Resections: An International Multicenter Study

Author

Goh, B. K. P., Han, H. -S., Chen, K. -H., Chua, D. W., Chan, C. -Y., Cipriani, F., Aghayan, D. L., Fretland, A. A., Sijberden, J., D'Silva, M., Siow, T. F., Kato, Y., Lim, C., Nghia, P. P., Herman, P., Marino, M. V., Mazzaferro, V., Chiow, A. K. H., Sucandy, I., Ivanecz, A., Choi, S. H., Lee, J. H., Gastaca, M., Vivarelli, M., Giuliante, Felice, Ruzzenente, A., Yong, C. -C., Yin, M., Chen, Z., Fondevila, C., Efanov, M., Rotellar, F., Choi, G. -H., Campos, R. R., Wang, X., Sutcliffe, R. P., Pratschke, J., Lai, E., Chong, C. C., D'Hondt, M., Monden, K., Lopez-Ben, S., Coelho, F. F., Kingham, T. P., Liu, R., Long, T. C. D., Ferrero, A., Sandri, G. B. L., Saleh, M., Cherqui, D., Scatton, O., Soubrane, O., Wakabayashi, G., Troisi, R. I., Cheung, T. -T., Sugioka, A., Hilal, M. A., Fuks, D., Edwin, B., Aldrighetti, L., Syn, N., Prieto, M., Schotte, H., De Meyere, C., Krenzien, F., Schmelzle, M., Lee, K. -F., Salimgereeva, D., Alikhanov, R., Lee, L. -S., Jang, J. Y., Kojima, M., Ghotbi, J., Kruger, J. A. P., Lopez-Lopez, V., Valle, B. D., Casellas I Robert, M., Mishima, K., Montalti, R., Giglio, M., Mazzotta, A., Lee, B., Wang, H. -P., Pascual, F., Kadam, P., Tang, C. -N., Yu, S., Ardito, Francesco, Vani, S., Giustizieri, U., Citterio, D., Mocchegiani, F., Ettorre, G. M., Colasanti, M., Guzman, Y., Giuliante F. (ORCID:0000-0001-9517-8220), Ardito F. (ORCID:0000-0003-1596-2862), Goh, B. K. P., Han, H. -S., Chen, K. -H., Chua, D. W., Chan, C. -Y., Cipriani, F., Aghayan, D. L., Fretland, A. A., Sijberden, J., D'Silva, M., Siow, T. F., Kato, Y., Lim, C., Nghia, P. P., Herman, P., Marino, M. V., Mazzaferro, V., Chiow, A. K. H., Sucandy, I., Ivanecz, A., Choi, S. H., Lee, J. H., Gastaca, M., Vivarelli, M., Giuliante, Felice, Ruzzenente, A., Yong, C. -C., Yin, M., Chen, Z., Fondevila, C., Efanov, M., Rotellar, F., Choi, G. -H., Campos, R. R., Wang, X., Sutcliffe, R. P., Pratschke, J., Lai, E., Chong, C. C., D'Hondt, M., Monden, K., Lopez-Ben, S., Coelho, F. F., Kingham, T. P., Liu, R., Long, T. C. D., Ferrero, A., Sandri, G. B. L., Saleh, M., Cherqui, D., Scatton, O., Soubrane, O., Wakabayashi, G., Troisi, R. I., Cheung, T. -T., Sugioka, A., Hilal, M. A., Fuks, D., Edwin, B., Aldrighetti, L., Syn, N., Prieto, M., Schotte, H., De Meyere, C., Krenzien, F., Schmelzle, M., Lee, K. -F., Salimgereeva, D., Alikhanov, R., Lee, L. -S., Jang, J. Y., Kojima, M., Ghotbi, J., Kruger, J. A. P., Lopez-Lopez, V., Valle, B. D., Casellas I Robert, M., Mishima, K., Montalti, R., Giglio, M., Mazzotta, A., Lee, B., Wang, H. -P., Pascual, F., Kadam, P., Tang, C. -N., Yu, S., Ardito, Francesco, Vani, S., Giustizieri, U., Citterio, D., Mocchegiani, F., Ettorre, G. M., Colasanti, M., Guzman, Y., Giuliante F. (ORCID:0000-0001-9517-8220), and Ardito F. (ORCID:0000-0003-1596-2862)

Abstract

Objective: To establish global benchmark outcomes indicators after laparoscopic liver resections (L-LR). Background: There is limited published data to date on the best achievable outcomes after L-LR. Methods: This is a post hoc analysis of a multicenter database of 11,983 patients undergoing L-LR in 45 international centers in 4 continents between 2015 and 2020. Three specific procedures: left lateral sectionectomy (LLS), left hepatectomy (LH), and right hepatectomy (RH) were selected to represent the 3 difficulty levels of L-LR. Fifteen outcome indicators were selected to establish benchmark cutoffs. Results: There were 3519 L-LR (LLS, LH, RH) of which 1258 L-LR (40.6%) cases performed in 34 benchmark expert centers qualified as low-risk benchmark cases. These included 659 LLS (52.4%), 306 LH (24.3%), and 293 RH (23.3%). The benchmark outcomes established for operation time, open conversion rate, blood loss ≥500 mL, blood transfusion rate, postoperative morbidity, major morbidity, and 90-day mortality after LLS, LH, and RH were 209.5, 302, and 426 minutes; 2.1%, 13.4%, and 13.0%; 3.2%, 20%, and 47.1%; 0%, 7.1%, and 10.5%; 11.1%, 20%, and 50%; 0%, 7.1%, and 20%; and 0%, 0%, and 0%, respectively. Conclusions: This study established the first global benchmark outcomes for L-LR in a large-scale international patient cohort. It provides an up-to-date reference regarding the "best achievable" results for L-LR for which centers adopting L-LR can use as a comparison to enable an objective assessment of performance gaps and learning curves.

Published
2023

34. AI technologies and employment: micro evidence from the supply side

Author

Damioli, Giacomo, Van Roy, V., Vertesy, D., Vivarelli, Marco, Damioli G., Vivarelli M. (ORCID:0000-0002-8746-9324), Damioli, Giacomo, Van Roy, V., Vertesy, D., Vivarelli, Marco, Damioli G., and Vivarelli M. (ORCID:0000-0002-8746-9324)

Abstract

In this work we investigate the possible job-creation impact of artificial intelligence (AI) technologies, focusing on the supply side, where the development of these technologies can be conceived as product innovations in upstream sectors. The empirical analysis is based on a worldwide longitudinal sample (obtained by merging the EPO PATSTAT and BvD-ORBIS databases) of more than 3,500 front-runner companies that patented AI-related inventions over the period 2000–2016. Based on system GMM estimates of dynamic panel models, our results show a positive and significant impact of AI patent families on employment, supporting the labour-friendly nature of AI product innovation.

Published
2023

35. Regret affects the choice between neoadjuvant therapy and upfront surgery for potentially resectable pancreatic cancer

Author

Cucchetti, A., Djulbegovic, B., Crippa, S., Hozo, I., Sbrancia, M., Tsalatsanis, A., Binda, C., Fabbri, C., Salvia, R., Falconi, M., Ercolani, G., Alfieri, Sergio, Amato, A., Amisano, M., Anderloni, A., Maestri, A., Coluccio, C., Brandi, G., Casadei-Gardini, A., Cennamo, V., Crino, S. F., Valle, R. D., De Angelis, C., Di Battista, M., Di Maio, M., Di Marco, M., Di Matteo, F., Di Mitri, R., Ettorre, G. M., Facciorusso, A., Farina, G., Ferrari, G., Fornaro, L., Frigerio, I., Frisone, D., Fuccio, L., Gardini, A., Garufi, C., Giampieri, R., Grazi, G. L., Jovine, E., Kauffmann, E., Langella, S., Larghi, Alberto Leonardo, Manno, M., Marciano, E., Marzioni, M., Merighi, A., Mutignani, M., Nardo, B., Niger, M., Palmisano, V., Partelli, S., Pinto, C., Piras, E., Rapposelli, I. G., Reni, M., Ricci, C., Rimassa, L., Siena, S., Spada, Cristiano, Sperti, E., Spezzaferro, M., Sposito, C., Tamberi, S., Troisi, R., Veneroni, L., Vivarelli, M., Zerbi, A., Alfieri S. (ORCID:0000-0002-0404-724X), Larghi A., Spada C. (ORCID:0000-0002-5692-0960), Cucchetti, A., Djulbegovic, B., Crippa, S., Hozo, I., Sbrancia, M., Tsalatsanis, A., Binda, C., Fabbri, C., Salvia, R., Falconi, M., Ercolani, G., Alfieri, Sergio, Amato, A., Amisano, M., Anderloni, A., Maestri, A., Coluccio, C., Brandi, G., Casadei-Gardini, A., Cennamo, V., Crino, S. F., Valle, R. D., De Angelis, C., Di Battista, M., Di Maio, M., Di Marco, M., Di Matteo, F., Di Mitri, R., Ettorre, G. M., Facciorusso, A., Farina, G., Ferrari, G., Fornaro, L., Frigerio, I., Frisone, D., Fuccio, L., Gardini, A., Garufi, C., Giampieri, R., Grazi, G. L., Jovine, E., Kauffmann, E., Langella, S., Larghi, Alberto Leonardo, Manno, M., Marciano, E., Marzioni, M., Merighi, A., Mutignani, M., Nardo, B., Niger, M., Palmisano, V., Partelli, S., Pinto, C., Piras, E., Rapposelli, I. G., Reni, M., Ricci, C., Rimassa, L., Siena, S., Spada, Cristiano, Sperti, E., Spezzaferro, M., Sposito, C., Tamberi, S., Troisi, R., Veneroni, L., Vivarelli, M., Zerbi, A., Alfieri S. (ORCID:0000-0002-0404-724X), Larghi A., and Spada C. (ORCID:0000-0002-5692-0960)

Abstract

Background: When treating potentially resectable pancreatic adenocarcinoma, therapeutic decisions are left to the sensibility of treating clinicians who, faced with a decision that post hoc can be proven wrong, may feel a sense of regret that they want to avoid. A regret-based decision model was applied to evaluate attitudes to-ward neoadjuvant therapy versus upfront surgery for potentially resectable pancreatic adenocarcinoma.Methods: Three clinical scenarios describing high-, intermediate-, and low-risk disease-specific mortality after upfront surgery were presented to 60 respondents (20 oncologists, 20 gastroenterologists, and 20 surgeons). Respondents were asked to report their regret of omission and commission regarding neo-adjuvant chemotherapy on a scale between 0 (no regret) and 100 (maximum regret). The threshold model and a multilevel mixed regression were applied to analyze respondents' attitudes toward neo-adjuvant therapy.Results: The lowest regret of omission was elicited in the low-risk scenario, and the highest regret in the high-risk scenario (P < .001). The regret of the commission was diametrically opposite to the regret of omission (P < .001). The disease-specific threshold mortality at which upfront surgery is favored over the neoadjuvant therapy progressively decreased from the low-risk to the high-risk scenarios (P <=.001). The nonsurgeons working in or with lower surgical volume centers (P = .010) and surgeons (P = .018) accepted higher disease-specific mortality after upfront surgery, which resulted in the lower likelihood of adopting neoadjuvant therapy.Conclusion: Regret drives decision making in the management of pancreatic adenocarcinoma. Being a surgeon or a specialist working in surgical centers with lower patient volumes reduces the likelihood of recommending neoadjuvant therapy.(c) 2023 Elsevier Inc. All rights reserved.

Published
2023

36. Comparison between the difficulty of laparoscopic limited liver resections of tumors located in segment 7 versus segment 8: An international multicenter propensity-score matched study

Author

Efanov, M., Salimgereeva, D., Alikhanov, R., Wu, A. G. R., Geller, D., Cipriani, F., Aghayan, D. L., Fretland, A. A., Sijberden, J., Belli, A., Marino, M. V., Mazzaferro, V., Chiow, A. K. H., Sucandy, I., Ivanecz, A., Choi, S. H., Lee, J. H., Prieto, M., Vivarelli, M., Giuliante, Felice, Ruzzenente, A., Yong, C. -C., Fondevila, C., Rotellar, F., Choi, G. -H., Robless Campos, R., Wang, X., Sutcliffe, R. P., Pratschke, J., Lai, E., Chong, C. C., D'Hondt, M., Monden, K., Lopez-Ben, S., Herman, P., Di Benedetto, F., Kingham, T. P., Liu, R., Long, T. C. D., Ferrero, A., Levi Sandri, G. B., Cherqui, D., Scatton, O., Wakabayashi, G., Troisi, R. I., Cheung, T. -T., Sugioka, A., Han, H. -S., Abu Hilal, M., Soubrane, O., Fuks, D., Aldrighetti, L., Edwin, B., Goh, B. K. P., Chan, C. -Y., Syn, N., D'Silva, M., Lee, B., Lim, C., Nghia, P. P., Gastaca, M., Schotte, H., De Meyere, C., Krenzien, F., Schmelzle, M., Lee, K. -F., Lee, L. S., Jang, J. Y., Kojima, M., Kato, Y., Ghotbi, J., Kruger, J. A. P., Coelho, F. F., Lopez-Lopez, V., Valle, B. D., Robert, M. C. I., Mishima, K., Montalti, R., Giglio, M., Wang, H. -P., Pascual, F., Saleh, M., Kadam, P., Tang, C. -N., Ardito, Francesco, Vani, S., Giustizieri, U., Citterio, D., Mocchegiani, F., Ettorre, G. M., Colasanti, M., Guzman, Y., Dogeas, E., Magistri, P., Mazzotta, A., Giuliante F. (ORCID:0000-0001-9517-8220), Ardito F. (ORCID:0000-0003-1596-2862), Efanov, M., Salimgereeva, D., Alikhanov, R., Wu, A. G. R., Geller, D., Cipriani, F., Aghayan, D. L., Fretland, A. A., Sijberden, J., Belli, A., Marino, M. V., Mazzaferro, V., Chiow, A. K. H., Sucandy, I., Ivanecz, A., Choi, S. H., Lee, J. H., Prieto, M., Vivarelli, M., Giuliante, Felice, Ruzzenente, A., Yong, C. -C., Fondevila, C., Rotellar, F., Choi, G. -H., Robless Campos, R., Wang, X., Sutcliffe, R. P., Pratschke, J., Lai, E., Chong, C. C., D'Hondt, M., Monden, K., Lopez-Ben, S., Herman, P., Di Benedetto, F., Kingham, T. P., Liu, R., Long, T. C. D., Ferrero, A., Levi Sandri, G. B., Cherqui, D., Scatton, O., Wakabayashi, G., Troisi, R. I., Cheung, T. -T., Sugioka, A., Han, H. -S., Abu Hilal, M., Soubrane, O., Fuks, D., Aldrighetti, L., Edwin, B., Goh, B. K. P., Chan, C. -Y., Syn, N., D'Silva, M., Lee, B., Lim, C., Nghia, P. P., Gastaca, M., Schotte, H., De Meyere, C., Krenzien, F., Schmelzle, M., Lee, K. -F., Lee, L. S., Jang, J. Y., Kojima, M., Kato, Y., Ghotbi, J., Kruger, J. A. P., Coelho, F. F., Lopez-Lopez, V., Valle, B. D., Robert, M. C. I., Mishima, K., Montalti, R., Giglio, M., Wang, H. -P., Pascual, F., Saleh, M., Kadam, P., Tang, C. -N., Ardito, Francesco, Vani, S., Giustizieri, U., Citterio, D., Mocchegiani, F., Ettorre, G. M., Colasanti, M., Guzman, Y., Dogeas, E., Magistri, P., Mazzotta, A., Giuliante F. (ORCID:0000-0001-9517-8220), and Ardito F. (ORCID:0000-0003-1596-2862)

Abstract

Background: Presently, according to different difficulty scoring systems, there is no difference in complexity estimation of laparoscopic liver resection (LLR) of segments 7 and 8. However, there is no published data supporting this assumption. To date, no studies have compared the outcomes of laparoscopic parenchyma-sparing resection of the liver segments 7 and 8. Methods: A post hoc analysis of patients undergoing LLR of segments 7 and 8 in 46 centers between 2004 and 2020 was performed. 1:1 Propensity score matching (PSM) was used to compare isolated LLR of segments 7 and 8. Subset analyses were also performed to compare atypical resections and segmentectomies of 7 and 8. Results: A total of 2411 patients were identified, and 1691 patients met the inclusion criteria. Comparison after PSM between the entire cohort of segment 7 and segment 8 resections revealed inferior results for segment 7 resection in terms of increased blood loss, blood transfusions, and conversions to open surgery. Subset analyses of only atypical resections similarly demonstrated poorer outcomes for segment 7 in terms of increased blood loss, operation time, blood transfusions, and conversions to open surgery. Conversely, a subgroup analysis of segmentectomies after PSM found better outcomes for segment 7 in terms of a shorter operation time and hospital stay. Conclusion: Differences in the outcomes of segments 7 and 8 resections suggest a greater difficulty of laparoscopic atypical resection of segment 7 compared to segment 8, and greater difficulty of segmentectomy 8 compared to segmentectomy 7.

Published
2023

37. The productivity impact of short-term labor mobility across industries

Author

Piva, Mariacristina, Tani, M., Vivarelli, Marco, Piva M. (ORCID:0000-0002-3347-8946), Vivarelli M. (ORCID:0000-0002-8746-9324), Piva, Mariacristina, Tani, M., Vivarelli, Marco, Piva M. (ORCID:0000-0002-3347-8946), and Vivarelli M. (ORCID:0000-0002-8746-9324)

Abstract

The restrictions on labor mobility imposed in the COVID-19 pandemic heighten the need to review in detail the role of mobility in improving productivity and fostering economic growth. In this study, we carry out a comprehensive analysis of business visits (BVs) understood as a productivity-enhancing intrapreneurial strategy, using the most extensive set of data available, covering 33 sectors and 14 countries during the period 1998–2013. Our database merges unique information on expenditures on BVs by sector, country, and year, sourced from the US National Business Travel Association, with OECD and World Bank productivity data. We find that BVs raise labor productivity in a significant way, but short-term labor mobility exhibits decreasing returns, being more crucial in those firms, sectors, and countries characterized by less mobility and by lower productivity performances.

Published
2023

38. Automation and related technologies: a mapping of the new knowledge base

Author

Santarelli, E., Staccioli, Jacopo, Vivarelli, Marco, Staccioli J. (ORCID:0000-0002-9068-2927), Vivarelli M. (ORCID:0000-0002-8746-9324), Santarelli, E., Staccioli, Jacopo, Vivarelli, Marco, Staccioli J. (ORCID:0000-0002-9068-2927), and Vivarelli M. (ORCID:0000-0002-8746-9324)

Abstract

Using the entire population of USPTO patent applications published between 2002 and 2019, and leveraging on both patent classification and semantic analysis, this paper aims to map the current knowledge base centred on robotics and AI technologies. These technologies are investigated both as a whole and distinguishing core and related innovations, along a 4-level core-periphery architecture. Merging patent applications with the Orbis IP firm-level database allows us to put forward a twofold analysis based on industry of activity and geographic location. In a nutshell, results show that: (i) rather than representing a technological revolution, the new knowledge base is strictly linked to the previous technological paradigm; (ii) the new knowledge base is characterised by a considerable—but not impressively widespread—degree of pervasiveness; (iii) robotics and AI are strictly related, converging (particularly among the related technologies and in more recent times) and jointly shaping a new knowledge base that should be considered as a whole, rather than consisting of two separate GPTs; (iv) the US technological leadership turns out to be confirmed (although declining in relative terms in favour of Asian countries such as South Korea, China and, more recently, India).

Published
2023

39. A phase I study of autologous mesenchymal stromal cells for severe steroid-dependent nephrotic syndrome

Author

Vivarelli, M., Colucci, M., Algeri, M., Zotta, F., Emma, F., L'Erario, I., Busutti, M., Rota, S., Capelli, C., Introna, M., Todeschini, M., Casiraghi, F., Perna, A., Peracchi, T., De Salvo, A., Rubis, N., Locatelli, Franco, Remuzzi, G., Ruggenenti, P., Locatelli F. (ORCID:0000-0002-7976-3654), Vivarelli, M., Colucci, M., Algeri, M., Zotta, F., Emma, F., L'Erario, I., Busutti, M., Rota, S., Capelli, C., Introna, M., Todeschini, M., Casiraghi, F., Perna, A., Peracchi, T., De Salvo, A., Rubis, N., Locatelli, Franco, Remuzzi, G., Ruggenenti, P., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

BACKGROUNDSevere forms of idiopathic nephrotic syndrome (INS) require prolonged immunosuppressive therapies and repeated courses of high-dose glucocorticoids. Mesenchymal stromal cells (MSCs) have promising immunomodulatory properties that may be employed therapeutically to reduce patient exposure to medications and their side effects.METHODSWe performed a phase I open-label trial assessing safety and feasibility of autologous bone marrow-derived MSCs (BM-MSCs) in children and young adults with severe forms of steroid-dependent nephrotic syndrome. Following autologous BM-MSC preparation and infusion, oral immunosuppression was tapered. Safety, efficacy, and immunomodulatory effects in vivo were monitored for 12 months.RESULTSSixteen patients (10 children, 6 adults) were treated. Adverse events were limited and not related to BM-MSC infusions. All patients relapsed during follow-up, but in the 10 treated children, time to first relapse was delayed (P = 0.02) and number of relapses was reduced (P = 0.002) after BM-MSC infusion, compared with the previous 12 months. Cumulative prednisone dose was also reduced at 12 months compared with baseline (P < 0.05). No treatment benefit was observed in adults.In children, despite tapering of immunosuppression, clinical benefit was mirrored by a significant reduction in total CD19+, mature, and memory B cells and an increase in regulatory T cells in vivo up to 3-6 months following BM-MSC infusionCONCLUSIONTreatment with autologous BM-MSCs is feasible and safely reduces relapses and immunosuppression at 12 months in children with severe steroid-dependent INS. Immunomodulatory studies suggest that repeating MSC infusions at 3-6 months may sustain benefit.TRIAL REGISTRATIONEudraCT 2016-004804-77.FUNDINGAIFA Ricerca Indipendente 2016-02364623.

Published
2023

40. WCN23-0584 A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 3 STUDY TO ASSESS THE EFFICACY AND SAFETY OF IPTACOPAN IN IDIOPATHIC IMMUNE COMPLEX-MEDIATED MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS (IC-MPGN)

Author

VELDANDI, U.K., primary, Kavanagh, D., additional, Vivarelli, M., additional, Bomback, A., additional, Wang, Y., additional, Bogdanowicz, K., additional, Webb, N., additional, Meier, M., additional, and Smith, R.J.H., additional

Published
2023
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43. Single Large Hepatocellular Carcinoma > 5 cm with Surgical Indication: Is it Mandatory a Major Hepatectomy? A Propensity-score Weighted Analysis

Author

Garancini, M., primary, Ferrero, A., additional, De Carlis, L., additional, Grazi, G.L., additional, Giuliante, F., additional, Cillo, U., additional, Cescon, M., additional, Valle, R. Dalla, additional, Vivarelli, M., additional, Torzilli, G., additional, Aldrighetti, L., additional, Romano, Fabrizio, additional, Donadon, Matteo, additional, Cipriani, Federica, additional, Serenari, Matteo, additional, Ardito, Francesco, additional, Lauterio, Andrea, additional, Vitale, Alessandro, additional, Fazio, Federico, additional, Nicolini, Daniele, additional, Perri, Pasquale, additional, Iaria, Giuseppe, additional, Famularo, Simone, additional, Dominioni, Tommaso, additional, Zanello, Matteo, additional, Lai, Quirino, additional, Conci, Simone, additional, Molfino, Sarah, additional, Ferrari, Cecilia, additional, Germani, Paola, additional, Scotti, Mauro Alessandro, additional, Zago, Mauro, additional, Zimmitti, Giuseppe, additional, La Barba Maurizio Romano, Giuliano, additional, Sciannamea, Ivano, additional, Fumagalli, Luca, additional, Troci, Albert, additional, Ferraro, Valentina, additional, Memeo, Riccardo, additional, Crespi, Michele, additional, Chiarelli, Marco, additional, Antonucci, Adelmo, additional, Zanus, Giacomo, additional, Ercolani, Giorgio, additional, Hilal, Moh’d Abu, additional, Pinotti, Enrico, additional, Tarchi, Paola, additional, Griseri, Guido, additional, Baiocchi, Gian Luca, additional, Ruzzenente, Andrea, additional, Rossi, Massimo, additional, Jovine, Elio, additional, and Maestri, Marcello, additional

Published
2023
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46. Comparison between the difficulty of laparoscopic limited liver resections of tumors located in segment 7 versus segment 8

Author

Efanov, M., Salimgereeva, D., Alikhanov, R., A. G. R., Wu, Geller, D., Cipriani, F., Aghayan, D. L., Fretland, A. A., Sijberden, J., Belli, A., Marino, M. V., Mazzaferro, V., Chiow, A. K. H., Sucandy, I., Ivanecz, A., Choi, S. H., Lee, J. H., Prieto, M., Vivarelli, M., Giuliante, Felice, Ruzzenente, A., Yong, C. -C., Fondevila, C., Rotellar, F., Choi, G. -H., Robless Campos, R., Wang, X., Sutcliffe, R. P., Pratschke, J., Lai, E., Chong, C. C., D'Hondt, M., Monden, K., Lopez-Ben, S., Herman, P., Di Benedetto, F., Kingham, T. P., Liu, R., Long, T. C. D., Ferrero, A., Levi Sandri, G. B., Cherqui, D., Scatton, O., Wakabayashi, G., Troisi, R. I., Cheung, T. -T., Sugioka, A., Han, H. -S., Abu Hilal, M., Soubrane, O., Fuks, D., Aldrighetti, L., Edwin, B., Goh, B. K. P., Chan, C. -Y., Syn, N., D'Silva, M., Lee, B., Lim, C., Nghia, P. P., Gastaca, M., Schotte, H., De Meyere, C., Krenzien, F., Schmelzle, M., Lee, K. -F., Lee, L. S., Jang, J. Y., Kojima, M., Kato, Y., Ghotbi, J., Kruger, J. A. P., Coelho, F. F., Lopez-Lopez, V., Valle, B. D., Robert, M. C. I., Mishima, K., Montalti, R., Giglio, M., Wang, H. -P., Pascual, F., Saleh, M., Kadam, P., Tang, C. -N., Ardito, Francesco, Vani, S., Giustizieri, U., Citterio, D., Mocchegiani, F., Ettorre, G. M., Colasanti, M., Guzman, Y., Dogeas, E., Magistri, P., Mazzotta, A., Graduate School, Surgery, CCA - Cancer Treatment and Quality of Life, Efanov, M., Salimgereeva, D., Alikhanov, R., Wu, A. G. R., Geller, D., Cipriani, F., Aghayan, D. L., Fretland, A. A., Sijberden, J., Belli, A., Marino, M. V., Mazzaferro, V., Chiow, A. K. H., Sucandy, I., Ivanecz, A., Choi, S. H., Lee, J. H., Prieto, M., Vivarelli, M., Giuliante, F., Ruzzenente, A., Yong, C. -C., Fondevila, C., Rotellar, F., Choi, G. -H., Robless Campos, R., Wang, X., Sutcliffe, R. P., Pratschke, J., Lai, E., Chong, C. C., D'Hondt, M., Monden, K., Lopez-Ben, S., Herman, P., Di Benedetto, F., Kingham, T. P., Liu, R., Long, T. C. D., Ferrero, A., Levi Sandri, G. B., Cherqui, D., Scatton, O., Wakabayashi, G., Troisi, R. I., Cheung, T. -T., Sugioka, A., Han, H. -S., Abu Hilal, M., Soubrane, O., Fuks, D., Aldrighetti, L., Edwin, B., Goh, B. K. P., Chan, C. -Y., Syn, N., D'Silva, M., Lee, B., Lim, C., Nghia, P. P., Gastaca, M., Schotte, H., De Meyere, C., Krenzien, F., Schmelzle, M., Lee, K. -F., Lee, L. S., Jang, J. Y., Kojima, M., Kato, Y., Ghotbi, J., Kruger, J. A. P., Coelho, F. F., Lopez-Lopez, V., Valle, B. D., Robert, M. C. I., Mishima, K., Montalti, R., Giglio, M., Wang, H. -P., Pascual, F., Saleh, M., Kadam, P., Tang, C. -N., Ardito, F., Vani, S., Giustizieri, U., Citterio, D., Mocchegiani, F., Ettorre, G. M., Colasanti, M., Guzman, Y., Dogeas, E., Magistri, P., Mazzotta, A., Efanov, Mikhail, Salimgereeva, Diana, Alikhanov, Ruslan, Wu, Andrew G R, Geller, David, Cipriani, Federica, Aghayan, Davit L, Fretland, Asmund Avdem, Sijberden, Jasper, Belli, Andrea, Marino, Marco V, Mazzaferro, Vincenzo, Chiow, Adrian K H, Sucandy, Iswanto, Ivanecz, Arpad, Choi, Sung Hoon, Lee, Jae Hoon, Prieto, Mikel, Vivarelli, Marco, Giuliante, Felice, Ruzzenente, Andrea, Yong, Chee-Chien, Fondevila, Constantino, Rotellar, Fernando, Choi, Gi-Hong, Robless Campos, Ricardo, Wang, Xiaoying, Sutcliffe, Robert P, Pratschke, Johann, Lai, Eric, Chong, Charing C, D'Hondt, Mathieu, Monden, Kazuteru, Lopez-Ben, Santiago, Herman, Paulo, Di Benedetto, Fabrizio, Kingham, T Peter, Liu, Rong, Long, Tran Cong Duy, Ferrero, Alessandro, Levi Sandri, Giovanni Battista, Cherqui, Daniel, Scatton, Olivier, Wakabayashi, Go, Troisi, Roberto I, Cheung, Tan-To, Sugioka, Atsushi, Han, Ho-Seong, Abu Hilal, Mohammad, Soubrane, Olivier, Fuks, David, Aldrighetti, Luca, Edwin, Bjorn, and Goh, Brian K P

Subjects
hepatectomy, laparoscopy, liver resection, posterosuperior segments, risk score, Hepatology, Settore MED/18 - CHIRURGIA GENERALE, Surgery, posterosuperior segment
Abstract

Background: Presently, according to different difficulty scoring systems, there is no difference in complexity estimation of laparoscopic liver resection (LLR) of segments 7 and 8. However, there is no published data supporting this assumption. To date, no studies have compared the outcomes of laparoscopic parenchyma-sparing resection of the liver segments 7 and 8. Methods: A post hoc analysis of patients undergoing LLR of segments 7 and 8 in 46 centers between 2004 and 2020 was performed. 1:1 Propensity score matching (PSM) was used to compare isolated LLR of segments 7 and 8. Subset analyses were also performed to compare atypical resections and segmentectomies of 7 and 8. Results: A total of 2411 patients were identified, and 1691 patients met the inclusion criteria. Comparison after PSM between the entire cohort of segment 7 and segment 8 resections revealed inferior results for segment 7 resection in terms of increased blood loss, blood transfusions, and conversions to open surgery. Subset analyses of only atypical resections similarly demonstrated poorer outcomes for segment 7 in terms of increased blood loss, operation time, blood transfusions, and conversions to open surgery. Conversely, a subgroup analysis of segmentectomies after PSM found better outcomes for segment 7 in terms of a shorter operation time and hospital stay. Conclusion: Differences in the outcomes of segments 7 and 8 resections suggest a greater difficulty of laparoscopic atypical resection of segment 7 compared to segment 8, and greater difficulty of segmentectomy 8 compared to segmentectomy 7.

Published
2022
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47. Current practice of normothermic regional perfusion and machine perfusion in donation after circulatory death liver transplants in Italy

Author

De Carlis, R., Lauterio, A., Centonze, L., Buscemi, V., Schlegel, A., Muiesan, P., De Carlis, L., Carraro, A., Ghinolfi, D., De Simone, P., Ravaioli, M., Cescon, M., Dondossola, D., Bongini, M., Mazzaferro, V., Pagano, D., Gruttadauria, S., Gringeri, E., Cillo, U., Patrono, D., Romagnoli, R., Camagni, S., Colledan, M., Olivieri, T., Di Benedetto, F., Vennarecci, G., Baccarani, U., Lai, Q., Rossi, M., Manzia, T. M., Tisone, G., Vivarelli, M., Scalera, I., Lupo, L. G., Andorno, E., Meniconi, R. L., Ettorre, G. M., Avolio, A. W., Agnes, S., Pellegrino, R. A., Zamboni, F., De Carlis, R, Lauterio, A, Centonze, L, Buscemi, V, Schlegel, A, Muiesan, P, De Carlis, L, Carraro, A, Ghinolfi, D, De Simone, P, Ravaioli, M, Cescon, M, Dondossola, D, Bongini, M, Mazzaferro, V, Pagano, D, Gruttadauria, S, Gringeri, E, Cillo, U, Patrono, D, Romagnoli, R, Camagni, S, Colledan, M, Olivieri, T, Di Benedetto, F, Vennarecci, G, Baccarani, U, Lai, Q, Rossi, M, Manzia, T, Tisone, G, Vivarelli, M, Scalera, I, Lupo, L, Andorno, E, Meniconi, R, Ettorre, G, Avolio, A, Agnes, S, Pellegrino, R, and Zamboni, F

Subjects
Warm ischemia, Hypothermic oxygenated perfusion, Ischemic-type biliary lesions, Liver preservation, Liver utilization, Graft Survival, Organ Preservation, Ischemic-type biliary lesion, Tissue Donors, Settore MED/18, Liver Transplantation, Perfusion, Humans, Surgery
Abstract

Background: Normothermic regional perfusion (NRP) and machine perfusion (MP) are variously used in many European centers to improve the outcomes after liver transplantation from donation after circulatory death (DCD). In Italy, a combination of NRP and subsequent MP has been used since the start of the activity. While NRP is mandatory for every DCD recovery, the subsequent use of MP is left to each center. Methods: We have designed a national survey to investigate practices and policies of these techniques. The questionnaire included 46 questions and was distributed to all the 21 Italian centers using an online form between June and July 2021. Results: The overall response rate was 100%. A local NRP program for controlled Maastricht type 3 DCD was active in 11/21 (52.4%) centers. Organization and availability of personnel were perceived as the main difficulties in starting such a program. Between 2015 and 2020, 119 DCD livers were transplanted, with an overall utilization rate of 69.2%. Pump flow and gross aspect were considered the most reliable parameters in liver selection during NRP. Eight (72.7%) centers adopted subsequent hypothermic MP, 1 (9.1%) center normothermic MP, and the remaining 2 (18.2%) used both MP types. Conclusion: This first snapshot survey shows that NRP with subsequent MP is the most used protocol in Italy for DCD livers, although some heterogeneity exists in the type and purpose of MP between centers. Overall, this policy ensures a high utilization rate, considering the high risk of the DCD donor population in Italy. Graphical abstract: [Figure not available: see fulltext.]

Published
2022

48. Impact of tumor size on the difficulty of laparoscopic left lateral sectionectomies

Author

Arizza, G., Russolillo, N., Ferrero, A., Syn, N. L., Cipriani, F., Aghayan, D., Marino, M. V., Memeo, R., Mazzaferro, V., Chiow, A. K. H., Sucandy, I., Ivanecz, A., Vivarelli, M., Di Benedetto, F., Choi, S. -H., Lee, J. H., Park, J. O., Gastaca, M., Fondevila, C., Efanov, M., Rotellar, F., Choi, G. -H., Robles-Campos, R., Wang, X., Sutcliffe, R. P., Pratschke, J., Tang, C. N., Chong, C. C., D'Hondt, M., Yong, C. C., Ruzzenente, A., Herman, P., Kingham, T. P., Scatton, O., Liu, R., Levi Sandri, G. B., Soubrane, O., Mejia, A., Lopez-Ben, S., Monden, K., Wakabayashi, G., Cherqui, D., Troisi, R. I., Yin, M., Giuliante, Felice, Geller, D., Sugioka, A., Edwin, B., Cheung, T. -T., Long, T. C. D., Hilal, M. A., Fuks, D., Chen, K. -H., Aldrighetti, L., Han, H. -S., Goh, B. K. P., Chan, C. -Y., Prieto, M., Meurs, J., De Meyere, C., Krenzien, F., Schmelzle, M., Lee, K. -F., K. K., Ng, Salimgereeva, D., Alikhanov, R., Lee, L. -S., Jang, J. Y., Labadie, K. P., Kato, Y., Kojima, M., Fretland, A. A., Ghotbi, J., Coelho, F. F., Kruger, J. A. P., Lopez-Lopez, V., Magistri, P., Robert, M. C. I., Mishima, K., Montalti, R., Giglio, M., Mazzotta, A., Lee, B., D'Silva, M., Wang, H. -P., Saleh, M., Pascual, F., Suhool, A., Nghia, P. P., Lim, C., Liu, Q., Kadam, P., Dalla Valle, B., Lai, E. C., Conticchio, M., Giustizieri, U., Citterio, D., Chen, Z., Yu, S., Ardito, Francesco, Vani, S., Dogeas, E., Siow, T. F., Mocchegianni, F., Ettorre, G. M., Colasanti, M., Guzman, Y., Arizza, G., Russolillo, N., Ferrero, A., Syn, N. L., Cipriani, F., Aghayan, D., Marino, M. V., Memeo, R., Mazzaferro, V., Chiow, A. K. H., Sucandy, I., Ivanecz, A., Vivarelli, M., Di Benedetto, F., Choi, S. -H., Lee, J. H., Park, J. O., Gastaca, M., Fondevila, C., Efanov, M., Rotellar, F., Choi, G. -H., Robles-Campos, R., Wang, X., Sutcliffe, R. P., Pratschke, J., Tang, C. N., Chong, C. C., D'Hondt, M., Yong, C. C., Ruzzenente, A., Herman, P., Kingham, T. P., Scatton, O., Liu, R., Levi Sandri, G. B., Soubrane, O., Mejia, A., Lopez-Ben, S., Monden, K., Wakabayashi, G., Cherqui, D., Troisi, R. I., Yin, M., Giuliante, F., Geller, D., Sugioka, A., Edwin, B., Cheung, T. -T., Long, T. C. D., Hilal, M. A., Fuks, D., Chen, K. -H., Aldrighetti, L., Han, H. -S., Goh, B. K. P., Chan, C. -Y., Prieto, M., Meurs, J., De Meyere, C., Krenzien, F., Schmelzle, M., Lee, K. -F., Ng, K. K., Salimgereeva, D., Alikhanov, R., Lee, L. -S., Jang, J. Y., Labadie, K. P., Kato, Y., Kojima, M., Fretland, A. A., Ghotbi, J., Coelho, F. F., Kruger, J. A. P., Lopez-Lopez, V., Magistri, P., Robert, M. C. I., Mishima, K., Montalti, R., Giglio, M., Mazzotta, A., Lee, B., D'Silva, M., Wang, H. -P., Saleh, M., Pascual, F., Suhool, A., Nghia, P. P., Lim, C., Liu, Q., Kadam, P., Dalla Valle, B., Lai, E. C., Conticchio, M., Giustizieri, U., Citterio, D., Chen, Z., Yu, S., Ardito, F., Vani, S., Dogeas, E., Siow, T. F., Mocchegianni, F., Ettorre, G. M., Colasanti, M., and Guzman, Y.

Subjects
difficulty, laparoscopic hepatectomy, laparoscopic liver, left lateral sectionectomy, size, Hepatology, Settore MED/18 - CHIRURGIA GENERALE, Surgery
Abstract

Background: Tumor size (TS) represents a critical parameter in the risk assessment of laparoscopic liver resections (LLR). Moreover, TS has been rarely related to the extent of liver resection. The aim of this study was to study the relationship between tumor size and difficulty of laparoscopic left lateral sectionectomy (L-LLS). Methods: The impact of TS cutoffs was investigated by stratifying tumor size at each 10 mm-interval. The optimal cutoffs were chosen taking into consideration the number of endpoints which show a statistically significant split around the cut-points of interest and the magnitude of relative risk after correction for multiple risk factors. Results: A total of 1910 L-LLS were included. Overall, open conversion and intraoperative blood transfusion were 3.1 and 3.3%, respectively. The major morbidity rate was 2.7% and 90-days mortality 0.6%. Three optimal TS cutoffs were identified: 40-, 70-, and 100-mm. All the selected cutoffs showed a significant discriminative power for the prediction of open conversion, operative time, blood transfusion and need of Pringle maneuver. Moreover, 70- and 100-mm cutoffs were both discriminative for estimated blood loss and major complications. A stepwise increase in rates of open conversion rate (Z = 3.90, P

Published
2022

49. An Italian survey on the use of T-tube in liver transplantation: old habits die hard!

Author

Pravisani, R, De Simone, P, Patrono, D, Lauterio, A, Cescon, M, Gringeri, E, Colledan, M, Di Benedetto, F, di Francesco, F, Antonelli, B, Manzia, T, Carraro, A, Vivarelli, M, Regalia, E, Vennarecci, G, Guglielmo, N, Cesaretti, M, Avolio, A, Valentini, M, Lai, Q, Baccarani, U, Pravisani R, De Simone P, Patrono D, Lauterio A, Cescon M, Gringeri E, Colledan M, Di Benedetto F, di Francesco F, Antonelli B, Manzia TM, Carraro A, Vivarelli M, Regalia E, Vennarecci G, Guglielmo N, Cesaretti M, Avolio AW, Valentini MF, Lai QRO, Baccarani U, Pravisani, R, De Simone, P, Patrono, D, Lauterio, A, Cescon, M, Gringeri, E, Colledan, M, Di Benedetto, F, di Francesco, F, Antonelli, B, Manzia, T, Carraro, A, Vivarelli, M, Regalia, E, Vennarecci, G, Guglielmo, N, Cesaretti, M, Avolio, A, Valentini, M, Lai, Q, Baccarani, U, Pravisani R, De Simone P, Patrono D, Lauterio A, Cescon M, Gringeri E, Colledan M, Di Benedetto F, di Francesco F, Antonelli B, Manzia TM, Carraro A, Vivarelli M, Regalia E, Vennarecci G, Guglielmo N, Cesaretti M, Avolio AW, Valentini MF, Lai QRO, and Baccarani U

Abstract

There is enough clinical evidence that a T-tube use in biliary reconstruction at adult liver transplantation (LT) does not significantly modify the risk of biliary stricture/leak, and it may even sustain infective and metabolic complications. Thus, the policy on T-tube use has been globally changing, with progressive application of more restrictive selection criteria. However, there are no currently standardized indications in such change, and many LT Centers rely only on own experience and routine. A nation-wide survey was conducted among all the 20 Italian adult LT Centers to investigate the current policy on T-tube use. It was found that 20% of Centers completely discontinued the T-tube use, while 25% Centers used it routinely in all LT cases. The remaining 55% of Centers applied a selective policy, based on criteria of technical complexity of biliary reconstruction (72.7%), followed by low-quality graft (63.6%) and high-risk recipient (36.4%). A T-tube use > 50% of annual caseload was not associated with high-volume Center status (> 70 LT per year), an active pediatric or living-donor transplant program, or use of DCD grafts. Only 10/20 (50%) Centers identified T-tube as a potential risk factor for complications other than biliary stricture/leak. In these cases, the suspected pathogenic mechanism comprised bacterial colonization (70%), malabsorption (70%), interruption of the entero-hepatic bile-acid cycle (50%), biliary inflammation due to an indwelling catheter (40%) and gut microbiota changes (40%). In conclusion, the prevalence of T-tube use among the Italian LT Centers is still relatively high, compared to the European trend (33%), and the potential detrimental effect of T-tube, beyond biliary stricture/leak, seems to be somehow underestimated.

Published
2021

50. Complications of Liver Transplantation

Author

Cavallari, A., Mazziotti, A., Vivarelli, M., Baert, A. L., editor, Sartor, K., editor, Bücheler, E., editor, Nicolas, V., editor, Broelsch, C. E., editor, Rogiers, X., editor, and Krupski, G., editor

Published
2003
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