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1. Is the significant risk of perioperative complications associated with radical surgery following non-curative endoscopic submucosal dissection for early colorectal cancer still acceptable?

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Rottoli, M, Gori, A, Pellino, G, Flacco, M, Spinelli, A, Poggioli, G, Romano, A, Belvedere, A, Lanci, A, Parlanti, D, Vago, G, Pezzuto, P, Canavese, A, Dajti, G, Cardelli, S, Catalioto, C, Russo, I, Violante, T, Morezzi, D, Maurino, L, Filippone, E, Bernante, P, Martellucci, C, Jovine, E, Lombardi, R, Masetti, M, Cipressi, C, Offi, M, Larotonda, C, Puglisi, S, Barbosa, A, Vaiana, R, Bianchi, P, Tonti, C, Codignola, C, Zorcolo, L, Restivo, A, Deidda, S, Marchetti, M, Ippolito, L, Spolverato, G, Pucciarelli, S, Marchegiani, F, Ghio, G, Zagolin, G, Glavas, D, Tomassi, M, Rosati, R, Elmore, U, Gozzini, L, Calef, R, Puccetti, F, Cossu, A, Vignali, A, Morino, M, Allaix, M, Cannata, G, Lombardi, E, Ammirati, C, Piceni, C, Buccianti, P, Balestri, R, Puccini, M, Pezzati, D, D'Ischia, R, Asta, V, Sargenti, B, Taddei, G, Bonari, F, Boni, G, Ferrero, A, Mineccia, M, Gonella, F, Palisi, M, Danese, F, Cherubini, V, Perotti, S, Carvello, M, Carbone, F, Luberto, A, Calafiore, E, Lucia, F, Sacchi, M, Sasia, D, Giuffrida, M, Ballauri, E, Cardile, M, Armentano, S, Beltrami, E, Preve, G, Vercellone, B, Mozzon, M, Folliero, C, Lirusso, C, Vecchiato, M, Ziccarelli, A, Gattesco, D, Moretti, L, Crestale, S, Banchini, F, Capelli, P, Romboli, A, Palmieri, G, Conti, L, Rizzi, N, Bonfili, D, Manzini, N, Germani, P, Osenda, E, Cortinovis, S, Giunta, C, Fracon, S, Abdallah, H, Bogoni, S, Portolani, N, Nascimbeni, R, Molfino, S, Tiberio, G, Garosio, I, Lamperti, G, Rigosa, D, Ercolani, G, Solaini, L, Cavaliere, D, Avanzolini, A, D'Acapito, F, Chiarella, L, Pietrantonio, D, Annunziata, D, Piccolo, R, Sorrentino, M, Pansini, M, Cojutti, A, Graziano, M, Callegari, F, Balzarotti, L, Dameno, V, Cattaneo, A, Santolamazza, G, Altieri, C, Magarini, R, Pietrabissa, A, Dominioni, T, Pugliese, L, Peri, A, Botti, M, Salvetti, F, Cassinotti, E, Baldari, L, Boni, L, Messina, V, D'Abrosca, V, Cianci, P, Tumolo, R, Gattulli, D, Restini, E, Minafra, M, Sederino, M, Bottalico, B, Pilati, P, Franzato, B, Mattara, G, Simoni, O, Barina, A, Tonello, M, Muratore, A, Calabro, M, Pipitone, N, Cuzzola, B, Nood, E, Passuello, N, Frasson, A, Mammano, E, Faccio, L, Vittadello, F, Bressan, A, Sarzo, G, Tamini, N, Oldani, M, Cigagna, L, Carissimi, F, Carlo, G, Baccalini, E, Nespoli, L, Giordano, A, Cantafio, S, Grifoni, L, Matani, D, Livi, S, Delogu, D, Scognamillo, F, Marrosu, A, Guerrini, L, Ugolini, G, Ghignone, F, Frascaroli, G, Albertini, N, Zattoni, D, Taffurelli, G, Montroni, I, Colombo, F, Danelli, P, Bondurri, A, Maffioli, A, Bonomi, A, Pezzoli, I, Cammarata, F, Goletti, O, Molteni, M, Assisi, A, Quartierini, G, Lio, C, Verdi, D, Mondi, I, Peluso, C, Macchi, L, Tanzanu, M, Zanzi, F, Pellegrini, S, Andreuccetti, J, D'Alessio, R, Pignata, G, Capua, M, Canfora, I, Ottaviani, L, Lepiane, P, Balla, A, Carlo, A, Saraceno, F, Scaramuzzo, R, Guida, A, Aguzzi, D, Bellora, P, Gentilli, S, Monni, M, Nikaj, H, Cillara, N, Cannavera, A, Deserra, A, Margiani, C, Cabula, R, Dettori, M, Gramignano, G, Lezoche, G, Ortenzi, M, Orlandoni, E, Curzi, F, Vitali, F, Capomagi, P, Palmieri, M, Rio, P, Bonati, E, Loderer, T, Cozzani, F, Rossini, M, Agnesi, S, Capolupo, G, Caricato, M, Carannante, F, Masciana, G, Marrelli, M, Miacci, V, Lauricella, S, Tonini, V, Cervellera, M, Pisconti, S, Lozito, C, Shahu, J, Mongelli, C, Morelli, G, Sartarelli, L, Sica, G, Siragusa, L, Bagaglini, G, Sensi, B, Franceschilli, M, Vinci, D, Taddei, A, Risaliti, M, Bartolini, I, Ringressi, M, Tirloni, L, Laface, L, Abate, E, Casati, M, Gobbi, P, Opocher, E, Mariani, N, Ceretti, A, Giovenzana, M, Giuliani, B, Sironi, M, Grossi, U, Zanus, G, Santoro, G, Brizzolari, M, Leo, E, Novello, S, Aquilino, K, Milardi, F, Olmi, S, Uccelli, M, Bonaldi, M, Cesana, G, Bindi, M, Galleano, R, Langone, A, Botto, M, Franceschi, A, Gambino, E, Ronconi, M, Casiraghi, S, Casole, G, Ciulla, S, Terrosu, G, Calandra, S, Scarpa, E, Cherchi, V, Calini, G, Martinuzzo, L, Clocchiatti, L, Muschitiello, D, Romanzi, A, Vignati, B, Vannelli, A, Scolaro, R, Milanesi, M, Rossi, F, Canonico, G, Anastasi, A, Nelli, T, Barlettai, M, Fratarcangeli, R, Martino, C, Damigella, A, Adinolfi, E, Birindelli, A, Taglietti, L, Dester, S, Fleres, F, Cucinotta, E, Viscosi, F, Biondo, S, Badessi, G, Catarsini, N, Mazzeo, C, Rega, D, Delrio, P, Cervone, C, Aversano, A, Franciscis, S, Marzo, M, Marra, B, Pace, U, Amato, A, Batistotti, P, Mina, E, Serventi, A, Lapolla, P, Mingoli, A, Sapienza, P, Brachini, G, Cirillo, B, Fiori, E, Crocetti, D, Clementi, I, Martines, G, Picciariello, A, Tomasicchio, G, Dibra, R, Trigiante, G, Rinaldi, M, Lantone, G, Porcu, A, Perra, T, Scanu, A, Feo, C, Fancellu, A, Cossu, M, Ginesu, G, Patriti, A, Coletta, D, Petrelli, F, Greco, P, Spadoni, C, Cassiani, G, Bianchini, F, Arganini, M, Bianchini, M, Perotti, B, Palmeri, M, Scabini, S, Deiana, S, Carganico, G, Pertile, D, Soriero, D, Fioravanti, E, Sperotto, B, Nardo, B, Paglione, D, Crocco, V, Doni, M, Osso, M, Perri, R, Sampietro, G, Corbellini, C, Lorusso, L, Manzo, C, Cigognini, M, Baldi, C, Palomba, G, Aprea, G, Capuano, M, Basile, R, Tutino, R, Massani, M, Marinelli, L, Canitano, N, Pilia, T, Podda, M, Pisanu, A, Murzi, V, Incani, S, Frongia, F, Esposito, G, Luglio, G, Tropeano, F, Pagano, G, Spina, E, Simone, G, Cricri, M, Catena, F, Vallicelli, C, Zanini, N, Ronconi, D, Favi, F, Mazzucchelli, C, Convertini, G, Vincenti, L, Andriola, V, Bizzoca, C, Fabbri, N, Fazzin, M, Pesce, A, Gennari, S, Torchiaro, M, Severi, S, Frontali, A, Bracchetti, G, Granieri, S, Cotsoglou, C, Carlini, M, Lisi, G, Spoletini, D, Mastrangeli, M, Campanelli, M, Manigrasso, M, Milone, M, Palma, G, Vertaldi, S, Chini, A, Maione, F, Marello, A, Selvaggi, F, Sciaudone, G, Selvaggi, L, Tasselli, F, Fuschillo, G, Oddis, L, Grande, S, Grande, M, Ascanelli, S, Chimisso, L, Aisoni, F, Rossin, E, Pepe, F, Marchetti, F, Picardi, B, Rossi, S, Monte, S, Picarelli, M, Muttillo, I, Ratto, C, Marra, A, Parello, A, Litta, F, Campenni, P, Simone, V, Pata, F, Riboni, C, Rausa, E, Celentano, V, Rottoli M., Gori A., Pellino G., Flacco M. E., Spinelli A., Poggioli G., Romano A., Belvedere A., Lanci A. L., Parlanti D., Vago G., Pezzuto P., Canavese A., Dajti G., Cardelli S., Catalioto C., Russo I. S., Violante T., Morezzi D., Maurino L., Filippone E., Bernante P., Martellucci C., Jovine E., Lombardi R., Masetti M., Cipressi C., Offi M. F., Larotonda C., Puglisi S. B., Barbosa A., Vaiana R., Bianchi P. M., Tonti C., Codignola C., Zorcolo L., Restivo A., Deidda S., Marchetti M. E., Ippolito L., Spolverato G., Pucciarelli S., Marchegiani F., Ghio G., Zagolin G., Glavas D., Tomassi M., Rosati R., Elmore U., Gozzini L., Calef R., Puccetti F., Cossu A., Vignali A., Morino M., Allaix M. E., Cannata G., Lombardi E., Ammirati C. A., Piceni C., Buccianti P., Balestri R., Puccini M., Pezzati D., D'Ischia R., Asta V. F., Sargenti B., Taddei G., Bonari F., Boni G., Ferrero A., Mineccia M., Gonella F., Palisi M., Danese F., Cherubini V., Perotti S., Carvello M., Carbone F., Luberto A., Calafiore E., Lucia F. D., Sacchi M., Sasia D., Giuffrida M. C., Ballauri E., Cardile M., Armentano S., Beltrami E., Preve G., Vercellone B., Mozzon M., Folliero C., Lirusso C., Vecchiato M., Ziccarelli A., Gattesco D., Moretti L., Crestale S., Banchini F., Capelli P., Romboli A., Palmieri G., Conti L., Rizzi N., Bonfili D., Manzini N. D., Germani P., Osenda E., Cortinovis S., Giunta C., Fracon S., Abdallah H., Bogoni S., Portolani N., Nascimbeni R., Molfino S., Tiberio G. A. M., Garosio I., Lamperti G., Rigosa D., Ercolani G., Solaini L., Cavaliere D., Avanzolini A., D'Acapito F., Chiarella L. L., Pietrantonio D. D., Annunziata D., Piccolo R., Sorrentino M., Pansini M., Cojutti A., Graziano M., Callegari F., Balzarotti L., Dameno V. R., Cattaneo A., Santolamazza G., Altieri C., Magarini R., Pietrabissa A., Dominioni T., Pugliese L., Peri A., Botti M., Salvetti F., Cassinotti E., Baldari L., Boni L., Messina V., D'Abrosca V., Cianci P., Tumolo R., Gattulli D., Restini E., Minafra M., Sederino M. G., Bottalico B., Pilati P., Franzato B., Mattara G., Simoni O. D., Barina A., Tonello M., Muratore A., Calabro M., Pipitone N. S. F., Cuzzola B., Nood E. H. V., Passuello N., Frasson A., Mammano E., Faccio L., Vittadello F., Bressan A., Sarzo G., Tamini N., Oldani M., Cigagna L., Carissimi F., Carlo G. D., Baccalini E., Nespoli L., Giordano A., Cantafio S., Grifoni L., Matani D., Livi S., Delogu D., Scognamillo F., Marrosu A., Guerrini L., Ugolini G., Ghignone F., Frascaroli G., Albertini N., Zattoni D., Taffurelli G., Montroni I., Colombo F., Danelli P., Bondurri A., Maffioli A., Bonomi A., Pezzoli I., Cammarata F., Goletti O., Molteni M., Assisi A., Quartierini G., Lio C. D., Verdi D., Mondi I., Peluso C., MacChi L., Tanzanu M., Zanzi F., Pellegrini S., Andreuccetti J., D'Alessio R., Pignata G., Capua M. D., Canfora I., Ottaviani L., Lepiane P., Balla A., Carlo A. D., Saraceno F., Scaramuzzo R., Guida A., Aguzzi D., Bellora P., Gentilli S., Monni M., Nikaj H., Cillara N., Cannavera A., Deserra A., Margiani C., Cabula R., Dettori M., Gramignano G., Lezoche G., Ortenzi M., Orlandoni E. S., Curzi F., Vitali F., Capomagi P., Palmieri M., Giuffrida M., Rio P. D., Bonati E., Loderer T., Cozzani F., Rossini M., Agnesi S., Capolupo G. T., Caricato M., Carannante F., Masciana G., Marrelli M., Miacci V., Lauricella S., Tonini V., Cervellera M., Pisconti S., Lozito C., Shahu J., Mongelli C., Morelli G., Sartarelli L., Sica G. S., Siragusa L., Bagaglini G., Sensi B., Guida A. M., Franceschilli M., Vinci D., Taddei A., Risaliti M., Bartolini I., Ringressi M. N., Tirloni L., Laface L., Abate E., Casati M., Gobbi P., Opocher E., Mariani N. M., Ceretti A. P., Giovenzana M., Giuliani B., Sironi M., Grossi U., Zanus G., Santoro G. A., Brizzolari M., Leo E. D., Novello S., Aquilino K., Milardi F., Olmi S., Uccelli M., Bonaldi M., Cesana G. C., Bindi M., Galleano R., Langone A., Botto M., Franceschi A., Gambino E., Ronconi M., Casiraghi S., Casole G., Ciulla S. L., Terrosu G., Calandra S., Scarpa E., Cherchi V., Calini G., Martinuzzo L., Clocchiatti L., Muschitiello D., Romanzi A., Vignati B., Vannelli A., Scolaro R., Milanesi M., Rossi F., Canonico G., Anastasi A., Nelli T., Barlettai M., Fratarcangeli R., Martino C. D., Damigella A., Adinolfi E., Birindelli A., Taglietti L., Dester S. E., Fleres F., Cucinotta E., Viscosi F., Biondo S. A., Badessi G., Catarsini N., Mazzeo C., Rega D., Delrio P., Cervone C., Aversano A., Franciscis S. D., Marzo M. D., Marra B., Pace U., Amato A., Batistotti P., Mina E., Serventi A., Lapolla P., Mingoli A., Sapienza P., Brachini G., Cirillo B., Fiori E., Crocetti D., Clementi I., Martines G., Picciariello A., Tomasicchio G., Dibra R., Trigiante G., Rinaldi M., Lantone G., Porcu A., Perra T., Scanu A. M., Feo C. F., Fancellu A., Cossu M. L., Ginesu G. C., Patriti A., Coletta D., Petrelli F., Greco P. A., Spadoni C., Cassiani G., Bianchini F., Arganini M., Bianchini M., Perotti B., Palmeri M., Scabini S., Deiana S., Carganico G., Pertile D., Soriero D., Fioravanti E., Sperotto B., Nardo B., Paglione D., Crocco V., Doni M., Osso M., Perri R., Sampietro G. M., Corbellini C., Lorusso L., Manzo C. A., Cigognini M., Baldi C., Palomba G., Aprea G., Capuano M., Basile R., Tutino R., Massani M., Marinelli L., Canitano N., Pilia T., Podda M., Pisanu A., Murzi V., Incani S., Frongia F., Esposito G., Luglio G., Tropeano F. P., Pagano G., Spina E., Simone G. D., Cricri M., Catena F., Vallicelli C., Zanini N., Ronconi D., Favi F., Mazzucchelli C., Convertini G., Vincenti L., Andriola V., Bizzoca C., Feo C. V., Fabbri N., Fazzin M., Pesce A., Gennari S., Torchiaro M., Severi S., Frontali A., Bracchetti G., Granieri S., Cotsoglou C., Carlini M., Lisi G., Spoletini D., Mastrangeli M. R., Campanelli M., Manigrasso M., Milone M., Palma G. D. D., Vertaldi S., Chini A., Maione F., Marello A., Selvaggi F., Sciaudone G., Selvaggi L., Tasselli F. M., Fuschillo G., Oddis L., Grande S., Grande M., Ascanelli S., Chimisso L., Aisoni F., Rossin E., Pepe F., Marchetti F., Picardi B., Rossi S., Monte S. R. D., Picarelli M., Muttillo I. A., Ratto C., Marra A. A., Parello A., Litta F., Campenni P., Simone V. D., Pata F., Riboni C., Rausa E., Celentano V., Rottoli, M, Gori, A, Pellino, G, Flacco, M, Spinelli, A, Poggioli, G, Romano, A, Belvedere, A, Lanci, A, Parlanti, D, Vago, G, Pezzuto, P, Canavese, A, Dajti, G, Cardelli, S, Catalioto, C, Russo, I, Violante, T, Morezzi, D, Maurino, L, Filippone, E, Bernante, P, Martellucci, C, Jovine, E, Lombardi, R, Masetti, M, Cipressi, C, Offi, M, Larotonda, C, Puglisi, S, Barbosa, A, Vaiana, R, Bianchi, P, Tonti, C, Codignola, C, Zorcolo, L, Restivo, A, Deidda, S, Marchetti, M, Ippolito, L, Spolverato, G, Pucciarelli, S, Marchegiani, F, Ghio, G, Zagolin, G, Glavas, D, Tomassi, M, Rosati, R, Elmore, U, Gozzini, L, Calef, R, Puccetti, F, Cossu, A, Vignali, A, Morino, M, Allaix, M, Cannata, G, Lombardi, E, Ammirati, C, Piceni, C, Buccianti, P, Balestri, R, Puccini, M, Pezzati, D, D'Ischia, R, Asta, V, Sargenti, B, Taddei, G, Bonari, F, Boni, G, Ferrero, A, Mineccia, M, Gonella, F, Palisi, M, Danese, F, Cherubini, V, Perotti, S, Carvello, M, Carbone, F, Luberto, A, Calafiore, E, Lucia, F, Sacchi, M, Sasia, D, Giuffrida, M, Ballauri, E, Cardile, M, Armentano, S, Beltrami, E, Preve, G, Vercellone, B, Mozzon, M, Folliero, C, Lirusso, C, Vecchiato, M, Ziccarelli, A, Gattesco, D, Moretti, L, Crestale, S, Banchini, F, Capelli, P, Romboli, A, Palmieri, G, Conti, L, Rizzi, N, Bonfili, D, Manzini, N, Germani, P, Osenda, E, Cortinovis, S, Giunta, C, Fracon, S, Abdallah, H, Bogoni, S, Portolani, N, Nascimbeni, R, Molfino, S, Tiberio, G, Garosio, I, Lamperti, G, Rigosa, D, Ercolani, G, Solaini, L, Cavaliere, D, Avanzolini, A, D'Acapito, F, Chiarella, L, Pietrantonio, D, Annunziata, D, Piccolo, R, Sorrentino, M, Pansini, M, Cojutti, A, Graziano, M, Callegari, F, Balzarotti, L, Dameno, V, Cattaneo, A, Santolamazza, G, Altieri, C, Magarini, R, Pietrabissa, A, Dominioni, T, Pugliese, L, Peri, A, Botti, M, Salvetti, F, Cassinotti, E, Baldari, L, Boni, L, Messina, V, D'Abrosca, V, Cianci, P, Tumolo, R, Gattulli, D, Restini, E, Minafra, M, Sederino, M, Bottalico, B, Pilati, P, Franzato, B, Mattara, G, Simoni, O, Barina, A, Tonello, M, Muratore, A, Calabro, M, Pipitone, N, Cuzzola, B, Nood, E, Passuello, N, Frasson, A, Mammano, E, Faccio, L, Vittadello, F, Bressan, A, Sarzo, G, Tamini, N, Oldani, M, Cigagna, L, Carissimi, F, Carlo, G, Baccalini, E, Nespoli, L, Giordano, A, Cantafio, S, Grifoni, L, Matani, D, Livi, S, Delogu, D, Scognamillo, F, Marrosu, A, Guerrini, L, Ugolini, G, Ghignone, F, Frascaroli, G, Albertini, N, Zattoni, D, Taffurelli, G, Montroni, I, Colombo, F, Danelli, P, Bondurri, A, Maffioli, A, Bonomi, A, Pezzoli, I, Cammarata, F, Goletti, O, Molteni, M, Assisi, A, Quartierini, G, Lio, C, Verdi, D, Mondi, I, Peluso, C, Macchi, L, Tanzanu, M, Zanzi, F, Pellegrini, S, Andreuccetti, J, D'Alessio, R, Pignata, G, Capua, M, Canfora, I, Ottaviani, L, Lepiane, P, Balla, A, Carlo, A, Saraceno, F, Scaramuzzo, R, Guida, A, Aguzzi, D, Bellora, P, Gentilli, S, Monni, M, Nikaj, H, Cillara, N, Cannavera, A, Deserra, A, Margiani, C, Cabula, R, Dettori, M, Gramignano, G, Lezoche, G, Ortenzi, M, Orlandoni, E, Curzi, F, Vitali, F, Capomagi, P, Palmieri, M, Rio, P, Bonati, E, Loderer, T, Cozzani, F, Rossini, M, Agnesi, S, Capolupo, G, Caricato, M, Carannante, F, Masciana, G, Marrelli, M, Miacci, V, Lauricella, S, Tonini, V, Cervellera, M, Pisconti, S, Lozito, C, Shahu, J, Mongelli, C, Morelli, G, Sartarelli, L, Sica, G, Siragusa, L, Bagaglini, G, Sensi, B, Franceschilli, M, Vinci, D, Taddei, A, Risaliti, M, Bartolini, I, Ringressi, M, Tirloni, L, Laface, L, Abate, E, Casati, M, Gobbi, P, Opocher, E, Mariani, N, Ceretti, A, Giovenzana, M, Giuliani, B, Sironi, M, Grossi, U, Zanus, G, Santoro, G, Brizzolari, M, Leo, E, Novello, S, Aquilino, K, Milardi, F, Olmi, S, Uccelli, M, Bonaldi, M, Cesana, G, Bindi, M, Galleano, R, Langone, A, Botto, M, Franceschi, A, Gambino, E, Ronconi, M, Casiraghi, S, Casole, G, Ciulla, S, Terrosu, G, Calandra, S, Scarpa, E, Cherchi, V, Calini, G, Martinuzzo, L, Clocchiatti, L, Muschitiello, D, Romanzi, A, Vignati, B, Vannelli, A, Scolaro, R, Milanesi, M, Rossi, F, Canonico, G, Anastasi, A, Nelli, T, Barlettai, M, Fratarcangeli, R, Martino, C, Damigella, A, Adinolfi, E, Birindelli, A, Taglietti, L, Dester, S, Fleres, F, Cucinotta, E, Viscosi, F, Biondo, S, Badessi, G, Catarsini, N, Mazzeo, C, Rega, D, Delrio, P, Cervone, C, Aversano, A, Franciscis, S, Marzo, M, Marra, B, Pace, U, Amato, A, Batistotti, P, Mina, E, Serventi, A, Lapolla, P, Mingoli, A, Sapienza, P, Brachini, G, Cirillo, B, Fiori, E, Crocetti, D, Clementi, I, Martines, G, Picciariello, A, Tomasicchio, G, Dibra, R, Trigiante, G, Rinaldi, M, Lantone, G, Porcu, A, Perra, T, Scanu, A, Feo, C, Fancellu, A, Cossu, M, Ginesu, G, Patriti, A, Coletta, D, Petrelli, F, Greco, P, Spadoni, C, Cassiani, G, Bianchini, F, Arganini, M, Bianchini, M, Perotti, B, Palmeri, M, Scabini, S, Deiana, S, Carganico, G, Pertile, D, Soriero, D, Fioravanti, E, Sperotto, B, Nardo, B, Paglione, D, Crocco, V, Doni, M, Osso, M, Perri, R, Sampietro, G, Corbellini, C, Lorusso, L, Manzo, C, Cigognini, M, Baldi, C, Palomba, G, Aprea, G, Capuano, M, Basile, R, Tutino, R, Massani, M, Marinelli, L, Canitano, N, Pilia, T, Podda, M, Pisanu, A, Murzi, V, Incani, S, Frongia, F, Esposito, G, Luglio, G, Tropeano, F, Pagano, G, Spina, E, Simone, G, Cricri, M, Catena, F, Vallicelli, C, Zanini, N, Ronconi, D, Favi, F, Mazzucchelli, C, Convertini, G, Vincenti, L, Andriola, V, Bizzoca, C, Fabbri, N, Fazzin, M, Pesce, A, Gennari, S, Torchiaro, M, Severi, S, Frontali, A, Bracchetti, G, Granieri, S, Cotsoglou, C, Carlini, M, Lisi, G, Spoletini, D, Mastrangeli, M, Campanelli, M, Manigrasso, M, Milone, M, Palma, G, Vertaldi, S, Chini, A, Maione, F, Marello, A, Selvaggi, F, Sciaudone, G, Selvaggi, L, Tasselli, F, Fuschillo, G, Oddis, L, Grande, S, Grande, M, Ascanelli, S, Chimisso, L, Aisoni, F, Rossin, E, Pepe, F, Marchetti, F, Picardi, B, Rossi, S, Monte, S, Picarelli, M, Muttillo, I, Ratto, C, Marra, A, Parello, A, Litta, F, Campenni, P, Simone, V, Pata, F, Riboni, C, Rausa, E, Celentano, V, Rottoli M., Gori A., Pellino G., Flacco M. E., Spinelli A., Poggioli G., Romano A., Belvedere A., Lanci A. L., Parlanti D., Vago G., Pezzuto P., Canavese A., Dajti G., Cardelli S., Catalioto C., Russo I. S., Violante T., Morezzi D., Maurino L., Filippone E., Bernante P., Martellucci C., Jovine E., Lombardi R., Masetti M., Cipressi C., Offi M. F., Larotonda C., Puglisi S. B., Barbosa A., Vaiana R., Bianchi P. M., Tonti C., Codignola C., Zorcolo L., Restivo A., Deidda S., Marchetti M. E., Ippolito L., Spolverato G., Pucciarelli S., Marchegiani F., Ghio G., Zagolin G., Glavas D., Tomassi M., Rosati R., Elmore U., Gozzini L., Calef R., Puccetti F., Cossu A., Vignali A., Morino M., Allaix M. E., Cannata G., Lombardi E., Ammirati C. A., Piceni C., Buccianti P., Balestri R., Puccini M., Pezzati D., D'Ischia R., Asta V. F., Sargenti B., Taddei G., Bonari F., Boni G., Ferrero A., Mineccia M., Gonella F., Palisi M., Danese F., Cherubini V., Perotti S., Carvello M., Carbone F., Luberto A., Calafiore E., Lucia F. D., Sacchi M., Sasia D., Giuffrida M. C., Ballauri E., Cardile M., Armentano S., Beltrami E., Preve G., Vercellone B., Mozzon M., Folliero C., Lirusso C., Vecchiato M., Ziccarelli A., Gattesco D., Moretti L., Crestale S., Banchini F., Capelli P., Romboli A., Palmieri G., Conti L., Rizzi N., Bonfili D., Manzini N. D., Germani P., Osenda E., Cortinovis S., Giunta C., Fracon S., Abdallah H., Bogoni S., Portolani N., Nascimbeni R., Molfino S., Tiberio G. A. M., Garosio I., Lamperti G., Rigosa D., Ercolani G., Solaini L., Cavaliere D., Avanzolini A., D'Acapito F., Chiarella L. L., Pietrantonio D. D., Annunziata D., Piccolo R., Sorrentino M., Pansini M., Cojutti A., Graziano M., Callegari F., Balzarotti L., Dameno V. R., Cattaneo A., Santolamazza G., Altieri C., Magarini R., Pietrabissa A., Dominioni T., Pugliese L., Peri A., Botti M., Salvetti F., Cassinotti E., Baldari L., Boni L., Messina V., D'Abrosca V., Cianci P., Tumolo R., Gattulli D., Restini E., Minafra M., Sederino M. G., Bottalico B., Pilati P., Franzato B., Mattara G., Simoni O. D., Barina A., Tonello M., Muratore A., Calabro M., Pipitone N. S. F., Cuzzola B., Nood E. H. V., Passuello N., Frasson A., Mammano E., Faccio L., Vittadello F., Bressan A., Sarzo G., Tamini N., Oldani M., Cigagna L., Carissimi F., Carlo G. D., Baccalini E., Nespoli L., Giordano A., Cantafio S., Grifoni L., Matani D., Livi S., Delogu D., Scognamillo F., Marrosu A., Guerrini L., Ugolini G., Ghignone F., Frascaroli G., Albertini N., Zattoni D., Taffurelli G., Montroni I., Colombo F., Danelli P., Bondurri A., Maffioli A., Bonomi A., Pezzoli I., Cammarata F., Goletti O., Molteni M., Assisi A., Quartierini G., Lio C. D., Verdi D., Mondi I., Peluso C., MacChi L., Tanzanu M., Zanzi F., Pellegrini S., Andreuccetti J., D'Alessio R., Pignata G., Capua M. D., Canfora I., Ottaviani L., Lepiane P., Balla A., Carlo A. D., Saraceno F., Scaramuzzo R., Guida A., Aguzzi D., Bellora P., Gentilli S., Monni M., Nikaj H., Cillara N., Cannavera A., Deserra A., Margiani C., Cabula R., Dettori M., Gramignano G., Lezoche G., Ortenzi M., Orlandoni E. S., Curzi F., Vitali F., Capomagi P., Palmieri M., Giuffrida M., Rio P. D., Bonati E., Loderer T., Cozzani F., Rossini M., Agnesi S., Capolupo G. T., Caricato M., Carannante F., Masciana G., Marrelli M., Miacci V., Lauricella S., Tonini V., Cervellera M., Pisconti S., Lozito C., Shahu J., Mongelli C., Morelli G., Sartarelli L., Sica G. S., Siragusa L., Bagaglini G., Sensi B., Guida A. M., Franceschilli M., Vinci D., Taddei A., Risaliti M., Bartolini I., Ringressi M. N., Tirloni L., Laface L., Abate E., Casati M., Gobbi P., Opocher E., Mariani N. M., Ceretti A. P., Giovenzana M., Giuliani B., Sironi M., Grossi U., Zanus G., Santoro G. A., Brizzolari M., Leo E. D., Novello S., Aquilino K., Milardi F., Olmi S., Uccelli M., Bonaldi M., Cesana G. C., Bindi M., Galleano R., Langone A., Botto M., Franceschi A., Gambino E., Ronconi M., Casiraghi S., Casole G., Ciulla S. L., Terrosu G., Calandra S., Scarpa E., Cherchi V., Calini G., Martinuzzo L., Clocchiatti L., Muschitiello D., Romanzi A., Vignati B., Vannelli A., Scolaro R., Milanesi M., Rossi F., Canonico G., Anastasi A., Nelli T., Barlettai M., Fratarcangeli R., Martino C. D., Damigella A., Adinolfi E., Birindelli A., Taglietti L., Dester S. E., Fleres F., Cucinotta E., Viscosi F., Biondo S. A., Badessi G., Catarsini N., Mazzeo C., Rega D., Delrio P., Cervone C., Aversano A., Franciscis S. D., Marzo M. D., Marra B., Pace U., Amato A., Batistotti P., Mina E., Serventi A., Lapolla P., Mingoli A., Sapienza P., Brachini G., Cirillo B., Fiori E., Crocetti D., Clementi I., Martines G., Picciariello A., Tomasicchio G., Dibra R., Trigiante G., Rinaldi M., Lantone G., Porcu A., Perra T., Scanu A. M., Feo C. F., Fancellu A., Cossu M. L., Ginesu G. C., Patriti A., Coletta D., Petrelli F., Greco P. A., Spadoni C., Cassiani G., Bianchini F., Arganini M., Bianchini M., Perotti B., Palmeri M., Scabini S., Deiana S., Carganico G., Pertile D., Soriero D., Fioravanti E., Sperotto B., Nardo B., Paglione D., Crocco V., Doni M., Osso M., Perri R., Sampietro G. M., Corbellini C., Lorusso L., Manzo C. A., Cigognini M., Baldi C., Palomba G., Aprea G., Capuano M., Basile R., Tutino R., Massani M., Marinelli L., Canitano N., Pilia T., Podda M., Pisanu A., Murzi V., Incani S., Frongia F., Esposito G., Luglio G., Tropeano F. P., Pagano G., Spina E., Simone G. D., Cricri M., Catena F., Vallicelli C., Zanini N., Ronconi D., Favi F., Mazzucchelli C., Convertini G., Vincenti L., Andriola V., Bizzoca C., Feo C. V., Fabbri N., Fazzin M., Pesce A., Gennari S., Torchiaro M., Severi S., Frontali A., Bracchetti G., Granieri S., Cotsoglou C., Carlini M., Lisi G., Spoletini D., Mastrangeli M. R., Campanelli M., Manigrasso M., Milone M., Palma G. D. D., Vertaldi S., Chini A., Maione F., Marello A., Selvaggi F., Sciaudone G., Selvaggi L., Tasselli F. M., Fuschillo G., Oddis L., Grande S., Grande M., Ascanelli S., Chimisso L., Aisoni F., Rossin E., Pepe F., Marchetti F., Picardi B., Rossi S., Monte S. R. D., Picarelli M., Muttillo I. A., Ratto C., Marra A. A., Parello A., Litta F., Campenni P., Simone V. D., Pata F., Riboni C., Rausa E., and Celentano V.

Published
2024

2. Are there any benefits of prolonged hypothermic oxygenated perfusion? - Results from a national retrospective study

Author

De Carlis, R, Lauterio, A, Schlegel, A, Gringeri, E, Patrono, D, Camagni, S, Dondossola, D, Pezzati, D, Olivieri, T, Pagano, D, Bongini, M, Montanelli, P, Ravaioli, M, Bernasconi, D, Valsecchi, M, Baccarani, U, Cescon, M, Andorno, E, Mazzaferro, V, Gruttadauria, S, Di Benedetto, F, Ghinolfi, D, Caccamo, L, Pinelli, D, Romagnoli, R, Cillo, U, De Carlis, L, Perin, L, Petronio, N, Del Prete, L, Balzano, E, Vacca, P, Germinario, G, Basilico, G, Romano, P, De Carlis R., Lauterio A., Schlegel A., Gringeri E., Patrono D., Camagni S., Dondossola D., Pezzati D., Olivieri T., Pagano D., Bongini M., Montanelli P., Ravaioli M., Bernasconi D., Valsecchi M. G., Baccarani U., Cescon M., Andorno E., Mazzaferro V., Gruttadauria S., Di Benedetto F., Ghinolfi D., Caccamo L., Pinelli D., Romagnoli R., Cillo U., De Carlis L., Perin L., Petronio N., Del Prete L., Balzano E., Vacca P., Germinario G., Basilico G., Romano P., De Carlis, R, Lauterio, A, Schlegel, A, Gringeri, E, Patrono, D, Camagni, S, Dondossola, D, Pezzati, D, Olivieri, T, Pagano, D, Bongini, M, Montanelli, P, Ravaioli, M, Bernasconi, D, Valsecchi, M, Baccarani, U, Cescon, M, Andorno, E, Mazzaferro, V, Gruttadauria, S, Di Benedetto, F, Ghinolfi, D, Caccamo, L, Pinelli, D, Romagnoli, R, Cillo, U, De Carlis, L, Perin, L, Petronio, N, Del Prete, L, Balzano, E, Vacca, P, Germinario, G, Basilico, G, Romano, P, De Carlis R., Lauterio A., Schlegel A., Gringeri E., Patrono D., Camagni S., Dondossola D., Pezzati D., Olivieri T., Pagano D., Bongini M., Montanelli P., Ravaioli M., Bernasconi D., Valsecchi M. G., Baccarani U., Cescon M., Andorno E., Mazzaferro V., Gruttadauria S., Di Benedetto F., Ghinolfi D., Caccamo L., Pinelli D., Romagnoli R., Cillo U., De Carlis L., Perin L., Petronio N., Del Prete L., Balzano E., Vacca P., Germinario G., Basilico G., and Romano P.

Abstract

Background: Dual hypothermic oxygenated perfusion (DHOPE) is increasingly being used to extend liver preservation to improve transplant logistics. However, little is known about its benefits in high-risk liver grafts. This study aimed to investigate whether prolonged DHOPE provides benefits other than improved logistics in all liver types. Methods: We performed a national retrospective cohort study of 177 liver transplants from 12 Italian centers preserved with DHOPE for ≥4h between 2015 and 2022. A control group of 177 DHOPEs of <4h during the same period was created using 1:1 propensity score matching. The impact of risk profiles and preservation times on the outcomes was assessed using univariable and multivariable regression models. Results: No significant differences in post-transplant outcomes were found between prolonged and short DHOPEs. However, the prolonged group had a significantly lower incidence of post-transplant acute kidney injury (AKI) compared to the short group (30.5% vs. 44.6%, p=0.008). Among prolonged DHOPEs, no differences in transplant outcomes were observed according to donor risk index (DRI), Eurotransplant definition for marginal grafts, and balance of risk (BAR) score. DHOPE duration was associated with a lower risk of AKI in multivariable models adjusted for DRI, Eutrotransplant marginal grafts, and BAR score. Prolonged HOPE confirmed its protective effect against AKI in a multivariable model adjusted for donor and recipient risk factors [OR: 0.412, 95%CI: 0.200-0.850, p=0.016]. Conclusions: Prolonged DHOPE is widely used to improve transplant logistics, provides good results with high-risk grafts, and appears to be associated with a lower risk of post-transplant AKI. These results provide further insight into the important role of DHOPE in preventing post-transplant complications.

Published
2024

3. Effect of centre volume on pathological outcomes and postoperative complications after surgery for colorectal cancer: results of a multicentre national study

Author

Rottoli, M, Spinelli, A, Pellino, G, Gori, A, Calini, G, Flacco, M, Manzoli, L, Poggioli, G, Romano, A, Belvedere, A, Lanci, A, Parlanti, D, Vago, G, Pezzuto, A, Canavese, A, Dajti, G, Cardelli, S, Catalioto, C, Russo, I, Violante, T, Morezzi, D, Maurino, L, Filippone, E, Cuicchi, D, Bernante, P, Jovine, E, Lombardi, R, Masetti, M, Cipressi, C, Offi, M, Larotonda, C, Puglisi, S, Barbosa, A, Vaiana, R, Bianchi, P, Tonti, C, Codignola, C, Zorcolo, L, Restivo, A, Deidda, S, Marchetti, M, Ippolito, L, Spolverato, G, Pucciarelli, S, Marchegiani, F, Ghio, G, Zagolin, G, Glavas, D, Tomassi, M, Rosati, R, Elmore, U, Gozzini, L, Calef, R, Puccetti, F, Cossu, A, Vignali, A, Morino, M, Allaix, M, Cannata, G, Lombardi, E, Ammirati, C, Piceni, C, Buccianti, P, Balestri, R, Puccini, M, Pezzati, D, D'Ischia, R, Asta, V, Sargenti, B, Taddei, G, Bonari, F, Boni, G, Ferrero, A, Mineccia, M, Gonella, F, Palisi, M, Danese, F, Cherubini, V, Perotti, S, Carvello, M, Carbone, F, Luberto, A, Calafiore, E, De Lucia, F, Sacchi, M, Sasia, D, Giuffrida, M, Ballauri, E, Cardile, M, Armentano, S, Beltrami, E, Preve, G, Vercellone, B, Mozzon, M, Folliero, C, Lirusso, C, Vecchiato, M, Ziccarelli, A, Gattesco, D, Moretti, L, Crestale, S, Banchini, F, Capelli, P, Romboli, A, Palmieri, G, Conti, L, Rizzi, N, Bonfili, D, De Manzini, N, Germani, P, Osenda, E, Cortinovis, S, Giunta, C, Fracon, S, Abdallah, H, Bogoni, S, Portolani, N, Nascimbeni, R, Molfino, S, Tiberio, G, Garosio, I, Lamperti, G, Rigosa, D, Ercolani, G, Solaini, L, Cavaliere, D, Avanzolini, A, D'Acapito, F, Chiarella, L, Di Pietrantonio, D, Annunziata, D, Piccolo, R, Sorrentino, M, Pansini, M, Cojutti, A, Graziano, M, Callegari, F, Balzarotti, L, Dameno, V, Cattaneo, A, Santolamazza, G, Altieri, C, Magarini, R, Pietrabissa, A, Dominioni, T, Pugliese, L, Peri, A, Botti, M, Salvetti, F, Boni, L, Cassinotti, E, Baldari, L, Messina, V, D'Abrosca, V, Cianci, P, Tumolo, R, Gattulli, D, Restini, E, Minafra, M, Sederino, M, Bottalico, B, Pilati, P, Franzato, B, Mattara, G, De Simoni, O, Barina, A, Tonello, M, Muratore, A, Calabro, M, Federico Pipitone, N, Cuzzola, B, Van Nood, E, Passuello, N, Frasson, A, Mammano, E, Faccio, L, Vittadello, F, Bressan, A, Sarzo, G, Tamini, N, Oldani, M, Cigagna, L, Carissimi, F, De Carlo, G, Baccalini, E, Nespoli, L, Giordano, A, Cantafio, S, Grifoni, L, Matani, D, Livi, S, Delogu, D, Scognamillo, F, Marrosu, A, Guerrini, L, Ugolini, G, Ghignone, F, Frascaroli, G, Albertini, N, Zattoni, D, Taffurelli, G, Montroni, I, Colombo, F, Danelli, P, Bondurri, A, Maffioli, A, Bonomi, A, Pezzoli, I, Cammarata, F, Goletti, O, Molteni, M, Assisi, A, Quartierini, G, Da Lio, C, Verdi, D, Mondi, I, Peluso, C, Macchi, L, Tanzanu, M, Zanzi, F, Pellegrini, S, Andreuccetti, J, D'Alessio, R, Pignata, G, De Capua, M, Canfora, I, Ottaviani, L, Lepiane, P, Balla, A, De Carlo, A, Saraceno, F, Scaramuzzo, R, Guida, A, Aguzzi, D, Bellora, P, Gentilli, S, Monni, M, Nikaj, H, Cillara, N, Cannavera, A, Deserra, A, Margiani, C, Cabula, R, Dettori, M, Gramignano, G, Lezoche, G, Ortenzi, M, Orlandoni, E, Curzi, F, Vitali, F, Capomagi, P, Palmieri, M, Del Rio, P, Bonati, E, Loderer, T, Cozzani, F, Rossini, M, Agnesi, S, Capolupo, G, Caricato, M, Carannante, F, Masciana, G, Marrelli, M, Miacci, V, Lauricella, S, Tonini, V, Cervellera, M, Pisconti, S, Lozito, C, Shahu, J, Mongelli, C, Morelli, G, Sartarelli, L, Sica, G, Siragusa, L, Bagaglini, G, Franceschilli, M, Bellato, V, Fiorani, C, Taddei, A, Risaliti, M, Bartolini, I, Ringressi, M, Tirloni, L, Laface, L, Abate, E, Casati, M, Gobbi, P, Opocher, E, Mariani, N, Ceretti, A, Giovenzana, M, Giuliani, B, Sironi, M, Grossi, U, Zanus, G, Santoro, G, Brizzolari, M, De Leo, E, Novello, S, Aquilino, K, Milardi, F, Olmi, S, Uccelli, M, Bonaldi, M, Cesana, G, Bindi, M, Galleano, R, Langone, A, Botto, M, Franceschi, A, Gambino, E, Ronconi, M, Casiraghi, S, Casole, G, Ciulla, S, Terrosu, G, Calandra, S, Scarpa, E, Cherchi, V, Martinuzzo, L, Clocchiatti, L, Muschitiello, D, Romanzi, A, Vignati, B, Vannelli, A, Scolaro, R, Milanesi, M, Rossi, F, Canonico, G, Anastasi, A, Nelli, T, Barlettai, M, Fratarcangeli, R, Di Martino, C, Damigella, A, Adinolfi, E, Birindelli, A, Taglietti, L, Dester, S, Fleres, F, Cucinotta, E, Viscosi, F, Biondo, S, Badessi, G, Catarsini, N, Mazzeo, C, Rega, D, Delrio, P, Cervone, C, Aversano, A, De Franciscis, S, Di Marzo, M, Marra, B, Pace, U, Amato, A, Batistotti, P, Mina, E, Serventi, A, Lapolla, P, Mingoli, A, Sapienza, P, Brachini, G, Cirillo, B, Fiori, E, Crocetti, D, Clementi, I, Martines, G, Picciariello, A, Tomasicchio, G, Dibra, R, Trigiante, G, Rinaldi, M, Lantone, G, Porcu, A, Perra, T, Scanu, A, Feo, C, Fancellu, A, Cossu, M, Ginesu, G, Patriti, A, Coletta, D, Petrelli, F, Greco, P, Spadoni, C, Cassiani, G, Bianchini, F, Arganini, M, Bianchini, M, Perotti, B, Palmeri, M, Scabini, S, Deiana, S, Carganico, G, Pertile, D, Soriero, D, Fioravanti, E, Sperotto, B, Nardo, B, Paglione, D, Crocco, V, Doni, M, Osso, M, Perri, R, Sampietro, G, Corbellini, C, Lorusso, L, Manzo, C, Cigognini, M, Baldi, C, Palomba, G, Aprea, G, Capuano, M, Basile, R, Tutino, R, Massani, M, Marinelli, L, Canitano, N, Pilia, T, Podda, M, Pisanu, A, Murzi, V, Incani, S, Frongia, F, Esposito, G, Luglio, G, Tropeano, F, Pagano, G, Spina, E, De Simone, G, Cricri, M, Catena, F, Vallicelli, C, Zanini, N, Ronconi, D, Favi, F, Mazzucchelli, C, Convertini, G, Vincenti, L, Andriola, V, Bizzoca, C, Fabbri, N, Fazzin, M, Pesce, A, Gennari, S, Torchiaro, M, Severi, S, Frontali, A, Bracchetti, G, Granieri, S, Cotsoglou, C, Carlini, M, Lisi, G, Spoletini, D, Mastrangeli, M, Campanelli, M, Manigrasso, M, Milone, M, De Palma, G, Vertaldi, S, Chini, A, Maione, F, Marello, A, Selvaggi, F, Sciaudone, G, Selvaggi, L, Tasselli, F, Fuschillo, G, Oddis, L, Grande, S, Grande, M, Ascanelli, S, Chimisso, L, Aisoni, F, Rossin, E, Pepe, F, Marchetti, F, Picardi, B, Rossi, S, Del Monte, S, Picarelli, M, Muttillo, I, Ratto, C, Marra, A, Parello, A, Litta, F, Campenni, P, De Simone, V, Pata, F, Riboni, C, Rausa, E, Celentano, V, Rottoli M., Spinelli A., Pellino G., Gori A., Calini G., Flacco M. E., Manzoli L., Poggioli G., Romano A., Belvedere A., Lanci A. L., Parlanti D., Vago G., Pezzuto A. P., Canavese A., Dajti G., Cardelli S., Catalioto C., Russo I. S., Violante T., Morezzi D., Maurino L., Filippone E., Cuicchi D., Bernante P., Jovine E., Lombardi R., Masetti M., Cipressi C., Offi M. F., Larotonda C., Puglisi S. B., Barbosa A., Vaiana R., Bianchi P. M., Tonti C., Codignola C., Zorcolo L., Restivo A., Deidda S., Marchetti M. E., Ippolito L., Spolverato G., Pucciarelli S., Marchegiani F., Ghio G., Zagolin G., Glavas D., Tomassi M., Rosati R., Elmore U., Gozzini L., Calef R., Puccetti F., Cossu A., Vignali A., Morino M., Allaix M. E., Cannata G., Lombardi E., Ammirati C. A., Piceni C., Buccianti P., Balestri R., Puccini M., Pezzati D., D'Ischia R., Asta V. F., Sargenti B., Taddei G., Bonari F., Boni G., Ferrero A., Mineccia M., Gonella F., Palisi M., Danese F., Cherubini V., Perotti S., Carvello M., Carbone F., Luberto A., Calafiore E., De Lucia F., Sacchi M., Sasia D., Giuffrida M. C., Ballauri E., Cardile M., Armentano S., Beltrami E., Preve G., Vercellone B., Mozzon M., Folliero C., Lirusso C., Vecchiato M., Ziccarelli A., Gattesco D., Moretti L., Crestale S., Banchini F., Capelli P., Romboli A., Palmieri G., Conti L., Rizzi N., Bonfili D., De Manzini N., Germani P., Osenda E., Cortinovis S., Giunta C., Fracon S., Abdallah H., Bogoni S., Portolani N., Nascimbeni R., Molfino S., Tiberio G. A. M., Garosio I., Lamperti G., Rigosa D., Ercolani G., Solaini L., Cavaliere D., Avanzolini A., D'Acapito F., Chiarella L. L., Di Pietrantonio D., Annunziata D., Piccolo R., Sorrentino M., Pansini M., Cojutti A., Graziano M., Callegari F., Balzarotti L., Dameno V. R., Cattaneo A., Santolamazza G., Altieri C., Magarini R., Pietrabissa A., Dominioni T., Pugliese L., Peri A., Botti M., Salvetti F., Boni L., Cassinotti E., Baldari L., Messina V., D'Abrosca V., Cianci P., Tumolo R., Gattulli D., Restini E., Minafra M., Sederino M. G., Bottalico B., Pilati P., Franzato B., Mattara G., De Simoni O., Barina A., Tonello M., Muratore A., Calabro M., Federico Pipitone N. S., Cuzzola B., Van Nood E. H., Passuello N., Frasson A., Mammano E., Faccio L., Vittadello F., Bressan A., Sarzo G., Tamini N., Oldani M., Cigagna L., Carissimi F., De Carlo G., Baccalini E., Nespoli L., Giordano A., Cantafio S., Grifoni L., Matani D., Livi S., Delogu D., Scognamillo F., Marrosu A., Guerrini L., Ugolini G., Ghignone F., Frascaroli G., Albertini N., Zattoni D., Taffurelli G., Montroni I., Colombo F., Danelli P., Bondurri A., Maffioli A., Bonomi A., Pezzoli I., Cammarata F., Goletti O., Molteni M., Assisi A., Quartierini G., Da Lio C., Verdi D., Mondi I., Peluso C., MacChi L., Tanzanu M., Zanzi F., Pellegrini S., Andreuccetti J., D'Alessio R., Pignata G., De Capua M., Canfora I., Ottaviani L., Lepiane P., Balla A., De Carlo A., Saraceno F., Scaramuzzo R., Guida A., Aguzzi D., Bellora P., Gentilli S., Monni M., Nikaj H., Cillara N., Cannavera A., Deserra A., Margiani C., Cabula R., Dettori M., Gramignano G., Lezoche G., Ortenzi M., Orlandoni E. S., Curzi F., Vitali F., Capomagi P., Palmieri M., Giuffrida M., Del Rio P., Bonati E., Loderer T., Cozzani F., Rossini M., Agnesi S., Capolupo G. T., Caricato M., Carannante F., Masciana G., Marrelli M., Miacci V., Lauricella S., Tonini V., Cervellera M., Pisconti S., Lozito C., Shahu J., Mongelli C., Morelli G., Sartarelli L., Sica G. S., Siragusa L., Bagaglini G., Guida A. M., Franceschilli M., Bellato V., Fiorani C., Taddei A., Risaliti M., Bartolini I., Ringressi M. N., Tirloni L., Laface L., Abate E., Casati M., Gobbi P., Opocher E., Mariani N. M., Ceretti A. P., Giovenzana M., Giuliani B., Sironi M., Grossi U., Zanus G., Santoro G. A., Brizzolari M., De Leo E., Novello S., Aquilino K., Milardi F., Olmi S., Uccelli M., Bonaldi M., Cesana G. C., Bindi M., Galleano R., Langone A., Botto M., Franceschi A., Gambino E., Ronconi M., Casiraghi S., Casole G., Ciulla S. L., Terrosu G., Calandra S., Scarpa E., Cherchi V., Martinuzzo L., Clocchiatti L., Muschitiello D., Romanzi A., Vignati B., Vannelli A., Scolaro R., Milanesi M., Rossi F., Canonico G., Anastasi A., Nelli T., Barlettai M., Fratarcangeli R., Di Martino C., Damigella A., Adinolfi E., Birindelli A., Taglietti L., Dester S. E., Fleres F., Cucinotta E., Viscosi F., Biondo S. A., Badessi G., Catarsini N., Mazzeo C., Rega D., Delrio P., Cervone C., Aversano A., De Franciscis S., Di Marzo M., Marra B., Pace U., Amato A., Batistotti P., Mina E., Serventi A., Lapolla P., Mingoli A., Sapienza P., Brachini G., Cirillo B., Fiori E., Crocetti D., Clementi I., Martines G., Picciariello A., Tomasicchio G., Dibra R., Trigiante G., Rinaldi M., Lantone G., Porcu A., Perra T., Scanu A. M., Feo C. F., Fancellu A., Cossu M. L., Ginesu G. C., Patriti A., Coletta D., Petrelli F., Greco P. A., Spadoni C., Cassiani G., Bianchini F., Arganini M., Bianchini M., Perotti B., Palmeri M., Scabini S., Deiana S., Carganico G., Pertile D., Soriero D., Fioravanti E., Sperotto B., Nardo B., Paglione D., Crocco V., Doni M., Osso M., Perri R., Sampietro G. M., Corbellini C., Lorusso L., Manzo C. A., Cigognini M., Baldi C., Palomba G., Aprea G., Capuano M., Basile R., Tutino R., Massani M., Marinelli L., Canitano N., Pilia T., Podda M., Pisanu A., Murzi V., Incani S., Frongia F., Esposito G., Luglio G., Tropeano F. P., Pagano G., Spina E., De Simone G., Cricri M., Catena F., Vallicelli C., Zanini N., Ronconi D., Favi F., Mazzucchelli C., Convertini G., Vincenti L., Andriola V., Bizzoca C., Feo C. V., Fabbri N., Fazzin M., Pesce A., Gennari S., Torchiaro M., Severi S., Frontali A., Bracchetti G., Granieri S., Cotsoglou C., Carlini M., Lisi G., Spoletini D., Mastrangeli M. R., Campanelli M., Manigrasso M., Milone M., De Palma G. D., Vertaldi S., Chini A., Maione F., Marello A., Selvaggi F., Sciaudone G., Selvaggi L., Tasselli F. M., Fuschillo G., Oddis L., Grande S., Grande M., Ascanelli S., Chimisso L., Aisoni F., Rossin E., Pepe F., Marchetti F., Picardi B., Rossi S., Del Monte S. R., Picarelli M., Muttillo I. A., Ratto C., Marra A. A., Parello A., Litta F., Campenni P., De Simone V., Pata F., Riboni C., Rausa E., Celentano V., Rottoli, M, Spinelli, A, Pellino, G, Gori, A, Calini, G, Flacco, M, Manzoli, L, Poggioli, G, Romano, A, Belvedere, A, Lanci, A, Parlanti, D, Vago, G, Pezzuto, A, Canavese, A, Dajti, G, Cardelli, S, Catalioto, C, Russo, I, Violante, T, Morezzi, D, Maurino, L, Filippone, E, Cuicchi, D, Bernante, P, Jovine, E, Lombardi, R, Masetti, M, Cipressi, C, Offi, M, Larotonda, C, Puglisi, S, Barbosa, A, Vaiana, R, Bianchi, P, Tonti, C, Codignola, C, Zorcolo, L, Restivo, A, Deidda, S, Marchetti, M, Ippolito, L, Spolverato, G, Pucciarelli, S, Marchegiani, F, Ghio, G, Zagolin, G, Glavas, D, Tomassi, M, Rosati, R, Elmore, U, Gozzini, L, Calef, R, Puccetti, F, Cossu, A, Vignali, A, Morino, M, Allaix, M, Cannata, G, Lombardi, E, Ammirati, C, Piceni, C, Buccianti, P, Balestri, R, Puccini, M, Pezzati, D, D'Ischia, R, Asta, V, Sargenti, B, Taddei, G, Bonari, F, Boni, G, Ferrero, A, Mineccia, M, Gonella, F, Palisi, M, Danese, F, Cherubini, V, Perotti, S, Carvello, M, Carbone, F, Luberto, A, Calafiore, E, De Lucia, F, Sacchi, M, Sasia, D, Giuffrida, M, Ballauri, E, Cardile, M, Armentano, S, Beltrami, E, Preve, G, Vercellone, B, Mozzon, M, Folliero, C, Lirusso, C, Vecchiato, M, Ziccarelli, A, Gattesco, D, Moretti, L, Crestale, S, Banchini, F, Capelli, P, Romboli, A, Palmieri, G, Conti, L, Rizzi, N, Bonfili, D, De Manzini, N, Germani, P, Osenda, E, Cortinovis, S, Giunta, C, Fracon, S, Abdallah, H, Bogoni, S, Portolani, N, Nascimbeni, R, Molfino, S, Tiberio, G, Garosio, I, Lamperti, G, Rigosa, D, Ercolani, G, Solaini, L, Cavaliere, D, Avanzolini, A, D'Acapito, F, Chiarella, L, Di Pietrantonio, D, Annunziata, D, Piccolo, R, Sorrentino, M, Pansini, M, Cojutti, A, Graziano, M, Callegari, F, Balzarotti, L, Dameno, V, Cattaneo, A, Santolamazza, G, Altieri, C, Magarini, R, Pietrabissa, A, Dominioni, T, Pugliese, L, Peri, A, Botti, M, Salvetti, F, Boni, L, Cassinotti, E, Baldari, L, Messina, V, D'Abrosca, V, Cianci, P, Tumolo, R, Gattulli, D, Restini, E, Minafra, M, Sederino, M, Bottalico, B, Pilati, P, Franzato, B, Mattara, G, De Simoni, O, Barina, A, Tonello, M, Muratore, A, Calabro, M, Federico Pipitone, N, Cuzzola, B, Van Nood, E, Passuello, N, Frasson, A, Mammano, E, Faccio, L, Vittadello, F, Bressan, A, Sarzo, G, Tamini, N, Oldani, M, Cigagna, L, Carissimi, F, De Carlo, G, Baccalini, E, Nespoli, L, Giordano, A, Cantafio, S, Grifoni, L, Matani, D, Livi, S, Delogu, D, Scognamillo, F, Marrosu, A, Guerrini, L, Ugolini, G, Ghignone, F, Frascaroli, G, Albertini, N, Zattoni, D, Taffurelli, G, Montroni, I, Colombo, F, Danelli, P, Bondurri, A, Maffioli, A, Bonomi, A, Pezzoli, I, Cammarata, F, Goletti, O, Molteni, M, Assisi, A, Quartierini, G, Da Lio, C, Verdi, D, Mondi, I, Peluso, C, Macchi, L, Tanzanu, M, Zanzi, F, Pellegrini, S, Andreuccetti, J, D'Alessio, R, Pignata, G, De Capua, M, Canfora, I, Ottaviani, L, Lepiane, P, Balla, A, De Carlo, A, Saraceno, F, Scaramuzzo, R, Guida, A, Aguzzi, D, Bellora, P, Gentilli, S, Monni, M, Nikaj, H, Cillara, N, Cannavera, A, Deserra, A, Margiani, C, Cabula, R, Dettori, M, Gramignano, G, Lezoche, G, Ortenzi, M, Orlandoni, E, Curzi, F, Vitali, F, Capomagi, P, Palmieri, M, Del Rio, P, Bonati, E, Loderer, T, Cozzani, F, Rossini, M, Agnesi, S, Capolupo, G, Caricato, M, Carannante, F, Masciana, G, Marrelli, M, Miacci, V, Lauricella, S, Tonini, V, Cervellera, M, Pisconti, S, Lozito, C, Shahu, J, Mongelli, C, Morelli, G, Sartarelli, L, Sica, G, Siragusa, L, Bagaglini, G, Franceschilli, M, Bellato, V, Fiorani, C, Taddei, A, Risaliti, M, Bartolini, I, Ringressi, M, Tirloni, L, Laface, L, Abate, E, Casati, M, Gobbi, P, Opocher, E, Mariani, N, Ceretti, A, Giovenzana, M, Giuliani, B, Sironi, M, Grossi, U, Zanus, G, Santoro, G, Brizzolari, M, De Leo, E, Novello, S, Aquilino, K, Milardi, F, Olmi, S, Uccelli, M, Bonaldi, M, Cesana, G, Bindi, M, Galleano, R, Langone, A, Botto, M, Franceschi, A, Gambino, E, Ronconi, M, Casiraghi, S, Casole, G, Ciulla, S, Terrosu, G, Calandra, S, Scarpa, E, Cherchi, V, Martinuzzo, L, Clocchiatti, L, Muschitiello, D, Romanzi, A, Vignati, B, Vannelli, A, Scolaro, R, Milanesi, M, Rossi, F, Canonico, G, Anastasi, A, Nelli, T, Barlettai, M, Fratarcangeli, R, Di Martino, C, Damigella, A, Adinolfi, E, Birindelli, A, Taglietti, L, Dester, S, Fleres, F, Cucinotta, E, Viscosi, F, Biondo, S, Badessi, G, Catarsini, N, Mazzeo, C, Rega, D, Delrio, P, Cervone, C, Aversano, A, De Franciscis, S, Di Marzo, M, Marra, B, Pace, U, Amato, A, Batistotti, P, Mina, E, Serventi, A, Lapolla, P, Mingoli, A, Sapienza, P, Brachini, G, Cirillo, B, Fiori, E, Crocetti, D, Clementi, I, Martines, G, Picciariello, A, Tomasicchio, G, Dibra, R, Trigiante, G, Rinaldi, M, Lantone, G, Porcu, A, Perra, T, Scanu, A, Feo, C, Fancellu, A, Cossu, M, Ginesu, G, Patriti, A, Coletta, D, Petrelli, F, Greco, P, Spadoni, C, Cassiani, G, Bianchini, F, Arganini, M, Bianchini, M, Perotti, B, Palmeri, M, Scabini, S, Deiana, S, Carganico, G, Pertile, D, Soriero, D, Fioravanti, E, Sperotto, B, Nardo, B, Paglione, D, Crocco, V, Doni, M, Osso, M, Perri, R, Sampietro, G, Corbellini, C, Lorusso, L, Manzo, C, Cigognini, M, Baldi, C, Palomba, G, Aprea, G, Capuano, M, Basile, R, Tutino, R, Massani, M, Marinelli, L, Canitano, N, Pilia, T, Podda, M, Pisanu, A, Murzi, V, Incani, S, Frongia, F, Esposito, G, Luglio, G, Tropeano, F, Pagano, G, Spina, E, De Simone, G, Cricri, M, Catena, F, Vallicelli, C, Zanini, N, Ronconi, D, Favi, F, Mazzucchelli, C, Convertini, G, Vincenti, L, Andriola, V, Bizzoca, C, Fabbri, N, Fazzin, M, Pesce, A, Gennari, S, Torchiaro, M, Severi, S, Frontali, A, Bracchetti, G, Granieri, S, Cotsoglou, C, Carlini, M, Lisi, G, Spoletini, D, Mastrangeli, M, Campanelli, M, Manigrasso, M, Milone, M, De Palma, G, Vertaldi, S, Chini, A, Maione, F, Marello, A, Selvaggi, F, Sciaudone, G, Selvaggi, L, Tasselli, F, Fuschillo, G, Oddis, L, Grande, S, Grande, M, Ascanelli, S, Chimisso, L, Aisoni, F, Rossin, E, Pepe, F, Marchetti, F, Picardi, B, Rossi, S, Del Monte, S, Picarelli, M, Muttillo, I, Ratto, C, Marra, A, Parello, A, Litta, F, Campenni, P, De Simone, V, Pata, F, Riboni, C, Rausa, E, Celentano, V, Rottoli M., Spinelli A., Pellino G., Gori A., Calini G., Flacco M. E., Manzoli L., Poggioli G., Romano A., Belvedere A., Lanci A. L., Parlanti D., Vago G., Pezzuto A. P., Canavese A., Dajti G., Cardelli S., Catalioto C., Russo I. S., Violante T., Morezzi D., Maurino L., Filippone E., Cuicchi D., Bernante P., Jovine E., Lombardi R., Masetti M., Cipressi C., Offi M. F., Larotonda C., Puglisi S. B., Barbosa A., Vaiana R., Bianchi P. M., Tonti C., Codignola C., Zorcolo L., Restivo A., Deidda S., Marchetti M. E., Ippolito L., Spolverato G., Pucciarelli S., Marchegiani F., Ghio G., Zagolin G., Glavas D., Tomassi M., Rosati R., Elmore U., Gozzini L., Calef R., Puccetti F., Cossu A., Vignali A., Morino M., Allaix M. E., Cannata G., Lombardi E., Ammirati C. A., Piceni C., Buccianti P., Balestri R., Puccini M., Pezzati D., D'Ischia R., Asta V. F., Sargenti B., Taddei G., Bonari F., Boni G., Ferrero A., Mineccia M., Gonella F., Palisi M., Danese F., Cherubini V., Perotti S., Carvello M., Carbone F., Luberto A., Calafiore E., De Lucia F., Sacchi M., Sasia D., Giuffrida M. C., Ballauri E., Cardile M., Armentano S., Beltrami E., Preve G., Vercellone B., Mozzon M., Folliero C., Lirusso C., Vecchiato M., Ziccarelli A., Gattesco D., Moretti L., Crestale S., Banchini F., Capelli P., Romboli A., Palmieri G., Conti L., Rizzi N., Bonfili D., De Manzini N., Germani P., Osenda E., Cortinovis S., Giunta C., Fracon S., Abdallah H., Bogoni S., Portolani N., Nascimbeni R., Molfino S., Tiberio G. A. M., Garosio I., Lamperti G., Rigosa D., Ercolani G., Solaini L., Cavaliere D., Avanzolini A., D'Acapito F., Chiarella L. L., Di Pietrantonio D., Annunziata D., Piccolo R., Sorrentino M., Pansini M., Cojutti A., Graziano M., Callegari F., Balzarotti L., Dameno V. R., Cattaneo A., Santolamazza G., Altieri C., Magarini R., Pietrabissa A., Dominioni T., Pugliese L., Peri A., Botti M., Salvetti F., Boni L., Cassinotti E., Baldari L., Messina V., D'Abrosca V., Cianci P., Tumolo R., Gattulli D., Restini E., Minafra M., Sederino M. G., Bottalico B., Pilati P., Franzato B., Mattara G., De Simoni O., Barina A., Tonello M., Muratore A., Calabro M., Federico Pipitone N. S., Cuzzola B., Van Nood E. H., Passuello N., Frasson A., Mammano E., Faccio L., Vittadello F., Bressan A., Sarzo G., Tamini N., Oldani M., Cigagna L., Carissimi F., De Carlo G., Baccalini E., Nespoli L., Giordano A., Cantafio S., Grifoni L., Matani D., Livi S., Delogu D., Scognamillo F., Marrosu A., Guerrini L., Ugolini G., Ghignone F., Frascaroli G., Albertini N., Zattoni D., Taffurelli G., Montroni I., Colombo F., Danelli P., Bondurri A., Maffioli A., Bonomi A., Pezzoli I., Cammarata F., Goletti O., Molteni M., Assisi A., Quartierini G., Da Lio C., Verdi D., Mondi I., Peluso C., MacChi L., Tanzanu M., Zanzi F., Pellegrini S., Andreuccetti J., D'Alessio R., Pignata G., De Capua M., Canfora I., Ottaviani L., Lepiane P., Balla A., De Carlo A., Saraceno F., Scaramuzzo R., Guida A., Aguzzi D., Bellora P., Gentilli S., Monni M., Nikaj H., Cillara N., Cannavera A., Deserra A., Margiani C., Cabula R., Dettori M., Gramignano G., Lezoche G., Ortenzi M., Orlandoni E. S., Curzi F., Vitali F., Capomagi P., Palmieri M., Giuffrida M., Del Rio P., Bonati E., Loderer T., Cozzani F., Rossini M., Agnesi S., Capolupo G. T., Caricato M., Carannante F., Masciana G., Marrelli M., Miacci V., Lauricella S., Tonini V., Cervellera M., Pisconti S., Lozito C., Shahu J., Mongelli C., Morelli G., Sartarelli L., Sica G. S., Siragusa L., Bagaglini G., Guida A. M., Franceschilli M., Bellato V., Fiorani C., Taddei A., Risaliti M., Bartolini I., Ringressi M. N., Tirloni L., Laface L., Abate E., Casati M., Gobbi P., Opocher E., Mariani N. M., Ceretti A. P., Giovenzana M., Giuliani B., Sironi M., Grossi U., Zanus G., Santoro G. A., Brizzolari M., De Leo E., Novello S., Aquilino K., Milardi F., Olmi S., Uccelli M., Bonaldi M., Cesana G. C., Bindi M., Galleano R., Langone A., Botto M., Franceschi A., Gambino E., Ronconi M., Casiraghi S., Casole G., Ciulla S. L., Terrosu G., Calandra S., Scarpa E., Cherchi V., Martinuzzo L., Clocchiatti L., Muschitiello D., Romanzi A., Vignati B., Vannelli A., Scolaro R., Milanesi M., Rossi F., Canonico G., Anastasi A., Nelli T., Barlettai M., Fratarcangeli R., Di Martino C., Damigella A., Adinolfi E., Birindelli A., Taglietti L., Dester S. E., Fleres F., Cucinotta E., Viscosi F., Biondo S. A., Badessi G., Catarsini N., Mazzeo C., Rega D., Delrio P., Cervone C., Aversano A., De Franciscis S., Di Marzo M., Marra B., Pace U., Amato A., Batistotti P., Mina E., Serventi A., Lapolla P., Mingoli A., Sapienza P., Brachini G., Cirillo B., Fiori E., Crocetti D., Clementi I., Martines G., Picciariello A., Tomasicchio G., Dibra R., Trigiante G., Rinaldi M., Lantone G., Porcu A., Perra T., Scanu A. M., Feo C. F., Fancellu A., Cossu M. L., Ginesu G. C., Patriti A., Coletta D., Petrelli F., Greco P. A., Spadoni C., Cassiani G., Bianchini F., Arganini M., Bianchini M., Perotti B., Palmeri M., Scabini S., Deiana S., Carganico G., Pertile D., Soriero D., Fioravanti E., Sperotto B., Nardo B., Paglione D., Crocco V., Doni M., Osso M., Perri R., Sampietro G. M., Corbellini C., Lorusso L., Manzo C. A., Cigognini M., Baldi C., Palomba G., Aprea G., Capuano M., Basile R., Tutino R., Massani M., Marinelli L., Canitano N., Pilia T., Podda M., Pisanu A., Murzi V., Incani S., Frongia F., Esposito G., Luglio G., Tropeano F. P., Pagano G., Spina E., De Simone G., Cricri M., Catena F., Vallicelli C., Zanini N., Ronconi D., Favi F., Mazzucchelli C., Convertini G., Vincenti L., Andriola V., Bizzoca C., Feo C. V., Fabbri N., Fazzin M., Pesce A., Gennari S., Torchiaro M., Severi S., Frontali A., Bracchetti G., Granieri S., Cotsoglou C., Carlini M., Lisi G., Spoletini D., Mastrangeli M. R., Campanelli M., Manigrasso M., Milone M., De Palma G. D., Vertaldi S., Chini A., Maione F., Marello A., Selvaggi F., Sciaudone G., Selvaggi L., Tasselli F. M., Fuschillo G., Oddis L., Grande S., Grande M., Ascanelli S., Chimisso L., Aisoni F., Rossin E., Pepe F., Marchetti F., Picardi B., Rossi S., Del Monte S. R., Picarelli M., Muttillo I. A., Ratto C., Marra A. A., Parello A., Litta F., Campenni P., De Simone V., Pata F., Riboni C., Rausa E., and Celentano V.

Abstract

Background: The association between volume, complications and pathological outcomes is still under debate regarding colorectal cancer surgery. The aim of the study was to assess the association between centre volume and severe complications, mortality, less-than-radical oncologic surgery, and indications for neoadjuvant therapy. Methods: Retrospective analysis of 16,883 colorectal cancer cases from 80 centres (2018-2021). Outcomes: 30-day mortality; Clavien-Dindo grade >2 complications; removal of ≥ 12 lymph nodes; non-radical resection; neoadjuvant therapy. Quartiles of hospital volumes were classified as LOW, MEDIUM, HIGH, and VERY HIGH. Independent predictors, both overall and for rectal cancer, were evaluated using logistic regression including age, gender, AJCC stage and cancer site. Results: LOW-volume centres reported a higher rate of severe postoperative complications (OR 1.50, 95% c.i. 1.15-1.096, P = 0.003). The rate of ≥ 12 lymph nodes removed in LOW-volume (OR 0.68, 95% c.i. 0.56-0.85, P < 0.001) and MEDIUM-volume (OR 0.72, 95% c.i. 0.62-0.83, P < 0.001) centres was lower than in VERY HIGH-volume centres. Of the 4676 rectal cancer patients, the rate of ≥ 12 lymph nodes removed was lower in LOW-volume than in VERY HIGH-volume centres (OR 0.57, 95% c.i. 0.41-0.80, P = 0.001). A lower rate of neoadjuvant chemoradiation was associated with HIGH (OR 0.66, 95% c.i. 0.56-0.77, P < 0.001), MEDIUM (OR 0.75, 95% c.i. 0.60-0.92, P = 0.006), and LOW (OR 0.70, 95% c.i. 0.52-0.94, P = 0.019) volume centres (vs. VERY HIGH). Conclusion: Colorectal cancer surgery in low-volume centres is at higher risk of suboptimal management, poor postoperative outcomes, and less-than-adequate oncologic resections. Centralisation of rectal cancer cases should be taken into consideration to optimise the outcomes.

Published
2024

8. Machine Perfusions in Liver Transplantation: The Evidence-Based Position Paper of the Italian Society of Organ and Tissue Transplantation

Author

Ghinolfi, D, Lai, Q, Dondossola, D, De Carlis, R, Zanierato, M, Patrono, D, Baroni, S, Bassi, D, Ferla, F, Lauterio, A, Lazzeri, C, Magistri, P, Melandro, F, Pagano, D, Pezzati, D, Ravaioli, M, Rreka, E, Toti, L, Zanella, A, Burra, P, Petta, S, Rossi, M, Dutkowski, P, Jassem, W, Muiesan, P, Quintini, C, Selzner, M, Cillo, U, Ghinolfi D., Lai Q., Dondossola D., De Carlis R., Zanierato M., Patrono D., Baroni S., Bassi D., Ferla F., Lauterio A., Lazzeri C., Magistri P., Melandro F., Pagano D., Pezzati D., Ravaioli M., Rreka E., Toti L., Zanella A., Burra P., Petta S., Rossi M., Dutkowski P., Jassem W., Muiesan P., Quintini C., Selzner M., Cillo U., Ghinolfi, D, Lai, Q, Dondossola, D, De Carlis, R, Zanierato, M, Patrono, D, Baroni, S, Bassi, D, Ferla, F, Lauterio, A, Lazzeri, C, Magistri, P, Melandro, F, Pagano, D, Pezzati, D, Ravaioli, M, Rreka, E, Toti, L, Zanella, A, Burra, P, Petta, S, Rossi, M, Dutkowski, P, Jassem, W, Muiesan, P, Quintini, C, Selzner, M, Cillo, U, Ghinolfi D., Lai Q., Dondossola D., De Carlis R., Zanierato M., Patrono D., Baroni S., Bassi D., Ferla F., Lauterio A., Lazzeri C., Magistri P., Melandro F., Pagano D., Pezzati D., Ravaioli M., Rreka E., Toti L., Zanella A., Burra P., Petta S., Rossi M., Dutkowski P., Jassem W., Muiesan P., Quintini C., Selzner M., and Cillo U.

Abstract

The use of machine perfusion (MP) in liver transplantation (LT) is spreading worldwide. However, its efficacy has not been demonstrated, and its proper clinical use has far to go to be widely implemented. The Società Italiana Trapianti d’Organo (SITO) promoted the development of an evidence-based position paper. A 3-step approach has been adopted to develop this position paper. First, SITO appointed a chair and a cochair who then assembled a working group with specific experience of MP in LT. The Guideline Development Group framed the clinical questions into a patient, intervention, control, and outcome (PICO) format, extracted and analyzed the available literature, ranked the quality of the evidence, and prepared and graded the recommendations. Recommendations were then discussed by all the members of the SITO and were voted on via the Delphi method by an institutional review board. Finally, they were evaluated and scored by a panel of external reviewers. All available literature was analyzed, and its quality was ranked. A total of 18 recommendations regarding the use and the efficacy of ex situ hypothermic and normothermic machine perfusion and sequential normothermic regional perfusion and ex situ MP were prepared and graded according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. A critical and scientific approach is required for the safe implementation of this new technology.

Published
2020

18. Long-Term Follow Up in ABO-Incompatible Adult Liver Transplantation

Author

Ghinolfi, D., primary, De Simone, P., additional, Fiorenza, G., additional, Catalano, G., additional, Tincani, G., additional, Coletti, L., additional, Carrai, P., additional, Leonardi, G., additional, Arenga, G., additional, Balzano, E., additional, Bocchi, F., additional, Pezzati, D., additional, and Filipponi, F., additional

Published
2012
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20. Use of Very Old Donors for Liver Transplantation

Author

Ghinolfi, D., primary, Fiorenza, G., additional, De Simone, P., additional, Carrai, P., additional, Catalano, G., additional, Pezzati, D., additional, Bocchi, F., additional, Coletti, L., additional, Leonardi, G., additional, Tincani, G., additional, Balzano, E., additional, Arenga, G., additional, and Filipponi, F., additional

Published
2012
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21. Machine Perfusions in Liver Transplantation: The Evidence‐Based Position Paper of the Italian Society of Organ and Tissue Transplantation

Author

Paolo Muiesan, Massimo Rossi, Damiano Patrono, F. Melandro, Daniele Pezzati, Markus Selzner, Alberto Zanella, Andrea Lauterio, Riccardo De Carlis, Cristiano Quintini, Stefano Baroni, Domenico Bassi, Davide Ghinolfi, Paolo Magistri, Fabio Ferla, Luca Toti, Marinella Zanierato, Matteo Ravaioli, Quirino Lai, Chiara Lazzeri, Wayel Jassem, Patrizia Burra, Daniele Dondossola, Duilio Pagano, Philippe Dutkowski, Umberto Cillo, Erion Rreka, Salvatore Petta, University of Zurich, Ghinolfi, Davide, Ghinolfi, D, Lai, Q, Dondossola, D, De Carlis, R, Zanierato, M, Patrono, D, Baroni, S, Bassi, D, Ferla, F, Lauterio, A, Lazzeri, C, Magistri, P, Melandro, F, Pagano, D, Pezzati, D, Ravaioli, M, Rreka, E, Toti, L, Zanella, A, Burra, P, Petta, S, Rossi, M, Dutkowski, P, Jassem, W, Muiesan, P, Quintini, C, Selzner, M, Cillo, U, Ghinolfi D., Lai Q., Dondossola D., De Carlis R., Zanierato M., Patrono D., Baroni S., Bassi D., Ferla F., Lauterio A., Lazzeri C., Magistri P., Melandro F., Pagano D., Pezzati D., Ravaioli M., Rreka E., Toti L., Zanella A., Burra P., Petta S., Rossi M., Dutkowski P., Jassem W., Muiesan P., Quintini C., Selzner M., and Cillo U.

Subjects
medicine.medical_specialty, Evidence-based practice, 2747 Transplantation, GRADE, donor after circulatory death, donor brain death, hypothermic machine, liver transplant, machine perfusion, normothermic machine, normothermic regional perfusion, position paper, medicine.medical_treatment, Delphi method, MEDLINE, 610 Medicine & health, liver, perfusion machine, 030230 surgery, Liver transplantation, liver, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Medical physics, 10217 Clinic for Visceral and Transplantation Surgery, HumansItaly, Transplantation, Machine perfusion, Hepatology, business.industry, Organ Preservation, perfusion machine, Institutional review board, Liver Transplantation, 2746 Surgery, Perfusion, Italy, Position paper, 2721 Hepatology, 030211 gastroenterology & hepatology, Surgery, business, Human
Abstract

The use of machine perfusion (MP) in liver transplantation (LT) is spreading worldwide. However, its efficacy has not been demonstrated, and its proper clinical use has far to go to be widely implemented. The Società Italiana Trapianti d’Organo (SITO) promoted the development of an evidence-based position paper. A 3-step approach has been adopted to develop this position paper. First, SITO appointed a chair and a cochair who then assembled a working group with specific experience of MP in LT. The Guideline Development Group framed the clinical questions into a patient, intervention, control, and outcome (PICO) format, extracted and analyzed the available literature, ranked the quality of the evidence, and prepared and graded the recommendations. Recommendations were then discussed by all the members of the SITO and were voted on via the Delphi method by an institutional review board. Finally, they were evaluated and scored by a panel of external reviewers. All available literature was analyzed, and its quality was ranked. A total of 18 recommendations regarding the use and the efficacy of ex situ hypothermic and normothermic machine perfusion and sequential normothermic regional perfusion and ex situ MP were prepared and graded according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. A critical and scientific approach is required for the safe implementation of this new technology.

Published
2020
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22. Recurrence and survival after robotic vs laparoscopic liver resection in very-early to early-stage (BCLC 0-A) hepatocellular carcinoma.

Author

Bernardi L, Balzano E, Roesel R, Senatore A, Pezzati D, Catalano G, Garo ML, Tincani G, Majno-Hurst P, Ghinolfi D, and Cristaudi A

Subjects
Humans, Male, Female, Retrospective Studies, Aged, Middle Aged, Neoplasm Staging, Propensity Score, Survival Rate, Treatment Outcome, Carcinoma, Hepatocellular surgery, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular pathology, Liver Neoplasms surgery, Liver Neoplasms mortality, Liver Neoplasms pathology, Hepatectomy methods, Neoplasm Recurrence, Local epidemiology, Laparoscopy methods, Robotic Surgical Procedures methods
Abstract

Background: Robotic (RLR) and laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) provide similar short-term outcomes, but data focused on recurrence and survival are still lacking. We hypothesized non-inferior oncologic results of RLR compared to LLR for HCC of stage BCLC 0-A., Methods: RLRs and LLRs on patients with HCC of stage BCLC 0-A and preserved liver function (Child A or B if cirrhosis) were retrospectively reviewed. Propensity score matching (PSM) was used to mitigate selection bias. The primary endpoints were recurrence-free (RFS) and overall survival (OS); secondary endpoints were incidence, pattern, and treatment of recurrences., Results: After 1:1 PSM, two groups (RLR = 68; LLR = 68) of patients with similar characteristics, liver function and HCC features were obtained: median age 71-years, males 73.5%, underlying cirrhosis 91.2% (Child A, 96.8%, MELD ≤ 9, 96.0%), portal hypertension 22.1%, single-HCC 90.4%. Two- and 5-year RFS were 78.0 vs 59.0% and 54.0 vs 53.0% (p = 0.107), while OS was 97.0 vs 90.0% and 87.0 vs 90.0% (p = 0.951) for RLR vs LLR, respectively. Incidence of HCC recurrence was similar (35.3 vs 39.7%; p = 0.723). Recurrences developed mostly within the liver (29.4 vs 30.9%; p = 1.000) and within 2 years after hepatectomy (19.1 vs 32.4%, p = 0.116) in RLR vs LLRs. Curative-intent treatment of recurrences did not differ (liver transplantation 19.6%, redo-resection 15.7%, locoregional treatments 52.9%) except for a tendency toward more redo-resections for recurrences after RLR., Conclusions: Oncologic outcomes of RLR were not inferior to those of LLR in selected HCC patients of stage BCLC 0-A with underlying cirrhosis. Both techniques guaranteed similar salvageability in case of HCC recurrence., Competing Interests: Declarations. Disclosures: Drs. Lorenzo Bernardi, Emanuele Balzano, Raffaello Roesel, Annamaria Senatore, Daniele Pezzati, Gabriele Catalano, Maria Luisa Garo, Giovanni Tincani, Pietro Majno-Hurst, Davide Ghinolfi, and Alessandra Cristaudi have no conflicts of interest or financial ties to disclose. Ethical approval: This study was conducted in accordance with the Declaration of Helsinki. The study was approved by the regional ethical committees of the institutions participating in the study. Informed consent: Patients provided informed consent to participate to the study at first referral at Pisa University Hospital as per institutional policy. Patients in Regional Hospital of Lugano were informed of the ongoing study and received a non-objection letter from the institution. Written informed consent for participants from Lugano was not required in accordance with local guidelines., (© 2025. The Author(s).)

Published
2025
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23. Association of perfusate cytokine concentrations during liver graft ex-situ normothermic perfusion to donor type and postoperative outcomes.

Author

Pezzati D, Torri F, Franzini M, Balzano E, Catalano G, Tincani G, Bronzoni J, Martinelli C, Trizzino A, Petagna L, Carrai P, Petruccelli S, Masini M, Rotondo MI, Babboni S, Del Turco S, Morganti R, De Tata V, Biancofiore G, Peris A, Lazzeri C, Basta G, Paolicchi A, and Ghinolfi D

Abstract

Background: The use of the so-called extended criteria donors increases the number of grafts available for transplantation. Many studies reported their good outcomes but their use is debated due to increased risk of complications. Ex situ liver perfusion has reduced graft discard rate and helped to test their function before implantation. Cytokines are known to be involved in ischemia reperfusion injury but their potential to predict liver function during normothermic machine perfusion (NMP) has not been fully investigated. The aim of this study was to compare cytokines levels during NMP in 3 different types of donors (DBD, DCD II, DCD III) and correlate these data to postoperative clinical and biochemical outcomes., Methods: All DBDs older than 70 years and DCDs transplanted after NMP were included. IL-6, IL-10 and TNF-α were measured during NMP and correlated with clinical outcomes., Results: Thirty liver grafts were transplanted after NMP: 16 DBD, 7 DCD-II and 7 DCD-III. There were 6 cases of EAD (20.0%), 10 of PRS (33.3%) and 11 cases of AKI (36.7%), with no major differences among groups. A positive correlation was found between perfusate IL-6 levels and the bilirubin peak within 7 days after LT while IL-10 was associated with the ICU stay and TNF-α to the INR peak within 7 days. IL-6 was negatively associated to post-operative ALT levels, IL-10 to bilirubin peak. A correlation between higher IL-6 levels at 2h and graft loss was found., Conclusions: This is the first study to compare cytokines profile during NMP in three different types of donors and correlate it to clinical outcomes. A correlation between IL-6 concentration and graft failure was found. The role and the significate of inflammatory markers in MP perfusate and their potential to assess graft viability and the risk of post-LT complications has to be further addressed., (Copyright © 2025 American Association for the Study of Liver Diseases.)

Published
2025
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24. Transabdominal Robotic-Assisted Partial Nephrectomy and CT-Guided Percutaneous Cryoablation for the Treatment of De Novo Kidney Tumors After Liver Transplantation.

Author

Balzano E, Bernardi L, Candita G, Trizzino A, Petagna L, Bozzi E, Scalise P, Cristaudi A, Tincani G, Pezzati D, Ghinolfi D, and Crocetti L

Abstract

The management of de novo kidney tumors (DKTs) after liver transplantation (LT) is challenging due to previous transplant surgery and calcineurin inhibitors (CNI)-related nephrotoxicity. Minimally invasive renal-sparing strategies like robot-assisted partial nephrectomy (RPN) are favored, but a transperitoneal approach may be limited by the previous transplant surgery and the location of the DKT; in such cases, CT-guided cryoablation may be an alternative option. In this retrospective cohort study, we aimed to compare RPN and cryoablation for the treatment of DKT in LT recipients. The primary endpoints were the efficacy (R0 resection in RPN, absence of the tumor at first follow-up for cryoablation) and the safety of the procedures (postoperative morbidity and increase in creatine level). The periprocedural costs and the oncologic efficacy (recurrence and overall survival) were the secondary endpoints. Twelve LT recipients (91.7% males, mean age 65 years) underwent RPN (n = 6) or cryoablation (n = 6) for DKT; the median interval between LT and diagnosis of DKT was 142.5 vs. 117.5 months, respectively. Efficacy was obtained in all patients after RPN and cryoablation. Postoperative morbidity was 16.7% in each group, and the postoperative increase in creatinine values was similar. Hospital stay was shorter following cryoablation vs. RPN (3.1 vs. 6.7 days; p = 0.03). The mean procedural costs were higher for RPN. There was no mortality and none of the patients had signs of recurrence after a median follow-up of 40.5 months. Both RPN and CT-guided cryoablation were safe and effective for the treatment of selected patients with DKT after LT. When applicable, cryoablation may be cost-effective and provide faster recovery.

Published
2025
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25. Perfusate Liver Arginase 1 Levels After End-Ischemic Machine Perfusion Are Associated with Early Allograft Dysfunction.

Author

Basta G, Babboni S, Pezzati D, Del Turco S, Balzano E, Catalano G, Russo L, Tincani G, Carrai P, Petruccelli S, Bronzoni J, Martinelli C, Palladino S, Trizzino A, Petagna L, Romagnoli R, Patrono D, Biancofiore G, Peris A, Lazzeri C, and Ghinolfi D

Abstract

Background/Objectives : The rising use of liver grafts from donation after circulatory death (DCD) has been enabled by advances in normothermic regional perfusion (NRP) and machine perfusion (MP) technologies. We aimed to identify predictive biomarkers in DCD grafts subjected to NRP, followed by randomization to either normothermic machine perfusion (NMP) or dual hypothermic oxygenated perfusion (D-HOPE). Methods : Among 57 DCD donors, 32 liver grafts were transplanted, and recipients were monitored for one week post-transplant. Biomarkers linked with oxidative stress, hepatic injury, mitochondrial dysfunction, inflammation, regeneration, and autophagy were measured during NRP, end-ischemic MP, and one week post-transplant. Results : Arginase-1 (ARG-1) levels were consistently higher in discarded grafts and in recipients who later developed early allograft dysfunction (EAD). Specifically, ARG-1 levels at the end of MP correlated with markers of hepatic injury. Receiver operating characteristic analysis indicated that ARG-1 at the end of MP had a good predictive accuracy for EAD (AUC = 0.713; p = 0.02). Lipid peroxidation (TBARS) elevated at the start of NRP, declined over time, with higher levels in D-HOPE than in NMP, suggesting a more oxidative environment in D-HOPE. Metabolites like flavin mononucleotide (FMN) and NADH exhibited significant disparities between perfusion types, due to differences in perfusate compositions. Inflammatory biomarkers rose during NRP and NMP but normalized post-transplantation. Regenerative markers, including osteopontin and hepatocyte growth factor, increased during NRP and NMP and normalized post-transplant. Conclusions : ARG-1 demonstrates strong potential as an early biomarker for assessing liver graft viability during perfusion, supporting timely and effective decision-making in transplantation.

Published
2025
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26. Are there any benefits of prolonged hypothermic oxygenated perfusion?: Results from a national retrospective study.

Author

De Carlis R, Lauterio A, Schlegel A, Gringeri E, Patrono D, Camagni S, Dondossola D, Pezzati D, Olivieri T, Pagano D, Bongini M, Montanelli P, Ravaioli M, Bernasconi D, Valsecchi MG, Baccarani U, Cescon M, Andorno E, Mazzaferro V, Gruttadauria S, Di Benedetto F, Ghinolfi D, Caccamo L, Pinelli D, Romagnoli R, Cillo U, and De Carlis L

Subjects
Humans, Retrospective Studies, Male, Female, Middle Aged, Italy epidemiology, Time Factors, Adult, Aged, Incidence, Propensity Score, Risk Factors, Postoperative Complications prevention & control, Postoperative Complications epidemiology, Postoperative Complications etiology, Treatment Outcome, Liver surgery, Graft Survival, Oxygen, Cold Ischemia adverse effects, Cold Ischemia statistics & numerical data, Liver Transplantation adverse effects, Liver Transplantation methods, Organ Preservation methods, Organ Preservation adverse effects, Organ Preservation statistics & numerical data, Perfusion methods, Perfusion adverse effects, Acute Kidney Injury prevention & control, Acute Kidney Injury epidemiology, Acute Kidney Injury etiology
Abstract

Dual hypothermic oxygenated perfusion (DHOPE) is increasingly being used to extend liver preservation to improve transplant logistics. However, little is known about its benefits in high-risk liver grafts. This study aimed to investigate whether prolonged DHOPE provides benefits other than improved logistics in all liver types. We performed a national retrospective cohort study of 177 liver transplants from 12 Italian centers preserved with DHOPE for ≥4 hours between 2015 and 2022. A control group of 177 DHOPEs of <4 hours during the same period was created using 1:1 propensity score matching. The impact of risk profiles and preservation times on the outcomes was assessed using univariable and multivariable regression models. No significant differences in posttransplant outcomes were found between prolonged and short DHOPEs. However, the prolonged group had a significantly lower incidence of posttransplant acute kidney injury (AKI) compared to the short group (30.5% vs. 44.6%, p = 0.008). Among prolonged DHOPEs, no differences in transplant outcomes were observed according to donor risk index, Eurotransplant definition for marginal grafts, and balance of risk score. DHOPE duration was associated with a lower risk of AKI in multivariable models adjusted for donor risk index, Eutrotransplant marginal grafts, and balance of risk score. Prolonged hypothermic oxygenated perfusion confirmed its protective effect against AKI in a multivariable model adjusted for donor and recipient risk factors [OR: 0.412, 95% CI: 0.200-0.850, p = 0.016]. Prolonged DHOPE is widely used to improve transplant logistics, provides good results with high-risk grafts, and appears to be associated with a lower risk of posttransplant AKI. These results provide further insight into the important role of DHOPE in preventing posttransplant complications., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Published
2025
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27. Cholangiocyte Organoids: The New Frontier in Regenerative Medicine for the Study and Treatment of Cholangiopathies.

Author

Babboni S, Vacca PG, Simonini L, Pezzati D, Martinelli C, Frongillo F, Bianco G, Marciano E, Basta G, Ghinolfi D, and Del Turco S

Abstract

Cholangiopathies include a group of chronic progressive disorders, affecting the cholangiocytes, the epithelial cells that line the biliary tree, leading to liver parenchymal fibrosis and eventually end-stage liver disease necessitating transplantation. Experimental modeling of these multifactorial cholestatic diseases faces challenges due to the lack of adequate experimental in vitro and in vivo models. A novel approach employs three-dimensional organoid systems that offer several advantages for modeling disease and testing drug response in vitro. Organoids mimic intercellular communication, replicate the architecture of organs, and maintain the cell's original phenotype. Cholangiocyte organoids provide an in vitro model to study the pathogenesis and pharmacotherapeutic treatment of cholangiopathies and show great promise for regenerative therapies. In particular, patient-derived organoids allow personalized medicine approaches and the study of individual disease characteristics. This review highlights the significance of cholangiocyte organoid models in advancing our understanding of cholangiopathies and driving advancements in regenerative medicine strategies.

Published
2024
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28. Two pumps or one pump? A comparison of human liver normothermic machine perfusion devices for transplantation.

Author

Liu Q, Del Prete L, Hassan A, Pezzati D, Bilancini M, D'Amico G, Diago Uso T, Hashimoto K, Aucejo F, Fujiki M, Sasaki K, Kwon CHD, Eghtesad B, Miller C, and Quintini C

Subjects
Hemoglobins, Hepatic Artery surgery, Humans, Liver physiology, Organ Preservation, Perfusion, Liver Transplantation
Abstract

Background: Normothermic machine perfusion provides continuous perfusion to ex situ hepatic grafts through the portal vein and the hepatic artery. Because the portal vein has high flow with low pressure and the hepatic artery has low flow with high pressure, different types of perfusion machines have been employed to match the two vessels' infusion hemodynamics., Methods: We compared transplanted human livers perfused through a 2-pump (n = 9) versus a 1-pump perfusion system (n = 6) where a C-clamp is used as a tubing constrictor to regulate hemodynamics., Results: There was no significant difference between groups in portal vein or hepatic artery flow rate. The 1-pump group had more hemoglobin in the perfusate. However, there was no significant difference in plasma hemoglobin between the 2-pump and 1-pump groups at each time point or in the change in levels, proving no hemolysis occurred due to C-clamp tube constriction. After transplantation, the 2-pump group had two cases of early allograft dysfunction (EAD), whereas the 1-pump group had no EAD. There was no graft failure or patient death in either group during follow-up ranging from 20-52 months., Conclusions: Our data show that the 1-pump design provided the same hemodynamic output as the 2-pump design, with no additional hemolytic risk, but with the benefits of lower costs, easier transport and faster and simpler setting., (© 2021 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Published
2022
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29. Sequential Use of Normothermic Regional and Ex Situ Machine Perfusion in Donation After Circulatory Death Liver Transplant.

Author

Ghinolfi D, Dondossola D, Rreka E, Lonati C, Pezzati D, Cacciatoinsilla A, Kersik A, Lazzeri C, Zanella A, Peris A, Maggioni M, Biancofiore G, Reggiani P, Morganti R, De Simone P, and Rossi G

Subjects
Graft Survival, Humans, Italy, Organ Preservation, Perfusion, Retrospective Studies, Tissue Donors, Liver Transplantation adverse effects
Abstract

In Italy, 20 minutes of a continuous flat line on an electrocardiogram are required for declaration of death. In the setting of donation after circulatory death (DCD), prolonged warm ischemia time prompted the introduction of abdominal normothermic regional perfusion (NRP) followed by postprocurement ex situ machine perfusion (MP). This is a retrospective review of DCD liver transplantations (LTs) performed at 2 centers using sequential NRP and ex situ MP. From January 2018 to April 2019, 34 DCD donors were evaluated. Three (8.8%) were discarded before NRP, and 11 (32.4%) were discarded based on NRP parameters (n = 1, 3.0%), liver macroscopic appearance at procurement and/or biopsy results (n = 9, 26.5%), or severe macroangiopathy at back-table evaluation (n = 1, 3.0%). A total of 20 grafts (58.8%; 11 uncontrolled DCDs, 9 controlled DCDs) were considered eligible for LT, procured and perfused ex situ (9 normothermic and 11 dual hypothermic MPs). In total, 18 (52.9%; 11 uncontrolled) livers were eventually transplanted. Median (interquartile range) no-flow time was 32.5 (30-39) minutes, whereas median functional warm ischemia time was 52.5 (47-74) minutes (controlled DCD), and median low-flow time was 112 minutes (105-129 minutes; uncontrolled DCD). There was no primary nonfunction, while postreperfusion syndrome occurred in 8 (44%) recipients. Early allograft dysfunction happened in 5 (28%) patients, while acute kidney injury occurred in 5 (28%). After a median follow-up of 15.1 (9.5-22.3) months, 1 case of ischemic-type biliary lesions and 1 patient death were reported. DCD LT is feasible even with the 20-minute no-touch rule. Strict NRP and ex situ MP selection criteria are needed to optimize postoperative results., (Copyright © 2020 by the American Association for the Study of Liver Diseases.)

Published
2021
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30. Comorbidities and Age in Brain-Dead Donors and Liver Transplantation: A 15-Year Retrospective Investigation.

Author

Lazzeri C, Bonizzoli M, Ghinolfi D, De Simone P, Pezzati D, Rreka E, Bombardi M, Migliaccio ML, and Peris A

Subjects
Age Factors, Brain Injuries diagnosis, Comorbidity, Coronary Artery Disease epidemiology, Diabetes Mellitus diagnosis, Female, Humans, Hypertension epidemiology, Incidence, Italy epidemiology, Male, Middle Aged, Retrospective Studies, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, Brain Death, Brain Injuries mortality, Diabetes Mellitus epidemiology, Donor Selection, Liver Transplantation adverse effects, Tissue Donors
Abstract

Objectives: Although livers from older donors (> 70 y) have been shown to be increasingly more efficiently used for transplant, donor comorbidities are considered additional risk factors. This is quite intriguing as comorbidities are known to increase with advancing age in the donor population., Materials and Methods: We assessed whether age and donor comorbidities influenced liver procurement over a 15-year period in a cohort of 1702 brain-dead donors in Tuscany, Italy., Results: Over the study period, age of potential donors significantly increased (P = .02) as well as the proportion of patients who were > 55 years old. The incidence of hypertension, diabetes mellitus, and previously known coronary artery disease also significantly increased. We observed a progressive increase in the number of transplanted livers from donors with advancing age despite an increase in comorbidities. The highest incidences of traumatic brain injury and anoxic brain injury were observed in the youngest donors. Transaminase levels and use of vasoactive drugs were lower in donors who were ≥ 72 years old., Conclusions: According to our results, criteria for liver donors have already changed. Although age does not seem to be a limiting factor, older donors deserve a more accurate donor selection due to the higher incidence of risk factors (primarily diabetes mellitus).

Published
2020
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31. Ex Situ Liver Machine Perfusion: The Impact of Fresh Frozen Plasma.

Author

Liu Q, Hassan A, Pezzati D, Soliman B, Lomaglio L, Grady P, Del Angel Diaz L, Simioni A, Maikhor S, Etterling J, D'Amico G, Iuppa G, Diago Uso T, Hashimoto K, Aucejo F, Fujiki M, Eghtesad B, Sasaki K, Kwon CHD, Cywinski J, Irefin S, Bennett A, Baldwin W, Miller C, and Quintini C

Subjects
Humans, Liver, Perfusion, Plasma, Liver Transplantation adverse effects, Organ Preservation
Abstract

The primary aim of this single-center, phase 1 exploratory study was to investigate the safety, feasibility, and impact on intrahepatic hemodynamics of a fresh frozen plasma (FFP)-based perfusate in ex situ liver normothermic machine perfusion (NMP) preservation. Using an institutionally developed perfusion device, 21 livers (13 donations after brain death and 8 donations after circulatory death) were perfused for 3 hours 21 minutes to 7 hours 52 minutes and successfully transplanted. Outcomes were compared in a 1:4 ratio to historical control patients matched according to donor and recipient characteristics and preservation time. Perfused livers presented a very low resistance state with high flow during ex situ perfusion (arterial and portal flows 340 ± 150 and 890 ± 70 mL/minute/kg liver, respectively). This hemodynamic state was maintained even after reperfusion as demonstrated by higher arterial flow observed in the NMP group compared with control patients (220 ± 120 versus 160 ± 80 mL/minute/kg liver, P = 0.03). The early allograft dysfunction (EAD) rate, peak alanine aminotransferase (ALT), and peak aspartate aminotransferase (AST) levels within 7 days after transplantation were lower in the NMP group compared with the control patients (EAD 19% versus 46%, P = 0.02; peak ALT 363 ± 318 versus 1021 ± 999 U/L, P = 0.001; peak AST 1357 ± 1492 versus 2615 ± 2541 U/L, P = 0.001 of the NMP and control groups, respectively). No patient developed ischemic type biliary stricture. One patient died, and all other patients are alive and well at a follow-up of 12-35 months. No device-related adverse events were recorded. In conclusion, with this study, we showed that ex situ NMP of human livers can be performed safely and effectively using a noncommercial device and an FFP-based preservation solution. Future studies should further investigate the impact of an FFP-based perfusion solution on liver hemodynamics during ex situ normothermic machine preservation., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

Published
2020
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33. Nonagenarian Grafts for Liver Transplantation.

Author

Ghinolfi D, Pezzati D, Rreka E, Balzano E, Catalano G, Coletti L, Tincani G, Carrai P, Petruccelli S, Martinelli C, Aglietti R, Bindi ML, Morganti R, Biancofiore G, and De Simone P

Subjects
Adult, Age Factors, Aged, 80 and over, Allografts statistics & numerical data, Allografts supply & distribution, Confounding Factors, Epidemiologic, Donor Selection standards, End Stage Liver Disease diagnosis, End Stage Liver Disease etiology, Female, Follow-Up Studies, Graft Rejection etiology, Graft Survival, Humans, Liver Transplantation adverse effects, Liver Transplantation standards, Male, Middle Aged, Propensity Score, Prospective Studies, Resource Allocation standards, Resource Allocation statistics & numerical data, Retrospective Studies, Severity of Illness Index, Donor Selection statistics & numerical data, End Stage Liver Disease surgery, Graft Rejection epidemiology, Liver Transplantation statistics & numerical data, Tissue Donors statistics & numerical data
Published
2019
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34. Pilot, Open, Randomized, Prospective Trial for Normothermic Machine Perfusion Evaluation in Liver Transplantation From Older Donors.

Author

Ghinolfi D, Rreka E, De Tata V, Franzini M, Pezzati D, Fierabracci V, Masini M, Cacciatoinsilla A, Bindi ML, Marselli L, Mazzotti V, Morganti R, Marchetti P, Biancofiore G, Campani D, Paolicchi A, and De Simone P

Subjects
Adult, Age Factors, Aged, Aged, 80 and over, Allografts blood supply, Allografts pathology, Allografts ultrastructure, Biopsy, Cold Ischemia adverse effects, Delayed Graft Function epidemiology, Delayed Graft Function etiology, Delayed Graft Function prevention & control, Donor Selection, End Stage Liver Disease mortality, Female, Graft Survival, Humans, Liver blood supply, Liver pathology, Liver ultrastructure, Liver Transplantation adverse effects, Male, Microscopy, Electron, Middle Aged, Organ Preservation instrumentation, Perfusion instrumentation, Pilot Projects, Prospective Studies, Reperfusion Injury etiology, Reperfusion Injury pathology, Survival Analysis, Treatment Outcome, End Stage Liver Disease surgery, Liver Transplantation methods, Organ Preservation methods, Perfusion methods, Reperfusion Injury prevention & control
Abstract

Ex situ normothermic machine perfusion (NMP) might minimize ischemia/reperfusion injury (IRI) of liver grafts. In this study, 20 primary liver transplantation recipients of older grafts (≥70 years) were randomized 1:1 to NMP or cold storage (CS) groups. The primary study endpoint was to evaluate graft and patient survival at 6 months posttransplantation. The secondary endpoint was to evaluate liver and bile duct biopsies; IRI by means of peak transaminases within 7 days after surgery; and incidence of biliary complications at month 6. Liver and bile duct biopsies were collected at bench surgery, end of ex situ NMP, and end of transplant surgery. Interleukin (IL) 6, IL10, and tumor necrosis factor α (TNF-α) perfusate concentrations were tested during NMP. All grafts were successfully transplanted. Median (interquartile range) posttransplant aspartate aminotransferase peak was 709 (371-1575) IU/L for NMP and 574 (377-1162) IU/L for CS (P = 0.597). There was 1 hepatic artery thrombosis in the NMP group and 1 death in the CS group. In NMP, we observed high TNF-α perfusate levels, and these were inversely correlated with lactate (P < 0.001). Electron microscopy showed decreased mitochondrial volume density and steatosis and an increased volume density of autophagic vacuoles at the end of transplantation in NMP versus CS patients (P < 0.001). Use of NMP with older liver grafts is associated with histological evidence of reduced IRI, although the clinical benefit remains to be demonstrated., (Copyright © 2018 by the American Association for the Study of Liver Diseases.)

Published
2019
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35. Successful Transplant of a Nonagenarian Liver Graft With Fully Replaced Right Hepatic Artery Reconstruction.

Author

Ghinolfi D, Gianardi D, Cirillo G, De Simone P, Pezzati D, Arenga G, Battaglia V, and Filipponi F

Subjects
Age Factors, Aged, 80 and over, Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular virology, Computed Tomography Angiography, Female, Hepatic Artery diagnostic imaging, Hepatitis B complications, Humans, Liver Neoplasms pathology, Liver Neoplasms virology, Middle Aged, Neoplasm Staging, Treatment Outcome, Ultrasonography, Doppler, Carcinoma, Hepatocellular surgery, Donor Selection, Hepatic Artery surgery, Liver Neoplasms surgery, Liver Transplantation methods, Plastic Surgery Procedures methods, Tissue Donors, Vascular Surgical Procedures methods
Abstract

Organ shortage and increasing donor age in liver transplant are stimulating transplant centers to accept otherwise discarded grafts due to donor age or vascular abnormalities; nevertheless, the use of nonagenarian donor grafts is uncommon because advanced age is associated with a higher risk of ischemic-type biliary lesions and worse long-term graft survival. We herein report the case of a 90-year-old donor with fully replaced right hepatic artery. After back-table vascular assessment, the donor right hepatic artery was anastomosed end-to-end with the gastroduodenal artery with 2 polypropylene 8/0 running sutures. Even if the back-table reconstruction of a replaced right hepatic artery is not associated with an enhanced risk of posttransplant vascular complications, vascular abnormalities might discourage the use of otherwise acceptable elderly grafts. The present case underscores that elderly liver grafts should not be discarded per se even in the presence of vascular variants.

Published
2019
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37. Use of Elderly Donors in Liver Transplantation: A Paired-match Analysis at a Single Center.

Author

Ghinolfi D, Lai Q, Pezzati D, De Simone P, Rreka E, and Filipponi F

Subjects
Adolescent, Adult, Age Factors, Aged, Female, Follow-Up Studies, Graft Survival, Humans, Male, Matched-Pair Analysis, Middle Aged, Postoperative Complications epidemiology, Postoperative Complications etiology, Propensity Score, Retrospective Studies, Risk Factors, Tissue Donors, Treatment Outcome, Young Adult, End Stage Liver Disease surgery, Liver Transplantation methods
Abstract

Objective: To evaluate the use of elderly donors in liver transplantation (LT) and identify risk factors associated with a worse outcome., Summary Background Data: Use of livers from very old donors could expand the donor pool but is not universally implemented., Methods: This is a retrospective, single-center medical record review. From January 2001 to December 2014, 1354 LTs were performed. After exclusion of donors <18 years, ABO-incompatible LT, re-LT and UNOS 1 status patients, LT recipients were stratified into 2 groups based on donor age: 18-69 (n=692) vs. ≥70 years (n=515) then matched using a propensity score approach. Two groups were finally matched (young group = 448 cases; old group = 515 cases)., Results: The median (interquartile range [IQR]) follow-up was 5.0 (2.0-8.4) years. Comparing the 2 identified groups, no differences were observed regarding early retransplants (1.8 vs. 2.9; P = 0.3), HCV-related death (7.6 vs. 8.7%; P = 0.6), vascular (5.8 vs. 5.0%; P = 0.7), and biliary complications (16.5 vs. 18.6%; P = 0.4). On multivariate analysis, independent risk factors for graft loss were: HCV-positive recipient (HR = 2.1; 95% CI = 1.6-2.7; P < 0.001), donor age (HR = 1.0; 95% CI = 1.0-1.0; P < 0.001), cold ischemia time (HR = 1.0; 95% CI = 1.0-1.0; P = 0.042), and donor history of diabetes mellitus (HR = 1.48; 95% CI = 1.03-2.13; P = 0.036)., Conclusions: Use of elderly donors is not associated per se with an increased risk of vascular and biliary complications. In the presence of cold ischemia time and diabetes mellitus, appropriate donor-to-recipient matching is warranted.

Published
2018
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38. Reply.

Author

Liu Q, Buccini L, Pezzati D, Hassan A, Diago Uso T, Miller C, and Quintini C

Published
2018
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39. Ex situ 86-hour liver perfusion: Pushing the boundary of organ preservation.

Author

Liu Q, Nassar A, Buccini L, Grady P, Soliman B, Hassan A, Pezzati D, Iuppa G, Diago Uso T, Miller C, and Quintini C

Subjects
Alanine Transaminase analysis, Aspartate Aminotransferases analysis, Biopsy, Humans, Middle Aged, Organ Preservation instrumentation, Perfusion instrumentation, Temperature, Time Factors, Liver, Liver Transplantation, Organ Preservation methods, Organ Preservation Solutions analysis, Perfusion methods
Published
2018
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40. Lipid metabolism and functional assessment of discarded human livers with steatosis undergoing 24 hours of normothermic machine perfusion.

Author

Liu Q, Nassar A, Buccini L, Iuppa G, Soliman B, Pezzati D, Hassan A, Blum M, Baldwin W, Bennett A, Chavin K, Okamoto T, Uso TD, Fung J, Abu-Elmagd K, Miller C, and Quintini C

Subjects
Adult, Aged, Bile metabolism, Biomarkers metabolism, Cholesterol metabolism, Donor Selection, Female, Hemodynamics, Humans, Lactic Acid metabolism, Liver pathology, Liver Circulation, Liver Transplantation adverse effects, Male, Middle Aged, Non-alcoholic Fatty Liver Disease pathology, Non-alcoholic Fatty Liver Disease physiopathology, Perfusion adverse effects, Time Factors, Triglycerides metabolism, Lipid Metabolism, Liver metabolism, Liver Transplantation methods, Non-alcoholic Fatty Liver Disease metabolism, Perfusion methods, Tissue Donors
Abstract

Normothermic machine perfusion (NMP) is an emerging technology to preserve liver allografts more effectively than cold storage (CS). However, little is known about the effect of NMP on steatosis and the markers indicative of hepatic quality during NMP. To address these points, we perfused 10 discarded human livers with oxygenated NMP for 24 hours after 4-6 hours of CS. All livers had a variable degree of steatosis at baseline. The perfusate consisted of packed red blood cells and fresh frozen plasma. Perfusate analysis showed an increase in triglyceride levels from the 1st hour (median, 127 mg/dL; interquartile range [IQR], 95-149 mg/dL) to 24th hour of perfusion (median, 203 mg/dL; IQR, 171-304 mg/dL; P = 0.004), but tissue steatosis did not decrease. Five livers produced a significant amount of bile (≥5 mL/hour) consistently throughout 24 hours of NMP. Lactate in the perfusate cleared to <3 mmol/L in most livers within 4-8 hours of NMP, which was independent of bile production rate. This is the first study to characterize the lipid profile and functional assessment of discarded human livers at 24 hours of NMP. Liver Transplantation 24 233-245 2018 AASLD., (© 2017 by the American Association for the Study of Liver Diseases.)

Published
2018
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41. Perfusion machines and hepatocellular carcinoma: a good match between a marginal organ and an advanced disease?

Author

Ghinolfi D, Rreka E, Pezzati D, Filipponi F, and De Simone P

Abstract

Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers, is the second leading cause of cancer-related deaths and the leading cause of death in patients with cirrhosis. Liver transplantation (LT) represents the ideal treatment for selected patients as it removes both the tumor and the underlying cirrhotic liver with 5-year survival rates higher than 70%. Unfortunately, due to tumor characteristics, patient co-morbidities or shortage of organs available for transplant, only 20% of patients can undergo curative treatment. Ex situ machine perfusion (MP) is a technology recently introduced that might potentially improve organ preservation, allow graft assessment and increase the pool of available organs. The purpose of this review is to provide an update on the current role of ex situ liver MP in liver transplantation for HCC patients., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Published
2017
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43. Use of donors with genitourinary malignancies for liver transplantation: a calculated risk?

Author

Pezzati D, Ghinolfi D, Lai Q, Cirillo G, Rreka E, Roffi N, Carrai P, Ringressi A, Simone P, and Filipponi F

Subjects
Carcinoma, Renal Cell diagnosis, Female, Humans, Incidental Findings, Kidney Neoplasms diagnosis, Liver Transplantation adverse effects, Male, Prostatic Neoplasms diagnosis, Risk Factors, Tissue and Organ Procurement, Liver Transplantation methods, Tissue Donors, Urogenital Neoplasms diagnosis
Published
2017
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46. Reply.

Author

Ghinolfi D, De Simone P, Pezzati D, Cirillo G, and Filipponi F

Published
2016
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48. Risk analysis of ischemic-type biliary lesions after liver transplant using octogenarian donors.

Author

Ghinolfi D, De Simone P, Lai Q, Pezzati D, Coletti L, Balzano E, Arenga G, Carrai P, Grande G, Pollina L, Campani D, Biancofiore G, and Filipponi F

Subjects
Aged, 80 and over, Algorithms, Biliary Tract pathology, End Stage Liver Disease surgery, Female, Graft Survival, Hemodynamics, Humans, Male, Proportional Hazards Models, ROC Curve, Retrospective Studies, Severity of Illness Index, Time Factors, Treatment Outcome, Biliary Tract injuries, Liver Transplantation adverse effects, Risk Assessment methods, Tissue Donors
Abstract

The use of octogenarian donors to increase the donor pool in liver transplantation (LT) is controversial because advanced donor age is associated with a higher risk of ischemic-type biliary lesions (ITBL). The aim of this study was to investigate retrospectively the role of a number of different pre-LT risk factors for ITBL in a selected population of recipients of octogenarian donor grafts. Between January 2003 and December 2013, 123 patients underwent transplantation at our institution with deceased donor grafts from donors of age ≥80 years. Patients were divided into 2 groups based on the presence of ITBL in the posttransplant course. Exclusion criteria were retransplantations, presence of vascular complications, and no availability of procurement liver biopsy. A total of 88 primary LTs were included, 73 (83.0%) with no posttransplant ITBLs and 15 (17.0%) with ITBLs. The median follow-up after LT was 2.1 years (range, 0.7-5.4 years). At multivariate analysis, donor hemodynamic instability (hazard ratio [HR], 7.6; P = 0.005), donor diabetes mellitus (HR, 9.5; P = 0.009), and donor age-Model for End-Stage Liver Disease (HR, 1.0; P = 0.04) were risk factors for ITBL. Transplantation of liver grafts from donors of age ≥80 years is associated with a higher risk for ITBL. However, favorable results can be achieved with accurate donor selection. Donor hemodynamic instability, a donor history of diabetes mellitus, and allocation to higher Model for End-Stage Liver Disease score recipient all increase the risk of ITBL and are associated with worse graft survival when octogenarian donors are used. Liver Transplantation 22 588-598 2016 AASLD., (© 2016 American Association for the Study of Liver Diseases.)

Published
2016
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49. Strategies to optimize the use of marginal donors in liver transplantation.

Author

Pezzati D, Ghinolfi D, De Simone P, Balzano E, and Filipponi F

Abstract

Liver transplantation is the treatment of choice for end stage liver disease, but availability of liver grafts is still the main limitation to its wider use. Extended criteria donors (ECD) are considered not ideal for several reasons but their use has dramatically grown in the last decades in order to augment the donor liver pool. Due to improvement in surgical and medical strategies, results using grafts from these donors have become acceptable in terms of survival and complications; nevertheless a big debate still exists regarding their selection, discharge criteria and allocation policies. Many studies analyzed the use of these grafts from many points of view producing different or contradictory results so that accepted guidelines do not exist and the use of these grafts is still related to non-standardized policies changing from center to center. The aim of this review is to analyze every step of the donation-transplantation process emphasizing all those strategies, both clinical and experimental, that can optimize results using ECD.

Published
2015
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