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2. Perspectives from Italy during the COVID-19 pandemic: nationwide survey-based focus on minimally invasive HPB surgery

Author

Aldrighetti, L, Boggi, U, Falconi, M, Giuliante, F, Cipriani, F, Ratti, F, Torzilli, G, Abu Hilal, M, Andrianello, S, Anselmo, A, Ardito, F, Gian, L, Banchini, F, Barabino, M, Barberis, A, Bassi, C, Batignani, G, Battiston, C, Belli, A, Berti, S, Bianco, P, Brolese, A, Brozzetti, S, Butturini, G, Calise, F, Carabott, K, Capretti, G, Casadei, R, Cescon, M, Cesaretti, M, Cillo, U, Cinardi, N, Colledan, M, Coppola, A, Cotsoglou, C, Crippa, S, Bona, E, Valle, R, De Angelis, M, De Carlis, L, Di Benedetto, F, Di Sebastiano, P, Dova, L, Ercolani, G, Esposito, A, Giuseppe, M, Fabris, A, Ferrero, A, Frena, A, Frigerio, I, Gianotti, L, Giuliani, A, Grazi, G, Gringeri, E, Griseri, G, Gruttadauria, S, Guglielmi, A, Izzo, F, Jovine, E, Lanza, E, Malleo, G, Manzini, L, Massani, M, Mazzaferro, V, Memeo, R, Minni, F, Morelli, L, Nappo, G, Nardo, B, Orlando, F, Partelli, S, Patriti, A, Patrone, R, Percivale, A, Piccolo, G, Ravaioli, M, Reggiani, P, Risaliti, M, Rocca, A, Romagnoli, R, Romano, F, Russolillo, N, Ruzzenente, A, Saladino, E, Salvia, R, Santambrogio, R, Tarchi, P, Troci, A, Troisi, R, Urbani, L, Veneroni, L, Vennarecci, G, Vigano, L, Viola, M, Vistoli, F, Vivarelli, M, Zanello, M, Zanus, G, Zerbi, A, Aldrighetti L., Boggi U., Falconi M., Giuliante F., Cipriani F., Ratti F., Torzilli G., Abu Hilal M., Andrianello S., Anselmo A., Ardito F., Gian L. B., Banchini F., Barabino M., Barberis A., Bassi C., Batignani G., Battiston C., Belli A., Berti S., Bianco P., Brolese A., Brozzetti S., Butturini G., Calise F., Carabott K., Capretti G., Casadei R., Cescon M., Cesaretti M., Cillo U., Cinardi N., Colledan M., Coppola A., Cotsoglou C., Crippa S., Bona E. D., Valle R. D., De Angelis M., De Carlis L., Di Benedetto F., Di Sebastiano P., Dova L., Ercolani G., Esposito A., Giuseppe M. E., Fabris A., Ferrero A., Frena A., Frigerio I., Gianotti L., Giuliani A., Grazi G., Gringeri E., Griseri G., Gruttadauria S., Guglielmi A., Izzo F., Jovine E., Lanza E., Malleo G., Manzini L., Massani M., Mazzaferro V., Memeo R., Minni F., Morelli L., Nappo G., Nardo B., Orlando F., Partelli S., Patriti A., Patrone R., Percivale A., Piccolo G., Ravaioli M., Reggiani P., Risaliti M., Rocca A., Romagnoli R., Romano F., Russolillo N., Ruzzenente A., Saladino E., Salvia R., Santambrogio R., Tarchi P., Troci A., Troisi R., Urbani L., Veneroni L., Vennarecci G., Vigano L., Viola M., Vistoli F., Vivarelli M., Zanello M., Zanus G., Zerbi A., Aldrighetti, L, Boggi, U, Falconi, M, Giuliante, F, Cipriani, F, Ratti, F, Torzilli, G, Abu Hilal, M, Andrianello, S, Anselmo, A, Ardito, F, Gian, L, Banchini, F, Barabino, M, Barberis, A, Bassi, C, Batignani, G, Battiston, C, Belli, A, Berti, S, Bianco, P, Brolese, A, Brozzetti, S, Butturini, G, Calise, F, Carabott, K, Capretti, G, Casadei, R, Cescon, M, Cesaretti, M, Cillo, U, Cinardi, N, Colledan, M, Coppola, A, Cotsoglou, C, Crippa, S, Bona, E, Valle, R, De Angelis, M, De Carlis, L, Di Benedetto, F, Di Sebastiano, P, Dova, L, Ercolani, G, Esposito, A, Giuseppe, M, Fabris, A, Ferrero, A, Frena, A, Frigerio, I, Gianotti, L, Giuliani, A, Grazi, G, Gringeri, E, Griseri, G, Gruttadauria, S, Guglielmi, A, Izzo, F, Jovine, E, Lanza, E, Malleo, G, Manzini, L, Massani, M, Mazzaferro, V, Memeo, R, Minni, F, Morelli, L, Nappo, G, Nardo, B, Orlando, F, Partelli, S, Patriti, A, Patrone, R, Percivale, A, Piccolo, G, Ravaioli, M, Reggiani, P, Risaliti, M, Rocca, A, Romagnoli, R, Romano, F, Russolillo, N, Ruzzenente, A, Saladino, E, Salvia, R, Santambrogio, R, Tarchi, P, Troci, A, Troisi, R, Urbani, L, Veneroni, L, Vennarecci, G, Vigano, L, Viola, M, Vistoli, F, Vivarelli, M, Zanello, M, Zanus, G, Zerbi, A, Aldrighetti L., Boggi U., Falconi M., Giuliante F., Cipriani F., Ratti F., Torzilli G., Abu Hilal M., Andrianello S., Anselmo A., Ardito F., Gian L. B., Banchini F., Barabino M., Barberis A., Bassi C., Batignani G., Battiston C., Belli A., Berti S., Bianco P., Brolese A., Brozzetti S., Butturini G., Calise F., Carabott K., Capretti G., Casadei R., Cescon M., Cesaretti M., Cillo U., Cinardi N., Colledan M., Coppola A., Cotsoglou C., Crippa S., Bona E. D., Valle R. D., De Angelis M., De Carlis L., Di Benedetto F., Di Sebastiano P., Dova L., Ercolani G., Esposito A., Giuseppe M. E., Fabris A., Ferrero A., Frena A., Frigerio I., Gianotti L., Giuliani A., Grazi G., Gringeri E., Griseri G., Gruttadauria S., Guglielmi A., Izzo F., Jovine E., Lanza E., Malleo G., Manzini L., Massani M., Mazzaferro V., Memeo R., Minni F., Morelli L., Nappo G., Nardo B., Orlando F., Partelli S., Patriti A., Patrone R., Percivale A., Piccolo G., Ravaioli M., Reggiani P., Risaliti M., Rocca A., Romagnoli R., Romano F., Russolillo N., Ruzzenente A., Saladino E., Salvia R., Santambrogio R., Tarchi P., Troci A., Troisi R., Urbani L., Veneroni L., Vennarecci G., Vigano L., Viola M., Vistoli F., Vivarelli M., Zanello M., Zanus G., and Zerbi A.

Abstract

The safety of minimally invasive procedures during COVID pandemic remains hotly debated, especially in a country, like Italy, where minimally invasive techniques have progressively and pervasively entered clinical practice, in both the hepatobiliary and pancreatic community. A nationwide snapshot of the management of HPB minimally invasive surgery activity during COVID-19 pandemic is provided: a survey was developed and conducted within AICEP (Italian Association of HepatoBilioPancreatic Surgeons) with the final aim of conveying the experience, knowledge, and opinions into a unitary report enabling more efficient crisis management. Results from the survey (81 respondents) show that, in Italian hospitals, minimally invasive surgery maintains its role despite the COVID-19 pandemic, with the registered reduction of cases being proportional to the overall reduction of the HPB surgical activity. Respondents agree that the switch from minimally invasive to open technique can be considered as a valid option for cases with a high technical complexity. Several issues merit specific attention: screening for virus positivity should be universally performed; only expert surgical teams should operate on positive patients and specific technical measures to lower the biological risk of contamination during surgery must be followed. Future studies specifically designed to establish the true risks in minimally invasive surgery are suggested. Furthermore, a standard and univocal process of prioritization of patients from Regional Healthcare Systems is advisable.

Published
2020

3. Economic Consequences of Investing in Anti-HCV Antiviral Treatment from the Italian NHS Perspective: A Real-World-Based Analysis of PITER Data

Author

Marcellusi, A, Viti, R, Kondili, L, Rosato, S, Vella, S, Mennini, F, Quaranta, M, Tosti, M, Weimer, L, Ferrigno, L, D'Angelo, F, Falzano, L, Benedetti, A, Schiada, L, Cucco, M, Giacometti, A, Brescini, L, Castelletti, S, Drenaggi, D, Mazzaro, C, Angarano, G, Milella, M, Dileo, A, Rendina, M, Contaldo, A, Iannone, A, La Fortezza, F, Rizzi, M, Cologni, G, Bolondi, L, Benevento, F, Serio, I, Andreone, P, Caraceni, P, Guarneri, V, Margotti, M, Simonetti, G, Mazzella, G, Verucchi, G, Donati, V, Mian, P, Rimenti, G, Rossini, A, Contessi, G, Castelli, F, Zaltron, S, Spinetti, A, Odolini, S, Leandro, G, Cozzolongo, R, Zappimbulso, M, Russello, M, Benigno, R, Coco, C, Torti, C, Costa, C, Greco, G, Mazzitelli, M, Pisani, V, Cosco, L, Quintieri, F, Desiena, M, Giancotti, F, Vecchiet, J, Falasca, K, Mastroianni, A, Apuzzo, G, Chidichimo, L, Foschi, F, Dall'Aglio, A, Libanore, M, Segala, D, Sighinolfi, L, Bartolozzi, D, Salomoni, E, Blanc, P, Baragli, F, Delpin, B, Mariabelli, E, Mazzotta, F, Poggi, A, Zignego, A, Monti, M, Madia, F, Xheka, A, Cela, E, Santantonio, T, Bruno, S, Viscoli, C, Alessandrini, A, Curti, C, Dibiagio, A, Nicolini, L, Balletto, E, Mastroianni, C, Blerta, K, Prati, D, Raffaele, L, Andreoletti, M, Perboni, G, Costa, P, Manzini, L, Raimondo, G, Filomia, R, Lazzarin, A, Morsica, G, Salpietro, S, Puoti, M, Baiguera, C, Vassalli, S, Rumi, M, Labanca, S, Zuin, M, Giorgini, A, Orellana, D, D'Arminiomonforte, A, Debona, A, Solaro, S, Fargion, S, Valenti, L, Periti, G, Pelusi, S, Galli, M, Calvi, E, Milazzo, L, Peri, A, Lampertico, P, Borghi, M, D'Ambrosio, R, Degasperi, E, Vinci, M, Villa, E, Bernabucci, V, Bristot, L, Pereira, F, Chessa, L, Pasetto, M, Loi, M, Gori, A, Beretta, I, Pastore, V, Soria, A, Strazzabosco, M, Ciaccio, A, Gemma, M, Borgia, G, Foggia, A, Zappulo, E, Gentile, I, Buonomo, A, Abrescia, N, Maddaloni, A, Caporaso, N, Morisco, F, Camera, S, Donnarumma, L, Coppola, C, Amoruso, D, Staiano, L, Saturnino, M, Coppola, N, Martini, S, Monari, C, Federico, A, Dallio, M, Loguercio, C, Gaeta, G, Brancaccio, G, Nardone, G, Sgamato, C, D'Adamo, G, Alberti, A, Gonzo, M, Piovesan, S, Chemello, L, Buggio, A, Cavalletto, L, Barbaro, F, Castelli, E, Floreani, A, Cazzagon, N, Franceschet, I, Russo, F, Zanetto, A, Franceschet, E, Madonia, S, Cannizzaro, M, Montalto, G, Licata, A, Capitano, A, Craxi, A, Petta, S, Calvaruso, V, Rini, F, Ferrari, C, Negri, E, Orlandini, A, Pesci, M, Bruno, R, Lombardi, A, Zuccaro, V, Gulminetti, R, Asti, A, Villaraggia, M, Mondelli, M, Ludovisi, S, Baldelli, F, Di Candilo, F, Parruti, G, Di Stefano, P, Sozio, F, Gizzi, M, Brunetto, M, Colombatto, P, Coco, B, Surace, L, Foti, G, Pellicano, S, Fornaciari, G, Schianchi, S, Vignoli, P, Massari, M, Corsini, R, Garlassi, E, Ballardini, G, Andreoni, M, Cerva, C, Angelico, M, Gasbarrini, A, Siciliano, M, De Siena, M, Nosotti, L, Taliani, G, Biliotti, E, Santori, M, Spaziante, M, Tamburini, F, Vullo, V, D'Ettorre, G, Cavallari, E, Gebremeskel, T, Pavone, P, Cauda, R, Cingolani, A, Lamonica, S, D'Offizi, G, Lionetti, R, Visco Comandini, U, Grieco, A, D'Aversa, F, Picardi, A, De Vincentis, A, Galati, G, Gallo, P, Dell'Unto, C, Aghemo, A, Gatti Comini, A, Persico, M, Masarone, M, Anselmo, M, De Leo, P, Marturano, M, Brunelli, E, Ridolfi, F, Schimizzi, A, Ayoubi Khajekini, M, Framarin, L, Di Perri, G, Cariti, G, Boglione, L, Cardellino, C, Marinaro, L, Saracco, G, Ciancio, A, Toniutto, P, Alterini, G, Capra, F, Ieluzzi, D, Marcellusi A., Viti R., Kondili L. A., Rosato S., Vella S., Mennini F. S., Quaranta M. G., Tosti M. E., Weimer L. E., Ferrigno L., D'Angelo F., Falzano L., Benedetti A., Schiada L., Cucco M., Giacometti A., Brescini L., Castelletti S., Drenaggi D., Mazzaro C., Angarano G., Milella M., DiLeo A., Rendina M., Contaldo A., Iannone A., La Fortezza F., Rizzi M., Cologni G., Bolondi L., Benevento F., Serio I., Andreone P., Caraceni P., Guarneri V., Margotti M., Simonetti G., Mazzella G., Verucchi G., Donati V., Mian P., Rimenti G., Rossini A., Contessi G. B., Castelli F., Zaltron S., Spinetti A., Odolini S., Leandro G., Cozzolongo R., Zappimbulso M., Russello M., Benigno R., Coco C., Torti C., Costa C., Greco G., Mazzitelli M., Pisani V., Cosco L., Quintieri F., DeSiena M., Giancotti F., Vecchiet J., Falasca K., Mastroianni A., Apuzzo G., Chidichimo L., Foschi F. G., Dall'Aglio A. C., Libanore M., Segala D., Sighinolfi L., Bartolozzi D., Salomoni E., Blanc P., Baragli F., DelPin B., Mariabelli E., Mazzotta F., Poggi A., Zignego A. L., Monti M., Madia F., Xheka A., Cela E. M., Santantonio T. A., Bruno S. R., Viscoli C., Alessandrini A. I., Curti C., DiBiagio A., Nicolini L. A., Balletto E., Mastroianni C., Blerta K., Prati D., Raffaele L., Andreoletti M., Perboni G., Costa P., Manzini L., Raimondo G., Filomia R., Lazzarin A., Morsica G., Salpietro S., Puoti M., Baiguera C., Vassalli S., Rumi M. G., Labanca S., Zuin M., Giorgini A., Orellana D., D'ArminioMonforte A., Debona A., Solaro S., Fargion S., Valenti L., Periti G., Pelusi S., Galli M., Calvi E., Milazzo L., Peri A., Lampertico P., Borghi M., D'Ambrosio R., Degasperi E., Vinci M., Villa E., Bernabucci V., Bristot L., Pereira F., Chessa L., Pasetto M. C., Loi M., Gori A., Beretta I., Pastore V., Soria A., Strazzabosco M., Ciaccio A., Gemma M., Borgia G., Foggia A., Zappulo E., Gentile I., Buonomo A. R., Abrescia N., Maddaloni A., Caporaso N., Morisco F., Camera S., Donnarumma L., Coppola C., Amoruso D. C., Staiano L., Saturnino M. R., Coppola N., Martini S., Monari C., Federico A., Dallio M., Loguercio C., Gaeta G. B., Brancaccio G., Nardone G., Sgamato C., D'Adamo G., Alberti A., Gonzo M., Piovesan S., Chemello L., Buggio A., Cavalletto L., Barbaro F., Castelli E., Floreani A., Cazzagon N., Franceschet I., Russo F. P., Zanetto A., Franceschet E., Madonia S., Cannizzaro M., Montalto G., Licata A., Capitano A. R., Craxi A., Petta S., Calvaruso V., Rini F., Ferrari C., Negri E., Orlandini A., Pesci M., Bruno R., Lombardi A., Zuccaro V., Gulminetti R., Asti A., Villaraggia M., Mondelli M., Ludovisi S., Baldelli F., Di Candilo F., Parruti G., Di Stefano P., Sozio F., Gizzi M. C., Brunetto M. R., Colombatto P., Coco B., Surace L., Foti G., Pellicano S., Fornaciari G., Schianchi S., Vignoli P., Massari M., Corsini R., Garlassi E., Ballardini G., Andreoni M., Cerva C., Angelico M., Gasbarrini A., Siciliano M., De Siena M., Nosotti L., Taliani G., Biliotti E., Santori M., Spaziante M., Tamburini F., Vullo V., D'Ettorre G., Cavallari E. N., Gebremeskel T. S., Pavone P., Cauda R., Cingolani A., Lamonica S., D'Offizi G., Lionetti R., Visco Comandini U., Grieco A., D'Aversa F., Picardi A., De Vincentis A., Galati G., Gallo P., Dell'Unto C., Aghemo A., Gatti Comini A., Persico M., Masarone M., Anselmo M., De Leo P., Marturano M., Brunelli E., Ridolfi F., Schimizzi A. M., Ayoubi Khajekini M., Framarin L., Di Perri G., Cariti G., Boglione L., Cardellino C., Marinaro L., Saracco G. M., Ciancio A., Toniutto P., Alterini G., Capra F., Ieluzzi D., Marcellusi, A, Viti, R, Kondili, L, Rosato, S, Vella, S, Mennini, F, Quaranta, M, Tosti, M, Weimer, L, Ferrigno, L, D'Angelo, F, Falzano, L, Benedetti, A, Schiada, L, Cucco, M, Giacometti, A, Brescini, L, Castelletti, S, Drenaggi, D, Mazzaro, C, Angarano, G, Milella, M, Dileo, A, Rendina, M, Contaldo, A, Iannone, A, La Fortezza, F, Rizzi, M, Cologni, G, Bolondi, L, Benevento, F, Serio, I, Andreone, P, Caraceni, P, Guarneri, V, Margotti, M, Simonetti, G, Mazzella, G, Verucchi, G, Donati, V, Mian, P, Rimenti, G, Rossini, A, Contessi, G, Castelli, F, Zaltron, S, Spinetti, A, Odolini, S, Leandro, G, Cozzolongo, R, Zappimbulso, M, Russello, M, Benigno, R, Coco, C, Torti, C, Costa, C, Greco, G, Mazzitelli, M, Pisani, V, Cosco, L, Quintieri, F, Desiena, M, Giancotti, F, Vecchiet, J, Falasca, K, Mastroianni, A, Apuzzo, G, Chidichimo, L, Foschi, F, Dall'Aglio, A, Libanore, M, Segala, D, Sighinolfi, L, Bartolozzi, D, Salomoni, E, Blanc, P, Baragli, F, Delpin, B, Mariabelli, E, Mazzotta, F, Poggi, A, Zignego, A, Monti, M, Madia, F, Xheka, A, Cela, E, Santantonio, T, Bruno, S, Viscoli, C, Alessandrini, A, Curti, C, Dibiagio, A, Nicolini, L, Balletto, E, Mastroianni, C, Blerta, K, Prati, D, Raffaele, L, Andreoletti, M, Perboni, G, Costa, P, Manzini, L, Raimondo, G, Filomia, R, Lazzarin, A, Morsica, G, Salpietro, S, Puoti, M, Baiguera, C, Vassalli, S, Rumi, M, Labanca, S, Zuin, M, Giorgini, A, Orellana, D, D'Arminiomonforte, A, Debona, A, Solaro, S, Fargion, S, Valenti, L, Periti, G, Pelusi, S, Galli, M, Calvi, E, Milazzo, L, Peri, A, Lampertico, P, Borghi, M, D'Ambrosio, R, Degasperi, E, Vinci, M, Villa, E, Bernabucci, V, Bristot, L, Pereira, F, Chessa, L, Pasetto, M, Loi, M, Gori, A, Beretta, I, Pastore, V, Soria, A, Strazzabosco, M, Ciaccio, A, Gemma, M, Borgia, G, Foggia, A, Zappulo, E, Gentile, I, Buonomo, A, Abrescia, N, Maddaloni, A, Caporaso, N, Morisco, F, Camera, S, Donnarumma, L, Coppola, C, Amoruso, D, Staiano, L, Saturnino, M, Coppola, N, Martini, S, Monari, C, Federico, A, Dallio, M, Loguercio, C, Gaeta, G, Brancaccio, G, Nardone, G, Sgamato, C, D'Adamo, G, Alberti, A, Gonzo, M, Piovesan, S, Chemello, L, Buggio, A, Cavalletto, L, Barbaro, F, Castelli, E, Floreani, A, Cazzagon, N, Franceschet, I, Russo, F, Zanetto, A, Franceschet, E, Madonia, S, Cannizzaro, M, Montalto, G, Licata, A, Capitano, A, Craxi, A, Petta, S, Calvaruso, V, Rini, F, Ferrari, C, Negri, E, Orlandini, A, Pesci, M, Bruno, R, Lombardi, A, Zuccaro, V, Gulminetti, R, Asti, A, Villaraggia, M, Mondelli, M, Ludovisi, S, Baldelli, F, Di Candilo, F, Parruti, G, Di Stefano, P, Sozio, F, Gizzi, M, Brunetto, M, Colombatto, P, Coco, B, Surace, L, Foti, G, Pellicano, S, Fornaciari, G, Schianchi, S, Vignoli, P, Massari, M, Corsini, R, Garlassi, E, Ballardini, G, Andreoni, M, Cerva, C, Angelico, M, Gasbarrini, A, Siciliano, M, De Siena, M, Nosotti, L, Taliani, G, Biliotti, E, Santori, M, Spaziante, M, Tamburini, F, Vullo, V, D'Ettorre, G, Cavallari, E, Gebremeskel, T, Pavone, P, Cauda, R, Cingolani, A, Lamonica, S, D'Offizi, G, Lionetti, R, Visco Comandini, U, Grieco, A, D'Aversa, F, Picardi, A, De Vincentis, A, Galati, G, Gallo, P, Dell'Unto, C, Aghemo, A, Gatti Comini, A, Persico, M, Masarone, M, Anselmo, M, De Leo, P, Marturano, M, Brunelli, E, Ridolfi, F, Schimizzi, A, Ayoubi Khajekini, M, Framarin, L, Di Perri, G, Cariti, G, Boglione, L, Cardellino, C, Marinaro, L, Saracco, G, Ciancio, A, Toniutto, P, Alterini, G, Capra, F, Ieluzzi, D, Marcellusi A., Viti R., Kondili L. A., Rosato S., Vella S., Mennini F. S., Quaranta M. G., Tosti M. E., Weimer L. E., Ferrigno L., D'Angelo F., Falzano L., Benedetti A., Schiada L., Cucco M., Giacometti A., Brescini L., Castelletti S., Drenaggi D., Mazzaro C., Angarano G., Milella M., DiLeo A., Rendina M., Contaldo A., Iannone A., La Fortezza F., Rizzi M., Cologni G., Bolondi L., Benevento F., Serio I., Andreone P., Caraceni P., Guarneri V., Margotti M., Simonetti G., Mazzella G., Verucchi G., Donati V., Mian P., Rimenti G., Rossini A., Contessi G. B., Castelli F., Zaltron S., Spinetti A., Odolini S., Leandro G., Cozzolongo R., Zappimbulso M., Russello M., Benigno R., Coco C., Torti C., Costa C., Greco G., Mazzitelli M., Pisani V., Cosco L., Quintieri F., DeSiena M., Giancotti F., Vecchiet J., Falasca K., Mastroianni A., Apuzzo G., Chidichimo L., Foschi F. G., Dall'Aglio A. C., Libanore M., Segala D., Sighinolfi L., Bartolozzi D., Salomoni E., Blanc P., Baragli F., DelPin B., Mariabelli E., Mazzotta F., Poggi A., Zignego A. L., Monti M., Madia F., Xheka A., Cela E. M., Santantonio T. A., Bruno S. R., Viscoli C., Alessandrini A. I., Curti C., DiBiagio A., Nicolini L. A., Balletto E., Mastroianni C., Blerta K., Prati D., Raffaele L., Andreoletti M., Perboni G., Costa P., Manzini L., Raimondo G., Filomia R., Lazzarin A., Morsica G., Salpietro S., Puoti M., Baiguera C., Vassalli S., Rumi M. G., Labanca S., Zuin M., Giorgini A., Orellana D., D'ArminioMonforte A., Debona A., Solaro S., Fargion S., Valenti L., Periti G., Pelusi S., Galli M., Calvi E., Milazzo L., Peri A., Lampertico P., Borghi M., D'Ambrosio R., Degasperi E., Vinci M., Villa E., Bernabucci V., Bristot L., Pereira F., Chessa L., Pasetto M. C., Loi M., Gori A., Beretta I., Pastore V., Soria A., Strazzabosco M., Ciaccio A., Gemma M., Borgia G., Foggia A., Zappulo E., Gentile I., Buonomo A. R., Abrescia N., Maddaloni A., Caporaso N., Morisco F., Camera S., Donnarumma L., Coppola C., Amoruso D. C., Staiano L., Saturnino M. R., Coppola N., Martini S., Monari C., Federico A., Dallio M., Loguercio C., Gaeta G. B., Brancaccio G., Nardone G., Sgamato C., D'Adamo G., Alberti A., Gonzo M., Piovesan S., Chemello L., Buggio A., Cavalletto L., Barbaro F., Castelli E., Floreani A., Cazzagon N., Franceschet I., Russo F. P., Zanetto A., Franceschet E., Madonia S., Cannizzaro M., Montalto G., Licata A., Capitano A. R., Craxi A., Petta S., Calvaruso V., Rini F., Ferrari C., Negri E., Orlandini A., Pesci M., Bruno R., Lombardi A., Zuccaro V., Gulminetti R., Asti A., Villaraggia M., Mondelli M., Ludovisi S., Baldelli F., Di Candilo F., Parruti G., Di Stefano P., Sozio F., Gizzi M. C., Brunetto M. R., Colombatto P., Coco B., Surace L., Foti G., Pellicano S., Fornaciari G., Schianchi S., Vignoli P., Massari M., Corsini R., Garlassi E., Ballardini G., Andreoni M., Cerva C., Angelico M., Gasbarrini A., Siciliano M., De Siena M., Nosotti L., Taliani G., Biliotti E., Santori M., Spaziante M., Tamburini F., Vullo V., D'Ettorre G., Cavallari E. N., Gebremeskel T. S., Pavone P., Cauda R., Cingolani A., Lamonica S., D'Offizi G., Lionetti R., Visco Comandini U., Grieco A., D'Aversa F., Picardi A., De Vincentis A., Galati G., Gallo P., Dell'Unto C., Aghemo A., Gatti Comini A., Persico M., Masarone M., Anselmo M., De Leo P., Marturano M., Brunelli E., Ridolfi F., Schimizzi A. M., Ayoubi Khajekini M., Framarin L., Di Perri G., Cariti G., Boglione L., Cardellino C., Marinaro L., Saracco G. M., Ciancio A., Toniutto P., Alterini G., Capra F., and Ieluzzi D.

Abstract

Objective: We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy. Methods: A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered. Results: The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively. Conclusions: This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV.

Published
2019

4. Economic Consequences of Investing in Anti-HCV Antiviral Treatment from the Italian NHS Perspective: A Real-World-Based Analysis of PITER Data

Author

Marcellusi, Andrea, Viti, Raffaella, Kondili, Loreta A., Rosato, Stefano, Vella, Stefano, Mennini, Francesco Saverio, Kondili, L. A., Vella, S., Quaranta, M. G., Rosato, S., Tosti, M. E., Weimer, L. E., Ferrigno, L., D’Angelo, F., Falzano, L., Benedetti, A., Schiadà, L., Cucco, M., Giacometti, A., Brescini, L., Castelletti, S., Drenaggi, D., Mazzaro, C., Angarano, G., Milella, M., Di Leo, A., Rendina, M., Contaldo, A., Iannone, A., La Fortezza, F., Rizzi, M., Cologni, G., Bolondi, L., Benevento, F., Serio, I., Andreone, P., Caraceni, P., Guarneri, V., Margotti, M., Simonetti, G., Mazzella, G., Verucchi, G., Donati, V., Mian, Peter, Rimenti, G., Rossini, A., Contessi, G. B., Castelli, Fulvio, Zaltron, S., Spinetti, A., Odolini, S., Leandro, G., Cozzolongo, R., Zappimbulso, M., Russello, M., Benigno, R., Coco, C., Torti, C., Costa, C., Greco, G., Mazzitelli, M., Pisani, V., Cosco, Lucia, Quintieri, F., De Siena, Martina, Giancotti, F., Vecchiet, J., Falasca, K., Mastroianni, A., Apuzzo, G., Chidichimo, L., Foschi, F. G., Dall’Aglio, A. C., Libanore, M., Segala, D., Sighinolfi, L., Bartolozzi, D., Salomoni, E., Blanc, P., Baragli, F., DelundefinedPin, B., Mariabelli, E., Mazzotta, F., Poggi, A., Zignego, A. L., Monti, M., Madia, Francesca, Xheka, A., Cela, E. M., Santantonio, T. A., Bruno, S. R., Viscoli, C., Alessandrini, A. I., Curti, C., DiundefinedBiagio, A., Nicolini, L. A., Balletto, E., Mastroianni, Chiara, Blerta, K., Prati, D., Raffaele, L., Andreoletti, M., Perboni, G., Costa, P., Manzini, L., Raimondo, G., Filomia, R., Lazzarin, A., Morsica, G., Salpietro, S., Puoti, M., Baiguera, C., Vassalli, S., Rumi, M. G., Labanca, S., Zuin, M., Giorgini, A., Orellana, D., D’ArminioundefinedMonforte, A., Debona, A., Solaro, S., Fargion, S., Valenti, L., Periti, G., Pelusi, S., Galli, M., Calvi, E., Milazzo, L., Peri, A., Lampertico, P., Borghi, Margherita, D’Ambrosio, R., Degasperi, E., Vinci, Maria Rosaria, Villa, E., Bernabucci, V., Bristot, Luca, Pereira, F., Chessa, L., Pasetto, M. C., Loi, M., Gori, A., Beretta, I., Pastore, V., Soria, A., Strazzabosco, M., Ciaccio, A., Gemma, M., Borgia, G., Foggia, A., Zappulo, E., Gentile, I., Buonomo, A. R., Abrescia, N., Maddaloni, A., Caporaso, N., Morisco, F., Camera, S., Donnarumma, L., Coppola, C., Amoruso, D. C., Staiano, L., Saturnino, M. R., Coppola, N., Martini, S., Monari, C., Federico, Alex, Dallio, M., Loguercio, C., Gaeta, G. B., Brancaccio, G., Nardone, G., Sgamato, C., D’Adamo, G., Alberti, A., Gonzo, M., Piovesan, S., Chemello, L., Buggio, A., Cavalletto, L., Barbaro, F., Castelli, Enrico, Floreani, A., Cazzagon, N., Franceschet, I., Russo, F. P., Zanetto, A., Franceschet, E., Madonia, S., Cannizzaro, Maria Chiara, Montalto, G., Licata, A., Capitano, A. R., Craxì, A., Petta, S., Calvaruso, V., Rini, F., Ferrari, C., Negri, E., Orlandini, A., Pesci, M., Bruno, R., Lombardi, A., Zuccaro, V., Gulminetti, R., Asti, A., Villaraggia, M., Mondelli, M., Ludovisi, S., Baldelli, F., Di Candilo, F., Parruti, G., Di Stefano, Paolo, Sozio, F., Gizzi, M. C., Brunetto, M. R., Colombatto, P., Coco, B., Surace, L., Foti, G., Pellicano, S., Fornaciari, G., Schianchi, S., Vignoli, P., Massari, M., Corsini, R., Garlassi, E., Ballardini, G., Andreoni, M., Cerva, C., Angelico, M., Gasbarrini, Antonio, Siciliano, M., Nosotti, L., Taliani, G., Biliotti, E., Santori, M., Spaziante, M., Tamburini, F., Vullo, V., D’Ettorre, G., Cavallari, E. N., Gebremeskel, T. S., Pavone, P., Cauda, Roberto, Cingolani, Antonella, Lamonica, S., D’Offizi, G., Lionetti, R., Visco Comandini, U., Grieco, Antonio, D’Aversa, F., Picardi, A., De Vincentis, A., Galati, G., Gallo, Patrizia, Dell’Unto, C., Aghemo, A., Gatti Comini, A., Persico, M., Masarone, M., Anselmo, M., De Leo, P., Marturano, Monia, Brunelli, E., Ridolfi, F., Schimizzi, A. M., Ayoubi Khajekini, M., Framarin, L., Di Perri, G., Cariti, G., Boglione, L., Cardellino, C., Marinaro, L., Saracco, G. M., Ciancio, A., Toniutto, P., Alterini, G., Capra, F., Ieluzzi, D., Marcellusi, A, Viti, R, Kondili, L, Rosato, S, Vella, S, Mennini, F, Quaranta, M, Tosti, M, Weimer, L, Ferrigno, L, D'Angelo, F, Falzano, L, Benedetti, A, Schiada, L, Cucco, M, Giacometti, A, Brescini, L, Castelletti, S, Drenaggi, D, Mazzaro, C, Angarano, G, Milella, M, Dileo, A, Rendina, M, Contaldo, A, Iannone, A, La Fortezza, F, Rizzi, M, Cologni, G, Bolondi, L, Benevento, F, Serio, I, Andreone, P, Caraceni, P, Guarneri, V, Margotti, M, Simonetti, G, Mazzella, G, Verucchi, G, Donati, V, Mian, P, Rimenti, G, Rossini, A, Contessi, G, Castelli, F, Zaltron, S, Spinetti, A, Odolini, S, Leandro, G, Cozzolongo, R, Zappimbulso, M, Russello, M, Benigno, R, Coco, C, Torti, C, Costa, C, Greco, G, Mazzitelli, M, Pisani, V, Cosco, L, Quintieri, F, Desiena, M, Giancotti, F, Vecchiet, J, Falasca, K, Mastroianni, A, Apuzzo, G, Chidichimo, L, Foschi, F, Dall'Aglio, A, Libanore, M, Segala, D, Sighinolfi, L, Bartolozzi, D, Salomoni, E, Blanc, P, Baragli, F, Delpin, B, Mariabelli, E, Mazzotta, F, Poggi, A, Zignego, A, Monti, M, Madia, F, Xheka, A, Cela, E, Santantonio, T, Bruno, S, Viscoli, C, Alessandrini, A, Curti, C, Dibiagio, A, Nicolini, L, Balletto, E, Mastroianni, C, Blerta, K, Prati, D, Raffaele, L, Andreoletti, M, Perboni, G, Costa, P, Manzini, L, Raimondo, G, Filomia, R, Lazzarin, A, Morsica, G, Salpietro, S, Puoti, M, Baiguera, C, Vassalli, S, Rumi, M, Labanca, S, Zuin, M, Giorgini, A, Orellana, D, D'Arminiomonforte, A, Debona, A, Solaro, S, Fargion, S, Valenti, L, Periti, G, Pelusi, S, Galli, M, Calvi, E, Milazzo, L, Peri, A, Lampertico, P, Borghi, M, D'Ambrosio, R, Degasperi, E, Vinci, M, Villa, E, Bernabucci, V, Bristot, L, Pereira, F, Chessa, L, Pasetto, M, Loi, M, Gori, A, Beretta, I, Pastore, V, Soria, A, Strazzabosco, M, Ciaccio, A, Gemma, M, Borgia, G, Foggia, A, Zappulo, E, Gentile, I, Buonomo, A, Abrescia, N, Maddaloni, A, Caporaso, N, Morisco, F, Camera, S, Donnarumma, L, Coppola, C, Amoruso, D, Staiano, L, Saturnino, M, Coppola, N, Martini, S, Monari, C, Federico, A, Dallio, M, Loguercio, C, Gaeta, G, Brancaccio, G, Nardone, G, Sgamato, C, D'Adamo, G, Alberti, A, Gonzo, M, Piovesan, S, Chemello, L, Buggio, A, Cavalletto, L, Barbaro, F, Castelli, E, Floreani, A, Cazzagon, N, Franceschet, I, Russo, F, Zanetto, A, Franceschet, E, Madonia, S, Cannizzaro, M, Montalto, G, Licata, A, Capitano, A, Craxi, A, Petta, S, Calvaruso, V, Rini, F, Ferrari, C, Negri, E, Orlandini, A, Pesci, M, Bruno, R, Lombardi, A, Zuccaro, V, Gulminetti, R, Asti, A, Villaraggia, M, Mondelli, M, Ludovisi, S, Baldelli, F, Di Candilo, F, Parruti, G, Di Stefano, P, Sozio, F, Gizzi, M, Brunetto, M, Colombatto, P, Coco, B, Surace, L, Foti, G, Pellicano, S, Fornaciari, G, Schianchi, S, Vignoli, P, Massari, M, Corsini, R, Garlassi, E, Ballardini, G, Andreoni, M, Cerva, C, Angelico, M, Gasbarrini, A, Siciliano, M, De Siena, M, Nosotti, L, Taliani, G, Biliotti, E, Santori, M, Spaziante, M, Tamburini, F, Vullo, V, D'Ettorre, G, Cavallari, E, Gebremeskel, T, Pavone, P, Cauda, R, Cingolani, A, Lamonica, S, D'Offizi, G, Lionetti, R, Visco Comandini, U, Grieco, A, D'Aversa, F, Picardi, A, De Vincentis, A, Galati, G, Gallo, P, Dell'Unto, C, Aghemo, A, Gatti Comini, A, Persico, M, Masarone, M, Anselmo, M, De Leo, P, Marturano, M, Brunelli, E, Ridolfi, F, Schimizzi, A, Ayoubi Khajekini, M, Framarin, L, Di Perri, G, Cariti, G, Boglione, L, Cardellino, C, Marinaro, L, Saracco, G, Ciancio, A, Toniutto, P, Alterini, G, Capra, F, Ieluzzi, D, Kondili LA, Vella S, Quaranta MG, Rosato S, Tosti ME, Weimer LE, Ferrigno L, D'Angelo F, Falzano L, Benedetti A, Schiadà L, Cucco M, Giacometti A, Brescini L, Castelletti S, Drenaggi D, Mazzaro C, Angarano G, Milella M, Di Leo A, Rendina M, Contaldo A, Iannone A, La Fortezza F, Rizzi M, Cologni G, Bolondi L, Benevento F, Serio I, Andreone P, Caraceni P, Guarneri V, Margotti M, Simonetti G, Mazzella G, Verucchi G, Donati V, Mian P, Rimenti G, Rossini A, Contessi GB, Castelli F, Zaltron S, Spinetti A, Odolini S, Leandro G, Cozzolongo R, Zappimbulso M, Russello M, Benigno R, Coco C, Torti C, Costa C, Greco G, Mazzitelli M, Pisani V, Cosco L, Quintieri F, De Siena M, Giancotti F, Vecchiet J, Falasca K, Mastroianni A, Apuzzo G, Chidichimo L, Foschi FG, Dall'Aglio AC, Libanore M, Segala D, Sighinolfi L, Bartolozzi D, Salomoni E, Blanc P, Baragli F, Del Pin B, Mariabelli E, Mazzotta F, Poggi A, Zignego AL, Monti M, Madia F, Xheka A, Cela EM, Santantonio TA, Bruno SR, Viscoli C, Alessandrini AI, Curti C, Di Biagio A, Nicolini LA, Balletto E, Mastroianni C, Blerta K, Prati D, Raffaele L, Andreoletti M, Perboni G, Costa P, Manzini L, Raimondo G, Filomia R, Lazzarin A, Morsica G, Salpietro S, Puoti M, Baiguera C, Vassalli S, Rumi MG, Labanca S, Zuin M, Giorgini A, Orellana D, D'Arminio Monforte A, Debona A, Solaro S, Fargion S, Valenti L, Periti G, Pelusi S, Galli M, Calvi E, Milazzo L, Peri A, Lampertico P, Borghi M, D'Ambrosio R, Degasperi E, Vinci M, Villa E, Bernabucci V, Bristot L, Pereira F, Chessa L, Pasetto MC, Loi M, Gori A, Beretta I, Pastore V, Soria A, Strazzabosco M, Ciaccio A, Gemma M, Borgia G, Foggia A, Zappulo E, Gentile I, Buonomo AR, Abrescia N, Maddaloni A, Caporaso N, Morisco F, Camera S, Donnarumma L, Coppola C, Amoruso DC, Staiano L, Saturnino MR, Coppola N, Martini S, Monari C, Federico A, Dallio M, Loguercio C, Gaeta GB, Brancaccio G, Nardone G, Sgamato C, D'Adamo G, Alberti A, Gonzo M, Piovesan S, Chemello L, Buggio A, Cavalletto L, Barbaro F, Castelli E, Floreani A, Cazzagon N, Franceschet I, Russo FP, Zanetto A, Franceschet E, Madonia S, Cannizzaro M, Montalto G, Licata A, Capitano AR, Craxì A, Petta S, Calvaruso V, Rini F, Ferrari C, Negri E, Orlandini A, Pesci M, Bruno R, Lombardi A, Zuccaro V, Gulminetti R, Asti A, Villaraggia M, Mondelli M, Ludovisi S, Baldelli F, Di Candilo F, Parruti G, Di Stefano P, Sozio F, Gizzi MC, Brunetto MR, Colombatto P, Coco B, Surace L, Foti G, Pellicano S, Fornaciari G, Schianchi S, Vignoli P, Massari M, Corsini R, Garlassi E, Ballardini G, Andreoni M, Cerva C, Angelico M, Gasbarrini A, Siciliano M, De Siena M, Nosotti L, Taliani G, Biliotti E, Santori M, Spaziante M, Tamburini F, Vullo V, D'Ettorre G, Cavallari EN, Gebremeskel TS, Pavone P, Cauda R, Cingolani A, Lamonica S, D'Offizi G, Lionetti R, Visco Comandini U, Grieco A, D'Aversa F, Picardi A, De Vincentis A, Galati G, Gallo P, Dell'Unto C, Aghemo A, Gatti Comini A, Persico M, Masarone M, Anselmo M, De Leo P, Marturano M, Brunelli E, Ridolfi F, Schimizzi AM, Ayoubi Khajekini M, Framarin L, Di Perri G, Cariti G, Boglione L, Cardellino C, Marinaro L, Saracco GM, Ciancio A, Toniutto P, Alterini G, Capra F, Ieluzzi D., Marcellusi, A., Viti, R., Kondili, L. A., Rosato, S., Vella, S., Mennini, F. S., Quaranta, M. G., Tosti, M. E., Weimer, L. E., Ferrigno, L., D'Angelo, F., Falzano, L., Benedetti, A., Schiada, L., Cucco, M., Giacometti, A., Brescini, L., Castelletti, S., Drenaggi, D., Mazzaro, C., Angarano, G., Milella, M., Dileo, A., Rendina, M., Contaldo, A., Iannone, A., La Fortezza, F., Rizzi, M., Cologni, G., Bolondi, L., Benevento, F., Serio, I., Andreone, P., Caraceni, P., Guarneri, V., Margotti, M., Simonetti, G., Mazzella, G., Verucchi, G., Donati, V., Mian, P., Rimenti, G., Rossini, A., Contessi, G. B., Castelli, F., Zaltron, S., Spinetti, A., Odolini, S., Leandro, G., Cozzolongo, R., Zappimbulso, M., Russello, M., Benigno, R., Coco, C., Torti, C., Costa, C., Greco, G., Mazzitelli, M., Pisani, V., Cosco, L., Quintieri, F., Desiena, M., Giancotti, F., Vecchiet, J., Falasca, K., Mastroianni, A., Apuzzo, G., Chidichimo, L., Foschi, F. G., Dall'Aglio, A. C., Libanore, M., Segala, D., Sighinolfi, L., Bartolozzi, D., Salomoni, E., Blanc, P., Baragli, F., Delpin, B., Mariabelli, E., Mazzotta, F., Poggi, A., Zignego, A. L., Monti, M., Madia, F., Xheka, A., Cela, E. M., Santantonio, T. A., Bruno, S. R., Viscoli, C., Alessandrini, A. I., Curti, C., Dibiagio, A., Nicolini, L. A., Balletto, E., Mastroianni, C., Blerta, K., Prati, D., Raffaele, L., Andreoletti, M., Perboni, G., Costa, P., Manzini, L., Raimondo, G., Filomia, R., Lazzarin, A., Morsica, G., Salpietro, S., Puoti, M., Baiguera, C., Vassalli, S., Rumi, M. G., Labanca, S., Zuin, M., Giorgini, A., Orellana, D., D'Arminiomonforte, A., Debona, A., Solaro, S., Fargion, S., Valenti, L., Periti, G., Pelusi, S., Galli, M., Calvi, E., Milazzo, L., Peri, A., Lampertico, P., Borghi, M., D'Ambrosio, R., Degasperi, E., Vinci, M., Villa, E., Bernabucci, V., Bristot, L., Pereira, F., Chessa, L., Pasetto, M. C., Loi, M., Gori, A., Beretta, I., Pastore, V., Soria, A., Strazzabosco, M., Ciaccio, A., Gemma, M., Borgia, G., Foggia, A., Zappulo, E., Gentile, I., Buonomo, A. R., Abrescia, N., Maddaloni, A., Caporaso, N., Morisco, F., Camera, S., Donnarumma, L., Coppola, C., Amoruso, D. C., Staiano, L., Saturnino, M. R., Coppola, N., Martini, S., Monari, C., Federico, A., Dallio, M., Loguercio, C., Gaeta, G. B., Brancaccio, G., Nardone, G., Sgamato, C., D'Adamo, G., Alberti, A., Gonzo, M., Piovesan, S., Chemello, L., Buggio, A., Cavalletto, L., Barbaro, F., Castelli, E., Floreani, A., Cazzagon, N., Franceschet, I., Russo, F. P., Zanetto, A., Franceschet, E., Madonia, S., Cannizzaro, M., Montalto, G., Licata, A., Capitano, A. R., Craxi, A., Petta, S., Calvaruso, V., Rini, F., Ferrari, C., Negri, E., Orlandini, A., Pesci, M., Bruno, R., Lombardi, A., Zuccaro, V., Gulminetti, R., Asti, A., Villaraggia, M., Mondelli, M., Ludovisi, S., Baldelli, F., Di Candilo, F., Parruti, G., Di Stefano, P., Sozio, F., Gizzi, M. C., Brunetto, M. R., Colombatto, P., Coco, B., Surace, L., Foti, G., Pellicano, S., Fornaciari, G., Schianchi, S., Vignoli, P., Massari, M., Corsini, R., Garlassi, E., Ballardini, G., Andreoni, M., Cerva, C., Angelico, M., Gasbarrini, A., Siciliano, M., De Siena, M., Nosotti, L., Taliani, G., Biliotti, E., Santori, M., Spaziante, M., Tamburini, F., Vullo, V., D'Ettorre, G., Cavallari, E. N., Gebremeskel, T. S., Pavone, P., Cauda, R., Cingolani, A., Lamonica, S., D'Offizi, G., Lionetti, R., Visco Comandini, U., Grieco, A., D'Aversa, F., Picardi, A., De Vincentis, A., Galati, G., Gallo, P., Dell'Unto, C., Aghemo, A., Gatti Comini, A., Persico, M., Masarone, M., Anselmo, M., De Leo, P., Marturano, M., Brunelli, E., Ridolfi, F., Schimizzi, A. M., Ayoubi Khajekini, M., Framarin, L., Di Perri, G., Cariti, G., Boglione, L., Cardellino, C., Marinaro, L., Saracco, G. M., Ciancio, A., Toniutto, P., Alterini, G., Capra, F., Ieluzzi, D., Marcellusi, Andrea, Viti, Raffaella, Kondili, Loreta A., Rosato, Stefano, Vella, Stefano, Mennini, Francesco Saverio, Kondili, L.A., Quaranta, M.G., Tosti, M.E., Weimer, L.E., D’Angelo, F., Schiadà, L., Di&nbsp, Leo, A., Contessi, G.B., De&nbsp, Siena, M., Foschi, F.G., Dall’Aglio, A.C., Del&nbsp, Pin, B., Zignego, A.L., Cela, E.M., Santantonio, T.A., Bruno, S.R., Alessandrini, A.I., Biagio, A., Nicolini, L.A., Rumi, M.G., D’Arminio&nbsp, Monforte, A., D’Ambrosio, R., Pasetto, M.C., Buonomo, A.R., Amoruso, D.C., Saturnino, M.R., Gaeta, G.B., D’Adamo, G., Russo, F.P., Capitano, A.R., Craxì, A., Gizzi, M.C., Brunetto, M.R., D’Ettorre, G., Cavallari, E.N., Gebremeskel, T.S., D’Offizi, G., D’Aversa, F., Dell’Unto, C., Schimizzi, A.M., Saracco, G.M., Cosco, Alfredo, Dall’Aglio, A. C., Salomoni, Valentina, Nicolini, Elvira, Calvi, Marta, Soria, Giovanni, D'Adamo, Danilo, ALONSO ALBERTI, MARIA PALOMA CARMEN, Orlandini, Giovanni, DE ASTIS, Fabio, Sozio, Concetta, Terzini, Angelico, DE SIENA, ANDREA URIEL, Taliani, Sabrina, Spaziante, Agata, Lamonica, Emilia, and Capra, Carlo

Subjects
Liver Cirrhosis, Pediatrics, Time Factors, Settore MED/09 - Medicina Interna, National Health Programs, ERADICATION, OUTBREAK, antiviral treatment, anti HCV, economic consequences, Hepacivirus, LIVER FIBROSIS, Severity of Illness Index, Health Services Accessibility, COST-EFFECTIVENESS, Indirect costs, 0302 clinical medicine, Epidemiology, virus infection, 030212 general & internal medicine, health care economics and organizations, cost effectiveness, 030503 health policy & services, Health Policy, Health services research, health, Hepatitis C, Markov Chains, chronic hepatitis C, virus infection, fibrosis progression, cost effectiveness, liver fibrosis, Italy, Pharmacology, Public Health, Environmental and Occupational Health, Cohort, Settore SECS-P/03 - Scienza delle Finanze, Disease Progression, Public Health, 0305 other medical science, Viral hepatitis, Anti-HCV antiviral treatment, CHRONIC HEPATITIS-C, medicine.medical_specialty, Genotype, Settore MED/12 - GASTROENTEROLOGIA, VIRUS-INFECTION, Antiviral Agents, NO, 03 medical and health sciences, Cost Savings, Humans, medicine, MANAGEMENT, chronic hepatitis C, INDUCED DISEASES, METAANALYSIS, Health economics, business.industry, Public health, Environmental and Occupational Health, medicine.disease, FIBROSIS PROGRESSION, business
Abstract

OBJECTIVE:\ud We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy.\ud \ud METHODS:\ud A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered.\ud \ud RESULTS:\ud The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively.\ud \ud CONCLUSIONS:\ud This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV.

Published
2019

8. Perspectives from Italy during the COVID-19 pandemic: nationwide survey-based focus on minimally invasive HPB surgery

Author

Aldrighetti, L., Boggi, U., Falconi, M., Giuliante, F., Cipriani, F., Ratti, F., Torzilli, G., Abu Hilal, M., Andrianello, S., Anselmo, A., Ardito, F., Gian, L. B., Banchini, F., Barabino, M., Barberis, A., Bassi, C., Batignani, G., Battiston, C., Belli, A., Berti, S., Bianco, P., Brolese, A., Brozzetti, S., Butturini, G., Calise, F., Carabott, K., Capretti, G., Casadei, R., Cescon, M., Cesaretti, M., Cillo, U., Cinardi, N., Colledan, M., Coppola, A., Cotsoglou, C., Crippa, S., Bona, E. D., Valle, R. D., De Angelis, M., De Carlis, L., Di Benedetto, F., Di Sebastiano, P., Dova, L., Ercolani, G., Esposito, A., Giuseppe, M. E., Fabris, A., Ferrero, A., Frena, A., Frigerio, I., Gianotti, L., Giuliani, A., Grazi, G., Gringeri, E., Griseri, G., Gruttadauria, S., Guglielmi, A., Izzo, F., Jovine, E., Lanza, E., Malleo, G., Manzini, L., Massani, M., Mazzaferro, V., Memeo, R., Minni, F., Morelli, L., Nappo, G., Nardo, B., Orlando, F., Partelli, S., Patriti, A., Patrone, R., Percivale, A., Piccolo, G., Ravaioli, M., Reggiani, P., Risaliti, M., Rocca, A., Romagnoli, R., Romano, F., Russolillo, N., Ruzzenente, A., Saladino, E., Salvia, R., Santambrogio, R., Tarchi, P., Troci, A., Troisi, R., Urbani, L., Veneroni, L., Vennarecci, G., Vigano, L., Viola, M., Vistoli, F., Vivarelli, M., Zanello, M., Zanus, G., Zerbi, A., Giuliante F. (ORCID:0000-0001-9517-8220), Ardito F. (ORCID:0000-0003-1596-2862), Aldrighetti, L., Boggi, U., Falconi, M., Giuliante, F., Cipriani, F., Ratti, F., Torzilli, G., Abu Hilal, M., Andrianello, S., Anselmo, A., Ardito, F., Gian, L. B., Banchini, F., Barabino, M., Barberis, A., Bassi, C., Batignani, G., Battiston, C., Belli, A., Berti, S., Bianco, P., Brolese, A., Brozzetti, S., Butturini, G., Calise, F., Carabott, K., Capretti, G., Casadei, R., Cescon, M., Cesaretti, M., Cillo, U., Cinardi, N., Colledan, M., Coppola, A., Cotsoglou, C., Crippa, S., Bona, E. D., Valle, R. D., De Angelis, M., De Carlis, L., Di Benedetto, F., Di Sebastiano, P., Dova, L., Ercolani, G., Esposito, A., Giuseppe, M. E., Fabris, A., Ferrero, A., Frena, A., Frigerio, I., Gianotti, L., Giuliani, A., Grazi, G., Gringeri, E., Griseri, G., Gruttadauria, S., Guglielmi, A., Izzo, F., Jovine, E., Lanza, E., Malleo, G., Manzini, L., Massani, M., Mazzaferro, V., Memeo, R., Minni, F., Morelli, L., Nappo, G., Nardo, B., Orlando, F., Partelli, S., Patriti, A., Patrone, R., Percivale, A., Piccolo, G., Ravaioli, M., Reggiani, P., Risaliti, M., Rocca, A., Romagnoli, R., Romano, F., Russolillo, N., Ruzzenente, A., Saladino, E., Salvia, R., Santambrogio, R., Tarchi, P., Troci, A., Troisi, R., Urbani, L., Veneroni, L., Vennarecci, G., Vigano, L., Viola, M., Vistoli, F., Vivarelli, M., Zanello, M., Zanus, G., Zerbi, A., Giuliante F. (ORCID:0000-0001-9517-8220), and Ardito F. (ORCID:0000-0003-1596-2862)

Abstract

The safety of minimally invasive procedures during COVID pandemic remains hotly debated, especially in a country, like Italy, where minimally invasive techniques have progressively and pervasively entered clinical practice, in both the hepatobiliary and pancreatic community. A nationwide snapshot of the management of HPB minimally invasive surgery activity during COVID-19 pandemic is provided: a survey was developed and conducted within AICEP (Italian Association of HepatoBilioPancreatic Surgeons) with the final aim of conveying the experience, knowledge, and opinions into a unitary report enabling more efficient crisis management. Results from the survey (81 respondents) show that, in Italian hospitals, minimally invasive surgery maintains its role despite the COVID-19 pandemic, with the registered reduction of cases being proportional to the overall reduction of the HPB surgical activity. Respondents agree that the switch from minimally invasive to open technique can be considered as a valid option for cases with a high technical complexity. Several issues merit specific attention: screening for virus positivity should be universally performed; only expert surgical teams should operate on positive patients and specific technical measures to lower the biological risk of contamination during surgery must be followed. Future studies specifically designed to establish the true risks in minimally invasive surgery are suggested. Furthermore, a standard and univocal process of prioritization of patients from Regional Healthcare Systems is advisable.

Published
2020

12. Changes in serum low molecular weight proteins from DL-PCB contaminated heifers

Author

Manzini, L., Badino, P., FLAVIA GIROLAMI, Scaloni, A., Renzone, G., Rychen, G., Nebbia, C., Universita di Torino, Consiglio Nazionale delle Ricerche (CNR), Unité de Recherches Animal et Fonctionnalités des Produits Animaux (URAFPA), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), and ProdInra, Migration

Subjects
[SDV] Life Sciences [q-bio], animal structures, [SDV]Life Sciences [q-bio], animal diseases, food and beverages, [INFO]Computer Science [cs], sense organs, [INFO] Computer Science [cs], skin and connective tissue diseases, serum, low molecular, weight proteins, ComputingMilieux_MISCELLANEOUS
Abstract

Changes in serum low molecular weight proteins from DL-PCB contaminated heifers

Published
2015

14. Role of Microbial Translocation (MT) and Immune Hyperactivation (IH) in Liver Disease Progression of HIV/HCV plus Patients with well documented HIV seroconversion date and preserved CD4 count

Author

Cozzi-Lepri, GMA, Bellistri, GM, Merlini, E, Leoncini, F, Baldelli, F, Antonucci, G, Castagna, A, Raise, E, Manzini, L, Manconi, PE, Puoti, M, De Luca, A, Monforte, AD, Cozzi-Lepri, Gma, Bellistri, Gm, Merlini, E, Leoncini, F, Baldelli, F, Antonucci, G, Castagna, A, Raise, E, Manzini, L, Manconi, Pe, Puoti, M, De Luca, A, and Monforte, Ad

Published
2010

19. Influence of a decontamination protocol on the blood redox status of dioxin-like PCB naturally contaminated heifers

Author

FLAVIA GIROLAMI, Rossetti, C., Manzini, L., Rychen, G., Nebbia, C., and Spagnuolo, M. S.

Subjects
Dioxin-like PCBs, heifers, blood redox homeostasis
Abstract

Introduction Exposure to dioxin-like (DL) compounds promotes reactive oxygen species (ROS) production and depression of several ROS quenching systems, leading to oxidative stress. We previously reported that dioxins impair the plasma antioxidant defence system (ADS) of lactating buffalos (1), and that the extent of damage to plasma proteins and lipids in dairy cows is correlated with the concentration of DL-PCBs in bulk milk (2). Aim of the study was to evaluate in naturally exposed heifers the effect of a decontamination procedure, based on the removal of animals from the polluted area and the feeding of a controlled diet, on specific markers of blood redox homeostasis. Materials and Methods Eight one-year old DL-PCB exposed heifers were removed from a contaminated area to be reared in an experimental facility under controlled conditions and diet. From each animal perirenal fat biopsies and blood samples were collected bimonthly 4 times (A-B-C-D). Fat PCB content was measured by GC-HR-MS with a validated method. Serum Retinol (Ret), alpha-Tocopherol (Toc), Ascorbate (Asc), the total antioxidant capacity (TAC), and the glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were used as indices of the ADS. Protein and lipid damage were assayed by serum Nitro-tyrosine (N-Tyr), protein-bound carbonyls (PC), and lipid hydroperoxides (LPO) measurement. Values were expressed as mean ± SEM and statistically analyzed by one-way ANOVA followed by Tukey's test. Correlation was calculated through the Pearson's coefficient. Results and Conclusions Initial DL-PCB TEQ values of each animal was higher than 20 pg/g fat, and decreased rapidly in sampling B (7.71± 0.32 pg/g fat), complying with legal limits in samplings C and D (below 5 pg/g fat) (3). According to previous data (2), sampling A displayed significantly lower (P

20. Perspectives from Italy during the COVID-19 pandemic: nationwide survey-based focus on minimally invasive HPB surgery

Author

Aldrighetti, aEmail Author, L., Boggi, U. b., Falconi, M. c., Giuliante, F. d., Cipriani, F. a., Ratti, Torzilli, G. e., Abu, Hilal, Andrianello, Anselmo, Ardito, Gian, L. B., Banchini, Barabino, Barberis, Bassi, Batignani, Battiston, Belli, Berti, Bianco, Brolese, Brozzetti, Butturini, Calise, Carabott, Capretti, Casadei, Cescon, Cesaretti, Cillo, Cinardi, Colledan, Coppola, Cotsoglou, Crippa, Bona, E. D., Valle, R. D., Angelis, De, Carlis, De, Benedetto, Di, Sebastiano, Di, Dova, Ercolani, Esposito, Giuseppe, M. E., Fabris, Ferrero, Frena, Frigerio, Gianotti, Giuliani, Grazi, Gringeri, Griseri, Gruttadauria, Guglielmi, Izzo, Jovine, Lanza, Malleo, Manzini, Massani, Mazzaferro, Memeo, Minni, Morelli, Nappo, Nardo, Orlando, Partelli, Patriti, Patrone, Percivale, Piccolo, Ravaioli, Reggiani, Risaliti, Rocca, A, Romagnoli, Romano, Russolillo, Ruzzenente, Saladino, Salvia, Santambrogio, Tarchi, Troci, Troisi, Urbani, Veneroni, Vennarecci, Vigano, Viola, Vistoli, Vivarelli, Zanello, Zanus, Zerbi, Italian Association of HepatoBilioPancreatic Surgeons-AICEP, Aldrighetti, L., Boggi, U., Falconi, M., Giuliante, F., Cipriani, F., Ratti, F., Torzilli, G., Abu Hilal, M., Andrianello, S., Anselmo, A., Ardito, F., Gian, L. B., Banchini, F., Barabino, M., Barberis, A., Bassi, C., Batignani, G., Battiston, C., Belli, A., Berti, S., Bianco, P., Brolese, A., Brozzetti, S., Butturini, G., Calise, F., Carabott, K., Capretti, G., Casadei, R., Cescon, M., Cesaretti, M., Cillo, U., Cinardi, N., Colledan, M., Coppola, A., Cotsoglou, C., Crippa, S., Bona, E. D., Valle, R. D., De Angelis, M., De Carlis, L., Di Benedetto, F., Di Sebastiano, P., Dova, L., Ercolani, G., Esposito, A., Giuseppe, M. E., Fabris, A., Ferrero, A., Frena, A., Frigerio, I., Gianotti, L., Giuliani, A., Grazi, G., Gringeri, E., Griseri, G., Gruttadauria, S., Guglielmi, A., Izzo, F., Jovine, E., Lanza, E., Malleo, G., Manzini, L., Massani, M., Mazzaferro, V., Memeo, R., Minni, F., Morelli, L., Nappo, G., Nardo, B., Orlando, F., Partelli, S., Patriti, A., Patrone, R., Percivale, A., Piccolo, G., Ravaioli, M., Reggiani, P., Risaliti, M., Rocca, A., Romagnoli, R., Romano, F., Russolillo, N., Ruzzenente, A., Saladino, E., Salvia, R., Santambrogio, R., Tarchi, P., Troci, A., Troisi, R., Urbani, L., Veneroni, L., Vennarecci, G., Vigano, L., Viola, M., Vistoli, F., Vivarelli, M., Zanello, M., Zanus, G., Zerbi, A., Aldrighetti L., Boggi U., Falconi M., Giuliante F., Cipriani F., Ratti F., Torzilli G., Abu Hilal M., Andrianello S., Anselmo A., Ardito F., Gian L.B., Banchini F., Barabino M., Barberis A., Bassi C., Batignani G., Battiston C., Belli A., Berti S., Bianco P., Brolese A., Brozzetti S., Butturini G., Calise F., Carabott K., Capretti G., Casadei R., Cescon M., Cesaretti M., Cillo U., Cinardi N., Colledan M., Coppola A., Cotsoglou C., Crippa S., Bona E.D., Valle R.D., De Angelis M., De Carlis L., Di Benedetto F., Di Sebastiano P., Dova L., Ercolani G., Esposito A., Giuseppe M.E., Fabris A., Ferrero A., Frena A., Frigerio I., Gianotti L., Giuliani A., Grazi G., Gringeri E., Griseri G., Gruttadauria S., Guglielmi A., Izzo F., Jovine E., Lanza E., Malleo G., Manzini L., Massani M., Mazzaferro V., Memeo R., Minni F., Morelli L., Nappo G., Nardo B., Orlando F., Partelli S., Patriti A., Patrone R., Percivale A., Piccolo G., Ravaioli M., Reggiani P., Risaliti M., Rocca A., Romagnoli R., Romano F., Russolillo N., Ruzzenente A., Saladino E., Salvia R., Santambrogio R., Tarchi P., Troci A., Troisi R., Urbani L., Veneroni L., Vennarecci G., Vigano L., Viola M., Vistoli F., Vivarelli M., Zanello M., Zanus G., and Zerbi A.

Subjects
Future studies, Settore MED/18 - CHIRURGIA GENERALE, Crisis management, Nationwide survey, 0302 clinical medicine, Pandemic, Pancrea, Medicine, Viral, Minimally invasive procedures, Liver Disease, Liver Diseases, COVID-19, Liver, Minimally invasive, Pancreas, Biliary Tract Diseases, Health Care Surveys, Humans, Italy, Pancreatic Diseases, Coronavirus Infections, Minimally Invasive Surgical Procedures, Pandemics, Pneumonia, Viral, 030220 oncology & carcinogenesis, Esophagus Resection, Original Article, 030211 gastroenterology & hepatology, Biliary Tract Disease, Human, Prioritization, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), NO, 03 medical and health sciences, High Volume Hospital, Centralization, LS7_4, Coronavirus Infection, business.industry, Minimally Invasive Surgical Procedure, Pneumonia, Surgery, Health Care Survey, Invasive surgery, Pancreatic Disease, business
Abstract

The safety of minimally invasive procedures during COVID pandemic remains hotly debated, especially in a country, like Italy, where minimally invasive techniques have progressively and pervasively entered clinical practice, in both the hepatobiliary and pancreatic community. A nationwide snapshot of the management of HPB minimally invasive surgery activity during COVID-19 pandemic is provided: a survey was developed and conducted within AICEP (Italian Association of HepatoBilioPancreatic Surgeons) with the final aim of conveying the experience, knowledge, and opinions into a unitary report enabling more efficient crisis management. Results from the survey (81 respondents) show that, in Italian hospitals, minimally invasive surgery maintains its role despite the COVID-19 pandemic, with the registered reduction of cases being proportional to the overall reduction of the HPB surgical activity. Respondents agree that the switch from minimally invasive to open technique can be considered as a valid option for cases with a high technical complexity. Several issues merit specific attention: screening for virus positivity should be universally performed; only expert surgical teams should operate on positive patients and specific technical measures to lower the biological risk of contamination during surgery must be followed. Future studies specifically designed to establish the true risks in minimally invasive surgery are suggested. Furthermore, a standard and univocal process of prioritization of patients from Regional Healthcare Systems is advisable. Electronic supplementary material The online version of this article (10.1007/s13304-020-00815-5) contains supplementary material, which is available to authorized users.

Published
2020

21. Development of post-COVID-19 cardiovascular events: an analysis of clinical features and risk factors from a single hospital retrospective study.

Author

Cuomo G, Puzzolante C, Iadisernia V, Santoro A, Menozzi M, Carli F, Digaetano M, Orlando G, Franceschini E, Bedini A, Meschiari M, Manzini L, Corradi L, Milic J, Borghi V, Brugioni L, Pietrangelo A, Clini E, Girardis M, Guaraldi G, and Mussini C

Abstract

Cardiovascular complications after a SARS-CoV-2 infection are a phenomenon of relevant scientific interest. The aim of this study was to analyze the onset of post-COVID-19 cardiovascular events in patients hospitalized in a tertiary care center. This is a retrospective study conducted on patients hospitalized over a period of three months. The patients were older than 18 years of age and had a diagnosis of COVID-19 infection confirmed from a nasopharyngeal swab sample. Anamnestic and clinical-laboratory data were collected. Cardiovascular events at 30 days were defined as follows: arrhythmias, myocardial infarction, myocarditis, and pulmonary embolism. Univariate analysis (Student's t-test or Mann-Whitney U test, as appropriate) and multivariate analysis (multinomial logistic regression) were applied to the data. A total of 394 patients were included; they were mostly males and had a median age of 65.5 years. Previous cardiovascular disease was present in 14.7% of patients. Oxygen therapy was required for 77.9%, and 53% received anticoagulant therapy. The overall 30-day mortality was 20.3%. A cardiovascular event developed in 15.7% of the subjects. These were mainly pulmonary embolism (9.4%), followed by arrhythmias (3.3%), myocardial infarction (2.3%), and myocarditis (0.8%). Patients who developed cardiovascular events upon univariate analysis were significantly older, with major comorbidities, a more compromised respiratory situation, and a higher mortality rate. Multivariate analysis revealed independent factors that were significantly associated with the development of cardiovascular events: hypertension, endotracheal intubation, and age older than 75 years. In patients with COVID-19, the development of a cardiovascular event occurs quite frequently and is mainly seen in elderly subjects with comorbidities (especially hypertension) in the presence of a severe respiratory picture., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2016 - 2021 InfezMed.)

Published
2021
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22. Oral plasmablastic lymphoma: A case report.

Author

Zizzo M, Zanelli M, Martiniani R, Sanguedolce F, De Marco L, Martino G, Parente P, Annessi V, Manzini L, and Ascani S

Subjects
Abscess diagnosis, Abscess drug therapy, Adult, Aftercare, Anti-Bacterial Agents therapeutic use, Antimetabolites, Antineoplastic administration & dosage, Antimetabolites, Antineoplastic therapeutic use, Drug Therapy, Combination, Edema etiology, HIV Infections complications, HIV Seropositivity blood, HIV-1 immunology, Humans, Injections, Spinal, Lymphoma, Non-Hodgkin pathology, Male, Methotrexate administration & dosage, Methotrexate therapeutic use, Plasma Cells pathology, Plasmablastic Lymphoma diagnostic imaging, Treatment Outcome, Antineoplastic Agents therapeutic use, Antiretroviral Therapy, Highly Active methods, Mouth pathology, Plasmablastic Lymphoma drug therapy
Abstract

Introduction: Plasmablastic lymphoma (PBL) is an uncommon and aggressive large B-cell lymphoma commonly diagnosed in human immunodeficiency viruses -positive patients. Oral cavity is the most commonly PBL affected site. Most oral PBLs presented as asymptomatic swellings, frequently associated with ulcerations and bleeding. Most cases lacked B-symptoms, suggesting a more local involvement of the disease. No standard treatment is yet for oral PBL. Five-year survival rate recorded no more than 33.5%., Patient Concerns: A 39-year-old male presented to Dental Clinic with 1 month swelling of the oral cavity, in absence of any other symptoms or signs. He followed antibiotic therapy just on suspicion of an oral abscess and later oral surgical treatment on suspicion of bone neoplasm., Diagnosis: Surgical specimen analysis highlighted a diffuse infiltrate of large-sized atypical cells with plasmablastic appearance and plasma cell phenotype. Oral cavity PBL was diagnosed. Blood tests recorded mild lymphopenia and positive human immunodeficiency viruses serology., Interventions: Patient underwent chemotherapy including intrathecal methotrexate prophylaxis, in addition to a highly active antiretroviral therapy., Outcomes: At 12 months from diagnosis, patient recorded complete hematological remission., Conclusions: Oral PBL diagnosis requires a high level of suspicion and awareness both by physicians and pathologists. They should be aware of the extent of such disease which is often mistaken as oral abscess or infected tooth, thus leading to delay the most appropriate diagnostic evaluation. As PBL is an aggressive non-Hodgkin lymphoma, a delayed diagnosis might negatively impact on both treatment and survival.

Published
2020
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24. Correction to: Management of duodenal stump fistula after gastrectomy for malignant disease: a systematic review of the literature.

Author

Zizzo M, Ugoletti L, Manzini L, Ruiz CC, Nita GE, Zanelli M, De Marco L, Besutti G, Scalzone R, Sassatelli R, Annessi V, Manenti A, and Pedrazzoli C

Abstract

Following publication of the original article [1], the authors have notified us that due to administrative reasons they would like to modify the first affiliation from.

Published
2019
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25. Management of duodenal stump fistula after gastrectomy for malignant disease: a systematic review of the literature.

Author

Zizzo M, Ugoletti L, Manzini L, Castro Ruiz C, Nita GE, Zanelli M, De Marco L, Besutti G, Scalzone R, Sassatelli R, Annessi V, Manenti A, and Pedrazzoli C

Subjects
Abdominal Abscess epidemiology, Duodenal Diseases etiology, Humans, Peritonitis epidemiology, Postoperative Complications epidemiology, Wound Healing, Gastrectomy methods, Intestinal Fistula etiology, Stomach Neoplasms surgery
Abstract

Background: Duodenal stump fistula (DSF) remains one of the most serious complications following subtotal or total gastrectomy, as it endangers patient's life. DSF is related to high mortality (16-20%) and morbidity (75%) rates. DSF-related morbidity always leads to longer hospitalization times due to medical and surgical complications such as wound infections, intra-abdominal abscesses, intra-abdominal bleeding, acute pancreatitis, acute cholecystitis, severe malnutrition, fluids and electrolytes disorders, diffuse peritonitis, and pneumonia. Our systematic review aimed at improving our understanding of such surgical complication, focusing on nonsurgical and surgical DSF management in patients undergoing gastric resection for gastric cancer., Methods: We performed a systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines. PubMed/MEDLINE, EMBASE, Scopus, Cochrane Library and Web of Science databases were used to search all related literature., Results: The 20 included articles covered an approximately 40 years-study period (1979-2017), with a total 294 patient population. DSF diagnosis occurred between the fifth and tenth postoperative day. Main DSF-related complications were sepsis, abdominal abscess, wound infection, pneumonia, and intra-abdominal bleeding. DSF treatment was divided into four categories: conservative (101 cases), endoscopic (4 cases), percutaneous (82 cases), and surgical (157 cases). Length of hospitalization was 21-39 days, ranging from 1 to 1035 days. Healing time was 19-63 days, ranging from 1 to 1035 days. DSF-related mortality rate recorded 18.7%., Conclusions: DSF is a rare but potentially lethal complication after gastrectomy for gastric cancer. Early DSF diagnosis is crucial in reducing DSF-related morbidity and mortality. Conservative and/or endoscopic/percutaneous treatments is/are the first choice. However, if the patient clinical condition worsens, surgery becomes mandatory and duodenostomy appears to be the most effective surgical procedure.

Published
2019
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26. Transmural Colonic Infarction after Routine Colonoscopy in a Young Patient without Risk Factors.

Author

Zizzo M, Castro Ruiz C, Ugoletti L, Giunta A, Bonacini S, Manzini L, Aguzzoli F, Colognesi A, and Pedrazzoli C

Abstract

Colonoscopy is one of the most widely used procedures in medical practice for the diagnosis and treatment of many benign and malignant diseases of the colorectal tract. Colonscopy has become the reference procedure for screening and surveillance of colorectal cancer. The overall rate of adverse events is estimated to be about 2.8 per 1,000 procedures, while complications requiring hospitalization are about 1.9 per 1,000 colonoscopies. Mortality from all causes and colonoscopy-specific mortality are estimated to be 0.07 and 0.007%, respectively. An exceptional fearsome postcolonoscopy complication is colon ischemia (CI); only few cases have been reported worldwide. We present the case of a 43-year-old woman who presented to the emergency department complaining of abdominal pain; fever and rectal bleeding appeared 12 h after a voluntary 'screening' colonoscopy. She had no risk factors for CI. Her laboratory tests showed alterations in inflammatory markers and a computed tomography scan showed a circumferential thickening in the left colon and free fluid in the abdomen. After 12 h of observation and conservative therapy, the clinical state of the patient worsened with the rising of signs of peritonitis. Laparoscopy showed that colon infarction extended from the distal third of the transverse colon to the proximal rectum. Laparotomy, resection of the pathological colon and terminal colostomy were performed. The specimen examined confirmed an extended ischemic colitis and transmural infarction on the antimesocolic side, in the absence of a vasculitis. The patient underwent recanalization after 8 months. CI after colonoscopy is a rare and alarming complication that must be known and taken into account in the differential diagnosis of symptomatic cases after colonoscopy, particularly in patients with known risk factors. The diagnosis is mainly based on clinical data, imaging and especially endoscopy. Treatment is almost always conservative but, in some cases in which the pathological process appears irreversible, surgery becomes mandatory.

Published
2016
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27. Experiencing brain cancer: what physicians should know about patients.

Author

Lucchiari C, Botturi A, Manzini L, Masiero M, and Pravettoni G

Abstract

Unlabelled: During the last 20 years, numerous studies have highlighted the need to consider Quality of Life (QoL) issues in the treatment of brain cancer. However, gaps in scientific knowledge are still present as we have poor data surrounding the whole experience in patients and regarding their needs. The present study was aimed at evaluating QoL in brain cancer patients and correlated aspects. In particular, we aimed to assess QoL, mood state, and emotional issues in order to describe the patients' experience to find out the critical aspects involved., Methods: We obtained data from 85 patients during chemotherapy treatment at the National Neurological Institute 'C. Besta' of Milan, Italy. We used standardised questionnaires to assess different aspects of patients' QoL. In particular, the functional assessment of cancer therapy-brain (FACT-Br) and the Hamilton scale were used. We also performed a semi-structured ad hoc interview in order to collect -narrative data about patients' experience., Results: Our data depict a difficult adjustment process to the illness, even though positive elements emerged. Indeed, patients reported a satisfying self-perceived QoL, although specific concerns are still present. Further, even if many patients report depressive symptoms, only a minority have a severe condition., Conclusion: Brain cancer may heavily affect patients' QoL and well being. However, some element of the context may improve the -adjustment to the disease. In particular, we found that most patients found psychosocial resources to cope with cancer and that spiritual well being also seems to play a key role. These issues deserve further studies in order to obtain significant clinical recommendations.

Published
2015
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28. West Nile virus outbreak in the Lombardy region, northern Italy, summer 2013.

Author

Rovida F, Sarasini A, Campanini G, Percivalle E, Gorini G, Mariani B, Pan A, Cuzzoli A, Possenti S, Manzini L, Castelli F, Bossini N, Grossi PA, Castilletti C, Calzolari M, Lelli D, Piatti A, and Baldanti F

Subjects
Animals, Female, Horses, Humans, Italy epidemiology, Male, Retrospective Studies, West Nile Fever virology, West Nile virus genetics, Birds virology, Culicidae virology, Disease Outbreaks, West Nile Fever epidemiology, West Nile virus isolation & purification
Abstract

In the summer of 2013, an outbreak of West Nile virus (WNV) infection occurred in the Lombardy, a region of northern Italy to the west of districts affected by WNV in previous years. Eighteen cases of human WNV infection were diagnosed--10 cases of acute WNV neuroinvasive disease and eight of WNV fever. In the same period, WNV was detected in birds (one crow) in horses (11 cases) and from mosquitoes (six pools).

Published
2015
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29. Constitutive expression of the AHR signaling pathway in a bovine mammary epithelial cell line and modulation by dioxin-like PCB and other AHR ligands.

Author

Girolami F, Spalenza V, Manzini L, Carletti M, and Nebbia C

Subjects
Animals, Cattle, Cell Line, Cytochrome P-450 CYP1A1 biosynthesis, Cytochrome P-450 CYP1A1 genetics, Cytochrome P-450 CYP1B1 biosynthesis, Cytochrome P-450 CYP1B1 genetics, Down-Regulation, Enzyme Induction, Epithelial Cells metabolism, Epithelial Cells pathology, Female, Glutathione Transferase genetics, Glutathione Transferase metabolism, Isoenzymes genetics, Isoenzymes metabolism, Ligands, Mammary Glands, Animal metabolism, Mammary Glands, Animal pathology, Receptors, Aryl Hydrocarbon metabolism, Time Factors, Benzo(a)pyrene toxicity, Environmental Pollutants toxicity, Epithelial Cells drug effects, Mammary Glands, Animal drug effects, Receptors, Aryl Hydrocarbon agonists, Signal Transduction drug effects, beta-Naphthoflavone toxicity
Abstract

Environmental pollutants, such as dioxin-like (DL) PCBs, benzo(a) pyrene (B[a]P), and flavonoids are aryl hydrocarbon receptor (AHR) ligands and may be excreted in dairy milk. The expression of AHR-target genes, particularly those involved in xenobiotic biotransformation, and their modulation by two DL-PCBs, B[a]P, and β-naphthoflavone was investigated in a bovine mammary epithelial cell line (BME-UV). As assessed by quantitative PCR, BME-UV cells expressed a functional AHR signaling pathway. All the AHR ligands induced a concentration-related increase in the transcription of cytochrome P450 1A1 and 1B1, known to be implicated in the bioactivation of several xenobiotics. Conversely, genes encoding for antioxidant and detoxifying enzymes, like quinone oxidoreductase or glutathione S-transferase A2, were not affected or even depressed. This study demonstrates the occurrence and the modulation by different AHR-ligands of genes involved in xenobiotic metabolism in BME-UV cells, with the potential generation of (re) active metabolites that may damage mammary tissue and/or affect animal or human health via the contaminated milk., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Published
2015
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30. T cell activation but not polyfunctionality after primary HIV infection predicts control of viral load and length of the time without therapy.

Author

Cossarizza A, Bertoncelli L, Nemes E, Lugli E, Pinti M, Nasi M, De Biasi S, Gibellini L, Montagna JP, Vecchia M, Manzini L, Meschiari M, Borghi V, Guaraldi G, and Mussini C

Subjects
Adult, Anti-HIV Agents therapeutic use, Antiretroviral Therapy, Highly Active, CD4-Positive T-Lymphocytes virology, CD8-Positive T-Lymphocytes virology, Female, HIV Infections drug therapy, HIV Infections virology, Humans, Longitudinal Studies, Male, Middle Aged, Viral Load, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, HIV Infections immunology, HIV-1 immunology, Lymphocyte Activation immunology
Abstract

Objective: Immune changes occurring after primary HIV infection (PHI) have a pivotal relevance. Our objective was to characterize the polyfunctionality of immune response triggered by PHI, and to characterize immune activation and regulatory T cells, correlating such features to disease progression., Patients and Methods: We followed 11 patients experiencing PHI for 4 years. By polychromatic flow cytometry, we studied every month, for the first 6 months, T lymphocyte polyfunctionality after cell stimulation with peptides derived from HIV-1 gag and nef. Tregs were identified by flow cytometry, and T cell activation studied by CD38 and HLA-DR expression., Results: An increase of anti-gag and anti-nef CD8+ specific T cells was observed 3 months after PHI; however, truly polyfunctional T cells, also able to produce IL-2, were never found. No gross changes in Tregs were present. T lymphocyte activation was maximal 1 and 2 months after PHI, and significantly decreased in the following period. The level of activation two months after PHI was strictly correlated to the plasma viral load 1 year after infection, and significantly influenced the length of period without therapy. Indeed, 80% of patients with less than the median value of activated CD8+ (15.5%) or CD4+ (0.9%) T cells remained free of therapy for >46 months, while all patients over the median value had to start treatment within 26 months., Conclusions: T cell activation after PHI, more than T cell polyfunctionality or Tregs, is a predictive marker for the control of viral load and for the time required to start treatment.

Published
2012
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31. Increased plasma levels of extracellular mitochondrial DNA during HIV infection: a new role for mitochondrial damage-associated molecular patterns during inflammation.

Author

Cossarizza A, Pinti M, Nasi M, Gibellini L, Manzini S, Roat E, De Biasi S, Bertoncelli L, Montagna JP, Bisi L, Manzini L, Trenti T, Borghi V, and Mussini C

Subjects
Adult, Aged, Anti-HIV Agents therapeutic use, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, CD8-Positive T-Lymphocytes pathology, Female, HIV Infections drug therapy, HIV Infections immunology, HIV Infections pathology, Humans, Inflammation metabolism, Lipopolysaccharide Receptors blood, Male, Middle Aged, Viral Load, Young Adult, DNA, Mitochondrial blood, HIV Infections blood, HIV-1 physiology
Abstract

HIV infection is characterized by a chronic inflammatory state. Recently, it has been shown that mitochondrial DNA (mtDNA) released from damaged or dead cells can bind Toll like receptor-9 (TLR9), an intracellular receptor that responds to bacterial or viral DNA molecules. The activation of TLR9 present within monocytes or neutrophils results in a potent inflammatory reaction, with the production of proinflammatory cytokines. We measured plasma levels of mtDNA in different groups of HIV(+) patients, i.e., those experiencing an acute HIV infection (AHI), long term non progressors (LTNP), late presenters (LP) taking antiretroviral therapy for the first time, and healthy controls. We found that in AHI and LP mtDNA plasma levels were significantly higher than in healthy individuals or in LTNP. Plasma mtDNA levels were not correlated to peripheral blood CD4(+) T cell count, nor to markers of immune activation, but had a significant correlation with plasma viral load, revealing a possible role for mtDNA in inflammation, or as a biomarker of virus-induced damage., (Copyright © 2011 © Elsevier B.V. and Mitochondria Research Society. All rights reserved. Published by Elsevier B.V. All rights reserved.)

Published
2011
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32. CD4+ T-cell differentiation, regulatory T cells and gag-specific T lymphocytes are unaffected by CD4-guided treatment interruption and therapy resumption.

Author

Nemes E, Lugli E, Bertoncelli L, Nasi M, Pinti M, Manzini S, Prati F, Manzini L, Del Giovane C, D'Amico R, Cossarizza A, and Mussini C

Subjects
Adult, Antiretroviral Therapy, Highly Active methods, CD4-Positive T-Lymphocytes drug effects, CD4-Positive T-Lymphocytes virology, Drug Administration Schedule, Female, Flow Cytometry, HIV Infections drug therapy, HIV Infections virology, Humans, Longitudinal Studies, Lymphocyte Activation drug effects, Male, Middle Aged, Prospective Studies, T-Lymphocytes, Regulatory drug effects, T-Lymphocytes, Regulatory virology, Viral Load, CD4-Positive T-Lymphocytes immunology, HIV Infections immunology, HIV-1 immunology, Lymphocyte Activation immunology, T-Lymphocytes, Regulatory immunology
Abstract

Objectives: Despite limiting exposure to antiretroviral drugs, structured treatment interruptions can influence multiple aspects of T-cell immunity, particularly those regarding CD4(+) T lymphocytes. We evaluated the impact of CD4-guided treatment interruption (CD4-GTI) and treatment resumption on regulatory T cells (Tregs), T-lymphocyte activation, differentiation and polyfunctional gag-specific response., Methods: Patients were analyzed just prior to treatment interruption, at 2 and 6 months after treatment interruption, just prior to treatment resumption and at 2 and 6 months after treatment resumption. Thawed peripheral blood mononuclear cells were stained immediately for phenotype analysis or stimulated with HIV-gag peptides and analyzed by polychromatic flow cytometry., Results: Treatment interruption resulted in a CD4(+) cell count decrease and plasma viral load (pVL) increase, but did not preclude a good immune reconstitution and a complete suppression of pVL after treatment resumption. Treatment interruption did not influence CD4(+) T-cell differentiation and Treg subsets. During treatment interruption, gag-specific CD4(+) T cells were not lost, although the frequency of HIV-specific CD8(+) cells increased. Most gag-specific CD4(+) T cells were potentially cytotoxic (CD107a(+)) and were not influenced by pVL or by HAART. Most helper (CD154(+)) gag-specific CD4(+) T lymphocytes did not produce interferon-γ or interleukin-2., Conclusion: CD4-GTI did not cause depletion of memory cells, Tregs or HIV-specific CD4(+) cells and, on the contrary, could induce HIV-specific responses. If guided by CD4(+) T-cell count, treatment interruption does not provoke irreversible immune damages.

Published
2011
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33. Predictive value of intracellular HIV-1 DNA levels during CD4-guided treatment interruption in HIV+ patients.

Author

Nasi M, Pinti M, Manzini S, Gibellini L, Manzini L, Bisi L, De Biasi S, Del Giovane C, D'Amico R, Borghi V, Mussini C, and Cossarizza A

Subjects
Adult, CD4 Lymphocyte Count, DNA, Viral genetics, DNA, Viral isolation & purification, Drug Administration Schedule, Female, HIV Infections virology, HIV-1 genetics, Humans, Male, Middle Aged, Predictive Value of Tests, Treatment Outcome, Anti-HIV Agents administration & dosage, Anti-HIV Agents therapeutic use, CD4-Positive T-Lymphocytes virology, DNA, Viral blood, HIV Infections drug therapy, HIV Infections immunology, HIV-1 drug effects
Abstract

The amount of HIV-1 DNA within peripheral blood mononuclear cells is an important marker of viral activity. We studied intracellular HIV-1 DNA content in purified CD4(+) T cells from 28 chronically HIV-1-infected adults with sustained CD4(+) T cell counts (>500 cells/microl) and undetectable plasma viral load (<50 copies/ml), who underwent CD4-guided treatment interruption (TI). Patients were followed up for 18 months during TI, and for 6 months after treatment resumption (TR). Six naïve HIV(+) patients starting therapy were also enrolled and followed up for 6 months. All patients were studied every 2 months; HIV-1 DNA copy number was quantified with real-time PCR. Considering all patients remaining off-treatment, in the first 18 months of TI, intracellular HIV-1 DNA levels (expressed as Log(10) copies/million cells) remained stable (mean, 3.82 and 3.77 at time 0 and after 18 months, respectively). Similarly, HIV-1 DNA values, either in patients who restarted treatment after TI (time 0, 4.90) or in naïve patients who started treatment for the first time (time 0, 4.37), did not change significantly in the first 6 months of therapy (4.42 and 3.67, respectively). Evaluating HIV-1 DNA variations during the first 2 months of TI, we found that patients with a stable level had a lower risk to reach a CD4(+) T cell count <350 cells/microl, and thus to restart therapy, whereas this risk was significantly higher in those with a marked increase of HIV-1 DNA. In conclusion, intracellular HIV-1 DNA is a predictive marker for the length of CD4-guided TI.

Published
2010
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34. Cytotoxic granule release dominates gag-specific CD4+ T-cell response in different phases of HIV infection.

Author

Nemes E, Bertoncelli L, Lugli E, Pinti M, Nasi M, Manzini L, Manzini S, Prati F, Borghi V, Cossarizza A, and Mussini C

Subjects
Adult, Aged, Blotting, Western, Female, Flow Cytometry, Gene Products, gag metabolism, Humans, Immunity, Cellular, Male, Middle Aged, Viral Load, Young Adult, CD4-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes metabolism, Cytotoxicity, Immunologic immunology, Gene Products, gag immunology, HIV Infections immunology, HIV-1 immunology
Abstract

Background: The activity of virus-specific T lymphocytes, among which those capable of a polyfunctional response against the viral protein gag, is crucial to control HIV infection., Objective: The objective of this study is to investigate the polyfunctionality of gag-specific T cells in different phases of HIV infection, analyzing markers related to T-helper cell 1 (Th1) and degranulation/cytotoxicity, and the production of Th1 cytokines in peripheral blood lymphocytes from patients experiencing an acute primary infection, long-term nonprogressors, patients naive for antiretroviral drugs, and patients taking HAART., Materials and Methods: Cells were stimulated with a pool of gag-derived peptides or with a superantigen (staphylococcal enterotoxin B). Using eight-color polychromatic flow cytometry, we analyzed the expression of interleukin-2, interferon-gamma, CD154, and CD107a by CD4 and CD8 T cells., Results: The main finding was that in all HIV-positive patients, about half gag-specific CD4 T cells were CD107a, that is, able to degranulate. CD4CD154 cells unable to produce Th1 cytokines were the second most represented population. Truly polyfunctional CD4 T cells were very rare and present only in a few long-term nonprogressors. Superantigen stimulation showed that CD4 T lymphocytes from all patients displayed a typical Th response, including interleukin-2 and interferon-gamma production, lacking CD107a expression., Conclusion: In all the aforementioned phases of HIV infection, the large majority of gag-specific CD4 T lymphocytes cannot be identified by the sole expression of interleukin-2 and interferon-gamma, which is early impaired. Degranulation and helper functions other than Th1 cytokine production are the predominant features of HIV-specific CD4 lymphocytes.

Published
2010
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35. [Invasive, non-surgical treatment of post-traumatic pancreatic pseudocyst. Report of a clinical case].

Author

Sinibaldi G, Ferrari G, Manzini L, and Pattaccini P

Subjects
Adolescent, Female, Humans, Pancreas injuries, Pancreatic Pseudocyst etiology, Drainage, Pancreatic Pseudocyst therapy
Abstract

The authors report on a pancreatic post-traumatic pseudocyst treated by a percutaneous drainage under ultrasonographic control, with a good outcome. The introduction in the past decade of new endoscopic techniques and interventional radiology, has increased the opportunity of treatment for pancreatic pseudocyst.

Published
1996

36. [New diagnostic and therapeutic prospects in peripheral nodules of the lung: surgical video thoracoscopy].

Author

Annessi V, Sgarbi G, Piccinini G, Ferrari G, Manzini L, and Lodini V

Subjects
Anesthesia, General, Female, Humans, Male, Television, Thoracoscopy methods, Lung Neoplasms diagnosis, Lung Neoplasms surgery, Thoracoscopy trends
Abstract

The new findings and results of laparoscopic surgery lead us to apply this technique in thoracic surgery. Thoracoscopy is an old diagnostic procedure, but advanced imaging techniques, improved optics and new classes of instrument have paved the way for many diagnostic and therapeutic approaches, before not feasible. Now it is possible to treat spontaneous pneumothorax, removal of mediastinal and peripheral tumors, with minimally invasive surgery. It is our belief that thoracoscopic surgery will be a valuable tool in the near future for a variety of chest disorders.

Published
1993

37. [The Roux loop syndrome: a postgastrectomy syndrome. Description of 2 clinical cases].

Author

Sinibaldi G, Manzini L, Manicardi L, and Sgarbi G

Subjects
Diagnosis, Differential, Female, Humans, Anastomosis, Roux-en-Y adverse effects, Postgastrectomy Syndromes diagnosis, Postgastrectomy Syndromes etiology
Abstract

The Roux-En-Y operation has been used to control enterogastric reflux occurring after previous distal gastric resection and it has been used extensively in the treatment of alkaline reflux. Recently a postgastrectomy syndrome characterized by chronic abdominal pain, persistent nausea and vomiting that is exacerbated by eating and that develops after the Roux-En-Y operation has been described. It has therefore been postulated that the Roux-En-Y limb acts as a functional obstruction and causes the symptoms.

Published
1992

38. [Treatment of perforation of the cervical esophagus during diagnostic endoscopy].

Author

Sinibaldi G, Piccinini G, Manzini L, and Mortilla MG

Subjects
Aged, Aged, 80 and over, Anti-Bacterial Agents therapeutic use, Drainage, Esophageal Perforation surgery, Esophageal Perforation therapy, Female, Humans, Male, Middle Aged, Endoscopy adverse effects, Esophageal Perforation etiology
Abstract

Early diagnosis of esophageal perforation is critical. We believe that the treatment of each case must be individualized. The management of perforation in our series has been "conservative" in two cases, for small perforations; and "operative", suture closure and drainage, in the remainder, for a large perforation with contamination of the mediastinum.

Published
1991

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