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1. AFP score and metroticket 2.0 perform similarly and could be used in a “within-ALL” clinical decision tool

Author

Piñero, F, Costentin, C, Degroote, H, Notarpaolo, A, Boin, I, Boudjema, K, Baccaro, C, Chagas, A, Bachellier, P, Ettorre, G, Poniachik, J, Muscari, F, Dibenedetto, F, Duque, S, Salame, E, Cillo, U, Marciano, S, Vanlemmens, C, Fagiuoli, S, Carrilho, F, Cherqui, D, Burra, P, Van Vlierberghe, H, Lai, Q, Silva, M, Rubinstein, F, Duvoux, C, Conti, F, Scatton, O, Bernard, P, Francoz, C, Durand, F, Dharancy, S, Woehl, M, Laurent, A, Radenne, S, Dumortier, J, Abergel, A, Barbier, L, Houssel-Debry, P, Pageaux, G, Chiche, L, Deledinghen, V, Hardwigsen, J, Gugenheim, J, Altieri, M, Hilleret, M, Decaens, T, Costa, P, de Ataide, E, Quiñones, E, Anders, M, Varón, A, Zerega, A, Soza, A, Machaca, M, Arufe, D, Menéndez, J, Zapata, R, Vilatoba, M, Muñoz, L, Menéndez, R, Maraschio, M, Podestá, L, Mccormack, L, Mattera, J, Gadano, A, Parente García, J, Magini, G, Miglioresi, L, Gambato, M, D'Ambrosio, C, Vitale, A, Colledan, M, Pinelli, D, Magistri, P, Vennarecci, G, Colasanti, M, Giannelli, V, Pellicelli, A, Eduard, C, Samuele, I, Jeroen, D, Jonas, S, Jacques, P, Chris, V, Dirk, Y, Peter, M, Valerio, L, Christophe, M, Olivier, D, Jean, D, Roberto, T, Paul, L, Piñero F., Costentin C., Degroote H., Notarpaolo A., Boin I. F., Boudjema K., Baccaro C., Chagas A., Bachellier P., Ettorre G. M., Poniachik J., Muscari F., Dibenedetto F., Duque S. H., Salame E., Cillo U., Marciano S., Vanlemmens C., Fagiuoli S., Carrilho F., Cherqui D., Burra P., Van Vlierberghe H., Lai Q., Silva M., Rubinstein F., Duvoux C., Conti F., Scatton O., Bernard P. H., Francoz C., Durand F., Dharancy S., Woehl M. l., Laurent A., Radenne S., Dumortier J., Abergel A., Barbier L., Houssel-Debry P., Pageaux G. P., Chiche L., Deledinghen V., Hardwigsen J., Gugenheim J., altieri M., Hilleret M. N., Decaens T., Costa P., de Ataide E. C., Quiñones E., Anders M., Varón A., Zerega A., Soza A., Machaca M. P., Arufe D., Menéndez J., Zapata R., Vilatoba M., Muñoz L., Menéndez R. C., Maraschio M., Podestá L. G., McCormack L., Mattera J., Gadano A., Parente García J. H., Magini G., Miglioresi L., Gambato M., D'Ambrosio C., Vitale A., Colledan M., Pinelli D., Magistri P., Vennarecci G., Colasanti M., Giannelli V., Pellicelli A., Eduard C., Samuele I., Jeroen D., Jonas S., Jacques P., Chris V., Dirk Y., Peter M., Valerio L., Christophe M., Olivier D., Jean D., Roberto T., Paul L. J., Piñero, F, Costentin, C, Degroote, H, Notarpaolo, A, Boin, I, Boudjema, K, Baccaro, C, Chagas, A, Bachellier, P, Ettorre, G, Poniachik, J, Muscari, F, Dibenedetto, F, Duque, S, Salame, E, Cillo, U, Marciano, S, Vanlemmens, C, Fagiuoli, S, Carrilho, F, Cherqui, D, Burra, P, Van Vlierberghe, H, Lai, Q, Silva, M, Rubinstein, F, Duvoux, C, Conti, F, Scatton, O, Bernard, P, Francoz, C, Durand, F, Dharancy, S, Woehl, M, Laurent, A, Radenne, S, Dumortier, J, Abergel, A, Barbier, L, Houssel-Debry, P, Pageaux, G, Chiche, L, Deledinghen, V, Hardwigsen, J, Gugenheim, J, Altieri, M, Hilleret, M, Decaens, T, Costa, P, de Ataide, E, Quiñones, E, Anders, M, Varón, A, Zerega, A, Soza, A, Machaca, M, Arufe, D, Menéndez, J, Zapata, R, Vilatoba, M, Muñoz, L, Menéndez, R, Maraschio, M, Podestá, L, Mccormack, L, Mattera, J, Gadano, A, Parente García, J, Magini, G, Miglioresi, L, Gambato, M, D'Ambrosio, C, Vitale, A, Colledan, M, Pinelli, D, Magistri, P, Vennarecci, G, Colasanti, M, Giannelli, V, Pellicelli, A, Eduard, C, Samuele, I, Jeroen, D, Jonas, S, Jacques, P, Chris, V, Dirk, Y, Peter, M, Valerio, L, Christophe, M, Olivier, D, Jean, D, Roberto, T, Paul, L, Piñero F., Costentin C., Degroote H., Notarpaolo A., Boin I. F., Boudjema K., Baccaro C., Chagas A., Bachellier P., Ettorre G. M., Poniachik J., Muscari F., Dibenedetto F., Duque S. H., Salame E., Cillo U., Marciano S., Vanlemmens C., Fagiuoli S., Carrilho F., Cherqui D., Burra P., Van Vlierberghe H., Lai Q., Silva M., Rubinstein F., Duvoux C., Conti F., Scatton O., Bernard P. H., Francoz C., Durand F., Dharancy S., Woehl M. l., Laurent A., Radenne S., Dumortier J., Abergel A., Barbier L., Houssel-Debry P., Pageaux G. P., Chiche L., Deledinghen V., Hardwigsen J., Gugenheim J., altieri M., Hilleret M. N., Decaens T., Costa P., de Ataide E. C., Quiñones E., Anders M., Varón A., Zerega A., Soza A., Machaca M. P., Arufe D., Menéndez J., Zapata R., Vilatoba M., Muñoz L., Menéndez R. C., Maraschio M., Podestá L. G., McCormack L., Mattera J., Gadano A., Parente García J. H., Magini G., Miglioresi L., Gambato M., D'Ambrosio C., Vitale A., Colledan M., Pinelli D., Magistri P., Vennarecci G., Colasanti M., Giannelli V., Pellicelli A., Eduard C., Samuele I., Jeroen D., Jonas S., Jacques P., Chris V., Dirk Y., Peter M., Valerio L., Christophe M., Olivier D., Jean D., Roberto T., and Paul L. J.

Abstract

Background & Aims: Two recently developed composite models, the alpha-fetoprotein (AFP) score and Metroticket 2.0, could be used to select patients with hepatocellular carcinoma (HCC) who are candidates for liver transplantation (LT). The aim of this study was to compare the predictive performance of both models and to evaluate the net risk reclassification of post-LT recurrence between them using each model's original thresholds. Methods: This multicenter cohort study included 2,444 adult patients who underwent LT for HCC in 47 centers from Europe and Latin America. A competing risk regression analysis estimating sub-distribution hazard ratios (SHRs) and 95% CIs for recurrence was used (Fine and Gray method). Harrell's adapted c-statistics were estimated. The net reclassification index for recurrence was compared based on each model's original thresholds. Results: During a median follow-up of 3.8 years, there were 310 recurrences and 496 competing events (20.3%). Both models predicted recurrence, HCC survival and survival better than Milan criteria (p <0.0001). At last tumor reassessment before LT, c-statistics did not significantly differ between the two composite models, either as original or threshold versions, for recurrence (0.72 vs. 0.68; p = 0.06), HCC survival, and overall survival after LT. We observed predictive gaps and overlaps between the model's thresholds, and no significant gain on reclassification. Patients meeting both models (“within-ALL”) at last tumor reassessment presented the lowest 5-year cumulative incidence of HCC recurrence (7.7%; 95% CI 5.1-11.5) and higher 5-year post-LT survival (70.0%; 95% CI 64.9-74.6). Conclusions: In this multicenter cohort, Metroticket 2.0 and the AFP score demonstrated a similar ability to predict HCC recurrence post-LT. The combination of these composite models might be a promising clinical approach. Impact and implications: Composite models were recently proposed for the selection of liver transplant (LT

Published
2023

3. R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation

Author

Costentin, C, Piñero, F, Degroote, H, Notarpaolo, A, Boin, I, Boudjema, K, Baccaro, C, Podestá, L, Bachellier, P, Ettorre, G, Poniachik, J, Muscari, F, Dibenedetto, F, Hoyos Duque, S, Salame, E, Cillo, U, Marciano, S, Vanlemmens, C, Fagiuoli, S, Burra, P, Van Vlierberghe, H, Cherqui, D, Lai, Q, Silva, M, Rubinstein, F, Duvoux, C, Conti, F, Scatton, O, Bernard, P, Francoz, C, Durand, F, Dharancy, S, Woehl, M, Laurent, A, Radenne, S, Dumortier, J, Abergel, A, Barbier, L, Houssel-Debry, P, Pageaux, G, Chiche, L, Deledinghen, V, Hardwigsen, J, Gugenheim, J, Altieri, M, Hilleret, M, Decaens, T, Chagas, A, Costa, P, Cristina de Ataide, E, Quiñones, E, Duque, S, Anders, M, Varón, A, Zerega, A, Soza, A, Machaca, M, Arufe, D, Menéndez, J, Zapata, R, Vilatoba, M, Muñoz, L, Menéndez, R, Maraschio, M, Mccormack, L, Mattera, J, Gadano, A, Fatima Boin, I, Parente García, J, Carrilho, F, Magini, G, Miglioresi, L, Gambato, M, Benedetto, F, D’Ambrosio, C, Vitale, A, Colledan, M, Pinelli, D, Magistri, P, Vennarecci, G, Colasanti, M, Giannelli, V, Pellicelli, A, Vlierberghe, H, Eduard, C, Samuele, I, Jeroen, D, Jonas, S, Jacques, P, Chris, V, Dirk, Y, Peter, M, Valerio, L, Christophe, M, Olivier, D, Jean, D, Roberto, T, Paul, L, Costentin, Charlotte, Piñero, Federico, Degroote, Helena, Notarpaolo, Andrea, Boin, Ilka F., Boudjema, Karim, Baccaro, Cinzia, Podestá, Luis G., Bachellier, Philippe, Ettorre, Giuseppe Maria, Poniachik, Jaime, Muscari, Fabrice, Dibenedetto, Fabrizio, Hoyos Duque, Sergio, Salame, Ephrem, Cillo, Umberto, Marciano, Sebastian, Vanlemmens, Claire, Fagiuoli, Stefano, Burra, Patrizia, Van Vlierberghe, Hans, Cherqui, Daniel, Lai, Quirino, Silva, Marcelo, Rubinstein, Fernando, Duvoux, Christophe, Conti, Filomena, Scatton, Olivier, Bernard, Pierre Henri, Francoz, Claire, Durand, Francois, Dharancy, Sébastien, Woehl, Marie-lorraine., Laurent, Alexis, Radenne, Sylvie, Dumortier, Jérôme, Abergel, Armand, Barbier, Louise, Houssel-Debry, Pauline, Pageaux, Georges Philippe, Chiche, Laurence, Deledinghen, Victor, Hardwigsen, Jean, Gugenheim, J., altieri, M., Hilleret, Marie Noelle, Decaens, Thomas, Chagas, Aline, Costa, Paulo, Cristina de Ataide, Elaine, Quiñones, Emilio, Duque, Sergio Hoyos, Marciano, Sebastián, Anders, Margarita, Varón, Adriana, Zerega, Alina, Soza, Alejandro, Machaca, Martín Padilla, Arufe, Diego, Menéndez, Josemaría, Zapata, Rodrigo, Vilatoba, Mario, Muñoz, Linda, Menéndez, Ricardo Chong, Maraschio, Martín, McCormack, Lucas, Mattera, Juan, Gadano, Adrian, Fatima Boin, Ilka SF., Parente García, Jose Huygens, Carrilho, Flair, Magini, Giulia, Miglioresi, Lucia, Gambato, Martina, Benedetto, Fabrizio Di, D’Ambrosio, Cecilia, Vitale, Alessandro, Colledan, Michele, Pinelli, Domenico, Magistri, Paolo, Vennarecci, Giovanni, Colasanti, Marco, Giannelli, Valerio, Pellicelli, Adriano, Baccaro, Cizia, Vlierberghe, Hans Van, Eduard, Callebout, Samuele, Iesari, Jeroen, Dekervel, Jonas, Schreiber, Jacques, Pirenne, Chris, Verslype, Dirk, Ysebaert, Peter, Michielsen, Valerio, Lucidi, Christophe, Moreno, Olivier, Detry, Jean, Delwaide, Roberto, Troisi, Paul, Lerut Jan, Costentin, C, Piñero, F, Degroote, H, Notarpaolo, A, Boin, I, Boudjema, K, Baccaro, C, Podestá, L, Bachellier, P, Ettorre, G, Poniachik, J, Muscari, F, Dibenedetto, F, Hoyos Duque, S, Salame, E, Cillo, U, Marciano, S, Vanlemmens, C, Fagiuoli, S, Burra, P, Van Vlierberghe, H, Cherqui, D, Lai, Q, Silva, M, Rubinstein, F, Duvoux, C, Conti, F, Scatton, O, Bernard, P, Francoz, C, Durand, F, Dharancy, S, Woehl, M, Laurent, A, Radenne, S, Dumortier, J, Abergel, A, Barbier, L, Houssel-Debry, P, Pageaux, G, Chiche, L, Deledinghen, V, Hardwigsen, J, Gugenheim, J, Altieri, M, Hilleret, M, Decaens, T, Chagas, A, Costa, P, Cristina de Ataide, E, Quiñones, E, Duque, S, Anders, M, Varón, A, Zerega, A, Soza, A, Machaca, M, Arufe, D, Menéndez, J, Zapata, R, Vilatoba, M, Muñoz, L, Menéndez, R, Maraschio, M, Mccormack, L, Mattera, J, Gadano, A, Fatima Boin, I, Parente García, J, Carrilho, F, Magini, G, Miglioresi, L, Gambato, M, Benedetto, F, D’Ambrosio, C, Vitale, A, Colledan, M, Pinelli, D, Magistri, P, Vennarecci, G, Colasanti, M, Giannelli, V, Pellicelli, A, Vlierberghe, H, Eduard, C, Samuele, I, Jeroen, D, Jonas, S, Jacques, P, Chris, V, Dirk, Y, Peter, M, Valerio, L, Christophe, M, Olivier, D, Jean, D, Roberto, T, Paul, L, Costentin, Charlotte, Piñero, Federico, Degroote, Helena, Notarpaolo, Andrea, Boin, Ilka F., Boudjema, Karim, Baccaro, Cinzia, Podestá, Luis G., Bachellier, Philippe, Ettorre, Giuseppe Maria, Poniachik, Jaime, Muscari, Fabrice, Dibenedetto, Fabrizio, Hoyos Duque, Sergio, Salame, Ephrem, Cillo, Umberto, Marciano, Sebastian, Vanlemmens, Claire, Fagiuoli, Stefano, Burra, Patrizia, Van Vlierberghe, Hans, Cherqui, Daniel, Lai, Quirino, Silva, Marcelo, Rubinstein, Fernando, Duvoux, Christophe, Conti, Filomena, Scatton, Olivier, Bernard, Pierre Henri, Francoz, Claire, Durand, Francois, Dharancy, Sébastien, Woehl, Marie-lorraine., Laurent, Alexis, Radenne, Sylvie, Dumortier, Jérôme, Abergel, Armand, Barbier, Louise, Houssel-Debry, Pauline, Pageaux, Georges Philippe, Chiche, Laurence, Deledinghen, Victor, Hardwigsen, Jean, Gugenheim, J., altieri, M., Hilleret, Marie Noelle, Decaens, Thomas, Chagas, Aline, Costa, Paulo, Cristina de Ataide, Elaine, Quiñones, Emilio, Duque, Sergio Hoyos, Marciano, Sebastián, Anders, Margarita, Varón, Adriana, Zerega, Alina, Soza, Alejandro, Machaca, Martín Padilla, Arufe, Diego, Menéndez, Josemaría, Zapata, Rodrigo, Vilatoba, Mario, Muñoz, Linda, Menéndez, Ricardo Chong, Maraschio, Martín, McCormack, Lucas, Mattera, Juan, Gadano, Adrian, Fatima Boin, Ilka SF., Parente García, Jose Huygens, Carrilho, Flair, Magini, Giulia, Miglioresi, Lucia, Gambato, Martina, Benedetto, Fabrizio Di, D’Ambrosio, Cecilia, Vitale, Alessandro, Colledan, Michele, Pinelli, Domenico, Magistri, Paolo, Vennarecci, Giovanni, Colasanti, Marco, Giannelli, Valerio, Pellicelli, Adriano, Baccaro, Cizia, Vlierberghe, Hans Van, Eduard, Callebout, Samuele, Iesari, Jeroen, Dekervel, Jonas, Schreiber, Jacques, Pirenne, Chris, Verslype, Dirk, Ysebaert, Peter, Michielsen, Valerio, Lucidi, Christophe, Moreno, Olivier, Detry, Jean, Delwaide, Roberto, Troisi, and Paul, Lerut Jan

Abstract

Background & Aims: Patients with hepatocellular carcinoma (HCC) are selected for liver transplantation (LT) based on pre-LT imaging ± alpha-foetoprotein (AFP) level, but discrepancies between pre-LT tumour assessment and explant are frequent. Our aim was to design an explant-based recurrence risk reassessment score to refine prediction of recurrence after LT and provide a framework to guide post-LT management. Methods: Adult patients who underwent transplantation between 2000 and 2018 for HCC in 47 centres were included. A prediction model for recurrence was developed using competing-risk regression analysis in a European training cohort (TC; n = 1,359) and tested in a Latin American validation cohort (VC; n=1,085). Results: In the TC, 76.4% of patients with HCC met the Milan criteria, and 89.9% had an AFP score of ≤2 points. The recurrence risk reassessment (R3)-AFP model was designed based on variables independently associated with recurrence in the TC (with associated weights): ≥4 nodules (sub-distribution of hazard ratio [SHR] = 1.88, 1 point), size of largest nodule (3–6 cm: SHR = 1.83, 1 point; >6 cm: SHR = 5.82, 5 points), presence of microvascular invasion (MVI; SHR = 2.69, 2 points), nuclear grade >II (SHR = 1.20, 1 point), and last pre-LT AFP value (101–1,000 ng/ml: SHR = 1.57, 1 point; >1,000 ng/ml: SHR = 2.83, 2 points). Wolber's c-index was 0.76 (95% CI 0.72–0.80), significantly superior to an R3 model without AFP (0.75; 95% CI 0.72–0.79; p = 0.01). Four 5-year recurrence risk categories were identified: very low (score = 0; 5.5%), low (1–2 points; 15.1%), high (3–6 points; 39.1%), and very high (>6 points; 73.9%). The R3-AFP score performed well in the VC (Wolber's c-index of 0.78; 95% CI 0.73–0.83). Conclusions: The R3 score including the last pre-LT AFP value (R3-AFP score) provides a user-friendly, standardised framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials for HCC not limited to the Milan

Published
2022

4. Reassessment of the risk of recurrence (R3) after liver transplantation for HCC: validation of the R3 score and comparison with existing models

Author

Costentin, C, Pinero, F, Degroote, H, Notarpaolo, A, Boin, I, Boudjema, K, Baccaro, C, Podesta, L, Bachellier, P, Ettorre, GM, Poniachik, J, Muscari, F, Dibenedetto, F, Duque, SH, Salame, E, Cillo, U, Gadano, A, Vanlemmens, C, Fagiuoli, S, Rubinstein, F, Burra, P, Van Vlierberghe, H, Cherqui, D, Silva, M, Duvoux, C, Costentin, C, Pinero, F, Degroote, H, Notarpaolo, A, Boin, I, Boudjema, K, Baccaro, C, Podesta, L, Bachellier, P, Ettorre, G, Poniachik, J, Muscari, F, Dibenedetto, F, Duque, S, Salame, E, Cillo, U, Gadano, A, Vanlemmens, C, Fagiuoli, S, Rubinstein, F, Burra, P, Van Vlierberghe, H, Cherqui, D, Silva, M, and Duvoux, C

Subjects
Cirrhosi, liver transplantation, alfa FP, HCC
Published
2021

6. Intermittent inflow occlusion in living liver donors: impact on safety and remnant function

Author

Miller CM, Masetti M, Cautero N, DiBenedetto F, Lauro A, Romano A, Quintini C, Siniscalchi A, Begliomini B, PINNA, ANTONIO DANIELE, Miller CM, Masetti M, Cautero N, DiBenedetto F, Lauro A, Romano A, Quintini C, Siniscalchi A, Begliomini B, and Pinna AD

Subjects
LIVER TRANSPLANTATION
Abstract

Clamping of the portal triad accomplishes complete inflow occlusion. This maneuver is commonly used during liver surgery to minimize blood loss but is not widely used in living donors undergoing resection for liver transplantation. We compared outcomes in living donors who underwent resection with and without inflow occlusion. We reviewed data on 2 nonsimultaneous living liver donor cohorts. The first 20 donors (group 1) underwent resection without inflow occlusion. In the next 15 donors (group 2), inflow occlusion was used during parenchymal transection, using cycles of 10-15 minutes occlusion and 6 minutes reperfusion. In donors, we recorded type of resection; ischemia times; blood loss; transfusions; peak ALT, AST, bilirubin, and INR in the first 5 days; hospital length of stay (LOS), and major complications. In recipients, we recorded peak ALT. In group 1, 19 of 20 donors underwent right hepatectomy. In group 2, 8 donors underwent right hepatectomy, and 7 donors had left lobectomies. Total ischemic time ranged from 16-49 minutes (mean, 31 +/- 9 minutes). In group 1, two donors received a total of 5 U of allogeneic blood. In group 2, no donor required transfusion. Mean peak ALT was significantly higher in group 1 (521 +/- 336 U/L) than group 2 (322 +/- 162 U/L; P = 0.03). Mean INR was significantly higher in group 1 (1.8 +/- 0.2) vs. group 2 (1.5 +/- 0.2; P = 0.001). There were 4 major complications in group 1 (incisional hernia, transient liver failure, biliary stricture, and biliary leak) and no major intraoperative or postoperative complications in group 2. Mean LOS was significantly longer in group 1 (7.9 +/- 2.9 days) than group 2 (6.2 +/- 1.1 days; P = 0.04). Mean peak ALT in recipients trended lower in group 2. In conclusion, inflow occlusion was associated with reduced blood loss and less ischemic injury to hepatic remnants in the donors and the grafts in the recipients. These benefits were associated with a diminished incidence of major complications and shorter LOS. Inflow occlusion should be an essential part of living donor hepatectomy.

Published
2004

7. Intermittent inflow occlusion in living liver donors: impact on safety and remnant function

Author

Miller, C. M., Masetti, M., Cautero, N., Dibenedetto, F., Lauro, A., Romano, A., Quintini, C., Siniscalchi, A., Begliomini, B., and Pinna, A. D.

Subjects
Adult, Male, living liver donors, inflow occlusion, Alanine Transaminase, Aspartate Aminotransferases, Blood Loss, Surgical, Constriction, Female, Hepatectomy, Humans, Length of Stay, Postoperative Period, Safety, Liver Transplantation, Living Donors, Portal System, Surgical, Blood Loss
Abstract

Clamping of the portal triad accomplishes complete inflow occlusion. This maneuver is commonly used during liver surgery to minimize blood loss but is not widely used in living donors undergoing resection for liver transplantation. We compared outcomes in living donors who underwent resection with and without inflow occlusion. We reviewed data on 2 nonsimultaneous living liver donor cohorts. The first 20 donors (group 1) underwent resection without inflow occlusion. In the next 15 donors (group 2), inflow occlusion was used during parenchymal transection, using cycles of 10-15 minutes occlusion and 6 minutes reperfusion. In donors, we recorded type of resection; ischemia times; blood loss; transfusions; peak ALT, AST, bilirubin, and INR in the first 5 days; hospital length of stay (LOS), and major complications. In recipients, we recorded peak ALT. In group 1, 19 of 20 donors underwent right hepatectomy. In group 2, 8 donors underwent right hepatectomy, and 7 donors had left lobectomies. Total ischemic time ranged from 16-49 minutes (mean, 31 +/- 9 minutes). In group 1, two donors received a total of 5 U of allogeneic blood. In group 2, no donor required transfusion. Mean peak ALT was significantly higher in group 1 (521 +/- 336 U/L) than group 2 (322 +/- 162 U/L; P = 0.03). Mean INR was significantly higher in group 1 (1.8 +/- 0.2) vs. group 2 (1.5 +/- 0.2; P = 0.001). There were 4 major complications in group 1 (incisional hernia, transient liver failure, biliary stricture, and biliary leak) and no major intraoperative or postoperative complications in group 2. Mean LOS was significantly longer in group 1 (7.9 +/- 2.9 days) than group 2 (6.2 +/- 1.1 days; P = 0.04). Mean peak ALT in recipients trended lower in group 2. In conclusion, inflow occlusion was associated with reduced blood loss and less ischemic injury to hepatic remnants in the donors and the grafts in the recipients. These benefits were associated with a diminished incidence of major complications and shorter LOS. Inflow occlusion should be an essential part of living donor hepatectomy.

Published
2004

9. A possible mechanism for the capture of microparticles by the earth and other planets of the solar system

Author

Dibenedetto, F

Subjects
Space Sciences
Abstract

By application of Lyttleton's theory for the formation of comets, it is shown that a possible mechanism for the origin and formation of a concentration of cosmic particles around the earth and the other planets of the solar system exists. In the vicinity of the neutral point, where the velocity of colliding particles is not greater than 6 km/s, it is found that if the solid particles after collision must remain in a solid state, there can be no possibility of accretion for Mercury, Mars, and the Moon, where the maximum value of the distance of the center of the planet to the asymptotic trajectory is less than the radius of the planet. On the other hand, the capture radii of microparticles in solid form varies from a minimum of 2.95 planetary radii for Venus and 3.47 for the Earth, to about 986 for Jupiter.

Published
1973

16. AFP score and metroticket 2.0 perform similarly and could be used in a 'within-ALL' clinical decision tool

Author

Federico Piñero, Charlotte Costentin, Helena Degroote, Andrea Notarpaolo, Ilka FSF. Boin, Karim Boudjema, Cinzia Baccaro, Aline Chagas, Philippe Bachellier, Giuseppe Maria Ettorre, Jaime Poniachik, Fabrice Muscari, Fabrizio Dibenedetto, Sergio Hoyos Duque, Ephrem Salame, Umberto Cillo, Sebastián Marciano, Claire Vanlemmens, Stefano Fagiuoli, Flair Carrilho, Daniel Cherqui, Patrizia Burra, Hans Van Vlierberghe, Quirino Lai, Marcelo Silva, Fernando Rubinstein, Christophe Duvoux, Filomena Conti, Olivier Scatton, Pierre Henri Bernard, Claire Francoz, Francois Durand, Sébastien Dharancy, Marie-lorraine Woehl, Alexis Laurent, Sylvie Radenne, Jérôme Dumortier, Armand Abergel, Louise Barbier, Pauline Houssel-Debry, Georges Philippe Pageaux, Laurence Chiche, Victor Deledinghen, Jean Hardwigsen, J. Gugenheim, M. altieri, Marie Noelle Hilleret, Thomas Decaens, Paulo Costa, Elaine Cristina de Ataide, Emilio Quiñones, Margarita Anders, Adriana Varón, Alina Zerega, Alejandro Soza, Martín Padilla Machaca, Diego Arufe, Josemaría Menéndez, Rodrigo Zapata, Mario Vilatoba, Linda Muñoz, Ricardo Chong Menéndez, Martín Maraschio, Luis G. Podestá, Lucas McCormack, Juan Mattera, Adrian Gadano, Jose Huygens Parente García, Giulia Magini, Lucia Miglioresi, Martina Gambato, Cecilia D’Ambrosio, Alessandro Vitale, Michele Colledan, Domenico Pinelli, Paolo Magistri, Giovanni Vennarecci, Marco Colasanti, Valerio Giannelli, Adriano Pellicelli, Callebout Eduard, Iesari Samuele, Dekervel Jeroen, Schreiber Jonas, Pirenne Jacques, Verslype Chris, Ysebaert Dirk, Michielsen Peter, Lucidi Valerio, Moreno Christophe, Detry Olivier, Delwaide Jean, Troisi Roberto, Lerut Jan Paul, Piñero, F, Costentin, C, Degroote, H, Notarpaolo, A, Boin, I, Boudjema, K, Baccaro, C, Chagas, A, Bachellier, P, Ettorre, G, Poniachik, J, Muscari, F, Dibenedetto, F, Duque, S, Salame, E, Cillo, U, Marciano, S, Vanlemmens, C, Fagiuoli, S, Carrilho, F, Cherqui, D, Burra, P, Van Vlierberghe, H, Lai, Q, Silva, M, Rubinstein, F, Duvoux, C, Conti, F, Scatton, O, Bernard, P, Francoz, C, Durand, F, Dharancy, S, Woehl, M, Laurent, A, Radenne, S, Dumortier, J, Abergel, A, Barbier, L, Houssel-Debry, P, Pageaux, G, Chiche, L, Deledinghen, V, Hardwigsen, J, Gugenheim, J, Altieri, M, Hilleret, M, Decaens, T, Costa, P, de Ataide, E, Quiñones, E, Anders, M, Varón, A, Zerega, A, Soza, A, Machaca, M, Arufe, D, Menéndez, J, Zapata, R, Vilatoba, M, Muñoz, L, Menéndez, R, Maraschio, M, Podestá, L, Mccormack, L, Mattera, J, Gadano, A, Parente García, J, Magini, G, Miglioresi, L, Gambato, M, D'Ambrosio, C, Vitale, A, Colledan, M, Pinelli, D, Magistri, P, Vennarecci, G, Colasanti, M, Giannelli, V, Pellicelli, A, Eduard, C, Samuele, I, Jeroen, D, Jonas, S, Jacques, P, Chris, V, Dirk, Y, Peter, M, Valerio, L, Christophe, M, Olivier, D, Jean, D, Roberto, T, and Paul, L

Subjects
recurrence, Hepatology, reclassification, Gastroenterology, Internal Medicine, Immunology and Allergy, Prediction, transplantation
Abstract

Background & Aims: Two recently developed composite models, the alpha-fetoprotein (AFP) score and Metroticket 2.0, could be used to select patients with hepatocellular carcinoma (HCC) who are candidates for liver transplantation (LT). The aim of this study was to compare the predictive performance of both models and to evaluate the net risk reclassification of post-LT recurrence between them using each model's original thresholds. Methods: This multicenter cohort study included 2,444 adult patients who underwent LT for HCC in 47 centers from Europe and Latin America. A competing risk regression analysis estimating sub-distribution hazard ratios (SHRs) and 95% CIs for recurrence was used (Fine and Gray method). Harrell's adapted c-statistics were estimated. The net reclassification index for recurrence was compared based on each model's original thresholds. Results: During a median follow-up of 3.8 years, there were 310 recurrences and 496 competing events (20.3%). Both models predicted recurrence, HCC survival and survival better than Milan criteria (p

Published
2023

17. R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation

Author

Charlotte Costentin, Federico Piñero, Helena Degroote, Andrea Notarpaolo, Ilka F. Boin, Karim Boudjema, Cinzia Baccaro, Luis G. Podestá, Philippe Bachellier, Giuseppe Maria Ettorre, Jaime Poniachik, Fabrice Muscari, Fabrizio Dibenedetto, Sergio Hoyos Duque, Ephrem Salame, Umberto Cillo, Sebastian Marciano, Claire Vanlemmens, Stefano Fagiuoli, Patrizia Burra, Hans Van Vlierberghe, Daniel Cherqui, Quirino Lai, Marcelo Silva, Fernando Rubinstein, Christophe Duvoux, Filomena Conti, Olivier Scatton, Pierre Henri Bernard, Claire Francoz, Francois Durand, Sébastien Dharancy, Marie-lorraine Woehl, Alexis Laurent, Sylvie Radenne, Jérôme Dumortier, Armand Abergel, Louise Barbier, Pauline Houssel-Debry, Georges Philippe Pageaux, Laurence Chiche, Victor Deledinghen, Jean Hardwigsen, J. Gugenheim, M. Altieri, Marie Noelle Hilleret, Thomas Decaens, Aline Chagas, Paulo Costa, Elaine Cristina de Ataide, Emilio Quiñones, Sebastián Marciano, Margarita Anders, Adriana Varón, Alina Zerega, Alejandro Soza, Martín Padilla Machaca, Diego Arufe, Josemaría Menéndez, Rodrigo Zapata, Mario Vilatoba, Linda Muñoz, Ricardo Chong Menéndez, Martín Maraschio, Lucas McCormack, Juan Mattera, Adrian Gadano, Ilka S.F. Fatima Boin, Jose Huygens Parente García, Flair Carrilho, Giulia Magini, Lucia Miglioresi, Martina Gambato, Fabrizio Di Benedetto, Cecilia D’Ambrosio, Alessandro Vitale, Michele Colledan, Domenico Pinelli, Paolo Magistri, Giovanni Vennarecci, Marco Colasanti, Valerio Giannelli, Adriano Pellicelli, Cizia Baccaro, Callebout Eduard, Iesari Samuele, Dekervel Jeroen, Schreiber Jonas, Pirenne Jacques, Verslype Chris, Ysebaert Dirk, Michielsen Peter, Lucidi Valerio, Moreno Christophe, Detry Olivier, Delwaide Jean, Troisi Roberto, Lerut Jan Paul, Costentin, C, Piñero, F, Degroote, H, Notarpaolo, A, Boin, I, Boudjema, K, Baccaro, C, Podestá, L, Bachellier, P, Ettorre, G, Poniachik, J, Muscari, F, Dibenedetto, F, Hoyos Duque, S, Salame, E, Cillo, U, Marciano, S, Vanlemmens, C, Fagiuoli, S, Burra, P, Van Vlierberghe, H, Cherqui, D, Lai, Q, Silva, M, Rubinstein, F, Duvoux, C, Conti, F, Scatton, O, Bernard, P, Francoz, C, Durand, F, Dharancy, S, Woehl, M, Laurent, A, Radenne, S, Dumortier, J, Abergel, A, Barbier, L, Houssel-Debry, P, Pageaux, G, Chiche, L, Deledinghen, V, Hardwigsen, J, Gugenheim, J, Altieri, M, Hilleret, M, Decaens, T, Chagas, A, Costa, P, Cristina de Ataide, E, Quiñones, E, Duque, S, Anders, M, Varón, A, Zerega, A, Soza, A, Machaca, M, Arufe, D, Menéndez, J, Zapata, R, Vilatoba, M, Muñoz, L, Menéndez, R, Maraschio, M, Mccormack, L, Mattera, J, Gadano, A, Fatima Boin, I, Parente García, J, Carrilho, F, Magini, G, Miglioresi, L, Gambato, M, Benedetto, F, D’Ambrosio, C, Vitale, A, Colledan, M, Pinelli, D, Magistri, P, Vennarecci, G, Colasanti, M, Giannelli, V, Pellicelli, A, Vlierberghe, H, Eduard, C, Samuele, I, Jeroen, D, Jonas, S, Jacques, P, Chris, V, Dirk, Y, Peter, M, Valerio, L, Christophe, M, Olivier, D, Jean, D, Roberto, T, Paul, L, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hôpital la Tronche, Universidad Austral de Chile, Ghent University Hospital, Arcispedale S Maria Nuova, Universidade Estadual de Campinas = University of Campinas (UNICAMP), CHU Pontchaillou [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), CHU Strasbourg, Universidad de Chile = University of Chile [Santiago] (UCHILE), Hôpital Universitaire de Rangueil, Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Universidad de Antioquia = University of Antioquia [Medellín, Colombia], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Instituto Universitario del Hospital Italiano [Buenos Aires, Argentina], Hôpital JeanMinjoz, Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), Hôpital Paul Brousse, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), CHU Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), None, French-Italian-Belgium and Latin American collaborative group for HCC and liver transplantation: Karim Boudjema, Philippe Bachellier, Filomena Conti, Olivier Scatton, Fabrice Muscari, Ephrem Salame, Pierre Henri Bernard, Claire Francoz, Francois Durand, Sébastien Dharancy, Marie-Lorraine Woehl, Claire Vanlemmens, Alexis Laurent, Sylvie Radenne, Jérôme Dumortier, Armand Abergel, Daniel Cherqui, Louise Barbier, Pauline Houssel-Debry, Georges Philippe Pageaux, Laurence Chiche, Victor Deledinghen, Jean Hardwigsen, J Gugenheim, M Altieri, Marie Noelle Hilleret, Thomas Decaens, Christophe Duvoux, Federico Piñero, Aline Chagas, Paulo Costa, Elaine Cristina de Ataide, Emilio Quiñones, Sergio Hoyos Duque, Sebastián Marciano, Margarita Anders, Adriana Varón, Alina Zerega, Jaime Poniachik, Alejandro Soza, Martín Padilla Machaca, Diego Arufe, Josemaría Menéndez, Rodrigo Zapata, Mario Vilatoba, Linda Muñoz, Ricardo Chong Menéndez, Martín Maraschio, Luis G Podestá, Lucas McCormack, Juan Mattera, Adrian Gadano, Ilka Sf Fatima Boin, Jose Huygens Parente García, Flair Carrilho, Marcelo Silva, Andrea Notarpaolo, Giulia Magini, Lucia Miglioresi, Martina Gambato, Fabrizio Di Benedetto, Cecilia D'Ambrosio, Giuseppe Maria Ettorre, Alessandro Vitale, Patrizia Burra, Stefano Fagiuoli, Umberto Cillo, Michele Colledan, Domenico Pinelli, Paolo Magistri, Giovanni Vennarecci, Marco Colasanti, Valerio Giannelli, Adriano Pellicelli, Cizia Baccaro, Quirino Lai, Helena Degroote, Hans Van Vlierberghe, Callebout Eduard, Iesari Samuele, Dekervel Jeroen, Schreiber Jonas, Pirenne Jacques, Verslype Chris, Ysebaert Dirk, Michielsen Peter, Lucidi Valerio, Moreno Christophe, Detry Olivier, Delwaide Jean, Troisi Roberto, Lerut Jan Paul, Université de Rennes (UR), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and CHU Henri Mondor [Créteil]

Subjects
TTR= time to recurrence, [SDV.CAN]Life Sciences [q-bio]/Cancer, Explants pathology, Liver cancer, Liver transplantation, Prediction, Recurrence, MVI= microvascular invasion, VC= validation cohort, VALIDATION, LT= liver transplantation, RETREAT SCORE, SHR= sub-distribution of hazard ratio, R3= recurrence risk reassessment, HBV= hepatitis B virus, SIROLIMUS-BASED IMMUNOSUPPRESSION, Internal Medicine, HCV= hepatitis C virus, Medicine and Health Sciences, IMPROVES, Immunology and Allergy, Hepatology, TC= test cohort, Gastroenterology, DEATH, COMPETING RISKS, MODEL, AFP= alpha-foetoprotein, SORAFENIB, SURVIVAL, HCC= hepatocellular carcinoma, RETREAT= Risk Estimation of Tumour Recurrence After Transplant
Abstract

Background & Aims: Patients with hepatocellular carcinoma (HCC) are selected for liver transplantation (LT) based on pre-LT imaging +/- alpha-foetoprotein (AFP) level, but discrepancies between pre-LT tumour assessment and explant are frequent. Our aim was to design an explant-based recurrence risk reassessment score to refine prediction of recurrence after LT and provide a framework to guide post-LT management.Methods: Adult patients who underwent transplantation between 2000 and 2018 for HCC in 47 centres were included. A prediction model for recurrence was developed using competing-risk regression analysis in a European training cohort (TC; n = 1,359) and tested in a Latin American validation cohort (VC; n=1,085).Results: In the TC, 76.4% of patients with HCC met the Milan criteria, and 89.9% had an AFP score of -4 nodules (sub-distribution of hazard ratio [SHR] = 1.88, 1 point), size of largest nodule (3-6 cm: SHR = 1.83,1 point; >6 cm: SHR = 5.82, 5 points), presence of microvascular invasion (MVI; SHR = 2.69, 2 points), nuclear grade >II (SHR = 1.20, 1 point), and last pre-LT AFP value (101-1,000 ng/ml: SHR = 1.57, 1 point; >1,000 ng/ml: SHR = 2.83, 2 points). Wolber's c-index was 0.76 (95% CI 0.72-0.80), significantly superior to an R3 model without AFP (0.75; 95% CI 0.72-0.79; p = 0.01). Four 5-year recurrence risk categories were identified: very low (score = 0; 5.5%), low (1-2 points; 15.1%), high (3-6 points; 39.1%), and very high (>6 points; 73.9%). The R3-AFP score performed well in the VC (Wolber's c-index of 0.78; 95% CI 0.73-0.83). Conclusions: The R3 score including the last pre-LT AFP value (R3-AFP score) provides a user-friendly, standardised framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials for HCC not limited to the Milan criteria.Clinical Trials Registration: NCT03775863.Lay summary: Considering discrepancies between pre-LT tumour assessment and explant are frequent, reassessing the risk of recurrence after LT is critical to further refine the management of patients with HCC. In a large and international cohort of patients who underwent transplantation for HCC, we designed and validated the R3-AFP model based on variables inde-pendently associated with recurrence post-LT (number of nodules, size of largest nodule, presence of MVI, nuclear grade, and last pre-LT AFP value). The R3-AFP model including last available pre-LT AFP value outperformed the original R3 model only based on explant features. The final R3-AFP scoring system provides a robust framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials, irrespective of criteria used to select patients with HCC for LT. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).

Published
2022

18. Utilization of existing assets

Author

Roelant, R., Pereira, C. S. M., Rodriguez, A. E., CAVANI, FABRIZIO, M. Aresta, A. Dibenedetto, F. Dumeignil, Roelant, R., Cavani, F., Pereira, C.S.M., and Rodriguez, A.E.

Subjects
maleic anhydride, colocation, 1-butanol
Abstract

The chapter deals with a study on the techno-economical feasibility of the process of maleic anhydride synthesis by oxidehydration of bio-1-butanol

Published
2015

19. Clinical Outcomes of Robotic Resection for Perihilar Cholangiocarcinoma: A First, Multicenter, Trans-Atlantic, Expert-Center, Collaborative Study.

Author

Sucandy I, Marques HP, Lippert T, Magistri P, Coelho JS, Ross SB, Chumbinho B, Di Sandro S, and DiBenedetto F

Subjects
Humans, Aged, Hepatectomy methods, Treatment Outcome, Retrospective Studies, Klatskin Tumor pathology, Robotic Surgical Procedures methods, Robotics, Bile Duct Neoplasms pathology, Cholangiocarcinoma surgery
Abstract

Introduction: Perihilar cholangiocarcinoma is a difficult cancer to treat with frequent vascular invasion, local recurrence, and poor survival. Due to the need for biliary anastomosis and potential vascular resection, the standard approach is an open operation. Suboptimal outcomes after laparoscopic resection had been sporadically reported by high-volume centers. In this first, Trans-Atlantic, multicenter study, we report our outcomes of robotic resection for perihilar cholangiocarcinoma. This is the largest study of its kind in the Western hemisphere., Methods: Between 2016 and 2023, we prospectively followed patients undergoing robotic resection for perihilar cholangiocarcinoma at three, high-volume, robotic, liver-surgery centers., Results: Thirty-eight patients underwent perihilar cholangiocarcinoma utilizing the robotic technique; Klatskin type-3 was the most common. The median age was 72 years, and 82% of the patients underwent preoperative biliary drainage. Median operative time was 481 minutes with a median estimated blood loss of 200 mL. The number of harvested lymph nodes was seven, and 11 (28%) patients yielded positive lymph nodes. Three patients required vascular reconstruction; 18% of patients had >1 biliary anastomosis. R0 resection margins were achieved in 82% of patients. Clavien-Dindo Grade ≥3 complications were seen in 16% of patients. The length of stay was 6 days. Five patients had an unplanned readmission within 30 days. One patient died within 30 days. With a median follow-up of 15 months, 68% of patients are alive without disease, 13% recurred, and 19% died., Conclusions: Application of the robotic platform for perihilar cholangiocarcinoma is safe and feasible with acceptable short-term clinical and oncological outcomes., (© 2023. Society of Surgical Oncology.)

Published
2024
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21. AFP score and metroticket 2.0 perform similarly and could be used in a "within-ALL" clinical decision tool.

Author

Piñero F, Costentin C, Degroote H, Notarpaolo A, Boin IF, Boudjema K, Baccaro C, Chagas A, Bachellier P, Ettorre GM, Poniachik J, Muscari F, Dibenedetto F, Duque SH, Salame E, Cillo U, Marciano S, Vanlemmens C, Fagiuoli S, Carrilho F, Cherqui D, Burra P, Van Vlierberghe H, Lai Q, Silva M, Rubinstein F, and Duvoux C

Abstract

Background & Aims: Two recently developed composite models, the alpha-fetoprotein (AFP) score and Metroticket 2.0, could be used to select patients with hepatocellular carcinoma (HCC) who are candidates for liver transplantation (LT). The aim of this study was to compare the predictive performance of both models and to evaluate the net risk reclassification of post-LT recurrence between them using each model's original thresholds., Methods: This multicenter cohort study included 2,444 adult patients who underwent LT for HCC in 47 centers from Europe and Latin America. A competing risk regression analysis estimating sub-distribution hazard ratios (SHRs) and 95% CIs for recurrence was used (Fine and Gray method). Harrell's adapted c-statistics were estimated. The net reclassification index for recurrence was compared based on each model's original thresholds., Results: During a median follow-up of 3.8 years, there were 310 recurrences and 496 competing events (20.3%). Both models predicted recurrence, HCC survival and survival better than Milan criteria ( p <0.0001). At last tumor reassessment before LT, c-statistics did not significantly differ between the two composite models, either as original or threshold versions, for recurrence (0.72 vs . 0.68; p  = 0.06), HCC survival, and overall survival after LT. We observed predictive gaps and overlaps between the model's thresholds, and no significant gain on reclassification. Patients meeting both models ( "within-ALL") at last tumor reassessment presented the lowest 5-year cumulative incidence of HCC recurrence (7.7%; 95% CI 5.1-11.5) and higher 5-year post-LT survival (70.0%; 95% CI 64.9-74.6)., Conclusions: In this multicenter cohort, Metroticket 2.0 and the AFP score demonstrated a similar ability to predict HCC recurrence post-LT. The combination of these composite models might be a promising clinical approach., Impact and Implications: Composite models were recently proposed for the selection of liver transplant (LT) candidates among individuals with hepatocellular carcinoma (HCC). We found that both the AFP score and Metroticket 2.0 predicted post-LT HCC recurrence and survival better than Milan criteria; the Metroticket 2.0 did not result in better reclassification for transplant selection compared to the AFP score, with predictive gaps and overlaps between the two models; patients who met low-risk thresholds for both models had the lowest 5-year recurrence rate. We propose prospectively testing the combination of both models, to further optimize the LT selection process for candidates with HCC., Competing Interests: The authors of this manuscript have no conflicts of interest to disclose as described by JHEP Reports. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 The Authors.)

Published
2022
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22. R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation.

Author

Costentin C, Piñero F, Degroote H, Notarpaolo A, Boin IF, Boudjema K, Baccaro C, Podestá LG, Bachellier P, Ettorre GM, Poniachik J, Muscari F, Dibenedetto F, Duque SH, Salame E, Cillo U, Marciano S, Vanlemmens C, Fagiuoli S, Burra P, Van Vlierberghe H, Cherqui D, Lai Q, Silva M, Rubinstein F, and Duvoux C

Abstract

Background & Aims: Patients with hepatocellular carcinoma (HCC) are selected for liver transplantation (LT) based on pre-LT imaging ± alpha-foetoprotein (AFP) level, but discrepancies between pre-LT tumour assessment and explant are frequent. Our aim was to design an explant-based recurrence risk reassessment score to refine prediction of recurrence after LT and provide a framework to guide post-LT management., Methods: Adult patients who underwent transplantation between 2000 and 2018 for HCC in 47 centres were included. A prediction model for recurrence was developed using competing-risk regression analysis in a European training cohort (TC; n = 1,359) and tested in a Latin American validation cohort (VC; n=1,085)., Results: In the TC, 76.4% of patients with HCC met the Milan criteria, and 89.9% had an AFP score of ≤2 points. The recurrence risk reassessment (R3)-AFP model was designed based on variables independently associated with recurrence in the TC (with associated weights): ≥4 nodules (sub-distribution of hazard ratio [SHR] = 1.88, 1 point), size of largest nodule (3-6 cm: SHR = 1.83, 1 point; >6 cm: SHR = 5.82, 5 points), presence of microvascular invasion (MVI; SHR = 2.69, 2 points), nuclear grade >II (SHR = 1.20, 1 point), and last pre-LT AFP value (101-1,000 ng/ml: SHR = 1.57, 1 point; >1,000 ng/ml: SHR = 2.83, 2 points). Wolber's c-index was 0.76 (95% CI 0.72-0.80), significantly superior to an R3 model without AFP (0.75; 95% CI 0.72-0.79; p  = 0.01). Four 5-year recurrence risk categories were identified: very low (score = 0; 5.5%), low (1-2 points; 15.1%), high (3-6 points; 39.1%), and very high (>6 points; 73.9%). The R3-AFP score performed well in the VC (Wolber's c-index of 0.78; 95% CI 0.73-0.83)., Conclusions: The R3 score including the last pre-LT AFP value (R3-AFP score) provides a user-friendly, standardised framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials for HCC not limited to the Milan criteria., Clinical Trials Registration: NCT03775863., Lay Summary: Considering discrepancies between pre-LT tumour assessment and explant are frequent, reassessing the risk of recurrence after LT is critical to further refine the management of patients with HCC. In a large and international cohort of patients who underwent transplantation for HCC, we designed and validated the R3-AFP model based on variables independently associated with recurrence post-LT (number of nodules, size of largest nodule, presence of MVI, nuclear grade, and last pre-LT AFP value). The R3-AFP model including last available pre-LT AFP value outperformed the original R3 model only based on explant features. The final R3-AFP scoring system provides a robust framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials, irrespective of criteria used to select patients with HCC for LT., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 The Author(s).)

Published
2022
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