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2. PD1 and TIM3 Expression is Associated with Very Early Hepatocellular Carcinoma Recurrence After Percutaneous Thermal Ablation

Author

Ghelfi J, Macek Jilkova Z, Sengel C, Brusset B, Teyssier Y, Costentin C, Mercey-Ressejac M, Dumolard L, Manceau M, Mathieu E, Bricault I, and Decaens T

Subjects
immune checkpoint molecules, predictive factors, hepatocellular carcinoma, percutaneous thermal ablation, intrahepatic distant recurrence., Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Julien Ghelfi,1– 3,&ast; Zuzana Macek Jilkova,1,3,4,&ast; Christian Sengel,2 Bleuenn Brusset,4 Yann Teyssier,2 Charlotte Costentin,1,3,4 Marion Mercey-Ressejac,3,4 Lucile Dumolard,1,3 Marc Manceau,5 Eliott Mathieu,2 Ivan Bricault,1,2 Thomas Decaens1,3,4 1University of Grenoble-Alpes, Saint Martin d’Hères, France; 2Department of Radiology, Grenoble-Alpes University Hospital, Grenoble, France; 3Institute for Advanced Biosciences - INSERM U1209/CNRS UMR 5309/University of Grenoble-Alpes, La Tronche, France; 4Department of Hepatology and Gastrointestinal Medical Oncology, Grenoble-Alpes University Hospital, Grenoble, France; 5Clinical Pharmacology Unit, Inserm Clinical Research Center, Grenoble-Alpes University Hospital, Grenoble, France&ast;These authors contributed equally to this workCorrespondence: Julien Ghelfi, Department of Radiology, Grenoble-Alpes University Hospital, Boulevard de la Chantourne, Grenoble, 38000, France, Tel +33 476768909, Email jghelfi@chu-grenoble.fr Zuzana Macek Jilkova, Department of Hepato-Gastroenterology, Grenoble-Alpes University Hospital, Boulevard de la Chantourne, Grenoble, 38000, France, Tel +33 669048426, Email zmacekjilkova@chu-grenoble.frPurpose: Percutaneous thermal ablation (PTA) is a cornerstone in the management of early-stage hepatocellular carcinoma (HCC). However, intrahepatic distant recurrence (IDR) occurs in the majority of patients after PTA. The aim of this study was to evaluate the immune signature associated with very early IDR.Patients and Methods: Thirty-one patients (26 men, 5 women; mean age:72.4 ± 8.6; age range:57– 86 years) who underwent PTA for HCC were included in this study. After PTA for HCC, patients were followed and later divided into two groups: a “very early recurrence” group in case of IDR within 12 months after PTA, and a “prolonged recurrence-free” group in case of no recurrence before 12 months of follow-up. Freshly harvested intratumoral and nontumoral liver tissues and peripheral blood were obtained before PTA and explored by multiparametric flow cytometry.Results: The frequency of PD1+CD4+ T cells was higher in the early recurrence group than in the prolonged recurrence-free group in the peripheral blood (24.3%, IQR: 22.3– 36.5 vs 14.0%, IQR: 11.5– 16.4, p< 0.0001), in the nontumoral liver (37.9%, IQR: 36.0– 50.0 vs 22.5%, IQR: 18.0– 29.9, p=0.0004), and in the tumor (37.6%, IQR: 32.3– 39.3 vs 24.0%, IQR: 20.0– 30.3, p=0.0137). Similarly, the frequency of TIM+CD8+ T cells was higher in the very early recurrence group in the peripheral blood (p=0.0021), non-tumoral liver (p=0.0012), and tumor (p=0.0239).Conclusion: The expression of immune checkpoint molecules, such as PD1 and TIM3 on T cells identified HCC patients at risk of very early IDR after PTA who would likely benefit from adjuvant immunotherapy. Thus, our study contributes to a better understanding of the potential association of PTA with adjuvant immunotherapies.Keywords: immune checkpoint molecules, predictive factors, hepatocellular carcinoma, percutaneous thermal ablation, intrahepatic distant recurrence

Published
2024

3. 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

7. 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

8. Clinical outcomes after treatment with direct antiviral agents: beyond the virological response in patients with previous HCV-related decompensated cirrhosis

Author

Pageaux, G. (Georges-Philippe), Nzinga, C. (Clovis Lusivika), Ganne, N. (Nathalie), Samuel, D. (Didier), Dorival, C. (Céline), Zoulim, F. (Fabien), Cagnot, C. (Carole), Decaens, T. (Thomas), Thabut, D. (Dominique), Asselah, T. (Tarik), Mathurin, P. (Philippe), Habersetzer, F. (Francois), Bronowicki, J. (Jean-Pierre), Guyader, D. (Dominique), Rosa, I. (Isabelle), Leroy, V. (Vincent), Chazouilleres, O. (Olivier), de Ledinghen, V. (Victor), Bourliere, M. (Marc), Causse, X. (Xavier), Cales, P. (Paul), Metivier, S. (Sophie), Loustaud-Ratti, V. (Véronique), Riachi, G. (Ghassan), Alric, L. (Laurent), Gelu-Simeon, M. (Moana), Minello, A. (Anne), Gournay, J. (Jérôme), Geist, C. (Claire), Tran, A. (Albert), Abergel, A. (Armand), Portal, I. (Isabelle), d'Alteroche, L. (Louis), Raffi, F. (François), Fontaine, H. (Hélène), Carrat, F. (Fabrice), Pol, S. (Stanislas), Baumert, Thomas F., Doffoel, M. (Michel), Mutter, C. (Catherine), Simo-Noumbissie, P. (Pauline), Razi, E. (Esma), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathogénèse et Traitement des Maladies du Foie, Hôpital Paul Brousse-Université Paris-Saclay, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), 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), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Physiopathologie des Maladies Inflammatoires de l'Intestin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHI Créteil, Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-Joseph [Marseille], Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université d'Angers (UA), CHU Toulouse [Toulouse], Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), French ANRS CO22 Hepather Cohort: Delphine Bonnet, Virginie Payssan-Sicart, Chloe Pomes, François Bailly, Marjolaine Beaudoin, Dominique Giboz, Kerstin Hartig-Lavie, Marianne Maynard, Eric Billaud, David Boutoille, Morane Cavellec, Caroline Chevalier, Isabelle Hubert, Pierre Goepfert, Adrien Lannes, Françoise Lunel, Jérôme Boursier, Nathalie Boyer, Nathalie Giuily, Corinne Castelnau, Giovanna Scoazec, Aziza Chibah, Sylvie Keser, Karim Bonardi, Anaïs Vallet-Pichard, Philippe Sogni, Juliette Foucher, Jean-Baptiste Hiriart, Amandine Legendre, Faiza Chermak, Marie Irlès-Depé, Si Nafa Si Ahmed, Christelle Ansaldi, Nisserine Ben Amara, Valérie Oules, Jacqueline Dunette, Rodolphe Anty, Eve Gelsi, Régine Truchi, Elena Luckina, Nadia Messaoudi, Joseph Moussali, Barbara De Dieuleveult, Héloïse Goin, Damien Labarrière, Pascal Potier, Si Nafa Si Ahmed, Véronique Grando-Lemaire, Pierre Nahon, Séverine Brulé, Rym Monard, Caroline Jezequel, Audrey Brener, Anne Laligant, Aline Rabot, Isabelle Renard, Thomas F Baumert, Michel Dofföel, Catherine Mutter, Pauline Simo-Noumbissie, Esma Razi, Hélène Barraud, Mouni Bensenane, Abdelbasset Nani, Sarah Hassani-Nani, Marie-Albertine Bernard, Georges-Philippe Pageaux, Michael Bismuth, Ludovic Caillo, Stéphanie Faure, Marie Pierre Ripault, Christophe Bureau, Sarah Launay, Jean Marie Peron, Marie Angèle Robic, Léa Tarallo, Marine Faure, Bruno Froissart, Marie-Noelle Hilleret, Jean-Pierre Zarski, Odile Goria, Victorien Grard, Hélène Montialoux, Muriel François, Christian Ouedraogo, Christelle Pauleau, Anne Varault, Tony Andreani, Bénédicte Angoulevant, Azeline Chevance, Lawrence Serfaty, Teresa Antonini, Audrey Coilly, Jean-Charles Duclos Vallée, Mariagrazia Tateo, Corinne Bonny, Chanteranne Brigitte, Géraldine Lamblin, Léon Muti, Abdenour Babouri, Virginie Filipe, Camille Barrault, Laurent Costes, Hervé Hagège, Soraya Merbah, Paul Carrier, Maryline Debette-Gratien, Jérémie Jacques, Guillaume Lassailly, Florent Artu, Valérie Canva, Sébastien Dharancy, Alexandre Louvet, Marianne Latournerie, Marc Bardou, Thomas Mouillot, Yannick Bacq, Didier Barbereau, Charlotte Nicolas, Caroline Chevalier, Isabelle Archambeaud, Sarah Habes, Nisserine Ben Amara, Danièle Botta-Fridlund, Eric Saillard, Marie-Josée Lafrance, Carole Cagnot, Alpha Diallo, Lena Wadouachi, Ventzi Petrov-Sanchez, Douae Ammour, Loubna Ayour, Jaouad Benhida, Fabrice Carrat, Frederic Chau, Céline Dorival, Audrey Gilibert, Isabelle Goderel, Warda Hadi, Clovis Luzivika Nzinga, Grégory Pannetier, François Pinot, Odile Stahl, François Téloulé, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Jonchère, Laurent

Subjects
Liver Cirrhosis, medicine.medical_specialty, Carcinoma, Hepatocellular, Survival, Hepatocellular carcinoma, [SDV]Life Sciences [q-bio], Decompensated cirrhosis, Infectious and parasitic diseases, RC109-216, Hepacivirus, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, complications, drug therapy, Gastroenterology, Antiviral Agents, Virological response, Internal medicine, Medicine, Humans, In patient, business.industry, Hepatitis C virus, Research, Liver Neoplasms, Hepatitis C, [SDV] Life Sciences [q-bio], Sustained virological response, Infectious Diseases, Direst-acting antiviral agents, therapeutic use, business, After treatment
Abstract

Background In HCV-infected patients with advanced liver disease, the direct antiviral agents-associated clinical benefits remain debated. We compared the clinical outcome of patients with a previous history of decompensated cirrhosis following treatment or not with direct antiviral agents from the French ANRS CO22 HEPATHER cohort. Methods We identified HCV patients who had experienced an episode of decompensated cirrhosis. Study outcomes were all-cause mortality, liver-related or non-liver-related deaths, hepatocellular carcinoma, liver transplantation. Secondary study outcomes were sustained virological response and its clinical benefits. Results 559 patients met the identification criteria, of which 483 received direct antiviral agents and 76 remained untreated after inclusion in the cohort. The median follow-up time was 39.7 (IQR: 22.7–51) months. After adjustment for multivariate analysis, exposure to direct antiviral agents was associated with a decrease in all-cause mortality (HR 0.45, 95% CI 0.24–0.84, p = 0.01) and non-liver-related death (HR 0.26, 95% CI 0.08–0.82, p = 0.02), and was not associated with liver-related death, decrease in hepatocellular carcinoma and need for liver transplantation. The sustained virological response was 88%. According to adjusted multivariable analysis, sustained virological response achievement was associated with a decrease in all-cause mortality (HR 0.29, 95% CI 0.15–0.54, p Conclusion Treatment with direct antiviral agents is associated with reduced risk for mortality. The sustained virological response was 88%. Thus, direct antiviral agents treatment should be considered for any patient with HCV-related decompensated cirrhosis. Trial registration: ClinicalTrials.gov registry number: NCT01953458.

Published
2022

14. Liver-targeted disruption of Apc in mice activates [beta]-catenin signaling and leads to hepatocellular carcinomas

Author

Colnot, S., Decaens, T., Niwa-Kawakita, M., Godard, C., Hamard, G., Kahn, A., Giovannini, M., and Perret, C.

Subjects
Liver -- Research, Science and technology
Abstract

Although inappropriate activation of the Wnt/[beta]-catenin pathway has been implicated in the development of hepatocellular carcinoma (HCC), the role of this signaling in liver carcinogenesis remains unclear. To investigate this issue, we constructed a mutant mouse strain, [Apc.sup.low/lox], in which exon 14 of the tumor-suppressor gene adenomatous polyposis coil (Apc) is flanked by loxP sequences, i.v. injection of adenovirus encoding Cre recombinase (AdCre) at high multiplicity [[10.sup.9] plaque-forming units (pfu) per mouse] inactivated the Apc gene in the liver and resulted in marked hepatomegaly, hepatocyte hyperplasia, and rapid mortality. [beta]-Catenin signaling activation was demonstrated by nuclear and cytoplasmic accumulation of [beta]-catenin in the hepatocytes and by the induction of [beta]-catenin target genes (glutamine synthetase, glutamate transporter 1, ornithine aminotransferase, and leukocyte cell-derived chemotaxin 2) in the liver. To test a long-term oncogenic effect, we inoculated mice with lower doses of AdCre (0.5 x [10.sup.9] pfu per mouse), compatible with both survival and persistence of [beta]-catenin-activated cells. In these conditions, 67% of mice developed HCC. [beta]-Catenin signaling was strongly activated in these Apc-inactivated HCCs. The HCCs were well, moderately, or poorly differentiated. Indeed, their histological and molecular features mimicked human HCC. Thus, deletion of Apc in the liver provides a valuable model of human HCC, and, in this model, activation of the Wnt/[beta]-catenin pathway by invalidation of Apc is required for liver tumorigenesis. adenomatous polyposis coil | hepatocarcinogenesis | mouse model

Published
2004

20. Biofunctool (R) : a new framework to assess the impact of land management on soil quality. Part A : concept and validation of the set of indicators

Author

Thoumazeaua, A., Bessoua, C., Renevier, M. S., Trap, Jean, Marichal, R., Mareschal, L., Decaens, T., Bottinelli, Nicolas, Jaillard, B., Chevallier, Tiphaine, Suvannang, N., Sajjaphan, K., Thaler, P., Gay, F., and Brauman, Alain

Subjects
Land management, Integrative approach, Indicators, Biofunctool (R), Soil functions, Soil quality
Abstract

The assessment of soil quality is a scientific issue that has been widely debated in the literature for the last twenty years. We developed the Biofunctool (R) framework to assess soil quality based on an integrative approach that accounts for the link between the physico-chemical properties and the biological activity of soils. Biofunctool (R) consists in a set of twelve in-field, time- and cost-effective indicators to assess three main soil functions: carbon transformation, nutrient cycling and structure maintenance. The indicators were applied in a network of mostly rubber plantations compared with three other land uses in Thailand. We collected 1952 indicators values in 180 sampling points over a wide range of pedo-climatic and agronomic contexts in order to assess the validity of the indicators. A reliability, redundancy and sensitivity analysis was performed to validate the capacity of the set of indicators to assess the impact of land management on soil quality. The results showed the relevance and consistence of each of the twelve indicators to assess the soil functioning. Improvements are finally discussed to guide further implementation of the indicators in various contexts and build a soil quality index.

Published
2019

21. Preliminary safety and pharmacokinetics of a new lysosomotropic oral agent, GNS561, in a first-in-human study in advanced primary liver cancer patients

Author

Awada, A.H., primary, Harding, J.J., additional, Kotecki, N., additional, Aftimos, P.G., additional, Decaens, T., additional, Dreyer, C., additional, Ansaldi, C., additional, Rachid, M., additional, Serdjebi, C., additional, Halfon, P., additional, Abou-Alfa, G.K., additional, and Raymond, E., additional

Published
2019
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23. CLINICAL AND EPIDEMIOLOGICAL MANIFESTATION OF HEPATOCELLULAR CARCINOMA IN PATIENTS BELONGING TO ETHNIC GROUPS OF CAUCASIANS AND ASIANS OF NORTH-EAST ASIA

Author

Yuschuk, N. D., primary, Malov, I. V., additional, Baatarkhuu, O. .., additional, Savilov, E. D., additional, Malov, S. I., additional, Rasulov, R. I., additional, Dvornichenko, V. V., additional, Lkhagva-Ochir, T. .., additional, Amarsanaa, J. .., additional, Decaens, T. .., additional, and Marche, P. N., additional

Published
2018
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24. CA209-9DX: Phase III, randomized, double-blind study of adjuvant nivolumab vs placebo for patients with hepatocellular carcinoma (HCC) at high risk of recurrence after curative resection or ablation

Author

Jimenez Exposito, M.J., primary, Akce, M., additional, Alvarez, J.L.M., additional, Assenat, E., additional, Balart, L.A., additional, Baron, A.D., additional, Decaens, T., additional, Heurgue-Berlot, A., additional, Martin, A.O., additional, Paik, S.W., additional, Poulart, V., additional, Sehbai, A.S., additional, Shimada, M., additional, Takemura, N., additional, and Yoon, J.-H., additional

Published
2018
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26. gestion des sols et biodiversite

Author

Sapijanskas, Jurgis, Podesta, Gwenael, BISPO, Antionio, Blanchart, E, Boutet, Didier, Chenu, Claire, Cluzeau, Daniel, Decaens, T., Dubs, Florence, Martin, E, Schwartz, D., Soubelet, H., Yengué, Jean-Louis, Direction de la recherche et de l’innovation du ministère en charge de l'Écologie., Ministère de l’écologie, de l’énergie, du développement durable et de la mer, programme Eaux et Territoires, Département de Recherche Déchet et Sol, Agence de l'Environnement et de la Maitrise de l'Energie, Laboratoire Biologie et Organisation des Sols Tropicaux, Institut pour la Recherche et le Développement, Cités, Territoires, Environnement et Sociétés (CITERES), Centre National de la Recherche Scientifique (CNRS)-Université de Tours (UT), Ecologie fonctionnelle et écotoxicologie des agroécosystèmes (ECOSYS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Ecosystèmes, biodiversité, évolution [Rennes] (ECOBIO), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR)-Centre National de la Recherche Scientifique (CNRS), Étude et compréhension de la biodiversité (ECODIV), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Université Pierre et Marie Curie - Paris 6 (UPMC), Unité bactériologie, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Quae, Bispo Antonio, Guellier Camille, Martin Elsa, Sapijanskas Jurgis, Soubelet Hélène, Chenu Clair, AgroParisTech, Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Ecologie fonctionnelle et biogéochimie des sols et des agro-écosystèmes (UMR Eco&Sols), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR), Université de Rennes (UR)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS), Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Université Paul-Valéry - Montpellier 3 (UPVM)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Laboratoire Image, Ville, Environnement (LIVE), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Ministère de l'Ecologie, Université de Tours-Centre National de la Recherche Scientifique (CNRS), Yengué, Jean-Louis, Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre National de la Recherche Scientifique (CNRS)-Université de Tours, Bispo, A. (coord.), Guellier, C. (coord.), Martin, E. (coord.), Sapijanskas, J (coord.), Soubelet, H. (coord.), and Chenu, C. (coord.)

Subjects
[SHS.ENVIR] Humanities and Social Sciences/Environmental studies, [SHS.GEO] Humanities and Social Sciences/Geography, [SHS.ENVIR]Humanities and Social Sciences/Environmental studies, gestion, [SHS.GEO]Humanities and Social Sciences/Geography, sols, ComputingMilieux_MISCELLANEOUS, biodiversité, services écosystémiques
Abstract

International audience

Published
2016

28. Practice patterns and deterioration of liver function after transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): Final analysis of OPTIMIS in Europe and Canada

Author

Raoul, J.-L., primary, Decaens, T., additional, Burak, K., additional, Koskinas, J., additional, Villadsen, G.E., additional, Heurgue-Berlot, A., additional, Bayh, I., additional, Cheng, A.-L., additional, Kudo, M., additional, Lee, H.C., additional, Nakajima, K., additional, and Peck-Radosavljevic, M., additional

Published
2018
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35. Biodiversity inventories in high gear:DNA barcoding facilitates a rapid biotic survey of a temperate nature reserve

Author

Telfer, A. C. (Angela C.), Young, M. R. (Monica R.), Quinn, J. (Jenna), Perez, K. (Kate), Sobel, C. N. (Crystal N.), Sones, J. E. (Jayme E.), Levesque-Beaudin, V. (Valerie), Derbyshire, R. (Rachael), Fernandez-Triana, J. (Jose), Rougerie, R. (Rodolphe), Thevanayagam, A. (Abinah), Boskovic, A. (Adrian), Borisenko, A. V. (Alex, V), Cadel, A. (Alex), Brown, A. (Allison), Pages, A. (Anais), Castillo, A. H. (Anibal H.), Nicolai, A. (Annegret), Mockford, B. M. (Barb Mockford Glenn), Bukowski, B. (Belen), Wilson, B. (Bill), Trojahn, B. (Brock), Lacroix, C. A. (Carole Ann), Brimblecombe, C. (Chris), Hay, C. (Christoper), Ho, C. (Christmas), Steinke, C. (Claudia), Warne, C. P. (Connor P.), Cortes, C. G. (Cristina Garrido), Engelking, D. (Daniel), Wright, D. (Danielle), Lijtmaer, D. A. (Dario A.), Gascoigne, D. (David), Martich, D. H. (David Hernandez), Morningstar, D. (Derek), Neumann, D. (Dirk), Steinke, D. (Dirk), DeBruin, D. D. (Donna Debruin Marco), Dobias, D. (Dylan), Sears, E. (Elizabeth), Richard, E. (Ellen), Damstra, E. (Emily), Zakharov, E. V. (Evgeny, V), Laberge, F. (Frederic), Collins, G. E. (Gemma E.), Blagoev, G. A. (Gergin A.), Grainge, G. (Gerrie), Ansell, G. (Graham), Meredith, G. (Greg), Hogg, I. (Ian), McKeown, J. (Jaclyn), Topan, J. (Janet), Bracey, J. (Jason), Guenther, J. (Jerry), Sills-Gilligan, J. (Jesse), Addesi, J. (Joseph), Persi, J. (Joshua), Layton, K. K. (Kara K. S.), D'Souza, K. (Kareina), Dorji, K. (Kencho), Grundy, K. (Kevin), Nghidinwa, K. (Kirsti), Ronnenberg, K. (Kylee), Lee, K. M. (Kyung Min), Xie, L. (Linxi), Lu, L. (Liuqiong), Penev, L. (Lyubomir), Gonzalez, M. (Mailyn), Rosati, M. E. (Margaret E.), Kekkonen, M. (Mari), Kuzmina, M. (Maria), Iskandar, M. (Marianne), Mutanen, M. (Marko), Fatahi, M. (Maryam), Pentinsaari, M. (Mikko), Bauman, M. (Miriam), Nikolova, N. (Nadya), Ivanova, N. V. (Natalia, V), Jones, N. (Nathaniel), Weerasuriya, N. (Nimalka), Monkhouse, N. (Norman), Lavinia, P. D. (Pablo D.), Jannetta, P. (Paul), Hanisch, P. E. (Priscila E.), McMullin, R. T. (R. Troy), Flores, R. O. (Rafael Ojeda), Mouttet, R. (Raphaelle), Vender, R. (Reid), Labbee, R. N. (Renee N.), Forsyth, R. (Robert), Lauder, R. (Rob), Dickson, R. (Ross), Kroft, R. (Ruth), Miller, S. E. (Scott E.), MacDonald, S. (Shannon), Panthi, S. (Sishir), Pedersen, S. (Stephanie), Sobek-Swant, S. (Stephanie), Naik, S. (Suresh), Lipinskaya, T. (Tatsiana), Eagalle, T. (Thanushi), Decaens, T. (Thibaud), Kosuth, T. (Thibault), Braukmann, T. (Thomas), Woodcock, T. (Tom), Roslin, T. (Tomas), Zammit, T. (Tony), Campbell, V. (Victoria), Dinca, V. (Vlad), Peneva, V. (Vlada), Hebert, P. D. (Paul D. N.), deWaard, J. R. (Jeremy R.), Telfer, A. C. (Angela C.), Young, M. R. (Monica R.), Quinn, J. (Jenna), Perez, K. (Kate), Sobel, C. N. (Crystal N.), Sones, J. E. (Jayme E.), Levesque-Beaudin, V. (Valerie), Derbyshire, R. (Rachael), Fernandez-Triana, J. (Jose), Rougerie, R. (Rodolphe), Thevanayagam, A. (Abinah), Boskovic, A. (Adrian), Borisenko, A. V. (Alex, V), Cadel, A. (Alex), Brown, A. (Allison), Pages, A. (Anais), Castillo, A. H. (Anibal H.), Nicolai, A. (Annegret), Mockford, B. M. (Barb Mockford Glenn), Bukowski, B. (Belen), Wilson, B. (Bill), Trojahn, B. (Brock), Lacroix, C. A. (Carole Ann), Brimblecombe, C. (Chris), Hay, C. (Christoper), Ho, C. (Christmas), Steinke, C. (Claudia), Warne, C. P. (Connor P.), Cortes, C. G. (Cristina Garrido), Engelking, D. (Daniel), Wright, D. (Danielle), Lijtmaer, D. A. (Dario A.), Gascoigne, D. (David), Martich, D. H. (David Hernandez), Morningstar, D. (Derek), Neumann, D. (Dirk), Steinke, D. (Dirk), DeBruin, D. D. (Donna Debruin Marco), Dobias, D. (Dylan), Sears, E. (Elizabeth), Richard, E. (Ellen), Damstra, E. (Emily), Zakharov, E. V. (Evgeny, V), Laberge, F. (Frederic), Collins, G. E. (Gemma E.), Blagoev, G. A. (Gergin A.), Grainge, G. (Gerrie), Ansell, G. (Graham), Meredith, G. (Greg), Hogg, I. (Ian), McKeown, J. (Jaclyn), Topan, J. (Janet), Bracey, J. (Jason), Guenther, J. (Jerry), Sills-Gilligan, J. (Jesse), Addesi, J. (Joseph), Persi, J. (Joshua), Layton, K. K. (Kara K. S.), D'Souza, K. (Kareina), Dorji, K. (Kencho), Grundy, K. (Kevin), Nghidinwa, K. (Kirsti), Ronnenberg, K. (Kylee), Lee, K. M. (Kyung Min), Xie, L. (Linxi), Lu, L. (Liuqiong), Penev, L. (Lyubomir), Gonzalez, M. (Mailyn), Rosati, M. E. (Margaret E.), Kekkonen, M. (Mari), Kuzmina, M. (Maria), Iskandar, M. (Marianne), Mutanen, M. (Marko), Fatahi, M. (Maryam), Pentinsaari, M. (Mikko), Bauman, M. (Miriam), Nikolova, N. (Nadya), Ivanova, N. V. (Natalia, V), Jones, N. (Nathaniel), Weerasuriya, N. (Nimalka), Monkhouse, N. (Norman), Lavinia, P. D. (Pablo D.), Jannetta, P. (Paul), Hanisch, P. E. (Priscila E.), McMullin, R. T. (R. Troy), Flores, R. O. (Rafael Ojeda), Mouttet, R. (Raphaelle), Vender, R. (Reid), Labbee, R. N. (Renee N.), Forsyth, R. (Robert), Lauder, R. (Rob), Dickson, R. (Ross), Kroft, R. (Ruth), Miller, S. E. (Scott E.), MacDonald, S. (Shannon), Panthi, S. (Sishir), Pedersen, S. (Stephanie), Sobek-Swant, S. (Stephanie), Naik, S. (Suresh), Lipinskaya, T. (Tatsiana), Eagalle, T. (Thanushi), Decaens, T. (Thibaud), Kosuth, T. (Thibault), Braukmann, T. (Thomas), Woodcock, T. (Tom), Roslin, T. (Tomas), Zammit, T. (Tony), Campbell, V. (Victoria), Dinca, V. (Vlad), Peneva, V. (Vlada), Hebert, P. D. (Paul D. N.), and deWaard, J. R. (Jeremy R.)

Abstract

Background: Comprehensive biotic surveys, or ‘all taxon biodiversity inventories’ (ATBI), have traditionally been limited in scale or scope due to the complications surrounding specimen sorting and species identification. To circumvent these issues, several ATBI projects have successfully integrated DNA barcoding into their identification procedures and witnessed acceleration in their surveys and subsequent increase in project scope and scale. The Biodiversity Institute of Ontario partnered with the rare Charitable Research Reserve and delegates of the 6th International Barcode of Life Conference to complete its own rapid, barcode-assisted ATBI of an established land trust in Cambridge, Ontario, Canada. New information: The existing species inventory for the rare Charitable Research Reserve was rapidly expanded by integrating a DNA barcoding workflow with two surveying strategies — a comprehensive sampling scheme over four months, followed by a one-day bioblitz involving international taxonomic experts. The two surveys resulted in 25,287 and 3,502 specimens barcoded, respectively, as well as 127 human observations. This barcoded material, all vouchered at the Biodiversity Institute of Ontario collection, covers 14 phyla, 29 classes, 117 orders, and 531 families of animals, plants, fungi, and lichens. Overall, the ATBI documented 1,102 new species records for the nature reserve, expanding the existing long-term inventory by 49%. In addition, 2,793 distinct Barcode Index Numbers (BINs) were assigned to genus or higher level taxonomy, and represent additional species that will be added once their taxonomy is resolved. For the 3,502 specimens, the collection, sequence analysis, taxonomic assignment, data release and manuscript submission by 100+ co-authors all occurred in less than one week. This demonstrates the speed at which barcode-assisted inventories can be completed and the utility that barcoding provides in minimizing and guiding valuable taxonomic spec

Published
2015

41. International network of cancer genome projects

Author

Hudson, TJ, Anderson, W, Aretz, A, Barker, AD, Bell, C, Bernabe, RR, Bhan, MK, Calvo, F, Eerola, I, Gerhard, DS, Guttmacher, A, Guyer, M, Hemsley, FM, Jennings, JL, Kerr, D, Klatt, P, Kolar, P, Kusuda, J, Lane, DP, Laplace, F, Lu, Y, Nettekoven, G, Ozenberger, B, Peterson, J, Rao, TS, Remacle, J, Schafer, AJ, Shibata, T, Stratton, MR, Vockley, JG, Watanabe, K, Yang, H, Yuen, MMF, Knoppers, M, Bobrow, M, Cambon-Thomsen, A, Dressler, LG, Dyke, SOM, Joly, Y, Kato, K, Kennedy, KL, Nicolas, P, Parker, MJ, Rial-Sebbag, E, Romeo-Casabona, CM, Shaw, KM, Wallace, S, Wiesner, GL, Zeps, N, Lichter, P, Biankin, AV, Chabannon, C, Chin, L, Clement, B, de Alava, E, Degos, F, Ferguson, ML, Geary, P, Hayes, DN, Johns, AL, Nakagawa, H, Penny, R, Piris, MA, Sarin, R, Scarpa, A, van de Vijver, M, Futreal, PA, Aburatani, H, Bayes, M, Bowtell, DDL, Campbell, PJ, Estivill, X, Grimmond, SM, Gut, I, Hirst, M, Lopez-Otin, C, Majumder, P, Marra, M, Ning, Z, Puente, XS, Ruan, Y, Stunnenberg, HG, Swerdlow, H, Velculescu, VE, Wilson, RK, Xue, HH, Yang, L, Spellman, PT, Bader, GD, Boutros, PC, Flicek, P, Getz, G, Guigo, R, Guo, G, Haussler, D, Heath, S, Hubbard, TJ, Jiang, T, Jones, SM, Li, Q, Lopez-Bigas, N, Luo, R, Pearson, JV, Quesada, V, Raphael, BJ, Sander, C, Speed, TP, Stuart, JM, Teague, JW, Totoki, Y, Tsunoda, T, Valencia, A, Wheeler, DA, Wu, H, Zhao, S, Zhou, G, Stein, LD, Lathrop, M, Ouellette, BFF, Thomas, G, Yoshida, T, Axton, M, Gunter, C, McPherson, JD, Miller, LJ, Kasprzyk, A, Zhang, J, Haider, SA, Wang, J, Yung, CK, Cross, A, Liang, Y, Gnaneshan, S, Guberman, J, Hsu, J, Chalmers, DRC, Hasel, KW, Kaan, TSH, Knoppers, BM, Lowrance, WW, Masui, T, Rodriguez, LL, Vergely, C, Cloonan, N, Defazio, A, Eshleman, JR, Etemadmoghadam, D, Gardiner, BA, Kench, JG, Sutherland, RL, Tempero, MA, Waddell, NJ, Wilson, PJ, Gallinger, S, Tsao, M-S, Shaw, PA, Petersen, GM, Mukhopadhyay, D, DePinho, RA, Thayer, S, Muthuswamy, L, Shazand, K, Beck, T, Sam, M, Timms, L, Ballin, V, Ji, J, Zhang, X, Chen, F, Hu, X, Yang, Q, Tian, G, Zhang, L, Xing, X, Li, X, Zhu, Z, Yu, Y, Yu, J, Tost, J, Brennan, P, Holcatova, I, Zaridze, D, Brazma, A, Egevad, L, Prokhortchouk, E, Banks, RE, Uhlen, M, Viksna, J, Ponten, F, Skryabin, K, Birney, E, Borg, A, Borresen-Dale, A-L, Caldas, C, Foekens, JA, Martin, S, Reis-Filho, JS, Richardson, AL, Sotiriou, C, van't Veer, L, Birnbaum, D, Blanche, H, Boucher, P, Boyault, S, Masson-Jacquemier, JD, Pauporte, I, Pivot, X, Vincent-Salomon, A, Tabone, E, Theillet, C, Treilleux, I, Bioulac-Sage, P, Decaens, T, Franco, D, Gut, M, Samuel, D, Zucman-Rossi, J, Eils, R, Brors, B, Korbel, JO, Korshunov, A, Landgraf, P, Lehrach, H, Pfister, S, Radlwimmer, B, Reifenberger, G, Taylor, MD, von Kalle, C, Majumder, PP, Pederzoli, P, Lawlor, RT, Delledonne, M, Bardelli, A, Gress, T, Klimstra, D, Zamboni, G, Nakamura, Y, Miyano, S, Fujimoto, A, Campo, E, de Sanjose, S, Montserrat, E, Gonzalez-Diaz, M, Jares, P, Himmelbaue, H, Bea, S, Aparicio, S, Easton, DF, Collins, FS, Compton, CC, Lander, ES, Burke, W, Green, AR, Hamilton, SR, Kallioniemi, OP, Ley, TJ, Liu, ET, Wainwright, BJ, Hudson, TJ, Anderson, W, Aretz, A, Barker, AD, Bell, C, Bernabe, RR, Bhan, MK, Calvo, F, Eerola, I, Gerhard, DS, Guttmacher, A, Guyer, M, Hemsley, FM, Jennings, JL, Kerr, D, Klatt, P, Kolar, P, Kusuda, J, Lane, DP, Laplace, F, Lu, Y, Nettekoven, G, Ozenberger, B, Peterson, J, Rao, TS, Remacle, J, Schafer, AJ, Shibata, T, Stratton, MR, Vockley, JG, Watanabe, K, Yang, H, Yuen, MMF, Knoppers, M, Bobrow, M, Cambon-Thomsen, A, Dressler, LG, Dyke, SOM, Joly, Y, Kato, K, Kennedy, KL, Nicolas, P, Parker, MJ, Rial-Sebbag, E, Romeo-Casabona, CM, Shaw, KM, Wallace, S, Wiesner, GL, Zeps, N, Lichter, P, Biankin, AV, Chabannon, C, Chin, L, Clement, B, de Alava, E, Degos, F, Ferguson, ML, Geary, P, Hayes, DN, Johns, AL, Nakagawa, H, Penny, R, Piris, MA, Sarin, R, Scarpa, A, van de Vijver, M, Futreal, PA, Aburatani, H, Bayes, M, Bowtell, DDL, Campbell, PJ, Estivill, X, Grimmond, SM, Gut, I, Hirst, M, Lopez-Otin, C, Majumder, P, Marra, M, Ning, Z, Puente, XS, Ruan, Y, Stunnenberg, HG, Swerdlow, H, Velculescu, VE, Wilson, RK, Xue, HH, Yang, L, Spellman, PT, Bader, GD, Boutros, PC, Flicek, P, Getz, G, Guigo, R, Guo, G, Haussler, D, Heath, S, Hubbard, TJ, Jiang, T, Jones, SM, Li, Q, Lopez-Bigas, N, Luo, R, Pearson, JV, Quesada, V, Raphael, BJ, Sander, C, Speed, TP, Stuart, JM, Teague, JW, Totoki, Y, Tsunoda, T, Valencia, A, Wheeler, DA, Wu, H, Zhao, S, Zhou, G, Stein, LD, Lathrop, M, Ouellette, BFF, Thomas, G, Yoshida, T, Axton, M, Gunter, C, McPherson, JD, Miller, LJ, Kasprzyk, A, Zhang, J, Haider, SA, Wang, J, Yung, CK, Cross, A, Liang, Y, Gnaneshan, S, Guberman, J, Hsu, J, Chalmers, DRC, Hasel, KW, Kaan, TSH, Knoppers, BM, Lowrance, WW, Masui, T, Rodriguez, LL, Vergely, C, Cloonan, N, Defazio, A, Eshleman, JR, Etemadmoghadam, D, Gardiner, BA, Kench, JG, Sutherland, RL, Tempero, MA, Waddell, NJ, Wilson, PJ, Gallinger, S, Tsao, M-S, Shaw, PA, Petersen, GM, Mukhopadhyay, D, DePinho, RA, Thayer, S, Muthuswamy, L, Shazand, K, Beck, T, Sam, M, Timms, L, Ballin, V, Ji, J, Zhang, X, Chen, F, Hu, X, Yang, Q, Tian, G, Zhang, L, Xing, X, Li, X, Zhu, Z, Yu, Y, Yu, J, Tost, J, Brennan, P, Holcatova, I, Zaridze, D, Brazma, A, Egevad, L, Prokhortchouk, E, Banks, RE, Uhlen, M, Viksna, J, Ponten, F, Skryabin, K, Birney, E, Borg, A, Borresen-Dale, A-L, Caldas, C, Foekens, JA, Martin, S, Reis-Filho, JS, Richardson, AL, Sotiriou, C, van't Veer, L, Birnbaum, D, Blanche, H, Boucher, P, Boyault, S, Masson-Jacquemier, JD, Pauporte, I, Pivot, X, Vincent-Salomon, A, Tabone, E, Theillet, C, Treilleux, I, Bioulac-Sage, P, Decaens, T, Franco, D, Gut, M, Samuel, D, Zucman-Rossi, J, Eils, R, Brors, B, Korbel, JO, Korshunov, A, Landgraf, P, Lehrach, H, Pfister, S, Radlwimmer, B, Reifenberger, G, Taylor, MD, von Kalle, C, Majumder, PP, Pederzoli, P, Lawlor, RT, Delledonne, M, Bardelli, A, Gress, T, Klimstra, D, Zamboni, G, Nakamura, Y, Miyano, S, Fujimoto, A, Campo, E, de Sanjose, S, Montserrat, E, Gonzalez-Diaz, M, Jares, P, Himmelbaue, H, Bea, S, Aparicio, S, Easton, DF, Collins, FS, Compton, CC, Lander, ES, Burke, W, Green, AR, Hamilton, SR, Kallioniemi, OP, Ley, TJ, Liu, ET, and Wainwright, BJ

Abstract

The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

Published
2010

44. Liver-targeted disruption of Apc in mice activates βcatenin signaling and leads to hepatocellular carcinomas.

Author

Colnot, S., Decaens, T., Niwa-Kawakita, M., Godard, C., Hamard, G., Kahn, A., Giovannini, M., and Perret, C.

Subjects
*BILIARY tract, *ABDOMEN, *LIVER cancer, *CARCINOGENESIS, *LIVER cells, *AMINO acids
Abstract

Although inappropriate activation of the Wnt/β-catenin pathway has been implicated in the development of hepatocellular carcinoma (HCC), the role of this signaling in liver carcinogenesis remains unclear. To investigate this issue, we constructed a mutant mouse strain, Apclox/lox, in which exon 14 of the tumor-suppressor gene adenomatous polyposis coli (Apc) is flanked by loxP sequences. i.v. injection of adenovirus encoding Cre recombinase (AdCre) at high multiplicity (109 plaque-forming units (pfu) per mouse) inactivated the Apc gene in the liver and resulted in marked hepatomegaly, hepatocyte hyperplasia, and rapid mortality. β-Catenin signaling activation was demonstrated by nuclear and cytoplasmic accumulation of β-catenin in the hepatocytes and by the induction of β-catenin target genes (glutamine synthetase, glutamate transporter 1, ornithine aminotransferase, and leukocyte cell-derived chemotaxin 2) in the liver. To test a long-term oncogenic effect, we inoculated mice with lower doses of AdCre (0.5 × 109 pfu per mouse), compatible with both survival and persistence of β-catenin-activated cells. In these conditions, 67% of mice developed HCC. β-Catenin signaling was strongly activated in these Apc-inactivated HCCs. The HCCs were well, moderately, or poorly differentiated. Indeed, their histological and molecular features mimicked human HCC. Thus, deletion of Apc in the liver provides a valuable model of human HCC, and, in this model, activation of the Wnt/β-catenin pathway by invalidation of Apc is required for liver tumorigenesis. [ABSTRACT FROM AUTHOR]

Published
2004
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48. IMPACT OF LAND MANAGEMENT ON SOIL MACROFAUNA IN THE ORIENTAL LLANOS OF COLOMBIA

Author

Decaens, T., Lavelle, P., Jimenez Jaen, J.J., Escobar, G., and Rippstein, G.

Subjects
DENSITE, Utilisation des terres, BIOMASSE, GESTION DU SOL, BIODIVERSITE, MACROFAUNE, FAUNE DU SOL, FORET GALERIE, Facteur du milieu, SAVANE, Faune du sol, E11 - Economie et politique foncières, Biomasse, LOMBRIC, Lumbricidae, Savane

49. 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

50. 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

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