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3. Posttransplant Outcomes in Older Patients With Hepatocellular Carcinoma Are Driven by Non–Hepatocellular Carcinoma Factors

Author

Adeniji, Nia, Arjunan, Vinodhini, Prabhakar, Vijay, Mannalithara, Ajitha, Ghaziani, Tara, Ahmed, Aijaz, Kwo, Paul, Nguyen, Mindie, Melcher, Marc L, Busuttil, Ronald W, Florman, Sander S, Haydel, Brandy, Ruiz, Richard M, Klintmalm, Goran B, Lee, David D, Taner, C Burcin, Hoteit, Maarouf A, Verna, Elizabeth C, Halazun, Karim J, Tevar, Amit D, Humar, Abhinav, Chapman, William C, Vachharajani, Neeta, Aucejo, Federico, Nydam, Trevor L, Markmann, James F, Mobley, Constance, Ghobrial, Mark, Langnas, Alan N, Carney, Carol A, Berumen, Jennifer, Schnickel, Gabriel T, Sudan, Debra L, Hong, Johnny C, Rana, Abbas, Jones, Christopher M, Fishbein, Thomas M, Agopian, Vatche, and Dhanasekaran, Renumathy

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Clinical Research, Liver Disease, Organ Transplantation, Transplantation, Rare Diseases, Cancer, Liver Cancer, Aging, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Good Health and Well Being, Aged, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Liver Transplantation, Middle Aged, Retrospective Studies, Risk Assessment, Survival Rate, United States, Surgery, Clinical sciences
Abstract

The incidence of hepatocellular carcinoma (HCC) is growing in the United States, especially among the elderly. Older patients are increasingly receiving transplants as a result of HCC, but the impact of advancing age on long-term posttransplant outcomes is not clear. To study this, we used data from the US Multicenter HCC Transplant Consortium of 4980 patients. We divided the patients into 4 groups by age at transplantation: 18 to 64 years (n = 4001), 65 to 69 years (n = 683), 70 to 74 years (n = 252), and ≥75 years (n = 44). There were no differences in HCC tumor stage, type of bridging locoregional therapy, or explant residual tumor between the groups. Older age was confirmed to be an independent and significant predictor of overall survival even after adjusting for demographic, etiologic, and cancer-related factors on multivariable analysis. A dose-response effect of age on survival was observed, with every 5-year increase in age older than 50 years resulting in an absolute increase of 8.3% in the mortality rate. Competing risk analysis revealed that older patients experienced higher rates of non-HCC-related mortality (P = 0.004), and not HCC-related death (P = 0.24). To delineate the precise cause of death, we further analyzed a single-center cohort of patients who received a transplant as a result of HCC (n = 302). Patients older than 65 years had a higher incidence of de novo cancer (18.1% versus 7.6%; P = 0.006) after transplantation and higher overall cancer-related mortality (14.3% versus 6.6%; P = 0.03). Even carefully selected elderly patients with HCC have significantly worse posttransplant survival rates, which are mostly driven by non-HCC-related causes. Minimizing immunosuppression and closer surveillance for de novo cancers can potentially improve the outcomes in elderly patients who received a transplant as a result of HCC.

Published
2021

8. Utilization of livers donated after circulatory death for transplantation - An international comparison

Author

Eden, J, Da Silva, R, Cortes-Cerisuelo, M, Croome, K, De Carlis, R, Hessheimer, A, Muller, X, de Goeij, F, Banz, V, Magini, G, Compagnon, P, Elmer, A, Lauterio, A, Panconesi, R, Widmer, J, Dondossola, D, Muiesan, P, Monbaliu, D, de Rosner van Rosmalen, M, Detry, O, Fondevila, C, Jochmans, I, Pirenne, J, Immer, F, Oniscu, G, de Jonge, J, Lesurtel, M, De Carlis, L, Taner, C, Heaton, N, Schlegel, A, Dutkowski, P, Eden, Janina, Da Silva, Richard Sousa, Cortes-Cerisuelo, Miriam, Croome, Kristopher, De Carlis, Riccardo, Hessheimer, Amelia J, Muller, Xavier, de Goeij, Femke, Banz, Vanessa, Magini, Giulia, Compagnon, Philippe, Elmer, Andreas, Lauterio, Andrea, Panconesi, Rebecca, Widmer, Jeannette, Dondossola, Daniele, Muiesan, Paolo, Monbaliu, Diethard, de Rosner van Rosmalen, Marieke, Detry, Olivier, Fondevila, Constantino, Jochmans, Ina, Pirenne, Jacques, Immer, Franz, Oniscu, Gabriel C, de Jonge, Jeroen, Lesurtel, Mickaël, De Carlis, Luciano G, Taner, C Burcin, Heaton, Nigel, Schlegel, Andrea, Dutkowski, Philipp, Eden, J, Da Silva, R, Cortes-Cerisuelo, M, Croome, K, De Carlis, R, Hessheimer, A, Muller, X, de Goeij, F, Banz, V, Magini, G, Compagnon, P, Elmer, A, Lauterio, A, Panconesi, R, Widmer, J, Dondossola, D, Muiesan, P, Monbaliu, D, de Rosner van Rosmalen, M, Detry, O, Fondevila, C, Jochmans, I, Pirenne, J, Immer, F, Oniscu, G, de Jonge, J, Lesurtel, M, De Carlis, L, Taner, C, Heaton, N, Schlegel, A, Dutkowski, P, Eden, Janina, Da Silva, Richard Sousa, Cortes-Cerisuelo, Miriam, Croome, Kristopher, De Carlis, Riccardo, Hessheimer, Amelia J, Muller, Xavier, de Goeij, Femke, Banz, Vanessa, Magini, Giulia, Compagnon, Philippe, Elmer, Andreas, Lauterio, Andrea, Panconesi, Rebecca, Widmer, Jeannette, Dondossola, Daniele, Muiesan, Paolo, Monbaliu, Diethard, de Rosner van Rosmalen, Marieke, Detry, Olivier, Fondevila, Constantino, Jochmans, Ina, Pirenne, Jacques, Immer, Franz, Oniscu, Gabriel C, de Jonge, Jeroen, Lesurtel, Mickaël, De Carlis, Luciano G, Taner, C Burcin, Heaton, Nigel, Schlegel, Andrea, and Dutkowski, Philipp

Abstract

Background and aim: Liver graft utilization rates are a hot topic due to the worldwide organ shortage and an increasing number of transplant candidates on waiting lists. Liver perfusion techniques have been introduced in several countries, and may help to increase the organ supply, as they potentially allow the assessment of livers before use. Methods: Liver offers were counted from donation after circulatory death (DCD) donors (Maastricht-type-III) arising during the past decade in eight countries, including Belgium, France, Italy, the Netherlands, Spain, Switzerland, UK, and US. Initial DCD-type-III liver offers were correlated with accepted, recovered and implanted livers. Results: A total number of 34`269 DCD livers were offered, resulting in 9`780 liver transplants (28.5%). The discard rates were highest in UK and US, ranging between 70 and 80%. In contrast, much lower DCD liver discard rates, e.g., between 30-40%, were found in Belgium, France, Italy, Spain and Switzerland. In addition, large differences were recognized in the use of various machine perfusion techniques, and in terms of risk factors in the cohorts of implanted livers. For example, the median donor age and functional donor warm ischemia were highest in Italy, e.g., >40minutes, followed by Switzerland, France, and the Netherlands. Importantly, such varying risk profiles of accepted DCD livers between countries did not translate into large differences in five-year graft survival rates, which ranged between 60-82% in this analysis. Conclusions: We highlight a significant number of discarded and consequently unused DCD liver offers. Countries with more routine use of in- and ex-situ machine perfusion strategies showed better DCD utilization rates without compromised outcome. Impact and implications: A significant number of Maastricht type III DCD livers are discarded across Europe and North America today. The overall utilization rate among eight Western countries is 28.5%, but varies significant

Published
2023

12. A multicentre outcome analysis to define global benchmarks for donation after circulatory death liver transplantation

Author

Schlegel, A, van Reeven, M, Croome, K, Parente, A, Dolcet, A, Widmer, J, Meurisse, N, De Carlis, R, Hessheimer, A, Jochmans, I, Mueller, M, van Leeuwen, O, Nair, A, Tomiyama, K, Sherif, A, Elsharif, M, Kron, P, van der Helm, D, Borja-Cacho, D, Bohorquez, H, Germanova, D, Dondossola, D, Olivieri, T, Camagni, S, Gorgen, A, Patrono, D, Cescon, M, Croome, S, Panconesi, R, Flores Carvalho, M, Ravaioli, M, Caicedo, J, Loss, G, Lucidi, V, Sapisochin, G, Romagnoli, R, Jassem, W, Colledan, M, De Carlis, L, Rossi, G, Di Benedetto, F, Miller, C, van Hoek, B, Attia, M, Lodge, P, Hernandez-Alejandro, R, Detry, O, Quintini, C, Oniscu, G, Fondevila, C, Malagó, M, Pirenne, J, Ijzermans, J, Porte, R, Dutkowski, P, Taner, C, Heaton, N, Clavien, P, Polak, W, Muiesan, P, Schlegel, Andrea, van Reeven, Marjolein, Croome, Kristopher, Parente, Alessandro, Dolcet, Annalisa, Widmer, Jeannette, Meurisse, Nicolas, De Carlis, Riccardo, Hessheimer, Amelia, Jochmans, Ina, Mueller, Matteo, van Leeuwen, Otto B, Nair, Amit, Tomiyama, Koji, Sherif, Ahmed, Elsharif, Mohamed, Kron, Philipp, van der Helm, Danny, Borja-Cacho, Daniel, Bohorquez, Humberto, Germanova, Desislava, Dondossola, Daniele, Olivieri, Tiziana, Camagni, Stefania, Gorgen, Andre, Patrono, Damiano, Cescon, Matteo, Croome, Sarah, Panconesi, Rebecca, Flores Carvalho, Mauricio, Ravaioli, Matteo, Caicedo, Juan Carlos, Loss, George, Lucidi, Valerio, Sapisochin, Gonzalo, Romagnoli, Renato, Jassem, Wayel, Colledan, Michele, De Carlis, Luciano, Rossi, Giorgio, Di Benedetto, Fabrizio, Miller, Charles M, van Hoek, Bart, Attia, Magdy, Lodge, Peter, Hernandez-Alejandro, Roberto, Detry, Olivier, Quintini, Cristiano, Oniscu, Gabriel C, Fondevila, Constantino, Malagó, Massimo, Pirenne, Jacques, IJzermans, Jan Nm, Porte, Robert J, Dutkowski, Philipp, Taner, C Burcin, Heaton, Nigel, Clavien, Pierre-Alain, Polak, Wojciech G, Muiesan, Paolo, Schlegel, A, van Reeven, M, Croome, K, Parente, A, Dolcet, A, Widmer, J, Meurisse, N, De Carlis, R, Hessheimer, A, Jochmans, I, Mueller, M, van Leeuwen, O, Nair, A, Tomiyama, K, Sherif, A, Elsharif, M, Kron, P, van der Helm, D, Borja-Cacho, D, Bohorquez, H, Germanova, D, Dondossola, D, Olivieri, T, Camagni, S, Gorgen, A, Patrono, D, Cescon, M, Croome, S, Panconesi, R, Flores Carvalho, M, Ravaioli, M, Caicedo, J, Loss, G, Lucidi, V, Sapisochin, G, Romagnoli, R, Jassem, W, Colledan, M, De Carlis, L, Rossi, G, Di Benedetto, F, Miller, C, van Hoek, B, Attia, M, Lodge, P, Hernandez-Alejandro, R, Detry, O, Quintini, C, Oniscu, G, Fondevila, C, Malagó, M, Pirenne, J, Ijzermans, J, Porte, R, Dutkowski, P, Taner, C, Heaton, N, Clavien, P, Polak, W, Muiesan, P, Schlegel, Andrea, van Reeven, Marjolein, Croome, Kristopher, Parente, Alessandro, Dolcet, Annalisa, Widmer, Jeannette, Meurisse, Nicolas, De Carlis, Riccardo, Hessheimer, Amelia, Jochmans, Ina, Mueller, Matteo, van Leeuwen, Otto B, Nair, Amit, Tomiyama, Koji, Sherif, Ahmed, Elsharif, Mohamed, Kron, Philipp, van der Helm, Danny, Borja-Cacho, Daniel, Bohorquez, Humberto, Germanova, Desislava, Dondossola, Daniele, Olivieri, Tiziana, Camagni, Stefania, Gorgen, Andre, Patrono, Damiano, Cescon, Matteo, Croome, Sarah, Panconesi, Rebecca, Flores Carvalho, Mauricio, Ravaioli, Matteo, Caicedo, Juan Carlos, Loss, George, Lucidi, Valerio, Sapisochin, Gonzalo, Romagnoli, Renato, Jassem, Wayel, Colledan, Michele, De Carlis, Luciano, Rossi, Giorgio, Di Benedetto, Fabrizio, Miller, Charles M, van Hoek, Bart, Attia, Magdy, Lodge, Peter, Hernandez-Alejandro, Roberto, Detry, Olivier, Quintini, Cristiano, Oniscu, Gabriel C, Fondevila, Constantino, Malagó, Massimo, Pirenne, Jacques, IJzermans, Jan Nm, Porte, Robert J, Dutkowski, Philipp, Taner, C Burcin, Heaton, Nigel, Clavien, Pierre-Alain, Polak, Wojciech G, and Muiesan, Paolo

Abstract

Background & Aims: The concept of benchmarking is established in the field of transplant surgery; however, benchmark values for donation after circulatory death (DCD) liver transplantation are not available. Thus, we aimed to identify the best possible outcomes in DCD liver transplantation and to propose outcome reference values. Methods: Based on 2,219 controlled DCD liver transplantations, collected from 17 centres in North America and Europe, we identified 1,012 low-risk, primary, adult liver transplantations with a laboratory MELD score of ≤20 points, receiving a DCD liver with a total donor warm ischemia time of ≤30 minutes and asystolic donor warm ischemia time of ≤15 minutes. Clinically relevant outcomes were selected and complications were reported according to the Clavien-Dindo-Grading and the comprehensive complication index (CCI). Corresponding benchmark cut-offs were based on median values of each centre, where the 75th-percentile was considered. Results: Benchmark cases represented between 19.7% and 75% of DCD transplantations in participating centres. The 1-year retransplant and mortality rates were 4.5% and 8.4% in the benchmark group, respectively. Within the first year of follow-up, 51.1% of recipients developed at least 1 major complication (≥Clavien-Dindo-Grade III). Benchmark cut-offs were ≤3 days and ≤16 days for ICU and hospital stay, ≤66% for severe recipient complications (≥Grade III), ≤16.8% for ischemic cholangiopathy, and ≤38.9 CCI points 1 year after transplant. Comparisons with higher risk groups showed more complications and impaired graft survival outside the benchmark cut-offs. Organ perfusion techniques reduced the complications to values below benchmark cut-offs, despite higher graft risk. Conclusions: Despite excellent 1-year survival, morbidity in benchmark cases remains high. Benchmark cut-offs targeting morbidity parameters offer a valid tool to assess the protective value of new preservation technologies in higher risk grou

Published
2022

13. Utilization of livers donated after circulatory death for transplantation – An international comparison

Author

Eden, Janina, Sousa Da Silva, Richard, Cortes-Cerisuelo, Miriam, Croome, Kristopher, De Carlis, Riccardo, Hessheimer, Amelia J., Muller, Xavier, de Goeij, Femke, Banz, Vanessa, Magini, Giulia, Compagnon, Philippe, Elmer, Andreas, Lauterio, Andrea, Panconesi, Rebecca, Widmer, Jeannette, Dondossola, Daniele, Muiesan, Paolo, Monbaliu, Diethard, de Rosner van Rosmalen, Marieke, Detry, Olivier, Fondevila, Constantino, Jochmans, Ina, Pirenne, Jacques, Immer, Franz, Oniscu, Gabriel C., de Jonge, Jeroen, Lesurtel, Mickaël, De Carlis, Luciano G., Taner, C. Burcin, Heaton, Nigel, Schlegel, Andrea, Dutkowski, Philipp, Eden, Janina, Sousa Da Silva, Richard, Cortes-Cerisuelo, Miriam, Croome, Kristopher, De Carlis, Riccardo, Hessheimer, Amelia J., Muller, Xavier, de Goeij, Femke, Banz, Vanessa, Magini, Giulia, Compagnon, Philippe, Elmer, Andreas, Lauterio, Andrea, Panconesi, Rebecca, Widmer, Jeannette, Dondossola, Daniele, Muiesan, Paolo, Monbaliu, Diethard, de Rosner van Rosmalen, Marieke, Detry, Olivier, Fondevila, Constantino, Jochmans, Ina, Pirenne, Jacques, Immer, Franz, Oniscu, Gabriel C., de Jonge, Jeroen, Lesurtel, Mickaël, De Carlis, Luciano G., Taner, C. Burcin, Heaton, Nigel, Schlegel, Andrea, and Dutkowski, Philipp

Abstract

Background & Aims: Liver graft utilization rates are a hot topic due to the worldwide organ shortage and the increasing number of transplant candidates on waiting lists. Liver perfusion techniques have been introduced in several countries, and may help to increase the organ supply, as they potentially enable the assessment of livers before use. Methods: Liver offers were counted from donation after circulatory death (DCD) donors (Maastricht type III) arising during the past decade in eight countries, including Belgium, France, Italy, the Netherlands, Spain, Switzerland, the UK, and the US. Initial type-III DCD liver offers were correlated with accepted, recovered and implanted livers. Results: A total number of 34,269 DCD livers were offered, resulting in 9,780 liver transplants (28.5%). The discard rates were highest in the UK and US, ranging between 70 and 80%. In contrast, much lower DCD liver discard rates, e.g. between 30-40%, were found in Belgium, France, Italy, Spain and Switzerland. In addition, we observed large differences in the use of various machine perfusion techniques, as well as in graft and donor risk factors. For example, the median donor age and functional donor warm ischemia time were highest in Italy, e.g. >40 min, followed by Switzerland, France, and the Netherlands. Importantly, such varying risk profiles of accepted DCD livers between countries did not translate into large differences in 5-year graft survival rates, which ranged between 60-82% in this analysis. Conclusions: Overall, DCD liver discard rates across the eight countries were high, although this primarily reflects the situation in the Netherlands, the UK and the US. Countries where in situ and ex situ machine perfusion strategies were used routinely had better DCD utilization rates without compromised outcomes. Impact and implications: A significant number of Maastricht type III DCD livers are discarded across Europe and North America today. The overall utilization rate

Published
2023

18. Recommendations for Donor and Recipient Selection and Risk Prediction: Working Group Report from the ILTS Consensus Conference in DCD Liver Transplantation

Author

Schlegel, A, Foley, D, Savier, E, Flores Carvalho, M, De Carlis, L, Heaton, N, Taner, C, Schlegel A., Foley D. P., Savier E., Flores Carvalho M., De Carlis L., Heaton N., Taner C. B., Schlegel, A, Foley, D, Savier, E, Flores Carvalho, M, De Carlis, L, Heaton, N, Taner, C, Schlegel A., Foley D. P., Savier E., Flores Carvalho M., De Carlis L., Heaton N., and Taner C. B.

Abstract

Although the utilization of donation after circulatory death donors (DCDs) for liver transplantation (LT) has increased steadily, much controversy remains, and no common acceptance criteria exist with regard to donor and recipient risk factors and prediction models. A consensus conference was organized by International Liver Transplantation Society on January 31, 2020, in Venice, Italy, to review the current clinical practice worldwide regarding DCD-LT and to develop internationally accepted guidelines. The format of the conference was based on the grade system. International experts in this field were allocated to 6 working groups and prepared evidence-based recommendations to answer-specific questions considering the currently available literature. Working group members and conference attendees served as jury to edit and confirm the final recommendations presented at the end of the conference by each working group separately. This report presents the final statements and recommendations provided by working group 2, covering the entire spectrum of donor and recipient risk factors and prediction models in DCD-LT.

Published
2021

27. Nonselective beta‐blockers are associated with a lower risk of hepatocellular carcinoma among cirrhotic patients in the United States

Author

Wijarnpreecha, Karn, primary, Li, Fang, additional, Xiang, Yang, additional, Xu, Xun, additional, Zhu, Cong, additional, Maroufy, Vahed, additional, Wang, Qing, additional, Tao, Wei, additional, Dang, Yifang, additional, Pham, Huy Anh, additional, Zhou, Yujia, additional, Li, Jianfu, additional, Zhang, Xinyuan, additional, Xu, Hua, additional, Taner, C. Burcin, additional, Yang, Liu, additional, and Tao, Cui, additional

Published
2021
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34. Endarterectomy for Iliac Occlusive Disease during Kidney Transplantation: A Multicenter Experience

Author

Sorrells, William S., additional, Mao, Shennen A., additional, Taner, Timucin, additional, Jadlowiec, Caroline C., additional, Farres, Houssam, additional, Davila, Victor, additional, Money, Samuel R., additional, Stone, William M., additional, Al-Khasawneh, Mohammad, additional, Da Rocha-Franco, Joao A. Da Rocha, additional, Oldenburg, Warner A., additional, Oderich, Gustavo S., additional, Taner, C. Burcin, additional, Hakaim, Albert G., additional, and Erben, Young, additional

Published
2020
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46. İkiz Eşinin İntrauterin Ölümü

Author

MUN, S., MUN, Semih, TANER, C. E., TANER, Cüneyt Eftal, ÖZTEKİN, Murat, ÖZTEKİN, M., ÇELİMLİ, F. H., and HORASAN ÇELİMLİ, Fatma

Subjects
İkiz eşinin ölümü,çoğul gebelik
Abstract

Amaç: Fetuslardan birinin uterus içinde ikinci veya üçüncü trimesterde öldüğü ikizgebeliklerde perinatal sonuçları incelemek.Gereç ve yöntem: Ocak 2003-Aralık 2004 tarihleri arasında hastanemizdegerçekleşen 21,593 doğumun kayıtları retrospektif olarak incelendi. Fetuslardanbirinin ikinci veya üçüncü trimesterde öldüğü 12 çoğul gebelik olgusu, perinatal sonuçları açısından incelendi.Bulgular: Toplam 21.593 doğumun 281’i (%1,3) ikiz gebelikti. Bu olgularının 12’si(%4,2) ikinci veya üçüncü trimesterde monofetal ölüm ile komplike olan gebeliklerdi.Gebelerin yaş ortalaması 28 idi. Monofetal ölümün gerçekleştiği ortalamagestasyonel hafta 22 idi ve olgular doğuma kadar ortalama 78 gün izlendi. Doğumların 7’si (%58) sezaryen ile gerçekleşti. 3 olgu (%25) monokoryonikdiamniyotik, 1 olgu (%8) monokoryonik monoamniyotik ve diğer olgular dikoryonikdiamniyotikti. Neonatal mortalite hızı %25 idi.Sonuç: Monofetal ölüm ile komplike olmuş ikiz gebeliklerde plasenta yapıları tespitedilmeli, tedavi ve takip seçeneği ona göre belirlenmelidir

Published
2015

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