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1. Long-term outcomes of ablation, liver resection, and liver transplant as first-line treatment for solitary HCC of 3 cm or less using an intention-to-treat analysis: A retrospective cohort study

Author

Ivanics, T., Rajendran, L., Abreu, P.A., Claasen, M.P.A.W., Shwaartz, C., Patel, M.S., Choi, W.J., Doyle, A., Muaddi, H., McGilvray, I.D., Selzner, M., Beecroft, R., Kachura, J., Bhat, M., Selzner, N., Ghanekar, A., Cattral, M., Sayed, B., Reichman, T., Lilly, L., and Sapisochin, G.

Published
2022
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3. Comparison of treatments for solitary, small hepatocellular carcinoma: a network meta-analysis

Author

Choi, W.J., primary, Ivanics, T., additional, Rajendran, L., additional, Li, Z., additional, Jones, O., additional, Gravely, A., additional, Claasen, M., additional, Yoon, P., additional, Ladak, F., additional, Rana, M., additional, Gotlieb, N., additional, Dini, Y., additional, Naccarato, K., additional, McCluskey, S., additional, Ferreira, R., additional, Msallak, H., additional, Chow, J., additional, Abreu, P., additional, Rabindranath, M., additional, Selvanathan, C., additional, Muaddi, H., additional, Magyar, C., additional, Englesakis, M., additional, Hansen, B., additional, and Sapisochin, G., additional

Published
2024
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7. The toronto management of initially unresectable liver metastases from colorectal cancer in a living donor liver transplant program

Author

Rajendran, L., primary, Claasen, M.P.A.W., additional, Ivanics, T., additional, McGilvray, I.D., additional, Cattral, M.S., additional, Ghanekar, A., additional, Selzner, N., additional, Moulton, C.A., additional, Reichman, T., additional, Shwaartz, C., additional, Burkes, R., additional, Winter, E., additional, Gallinger, S., additional, and Sapisochin, G., additional

Published
2023
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10. Novel benchmark values for redo liver transplantation – does the outcome justify the effort?

Author

UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service de chirurgie et transplantation abdominale, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, Abbassi, F, Gero, D, Muller, X, Bueno, A, Figiel, W, Robin, F, Laroche, S, Picard, B, Shankar, S, Ivanics, T, van Reeven, M, van Leeuwen, O B, Braun, H J, Monbaliu, D, Breton, A, Vachharajani, N, Bonaccorsi Riani, Eliano, Nowak, G, McMillan, R R, Abu-Gazala, S, Nair, A, Bruballa, R, Paterno, F, Weppler Sears, D, Pinna, A D, Guarrera, J V, de Santibañes, E, de Santibañes, M, Hernandez-Aleja, R, Olthoff, K, Ghobrial, R M, Ericzon, B-G, Ciccarelli, Olga, Chapman, W C, Mabrut, J-Y, Pirenne, J, Müllhaupt, B, Ascher, N L, Porte, R J, de Meier, V E, Polak, W G, Sapisochin, G, Attia, M, Weiss, E, Adam, R A, Cherqui, D, Boudjema, K, Zienewicz, K, Jassem, W, Puhan, M, Dutkowski, P, Clavien, P-A, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service de chirurgie et transplantation abdominale, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, Abbassi, F, Gero, D, Muller, X, Bueno, A, Figiel, W, Robin, F, Laroche, S, Picard, B, Shankar, S, Ivanics, T, van Reeven, M, van Leeuwen, O B, Braun, H J, Monbaliu, D, Breton, A, Vachharajani, N, Bonaccorsi Riani, Eliano, Nowak, G, McMillan, R R, Abu-Gazala, S, Nair, A, Bruballa, R, Paterno, F, Weppler Sears, D, Pinna, A D, Guarrera, J V, de Santibañes, E, de Santibañes, M, Hernandez-Aleja, R, Olthoff, K, Ghobrial, R M, Ericzon, B-G, Ciccarelli, Olga, Chapman, W C, Mabrut, J-Y, Pirenne, J, Müllhaupt, B, Ascher, N L, Porte, R J, de Meier, V E, Polak, W G, Sapisochin, G, Attia, M, Weiss, E, Adam, R A, Cherqui, D, Boudjema, K, Zienewicz, K, Jassem, W, Puhan, M, Dutkowski, P, and Clavien, P-A

Published
2022

11. Long-term outcomes of ablation, liver resection, and liver transplant as first-line treatment for solitary HCC of 3 cm or less using an intention-to-treat analysis:A retrospective cohort study

Author

Ivanics, T., Rajendran, L., Abreu, P. A., Claasen, M. P. A. W., Shwaartz, C., Patel, M. S., Choi, W. J., Doyle, A., Muaddi, H., McGilvray, I. D., Selzner, M., Beecroft, R., Kachura, J., Bhat, M., Selzner, N., Ghanekar, A., Cattral, M., Sayed, B., Reichman, T., Lilly, L., Sapisochin, G., Ivanics, T., Rajendran, L., Abreu, P. A., Claasen, M. P. A. W., Shwaartz, C., Patel, M. S., Choi, W. J., Doyle, A., Muaddi, H., McGilvray, I. D., Selzner, M., Beecroft, R., Kachura, J., Bhat, M., Selzner, N., Ghanekar, A., Cattral, M., Sayed, B., Reichman, T., Lilly, L., and Sapisochin, G.

Abstract

Background: Curative-intent therapies for hepatocellular carcinoma (HCC) include radiofrequency ablation (RFA), liver resection (LR), and liver transplantation (LT). Controversy exists in treatment selection for early-stage tumours. We sought to evaluate the oncologic outcomes of patients who received either RFA, LR, or LT as first-line treatment for solitary HCC ≤ 3 cm in an intention-to-treat analysis. Materials and methods: All patients with solitary HCC ≤ 3 cm who underwent RFA, LR, or were listed for LT between Feb-2000 and Nov-2018 were analyzed. Cox regression analysis was then performed to compare intention-to-treat (ITT) survival by initial treatment allocation and disease-free survival (DFS) by treatment received in patients eligible for all three treatments. Results: A total of 119 patients were identified (RFA n = 83; LR n = 25; LT n = 11). The overall intention-to-treat survival was similar between the three groups. The overall DFS was highest for the LT group. This was significantly higher than RFA (p = 0.02), but not statistically significantly different from LR (p = 0.14). After multivariable adjustment, ITT survival was similar in the LR and LT groups relative to RFA (LR HR:1.13, 95%CI 0.33–3.82; p = 0.80; LT HR:1.39, 95%CI 0.35–5.44; p = 0.60). On multivariable DFS analysis, only LT was better relative to RFA (LR HR:0.52, 95%CI 0.26–1.02; p = 0.06; LT HR:0.15, 95%CI 0.03–0.67; p = 0.01). Compared to LR, LT was associated with a numerically lower hazard on multivariable DFS analysis, though this did not reach statistical significance (HR 0.30, 95%CI 0.06–1.43; p = 0.13) Conclusion: For treatment-naïve patients with solitary HCC ≤ 3 cm who are eligible for RFA, LR, and LT, adjusted ITT survival is equivalent amongst the treatment modalities, however, DFS is better with LR and LT, compared with RFA. Differences in recurrence between treatment modalities and equipoise in ITT survival provides support for a future prospective trial in this setting.

Published
2022

12. Experience with solid organ transplantation in patients with previous immunotherapy treatment is still limited but this is changing: The survey-based view of the global transplant society

Author

Ivanics, T., Claasen, M. paw, Al-Adra, D., Sapisochin, G., Ivanics, T., Claasen, M. paw, Al-Adra, D., and Sapisochin, G.

Abstract

Background: The use of immunotherapy for cancer is increasing and is expected to continue growing. The outcomes after solid organ transplantation(SOT) in patients who received immunotherapy before SOT remain unclear. We evaluated the global transplant surgery community's attitude towards and experience with patients who received immunotherapy for malignancy before SOT. Methods: An online-based survey was sent to North American transplant program directors in December-2020 and members of the International Liver Transplant Society in November-2021 evaluating experiences with and attitudes towards SOT in recipients with previous immunotherapy for cancer. Results: A total of 119 respondents completed the survey(119/175;completion rate:68%), representing centers from North America, South America, Europe, Asia, and Australia. Seventy-one(62%) respondents would consider SOT in patients with a previous history of immunotherapy for cancer, whereas thirty-nine(34%) were aware of such immunotherapy-treated recipients being transplanted, with an increasing trend over the last few years(2016[n = 1]-2020[n = 14]). Institutional clinical management policies in this setting were lacking in most centers(n = 85[75%]). Conclusions: The international transplant community is receptive to transplanting transplant candidates previously treated with immunotherapy for cancer, although experience is still limited. In this context, more centers have started to offer SOT to patients with a history of immunotherapy for cancer in recent years. However, support from clear and robust institutional policies in this endeavor is scant. Therefore, there is a high need for consensus guidelines to inform future clinical management, especially as immunotherapy for cancer is likely to continue to increase in the coming years.

Published
2022

13. Novel benchmark values for redo liver transplantation – does the outcome justify the effort?

Author

Abbassi, F, primary, Gero, D, additional, Muller, X, additional, Bueno, A, additional, Figiel, W, additional, Robin, F, additional, Laroche, S, additional, Picard, B, additional, Shankar, S, additional, Ivanics, T, additional, van Reeven, M, additional, van Leeuwen, O B, additional, Braun, H J, additional, Monbaliu, D, additional, Breton, A, additional, Vachharajani, N, additional, Bonaccorsi Riani, E, additional, Nowak, G, additional, McMillan, R R, additional, Abu-Gazala, S, additional, Nair, A, additional, Bruballa, R, additional, Paterno, F, additional, Weppler Sears, D, additional, Pinna, A D, additional, Guarrera, J V, additional, de Santibañes, E, additional, de Santibañes, M, additional, Hernandez-Aleja, R, additional, Olthoff, K, additional, Ghobrial, R M, additional, Ericzon, B-G, additional, Ciccarelli, O, additional, Chapman, W C, additional, Mabrut, J-Y, additional, Pirenne, J, additional, Müllhaupt, B, additional, Ascher, N L, additional, Porte, R J, additional, de Meier, V E, additional, Polak, W G, additional, Sapisochin, G, additional, Attia, M, additional, Weiss, E, additional, Adam, R A, additional, Cherqui, D, additional, Boudjema, K, additional, Zienewicz, K, additional, Jassem, W, additional, Puhan, M, additional, Dutkowski, P, additional, and Clavien, P-A, additional

Published
2022
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20. Regorafenib improves survival after sorafenib in patients with recurrent HCC after liver transplantation

Author

Iavarone, M., primary, Invernizzi, F., additional, Ivanics, T., additional, Mazza, S., additional, Zavaglia, C., additional, Sanduzzi-Zamparelli, M., additional, Fraile-López, M., additional, Czauderna, C., additional, Costanzo, G. Di, additional, Bhoori, S., additional, Pinter, M., additional, Manini, M.A., additional, Amaddeo, G., additional, Yunquera, A. Fernandez, additional, Piñero, F., additional, Rodríguez, M.J. Blanco, additional, Anders, M., additional, Soteras, G. Aballay, additional, Villadsen, G.E., additional, Yoon, P. Daechul, additional, Cesarini, L., additional, Díaz-González, Á., additional, González-Diéguez, M.L., additional, Tortora, R., additional, Weinmann, A., additional, Mazzaferro, V., additional, Cristóbal, M. Romero, additional, Crespo, G., additional, Regnault, H., additional, De Giorgio, M., additional, Varela, M., additional, Prince, R., additional, Scuddeler, L., additional, Donato, M.F., additional, Wörns, M.A., additional, Bruix, J., additional, Sapisochin, G., additional, Lampertico, P., additional, and Reig, M., additional

Published
2021
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23. Laparoscopic segment 8 liver resection

Author

Shwaartz, C., primary, Fung, A., additional, Kelly, P., additional, Qu, Joy, additional, Lin, J., additional, Ivanics, T., additional, Sapisochin, G., additional, McGilvray, I., additional, and Reichman, T.W., additional

Published
2021
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42. A Novel Model for the in VivoMonitoring of Uterine Microcirculation and Intracellular Free Calcium Changes in Rat

Author

Ruttner, Z., Ivanics, T., Slaaf, D.W., Reneman, R.S., Ligeti, L., and Toth, A.

Abstract

The aim of this work was to develop a model to study the microcirculation and relative levels of intracellular free calcium in the myometrium of pregnant rats. On Day 21 of gestation a lobe of uterus was prepared free, flipped over, and mounted in a superfusion chamber leaving the radix and thereby the innervation and circulation intact. RBC velocity and arteriolar diameters were determined by means of intravital video microscopy before and after stimulation (norepinephrine). To study intracellular free calcium changes, the fluorescent dye Indo-1 AM was added to the superfusate in the chamber. Fluorescence images were recorded and ratios of the images collected at 400 and 506 nm were calculated and changes thereof were assumed to represent intracellular free calcium changes. RBC velocity and arteriolar diameter did not change for at least 1 h, while the response to norepinephrine was similar at the beginning of the experiment and after 120 min. In four separate interventions, the uterus was challenged with 5 × 10−4IU/ml oxytocin, 4.5 mM calcium, 5 × 10−4IU/ml oxytocin with 4.5 mM calcium, and 5 μM ionomycin, resulting in an increase of the 400/506 nm ratio of 27, 31, 76, and 103%, respectively, representing a relative increase in intracellular free calcium. This novel in vivomodel is suitable for monitoring intracellular free calcium changes and to record RBC velocities and blood vessel diameters in the myometrium of pregnant rats.

Published
2000
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44. Altered calcium handling is an early sign of streptozotocin-induced diabetic cardiomyopathy

Author

Ligeti, L., Szenczi, O., Prestia, C. M., Szabo, C., Horvath, K., Marcsek, Z. L., R.G.P.M. Stiphout, van, Natal van Riel, Op Den Buijs, J., Ger Vusse, van der, Ivanics, T., Control Systems, and Computational Biology

Subjects
SDG 3 - Good Health and Well-being, cardiovascular system
Abstract

The main objective of the present study was to determine alterations of calcium handling in the diabetic rat heart during the transition from adaptive to maladaptive phase of cardiomyopathy. By inhibiting the nuclear enzyme poly(ADP-ribose) polymerase (PARP), we also investigated the possible role of this enzyme in the sequence of pathological events. Six weeks after induction of type I diabetes by injection of streptozotocin in rats, the hearts were perfused according to Langendorff. Intracellular-free calcium (Ca2+i) levels were measured by surface fluorometry using Indo-1 AM. Cyclic changes in Ca2+i concentrations and hemodynamic parameters were measured simultaneously. The hearts were challenged by infusion of isoproterenol. Six weeks of diabetes resulted in reduced inotropy and lusitropy. The diabetic hearts (DM) expressed a significantly elevated end-diastolic Ca2+i level (control, 111±20 vs DM, 221±35 nM). The maximal transport capacity of SERCA2a and conductance of RyR2 were reduced. These changes were not accompanied by major alterations in the tissue content of SERCA2a, RyR2, phospholamban and Na+/Ca2+ exchanger. In response to ß-adrenergic activation, SERCA2a transport capacity and RyR2 conductance were stunted in the DM hearts. Inhibition of PARP induced minor changes in the mechanical function and calcium handling of the DM hearts. In conclusion, the observed changes in contractility and in Ca2+i handling are most likely attributable to functional disturbances of SERCA2a and RyR2 in this transitional phase of diabetes. At this stage of diabetes, PARP does not appear to play a significant pathogenetic role in the alterations in contractile function and calcium handling

49. Liver transplantation for primary and secondary liver tumours. patient-level meta-analyses compared to unos conventional indications.

Author

Ciria R, Ivanics T, Aliseda D, Claasen M, Alconchel F, Gaviria F, Briceño J, Berardi G, Rotellar F, and Sapisochin G

Abstract

Background Aims: Liver transplant (LT) for Transplant Oncology (TO) indications is being slowly adopted worldwide and has been recommended to be incorporated cautiously due to concerns on mid-long term survival and its impact on waiting list., Approach Results: We conducted four systematic reviews of all series on TO indications (intrahepatic (iCC) and perihilar cholangiocarcinoma (phCC)), liver metastases from neuroendocrine tumors (NET) and colorectal cancer (CRLM)) and compared them using patient-level meta-analyses to data obtained from UNOS database considering conventional daily-practice indications. Secondary analyses were done for specific selection criteria (Mayo-like protocols for phCC, SECA-2 for CRLM and Milan criteria for NET). A total of 112.014 LT were analyzed from 2005 to 2020 from the UNOS databases and compared with 345, 721, 494 and 103 patients obtained from meta-analyses on iCC and phCC, and liver metastases from NET and CRLM, respectively. Five-years overall survival was 53,3%, 56,4%, 68,6% and 53,8%, respectively. In Mantel-Cox one-to-one comparisons, survival of TO indications was superior to combined LT, second and third LT and and not statistically significant different to LT in recipients>70 years and high BMI., Conclusions: Liver transplantation for TO indications has adequate 5-years survival rates, mostly when performed under the selection criteria available in literature (Mayo-like protocols for phCC, SECA-2 for CRLM and Milan for NET). Despite concerns on its impact on waiting list, some other LT indications are being performed with lower survival. These oncological patients should be given the opportunity to have a definitive curative therapy within validated criteria., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Published
2024
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50. Temporal evolution of living donor liver transplantation survival-A United Network for Organ Sharing registry study.

Author

Magyar CTJ, Li Z, Aceituno L, Claasen MPAW, Ivanics T, Choi WJ, Rajendran L, Sayed BA, Bucur R, Rukavina N, Selzner N, Ghanekar A, Cattral M, and Sapisochin G

Abstract

Living donor liver transplantation (LDLT) is a curative treatment for various liver diseases, reducing waitlist times and associated mortality. We aimed to assess the overall survival (OS), identify predictors for mortality, and analyze differences in risk factors over time. Adult patients undergoing LDLT were selected from the United Network for Organ Sharing database from inception (1987) to 2023. The Kaplan-Meier method was used for analysis, and multivariable Cox proportional hazard models were conducted. In total, 7257 LDLT recipients with a median age of 54 years (interquartile range [IQR]: 45-61 years), 54% male, 80% non-Hispanic White, body mass index of 26.3 kg/m 2 (IQR: 23.2-30.0 kg/m 2 ), and model for end-stage liver disease score of 15 (IQR: 11-19) were included. The median cold ischemic time was 1.6 hours (IQR: 1.0-2.3 hours) with 88% right lobe grafts. The follow-up was 4.0 years (IQR: 1.0-9.2 years). The contemporary reached median OS was 17.0 years (95% CI: 16.1, 18.1 years), with the following OS estimates: 1 year 95%; 3 years 89%; 5 years 84%; 10 years 72%; 15 years 56%; and 20 years 43%. Nine independent factors associated with mortality were identified, with an independent improved OS in the recent time era (adjusted hazards ratio: 0.53; 95% CI: 0.39, 0.71). The median center-caseload per year was 5 (IQR: 2-10), with observed center-specific improvement of OS. LDLT is a safe procedure with excellent OS. Its efficacy has improved despite an increase of risk parameters, suggesting its limits are yet to be met., Competing Interests: Declaration of competing interests The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. G. Sapisochin discloses consultancy for Astra-Zeneca, Roche, Evidera, Novartis, HepaRegenix, and Integra; has received financial compensation for talks for Roche, Astra-Zeneca, Chiesi, and Integra; and has received a grant from Roche. None of the other authors have any conflicts of interest to declare., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Published
2024
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