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1. Transplantation of a human liver following 3 days of ex situ normothermic preservation

Author

Clavien, Pierre-Alain, Dutkowski, Philipp, Mueller, Matteo, Eshmuminov, Dilmurodjon, Bautista Borrego, Lucia, Weber, Achim, Muellhaupt, Beat, Sousa Da Silva, Richard X, Burg, Brian R, Rudolf von Rohr, Philipp, Schuler, Martin J, Becker, Dustin, Hefti, Max, Tibbitt, Mark W, University of Zurich, and Clavien, Pierre-Alain

Subjects
1502 Bioengineering, Biomedical Engineering, 2204 Biomedical Engineering, 610 Medicine & health, Bioengineering, Organ Preservation, Applied Microbiology and Biotechnology, Liver Transplantation, Perfusion, 10219 Clinic for Gastroenterology and Hepatology, Liver, 10049 Institute of Pathology and Molecular Pathology, 1313 Molecular Medicine, 1305 Biotechnology, Quality of Life, 2402 Applied Microbiology and Biotechnology, Humans, Molecular Medicine, Biotechnology
Abstract

Current organ preservation methods provide a narrow window (usually12 hours) to assess, transport and implant donor grafts for human transplantation. Here we report the transplantation of a human liver discarded by all centers, which could be preserved for several days using ex situ normothermic machine perfusion. The transplanted liver exhibited normal function, with minimal reperfusion injury and the need for only a minimal immunosuppressive regimen. The patient rapidly recovered a normal quality of life without any signs of liver damage, such as rejection or injury to the bile ducts, according to a 1-year follow up. This inaugural clinical success opens new horizons in clinical research and promises an extended time window of up to 10 days for assessment of viability of donor organs as well as converting an urgent and highly demanding surgery into an elective procedure.

Published
2022

4. Real-time assessment of kidney allografts during HOPE using flavin mononucleotide (FMN) — a preclinical study

Author

Sousa Da Silva, Richard X., Darius, Tom, Mancina, Leandro, Eden, Janina, Wernlé, Kendra, Ghoneima, Ahmed S., Barlow, Adam D., Clavien, Pierre-Alain, Dutkowski, Philipp, and Kron, Philipp

Abstract

IntroductionThe gap between available donor grafts and patients on the waiting lists is constantly growing. This leads to an increased utilization of high-risk and therefore more vulnerable kidney grafts. The use of high-risk organs requires further optimization of machine preservation and assessment strategies before transplantation. Hypothermic machine perfusion (HMP) is the standard of care for kidneys originating from donation after circulatory death (DCD), whereas the evidence of HMP with additional oxygen (HOPE) is still very limited. Furthermore, an objective quality assessment of HMP-perfused kidneys is lacking. Recently, the release of mitochondria derived fragments, i.e., flavin mononucleotide (FMN) of complex I during machine liver perfusion was shown to be predictive for liver graft function before implantation. Therefore, the aim of this study was to evaluate, if FMN is useful also for assessment of kidney injury before use.MethodsA porcine perfusion model was used to investigate the feasibility of assessment of kidney grafts during hypothermic oxygenated perfusion (HOPE) with either 0, 30 or 60 minutes of warm ischemia. The model with warm ischemia times (WIT) of 30 min and 60 min, was used to mimic a clinically relevant scenario. A group with no warm ischemia time (0′ WIT) served as control group. The groups underwent minimal static cold storage (SCS) of 2 h followed by 2 h of end-ischemic HOPE with repeated real-time FMN measurements. In a further step, these values were related to the release of damage-associated molecular patterns (DAMPs) and to the functionality of the respiratory chain, represented by the capacity of ATP production.ResultsWe demonstrate, first, feasibility of perfusate FMN measurements in perfused kidneys, and secondly its correlation with donor warm ischemia time. Accordingly, FMN measurement showed significantly higher release in the 60-minute WIT group (n = 4) compared to the 30-minute WIT (n = 4) and the control group (n = 4). FMN release correlated also with DAMP signaling, such as the release of 8-OHdG and HMGB1. Finally, ATP replenishment proved to be best in control kidneys, followed by kidneys with 30 min and then by kidneys with 60 min of WIT.DiscussionThis study demonstrates the feasibility of FMN measurement in kidneys during HOPE. In addition, we show a correlation between FMN quantification and pre-existing kidney graft injury. Based on this, real-time FMN measurement during HOPE may be an objective assessment tool to accept high-risk kidneys for transplantation while minimizing post-transplant dysfunction, moving away from former “gut feeling” towards objective criteria in accepting marginal kidney grafts for transplantation. Graft evaluation based on these results may close the gap between available grafts and patients on the waiting lists by increasing utilization rates without significant impact for the recipients.

Published
2023

5. Normalization of lipid oxidation defects arising from hypoxia early posthepatectomy prevents liver failure in mouse

Author

Birrer, Dominique Lisa, Kachaylo, Ekaterina, Breuer, Eva, Linecker, Michael, Kron, Philipp, Ungethüm, Udo, Hagedorn, Catherine, Steiner, Regula, Kälin, Carola, Borrego, Lucia Bautista, Dufour, Jean-François, Foti, Michelangelo, Hornemann, Thorsten, Clavien, Pierre-Alain, Humar, Bostjan, University of Zurich, and Humar, Bostjan

Subjects
Transplantation, 2747 Transplantation, 540 Chemistry, 2723 Immunology and Allergy, Immunology and Allergy, 2736 Pharmacology (medical), Pharmacology (medical), 610 Medicine & health, 10038 Institute of Clinical Chemistry
Published
2023

6. A Spectrofluorometric Method for Real-Time Graft Assessment and Patient Monitoring

Author

Huwyler, Florian, Eden, Janina, Binz, Jonas, Cunningham, Leslie, Sousa Da Silva, Richard X., Clavien, Pierre-Alain, Dutkowski, Philipp, Tibbitt, Mark, and Hefti, Max

Subjects
liver transplantation, translational research, biomarkers, biomedical engineering, biosensors
Abstract

Biomarkers are powerful clinical diagnostics and predictors of patient outcome. However, robust measurements often require time and expensive laboratory equipment, which is insufficient to track rapid changes and limits direct use in the operating room. Here, this study presents a portable spectrophotometric device for continuous real-time measurements of fluorescent and non-fluorescent biomarkers at the point of care. This study measures the mitochondrial damage biomarker flavin mononucleotide (FMN) in 26 extended criteria human liver grafts undergoing hypothermic oxygenated perfusion to guide clinical graft assessment. Real-time data identified seven organs unsuitable for transplant that are discarded. The remaining grafts are transplanted and FMN values correlated with post-transplant indicators of liver function and patient recovery. Further, this study shows how this device can be used to monitor dialysis patients by measuring creatinine in real-time. Our approach provides a simple method to monitor biomarkers directly within biological fluids to improve organ assessment, patient care, and biomarker discovery., Advanced Science, ISSN:2198-3844

Published
2023
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7. Low-dose aspirin confers protection against acute cellular allograft rejection after primary liver transplantation

Author

Oberkofler, Christian E, Raptis, Dimitri A, Müller, Philip C, Sousa da Silva, Richard X, Lehmann, Kuno, Ito, Takahiro, Owen, Timothy, Pollok, Joerg-Matthias, Parente, Alessandro, Schlegel, Andrea, Peralta, Peregrina, Winter, Erin, Selzner, Markus, Fodor, Margot, Maglione, Manuel, Jaklitsch, Manuel, Marques, Hugo P, Chavez-Villa, Mariana, Contreras, Alan, Kron, Philipp, Lodge, Peter, Alford, Scott, Rana, Abbas, Magistri, Paolo, Di Benedetto, Fabrizio, Johnson, Bethany, Kirchner, Varvara, Bauldrick, Francis, Halazun, Karim J, Ghamarnedjad, Omid, Mehrabi, Arianeb, Basto, Samanta Teixeira, Fernandes, Eduardo SM, Paladini, Jose, de Santibañes, Martin, Florman, Sander, Tabrizian, Parissa, Dutkowski, Philipp, Clavien, Pierre-Alain, Busuttil, Ronald W, Kaldas, Fady M, and Petrowsky, Henrik

Subjects
Graft Rejection, Adult, Transplantation, Prevention, Liver Disease, Graft Survival, Clinical Sciences, Thrombosis, Organ Transplantation, Allografts, Liver Transplantation, Cohort Studies, Risk Factors, Clinical Research, Humans, Surgery, Digestive Diseases, Retrospective Studies
Abstract

This study investigated the effect of low-dose aspirin in primary adult liver transplantation (LT) on acute cellular rejection (ACR) as well as arterial patency rates. The use of low-dose aspirin after LT is practiced by many transplant centers to minimize the risk of hepatic artery thrombosis (HAT), although solid recommendations do not exist. However, aspirin also possesses potent anti-inflammatory properties and might mitigate inflammatory processes after LT, such as rejection. Therefore, we hypothesized that the use of aspirin after LT has a protective effect against ACR. This is an international, multicenter cohort study of primary adult deceased donor LT. The study included 17 high-volume LT centers and covered the 3-year period from 2013 to 2015 to allow a minimum 5-year follow-up. In this cohort of 2365 patients, prophylactic antiplatelet therapy with low-dose aspirin was administered in 1436 recipients (61%). The 1-year rejection-free survival rate was 89% in the aspirin group versus 82% in the no-aspirin group (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.63-0.94; p=0.01). The 1-year primary arterial patency rates were 99% in the aspirin group and 96% in the no-aspirin group with an HR of 0.23 (95% CI, 0.13-0.40; p

Published
2022

8. Novel Benchmark Values for Redo Liver Transplantation. Does the Outcome Justify the Effort?: Does the Outcome Justify the Effort?

Author

Abbassi, Fariba, Gero, Daniel, Muller, Xavier, Bueno, Alba, Figiel, Wojciech, Robin, Fabien, Laroche, Sophie, Picard, Benjamin, Shankar, Sadhana, Ivanics, Tommy, van Reeven, Marjolein, van Leeuwen, Otto B, Braun, Hillary J, Monbaliu, Diethard, Breton, Antoine, Vachharajani, Neeta, Bonaccorsi Riani, Eliano, Nowak, Greg, McMillan, Robert R, Abu-Gazala, Samir, Nair, Amit, Bruballa, Rocio, Paterno, Flavio, Weppler Sears, Deborah, Pinna, Antonio D, Guarrera, James V, de Santibañes, Eduardo, de Santibañes, Martin, Hernandez-Alejandro, Roberto, Olthoff, Kim, Ghobrial, R Mark, Ericzon, Bo-Göran, Ciccarelli, Olga, Chapman, William C, Mabrut, Jean-Yves, Pirenne, Jacques, Müllhaupt, Beat, Ascher, Nancy L, Porte, Robert J, de Meijer, Vincent E, Polak, Wojciech G, Sapisochin, Gonzalo, Attia, Magdy, Weiss, Emmanuel, Adam, René A, Cherqui, Daniel, Boudjema, Karim, Zienewicz, Krzysztof, Jassem, Wayel, Dutkowski, Philipp, Clavien, Pierre-Alain, Groningen Institute for Organ Transplantation (GIOT), and Center for Liver, Digestive and Metabolic Diseases (CLDM)

Subjects
retransplantation, benchmark, redo liver transplantation
Abstract

OBJECTIVE: To define benchmark cutoffs for redo liver transplantation (redo-LT). BACKGROUND: In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, there is a lack of benchmark data to reliably evaluate outcomes after redo-LT. METHODS: We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with MELD score ≤25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary non-function (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers. RESULTS: Out of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index (CCI®) at 1-year of ≤72, and in-hospital and 1-year mortality rates of ≤13% and ≤15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redo-LT benchmarks. CONCLUSION: This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This major analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources.

Published
2022

9. Synthesis of coagulation factors during long-term ex situ liver perfusion

Author

Eshmuminov, Dilmurodjon, Hefti, Max, Mueller, Matteo, Schuler, Martin J, Bautista Borrego, Lucia, Schneider, Marcel André, Koch, Karin, Weisskopf, Miriam, Tibbitt, Mark W, Dutkowski, Philipp, Rudolf von Rohr, Philipp, Studt, Jan-Dirk, Becker, Dustin, Clavien, Pierre-Alain, University of Zurich, and Clavien, Pierre-Alain

Subjects
1502 Bioengineering, 10032 Clinic for Oncology and Hematology, 2502 Biomaterials, 2204 Biomedical Engineering, 610 Medicine & health, 2701 Medicine (miscellaneous), 10217 Clinic for Visceral and Transplantation Surgery
Published
2022

10. Sources and prevention of graft infection during long-term ex situ liver perfusion

Author

Eshmuminov, Dilmurodjon, Mueller, Matteo, Brugger, Silvio D, Bautista Borrego, Lucia, Becker, Dustin, Hefti, Max, Hagedorn, Catherine, Duskabilova, Muhayyo, Tibbitt, Mark W, Dutkowski, Philipp, Rudolf von Rohr, Philipp, Schuler, Martin J, Mueller, Nicolas J, Clavien, Pierre-Alain, University of Zurich, and Clavien, Pierre-Alain

Subjects
10234 Clinic for Infectious Diseases, 2747 Transplantation, 610 Medicine & health, 2725 Infectious Diseases, 10217 Clinic for Visceral and Transplantation Surgery
Published
2021

11. Neoadjuvant Therapy for Resectable Pancreatic Cancer: A New Standard of Care. Pooled Data from Three Randomized Controlled Trials

Author

Birrer, Dominique L, Golcher, Henriette, Casadei, Riccardo, Haile, Sarah R, Fritsch, Ralph, Hussung, Saskia, Brunner, Thomas B, Fietkau, Rainer, Meyer, Thomas, Grützmann, Robert, Merkel, Susanne, Ricci, Claudio, Ingaldi, Carlo, Di Marco, Mariacristina, Guido, Alessandra, Serra, Carla, Minni, Francesco, Pestalozzi, Bernhard, Petrowsky, Henrik, DeOliveira, Michelle, Bechstein, Wolf O, Bruns, Christiane J, Oberkofler, Christian E, Puhan, Milo, Lesurtel, Mickaël, Heinrich, Stefan, Clavien, Pierre-Alain, and University of Zurich

Subjects
10032 Clinic for Oncology and Hematology, 610 Medicine & health, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), 10217 Clinic for Visceral and Transplantation Surgery
Published
2021

13. Long-term Normothermic Machine Preservation of Partial Livers: First Experience With 21 Human Hemi-livers

Author

Mueller, Matteo, Hefti, Max, Eshmuminov, Dilmurodjon, Schuler, Martin J, Sousa Da Silva, Richard X, Petrowsky, Henrik, De Oliveira, Michelle L, Oberkofler, Christian E, Hagedorn, Catherine, Mancina, Leandro, Weber, Achim, Burg, Brian, Tibbitt, Mark W, Rudolf von Rohr, Philipp, Dutkowski, Philipp, Becker, Dustin, Bautista Borrego, Lucia, Clavien, Pierre-Alain, and University of Zurich

Subjects
610 Medicine & health, Surgery, 10217 Clinic for Visceral and Transplantation Surgery, 2746 Surgery
Published
2021

14. Modern therapeutic approaches for the treatment of malignant liver tumours

Author

Petrowsky, Henrik, Fritsch, Ralph, Guckenberger, Matthias, De Oliveira, Michelle L, Dutkowski, Philipp, Clavien, Pierre-Alain, University of Zurich, and Clavien, Pierre-Alain

Subjects
10032 Clinic for Oncology and Hematology, 610 Medicine & health, 2721 Hepatology, 2715 Gastroenterology, 10217 Clinic for Visceral and Transplantation Surgery
Published
2020

15. Reply to: Lactate Measurements in an Integrated Perfusion Machine for Human Livers

Author

Dutkowski, Philipp, Mueller, Matteo, Eshmuminov, Dilmurodjon, Bautista Borrego, Lucia, Becker, Dustin, Hefti, Max, Schuler, Martin J, Rudolf von Rohr, Philipp, Clavien, Pierre-Alain, University of Zurich, and Clavien, Pierre-Alain

Subjects
1502 Bioengineering, 1313 Molecular Medicine, 1305 Biotechnology, Biomedical Engineering, 2402 Applied Microbiology and Biotechnology, 2204 Biomedical Engineering, Molecular Medicine, 610 Medicine & health, Bioengineering, Applied Microbiology and Biotechnology, 10217 Clinic for Visceral and Transplantation Surgery, Biotechnology
Published
2020

16. Recurrence of primary sclerosing cholangitis after liver transplantation: Analysing the European Liver Transplant Registry and beyond

Author

Visseren, Thijmen, Erler, Nicole Stephanie, Polak, Wojciech Grzegorz, Adam, René, Karam, Vincent, Vondran, Florian Wolfgang Rudolf, Ericzon, Bo‐Goran, Thorburn, Douglas, IJzermans, Jan Nicolaas Maria, Paul, Andreas, Heide, Frans, Taimr, Pavel, Nemec, Petr, Pirenne, Jacques, Romagnoli, Renato, Metselaar, Herold Johnny, Darwish Murad, Sarwa, Vondran, Florian, Bergquist, Annika, Lindström, Lina, Snowdon, Victoria, van der Heide, Frans, Trunecka, Pavel, Salizzoni, Mauro, Arendtsen Rostved, Andreas, Arenga, Giuseppe, Berlakovich, Gabriela A, Candinas, Daniel, Markovic, Sasa, Troisi, Roberto, van Hoek, Bart, Kanmaz, Turan, Dayangac, Murat, Berney, Thierry, Sforza, Daniele, Gridelli, Bruno, Clavien, Pierre‐Alain, Hoppe‐Lotichius, Maria, Senninger, Norbert, Lorf, Thomas, Settmacher, Utz, Cuervas‐Mons, Valentín, Bacakoğlu, Aylin, Nadalin, Silvio, Serra, Valentina, Pacholczyk, Marek, Baccarani, Umberto, Dopazo Taboada, Cristina, Berenguer, Marina, San Juan, Fernando, Detry, Olivier, Stippel, Dirk, Evrard, Philippe, Gugenheim, Jean, Kiliç, Murat, Fernández Selles, Carlos, Norena, Luis Antonio Herrera, Melandro, Fabio, Gonzalez‐Pinto, Ignacio, Nicolini, Daniele, Pardo Sánchez, Fernando, Neumann‐Haefelin, Christoph, Gastroenterology & Hepatology, Surgery, Epidemiology, Visseren, T., Erler, N. S., Polak, W. G., Adam, R., Karam, V., Vondran, F. W. R., Ericzon, B. -G., Thorburn, D., Ijzermans, J. N. M., Paul, A., van der Heide, F., Taimr, P., Nemec, P., Pirenne, J., Romagnoli, R., Metselaar, H. J., Darwish Murad, S., Vondran, F., Bergquist, A., Lindstrom, L., Snowdon, V., Trunecka, P., Salizzoni, M., Arendtsen Rostved, A., Arenga, G., Berlakovich, G. A., Candinas, D., Markovic, S., Troisi, R., van Hoek, B., Kanmaz, T., Dayangac, M., Berney, T., Sforza, D., Gridelli, B., Clavien, P. -A., Hoppe-Lotichius, M., Senninger, N., Lorf, T., Settmacher, U., Cuervas-Mons, V., Bacakoglu, A., Nadalin, S., Serra, V., Pacholczyk, M., Baccarani, U., Dopazo Taboada, C., Berenguer, M., San Juan, F., Detry, O., Stippel, D., Evrard, P., Gugenheim, J., Kilic, M., Fernandez Selles, C., Norena, L. A. H., Melandro, F., Gonzalez-Pinto, I., Nicolini, D., Pardo Sanchez, F., and Neumann-Haefelin, C.

Subjects
Registrie, IMPACT, medicine.medical_treatment, Medizin, 030230 surgery, Liver transplantation, DISEASE, 0302 clinical medicine, Risk Factors, Recurrence, Retrospective Studie, EPIDEMIOLOGY, Registries, POPULATION, bayesian statistics, OUTCOMES, disease recurrence, liver transplantation, patient and graft survival, primary sclerosing cholangitis, surgical procedures, operative, Cohort, primary sclerosing cholangiti, 030211 gastroenterology & hepatology, Registry data, Life Sciences & Biomedicine, Human, bayesian statistic, medicine.medical_specialty, Cholangitis, Sclerosing, Detailed data, Primary sclerosing cholangitis, 03 medical and health sciences, Internal medicine, medicine, Humans, Retrospective Studies, Transplantation, Science & Technology, Proportional hazards model, business.industry, Risk Factor, Bayes Theorem, Patient survival, NATURAL-HISTORY, medicine.disease, RISK-FACTORS, Graft survival, Surgery, business
Abstract

Liver transplantation for primary sclerosing cholangitis (PSC) can be complicated by recurrence of PSC (rPSC). This may compromise graft survival but the effect on patient survival is less clear. We investigated the effect of post-transplant rPSC on graft and patient survival in a large European cohort. Registry data from the European Liver Transplant Registry regarding all first transplants for PSC between 1980 and 2015 were supplemented with detailed data on rPSC from 48 out of 138 contributing transplant centres, involving 1,549 patients. Bayesian proportional hazards models were used to investigate the impact of rPSC and other covariates on patient and graft survival. Recurrence of PSC was diagnosed in 259 patients (16.7%) after a median follow-up of 5.0 years (quantile 2.5%-97.5%: 0.4-18.5), with a significant negative impact on both graft (HR 6.7; 95% CI 4.9-9.1) and patient survival (HR 2.3; 95% CI 1.5-3.3). Patients with rPSC underwent significantly more re-transplants than those without rPSC (OR 3.6, 95% CI 2.7-4.8). PSC recurrence has a negative impact on both graft and patient survival, independent of transplant-related covariates. Recurrence of PSC leads to higher number of re-transplantations and a 33% decrease in 10-year graft survival. ispartof: TRANSPLANT INTERNATIONAL vol:34 issue:8 pages:1455-1467 ispartof: location:Switzerland status: published

Published
2021

17. Proposal of a New Comprehensive Notation for Hepatectomy

Author

Nagino, Masato, DeMatteo, Ronald, Lang, Hauke, Cherqui, Daniel, Malago, Massimo, Kawakatsu, Shoji, DeOliveira, Michelle L, Adam, René, Aldrighetti, Luca, Boudjema, Karim, Chapman, William, Clary, Bryan, de Santibañes, Eduardo, Dong, Jiahong, Ebata, Tomoki, Endo, Itaru, Geller, David, Guglielmi, Alfredo, Kato, Tomoaki, Lee, Sung-Gyu, Lodge, Peter, Nadalin, Silvio, Pinna, Antonio, Polak, Wojciech, Soubrane, Olivier, Clavien, Pierre-Alain, and University of Zurich

Subjects
610 Medicine & health, Surgery, 10217 Clinic for Visceral and Transplantation Surgery, 2746 Surgery
Published
2021

18. FDG-PET/CT: novel method for viability assessment of livers perfused ex vivo

Author

Orita, Erika, Becker, Dustin, Mueller, Matteo, Hefti, Max, Schuler, Martin J, Bautista Borrego, Lucia, Dutkowski, Philipp, Zeimpekis, Konstantinos, Treyer, Valerie, Kaufmann, Philipp A, Eshmuminov, Dilmurodjon, Clavien, Pierre-Alain, Huellner, Martin W, and University of Zurich

Subjects
610 Medicine & health, 10181 Clinic for Nuclear Medicine, 10217 Clinic for Visceral and Transplantation Surgery
Published
2021

19. Hepatic Vein Embolization for Safer Liver Surgery

Author

Clavien, Pierre-Alain, University of Zurich, and Clavien, Pierre-Alain

Subjects
610 Medicine & health, Surgery, 10217 Clinic for Visceral and Transplantation Surgery, 2746 Surgery
Published
2020

20. Exercise Improves Outcomes of Surgery on Fatty Liver in Mice

Author

Linecker, Michael, Frick, Lukas, Kron, Philipp, Limani, Perparim, Kambakamba, Patryk, Tschuor, Christoph, Langiewicz, Magda, Kachaylo, Ekaterina, Tian, Yinghua, Schneider, Marcel A, Ungethüm, Udo, Calo, Nicolas, Foti, Michelangelo, Dufour, Jean-François, Graf, Rolf, Humar, Bostjan, Clavien, Pierre-Alain, University of Zurich, and Clavien, Pierre-Alain

Subjects
610 Medicine & health, Surgery, 10217 Clinic for Visceral and Transplantation Surgery, 2746 Surgery
Published
2020

21. Liver Metastases

Author

Tsilimigras, Diamantis I, Brodt, Pnina, Clavien, Pierre-Alain, Muschel, Ruth J, D’Angelica, Michael I, Endo, Itaru, Parks, Rowan W, Doyle, Majella, de Santibañes, Eduardo, Pawlik, Timothy M, University of Zurich, and Pawlik, Timothy M

Subjects
610 Medicine & health, 2700 General Medicine, General Medicine, 10217 Clinic for Visceral and Transplantation Surgery
Abstract

Liver metastases are commonly detected in a range of malignancies including colorectal cancer (CRC), pancreatic cancer, melanoma, lung cancer and breast cancer, although CRC is the most common primary cancer that metastasizes to the liver. Interactions between tumour cells and the tumour microenvironment play an important part in the engraftment, survival and progression of the metastases. Different cells including liver sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, parenchymal hepatocytes, dendritic cells, resident natural killer cells as well as other immune cells such as monocytes, macrophages and neutrophils are implicated in promoting and sustaining metastases in the liver. Four key phases (microvascular, pre-angiogenic, angiogenic and growth phase) have been identified in the process of liver metastasis. Imaging modalities such as ultrasonography, CT, MRI and PET scans are typically utilized for the diagnosis of liver metastases. Surgical resection remains the main potentially curative treatment among patients with resectable liver metastases. The role of liver transplantation in the management of liver metastasis remains controversial. Systemic therapies, newer biological agents (for example, bevacizumab and cetuximab) and immunotherapeutic agents have revolutionized the treatment options of liver metastases. Moving forward, ncorporation of genetic tests can provide more accurate information to guide clinical decision making and predict prognosis among patients with liver metastases.

Published
2021

22. Automated insulin delivery - Continuous blood glucose control during ex situ liver perfusion

Author

Becker, Dustin, Eshmuminov, Dilmurodjon, Keller, Roman, Mueller, Matteo, Bautista Borrego, Lucia, Hagedorn, Catherine, Duskabilova, Muhayyo, Tibbitt, Mark W, Onder, Christopher, Clavien, Pierre-Alain, Rudolf von Rohr, Philipp, Schuler, Martin, Hefti, Max, and University of Zurich

Subjects
Biomedical Engineering, 2204 Biomedical Engineering, 610 Medicine & health, 10217 Clinic for Visceral and Transplantation Surgery
Published
2021

23. Improved Survival in Liver Transplant Patients Receiving Prolonged-release Tacrolimus-based Immunosuppression in the European Liver Transplant Registry (ELTR): An Extension Study

Author

Adam, René, Karam, Vincent, Cailliez, Valérie, Trunečka, Pavel, Samuel, Didier, Tisone, Giuseppe, Němec, Petr, Soubrane, Olivier, Schneeberger, Stefan, Gridelli, Bruno, Bechstein, Wolf O., Risaliti, Andrea, Line, Pal-Dag, Vivarelli, Marco, Rossi, Massimo, Pirenne, Jacques, Klempnauer, Jurgen L., Rummo, Aleh, Di Benedetto, Fabrizio, Zieniewicz, Krzysztof, Troisi, Roberto, Paul, Andreas, Vali, Toomas, Kollmar, Otto, Boudjema, Karim, Hoti, Emir, Colledan, Michele, Pratschke, Johan, Lang, Hauke, Popescu, Irinel, Ericzon, Bo-Goran, Strupas, Kestutis, De Simone, Paolo, Kochs, Eberhard, Heyd, Bruno, Gugenheim, Jean, Pinna, Antonio D., Bennet, William, Kazimi, Mirjalal, Bachellier, Philippe, Wigmore, Stephen J., Rasmussen, Allan, Clavien, Pierre-Alain, Hidalgo, Ernest, O'Grady, John G., Zamboni, Frausto, Kilic, Murat, Duvoux, Christophe, O’Grady, John G., Adam, R, Karam, V, Cailliez, V, Trunecka, P, Samuel, D, Tisone, G, Nemec, P, Soubrane, O, Schneeberger, S, Gridelli, B, Bechstein, W, Risaliti, A, Line, P, Vivarelli, M, Rossi, M, Pirenne, J, Klempnauer, J, Rummo, A, Di Benedetto, F, Zieniewicz, K, Troisi, R, Paul, A, Vali, T, Kollmar, O, Boudjema, K, Hoti, E, Colledan, M, Pratschke, J, Lang, H, Popescu, I, Ericzon, B, Strupas, K, De Simone, P, Kochs, E, Heyd, B, Gugenheim, J, Pinna, A, Bennet, W, Kazimi, M, Bachellier, P, Wigmore, S, Rasmussen, A, Clavien, P, Hidalgo, E, O'Grady, J, Zamboni, F, Kilic, M, and Duvoux, C

Subjects
Graft Rejection, Male, medicine.medical_specialty, Time Factors, Drug Compounding, medicine.medical_treatment, Calcineurin Inhibitors, Medizin, MEDLINE, chemical and pharmacologic phenomena, Liver Transplant, 030230 surgery, Liver transplantation, Risk Assessment, Tacrolimus, all contributing centers (www.eltr.org) and the European Liver and Intestine Transplant Association (ELITA), 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Prolonged release, Internal medicine, medicine, Humans, Aged, Delayed-Action Preparations, Europe, Female, Graft Survival, Immunosuppressive Agents, Middle Aged, Registries, Retrospective Studies, Treatment Outcome, Liver Transplantation, Transplantation, business.industry, Immunosuppression, Retrospective cohort study, Settore MED/18, 3. Good health, surgical procedures, operative, 030211 gastroenterology & hepatology, Transplant patient, business, Risk assessment
Abstract

BACKGROUND: We compared, through the European Liver Transplant Registry, long-term liver transplantation outcomes with prolonged-release tacrolimus (PR-T) versus immediate-release tacrolimus (IR-T)-based immunosuppression. This retrospective analysis comprises up to 8-year data collected between 2008 and 2016, in an extension of our previously published study. METHODS: Patients with

Published
2019

27. Response to the Comment on 'Injury or Function-What Is Best to Assess Organ Viability Before Liver Graft Implantation?'

Author

Muller Xavier, Philipp Dutkowski, Schlegel Andrea, Clavien Pierre-Alain, University of Zurich, and Dutkowski, Philipp

Subjects
Organ Viability, Tissue Survival, medicine.medical_specialty, business.industry, Urology, 610 Medicine & health, Organ Preservation, 2746 Surgery, Liver Transplantation, Liver graft, Liver, Medicine, Humans, Surgery, business, Function (biology), 10217 Clinic for Visceral and Transplantation Surgery
Published
2020

28. Toward a Consensus on Centralization in Surgery

Author

Vonlanthen, René, Lodge, Peter, Barkun, Jeffrey S, et al, Käser, S A, Petrowsky, Henrik, Clavien, Pierre-Alain, University of Zurich, and Clavien, Pierre-Alain

Subjects
610 Medicine & health, 10217 Clinic for Visceral and Transplantation Surgery, 2746 Surgery
Published
2018

29. Hypothermic Oxygenated Liver Perfusion (HOPE) Prevents Tumor Recurrence in Liver Transplantation From Donation After Circulatory Death

Author

Mueller, Matteo, Kalisvaart, Marit, O'Rourke, Joanne, Shetty, Shishir, Parente, Alessandro, Muller, Xavier, Isaac, John, Muellhaupt, Beat, Muiesan, Paolo, Shah, Tahir, Clavien, Pierre-Alain, Schlegel, Andrea, Dutkowski, Philipp, and University of Zurich

Subjects
10219 Clinic for Gastroenterology and Hepatology, 610 Medicine & health, 10217 Clinic for Visceral and Transplantation Surgery, 2746 Surgery
Published
2020

31. Large-Scale Profiling of Signaling Pathways Reveals a Distinct Demarcation between Normal and Extended Liver Resection

Author

Borger, Pieter, Buzdin, Anton, Sorokin, Maksim, Kachaylo, Ekaterina, Humar, Bostjan, Graf, Rolf, Clavien, Pierre-Alien, and University of Zurich

Subjects
Time Factors, extended liver resection, Oncofinder, Gene Expression Profiling, intracellular signaling pathways, liver failure, 610 Medicine & health, 2700 General Medicine, RNAseq, Article, Mice, Inbred C57BL, MicroRNAs, Liver, lcsh:Biology (General), Animals, Hepatectomy, normal liver resection, RNA, Messenger, Transcriptome, lcsh:QH301-705.5, small-for-size syndrome, Signal Transduction, 10217 Clinic for Visceral and Transplantation Surgery
Abstract

Despite numerous studies addressing normal liver regeneration, we still lack comprehensive understanding of the biological processes underlying failed liver regeneration. Therefore, we analyzed the activity of 271 intracellular signaling pathways (ISPs) by genome wide profiling of differentially expressed RNAs in murine liver tissue biopsies after normal hepatectomy (nHx, 68% of liver removed) and extended hepatectomy (eHx, 86% of liver removed). Comprehensive, genome-wide transcriptome profiling using RNAseq was performed in liver tissue obtained from mice (sham, nHx, and eHx) harvested 1, 8, 16, 32, and 48 h after operation (n = 3 per group) and the OncoFinder toolkit was used for an unsupervised, unbiased identification of intracellular signaling pathways (ISP) activity. We observed that the normal regenerative process requires a transient activation and silencing of approximately two dozen of ISPs. After nHx, the Akt Pathway represented with 13 branches, the Chromatin Pathway and the DDR Pathways dominated. After eHx, the ATM main pathway and two of its branches (Cell Survival, G2_M Checkpoint Arrest) dominated, as well as the Hypoxia Pathways. Further, 14 ISPs demonstrated a strong inverse regulation, with the Hedgehog and the Brca1 Main Pathways as chief activators after nHx, and the ATM Pathway (G2_M Checkpoint Arrest) as the dominating constraining response after eHx.

Published
2020
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33. Model assisted analysis of the hepatic arterial buffer response during ex vivo porcine liver perfusion

Author

Becker, Dustin, Hefti, Max, Schuler, Martin J, Bautista Borrego, Lucia, Hagedorn, Catherine, Muller, Xavier, Graf, Rolf, Dutkowski, Philipp, Tibbitt, Mark W, Onder, Christopher, Clavien, Pierre-Alain, Eshmuminov, Dilmurodjon, Rudolf von Rohr, Philipp, University of Zurich, and Becker, Dustin

Subjects
2204 Biomedical Engineering, 610 Medicine & health, 10217 Clinic for Visceral and Transplantation Surgery
Published
2020

34. Defining Benchmarks in Liver Transplantation: A Multicenter Outcome Analysis Determining Best Achievable Results

Author

Muller, Xavier, Marcon, Francesca, Sapisochin, Gonzalo, Marquez, Max, Dondero, Federica, Rayar, Michel, Doyle, Majella M B, Callans, Lauren, Li, Jun, Clavien, Pierre-Alain, Puhan, Milo, et al, University of Zurich, and Clavien, Pierre-Alain

Subjects
610 Medicine & health, Surgery, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), 10217 Clinic for Visceral and Transplantation Surgery, 2746 Surgery
Published
2018

36. Performance validation of the ALPPS risk model

Author

Linecker, Michael, Kuemmerli, Christoph, Kambakamba, Patryk, Schlegel, Andrea, Muiesan, Paolo, Capobianco, Ivan, Nadalin, Silvio, Torres, Orlando J, Mehrabi, Arianeb, Stavrou, Gregor A, Oldhafer, Karl J, Lurje, Georg, Balci, Deniz, Lang, Hauke, Robles-Campos, Ricardo, Hernandez-Alejandro, Roberto, Malago, Massimo, De Santibanes, Eduardo, Clavien, Pierre-Alain, Petrowsky, Henrik, University of Zurich, and Petrowsky, Henrik

Subjects
610 Medicine & health, 2721 Hepatology, 2715 Gastroenterology, 10217 Clinic for Visceral and Transplantation Surgery
Published
2019

38. A systematic review and meta-analysis of rescue revascularization with arterial conduits in liver transplantation

Author

Reese, Tim, Raptis, Dimitri A, Oberkofler, Christian E, de Rougemont, Olivier, Györi, Georg P, Gosteli-Peter, Martina, Dutkowski, Philipp, Clavien, Pierre-Alain, Petrowsky, Henrik, University of Zurich, and Petrowsky, Henrik

Subjects
Transplantation, 2747 Transplantation, 2723 Immunology and Allergy, 2736 Pharmacology (medical), Immunology and Allergy, 610 Medicine & health, Pharmacology (medical), 10217 Clinic for Visceral and Transplantation Surgery
Published
2019

39. Reply to 'Ex situ normothermic machine perfusion of donor livers using a haemoglobin-based oxygen carrier: a viable alternative to red blood cells'

Author

Eshmuminov, Dilmurodjon, Leoni, Filippo, Schneider, Marcel André, Becker, Dustin, Muller, Xavier, Hefti, Max, Schuler, Martin J, Onder, Christopher, Dutkowski, Philipp, Graf, Rolf, Rudolf von Rohr, Philipp, Clavien, Pierre-Alain, Bautista Borrego, Lucia, and University of Zurich

Subjects
2747 Transplantation, 610 Medicine & health, 10217 Clinic for Visceral and Transplantation Surgery
Published
2018

42. Histological findings to five years after early conversion of kidney transplant patients from cyclosporine to everolimus: an analysis from the randomized ZEUS study

Author

Eisenberger, Ute, Budde, Klemens, Mühlfeld, Anja, Hauser, Ingeborg A., Nadalin, Silvio, Porstner, Martina, Arns, Wolfgang, ZEUS Study Investigators, Lehner, Frank, Klempnauer, Jürgen, Neumayer, Hans-H., Gerke, Peter, Klehr, Hans Ulrich, Mühlfeld, Anja Susanne, Witzke, Oliver, Pietruck, Frank, Heller, Katharina, Reinke, Petra, Senninger, Norbert, Sommerer, Claudia, Wolters, Heiner H., Suwelack, Barbara, Zeier, Martin, Stahl, Rolf, Thorban, Stefan, Stangl, Manfred, Steurer, Wolfgang, Frey, Felix, Wüthrich, Rudolf P., Clavien, Pierre-Alain, ZEUS Study Investigators (Beitragende*r), University of Zurich, Eisenberger, Ute, Dunstall, Caroline, Grünewald, Elisabeth, and ZEUS Study Investigators

Subjects
Male, Nephrology, Time Factors, mTOR inhibitor, Biopsy, medicine.medical_treatment, Medizin, 030232 urology & nephrology, 030230 surgery, lcsh:RC870-923, law.invention, Kidney transplantation, 0302 clinical medicine, Randomized controlled trial, Medizinische Fakultät, law, 2727 Nephrology, medicine.diagnostic_test, Drug Substitution, Graft Survival, Immunosuppression, Middle Aged, Cyclosporine, Female, Immunosuppressive Agents, Research Article, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Randomized, Urology, 610 Medicine & health, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, ddc:610, Everolimus, Aged, 10217 Clinic for Visceral and Transplantation Surgery, business.industry, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, 10040 Clinic for Neurology, Transplantation, Regimen, Antibody-mediated rejection, business
Abstract

Background Conversion from calcineurin inhibitor (CNI) therapy to everolimus within 6 months after kidney transplantation improves long-term graft function but can increase the risk of mild biopsy-proven acute cellular rejection (BPAR). We performed a post-hoc analysis of histological data from a randomized trial in order to further analyze histologic information obtained from indication and protocol biopsies up to 5 years after transplantation. Methods Biopsy samples obtained up to 5 years post-transplant were analyzed from the randomized ZEUS study, in which kidney transplant patients were randomized at month 4.5 to switch to everolimus (n = 154) or remain on cyclosporine (CsA)-based immunosuppression (n = 146). All patients received mycophenolate and steroids. Results At least one investigator-initiated biopsy was undertaken in 53 patients in each group between randomization and year 5, with a mean (SD) of 2.6 (1.7) and 2.2 (1.4) biopsies per patient in the everolimus and CsA groups, respectively. In the everolimus and CsA groups, investigator-initiated biopsies showed (i) BPAR in 12.3 and 7.5% (p = 0.182) of patients, respectively, with episodes graded mild in 22/24 and 18/20 cases (ii) CsA toxicity lesions in 4.5 and 10.3% of patients (p = 0.076) (iii) antibody-mediated rejection in 0.6 and 2.7% of patients (p = 0.204), respectively. Conclusions This analysis of histological findings in the ZEUS study to 5 years after kidney transplantation shows no increase in antibody-mediated rejection under everolimus-based therapy with a lower rate of CNI-related toxicity compared to a conventional CsA-based regimen, and confirms the preponderance of mild BPAR seen in the main study after the early switch to CsA-free everolimus therapy. Trial registration ClinicalTrials.gov NCT00154310. Date of registration: September 12, 2005. Electronic supplementary material The online version of this article (10.1186/s12882-018-0950-1) contains supplementary material, which is available to authorized users.

Published
2018

44. Reply

Author

Clavien, Pierre-Alain and Dindo, Daniel

Published
2018

45. Impact of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) on growth of colorectal liver metastases

Author

Kambakamba, Patryk, Linecker, Michael, Schneider, Marcel, Reiner, Cäcilia S, Nguyen-Kim, Thi Dan Linh, Limani, Perparim, Romic, Ivan, Figueras, Joan, Petrowsky, Henrik, Clavien, Pierre-Alain, Lesurtel, Mickaël, University of Zurich, and Lesurtel, Mickaël

Subjects
10042 Clinic for Diagnostic and Interventional Radiology, 610 Medicine & health, Surgery, 10217 Clinic for Visceral and Transplantation Surgery, 2746 Surgery
Published
2018

49. ALPPS as a salvage procedure after insufficient future liver remnant hypertrophy following portal vein occlusion

Author

Enne, Marcelo, Schadde, Erik, Björnsson, Bergthór, Hernandez-Alejandro, Roberto, Steinbruck, Klaus, Viana, Eduardo, Robles Campos, Ricardo, Malago, Massimo, Clavien, Pierre-Alain, De Santibanes, Eduardo, Gayet, Brice, ALPPS Registry Group, University of Zurich, and Enne, Marcelo

Subjects
610 Medicine & health, 2721 Hepatology, 2715 Gastroenterology, 10217 Clinic for Visceral and Transplantation Surgery
Published
2017

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